FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nicholson, AM Finch, NA Almeida, M Perkerson, RB van Blitterswijk, M Wojtas, A Cenik, B Rotondo, S Inskeep, V Almasy, L Dyer, T Peralta, J Jun, G Wood, AR Frayling, TM Fuchsberger, C Fowler, S Teslovich, TM Manning, AK Kumar, S Curran, J Lehman, D Abecasis, G Duggirala, R Pottier, C Zahir, HA Crook, JE Karydas, A Mitic, L Sun, Y Dickson, DW Bu, GJ Herz, J Yu, G Miller, BL Ferguson, S Petersen, RC Graff-Radford, N Blangero, J Rademakers, R AF Nicholson, Alexandra M. Finch, NiCole A. Almeida, Marcio Perkerson, Ralph B. van Blitterswijk, Marka Wojtas, Aleksandra Cenik, Basar Rotondo, Sergio Inskeep, Venette Almasy, Laura Dyer, Thomas Peralta, Juan Jun, Goo Wood, Andrew R. Frayling, Timothy M. Fuchsberger, Christian Fowler, Sharon Teslovich, Tanya M. Manning, Alisa K. Kumar, Satish Curran, Joanne Lehman, Donna Abecasis, Goncalo Duggirala, Ravindranath Pottier, Cyril Zahir, Haaris A. Crook, Julia E. Karydas, Anna Mitic, Laura Sun, Ying Dickson, Dennis W. Bu, Guojun Herz, Joachim Yu, Gang Miller, Bruce L. Ferguson, Shawn Petersen, Ronald C. Graff-Radford, Neill Blangero, John Rademakers, Rosa TI Prosaposin is a regulator of progranulin levels and oligomerization SO NATURE COMMUNICATIONS LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; TRAUMATIC BRAIN-INJURY; DISEASE MOUSE MODELS; NEUROTROPHIC FACTOR; NEURITE OUTGROWTH; GENE-EXPRESSION; RISK-FACTOR; PROTEIN; DEMENTIA; SORTILIN AB Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer's and Parkinson's disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction. PSAP-induced changes in PGRN levels and oligomerization replicate in human-derived fibroblasts obtained from a GRN mutation carrier, further supporting PSAP as a potential PGRN-related therapeutic target. Future studies should focus on addressing the relevance and cellular mechanism by which PGRN oligomeric species provide neuroprotection. C1 [Nicholson, Alexandra M.; Finch, NiCole A.; Perkerson, Ralph B.; van Blitterswijk, Marka; Wojtas, Aleksandra; Pottier, Cyril; Zahir, Haaris A.; Crook, Julia E.; Dickson, Dennis W.; Bu, Guojun; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Almeida, Marcio; Almasy, Laura; Dyer, Thomas; Peralta, Juan; Kumar, Satish; Curran, Joanne; Duggirala, Ravindranath; Blangero, John] Univ Texas Rio Grande Valley Sch Med, South Texas Diabet & Obes Inst, Brownsville, TX 78520 USA. [Cenik, Basar] Univ Texas Southwestern Med Ctr, Dept Neurosci Mol Genet & Psychiat, Dallas, TX 75390 USA. [Rotondo, Sergio; Ferguson, Shawn] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. [Rotondo, Sergio; Ferguson, Shawn] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT 06510 USA. [Inskeep, Venette; Sun, Ying] Cincinnati Childrens Hosp Res Fdn, Div Human Genet, Cincinnati, OH 45229 USA. [Jun, Goo] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, St Lukes Campus, Exeter EX1 2LU, Devon, England. [Fuchsberger, Christian; Teslovich, Tanya M.; Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Fowler, Sharon] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lehman, Donna] Univ Texas Hlth Sci Ctr, Dept Med Cardiol & Cellular & Struct Biol, San Antonio, TX 78229 USA. [Karydas, Anna; Mitic, Laura; Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Herz, Joachim; Yu, Gang] Univ Texas SW Med Ctr Dallas, Dept Mol Genet Neurosci Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN 55902 USA. [Graff-Radford, Neill] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Rademakers, R (reprint author), Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. EM rademakers.rosa@mayo.edu RI Jun, Goo/F-1941-2017 OI Jun, Goo/0000-0003-0891-0204 FU NIH [R01 NS076471, P50 AG016574, UO1 AG006786, U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526, U01 DK085545, P01 HL045222, R01 DK047482, R01 DK053889]; Younkin Scholarship; Consortium for Frontotemporal Degeneration Research FX We are deeply indebted to Richard Gibson (deceased) for his many years of commitment to science, the Department of Molecular Genetics at UT Southwestern and for his help with producing anti-progranulin antibodies. We thank the T2D-GENES consortium for sequencing data sharing. This work was funded by NIH grants R01 NS076471, P50 AG016574 and UO1 AG006786 awarded to Rosa Rademakers, the Younkin Scholarship awarded to Alexandra Nicholson, and the Consortium for Frontotemporal Degeneration Research. T2D-GENES Consortium is supported by NIH grants U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526 and U01 DK085545. The San Antonio Family Studies is supported by NIH grants P01 HL045222, R01 DK047482 and R01 DK053889. NR 63 TC 0 Z9 0 U1 2 U2 3 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 JUN PY 2016 VL 7 AR 11992 DI 10.1038/ncomms11992 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3NN UT WOS:000379109100001 PM 27356620 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI What is the meaning of "small-fiber polyneuropathy" in fibromyalgia? An alternate answer SO PAIN LA English DT Letter ID POSTURAL TACHYCARDIA SYNDROME; SKIN BIOPSIES; PAIN; NEUROPATHY; CONNECTIVITY; INNERVATION; FATIGUE; DENSITY C1 [Oaklander, Anne Louise] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.; Oaklander, AL (reprint author), Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. EM aloaklander@mgh.harvard.edu FU NINDS NIH HHS [R01 NS093653] NR 23 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN PY 2016 VL 157 IS 6 BP 1366 EP 1367 DI 10.1097/j.pain.0000000000000526 PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DQ0GG UT WOS:000378876300026 PM 27183448 ER PT J AU Sheridan, R AF Sheridan, Rob TI Y Less Is More-Revisiting Burn Resuscitation SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Editorial Material DE albumin; burns; colloid; resuscitation ID SHOCK C1 [Sheridan, Rob] Massachusetts Gen Hosp, Dept Surg, Boston Shriners Hosp Children, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston Shriners Hosp Children, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JUN PY 2016 VL 17 IS 6 BP 578 EP 579 DI 10.1097/PCC.0000000000000747 PG 2 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA DR0LL UT WOS:000379598900026 PM 27261654 ER PT J AU Poelwijk, FJ Krishna, V Ranganathan, R AF Poelwijk, Frank J. Krishna, Vinod Ranganathan, Rama TI The Context-Dependence of Mutations: A Linkage of Formalisms SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID FITNESS LANDSCAPES; K+ CHANNEL; PROTEIN-STRUCTURE; SIGN EPISTASIS; COMPLEX TRAITS; MUTANT CYCLES; PDZ DOMAIN; SEQUENCE; SYSTEMS; ARCHITECTURE AB Defining the extent of epistasis-the nonindependence of the effects of mutations-is essential for understanding the relationship of genotype, phenotype, and fitness in biological systems. The applications cover many areas of biological research, including biochemistry, genomics, protein and systems engineering, medicine, and evolutionary biology. However, the quantitative definitions of epistasis vary among fields, and its analysis beyond just pairwise effects remains problematic in general. Here, we bring together a number of previous results that show that different definitions of epistasis are versions of a single mathematical formalismthe weighted Walsh-Hadamard transform. We demonstrate that one of the definitions, the background-averaged epistasis, may be the most informative for describing the epistatic structure of a biological system. Key issues are the choice of effective ensembles for averaging and to practically contend with the vast combinatorial complexity of mutations. In this regard, we discuss strategies for optimally learning the epistatic structure of biological systems. C1 [Poelwijk, Frank J.; Krishna, Vinod] Univ Texas Southwestern Med Ctr, Green Ctr Syst Biol, Dallas, TX USA. [Ranganathan, Rama] Univ Texas Southwestern Med Ctr, Green Ctr Syst Biol, Dallas, TX USA. [Ranganathan, Rama] Univ Texas Southwestern Med Ctr, Dept Biophys, Dallas, TX USA. [Ranganathan, Rama] Univ Texas Southwestern Med Ctr, Dept Pharmacol, Dallas, TX USA. [Poelwijk, Frank J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Krishna, Vinod] Janssen Pharmaceut Res & Dev, Spring House, PA USA. RP Poelwijk, FJ (reprint author), Univ Texas Southwestern Med Ctr, Green Ctr Syst Biol, Dallas, TX USA.; Ranganathan, R (reprint author), Univ Texas Southwestern Med Ctr, Green Ctr Syst Biol, Dallas, TX USA.; Ranganathan, R (reprint author), Univ Texas Southwestern Med Ctr, Dept Biophys, Dallas, TX USA.; Ranganathan, R (reprint author), Univ Texas Southwestern Med Ctr, Dept Pharmacol, Dallas, TX USA.; Poelwijk, FJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM poelwijk@gmail.com; rama.ranganathan@utsouthwestern.edu FU Robert A. Welch Foundation [I-1366]; Green Center for Systems Biology FX This work was supported by the Robert A. Welch Foundation (I-1366, RR) and the Green Center for Systems Biology. FJP was an HHMI fellow of the Helen Hay Whitney Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 91 TC 1 Z9 1 U1 4 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2016 VL 12 IS 6 AR e1004771 DI 10.1371/journal.pcbi.1004771 PG 19 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA DQ6XN UT WOS:000379349700004 PM 27337695 ER PT J AU Matias, WR Falkard, B Charles, RC Mayo-Smith, LM Teng, JE Xu, P Kovac, P Ryan, ET Qadri, F Franke, MF Ivers, LC Harris, JB AF Matias, Wilfredo R. Falkard, Brie Charles, Richelle C. Mayo-Smith, Leslie M. Teng, Jessica E. Xu, Peng Kovac, Pavol Ryan, Edward T. Qadri, Firdausi Franke, Molly F. Ivers, Louise C. Harris, Jason B. TI Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID MEMORY B-CELL; O-SPECIFIC POLYSACCHARIDE; VIBRIO-CHOLERAE; IMMUNE-RESPONSES; WHOLE-CELL; KILLED CHOLERA; INFECTION; CHILDREN; BANGLADESH; LIPOPOLYSACCHARIDE AB Background The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. Methodology/Principal Findings We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. Conclusions/Significance Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a choleraendemic area. C1 [Matias, Wilfredo R.; Franke, Molly F.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Matias, Wilfredo R.; Ivers, Louise C.] Partners In Hlth, Boston, MA USA. [Falkard, Brie; Charles, Richelle C.; Mayo-Smith, Leslie M.; Ryan, Edward T.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.] Harvard Univ, Sch Med, Boston, MA USA. [Teng, Jessica E.; Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Qadri, Firdausi] Icddr B, Dhaka, Bangladesh. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.; Harris, JB (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM jbharris@mgh.harvard.edu RI Xu, Peng/K-7036-2012 FU Doris Duke Charitable Foundation; Doris Duke Charitable Foundation - National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI099243, AI103055, AI106878, K08 AI089721]; Intramural Research Program of the NIH; NIDDK; Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program; Abundance foundation FX This research was supported by core grants to the icddr,b, the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at Harvard Medical School (WRM), through programs funded by the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI099243 [JBH and LCI], AI103055 [JBH], AI106878 [ETR and FQ], and K08 AI089721 [RCC]), and the Intramural Research Program of the NIH and NIDDK (PX and PK), the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program [RCC], the Abundance foundation [LCI]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 1 Z9 1 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2016 VL 10 IS 6 AR e0004753 DI 10.1371/journal.pntd.0004753 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DQ6WL UT WOS:000379346200021 PM 27308825 ER PT J AU Held, KD Blakely, EA Story, MD Lowenstein, DI AF Held, Kathryn D. Blakely, Eleanor A. Story, Michael D. Lowenstein, Derek I. TI Use of the NASA Space Radiation Laboratory at Brookhaven National Laboratory to Conduct Charged Particle Radiobiology Studies Relevant to Ion Therapy SO RADIATION RESEARCH LA English DT Editorial Material ID PLATFORM AB Although clinical studies with carbon ions have been conducted successfully in Japan and Europe, the limited radiobiological information about charged particles that are heavier than protons remains a significant impediment to exploiting the full potential of particle therapy. There is growing interest in the U.S. to build a cancer treatment facility that utilizes charged particles heavier than protons. Therefore, it is essential that additional radiobiological knowledge be obtained using state-of-the-art technologies and biological models and end points relevant to clinical outcome. Currently, most such ion radiotherapy-related research is being conducted outside the U.S. This article addresses the substantial contributions to that research that are possible at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), which is the only facility in the U.S. at this time where heavy-ion radiobiology research with the ion species and energies of interest for therapy can be done. Here, we briefly discuss the relevant facilities at NSRL and how selected charged particle biology research gaps could be addressed using those facilities. (C) 2016 by Radiation Research Society C1 [Held, Kathryn D.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Blakely, Eleanor A.] Lawrence Berkeley Natl Lab, Berkeley, CA USA. [Story, Michael D.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Lowenstein, Derek I.] Brookhaven Natl Lab, Upton, NY 11973 USA. RP Held, KD (reprint author), Massachusetts Gen Hosp, Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM kheld@mgh.harvard.edu FU NCI NIH HHS [P20 CA183639, P20 CA183640, R21 CA182259] NR 14 TC 1 Z9 1 U1 6 U2 8 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2016 VL 185 IS 6 BP 563 EP 567 DI 10.1667/RR14412.1 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DR2QV UT WOS:000379749900001 PM 27195609 ER PT J AU Shea-Donohue, T Fasano, A Zhao, AP Notari, L Yan, S Sun, R Bohl, JA Desai, N Tudor, G Morimoto, M Booth, C Bennett, A Farese, AM MacVittie, TJ AF Shea-Donohue, Terez Fasano, Alessio Zhao, Aiping Notari, Luigi Yan, Shu Sun, Rex Bohl, Jennifer A. Desai, Neemesh Tudor, Greg Morimoto, Motoko Booth, Catherine Bennett, Alexander Farese, Ann M. MacVittie, Thomas J. TI Mechanisms Involved in the Development of the Chronic Gastrointestinal Syndrome in Nonhuman Primates after Total-Body Irradiation with Bone Marrow Shielding SO RADIATION RESEARCH LA English DT Article ID POTENTIALLY LETHAL; RADIATION; INFLAMMATION; COLITIS; BARRIER; IMMUNE AB In this study, nonhuman primates (NHPs) exposed to lethal doses of total body irradiation (TBI) within the gastrointestinal (GI) acute radiation syndrome range, sparing; 5% of bone marrow (TBI-BM5), were used to evaluate the mechanisms involved in development of the chronic GI syndrome. TBI increased mucosal permeability in the jejunum (12-14 Gy) and proximal colon (13-14 Gy). TBI-BM5 also impaired mucosal barrier function at doses ranging from 10-12.5 Gy in both small intestine and colon. Timed necropsies of NHPs at 6-180 days after 10 Gy TBIBM5 showed that changes in small intestine preceded those in the colon. Chronic GI syndrome in NHPs is characterized by continued weight loss and intermittent GI syndrome symptoms. There was a long-lasting decrease in jejunal glucose absorption coincident with reduced expression of the sodium-linked glucose transporter. The small intestine and colon showed a modest upregulation of several different pro-inflammatory mediators such as NOS-2. The persistent inflammation in the post-TBI-BM5 period was associated with a long-lasting impairment of mucosal restitution and a reduced expression of intestinal and serum levels of alkaline phosphatase (ALP). Mucosal healing in the postirradiation period is dependent on sparing of stem cell crypts and maturation of crypt cells into appropriate phenotypes. At 30 days after 10 Gy TBI-BM5, there was a significant downregulation in the gene and protein expression of the stem cell marker Lgr5 but no change in the gene expression of enterocyte or enteroendocrine lineage markers. These data indicate that even a threshold dose of 10 Gy TBI-BM5 induces a persistent impairment of both mucosal barrier function and restitution in the GI tract and that ALP may serve as a biomarker for these events. These findings have important therapeutic implications for the design of medical countermeasures. (C) 2016 by Radiation Research Society C1 [Shea-Donohue, Terez; Zhao, Aiping; Desai, Neemesh; Bennett, Alexander; Farese, Ann M.; MacVittie, Thomas J.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Shea-Donohue, Terez; Zhao, Aiping; Notari, Luigi; Yan, Shu; Sun, Rex; Bohl, Jennifer A.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Fasano, Alessio] Massachusetts Gen Hosp, Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. [Tudor, Greg; Booth, Catherine] Epistem Ltd, Manchester, Lancs, England. [Morimoto, Motoko] Miyagi Univ, Sch Food Agr & Environm Studies, Kurokawa, Miyagi, Japan. RP Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Dept Radiat Oncol, Div Translat Radiat Sci, Baltimore, MD 21201 USA. EM tdonohue@mbrc.umaryland.edu FU National Institute of Allergy and Infectious Diseases [NIAID] [RCI AI78520, HHSN266200500043C, HHSN272201000046C] FX This work was supported by the National Institute of Allergy and Infectious Diseases [NIAID; contract nos. RCI AI78520, HHSN266200500043C (TSD) and HHSN272201000046C (TM)]. NR 19 TC 1 Z9 1 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2016 VL 185 IS 6 BP 591 EP 603 DI 10.1667/RR14024.1 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DR2QV UT WOS:000379749900004 PM 27223826 ER PT J AU Thrall, JH AF Thrall, James H. TI Trends and Developments Shaping the Future of Diagnostic Medical Imaging: 2015 Annual Oration in Diagnostic Radiology SO RADIOLOGY LA English DT Editorial Material ID CLINICAL DECISION-SUPPORT; STAGE HODGKINS LYMPHOMA; CORONARY CT ANGIOGRAPHY; SPOT SIGN SCORE; INTRACEREBRAL HEMORRHAGE; VALIDATION; PET; TOMOGRAPHY; BIOMARKERS; EFFICACY C1 [Thrall, James H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400, Boston, MA 02114 USA. EM jthrall@mgh.harvard.edu NR 43 TC 0 Z9 0 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2016 VL 279 IS 3 BP 660 EP 666 DI 10.1148/radiol.2016160293 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8AG UT WOS:000378719700002 PM 27183401 ER PT J AU Gainor, JF AF Gainor, Justin F. TI Alectinib-a new chapter in the management of ALK-positive lung cancer SO TRANSLATIONAL LUNG CANCER RESEARCH LA English DT Editorial Material ID INHIBITOR ALECTINIB; BRAIN METASTASES; CRIZOTINIB; RESISTANCE; CERITINIB; CHEMOTHERAPY; DISEASE; SAFETY; MODELS C1 [Gainor, Justin F.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. RP Gainor, JF (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jgainor@partners.org NR 24 TC 0 Z9 0 U1 2 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2218-6751 EI 2226-4477 J9 TRANSL LUNG CANCER R JI Transl. Lung Cancer Res. PD JUN PY 2016 VL 5 IS 3 BP 343 EP 346 DI 10.21037/tlcr.2016.03.05 PG 4 WC Oncology SC Oncology GA DR1KX UT WOS:000379665500021 PM 27411885 ER PT J AU Closser, S Finley, EP AF Closser, Svea Finley, Erin P. TI A New Reflexivity: Why Anthropology Matters in Contemporary Health Research and Practice, and How to Make It Matter More SO AMERICAN ANTHROPOLOGIST LA English DT Editorial Material ID EVIDENCE-BASED PSYCHOTHERAPIES; ROUTINE IMMUNIZATION; POLIO ERADICATION; CARE; PROGRAMS; IMPACT C1 [Closser, Svea] Middlebury Coll, Dept Sociol & Anthropol, Middlebury, VT 05753 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Div Hosp Med, Dept Med, San Antonio, TX 78229 USA. [Finley, Erin P.] South Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Closser, S (reprint author), Middlebury Coll, Dept Sociol & Anthropol, Middlebury, VT 05753 USA. OI Finley, Erin/0000-0003-4497-7721 NR 18 TC 1 Z9 1 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-7294 EI 1548-1433 J9 AM ANTHROPOL JI Am. Anthropol. PD JUN PY 2016 VL 118 IS 2 BP 385 EP 390 DI 10.1111/aman.12532 PG 6 WC Anthropology SC Anthropology GA DQ2GB UT WOS:000379019400017 ER PT J AU Yang, SH Imamura, Y Jenkins, RW Canadas, I Kitajima, S Aref, A Brannon, A Oki, E Castoreno, A Zhu, ZH Thai, T Reibel, J Qian, ZR Ogino, S Wong, KK Baba, H Kimmelman, AC Di Magliano, MP Barbie, DA AF Yang, Shenghong Imamura, Yu Jenkins, Russell W. Canadas, Israel Kitajima, Shunsuke Aref, Amir Brannon, Arthur Oki, Eiji Castoreno, Adam Zhu, Zehua Tran Thai Reibel, Jacob Qian, Zhirong Ogino, Shuji Wong, Kwok K. Baba, Hideo Kimmelman, Alec C. Di Magliano, Marina Pasca Barbie, David A. TI Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID INNATE IMMUNITY; SELECTIVE AUTOPHAGY; CELL-SURVIVAL; TUMOR-GROWTH; CANCER; PHOSPHORYLATION; ACTIVATION; RESTRICTS; PATHWAY; ADENOCARCINOMA AB Autophagy promotes tumor progression downstream of oncogenic KRAS, yet also restrains inflammation and dysplasia through mechanisms that remain incompletely characterized. Understanding the basis of this paradox has important implications for the optimal targeting of autophagy in cancer. Using a mouse model of cerulein-induced pancreatitis, we found that loss of autophagy by deletion of Atg5 enhanced activation of the IkB kinase (IKK)-related kinase TBK1 in vivo, associated with increased neutrophil and T-cell infiltration and PD-L1 upregulation. Consistent with this observation, pharmacologic or genetic inhibition of autophagy in pancreatic ductal adenocarcinoma cells, including suppression of the autophagy receptors NDP52 or p62, prolonged TBK1 activation and increased expression of CCL5, IL6, and several other T-cell and neutrophil chemotactic cytokines in vitro. Defective autophagy also promoted PD-L1 upregulation, which is particularly pronounced downstream of IFN gamma signaling and involves JAK pathway activation. Treatment with the TBK1/IKKe/JAK inhibitor CYT387 (also known as momelotinib) not only inhibits autophagy, but also suppresses this feedback inflammation and reduces PD-L1 expression, limiting KRAS-driven pancreatic dysplasia. These findings could contribute to the dual role of autophagy in oncogenesis and have important consequences for its therapeutic targeting. (C) 2016 AACR. C1 [Yang, Shenghong; Jenkins, Russell W.; Canadas, Israel; Kitajima, Shunsuke; Aref, Amir; Zhu, Zehua; Tran Thai; Reibel, Jacob; Qian, Zhirong; Ogino, Shuji; Wong, Kwok K.; Barbie, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yang, Shenghong; Jenkins, Russell W.; Canadas, Israel; Kitajima, Shunsuke; Castoreno, Adam; Zhu, Zehua; Tran Thai; Barbie, David A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Imamura, Yu; Baba, Hideo] Kumamoto Univ, Grad Sch Med Sci, Dept Gastroenterol Surg, Kumamoto, Japan. [Imamura, Yu] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Gastroenterol Surg, Tokyo, Japan. [Imamura, Yu; Oki, Eiji] Kyushu Univ, Grad Med Sci, Dept Surg & Sci, Fukuoka, Japan. [Brannon, Arthur; Di Magliano, Marina Pasca] Univ Michigan, Ctr Comprehens Canc, Dept Surg, Ann Arbor, MI 48109 USA. [Brannon, Arthur; Di Magliano, Marina Pasca] Univ Michigan, Ctr Comprehens Canc, Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Qian, Zhirong; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Qian, Zhirong; Ogino, Shuji] Harvard Med Sch, Boston, MA USA. [Qian, Zhirong; Ogino, Shuji] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Kimmelman, Alec C.] Dana Farber Canc Inst, Radiat Oncol, Boston, MA 02115 USA. RP Barbie, DA (reprint author), 450 Brookline Ave,D819, Boston, MA 02215 USA. EM dbarbie@partners.org FU NCI NIH HHS [P01 CA154303, R01 CA130988, K08 CA138918, R01 CA151588, R01 CA151993, R01 CA157490, R01 CA190394]; NIGMS NIH HHS [T32 GM007863] NR 43 TC 5 Z9 6 U1 7 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JUN PY 2016 VL 4 IS 6 BP 520 EP 530 DI 10.1158/2326-6066.CIR-15-0235 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DQ8ZB UT WOS:000379499100007 PM 27068336 ER PT J AU Emmens, JE ter Maaten, JM Matsue, Y Metra, M O'Connor, CM Ponikowski, P Teerlink, JR Cotter, G Davison, B Cleland, JG Givertz, MM Bloomfield, DM Dittrich, HC Todd, J van Veldhuisen, DJ Hillege, HL Damman, K van der Meer, P Voors, AA AF Emmens, Johanna E. ter Maaten, Jozine M. Matsue, Yuya Metra, Marco O'Connor, Christopher M. Ponikowski, Piotr Teerlink, John R. Cotter, Gad Davison, Beth Cleland, John G. Givertz, Michael M. Bloomfield, Daniel M. Dittrich, Howard C. Todd, John van Veldhuisen, Dirk J. Hillege, Hans L. Damman, Kevin van der Meer, Peter Voors, Adriaan A. TI Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Plasma KIM-1; Heart failure; Prognosis ID GLOMERULAR-FILTRATION-RATE; TUBULAR DAMAGE; DISEASE; METAANALYSIS; ROLOFYLLINE; ANTAGONIST; MORTALITY; BIOMARKER; RECEPTOR; KIM-1 AB AimsUrinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF. Methods and resultsIn a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([I-131]hippuran clearance) and measured glomerular filtration rate (GFR; [I-125]iothalamate)} and urinary tubular damage markers. The association between plasma KIM-1, plasma creatinine, and clinical outcome was further explored in a cohort of 2033 acute HF patients. Median plasma KIM-1 was 171.5pg/mL (122.8-325.7) in chronic (n = 99) and 295.1pg/mL (182.2-484.2) in acute HF (n = 1588). In chronic HF, plasma KIM-1 was associated with GFR (P < 0.001), creatinine, and cystatin C. Plasma KIM-1 was associated with urinary N-acetyl--d-glucosaminidase (NAG), but not with other urinary tubular damage markers. Log plasma KIM-1 predicted adverse clinical outcome after adjustment for age, gender, and GFR [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.07-3.53, P = 0.030]. Statistical significance was lost after correction for NT-proBNP (HR 1.61, 95% CI 0.81-3.20, P = 0.175). In acute HF, higher plasma KIM-1 levels were associated with higher creatinine, lower albumin, and presence of diabetes. Log plasma KIM-1 predicted 60-day HF rehospitalization (HR 1.27, 95% CI 1.03-1.55, P = 0.024), but not 180-day mortality or 60-day death or renal or cardiovascular rehospitalization. ConclusionsPlasma KIM-1 is associated with glomerular filtration and urinary NAG, but not with other urinary tubular damage markers. Plasma KIM-1 does not predict outcome in chronic HF after correction for NT-proBNP. In acute HF, plasma KIM-1 predicts HF rehospitalization in multivariable analysis. C1 [Emmens, Johanna E.; ter Maaten, Jozine M.; Matsue, Yuya; van Veldhuisen, Dirk J.; Hillege, Hans L.; Damman, Kevin; van der Meer, Peter; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Metra, Marco] Univ Brescia, Brescia, Italy. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] Univ Iowa, Carver Coll Med, Cardiovasc Res Ctr, Iowa City, IA USA. [Todd, John] Singulex Inc, Alameda, CA USA. [Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016 NR 22 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2016 VL 18 IS 6 BP 641 EP 649 DI 10.1002/ejhf.426 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DQ5PL UT WOS:000379257200009 PM 26511274 ER PT J AU Vaduganathan, M Pallais, JC Fenves, AZ Butler, J Gheorghiade, M AF Vaduganathan, Muthiah Pallais, J. Carl Fenves, Andrew Z. Butler, Javed Gheorghiade, Mihai TI Serum chloride in heart failure: a salty prognosis SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID REDUCED EJECTION FRACTION; EVEREST TRIAL; CLINICAL-COURSE; TOLVAPTAN; HOSPITALIZATION; HYPONATREMIA; METAANALYSIS; OSMOLALITY; SODIUM C1 [Vaduganathan, Muthiah] Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. [Vaduganathan, Muthiah] Harvard Med Sch, Boston, MA USA. [Pallais, J. Carl; Fenves, Andrew Z.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA. [Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron,Galter 3-150, Chicago, IL 60601 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 201 East Huron,Galter 3-150, Chicago, IL 60601 USA. EM m-gheorghiade@northwestern.edu NR 24 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUN PY 2016 VL 18 IS 6 BP 669 EP 671 DI 10.1002/ejhf.546 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DQ5PL UT WOS:000379257200013 PM 27121684 ER PT J AU Zukerberg, L Mahadevan, K Selig, M Deshpande, V AF Zukerberg, Lawrence Mahadevan, Krishnan Selig, Martin Deshpande, Vikram TI Oesophageal intrasquamous IgG4 deposits: an adjunctive marker to distinguish eosinophilic oesophagitis from reflux oesophagitis SO HISTOPATHOLOGY LA English DT Article DE eosinophilic oesophagitis; IgG4; IgG4-related disease; reflux oesophagitis; ultrastructural evaluation ID CONSENSUS RECOMMENDATIONS; IGG4-RELATED DISEASE; EXPRESSION PROFILE; ADULTS; DIAGNOSIS; PANCREATITIS; MECHANISMS; EOTAXIN-3; FEATURES; CHILDREN AB Aims: To explore the utility of an IgG4 immunohistochemical stain to help distinguish eosinophilic oesophagitis from gastroesophageal reflux disease. Methods and results: We examined 21 cases of eosinophilic oesophagitis and 25 cases of gastroesophageal reflux disease. The diagnosis of eosinophilic oesophagitis was based on the presence of oesophageal dysfunction, >15 eosinophils per high-power field, and a lack of response to proton pump inhibitors. Gastroesophageal reflux disease showed intraepithelial eosinophils, but a clinical and/or histological response to proton pump inhibitor therapy. We also evaluated an additional cohort of 22 cases with intraepithelial eosinophils. Immunohistochemical staining for IgG4 was performed. Sixteen of 21 (76%) eosinophilic oesophagitis cases showed intrasquamous extracellular IgG4 deposits, whereas all 25 gastroesophageal reflux disease cases were negative. Mucosal IgG4-positive plasma cells were identified in eosinophilic oesophagitis and gastroesophageal reflux disease cases in 58% and 40% of cases, respectively. Eosinophilic oesophagitis patients receiving treatment were less likely to be positive for intraepithelial IgG4 deposits (88% versus 53%). In the validation cohort, the sensitivity and specificity for eosinophilic oesophagitis were 88% and 100%, respectively. Conclusions: The presence of intrasquamous IgG4 deposits is a useful adjunctive marker in the distinction between eosinophilic oesophagitis and gastroesophageal reflux disease. C1 [Zukerberg, Lawrence; Mahadevan, Krishnan; Selig, Martin; Deshpande, Vikram] Harvard Med Sch, Dept Pathol, Massachusetts Gen Hosp, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM vikramdirdeshpande@gmail.com NR 23 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD JUN PY 2016 VL 68 IS 7 BP 968 EP 976 DI 10.1111/his.12892 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DQ1BG UT WOS:000378935100002 PM 26466342 ER PT J AU Cottreau, J Gruchy, S Kamionek, M Lauwers, GY Arnason, T AF Cottreau, Jonathan Gruchy, Steven Kamionek, Michal Lauwers, Gregory Y. Arnason, Thomas TI Prevalence of oesophageal epidermoid metaplasia in 1048 consecutive patients and 58 patients with squamous neoplasms SO HISTOPATHOLOGY LA English DT Article DE epidermoid metaplasia; oesophagus; squamous cell carcinoma; squamous dysplasia ID EPIDEMIOLOGY; CARCINOMA; CANCER AB Aims: Oesophageal epidermoid metaplasia is defined by a dense granular layer with overlying hyperorthokeratosis, resembling the epidermis of skin. A possible association between epidermoid metaplasia, squamous dysplasia and squamous cell carcinoma has been proposed. The aim of this study was to compare the prevalence of epidermoid metaplasia in patients with oesophageal squamous neoplasms with that in a control cohort. Methods and results: Medical records and slides from 1048 consecutive oesophageal biopsies and resections for any indication and 58 patients with oesophageal squamous neoplasms were reviewed. Two cases (0.19%) of epidermoid metaplasia were identified in the 1048-patient control group. The prevalence of epidermoid metaplasia was significantly higher (P<0.05) in the 58 patients with oesophageal squamous neoplasms, two of whom (3.5%) had concurrent epidermoid metaplasia (odds ratio 18.1, 95% confidence interval 2.5-131). One case was associated with a verrucous carcinoma and the other with a well-differentiated, superficial (pT1), exophytic squamous cell carcinoma. No patients had epidermoid metaplasia in a biopsy prior to the diagnosis of squamous neoplasia. Conclusions: The increased prevalence of epidermoid metaplasia observed in patients with squamous neoplasms provides some additional support for the proposed association. The hypothesis that epidermoid metaplasia is a precursor to squamous neoplasms remains unproven. C1 [Cottreau, Jonathan; Gruchy, Steven; Arnason, Thomas] Dalhousie Univ, Sch Med, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada. [Gruchy, Steven] Queen Elizabeth 2 Hlth Sci Ctr, Div Gastroenterol, Halifax, NS, Canada. [Kamionek, Michal] Carolinas Pathol Grp, Charlotte, NC USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arnason, Thomas] Queen Elizabeth 2 Hlth Sci Ctr, Div Anat Pathol, 734a MacKenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. RP Arnason, T (reprint author), Queen Elizabeth 2 Hlth Sci Ctr, Div Anat Pathol, 734a MacKenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada.; Arnason, T (reprint author), Dalhousie Univ, 734a MacKenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. EM thomas.arnason@nshealth.ca FU Dalhousie Medical Research Foundation (DMRF) FX J. Cottreau received funding for his summer research work from the Dalhousie Medical Research Foundation (DMRF) Music-in-Medicine Summer Studentship as part of the Research in Medicine program. NR 13 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 EI 1365-2559 J9 HISTOPATHOLOGY JI Histopathology PD JUN PY 2016 VL 68 IS 7 BP 988 EP 995 DI 10.1111/his.12886 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DQ1BG UT WOS:000378935100004 PM 26426946 ER PT J AU Chevalier, FD Le Clech, W Eng, N Rugel, AR de Assis, RR Oliveira, G Holloway, SP Cao, XH Hart, PJ LoVerde, PT Anderson, TJC AF Chevalier, Frederic D. Le Clech, Winka Eng, Nina Rugel, Anastasia R. de Assis, Rafael Ramiro Oliveira, Guilherme Holloway, Stephen P. Cao, Xiaohang Hart, P. John LoVerde, Philip T. Anderson, Timothy J. C. TI Independent origins of loss-of-function mutations conferring oxamniquine resistance in a Brazilian schistosome population SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Schistosoma mansoni; Oxamniquine resistance; Sulfotransferase; Loss-of-function; Biochemical assay; Soft selective event ID GENETIC COMPLEMENTATION ANALYSIS; NUCLEOTIDE SUBSTITUTIONS; HYCANTHONE RESISTANCE; CLINICAL-TRIALS; DISEASE-CONTROL; MANSONI; DNA; COMBINATION; ATOVAQUONE; STANDARD AB Molecular surveillance provides a powerful approach to monitoring the resistance status of parasite populations in the field and for understanding resistance evolution. Oxamniquine was used to treat Brazilian schistosomiasis patients (mid-1970s to mid-2000s) and several cases of parasite infections resistant to treatment were recorded. The gene underlying resistance (SmSULT-OR) encodes a sulfotransferase required for intracellular drug activation. Resistance has a recessive basis and occurs when both SmSULT-OR alleles encode for defective proteins. Here we examine SmSULT-OR sequence variation in a natural schistosome population in Brazil similar to 40 years after the first use of this drug. We sequenced SmSULT-OR from 189 individual miracidia (1-11 per patient) recovered from 49 patients, and tested proteins expressed from putative resistance alleles for their ability to activate oxamniquine. We found nine mutations (four non-synonymous single nucleotide polymorphisms, three non-coding single nucleotide polymorphisms and two indels). Both mutations (p.E142del and p.C35R) identified previously were recovered in this field population. We also found two additional mutations (a splice site variant and 1 bp coding insertion) predicted to encode non-functional truncated proteins. Two additional substitutions (p.G206V, p.N215Y) tested had no impact on oxamniquine activation. Three results are of particular interest: (i) we recovered the p.E142del mutation from the field: this same deletion is responsible for resistance in an oxamniquine selected laboratory parasite population; (ii) frequencies of resistance alleles are extremely low (0.27-0.8%), perhaps due to fitness costs associated with carriage of these alleles; (iii) that four independent resistant alleles were found is consistent with the idea that multiple mutations can generate loss-of-function alleles. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. C1 [Chevalier, Frederic D.; Le Clech, Winka; Eng, Nina; Anderson, Timothy J. C.] Texas Biomed Res Inst, Dept Genet, POB 760549, San Antonio, TX 78245 USA. [Rugel, Anastasia R.; Holloway, Stephen P.; Cao, Xiaohang; Hart, P. John; LoVerde, Philip T.] Univ Texas Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. [Rugel, Anastasia R.; Holloway, Stephen P.; Cao, Xiaohang; Hart, P. John; LoVerde, Philip T.] Univ Texas Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. [de Assis, Rafael Ramiro; Oliveira, Guilherme] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Ave Augusta Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil. [Oliveira, Guilherme] Vale Inst Technol, Rua Boaventura da Silva 955, BR-66055090 Belem, Para, Brazil. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. RP Chevalier, FD; Anderson, TJC (reprint author), Texas Biomed Res Inst, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM fcheval@txbiomed.org; tanderso@txbiomed.org OI CHEVALIER, Frederic/0000-0003-2611-8106; Oliveira, Guilherme/0000-0003-0054-3438 FU NIH [R01-A1097576, 1R01A1115691, P50 AI 098507]; World Health Organization [HQNTD1206356]; UTHSCSA Presidents Collaborative Research Fund; Robert A. Welch Foundation [AQ-1399]; National Center for Research Resources (NIH) [C06 RR013556]; ATT Foundation; National Center for Research Resources Grant [S10 RR029392]; University of Texas Health Science Center, San Antonio; Office of the Vice President for Research; San Antonio Cancer Institute [P30 CA054174]; Texas Biomedical Research Institute; City of San Antonio Summer Ambassador Program; CNPq [168260/2014-0, 309312/20124]; CAPES [070/13, REDE 21/2015]; FAPEMIG [RED-00014-14, PPM-00439-10] FX This study was supported by NIH grants [R01-A1097576 (T.J.C. A.), 1R01A1115691 and P50 AI 098507 (P.T.L./P.J.H.)], World Health Organization [HQNTD1206356 (P.T.L.)], the UTHSCSA Presidents Collaborative Research Fund (P.T.L./P.J.H.) and the Robert A. Welch Foundation [AQ-1399 (P.J.H.)]. The molecular work at TBRI was conducted in facilities constructed with support from Research Facilities Improvement Program Grant (C06 RR013556) from the National Center for Research Resources (NIH). The AT&T Genomics Computing Center supercomputing facilities were supported by the AT&T Foundation and the National Center for Research Resources Grant (S10 RR029392). The X-ray Crystallography Core Laboratory is supported by the University of Texas Health Science Center, San Antonio, Office of the Vice President for Research and by the San Antonio Cancer Institute Grant (P30 CA054174). W.L was supported by a Cowles fellowship from Texas Biomedical Research Institute. N.E. was supported by the City of San Antonio Summer Ambassador Program. R.R.A. received support from CNPq (168260/2014-0). G.O. received support from CNPq (309312/20124), CAPES (070/13, REDE 21/2015) and FAPEMIG (RED-00014-14, PPM-00439-10). We thank Guilherme Oliveira, Dr. Fernanda Ludolf Ribeiro, Maycon Bruno and Nilvande Ferreira for technical assistance during stool processing and miracidia sampling, Dr. Andrea Gazzinelli and Dr. Leonardo Matoso for stool sampling at Ponto dos Volantes, Dr. Ricardo Toshio Fujiwara at Universidade Federal de Minas Gerais and Dr. Rodrigo Correa -Oliveira at Centro de Pesquisas Rene Rachou for providing laboratory space for stool processing and miracidia sampling, and Joanne Curran for use of a capillary sequencer. NR 44 TC 1 Z9 1 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-7519 EI 1879-0135 J9 INT J PARASITOL JI Int. J. Parasit. PD JUN PY 2016 VL 46 IS 7 BP 417 EP 424 DI 10.1016/j.ijpara.2016.03.006 PG 8 WC Parasitology SC Parasitology GA DQ1NV UT WOS:000378968600007 PM 27073078 ER PT J AU So, WKW Cummings, GG de Calvo, LEA Day, SW Houlahan, K Nevidjon, BM Schneider, J Teahon, M Were, PA AF So, Winnie K. W. Cummings, Greta G. de Calvo, Luz E. Ayala Day, Sara W. Houlahan, Kathy Nevidjon, Brenda M. Schneider, Julie Teahon, Marina Were, Pamela A. TI Enhancement of oncology nursing education in low- and middle-income countries: Challenges and strategies SO JOURNAL OF CANCER POLICY LA English DT Article DE Low- and middle-income countries; Cancer burden; Oncology nursing; Continuing education ID INTERNATIONAL BREAST HEALTH; PEDIATRIC ONCOLOGY; CANCER CARE; NURSES; PROGRAM; ENVIRONMENTS; EXPERIENCE; KNOWLEDGE; OUTCOMES; LESSONS AB Cancer prevalence is estimated to increase in low- and middle-income countries (LMICs) in the coming years, imposing a significant burden on these countries. Therefore, an effective oncology nursing workforce will become increasingly important. Previous studies have suggested that advances in oncology nursing education may contribute to both a reduction of the current cancer burden and improved patient outcomes. However, such education in LMICs is comparatively underdeveloped. Contributing to this phenomenon are the lack of educational pathways and legislation for mandatory training of nurses to specialize in oncology, insufficient opportunities for continuing education and inadequate time for nurses to undertake training. Therefore, strategies need to be developed and implemented to enhance oncology nursing education in LMICs. We discuss the challenges currently faced by LMICs in implementing effective oncology nursing training, and suggests recommended strategies to address these challenges. (C) 2016 Elsevier Ltd. All rights reserved. C1 [So, Winnie K. W.] Chinese Univ Hong Kong, Nethersole Sch Nursing, Shatin, Hong Kong, Peoples R China. [Cummings, Greta G.] Univ Alberta, Fac Nursing, Edmonton, AB, Canada. [de Calvo, Luz E. Ayala] AEOC, Colombian Oncol Nursing Assoc, Bogota, Colombia. [Day, Sara W.] St Jude Childrens Res Hosp, Memphis, TN USA. [Houlahan, Kathy] Dana Farber Canc Inst, Boston, MA USA. [Nevidjon, Brenda M.] Oncol Nursing Soc, Pittsburgh, PA USA. [Schneider, Julie] Dept Hlth & Human Serv, Washington, DC USA. [Teahon, Marina] Union Int Canc Control, Geneva, Switzerland. [Were, Pamela A.] Moi Univ, Sch Med, Dept Child Hlth & Paediat, Eldoret, Kenya. RP So, WKW (reprint author), Chinese Univ Hong Kong, Nethersole Sch Nursing, Shatin, Hong Kong, Peoples R China. EM winnieso@cuhk.edu.hk; gretac@ualberta.ca; leayalace@yahoo.com; sara.day@stjude.org; Kathleen.houlahan@childrens.harvard.edu; brenda.nevidjon@duke.edu; julie.schneider@hhs.gov; teahon@uicc.org; aki_otieno2@yahoo.co.uk NR 61 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-5383 J9 J Cancer Policy JI J. CANCER POLICY PD JUN PY 2016 VL 8 BP 10 EP 16 DI 10.1016/j.jcpo.2016.03.002 PG 7 WC Health Policy & Services SC Health Care Sciences & Services GA DQ5NT UT WOS:000379252800004 ER PT J AU Scott, A Rouch, JD Jabaji, Z Khalil, HA Solorzano, S Lewis, M Martin, MG Stelzner, MG Dunn, JCY AF Scott, Andrew Rouch, Joshua D. Jabaji, Ziyad Khalil, Hassan A. Solorzano, Sergio Lewis, Michael Martin, Martin G. Stelzner, Matthias G. Dunn, James C. Y. TI Long-term renewable human intestinal epithelial stem cells as monolayers: A potential for clinical use SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Section-on-Surgery of the American-Academy-of-Pediatrics CY OCT 23-25, 2015 CL Washington, DC SP Amer Acad Pediat, Sect Surg DE Human intestinal epithelial stem cells; Monolayers; Differentiation; Type I collagen; Human laminin; Spheroids; Enteroids; In vitro culture ID IN-VITRO; CULTURE-SYSTEM; GROWTH-FACTORS; SELF-RENEWAL; ORGANOIDS; TISSUE; COLON; DIFFERENTIATION; EXPANSION; NICHE AB Purpose: Current culture schema for human intestinal stem cells (hISCs) frequently rely on a 3D culture system using Matrigel (TM), a laminin-rich matrix derived from murine sarcoma that is not suitable for clinical use. We have developed a novel 2D culture system for the in vitro expansion of hISCs as an intestinal epithelial monolayer without the use of Matrigel. Methods: Cadaveric duodenal samples were processed to isolate intestinal crypts from the mucosa. Crypts were cultured on a thin coat of type I collagen or laminin. Intestinal epithelial monolayers were supported with growth factors to promote self-renewal or differentiation of the hISCs. Proliferating monolayers were sub-cultured every 4-5 days. Results: Intestinal epithelial monolayers were capable of long-term cell renewal. Less differentiated monolayers expressed high levels of gene marker LGR5, while more differentiated monolayers had higher expressions of CDX2, MUC2, LYZ, DEF5, and CHGA. Furthermore, monolayers were capable of passaging into a 3D culture system to generate spheroids and enteroids. Conclusion: This 2D system is an important step to expand hISCs for further experimental studies and for clinical cell transplantation. (C) 2016 Elsevier Inc. All rights reserved. C1 [Scott, Andrew; Rouch, Joshua D.; Jabaji, Ziyad; Khalil, Hassan A.; Dunn, James C. Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Pediat Surg, Los Angeles, CA 90095 USA. [Solorzano, Sergio; Martin, Martin G.] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Gastroenterol & Nutr, Dept Pediat, Los Angeles, CA USA. [Solorzano, Sergio; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Martin, Martin G.; Dunn, James C. Y.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA. [Lewis, Michael] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. [Stelzner, Matthias G.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Dunn, James C. Y.] Univ Calif Los Angeles, Sch Engn, Dept Bioengn, Los Angeles, CA USA. RP Dunn, JCY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Surg, Box 709818, Los Angeles, CA 90095 USA. EM jdunn@mednet.ucla.edu OI Khalil, Hassan/0000-0002-3835-1290 FU NIDDK NIH HHS [P30 DK041301, R01 DK083319, R01 DK083762, U01 DK085535] NR 31 TC 1 Z9 1 U1 2 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 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUN PY 2016 VL 51 IS 6 BP 995 EP 1000 DI 10.1016/j.jpedsurg.2016.02.074 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA DQ0RW UT WOS:000378908600025 PM 26995514 ER PT J AU Saxena, V Koraishy, FM Sise, ME Lim, JK Schmidt, M Chung, RT Liapakis, A Nelson, DR Fried, MW Terrault, NA AF Saxena, Varun Koraishy, Farrukh M. Sise, Meghan E. Lim, Joseph K. Schmidt, Monica Chung, Raymond T. Liapakis, Annmarie Nelson, David R. Fried, Michael W. Terrault, Norah A. CA HCV-TARGET TI Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function SO LIVER INTERNATIONAL LA English DT Article DE decompensated cirrhosis; haemodialysis; liver transplantation; sustained virologic response ID LIVER-TRANSPLANTATION; SIMEPREVIR; RIBAVIRIN; THERAPY; COMBINATION; TELAPREVIR; CIRRHOSIS; DISEASE AB Background & Aims: Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). Methods: HCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort. Results: A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR <= 45 (18 with eGFR <= 30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2). Patients with baseline eGFR <= 45 vs. >45 differed in being female (55% vs. 36%), age >= 65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR <= 45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR <= 45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR <= 30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes. Conclusions: Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR <= 45 ml/min/1.73 m(2)) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens. C1 [Saxena, Varun; Terrault, Norah A.] Univ Calif San Francisco, Box 0538,513 Parnassus Ave,S357, San Francisco, CA 94143 USA. [Koraishy, Farrukh M.] St Louis Univ, Sch Med, St Louis, MO USA. [Sise, Meghan E.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lim, Joseph K.; Liapakis, Annmarie] Yale Univ, Sch Med, New Haven, CT USA. [Schmidt, Monica; Fried, Michael W.] Univ N Carolina, Chapel Hill, NC USA. [Nelson, David R.] Univ Florida, Gainesville, FL USA. RP Terrault, NA (reprint author), Univ Calif San Francisco, Box 0538,513 Parnassus Ave,S357, San Francisco, CA 94143 USA. EM norah.terrault@ucsf.edu FU University of Florida, Gainesville, FL; University of North Carolina at Chapel Hill, Chapel Hill, NC; AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Kadmon; Merck; Vertex; CTSA [UF UL1TR000064]; NIH Mid-Career Mentoring Award [K24 DK066144]; NIH [T32 DK060414] FX HCV-TARGET is an investigator-initiated study jointly sponsored by The University of Florida, Gainesville, FL (PI: Nelson), and The University of North Carolina at Chapel Hill, Chapel Hill, NC (PI: Fried). It was funded in part by AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Kadmon, Merck, and Vertex. Funded in part by CTSA UF UL1TR000064. Dr Fried was funded in part by NIH Mid-Career Mentoring Award K24 DK066144. The author V. S. was supported in part by an NIH-funded postdoctoral research training program grant (T32 DK060414). N. T. is UCSF Liver Center member (NIH P30 DK 026743). NR 22 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD JUN PY 2016 VL 36 IS 6 BP 807 EP 816 DI 10.1111/liv.13102 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ3EG UT WOS:000379085000007 PM 26923436 ER PT J AU Eftekharzadeh, B Hyman, BT Wegmann, S AF Eftekharzadeh, Bahareh Hyman, Bradley T. Wegmann, Susanne TI Structural studies on the mechanism of protein aggregation in age related neurodegenerative diseases SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Neurodegenerative diseases; Amyloid-like proteins; Oligomers; Aggregates; Aging ID AMYOTROPHIC-LATERAL-SCLEROSIS; INTRINSICALLY DISORDERED PROTEINS; ALPHA-SYNUCLEIN OLIGOMERS; PAIRED HELICAL FILAMENTS; BETA-AMYLOID FIBRILS; C-TERMINAL FRAGMENTS; CONTAINING HUNTINGTIN FRAGMENTS; CU,ZN SUPEROXIDE-DISMUTASE; GAIN-OF-FUNCTION; SOLID-STATE NMR AB The progression of many neurodegenerative diseases is assumed to be caused by misfolding of specific characteristic diseases related proteins, resulting in aggregation and fibril formation of these proteins. Protein misfolding associated age related diseases, although different in disease manifestations, share striking similarities. In all cases, one disease protein aggregates and loses its function or additionally shows a toxic gain of function. However, the clear link between these individual amyloid-like protein aggregates and cellular toxicity is often still uncertain. The similar features of protein misfolding and aggregation in this group of proteins, all involved in age related neurodegenerative diseases, results in high interest in characterization of their structural properties. We review here recent findings on structural properties of some age related disease proteins, in the context of their biological importance in disease. Published by Elsevier Ireland Ltd C1 [Eftekharzadeh, Bahareh] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Eftekharzadeh, B (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM beftekharzadeh@mgh.harvard.edu NR 269 TC 1 Z9 2 U1 8 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUN PY 2016 VL 156 BP 1 EP 13 DI 10.1016/j.mad.2016.03.001 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DQ1JT UT WOS:000378958000001 PM 27005270 ER PT J AU Carter, DR Sutton, SK Pajic, M Murray, J Sekyere, EO Fletcher, J Beckers, A De Preter, K Speleman, F George, RE Haber, M Norris, MD Cheung, BB Marshall, GM AF Carter, Daniel R. Sutton, Selina K. Pajic, Marina Murray, Jayne Sekyere, Eric O. Fletcher, Jamie Beckers, Anneleen De Preter, Katleen Speleman, Frank George, Rani E. Haber, Michelle Norris, Murray D. Cheung, Belamy B. Marshall, Glenn M. TI Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis SO MOLECULAR ONCOLOGY LA English DT Article DE Neuroblastoma; MYCN; Glutathione; Metabolomics; Tumorigenesis; BSO ID MULTIDRUG-RESISTANCE; N-MYC; CHILDHOOD NEUROBLASTOMA; GLUTAMINE-METABOLISM; OXIDATIVE STRESS; CANCER; EXPRESSION; CELLS; AMPLIFICATION; INHIBITION AB The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease. Crown Copyright (C) 2016 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. All rights reserved. C1 [Carter, Daniel R.; Sutton, Selina K.; Murray, Jayne; Fletcher, Jamie; Haber, Michelle; Norris, Murray D.; Cheung, Belamy B.; Marshall, Glenn M.] Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst, Randwick, NSW 2031, Australia. [Carter, Daniel R.; Cheung, Belamy B.] UNSW Australia, Sch Womens & Childrens Hlth, Randwick, NSW 2031, Australia. [Pajic, Marina] Univ New S Wales, Garvan Inst Med Res, Canc Div, Kinghorn Canc Ctr, 384 Victoria St, Sydney, NSW 2010, Australia. [Pajic, Marina] Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW 2010, Australia. [Sekyere, Eric O.] Endeavour Coll Nat Hlth, Sydney, NSW 2000, Australia. [Beckers, Anneleen; De Preter, Katleen; Speleman, Frank] Univ Ghent, Ctr Med Genet CMGG, Med Res Bldg MRB1,De Pintelaan 185, B-9000 Ghent, Belgium. [George, Rani E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA USA. [George, Rani E.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Norris, Murray D.] Univ New S Wales, Ctr Childhood Canc Res, Randwick, NSW 2031, Australia. [Marshall, Glenn M.] Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW 2031, Australia. RP Cheung, BB; Marshall, GM (reprint author), Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst, Randwick, NSW 2031, Australia. EM BCheung@ccia.unsw.edu.au; g.marshall@unsw.edu.au FU Balnaves Foundation Young Researchers Fund; NHMRC Australia [APP1016699]; Cancer Institute NSW [10/TPG/1-03]; Cancer Council NSW [PG-11-06] FX This work was supported by a Project grant from The Balnaves Foundation Young Researchers Fund and Program Grants from the NHMRC Australia (grant number APP1016699); Cancer Institute NSW (grant number 10/TPG/1-03); and Cancer Council NSW (grant numbers PG-11-06). NR 46 TC 0 Z9 1 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD JUN PY 2016 VL 10 IS 6 BP 866 EP 878 DI 10.1016/j.molonc.2016.02.004 PG 13 WC Oncology SC Oncology GA DQ7FJ UT WOS:000379372000007 PM 26996379 ER PT J AU He, LL de Val, N Morris, CD Vora, N Thinnes, TC Kong, L Azadnia, P Sok, D Zhou, B Burton, DR Wilson, IA Nemazee, D Ward, AB Zhu, J AF He, Linling de Val, Natalia Morris, Charles D. Vora, Nemil Thinnes, Therese C. Kong, Leopold Azadnia, Parisa Sok, Devin Zhou, Bin Burton, Dennis R. Wilson, Ian A. Nemazee, David Ward, Andrew B. Zhu, Jiang TI Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles SO NATURE COMMUNICATIONS LA English DT Article ID VIRUS-LIKE PARTICLES; BROADLY NEUTRALIZING ANTIBODIES; ENV TRIMERS; ENVELOPE TRIMER; VACCINE DESIGN; POTENT NEUTRALIZATION; GP41-GP120 INTERFACE; DEPENDENT EPITOPE; CRYSTAL-STRUCTURE; RESPONSES AB Structures of BG505 SOSIP. 664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development. C1 [He, Linling; Morris, Charles D.; Vora, Nemil; Thinnes, Therese C.; Azadnia, Parisa; Sok, Devin; Burton, Dennis R.; Nemazee, David; Zhu, Jiang] Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. [de Val, Natalia; Kong, Leopold; Wilson, Ian A.; Ward, Andrew B.; Zhu, Jiang] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [de Val, Natalia; Kong, Leopold; Sok, Devin; Burton, Dennis R.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [de Val, Natalia; Kong, Leopold; Sok, Devin; Burton, Dennis R.; Wilson, Ian A.; Ward, Andrew B.] Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA. [de Val, Natalia; Kong, Leopold; Sok, Devin; Burton, Dennis R.; Wilson, Ian A.; Ward, Andrew B.; Zhu, Jiang] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA. [Zhou, Bin] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA. [Wilson, Ian A.] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Zhu, J (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.; Ward, AB; Zhu, J (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.; Ward, AB (reprint author), Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.; Ward, AB; Zhu, J (reprint author), Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA.; Ward, AB; Zhu, J (reprint author), Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA. EM abward@scripps.edu; jiang@scripps.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU International AIDS Vaccine Initiative Neutralizing Antibody Center; CAVD; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [CHAVI-ID UM1 AI00663]; HIV Vaccine Research and Design (HIVRAD) programme [P01 AI110657]; Joint Center of Structural Genomics (JCSG) - NIH NIGMS, Protein Structure Initiative [U54 GM094586, AI073148, AI084817] FX EM data were collected at the Scripps Research Institute EM Facility. This work was supported by the International AIDS Vaccine Initiative Neutralizing Antibody Center and CAVD, by the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID UM1 AI00663) (A.B.W., I.A.W. and J.Z.), by the HIV Vaccine Research and Design (HIVRAD) programme (P01 AI110657) (A.B.W. and I.A.W.), by the Joint Center of Structural Genomics (JCSG) funded by the NIH NIGMS, Protein Structure Initiative (U54 GM094586) (I.A.W.), AI073148 (D.N.) and AI084817 (I.A.W. and A.B.W.). NR 69 TC 7 Z9 7 U1 12 U2 30 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 JUN PY 2016 VL 7 AR 12041 DI 10.1038/ncomms12041 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3OG UT WOS:000379111000001 PM 27349934 ER PT J AU Hong, AL Tseng, YY Cowley, GS Jonas, O Cheah, JH Kynnap, BD Doshi, MB Oh, C Meyer, SC Church, AJ Gill, S Bielski, CM Keskula, P Imamovic, A Howell, S Kryukov, GV Clemons, PA Tsherniak, A Vazquez, F Crompton, BD Shamji, AF Rodriguez-Galindo, C Janeway, KA Roberts, CWM Stegmaier, K van Hummelen, P Cima, MJ Langer, RS Garraway, LA Schreiber, SL Root, DE Hahn, WC Boehm, JS AF Hong, Andrew L. Tseng, Yuen-Yi Cowley, Glenn S. Jonas, Oliver Cheah, Jaime H. Kynnap, Bryan D. Doshi, Mihir B. Oh, Coyin Meyer, Stephanie C. Church, Alanna J. Gill, Shubhroz Bielski, Craig M. Keskula, Paula Imamovic, Alma Howell, Sara Kryukov, Gregory V. Clemons, Paul A. Tsherniak, Aviad Vazquez, Francisca Crompton, Brian D. Shamji, Alykhan F. Rodriguez-Galindo, Carlos Janeway, Katherine A. Roberts, Charles W. M. Stegmaier, Kimberly van Hummelen, Paul Cima, Michael J. Langer, Robert S. Garraway, Levi A. Schreiber, Stuart L. Root, David E. Hahn, William C. Boehm, Jesse S. TI Integrated genetic and pharmacologic interrogation of rare cancers SO NATURE COMMUNICATIONS LA English DT Article ID CELL-LINES; SEQUENCING DATA; SENSITIVITY; TUMORS; DEPENDENCIES; MODELS; TARGET AB Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma. Here, we confirm that this cell line recapitulates the histology and harbours the majority of the somatic genetic alterations found in a metastatic lesion isolated at first relapse. We then perform pooled CRISPR-Cas9 and RNAi loss-of-function screens and a small-molecule screen focused on druggable cancer targets. Integrating these three complementary and orthogonal methods, we identify CDK4 and XPO1 as potential therapeutic targets in this cancer, which has no known alterations in these genes. These observations establish an approach that integrates new patient-derived models, functional genomics and chemical screens to facilitate the discovery of targets in rare cancers. C1 [Hong, Andrew L.; Meyer, Stephanie C.; Church, Alanna J.; Crompton, Brian D.; Rodriguez-Galindo, Carlos; Janeway, Katherine A.; Roberts, Charles W. M.; Stegmaier, Kimberly] Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. [Hong, Andrew L.; Kynnap, Bryan D.; Doshi, Mihir B.; Meyer, Stephanie C.; Imamovic, Alma; Crompton, Brian D.; Rodriguez-Galindo, Carlos; Janeway, Katherine A.; Roberts, Charles W. M.; Stegmaier, Kimberly; Garraway, Levi A.; Hahn, William C.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Hong, Andrew L.; Tseng, Yuen-Yi; Cowley, Glenn S.; Doshi, Mihir B.; Oh, Coyin; Gill, Shubhroz; Bielski, Craig M.; Keskula, Paula; Imamovic, Alma; Howell, Sara; Kryukov, Gregory V.; Clemons, Paul A.; Tsherniak, Aviad; Vazquez, Francisca; Shamji, Alykhan F.; Stegmaier, Kimberly; Garraway, Levi A.; Schreiber, Stuart L.; Root, David E.; Hahn, William C.; Boehm, Jesse S.] Harvard & MIT, Broad Inst, 415 Main St, Cambridge, MA 02142 USA. [Jonas, Oliver; Cheah, Jaime H.; Cima, Michael J.; Langer, Robert S.] MIT, Koch Inst Integrat Canc Res, 500 Main St, Cambridge, MA 02139 USA. [Kryukov, Gregory V.; Garraway, Levi A.; Hahn, William C.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Garraway, Levi A.; Schreiber, Stuart L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Cowley, Glenn S.; Bielski, Craig M.; Rodriguez-Galindo, Carlos; Roberts, Charles W. M.] Janssen R&D J&J, Discovery Sci, 1400 McKean Rd, Spring House, PA 19477 USA. [Bielski, Craig M.] Mem Sloan Kettering Canc Ctr, 417 E 68th St, New York, NY 10065 USA. [Rodriguez-Galindo, Carlos; Roberts, Charles W. M.] St Jude Childrens Res Hosp, 262 Danny Thomas Pl, Memphis, TN 38120 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Hahn, WC; Boehm, JS (reprint author), Harvard & MIT, Broad Inst, 415 Main St, Cambridge, MA 02142 USA.; Hahn, WC (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu; boehm@broadinstitute.org OI Hong, Andrew/0000-0003-0374-1667; Oh, Coyin/0000-0002-5732-3471 FU Merkin Family Foundation; NCI [U01 CA176058, U01 CA176152]; NIH [T32 CA136432, K12 HD052896-08, R25 CA174650-01A1]; CureSearch for Children's Cancer; Pedals for Pediatrics; Friends of Dana-Farber FX We thank Rebecca Modiste and Prafulla Gokhale from the Belfer Institute for Applied Cancer Science for performing the tolerability and efficacy in vivo studies. We thank Tamara Mason, Sara Seepo and Adam Tracy in coordinating and sequencing these samples. We thank the Hahn lab, Boehm lab, Cichowski lab, Keith Ligon, Rosalind Segal, David Kwiatkowski, Rameen Beroukhim, Lisa Diller and Stephen Sallan for critical discussions and/or reading of the manuscript. This work was supported in part by the Merkin Family Foundation (JSB), NCI U01 CA176058 (WCH), NCI U01 CA176152 (SLS), NIH T32 CA136432 (ALH), CureSearch for Children's Cancer (ALH), NIH K12 HD052896-08 (ALH), Pedals for Pediatrics (ALH), Friends of Dana-Farber (ALH) and NIH R25 CA174650-01A1 (BDK). NR 39 TC 2 Z9 2 U1 5 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2016 VL 7 AR 11987 DI 10.1038/ncomms11987 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3GA UT WOS:000379089600001 PM 27329820 ER PT J AU Kong, L He, LL de Val, N Vora, N Morris, CD Azadnia, P Sok, D Zhou, B Burton, DR Ward, AB Wilson, IA Zhu, J AF Kong, Leopold He, Linling de Val, Natalia Vora, Nemil Morris, Charles D. Azadnia, Parisa Sok, Devin Zhou, Bin Burton, Dennis R. Ward, Andrew B. Wilson, Ian A. Zhu, Jiang TI Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability SO NATURE COMMUNICATIONS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRYO-EM STRUCTURE; BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; ENV TRIMERS; GP41-GP120 INTERFACE; VACCINE DEVELOPMENT; DEPENDENT EPITOPE; GLYCOPROTEIN AB The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains. C1 [Kong, Leopold; de Val, Natalia; Ward, Andrew B.; Wilson, Ian A.; Zhu, Jiang] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Kong, Leopold; de Val, Natalia; Sok, Devin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Kong, Leopold; de Val, Natalia; Sok, Devin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA. [Kong, Leopold; de Val, Natalia; Sok, Devin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Zhu, Jiang] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA. [He, Linling; Vora, Nemil; Morris, Charles D.; Azadnia, Parisa; Sok, Devin; Burton, Dennis R.; Zhu, Jiang] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Zhou, Bin] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Wilson, Ian A.] Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Wilson, IA; Zhu, J (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.; Wilson, IA (reprint author), Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.; Wilson, IA (reprint author), Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA.; Wilson, IA; Zhu, J (reprint author), Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.; Zhu, J (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.; Wilson, IA (reprint author), Scripps Res Inst, Joint Ctr Struct Genom, La Jolla, CA 92037 USA.; Wilson, IA (reprint author), Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. EM wilson@scripps.edu; jiang@scripps.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; DOE Office of Biological and Environmental Research; NIH, National Institute of General Medical Sciences [P41GM103393]; National Center for Research Resources [P41RR001209]; International AIDS Vaccine Initiative Neutralizing Antibody Center; CAVD [OPP1084519, OPP1115782]; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [CHAVI-ID UM1 AI100663]; HIV Vaccine Research and Design (HIVRAD) programme [P01 AI110657]; Joint Center of Structural Genomics (JCSG) - NIH NIGMS, Protein Structure Initiative [U54 GM094586]; American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research; [AI084817] FX We are very grateful to R. Stanfield for helpful discussions, M. Elsliger for computer support and H. Tien for crystallization screening; X-ray data sets were collected at the Advanced Photon Source (APS) beamline 23ID-B and Stanford Synchrotron Radiation Lightsource (SSRL) BL12-2. Use of the APS was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357. SSRL is a Directorate of SLAC National Accelerator Laboratory and an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Stanford University. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the NIH, National Institute of General Medical Sciences (including P41GM103393) and the National Center for Research Resources (P41RR001209). Electron microscopy data were collected at the Scripps Research Institute EM Facility. This work was supported by the International AIDS Vaccine Initiative Neutralizing Antibody Center and CAVD (OPP1084519 and OPP1115782), by the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID UM1 AI100663) (A.B.W., I.A.W., J.Z. and D.R.B.), by the HIV Vaccine Research and Design (HIVRAD) programme (P01 AI110657) (A.B.W. and I.A.W.), by the Joint Center of Structural Genomics (JCSG) funded by the NIH NIGMS, Protein Structure Initiative (U54 GM094586) (I.A.W.), and AI084817 (I.A.W., A.B.W.). A portion of this work was supported by an American Foundation for AIDS Research Mathilde Krim Fellowship in Basic Biomedical Research (L.K.). NR 67 TC 6 Z9 6 U1 4 U2 9 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 JUN PY 2016 VL 7 AR 12040 DI 10.1038/ncomms12040 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3OF UT WOS:000379110900001 PM 27349805 ER PT J AU Mirzamohammadi, F Papaioannou, G Inloes, JB Rankin, EB Xie, HF Schipani, E Orkin, SH Kobayashi, T AF Mirzamohammadi, Fatemeh Papaioannou, Garyfallia Inloes, Jennifer B. Rankin, Erinn B. Xie, Huafeng Schipani, Ernestina Orkin, Stuart H. Kobayashi, Tatsuya TI Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-beta signalling SO NATURE COMMUNICATIONS LA English DT Article ID EMBRYONIC STEM-CELLS; ENDOCHONDRAL BONE; CHONDROCYTE DIFFERENTIATION; DEVELOPMENTAL REGULATORS; CONSTITUTIVE ACTIVATION; TRANSGENIC MICE; SELF-RENEWAL; II RECEPTOR; EZH2; CARTILAGE AB Polycomb repressive complex 2 (PRC2) controls maintenance and lineage determination of stem cells by suppressing genes that regulate cellular differentiation and tissue development. However, the role of PRC2 in lineage-committed somatic cells is mostly unknown. Here we show that Eed deficiency in chondrocytes causes severe kyphosis and a growth defect with decreased chondrocyte proliferation, accelerated hypertrophic differentiation and cell death with reduced Hif1a expression. Eed deficiency also causes induction of multiple signalling pathways in chondrocytes. Wnt signalling overactivation is responsible for the accelerated hypertrophic differentiation and kyphosis, whereas the overactivation of TGF-beta signalling is responsible for the reduced proliferation and growth defect. Thus, our study demonstrates that PRC2 has an important regulatory role in lineage-committed tissue cells by suppressing overactivation of multiple signalling pathways. C1 [Mirzamohammadi, Fatemeh; Papaioannou, Garyfallia; Inloes, Jennifer B.; Kobayashi, Tatsuya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. [Rankin, Erinn B.] Stanford Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Ctr Clin Sci Res, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. [Xie, Huafeng; Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. [Schipani, Ernestina] Univ Michigan, Sch Med, Dept Orthopaed Surg, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RP Kobayashi, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM tkobayashi1@mgh.harvard.edu FU National Institutes of Health [AR056645]; Harvard Stem Cell Institute [SG-0090-13] FX We thank BIDMC Genomics and Proteomics Center for microarray analysis, Otogenetics for ChIP-seq analysis and the Center for Skeletal Research Core (NIH P30 AR066261) for histological analysis. This work was supported by the National Institutes of Health (AR056645 to T.K.) and Harvard Stem Cell Institute (SG-0090-13 to T.K.). NR 56 TC 1 Z9 1 U1 3 U2 3 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 JUN PY 2016 VL 7 AR 12047 DI 10.1038/ncomms12047 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3GZ UT WOS:000379092100001 PM 27329220 ER PT J AU Montelongo, Y Yetisen, AK Butt, H Yun, SH AF Montelongo, Yunuen Yetisen, Ali K. Butt, Haider Yun, Seok-Hyun TI Reconfigurable optical assembly of nanostructures SO NATURE COMMUNICATIONS LA English DT Article ID REFRACTIVE-INDEX; STANDING-WAVE; LASER; THERMOPHORESIS; NANOPARTICLES; METAMATERIAL; TRANSPORT; HOLOGRAMS; NANORODS; FORCES AB Arrangements of nanostructures in well-defined patterns are the basis of photonic crystals, metamaterials and holograms. Furthermore, rewritable optical materials can be achieved by dynamically manipulating nanoassemblies. Here we demonstrate a mechanism to configure plasmonic nanoparticles (NPs) in polymer media using nanosecond laser pulses. The mechanism relies on optical forces produced by the interference of laser beams, which allow NPs to migrate to lower-energy configurations. The resulting NP arrangements are stable without any external energy source, but erasable and rewritable by additional recording pulses. We demonstrate reconfigurable optical elements including multilayer Bragg diffraction gratings, volumetric photonic crystals and lenses, as well as dynamic holograms of three-dimensional virtual objects. We aim to expand the applications of optical forces, which have been mostly restricted to optical tweezers. Holographic assemblies of nanoparticles will allow a new generation of programmable composites for tunable metamaterials, data storage devices, sensors and displays. C1 [Montelongo, Yunuen] Univ London Imperial Coll Sci Technol & Med, Dept Chem, Exhibit Rd, London SW7 2AZ, England. [Yetisen, Ali K.; Yun, Seok-Hyun] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Butt, Haider] Univ Birmingham, Sch Mech Engn, Microengn & Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Yun, Seok-Hyun] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Montelongo, Y (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Chem, Exhibit Rd, London SW7 2AZ, England.; Yetisen, AK (reprint author), Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. EM y.montelongo@imperial.ac.uk; ayetisen@mgh.harvard.edu OI Butt, Haider/0000-0003-2434-9525 NR 42 TC 7 Z9 7 U1 49 U2 76 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 JUN PY 2016 VL 7 AR 12002 DI 10.1038/ncomms12002 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ3GI UT WOS:000379090400001 PM 27337216 ER PT J AU Goto, T Tsugawa, Y Mansbach, JM Camargo, CA Hasegawa, K AF Goto, Tadahiro Tsugawa, Yusuke Mansbach, Jonathan M. Camargo, Carlos A., Jr. Hasegawa, Kohei TI Trends in Infectious Disease Hospitalizations in US Children, 2000 to 2012 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE trend; infectious disease; hospitalization; mortality; cost ID PNEUMOCOCCAL CONJUGATE VACCINE; RESISTANT STAPHYLOCOCCUS-AUREUS; EMERGENCY-DEPARTMENT VISITS; UNITED-STATES; RACIAL DISPARITIES; ROTAVIRUS VACCINE; IMPLEMENTATION; MENINGITIS; PNEUMONIA; MORTALITY AB Background: Although infectious diseases (IDs) remain a major public health problem in US children, there have been no recent efforts to examine comprehensively the change in epidemiology of ID hospitalizations. Methods: A serial cross-sectional analysis using the Kids' Inpatient Database 2000, 2003, 2006, 2009, and 2012. We identified children <= 19 years of age with a primary diagnosis of IDs. Outcomes were national rate of ID hospitalizations, in-hospital mortality, length-of-stay and hospitalization-related direct costs. Negative binomial and multivariable logistic models were constructed to test the change in hospitalization rate and in-hospital mortality, respectively. Results: We identified 3,691,672 weighted hospitalizations for IDs, accounting for 24.5% of all pediatric hospitalizations. From 2000 to 2012, the rate of overall ID hospitalizations decreased from 91.0 to 75.8 per 10,000 US children (P < 0.001). The most frequently listed ID subgroup was lower respiratory infections (42.8% of all ID hospitalizations in 2012). Although the hospitalization rate for most ID subgroups decreased, the hospitalization rate for skin infections significantly increased (67.6% increase; P < 0.001). The multivariable model demonstrated a significant decline in in-hospital mortality (odds ratio for comparison of 2012 with 2000, 0.63; 95% confidence interval, 0.51-0.79). From 2000 to 2012, there was no significant change in the median length-of-stay (2 days in 2000 to 2 days in 2012; P-trend = 0.33). The median direct cost for ID hospitalization increased from $3452 in 2003 to $3784 in 2012 (P = 0.007), with the nationwide direct cost of $4.4 billion in 2012. Conclusions: We found a statistically significant decline in overall ID hospitalization rate among US children from 2000 to 2012, whereas skin infections statistically significantly increased. In addition, the median direct cost per ID hospitalization increased by 10% during the study period. C1 [Goto, Tadahiro; Camargo, Carlos A., Jr.; Hasegawa, Kohei] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Univ, Harvard Interfac Initiat Hlth Policy, Boston, MA USA. [Mansbach, Jonathan M.] Harvard Med Sch, Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Goto, T (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Suite 920, Boston, MA 02114 USA. EM tgoto1@mgh.harvard.edu FU National Institutes of Health (Bethesda, MD) [U01 AI-67693, R01 AI-114552, R01 AI-108588] FX C.A.C. was supported by grant U01 AI-67693 and R01 AI-114552 from the National Institutes of Health (Bethesda, MD). J.M.M. was supported by the grant from R01 AI-108588 from the National Institutes of Health (Bethesda, MD). NR 34 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2016 VL 35 IS 6 BP E158 EP E163 DI 10.1097/INF.0000000000001134 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA DQ6VN UT WOS:000379343700001 PM 26967815 ER PT J AU Mota, NP Tsai, J Sareen, J Marx, BP Wisco, BE Harpaz-Rotem, I Southwick, SM Krystal, JH Pietrzak, RH AF Mota, Natalie P. Tsai, Jack Sareen, Jitender Marx, Brian P. Wisco, Blair E. Harpaz-Rotem, Ilan Southwick, Steven M. Krystal, John H. Pietrzak, Robert H. TI High burden of subthreshold DSM-5 post-traumatic stress disorder in US military veterans SO WORLD PSYCHIATRY LA English DT Letter ID NATIONAL-HEALTH; RESILIENCE C1 [Mota, Natalie P.] Univ Manitoba, Dept Clin Hlth Psychol, Winnipeg, MB, Canada. [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Tsai, Jack; Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sareen, Jitender] Univ Manitoba, Dept Psychiat, Winnipeg, MB, Canada. [Sareen, Jitender] Univ Manitoba, Dept Psychol, Winnipeg, MB, Canada. [Sareen, Jitender] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB, Canada. [Marx, Brian P.] Boston Univ, Sch Med, VA Boston Healthcare Syst, US Dept Vet Affairs,Natl Ctr Posttraumat Stress D, Boston, MA 02118 USA. [Marx, Brian P.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. [Wisco, Blair E.] Univ North Carolina Greensboro, Dept Psychol, Greensboro, NC USA. [Harpaz-Rotem, Ilan; Southwick, Steven M.; Krystal, John H.; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, West Haven, CT USA. RP Mota, NP (reprint author), Univ Manitoba, Dept Clin Hlth Psychol, Winnipeg, MB, Canada. FU U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder FX The National Health and Resilience in Veterans Study was supported by the U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder and a private donation. NR 10 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD JUN PY 2016 VL 15 IS 2 BP 185 EP 186 DI 10.1002/wps.20313 PG 3 WC Psychiatry SC Psychiatry GA DQ6GI UT WOS:000379302100028 PM 27265715 ER PT J AU Goldman, A Kulkarni, A Kohandel, M Pandey, P Rao, P Natarajan, SK Sabbisetti, V Sengupta, S AF Goldman, Aaron Kulkarni, Ashish Kohandel, Mohammad Pandey, Prithvi Rao, Poornima Natarajan, Siva Kumar Sabbisetti, Venkata Sengupta, Shiladitya TI Rationally Designed 2-in-1 Nanoparticles Can Overcome Adaptive Resistance in Cancer SO ACS NANO LA English DT Article DE drug resistance; tumor heterogeneity; nanotechnology; drug delivery; targeted therapy ID BREAST-CANCER; ANTITUMOR EFFICACY; ANTICANCER DRUGS; DELIVERY-SYSTEM; CO-DELIVERY; IN-VITRO; CELLS; CHEMOTHERAPY; COMBINATION; CISPLATIN AB The development of resistance is the major cause of mortality in cancer. Combination chemotherapy is used clinically to reduce the probability of evolution of resistance. A similar trend toward the use of combinations of drugs is also emerging in the application of cancer nanomedicine. However, should a combination of two drugs be delivered from a single nanoparticle or should they be delivered in two different nanoparticles for maximal efficacy? We explored these questions in the context of adaptive resistance, which emerges as a phenotypic response of cancer cells to chemotherapy. We studied the phenotypic dynamics of breast cancer cells under cytotoxic chemotherapeutic stress and analyzed the data using a phenomenological mathematical model. We demonstrate that cancer cells can develop adaptive resistance by entering into a predetermined transitional trajectory that leads to phenocopies of inherently chemoresistant cancer cells. Disrupting this deterministic program requires a unique combination of inhibitors and cytotoxic agents. Using two such combinations, we demonstrate that a 2-in-1 nanomedicine can induce greater antitumor efficacy by ensuring that the origins of adaptive resistance are terminated by deterministic spatially constrained delivery of both drugs to the target cells. In contrast, a combination of free-form drugs or two nanoparticles, each carrying a single payload, is less effective, arising from a stochastic distribution to cells. These findings suggest that 2-in-1 nanomedicines could emerge as an important strategy for targeting adaptive resistance, resulting in increased antitumor efficacy. C1 [Goldman, Aaron; Kulkarni, Ashish; Natarajan, Siva Kumar; Sabbisetti, Venkata; Sengupta, Shiladitya] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Goldman, Aaron; Kulkarni, Ashish; Sengupta, Shiladitya] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Goldman, Aaron; Kulkarni, Ashish; Rao, Poornima; Sengupta, Shiladitya] Brigham & Womens Hosp, Dept Med, Div Biomed Engn, 75 Francis St, Boston, MA 02115 USA. [Goldman, Aaron] Harvard Digest Dis Ctr, Boston, MA 02115 USA. [Kohandel, Mohammad] Univ Waterloo, Dept Appl Math, Waterloo, ON N2L 3G1, Canada. [Pandey, Prithvi] India Innovat Res Ctr, Invictus Oncol, New Delhi 92, India. [Sengupta, Shiladitya] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sengupta, S (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.; Sengupta, S (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.; Sengupta, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Biomed Engn, 75 Francis St, Boston, MA 02115 USA.; Sengupta, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM shiladit@mit.edu OI Natarajan, Siva Kumar /0000-0002-9663-079X FU DoD BCRP Collaborative Innovator Grant [W81XWH-09-1-0700]; NIH [1R01CA135242-01A2]; DoD Breakthrough Award [BC132168]; American Lung Association Innovation Award [LCD-259932-N]; IUSSTF; American Cancer Society [122854-PF-12-226-01-CDD] FX We thank the Dana Farber Cancer Institute Flow Cytometry Core Facility for their expertise, consulting, and assistance with cell sorting experiments. The authors also thank Dr. D. Goldman, MD, for consultation of histology and IHC, and Dr. Mehran Kardar, PhD, for his helpful discussion during experimental designs and computational modeling. S.S. is supported by a DoD BCRP Collaborative Innovator Grant (W81XWH-09-1-0700), a NIH RO1 (1R01CA135242-01A2), a DoD Breakthrough Award (BC132168), an American Lung Association Innovation Award (LCD-259932-N), and an Indo US Joint Center Grant from IUSSTF. A.G. is supported by an American Cancer Society Postdoctoral Fellowship (122854-PF-12-226-01-CDD). Some images in schematics were obtained from servier.com medical image bank. NR 43 TC 2 Z9 2 U1 12 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JUN PY 2016 VL 10 IS 6 BP 5823 EP 5834 DI 10.1021/acsnano.6b00320 PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DQ1PU UT WOS:000378973700025 PM 27257911 ER PT J AU Chen, AL Tambouret, RH Roberts, DJ AF Chen, Athena L. Tambouret, Rosemary H. Roberts, Drucilla J. TI Touch Preps of Products of Conception for Rule-Out Ectopic Pregnancy A Viable Alternative to Frozen Section SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Cytopathology; Touch prep; Ectopic pregnancy ID UTERINE CURETTINGS; UNKNOWN LOCATION; RAPID DIAGNOSIS; IDENTIFICATION; ABORTION; VILLI AB Objectives: Tissue confirmation of the intrauterine location of a pregnancy can be difficult grossly, necessitating a frozen section diagnosis. First-trimester tissue is often scant and can be exhausted by frozen section. We examined 39 endometrial curettings performed for rule-out ectopic pregnancy by touch prep to examine the utility of cytopathology in documenting trophoblast or chorionic villi (products of conception [POC]). Methods: First-trimester curettage specimens sent to the Massachusetts General Hospital Pathology Department-received a gross examination followed by a touch prep of the area most suspicious for villi. Touch preps were reviewed blinded to the final diagnosis and then compared. Results: Thirty-three of the 39 touch preps and histology specimens were concordant, including all 11 negative histology specimens and 22 of the 28 positive histology specimens. Conclusions: POC can be diagnosed by touch prep and may offer confirmation of grossly identified villi. Positive predictive value is 100%. Negative touch preps should receive further evaluation. C1 [Chen, Athena L.; Tambouret, Rosemary H.; Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 219, Boston, MA 02114 USA. EM djroberts@partners.org NR 11 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2016 VL 145 IS 6 BP 752 EP 756 DI 10.1093/AJCP/AQW048 PG 5 WC Pathology SC Pathology GA DQ0LX UT WOS:000378891900003 PM 27317440 ER PT J AU Luo, Y Szolovits, P Dighe, AS Baron, JM AF Luo, Yuan Szolovits, Peter Dighe, Anand S. Baron, Jason M. TI Using Machine Learning to Predict Laboratory Test Results SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Machine learning; Ferritin; Clinical decision support; Statistical diagnosis; Imputation; Computational pathology ID IRON-DEFICIENCY; IMPUTATION AB Objectives: While clinical laboratories report most test results as individual numbers, findings, or observations, clinical diagnosis usually relies on the results of multiple tests. Clinical decision support that integrates multiple elements of laboratory data could be highly useful in enhancing laboratory diagnosis. Methods: Using the analyte ferritin in a proof of concept, we extracted clinical laboratory data from patient testing and applied a variety of machine-learning algorithms to predict ferritin test results using the results from other tests. We compared predicted with measured results and reviewed selected cases to assess the clinical value of predicted ferritin. Results: We show that patient demographics and results of other laboratory tests can discriminate normal from abnormal ferritin results with a high degree of accuracy (area under the curve as high as 0.97, held-out test data). Case review indicated that predicted ferritin results may sometimes better reflect underlying iron status than measured ferritin. Conclusions: These findings highlight the substantial informational redundancy present in patient test results and offer a potential foundation for a novel type of clinical decision support aimed at integrating, interpreting, and enhancing the diagnostic value of multianalyte sets of clinical laboratory test results. C1 [Luo, Yuan; Szolovits, Peter] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Dighe, Anand S.; Baron, Jason M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dighe, Anand S.; Baron, Jason M.] Harvard Univ, Sch Med, Boston, MA USA. RP Baron, JM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jmbaron@partners.org FU MGH-MIT Strategic Partnership FX This work was supported by a grant from the MGH-MIT Strategic Partnership. NR 16 TC 0 Z9 0 U1 5 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2016 VL 145 IS 6 BP 778 EP 788 DI 10.1093/AJCP/AQW064 PG 11 WC Pathology SC Pathology GA DQ0LX UT WOS:000378891900006 PM 27329638 ER PT J AU Miano, JM Zhu, QM Lowenstein, CJ AF Miano, Joseph M. Zhu, Qiuyu Martin Lowenstein, Charles J. TI A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE epitope; frameshift mutation; genetics; genome editing; genotype; nucleotide ID ONE-STEP GENERATION; LONG NONCODING RNA; REGULATORY DNA ELEMENTS; GUIDED CAS9 NUCLEASES; MEDIATED KNOCK-IN; MUSCULAR-DYSTROPHY; ENDOTHELIAL-CELLS; FUNCTIONAL-CHARACTERIZATION; ENDONUCLEASE CAS9; MAMMALIAN-CELLS AB Previous efforts to target the mouse genome for the addition, subtraction, or substitution of biologically informative sequences required complex vector design and a series of arduous steps only a handful of laboratories could master. The facile and inexpensive clustered regularly interspaced short palindromic repeats (CRISPR) method has now superseded traditional means of genome modification such that virtually any laboratory can quickly assemble reagents for developing new mouse models for cardiovascular research. Here, we briefly review the history of CRISPR in prokaryotes, highlighting major discoveries leading to its formulation for genome modification in the animal kingdom. Core components of CRISPR technology are reviewed and updated. Practical pointers for 2-component and 3-component CRISPR editing are summarized with many applications in mice including frameshift mutations, deletion of enhancers and noncoding genes, nucleotide substitution of protein-coding and gene regulatory sequences, incorporation of loxP sites for conditional gene inactivation, and epitope tag integration. Genotyping strategies are presented and topics of genetic mosaicism and inadvertent targeting discussed. Finally, clinical applications and ethical considerations are addressed as the biomedical community eagerly embraces this astonishing innovation in genome editing to tackle previously intractable questions. C1 [Miano, Joseph M.; Zhu, Qiuyu Martin; Lowenstein, Charles J.] Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, 601 Elmwood Ave,Box CVRI, Rochester, NY 14642 USA. [Zhu, Qiuyu Martin] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Miano, JM (reprint author), Univ Rochester, Sch Med & Dent, Aab Cardiovasc Res Inst, 601 Elmwood Ave,Box CVRI, Rochester, NY 14642 USA. EM j.m.miano@rochester.edu FU National Institutes of Health [HL-112793, HL-117907, HL-124042, HL-108372]; American Heart Association [14GRNT19020033] FX CRISPR work is supported by National Institutes of Health grants HL-112793 and HL-117907 to J.M. Miano and HL-124042 and HL-108372 and American Heart Association grant 14GRNT19020033 to C.J. Lowenstein. NR 149 TC 4 Z9 4 U1 6 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2016 VL 36 IS 6 BP 1058 EP + DI 10.1161/ATVBAHA.116.304790 PG 30 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DP2DK UT WOS:000378298100005 PM 27102963 ER PT J AU Ren, B Best, B Ramakrishnan, DP Walcott, BP Storz, P Silverstein, RL AF Ren, Bin Best, Brad Ramakrishnan, Devi Prasadh Walcott, Brian P. Storz, Peter Silverstein, Roy L. TI LPA/PKD-1-FoxO1 Signaling Axis Mediates Endothelial Cell CD36 Transcriptional Repression and Proangiogenic and Proarteriogenic Reprogramming SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiogenesis; biotin; differentiation; endothelial cell; ischemia; obesity; signal transduction ID PROTEIN-KINASE-D; LYSOPHOSPHATIDIC ACID; GENE-EXPRESSION; GROWTH-FACTOR; ANGIOGENESIS; PHOSPHORYLATION; THROMBOSPONDIN-1; DISEASE; NEOVASCULARIZATION; PLASTICITY AB Objective-CD36 is a scavenger and antiangiogenic receptor that is important in atherothrombotic diseases, diabetes mellitus, cancer, and obesity. Lysophosphatidic acid, a phospholipid signaling mediator, abolishes endothelial cell responses to antiangiogenic proteins containing thrombospondin type 1 homology domains by downregulating endothelial CD36 transcription via protein kinase D1 (PKD-1) signaling. We aimed to understand mechanisms by which lysophosphatidic acid-mediated angiogenic signaling is integrated to regulate CD36 transcription and endothelial cell function via a nuclear transcriptional complex. Approach and Results-Microvascular endothelial cells expressing CD36 were used for studying angiogenic signaling and CD36 transcription. Gene transfection and transduction, RT-qPCR, avidin-biotin-conjugated DNA-binding assay, chromatin immunoprecipitation assay, co-immunoprecipitation, proximal ligation assay, and immunofluorescence microscopy showed that lysophosphatidic acid-mediated CD36 transcriptional repression involved PKD-1 signaling mediated formation of forkhead box protein O1-histone deacetylase 7 complex in the nucleus. Unexpectedly, turning off CD36 transcription initiated reprogramming microvascular endothelial cells to express ephrin B2, a critical molecular signature involved in angiogenesis and arteriogenesis. Spheroid-based angiogenesis and in vivo Matrigel angiogenesis assays indicated that angiogenic branching morphogenesis and in vivo angiogenesis were dependent on PKD-1 signaling. A mouse tumor angiogenesis model revealed enhanced PKD-1 signaling and expression of ephrin B2 and smooth muscle actin in neovessels of Lewis Lung Carcinomas, along with low-CD36 expression or CD36 deficiency. Conclusions-Lysophosphatidic acid/PKD-1 signaling leads to nuclear accumulation of histone deacetylase 7, where it interacts with forkhead box protein O1 to suppress endothelial CD36 transcription and mediates silencing of antiangiogenic switch, resulting in proangiogenic and proarteriogenic reprogramming. Targeting this signaling cascade could be a novel approach for ischemic cardiovascular disease and cancer. C1 [Ren, Bin; Silverstein, Roy L.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Ren, Bin; Best, Brad; Ramakrishnan, Devi Prasadh; Silverstein, Roy L.] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA. [Walcott, Brian P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Neurol Surg, Boston, MA 02114 USA. [Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA USA. [Storz, Peter] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA. RP Ren, B (reprint author), Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. EM bren@mcw.edu FU American Heart Association; American Cancer Society [86-004-26]; Central Society of Clinical and Translational Research; National Institutes of Health [HL085718, CA140182] FX This work was supported by a National Scientific Development Grant from the American Heart Association (B. Ren), an Institutional Research Grant (No. 86-004-26) from American Cancer Society (B. Ren) and a Career Development Award from The Central Society of Clinical and Translational Research (B. Ren), and the National Institutes of Health (HL085718 to R.L. Silverstein and CA140182 to P. Storz). NR 50 TC 1 Z9 1 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2016 VL 36 IS 6 BP 1197 EP + DI 10.1161/ATVBAHA.116.307421 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DP2DK UT WOS:000378298100018 PM 27013613 ER PT J AU Fu, Z Ye, QF Zhang, Y Zhong, ZB Xiong, Y Wang, YF Hu, L Wang, W Huang, W Ko, DSC AF Fu, Zhen Ye, Qifa Zhang, Yang Zhong, Zibiao Xiong, Yan Wang, Yanfeng Hu, Long Wang, Wei Huang, Wei Ko, Dicken Shiu-Chung TI Hypothermic Machine Perfusion Reduced Inflammatory Reaction by Downregulating the Expression of Matrix Metalloproteinase 9 in a Reperfusion Model of Donation After Cardiac Death SO ARTIFICIAL ORGANS LA English DT Article DE Donation after cardiac death; Hypothermic machine perfusion; Cold storage; Matrix metalloproteinase-9; Ischemia-reperfusion ID HEPATIC ISCHEMIA/REPERFUSION INJURY; DELAYED GRAFT FUNCTION; RAT-BRAIN ASTROCYTES; MATRIX METALLOPROTEINASES; COLD PRESERVATION; MOLECULAR-BIOLOGY; EPITHELIAL-CELLS; GELATINASE-B; TNF-ALPHA; KAPPA-B AB The exact mechanism by which hypothermic machine perfusion (HMP) improves the graft quality in kidney transplantation of donation after cardiac death (DCD) remains unclear. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase 9 (MMP-9) and inflammatory reaction in kidney ischemia-reperfusion (I/R) injury injury followed by cold storage (CS) or HMP model of DCD. New Zealand white rabbit kidneys were subjected to 35min of warm ischemia and 1h reperfusion, then preserved by either 1h reperfusion (sham-operated group), 4h CS or 4h HMP in vivo. Kidneys were reperfused 24h followed by further analysis. No treatment was given to rabbits in the normal control group. The expression of MMP-9, nuclear factor-B (NF-B), and MMP-2 mRNA were detected by real-time PCR (RT-PCR). MMP-9 was located by immunohistochemistry and immunofluorescence methods. Tumor necrosis factor- (TNF-), interleukin-6 (IL-6), myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by kits for each groups. Compared with the CS group, the expression of MMP-9 and NF-B mRNA were downregulated in HMP group (P<0.05). In contrast, expression of MMP-2 mRNA had no statistical significance between CS group and HMP group (P>0.05). In normal control and sham-operated groups, a low level of MMP-9 expression was detected in glomeruli. However, positive signals of MMP-9 were mostly located in the tubulointerstitium and the vascular wall of CS and HMP groups. Expression of TNF-, IL-6, MDA, and activity of MPO decreased while activity of SOD in the HMP group increased in contrast to the CS group (P<0.05). In conclusion, inflammatory cytokines mediated MMP-9 expression through NF-B band to MMP-9 promoter region, resulting in renal injury. Therefore, HMP reduced inflammatory reaction by downregulating the expression of MMP-9, which may be the mechanism of kidney protection in I/R injury. C1 [Fu, Zhen; Ye, Qifa; Zhang, Yang; Hu, Long; Wang, Wei] Cent S Univ, Xiangya Hosp 3, Natl Hlth Minist Transplantat Med Engn & Technol, Res Ctr, Changsha, Hunan, Peoples R China. [Fu, Zhen; Ye, Qifa; Zhang, Yang; Zhong, Zibiao; Xiong, Yan; Wang, Yanfeng; Hu, Long; Wang, Wei; Huang, Wei] Wuhan Univ, Zhongnan Hosp, Inst Hepatobiliary Dis, Transplant Ctr,Hubei Key Lab Med Technol Transpla, 169 Donghu Rd, Wuhan 430071, Hubei, Peoples R China. [Ko, Dicken Shiu-Chung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Ye, QF (reprint author), Wuhan Univ, Zhongnan Hosp, Inst Hepatobiliary Dis, Transplant Ctr,Hubei Key Lab Med Technol Transpla, 169 Donghu Rd, Wuhan 430071, Hubei, Peoples R China. EM yqf_china@163.com FU Fundamental Research Funds for the Central Universities of Central South University [2014zzts376]; National Natural Science Foundation of China [U1403222] FX This work was supported by the Fundamental Research Funds for the Central Universities of Central South University (No: 2014zzts376) and by the National Natural Science Foundation of China (U1403222). NR 35 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-564X EI 1525-1594 J9 ARTIF ORGANS JI Artif. Organs PD JUN PY 2016 VL 40 IS 6 BP E102 EP E111 DI 10.1111/aor.12658 PG 10 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA DP5MQ UT WOS:000378542100002 PM 26813475 ER PT J AU Zhang, YF Trippa, L Parmigiani, G AF Zhang, Yifan Trippa, Lorenzo Parmigiani, Giovanni TI Optimal Bayesian adaptive trials when treatment efficacy depends on biomarkers SO BIOMETRICS LA English DT Article DE Biomarkers; Bayesian adaptive designs; Dynamic programming; Optimal strategy; Personalized medicine ID PLAY-WINNER RULE; I-SPY 2; CLINICAL-TRIALS; LUNG-CANCER; RANDOMIZATION; THERAPY; GLIOBLASTOMA; MUTATIONS; MEDICINE; DESIGN AB Clinical biomarkers play an important role in precision medicine and are now extensively used in clinical trials, particularly in cancer. A response adaptive trial design enables researchers to use treatment results about earlier patients to aid in treatment decisions of later patients. Optimal adaptive trial designs have been developed without consideration of biomarkers. In this article, we describe the mathematical steps for computing optimal biomarker-integrated adaptive trial designs. These designs maximize the expected trial utility given any pre-specified utility function, though we focus here on maximizing patient responses within a given patient horizon. We describe the performance of the optimal design in different scenarios. We compare it to Bayesian Adaptive Randomization (BAR), which is emerging as a practical approach to develop adaptive trials. The difference in expected utility between BAR and optimal designs is smallest when the biomarker subgroups are highly imbalanced. We also compare BAR, a frequentist play-the-winner rule with integrated biomarkers and a marker-stratified balanced randomization design (BR). We show that, in contrasting two treatments, BR achieves a nearly optimal expected utility when the patient horizon is relatively large. Our work provides novel theoretical solution, as well as an absolute benchmark for the evaluation of trial designs in personalized medicine. C1 [Zhang, Yifan; Trippa, Lorenzo; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Trippa, Lorenzo; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Parmigiani, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.; Parmigiani, G (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM gp@jimmy.harvard.edu FU FAS Division of Science, Research Computing Group at Harvard University; Claudia Adams Barr Program in Innovative Cancer Research; [5P30 CA006516-50]; [R01 AI024643] FX Computing was performed on the Dana-Farber Cancer Institute high performance cluster and on the Odyssey cluster supported by the FAS Division of Science, Research Computing Group at Harvard University. This project has been supported by grant 5P30 CA006516-50, grant R01 AI024643 and the Claudia Adams Barr Program in Innovative Cancer Research. NR 25 TC 0 Z9 0 U1 2 U2 6 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2016 VL 72 IS 2 BP 414 EP 421 DI 10.1111/biom.12437 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA DP5HW UT WOS:000378527900011 PM 26575199 ER PT J AU Williams, ME Hong, FX Gascoyne, RD Wagner, LI Krauss, JC Habermann, TM Swinnen, LJ Schuster, SJ Peterson, CG Sborov, MD Martin, SE Weiss, M Ehmann, WC Horning, SJ Kahl, BS AF Williams, Michael E. Hong, Fangxin Gascoyne, Randy D. Wagner, Lynne I. Krauss, John C. Habermann, Thomas M. Swinnen, Lode J. Schuster, Stephen J. Peterson, Christopher G. Sborov, Mark D. Martin, S. Eric Weiss, Matthias Ehmann, W. Christopher Horning, Sandra J. Kahl, Brad S. TI Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE B-cell lymphoma; indolent lymphoma; rituximab; maintenance ID PHASE-II TRIAL; THERAPY; PROGRAM AB The rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub-study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly x 4 were randomized to MR (single dose rituximab every 3months until treatment failure) or RR (rituximab weekly x 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n=57), MZL (n=71) and unclassifiable small B-cell lymphoma (n=3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31-49%; SLL ORR 228%; MZL ORR 521%]; all 52 responders were randomized. At a median of 43years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 14years for RR and 48years for MR (P=0012); median time to first cytotoxic therapy was 63years for RR and not reached for MR (P=00002). Survival did not differ (P=072). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR. C1 [Williams, Michael E.] Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada. [Wagner, Lynne I.] Northwestern Univ, Chicago, IL 60611 USA. [Krauss, John C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Swinnen, Lode J.] Johns Hopkins Univ, Baltimore, MD USA. [Schuster, Stephen J.] Univ Penn, Philadelphia, PA 19104 USA. [Peterson, Christopher G.] Aspirus Reg Canc Ctr, Wausau, WI USA. [Sborov, Mark D.] Fairview Southdale Hosp, St Louis Pk, MN USA. [Martin, S. Eric] Christiana Care CCOP, Newark, DE USA. [Martin, S. Eric] Helen F Graham Canc Network, Newark, DE USA. [Weiss, Matthias] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. [Ehmann, W. Christopher] Penn State Canc Inst, Hershey, PA USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. [Kahl, Brad S.] Washington Univ, Sch Med, St Louis, MO USA. RP Williams, ME (reprint author), Univ Virginia, Sch Med, Hematol Oncol Div, Jefferson Pk Ave, Charlottesville, VA 22908 USA.; Williams, ME (reprint author), Univ Virginia, Sch Med, Ctr Canc, Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM mew4p@virginia.edu FU Public Health Service from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services [CA21115, CA23318, CA66636, CA49957, CA21076, CA17145, CA13650] FX The authors wish to acknowledge the ECOG Coordinating and Statistical Centers for their expert assistance throughout this clinical trial, the Cancer Trials Support Unit and our many co-investigators. We also offer our sincere thanks to the patients and families who took part in the E4402/RESORT study. This trial was supported in part by Public Health Service Grants CA21115, CA23318, CA66636, CA49957, CA21076, CA17145 and CA13650 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 16 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2016 VL 173 IS 6 BP 867 EP 875 DI 10.1111/bjh.14007 PG 9 WC Hematology SC Hematology GA DP6XW UT WOS:000378644100005 PM 26970533 ER PT J AU Liao, YF Feng, Y Shen, J Hornicek, FJ Duan, ZF AF Liao, Yunfei Feng, Yong Shen, Jacson Hornicek, Francis J. Duan, Zhenfeng TI The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Cyclin-dependent kinase; Sarcoma; Kinase inhibitor; Targeted therapy ID SOFT-TISSUE SARCOMA; RNA-POLYMERASE-II; CELL-CYCLE; OSTEOSARCOMA CELLS; CDK4/6 INHIBITION; TUMOR-SUPPRESSOR; CANCER-THERAPY; DNA-DAMAGE; K/CDK12 COMPLEX; DOWN-REGULATION AB Uncontrolled proliferation and cell growth is the hallmark of many different malignant diseases, including sarcomas. Cyclin-dependent kinases (CDKs) are members of the serine/threonine protein kinase family and play crucial roles in tumor cell proliferation and growth by controlling cell cycle, transcription, and RNA splicing. In addition, several CDKs influence multiple targets and phosphorylate transcription factors involved in tumorigenesis. There are many examples linking dysregulated activation and expression of CDKs to tumors, and targeting CDKs in tumor cells has become a promising therapeutic strategy. More recently, the Food and Drug Administration (FDA) has approved the CDK4/6 inhibitor palbociclib for treating metastatic breast cancer. In sarcomas, high levels of CDK mRNA and protein expression have been found in most human sarcoma cells and patient tissues. Many studies have demonstrated consistent results in which inhibition of different CDKs decrease sarcoma cell growth and induce apoptosis. Therefore, CDKs comprise an attractive set of targets for novel anti-sarcoma drug development. In this review, we discuss the roles of different members of CDKs in various sarcomas and provide a pre-clinical overview of promising therapeutic potentials of targeting CDKs with a special emphasis on sarcoma. C1 [Liao, Yunfei; Feng, Yong; Shen, Jacson; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Liao, Yunfei; Feng, Yong; Shen, Jacson; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Med Sch, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Liao, Yunfei; Feng, Yong] Huazhong Univ Sci & Technol, Wuhan Union Hosp, Tongji Med Coll, 1277 Jie Fang Ave, Wuhan 430022, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Med Sch, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Gattegno and Wechsler funds; Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [CA 151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopaedics FX This work was supported, in part, by the Gattegno and Wechsler funds, and the Kenneth Stanton Fund. Dr. Duan is supported, in part, through a grant from the Sarcoma Foundation of America (SFA); a grant from the National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452-01; a pilot grant from Sarcoma SPORE/NIH; and a grant from an Academic Enrichment Fund of MGH Orthopaedics. NR 119 TC 1 Z9 1 U1 6 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 EI 1573-7233 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2016 VL 35 IS 2 BP 151 EP 163 DI 10.1007/s10555-015-9601-1 PG 13 WC Oncology SC Oncology GA DP8TX UT WOS:000378771900001 PM 26669603 ER PT J AU Barallobre-Barreiro, J Oklu, R Lynch, M Fava, M Baig, F Yin, XK Barwari, T Potier, DN Albadawi, H Jahangiri, M Porter, KE Watkins, MT Misra, S Stoughton, J Mayr, M AF Barallobre-Barreiro, Javier Oklu, Rahmi Lynch, Marc Fava, Marika Baig, Ferheen Yin, Xiaoke Barwari, Temo Potier, David N. Albadawi, Hassan Jahangiri, Marjan Porter, Karen E. Watkins, Michael T. Misra, Sanjay Stoughton, Julianne Mayr, Manuel TI Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins SO CARDIOVASCULAR RESEARCH LA English DT Article DE Venous; Extracellular matrix; Smooth Muscle; Protease ID MAST-CELL CHYMASE; SMOOTH-MUSCLE-CELLS; APOPTOSIS; METALLOPROTEINASE; INSUFFICIENCY; PATHOGENESIS; MODULATION; ROLES; WALL AB Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of > 150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase beta 1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase beta 1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis. C1 [Barallobre-Barreiro, Javier; Lynch, Marc; Fava, Marika; Baig, Ferheen; Yin, Xiaoke; Barwari, Temo; Potier, David N.; Mayr, Manuel] Kings Coll London, Kings British Heart Fdn Ctr, 125 Coldharbour Lane, London SE5 9NU, England. [Oklu, Rahmi] Mayo Clin, Div Vasc & Intervent Radiol, Scottsdale, AZ USA. [Fava, Marika; Jahangiri, Marjan] NHS Trust, St Georges Hosp, London, England. [Albadawi, Hassan; Watkins, Michael T.; Stoughton, Julianne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA USA. [Porter, Karen E.] Univ Leeds, Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England. [Misra, Sanjay] Mayo Clin, Div Vasc & Intervent Radiol, Rochester, MN USA. RP Mayr, M (reprint author), Kings Coll London, Kings British Heart Fdn Ctr, 125 Coldharbour Lane, London SE5 9NU, England. EM manuel.mayr@kcl.ac.uk OI Mayr, Manuel/0000-0002-0597-829X FU American College of Phlebology; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London; King's College Hospital; excellence initiative (Competence Centers for Excellent Technologies COMET) of the Austrian Research Promotion Agency FFG: 'Research Center of Excellence in Vascular Ageing - Tyrol, VASCage' - BMVIT [843536]; BMWFW; Wirtschaftsagentur Wien; Standortagentur Tirol; Massachusetts General Hospital, Department of Surgery, Division of Vascular and Endovascular Surgery, Henry & Nod Meyer Research Fund FX This work was supported by the American College of Phlebology (R.O.) and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London in partnership with King's College Hospital and an excellence initiative (Competence Centers for Excellent Technologies COMET) of the Austrian Research Promotion Agency FFG: 'Research Center of Excellence in Vascular Ageing - Tyrol, VASCage' (K-Project Nr. 843536) funded by the BMVIT, BMWFW, the Wirtschaftsagentur Wien, and the Standortagentur Tirol. H.A. is funded by Massachusetts General Hospital, Department of Surgery, Division of Vascular and Endovascular Surgery, Henry & Nod Meyer Research Fund. M.M. is a Senior Fellow of the British Heart Foundation. NR 39 TC 2 Z9 2 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUN 1 PY 2016 VL 110 IS 3 BP 419 EP 430 DI 10.1093/cvr/cvw075 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DP4CJ UT WOS:000378442700016 PM 27068509 ER PT J AU de Vries, B Anttila, V Freilinger, T Wessman, M Kaunisto, MA Kallela, M Artto, V Vijfhuizen, LS Gobel, H Dichgans, M Kubisch, C Ferrari, MD Palotie, A Terwindt, GM van den Maagdenberg, AMJM AF de Vries, Boukje Anttila, Verneri Freilinger, Tobias Wessman, Maija Kaunisto, Mari A. Kallela, Mikko Artto, Ville Vijfhuizen, Lisanne S. Goebel, Hartmut Dichgans, Martin Kubisch, Christian Ferrari, Michel D. Palotie, Aarno Terwindt, Gisela M. van den Maagdenberg, Arn M. J. M. CA Int Headache Genetics Consortium TI Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set SO CEPHALALGIA LA English DT Article DE Migraine; candidate genes; SNP; GWAS data ID FAMILIAL HEMIPLEGIC MIGRAINE; INSULIN-RECEPTOR GENE; SUSCEPTIBILITY LOCI; MOLECULAR-GENETICS; MTHFR C677T; AURA; POLYMORPHISM; METAANALYSIS; POPULATION; COMMON AB BackgroundBefore the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set. MethodsWe selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls. ResultsNone of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately. ConclusionThe available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine. C1 [de Vries, Boukje; Vijfhuizen, Lisanne S.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Human Genet, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. [Anttila, Verneri; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Anttila, Verneri] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst Har000000000000, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Freilinger, Tobias; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Freilinger, Tobias] Univ Tubingen, Dept Neurol & Epileptol, Tubingen, Germany. [Freilinger, Tobias] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Wessman, Maija; Kaunisto, Mari A.; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland. [Wessman, Maija; Kaunisto, Mari A.] Folkhalsan Res Ctr, Helsinki, Finland. [Kallela, Mikko; Artto, Ville] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. [Goebel, Hartmut] Kiel Pain & Headache Ctr, Kiel, Germany. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany. [Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Terwindt, GM (reprint author), Leiden Univ, Med Ctr, Dept Neurol, Albinusdreef 2,POB 9600, NL-2300 RC Leiden, Netherlands. EM G.M.Terwindt@lumc.nl RI Kubisch, Christian/F-1893-2011; OI Kubisch, Christian/0000-0003-4220-0978; Kaunisto, Mari/0000-0002-6946-9195 FU Netherlands Organization for the Health Research and Development (ZonMw) [90700217]; VIDI (ZonMw) [91711319]; Netherlands Organisation for Scientific Research (NWO) VICI [918.56.602]; Spinoza; EuroHead project [LSM-CT-2004-504837]; EUROHEADPAIN project [602633]; Center for Medical Systems Biology (CMSB) established in the Netherlands Genomics Initiative/ Netherlands Organisation for Scientific Research (NGI/NWO) [050-060-409]; Wellcome Trust [098051]; Academy of Finland [251704, 139795]; Academy of Finland, Center of Excellence in Complex Disease Genetics [213506, 129680]; ENGAGE Consortium [HEALTH-F4-2007-201413]; EU/SYNSYS-Synaptic Systems [242167]; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Medicinska Understodsforeningen Liv Halsa; Helsinki University Central Hospital FX This work was supported by grants from the Netherlands Organization for the Health Research and Development (ZonMw) no. 90700217 and VIDI (ZonMw) no. 91711319 (to G.M.T.); the Netherlands Organisation for Scientific Research (NWO) VICI (918.56.602) and Spinoza (2009) grants (to M.D.F.); the EuroHead project (LSM-CT-2004-504837); the EUROHEADPAIN project (grant number 602633); and the Center for Medical Systems Biology (CMSB) established in the Netherlands Genomics Initiative/ Netherlands Organisation for Scientific Research (NGI/NWO), project nr. 050-060-409 (to R.R.F., M.D.F. and A.M.J.M.v.d.M.). The Wellcome Trust (grant number 098051 to AP); the Academy of Finland (grant number 251704 to AP, and 139795 to MW); the Academy of Finland, Center of Excellence in Complex Disease Genetics, (grant numbers 213506 and 129680 to AP); ENGAGE Consortium, (grant agreement HEALTH-F4-2007-201413); EU/SYNSYS-Synaptic Systems (grant number 242167 to AP); the Sigrid Juselius Foundation (to AP); the Folkhalsan Research Foundation (to MW); the Medicinska Understodsforeningen Liv & Halsa (to MW); the Helsinki University Central Hospital (to MK, VAr). NR 53 TC 4 Z9 4 U1 3 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2016 VL 36 IS 7 SI SI BP 604 EP 614 DI 10.1177/0333102414566820 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP3RQ UT WOS:000378413000002 PM 25633374 ER PT J AU Eising, E de Leeuw, C Min, JL Anttila, V Verheijen, MHG Terwindt, GM Dichgans, M Freilinger, T Kubisch, C Ferrari, MD Smit, AB de Vries, B Palotie, A van den Maagdenberg, AMJM Posthuma, D AF Eising, Else de Leeuw, Christiaan Min, Josine L. Anttila, Verneri Verheijen, Mark H. G. Terwindt, Gisela M. Dichgans, Martin Freilinger, Tobias Kubisch, Christian Ferrari, Michel D. Smit, August B. de Vries, Boukje Palotie, Aarno van den Maagdenberg, Arn M. J. M. Posthuma, Danielle CA Int Headache Genetics Consortium TI Involvement of astrocyte and oligodendrocyte gene sets in migraine SO CEPHALALGIA LA English DT Article DE Migraine; GWAS; pathway analysis; astrocytes; oligodendrocytes; synapse ID GENOME-WIDE ASSOCIATION; HEMIPLEGIC MIGRAINE; SUSCEPTIBILITY LOCI; CEREBRAL-CORTEX; MUTANT MICE; HUMAN BRAIN; EXPRESSION; TRANSCRIPTOME; MICROGLIA; ATP1A2 AB Background Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background. C1 [Eising, Else; de Vries, Boukje; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Human Genet, POB 9600, NL-2300 RC Leiden, Netherlands. [de Leeuw, Christiaan; Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Complex Trait Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands. [de Leeuw, Christiaan] Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands. [Min, Josine L.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England. [Anttila, Verneri; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri; Palotie, Aarno] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Verheijen, Mark H. G.; Smit, August B.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res Neurosci, Dept Mol & Cellular Neurobiol, Campus Amsterdam, Amsterdam, Netherlands. [Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, POB 9600, NL-2300 RC Leiden, Netherlands. [Dichgans, Martin; Freilinger, Tobias] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Freilinger, Tobias] Univ Tubingen, Dept Neurol & Epileptol, Tubingen, Germany. [Freilinger, Tobias] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Kubisch, Christian] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany. [Palotie, Aarno] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland. [Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. RP van den Maagdenberg, AMJM (reprint author), Leiden Univ, Med Ctr, Dept Human Genet, POB 9600, NL-2300 RC Leiden, Netherlands.; van den Maagdenberg, AMJM (reprint author), Leiden Univ, Med Ctr, Dept Neurol, POB 9600, NL-2300 RC Leiden, Netherlands. EM A.M.J.M.van_den_Maagdenberg@lumc.nl RI Kubisch, Christian/F-1893-2011 OI Kubisch, Christian/0000-0003-4220-0978 FU Netherlands Organization for Scientific Research (NWO) VIDI (ZonMw) [91711319]; EUROHEADPAIN project [602633]; Center for Medical Systems Biology (CMSB) in the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NGI/NWO) [050-060-409]; Wellcome Trust [098051]; Academy of Finland [251704, 139795]; Academy of Finland, Center of Excellence in Complex Disease Genetics [213506, 129680]; ENGAGE Consortium [HEALTH-F4-2007-201413]; EU/SYNSYS-Synaptic Systems [242167]; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Medicinska Understodsforeningen Liv Halsa; Helsinki University Central Hospital; NWO Complexity project [645.000.003]; NWO [480-05-003] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: grants from the Netherlands Organization for Scientific Research (NWO) VIDI (ZonMw) (grant number 91711319 to G.M.T.); the EUROHEADPAIN project (grant number 602633 to M.D.F., A.M.J.M.v.d.M. and A.P.); the Center for Medical Systems Biology (CMSB) established in the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NGI/NWO) (grant number 050-060-409 to A.M.J.M.v.d.M.); the Wellcome Trust (grant number 098051 to A.P.); the Academy of Finland (grant number 251704 to A.P., and 139795 to M.W.); the Academy of Finland, Center of Excellence in Complex Disease Genetics (grant number 213506 and 129680 to A.P.); ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413); EU/SYNSYS-Synaptic Systems (grant number 242167 to A.P.); the Sigrid Juselius Foundation (to A.P.); the Folkhalsan Research Foundation (to M.W.); the Medicinska Understodsforeningen Liv & Halsa (to M.W.); the Helsinki University Central Hospital (to M.K. and V.A); and the NWO Complexity project (grant number 645.000.003 to C.A.d.L). Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the NWO (grant number 480-05-003 to D.P.). NR 42 TC 2 Z9 2 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2016 VL 36 IS 7 SI SI BP 640 EP 647 DI 10.1177/0333102415618614 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP3RQ UT WOS:000378413000005 PM 26646788 ER PT J AU Zhao, HY Eising, E de Vries, B Vijfhuizen, LS Anttila, V Winsvold, BS Kurth, T Stefansson, H Kallela, M Malik, R Stam, AH Ikram, MA Ligthart, L Freilinger, T Alexander, M Muller-Myhsok, B Schreiber, S Meitinger, T Aromas, A Eriksson, JG Boomsma, DI van Duijn, CM Zwart, JA Quaye, L Kubisch, C Dichgans, M Wessman, M Stefansson, K Chasman, DI Palotie, A Martin, NG Montgomery, GW Ferrari, MD Terwindt, GM van den Maagdenberg, AMJM Nyholt, DR AF Zhao, Huiying Eising, Else de Vries, Boukje Vijfhuizen, Lisanne S. Anttila, Verneri Winsvold, Bendik S. Kurth, Tobias Stefansson, Hreinn Kallela, Mikko Malik, Rainer Stam, Anine H. Ikram, M. Arfan Ligthart, Lannie Freilinger, Tobias Alexander, Michael Mueller-Myhsok, Bertram Schreiber, Stefan Meitinger, Thomas Aromas, Arpo Eriksson, Johan G. Boomsma, Dorret I. van Duijn, Cornelia M. Zwart, John-Anker Quaye, Lydia Kubisch, Christian Dichgans, Martin Wessman, Maija Stefansson, Kari Chasman, Daniel I. Palotie, Aarno Martin, Nicholas G. Montgomery, Grant W. Ferrari, Michel D. Terwindt, Gisela M. van den Maagdenberg, Arn M. J. M. Nyholt, Dale R. CA Int Headache Genetics Consortium TI Gene-based pleiotropy across migraine with aura and migraine without aura patient groups SO CEPHALALGIA LA English DT Article DE Migraine; aura; genome-wide; association; gene-based; pleiotropy ID GENOME-WIDE ASSOCIATION; CORTICAL SPREADING DEPRESSION; SUSCEPTIBILITY LOCI; NOTCH; POPULATION; RECEPTOR; REVEALS; PATHWAY; STROKE; CANCER AB Introduction It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Aim Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. Results We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (p(gene-based)0.05) in the MA subgroup, 107 also produced p(gene-based)0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (p(binomial-test) = 1.5x10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Conclusions Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine. C1 [Zhao, Huiying; Chasman, Daniel I.; Nyholt, Dale R.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, GPO Box 2434, Brisbane, Qld 4001, Australia. [Zhao, Huiying; Martin, Nicholas G.; Montgomery, Grant W.; Nyholt, Dale R.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Eising, Else; de Vries, Boukje; Vijfhuizen, Lisanne S.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RA Leiden, Netherlands. [Anttila, Verneri; Wessman, Maija; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Anttila, Verneri] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Anttila, Verneri; Palotie, Aarno] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Winsvold, Bendik S.; Zwart, John-Anker] Oslo Univ Hosp, FORMI, Oslo, Norway. [Winsvold, Bendik S.; Zwart, John-Anker] Oslo Univ Hosp, Dept Neurol, Oslo, Norway. [Winsvold, Bendik S.; Zwart, John-Anker] Univ Oslo, N-0316 Oslo, Norway. [Kurth, Tobias] INSERM, U897, Res Ctr Epidemiol & Biostat, Team Neuroepidemiol, F-75654 Paris 13, France. [Kurth, Tobias] Univ Bordeaux, Bordeaux, France. [Kurth, Tobias] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Cambridge, MA 02138 USA. [Stefansson, Hreinn; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland. [Kallela, Mikko] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. [Malik, Rainer; Freilinger, Tobias; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Stam, Anine H.; Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. [Ikram, M. Arfan; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, NL-3000 DR Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, NL-3000 DR Rotterdam, Netherlands. [Ligthart, Lannie; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Ligthart, Lannie] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Freilinger, Tobias] Univ Tubingen, Dept Neurol & Epileptol, Tubingen, Germany. [Freilinger, Tobias] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. [Alexander, Michael] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Alexander, Michael] Univ Bonn, Inst Human Genet, Bonn, Germany. [Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, Munich, Germany. [Mueller-Myhsok, Bertram; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Schreiber, Stefan] Univ Kiel, Dept Internal Med 1, Kiel, Germany. [Meitinger, Thomas] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany. [Aromas, Arpo; Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, Johan G.; Wessman, Maija] Folkhalsan Res Ctr, Inst Genet, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Dept Gen Practice, FIN-00014 Helsinki, Finland. [Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland. [Quaye, Lydia] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Kubisch, Christian] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany. [Stefansson, Kari] Univ Iceland, Sch Med, IS-101 Reykjavik, Iceland. [Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Nyholt, DR (reprint author), Queensland Univ Technol, Inst Hlth & Biomed Innovat, GPO Box 2434, Brisbane, Qld 4001, Australia. EM d.nyholt@qut.edu.au RI Kubisch, Christian/F-1893-2011; OI Kubisch, Christian/0000-0003-4220-0978; Winsvold, Bendik Slagsvold/0000-0003-4171-8919 FU National Health and Medical Research Council (NHMRC) [APP1075175]; European Union [602633] FX This work was supported by a grant from the National Health and Medical Research Council (NHMRC) (APP1075175), and by the European Union's Seventh Framework program (2007-2013) under grant agreement no. 602633 (EUROHEADPAIN). NR 41 TC 5 Z9 5 U1 3 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2016 VL 36 IS 7 SI SI BP 648 EP 657 DI 10.1177/0333102415591497 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP3RQ UT WOS:000378413000006 PM 26660531 ER PT J AU Chen, SP Tolner, EA Eikermann-Haerter, K AF Chen, Shih-Pin Tolner, Else A. Eikermann-Haerter, Katharina TI Animal models of monogenic migraine SO CEPHALALGIA LA English DT Review DE Genetic animal model; migraine without aura; pathophysiology ID FAMILIAL HEMIPLEGIC MIGRAINE; CORTICAL SPREADING DEPRESSION; AUTOSOMAL-DOMINANT ARTERIOPATHY; GENE-RELATED PEPTIDE; TYPE-1 MUTANT MICE; ENHANCED EXCITATORY TRANSMISSION; VISUAL-CORTEX EXCITABILITY; TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; RESTLESS LEGS SYNDROME AB Migraine is a highly prevalent and disabling neurological disorder with a strong genetic component. Rare monogenic forms of migraine, or syndromes in which migraine frequently occurs, help scientists to unravel pathogenetic mechanisms of migraine and its comorbidities. Transgenic mouse models for rare monogenic mutations causing familial hemiplegic migraine (FHM), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and familial advanced sleep-phase syndrome (FASPS), have been created. Here, we review the current state of research using these mutant mice. We also discuss how currently available experimental approaches, including epigenetic studies, biomolecular analysis and optogenetic technologies, can be used for characterization of migraine genes to further unravel the functional and molecular pathways involved in migraine. C1 [Chen, Shih-Pin] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei, Taiwan. [Chen, Shih-Pin] Natl Yang Ming Univ, Sch Med, Fac Med, Taipei 112, Taiwan. [Chen, Shih-Pin; Eikermann-Haerter, Katharina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Cambridge, MA 02138 USA. [Tolner, Else A.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RA Leiden, Netherlands. [Tolner, Else A.] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RA Leiden, Netherlands. RP Eikermann-Haerter, K (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM khaerter@mgh.harvard.edu FU American Heart Association [10SDG2610275]; Massachusetts General Hospital; EU [612360, 602633]; Taipei Veterans General Hospital [V104C-174]; Ministry of Science and Technology of Taiwan [MOST 104-2314-B-075-006-MY3] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded in part by the American Heart Association (10SDG2610275 to K.E.-H.) and the Massachusetts General Hospital (Claflin Distinguished Award to K.E.-H.). EU Marie Curie IAPP Program 'BRAINPATH' (no. 612360) (E.A.T.), EU 'EUROHEADPAIN' grant (no. 602633) (E.A.T.); Taipei Veterans General Hospital (V104C-174 to S.P.C) and Ministry of Science and Technology of Taiwan (MOST 104-2314-B-075-006-MY3 to S.P.C). NR 203 TC 1 Z9 1 U1 3 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2016 VL 36 IS 7 SI SI BP 704 EP 721 DI 10.1177/0333102416645933 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP3RQ UT WOS:000378413000011 PM 27154999 ER PT J AU Harris, JB AF Harris, Jason B. TI Resurrecting a Live Oral Cholera Vaccine SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE cholera; oral cholera vaccine; attenuated vaccine; CVD 103-HgR ID CVD 103-HGR; EFFICACY; TRIAL C1 [Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org NR 6 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2016 VL 62 IS 11 BP 1336 EP 1337 DI 10.1093/cid/ciw149 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DP3YX UT WOS:000378433400007 PM 27001802 ER PT J AU Ouattara, EN Robine, M Eholie, SP MacLean, RL Moh, R Losina, E Gabillard, D Paltiel, AD Danel, C Walensky, RP Anglaret, X Freedberg, KA AF Ouattara, Eric N. Robine, Marion Eholie, Serge P. MacLean, Rachel L. Moh, Raoul Losina, Elena Gabillard, Delphine Paltiel, A. David Danel, Christine Walensky, Rochelle P. Anglaret, Xavier Freedberg, Kenneth A. TI Laboratory Monitoring of Antiretroviral Therapy for HIV Infection: Cost-Effectiveness and Budget Impact of Current and Novel Strategies SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; laboratory monitoring; viral load; cost-effectiveness; ART ID RESOURCE-LIMITED SETTINGS; COTE-DIVOIRE; VIRAL LOAD; VIROLOGICAL FAILURE; RANDOMIZED-TRIAL; ADULTS; AFRICA; PREVENTION; MORTALITY; BENEFITS AB Background. Optimal laboratory monitoring of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) remains controversial. We evaluated current and novel monitoring strategies in Cote d'Ivoire, West Africa. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications-International model to compare clinical outcomes, cost-effectiveness, and budget impact of 11 ART monitoring strategies varying by type (CD4 and/or viral load [VL]) and frequency. We included "adaptive" strategies (biannual then annual monitoring for patients on ART/suppressed). Mean CD4 count at ART initiation was 154/mu L. Laboratory test costs were CD4=$11 and VL=$33. The standard of care (SOC; biannual CD4) was the comparator. We assessed cost-effectiveness relative to Cote d'Ivoire's 2013 per capita GDP ($1500). Results. Discounted life expectancy was 16.69 years for SOC, 16.97 years with VL confirmation of immunologic failure, and 17.25 years for adaptive VL. Mean time on failed first-line ART was 3.7 years for SOC and <0.9 years for all routine/adaptive VL strategies. VL failure confirmation was cost-saving compared with SOC. Adaptive VL had an incremental cost-effectiveness ratio (ICER) of $4100/year of life saved compared with VL confirmation and increased the 5-year budget by $310/patient compared with SOC. Adaptive VL achieved an ICER <1x GDP if second-line ART and VL costs simultaneously decreased to $156 and $13, respectively. Conclusions. VL confirmation of immunologic failure is more effective and less costly than CD4 monitoring in Cote d'Ivoire. Adaptive VL monitoring reduces time on failing ART, is cost-effective, and should become standard in Cote d'Ivoire and similar settings. C1 [Ouattara, Eric N.; Gabillard, Delphine; Danel, Christine; Anglaret, Xavier] Univ Bordeaux, INSERM, Ctr 897, Bordeaux, France. [Ouattara, Eric N.; Gabillard, Delphine; Danel, Christine; Anglaret, Xavier] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Bordeaux, France. [Ouattara, Eric N.; Eholie, Serge P.; Moh, Raoul; Danel, Christine; Anglaret, Xavier] Treichville Univ Hosp Ctr, Programme PACCI, Agence Natl Rech SIDA & Hepatites Virales Res Sit, Abidjan, Cote Ivoire. [Ouattara, Eric N.] Univ Hosp Ctr, Div Infect & Trop Dis, Dept Med, Interdept Ctr Trop Med & Clin Int Hlth, Bordeaux, France. [Robine, Marion; MacLean, Rachel L.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Robine, Marion; MacLean, Rachel L.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Eholie, Serge P.; Moh, Raoul] Treichville Univ Hosp, Dept Infect & Trop Dis, Abidjan, Cote Ivoire. [Losina, Elena] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Freedberg, Kenneth A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ouattara, EN (reprint author), CHU Treichville, Programme PACCI, 18 BP 1954, Abidjan 18, Cote Ivoire. EM eric.ouattara@isped.u-bordeaux2.fr FU National Institute of Allergy and Infectious Diseases [R01 AI058736]; Agence Nationale de Recherches sur le SIDA et les hepatites virales in Paris, France FX This work was funded by the National Institute of Allergy and Infectious Diseases (R01 AI058736) and the Agence Nationale de Recherches sur le SIDA et les hepatites virales in Paris, France. NR 41 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2016 VL 62 IS 11 BP 1454 EP 1462 DI 10.1093/cid/ciw117 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DP3YX UT WOS:000378433400026 PM 26936666 ER PT J AU Cortes, JA Gomez, G Ehnerd, C Gurnsey, K Nicolazzo, J Bradberry, CW Jedema, HP AF Cortes, Jennifer A. Gomez, Gustavo Ehnerd, Carol Gurnsey, Kate Nicolazzo, Jessica Bradberry, Charles W. Jedema, Hank P. TI Altered activity-based sleep measures in rhesus monkeys following cocaine self-administration and abstinence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cocaine; Rhesus macaque; Sleep efficiency; Stimulant; Cognition; Actigraphy ID MACACA-MULATTA; ADMINISTERED COCAINE; ACTIGRAPHY; DEPENDENCE; USERS; ARCHITECTURE; DISORDERS; DOPAMINE; INSOMNIA; RHYTHMS AB Background: Impairments in sleep and cognitive function have been observed in patients with substance abuse disorders and may be potential factors contributing to drug relapse. In addition, sleep disruption may itself contribute to cognitive deficits. In the present study we examined the impact of prolonged cocaine self-administration and abstinence on actigraphy-based measures of night-time activity in rhesus macaques as an inferential measure of sleep, and determined whether sleep-efficiency correlated with cognitive impairments in the same subjects on drug free days. Methods: Actigraphy data was obtained from a group of rhesus macaques intravenously self-administering cocaine (n=6) and a control group (n=5). Periods were evaluated during which the mean cumulative doses of cocaine were 3.0 + 0.0 and 4.5 + 0.2 mg/kg/day for 4 days (Tuesday Thursday) each week. Results: Actigraphy-based sleep efficiency decreased during days of cocaine self-administration in a dose dependent manner. Consistent with this observation, sleep became more fragmented. Activity-based sleep efficiency normalized during the weekend without cocaine prior to cognitive assessment on Monday. The magnitude of activity-based sleep disruption during self-administration did not correlate with the level of cognitive impairment on drug free days. With continued self-administration, the impact of cocaine on activity-based sleep efficiency declined indicating the development of tolerance. Conclusions: Cocaine self-administration disrupted sleep efficiency in rhesus macaques as measured by actigraphy, but normalized quickly in the absence of cocaine. The cognitive impairment observed on drug free days was unlikely to be related to disruption of the nightly activity patterns on days of cocaine self-administration. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Cortes, Jennifer A.] Univ Pittsburgh, Dept Bioengn, 3501 Fifth Ave, Pittsburgh, PA 15261 USA. [Gomez, Gustavo; Bradberry, Charles W.] Univ Pittsburgh, Dept Neurosci, 3501 Fifth Ave, Pittsburgh, PA 15261 USA. [Ehnerd, Carol; Gurnsey, Kate; Nicolazzo, Jessica; Bradberry, Charles W.; Jedema, Hank P.] Univ Pittsburgh, Dept Psychiat, 3501 Fifth Ave, Pittsburgh, PA 15261 USA. [Bradberry, Charles W.] VA Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. RP Jedema, HP (reprint author), Univ Pittsburgh, Dept Psychiat, 3501 Fifth Ave, Pittsburgh, PA 15261 USA. EM Jedema@pitt.edu FU VA Medical Research Award [VA BLRD1IO1BX000782]; [NIH/NIDADA025636] FX This research was supported by NIH/NIDADA025636 and VA Medical Research Award VA BLR&D1IO1BX000782. NR 39 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2016 VL 163 BP 202 EP 208 DI 10.1016/j.drugalcdep.2016.04.014 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DP4HM UT WOS:000378457000026 PM 27114202 ER PT J AU Clerc, P Lipnick, S Willett, C AF Clerc, Pascaline Lipnick, Scott Willett, Catherine TI A look into the future of ALS research SO DRUG DISCOVERY TODAY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; CANINE DEGENERATIVE MYELOPATHY; MOTOR-NEURON DEGENERATION; FRONTOTEMPORAL LOBAR DEGENERATION; TRANSGENIC MOUSE MODEL; WELSH-CORGI DOGS; MUTANT SOD1; WILD-TYPE; CAENORHABDITIS-ELEGANS; HEXANUCLEOTIDE REPEAT AB Although amyotrophic lateral sclerosis (ALS), also referred as 'Lou Gehrig's Disease,' was first described in 1869 and the first disease-associated gene was discovered almost 20 years ago, the disease etiology is still not fully understood and treatment options are limited to one drug approved by the US Food and Drug Administration (FDA). The slow translational progress suggests that current research models are not ideal to study such a complicated disease and need to be re-examined. Progress will require greater insight into human genes and biology involved in ALS susceptibility, as well as a deeper understanding of disease phenotype at the histological and molecular levels. Improving human disease outcome will require directing focus toward improved assessment technologies and innovative approaches. C1 [Clerc, Pascaline; Willett, Catherine] Humane Soc United States, 700 Professional Dr, Gaithersburg, MD 20879 USA. [Lipnick, Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St, Boston, MA 02114 USA. RP Clerc, P (reprint author), Humane Soc United States, 700 Professional Dr, Gaithersburg, MD 20879 USA. EM pclerc@humanesociety.org NR 107 TC 3 Z9 3 U1 9 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUN PY 2016 VL 21 IS 6 BP 939 EP 949 DI 10.1016/j.drudis.2016.02.002 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DP7HZ UT WOS:000378671100009 PM 26861067 ER PT J AU Chng, KR Chan, SH Ng, AHQ Li, CH Jusakul, A Bertrand, D Wilm, A Choo, SP Tan, DMY Lim, KH Soetinko, R Ong, CK Duda, DG Dima, S Popescu, I Wongkham, C Feng, Z Yeoh, KG Teh, BT Yongvanit, P Wongkham, S Bhudhisawasd, V Khuntikeo, N Tan, P Pairojkul, C Ngeow, J Nagarajan, N AF Chng, Kern Rei Chan, Sock Hoai Ng, Amanda Hui Qi Li, Chenhao Jusakul, Apinya Bertrand, Denis Wilm, Andreas Choo, Su Pin Tan, Damien Meng Yew Lim, Kiat Hon Soetinko, Roy Ong, Choon Kiat Duda, Dan G. Dima, Simona Popescu, Irinel Wongkham, Chaisiri Feng, Zhu Yeoh, Khay Guan Teh, Bin Tean Yongvanit, Puangrat Wongkham, Sopit Bhudhisawasd, Vajaraphongsa Khuntikeo, Narong Tan, Patrick Pairojkul, Chawalit Ngeow, Joanne Nagarajan, Niranjan TI Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma SO EBIOMEDICINE LA English DT Article DE Microbiome; Cancer; Cholangiocarcinoma; Liver fluke ID GUT MICROBIOTA; BILE-DUCT; SEQUENCING DATA; GENE-SEQUENCES; IMMUNE-SYSTEM; CANCER; INFECTION; MICROENVIRONMENT; CARCINOGENESIS; RECONSTRUCTION AB Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer. (C) 2016 The Authors. Published by Elsevier B.V. C1 [Chng, Kern Rei; Ng, Amanda Hui Qi; Li, Chenhao; Bertrand, Denis; Wilm, Andreas; Tan, Patrick; Nagarajan, Niranjan] Genome Inst Singapore, 60 Biopolis St,02-01 Genome, Singapore 138672, Singapore. [Chan, Sock Hoai; Choo, Su Pin; Ngeow, Joanne] Natl Canc Ctr Singapore, Div Med Oncol, 11 Hosp Dr, Singapore 169610, Singapore. [Jusakul, Apinya; Ong, Choon Kiat; Teh, Bin Tean] Natl Canc Ctr Singapore, Lab Canc Epigenome, 11 Hosp Dr, Singapore 169610, Singapore. [Tan, Damien Meng Yew; Soetinko, Roy] Singapore Gen Hosp, Dept Gastroenterol & Hepatol, Outram Rd, Singapore 169608, Singapore. [Lim, Kiat Hon] Singapore Gen Hosp, Dept Pathol, Outram Rd, Singapore 169608, Singapore. [Teh, Bin Tean; Tan, Patrick] Duke NUS Grad Med Sch, Canc Sci & Stem Cell Biol, 8 Coll Rd, Singapore 169857, Singapore. [Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs Tumor Biol, Boston, MA 02114 USA. [Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA USA. [Dima, Simona; Popescu, Irinel] Fundeni Clin Inst, Ctr Digest Dis & Liver Transplantat, Bucharest, Romania. [Wongkham, Chaisiri; Yongvanit, Puangrat; Wongkham, Sopit; Bhudhisawasd, Vajaraphongsa; Khuntikeo, Narong; Pairojkul, Chawalit] Khon Kaen Univ, Liver Fluke & Cholangiocarcinoma Res Ctr, Fac Med, Khon Kaen 40002, Thailand. [Feng, Zhu; Yeoh, Khay Guan] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Yeoh, Khay Guan] Natl Univ Hlth Syst, Dept Gastroenterol & Hepatol, Singapore, Singapore. [Ngeow, Joanne] Duke NUS Grad Med Sch, Oncol Acad Clin Program, 8 Coll Rd, Singapore 169857, Singapore. RP Nagarajan, N (reprint author), Genome Inst Singapore, 60 Biopolis St,02-01 Genome, Singapore 138672, Singapore.; Pairojkul, C (reprint author), Khon Kaen Univ, Dept Pathol, Fac Med, Khon Kaen 40002, Thailand.; Ngeow, J (reprint author), Natl Canc Ctr, Div Med Oncol, Canc Genet Serv, Singapore 169610, Singapore. EM chawalit-pjk2011@hotmail.com; Joanne.Ngeow.Yuen.Yie@nccs.com.sg; nagarajann@gis.a-star.edu.sg RI Buligescu, Irina/O-4743-2016; POPESCU, IRINEL/B-3048-2008; Dima, Simona Olimpia/B-8822-2017 FU NCI NIH HHS [P01 CA080124, R01 CA159258] NR 59 TC 4 Z9 4 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JUN PY 2016 VL 8 BP 195 EP 202 DI 10.1016/j.ebiom.2016.04.034 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DP6QI UT WOS:000378622200031 PM 27428430 ER PT J AU Rosenberg, SM King, TA AF Rosenberg, Shoshana M. King, Tari A. TI Contralateral prophylactic mastectomy and quality of life: answering the unanswered questions? SO GLAND SURGERY LA English DT Editorial Material ID RECONSTRUCTION; SATISFACTION; OUTCOMES C1 [Rosenberg, Shoshana M.; King, Tari A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP King, TA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM tking7@partners.org FU AHRQ HHS [K01 HS023680] NR 7 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2227-684X EI 2227-8575 J9 GLAND SURG JI Gland Surg. PD JUN PY 2016 VL 5 IS 3 BP 261 EP 262 DI 10.21037/gs.2016.04.05 PG 2 WC Surgery SC Surgery GA DP6TV UT WOS:000378632600001 PM 27294031 ER PT J AU Mota, N Pietrzak, RH Sareen, J AF Mota, Natalie Pietrzak, Robert H. Sareen, Jitender TI Preventing Veteran Homelessness by Reducing Military Sexual Trauma Ensuring a Welcome Home SO JAMA PSYCHIATRY LA English DT Editorial Material ID US VETERANS C1 [Mota, Natalie] Univ Manitoba, Dept Clin Hlth Psychol, Winnipeg, MB, Canada. [Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sareen, Jitender] Univ Manitoba, Psychiat Psychol & Community Hlth Sci, Winnipeg, MB, Canada. RP Sareen, J (reprint author), PZ 430 PsycHlth Ctr, 771 Bannatyne Ave, Winnipeg, MB R3E 3N4, Canada. EM jitender.sareen@umanitoba.ca NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUN PY 2016 VL 73 IS 6 BP 551 EP 552 DI 10.1001/jamapsychiatry.2016.0136 PG 2 WC Psychiatry SC Psychiatry GA DQ0DH UT WOS:000378868100004 PM 27096528 ER PT J AU Holt, DJ AF Holt, Daphne J. TI A Pathway to Understanding Emotional Dysfunction in Schizophrenia SO JAMA PSYCHIATRY LA English DT Editorial Material C1 [Holt, Daphne J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holt, Daphne J.] Harvard Med Sch, Boston, MA USA. [Holt, Daphne J.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. EM dholt@partners.org NR 9 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUN PY 2016 VL 73 IS 6 BP 555 EP 556 DI 10.1001/jamapsychiatry.2016.0172 PG 2 WC Psychiatry SC Psychiatry GA DQ0DH UT WOS:000378868100006 PM 27145062 ER PT J AU Goes, FS Pirooznia, M Parla, JS Kramer, M Ghiban, E Mavruk, S Chen, YC Monson, ET Willour, VL Karchin, R Flickinger, M Locke, AE Levy, SE Scott, LJ Boehnke, M Stahl, E Moran, JL Hultman, CM Landen, M Purcell, SM Sklar, P Zandi, PP McCombie, WR Potash, JB AF Goes, Fernando S. Pirooznia, Mehdi Parla, Jennifer S. Kramer, Melissa Ghiban, Elena Mavruk, Senem Chen, Yun-Ching Monson, Eric T. Willour, Virginia L. Karchin, Rachel Flickinger, Matthew Locke, Adam E. Levy, Shawn E. Scott, Laura J. Boehnke, Michael Stahl, Eli Moran, Jennifer L. Hultman, Christina M. Landen, Mikael Purcell, Shaun M. Sklar, Pamela Zandi, Peter P. McCombie, W. Richard Potash, James B. TI Exome Sequencing of Familial Bipolar Disorder SO JAMA PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; AUTISM SPECTRUM DISORDER; DE-NOVO MUTATIONS; PSYCHIATRIC-DISORDERS; SWEDISH POPULATION; GENETIC-VARIANTS; RARE VARIANTS; SCHIZOPHRENIA; DISEASE; SUSCEPTIBILITY AB IMPORTANCE Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing. OBJECTIVE To utilize a combined family-based and case-control approach to exome sequencing in BD using multiplex families as an initial discovery strategy, followed by association testing in a large case-control meta-analysis. DESIGN, SETTING, AND PARTICIPANTS We performed exome sequencing of 36 affected members with BD from 8 multiplex families and tested rare, segregating variants in 3 independent case-control samples consisting of 3541 BD cases and 4774 controls. MAIN OUTCOMES AND MEASURES We used penalized logistic regression and 1-sided gene-burden analyses to test for association of rare, segregating damaging variants with BD. Permutation-based analyses were performed to test for overall enrichment with previously identified gene sets. RESULTS We found 84 rare (frequency <1%), segregating variants that were bioinformatically predicted to be damaging. These variants were found in 82 genes that were enriched for gene sets previously identified in de novo studies of autism (19 observed vs. 10.9 expected, P = .0066) and schizophrenia (11 observed vs. 5.1 expected, P = .0062) and for targets of the fragile X mental retardation protein (FMRP) pathway (10 observed vs. 4.4 expected, P = .0076). The case-control meta-analyses yielded 19 genes that were nominally associated with BD based either on individual variants or a gene-burden approach. Although no gene was individually significant after correction for multiple testing, this group of genes continued to show evidence for significant enrichment of de novo autism genes (6 observed vs 2.6 expected, P = .028). CONCLUSIONS AND RELEVANCE Our results are consistent with the presence of prominent locus and allelic heterogeneity in BD and suggest that very large samples will be required to definitively identify individual rare variants or genes conferring risk for this disorder. However, we also identify significant associations with gene sets composed of previously discovered de novo variants in autism and schizophrenia, as well as targets of the FRMP pathway, providing preliminary support for the overlap of potential autism and schizophrenia risk genes with rare, segregating variants in families with BD. C1 [Goes, Fernando S.; Pirooznia, Mehdi] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Meyer 4-119A,600 N Wolfe St, Baltimore, MD 21287 USA. [Parla, Jennifer S.; Kramer, Melissa; Ghiban, Elena; Mavruk, Senem; McCombie, W. Richard] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA. [Chen, Yun-Ching; Karchin, Rachel] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Chen, Yun-Ching; Karchin, Rachel] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA. [Monson, Eric T.; Willour, Virginia L.; Potash, James B.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Flickinger, Matthew; Locke, Adam E.; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Flickinger, Matthew; Locke, Adam E.; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Levy, Shawn E.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Stahl, Eli; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Stahl, Eli; Purcell, Shaun M.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Moran, Jennifer L.; Purcell, Shaun M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Hultman, Christina M.; Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Purcell, Shaun M.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA. [Purcell, Shaun M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Sklar, Pamela] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. RP Goes, FS (reprint author), Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Meyer 4-119A,600 N Wolfe St, Baltimore, MD 21287 USA. EM fgoes1@jhmi.edu OI Locke, Adam/0000-0001-6227-198X; Moran, Jennifer/0000-0002-5664-4716 FU National Institute of Mental Health [R00MH86049, K01MH093809, R01MH087992, MH09414501, MH105653, R01MH087979]; National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award FX This work was supported by grants R00MH86049 (Dr Goes), K01MH093809 (Dr Pirooznia), R01MH087992 (Dr McCombie), MH09414501 and MH105653 (Dr Boehnke), and R01MH087979 (Dr Potash) from the National Institute of Mental Health and by a National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (Dr Stahl). NR 37 TC 2 Z9 2 U1 3 U2 5 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 JUN PY 2016 VL 73 IS 6 BP 590 EP 597 DI 10.1001/jamapsychiatry.2016.0251 PG 8 WC Psychiatry SC Psychiatry GA DQ0DH UT WOS:000378868100011 PM 27120077 ER PT J AU Brandi, ML Bilezikian, JP Shoback, D Bouillon, R Clarke, BL Thakker, RV Khan, AA Potts, JT AF Brandi, Maria Luisa Bilezikian, John P. Shoback, Dolores Bouillon, Roger Clarke, Bart L. Thakker, Rajesh V. Khan, Aliya A. Potts, John T., Jr. TI Management of Hypoparathyroidism: Summary Statement and Guidelines SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN PARATHYROID-HORMONE; QUALITY-OF-LIFE; BASAL GANGLIA CALCIFICATION; RANDOMIZED CONTROLLED-TRIAL; 1-34 REPLACEMENT THERAPY; BONE-MINERAL DENSITY; LONG-TERM TREATMENT; VITAMIN-D; POSTSURGICAL HYPOPARATHYROIDISM; FOLLOW-UP AB Objective: Hypoparathyroidism is a rare disorder characterized by hypocalcemia and absent or deficient PTH. This report presents a summary of current information about epidemiology, presentation, diagnosis, clinical features, and management and proposes guidelines to help clinicians diagnose, evaluate, and manage this disorder. Participants: Participants in the First International Conference on the Management of Hypoparathyroidism represented a worldwide constituency with acknowledged interest and expertise in key basic, translational, and clinical aspects of hypoparathyroidism. Three Workshop Panels were constituted to address questions for presentation and discussion at the Conference held in Florence, Italy, May 7-9, 2015. At that time, a series of presentations were made, followed by in-depth discussions in an open forum. Each Workshop Panel also met in closed sessions to formulate the three evidence-based reports that accompany this summary statement. An Expert Panel then considered this information, developed summaries, guidelines, and a research agenda that constitutes this summary statement. Evidence: Preceding the conference, each Workshop Panel conducted an extensive literature search as noted in the individual manuscripts accompanying this report. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature. Consensus Process: This report represents the Expert Panel's synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of hypoparathyroidism. Conclusions: This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of hypoparathyroidism. C1 [Brandi, Maria Luisa] Univ Florence, Dept Surg & Translat Med, I-50121 Florence, Italy. [Bilezikian, John P.] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Shoback, Dolores] Univ Calif San Francisco, San Francisco Dept Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94121 USA. [Bouillon, Roger] Katholieke Univ Leuven, Clin & Lab Expt Endocrinol, B-3000 Leuven, Belgium. [Clarke, Bart L.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA. [Thakker, Rajesh V.] Univ Oxford, Acad Endocrine Unit, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med,Churchill Hosp, Oxford OX3 7LJ, England. [Khan, Aliya A.] McMaster Univ, Calcium Disorders Clin, Hamilton, ON L8S 4L8, Canada. [Potts, John T., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brandi, ML (reprint author), Univ Florence, Dept Surg & Translat Med, Viale Pieraccini 6, I-50139 Florence, Italy.; Bilezikian, JP (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 West 168th St, New York, NY 10032 USA. EM marialuisa.brandi@unifi.it; jpb2@cumc.columbia.edu OI Thakker, Rajesh/0000-0002-1438-3220 FU Menarini Foundation FX The Menarini Foundation provided full financial and logistical support. It did not have any participatory role in the selection of topics, speakers, or conclusions of the conference. NR 90 TC 10 Z9 12 U1 1 U2 6 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2016 VL 101 IS 6 BP 2273 EP 2283 DI 10.1210/jc.2015-3907 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9MU UT WOS:000378821100002 PM 26943719 ER PT J AU Clarke, BL Brown, EM Collins, MT Juppner, H Lakatos, P Levine, MA Mannstadt, MM Bilezikian, JP Romanischen, AF Thakker, RV AF Clarke, Bart L. Brown, Edward M. Collins, Michael T. Juppner, Harald Lakatos, Peter Levine, Michael A. Mannstadt, Michael M. Bilezikian, John P. Romanischen, Anatoly F. Thakker, Rajesh V. TI Epidemiology and Diagnosis of Hypoparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PSEUDOHYPOPARATHYROIDISM TYPE IB; BASAL GANGLIA CALCIFICATION; PROGRESSIVE OSSEOUS HETEROPLASIA; XL-ALPHA-S; PARATHYROID-HORMONE; TOTAL THYROIDECTOMY; GNAS MUTATIONS; POSTSURGICAL HYPOPARATHYROIDISM; PSEUDO-PSEUDOHYPOPARATHYROIDISM; IDIOPATHIC HYPOPARATHYROIDISM AB Context: Hypoparathyroidism is a disorder characterized by hypocalcemia due to insufficient secretion of PTH. Pseudohypoparathyroidism is a less common disorder due to target organ resistance to PTH. This report summarizes the results of the findings and recommendations of the Working Group on Epidemiology and Diagnosis of Hypoparathyroidism. Evidence Acquisition: Each contributing author reviewed the recent published literature regarding epidemiology and diagnosis of hypoparathyroidism using PubMed and other medical literature search engines. Evidence Synthesis: The prevalence of hypoparathyroidism is an estimated 37 per 100 000 person-years in the United States and 22 per 100 000 person-years in Denmark. The incidence inDenmarkis approximately 0.8 per 100 000 person-years. Estimates of prevalence and incidence of hypoparathyroidism are currently lacking inmostother countries. Hypoparathyroidism increases the risk of renal insufficiency, kidney stones, posterior subcapsular cataracts, and intracerebral calcifications, but it does not appear to increase overall mortality, cardiovascular disease, fractures, or malignancy. The diagnosis depends upon accurate measurement of PTH by second-and third-generation assays. The most common etiology is postsurgical hypoparathyroidism, followed by autoimmune disorders and rarely genetic disorders. Even more rare are etiologies including parathyroid gland infiltration, external radiation treatment, and radioactive iodine therapy for thyroid disease. Differentiation between these different etiologies is aided by the clinical presentation, serum biochemistries, and in some cases, genetic testing. Conclusions: Hypoparathyroidism is often associated with complications and comorbidities. It is important for endocrinologists and other physicians who care for these patients to be aware of recent advances in the epidemiology, diagnosis, and genetics of this disorder. C1 [Clarke, Bart L.] Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA. [Brown, Edward M.] Harvard Univ, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Juppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Juppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Juppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lakatos, Peter] Semmelweis Univ, Sch Med, Dept Med 1, H-1085 Budapest, Hungary. [Levine, Michael A.] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Endocrinol & Diabet,Dept Pediat, Philadelphia, PA 19104 USA. [Mannstadt, Michael M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bilezikian, John P.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Romanischen, Anatoly F.] St Petersburg State Pediat Med Acad, Dept Hosp Surg & Oncol, St Petersburg 194100, Russia. [Thakker, Rajesh V.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Acad Endocrine Unit,Radcliffe Dept Med, Oxford OX3 7LJ, England. RP Clarke, BL (reprint author), Mayo Clin, Div Endocrinol Diabet Metab & Nutr, Med, 200 First St SW, Rochester, MN 55905 USA. EM clarke.bart@mayo.edu OI Thakker, Rajesh/0000-0002-1438-3220; Levine, Michael/0000-0003-0036-7809 FU Shire Pharmaceuticals FX B.L.C. receives research support from Shire Pharmaceuticals and serves on two Data Monitoring Committees: Denosumab Oncology and Glucocorticoid-Induced Osteoporosis (Amgen). E.M.B. has a financial interest in the calcimimetic, Cinacalcet. M.A.L. is a member of the Scientific Advisory Board and receives research support from Shire Pharmaceuticals. M.M.M. is a member of the Scientific Advisory Board for Shire Pharmaceuticals. J.P.B. is a consultant for Amgen, Radius, Lilly, and Merck and receives research support from Shire Pharmaceuticals. R.V.T. serves in an advisory capacity for ENETS, Novartis, and Ipsen and is a consultant for AstraZeneca. The other authors have no disclosures to report. NR 75 TC 3 Z9 4 U1 5 U2 10 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2016 VL 101 IS 6 BP 2284 EP 2299 DI 10.1210/jc.2015-3908 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9MU UT WOS:000378821100003 PM 26943720 ER PT J AU Bilezikian, JP Brandi, ML Cusano, NE Mannstadt, M Rejnmark, L Rizzoli, R Rubin, MR Winer, KK Liberman, UA Potts, JT AF Bilezikian, John P. Brandi, Maria Luisa Cusano, Natalie E. Mannstadt, Michael Rejnmark, Lars Rizzoli, Rene Rubin, Mishaela R. Winer, Karen K. Liberman, Uri A. Potts, John T., Jr. TI Management of Hypoparathyroidism: Present and Future SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN PARATHYROID-HORMONE; QUALITY-OF-LIFE; DIETARY CALCIUM SUPPLEMENTS; RANDOMIZED CONTROLLED-TRIAL; 1-34 REPLACEMENT THERAPY; VITAMIN-D DEFICIENCY; LONG-TERM TREATMENT; CROSS-OVER TRIAL; DOUBLE-BLIND; FOLLOW-UP AB Context: Conventional management of hypoparathyroidism has focused upon maintaining the serum calcium with oral calcium and active vitamin D, often requiring high doses and giving rise to concerns about long-term consequences including renal and brain calcifications. Replacement therapy with PTH has recently become available. This paper summarizes the results of the findings and recommendations of the Working Group on Management of Hypoparathyroidism. Evidence Acquisition: Contributing authors reviewed the literature regarding physiology, pathophysiology, and nutritional aspects of hypoparathyroidism, management of acute hypocalcemia, clinical aspects of chronic management, and replacement therapy of hypoparathyroidism with PTH peptides. PubMed and other literature search engines were utilized. Evidence synthesis: Under normal circumstances, interactions between PTH and active vitamin D along with the dynamics of calcium and phosphorus absorption, renal tubular handing of those ions, and skeletal responsiveness help to maintain calcium homeostasis and skeletal health. In the absence of PTH, the gastrointestinal tract, kidneys, and skeleton are all affected, leading to hypocalcemia, hyperphosphatemia, reduced bone remodeling, and an inability to conserve filtered calcium. Acute hypocalcemia can be a medical emergency presenting with neuromuscular irritability. The recent availability of recombinant human PTH (1-84) has given hope that management of hypoparathyroidism with the missing hormone in this disorder will provide better control and reduced needs for calcium and vitamin D. Conclusions: Hypoparathyroidism is associated with abnormal calcium and skeletal homeostasis. Control with calcium and active vitamin D can be a challenge. The availability of PTH (1-84) replacement therapy may usher new opportunities for better control with reduced supplementation requirements. C1 [Bilezikian, John P.; Cusano, Natalie E.; Rubin, Mishaela R.] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Brandi, Maria Luisa] Univ Florence, Dept Surg & Translat Med, I-50121 Florence, Italy. [Mannstadt, Michael; Potts, John T., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rejnmark, Lars] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Rizzoli, Rene] Geneva Univ Hosp & Fac Med, CH-1205 Geneva, Switzerland. [Winer, Karen K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Liberman, Uri A.] Tel Aviv Univ, Sackler Sch Med, IL-6997801 Tel Aviv, Israel. RP Bilezikian, JP (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 West 168th St,PH8W-864, New York, NY 10032 USA. EM jpb2@cumc.columbia.edu FU Shire Pharmaceuticals; Amgen; Eli Lilly; Merck; Chugai FX J.P.B. is a consultant for Amgen, Radius, and Merck and receives research support from Shire Pharmaceuticals. M.R.R. receives research support from Shire Pharmaceuticals. M.L.B. is a consultant for Alexion, Abiogen, Amgen, Bruno Farmaceutici, Eli Lilly, Merck, Shire Pharmaceuticals, SPA, and Servier and receives research support from Shire Pharmaceuticals, Amgen, Eli Lilly, and Merck. J.T.P. is a founder and consultant for Radius and a consultant for Merck and receives research support from Chugai. The other co-authors report no conflicts of interest. NR 90 TC 5 Z9 6 U1 1 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2016 VL 101 IS 6 BP 2313 EP 2324 DI 10.1210/jc.2015-3910 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9MU UT WOS:000378821100005 PM 26938200 ER PT J AU Barr, ML Chiu, HK Li, N Yeh, MW Rhee, CM Casillas, J Iskander, PJ Leung, AM AF Barr, Meaghan L. Chiu, Harvey K. Li, Ning Yeh, Michael W. Rhee, Connie M. Casillas, Jacqueline Iskander, Paul J. Leung, Angela M. TI Thyroid Dysfunction in Children Exposed to Iodinated Contrast Media SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL HEART-DISEASE; HYPOTHYROIDISM; INFANTS AB Context: Iodinated contrast media (ICM) is routinely used in imaging studies and contains several 100-fold the recommended daily allowance of iodine. Objective: To determine whether children exposed to ICM have a higher risk of iodine-induced thyroid dysfunction. Design: This was a single-institution case-control study, examining patients with incident thyroid dysfunction aged less than 18 years from 2001 to 2015. Cases were matched 1:1 to euthyroid controls by age, sex, and race. Setting: This was a single-institution case-control study occurring at tertiary care center. Participants: Cases were defined as those with thyroid dysfunction (by International Classification of Diseases, Ninth Revision diagnosis codes and/or 2 consecutive abnormal serum TSH values <6 mo apart). We analyzed 870 cases matched to 870 controls (64% female, 51% White). Main Outcomes Measures: Using conditional logistic regression, the association between ICM exposure and the primary outcome, thyroid dysfunction, occurring within 2 years of exposure was assessed. Results: Sixty-nine patients received ICM, including 53 (6%) among cases and 16 (2%) among controls. The risk of incident hypothyroidism was significantly higher after ICM exposure (odds ratio 2.60; 95% confidence interval, 1.43-4.72; P < .01). The median interval between exposureand onset of hypothyroidism was 10.8 months (interquartile range, 6.6-17.9). In hypothyroid cases, the median serum TSH concentration was 6.5 mIU/L (interquartile range, 5.8-9.6). Conclusions: ICM exposure increases the risk of incident hypothyroidism in pediatric patients. Children receiving ICM should be monitored for iodine-induced thyroid dysfunction, particularly during the first year after exposure. C1 [Barr, Meaghan L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. [Chiu, Harvey K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Pediat Endocrinol, Los Angeles, CA 90073 USA. [Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90073 USA. [Yeh, Michael W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Sect Endocrine Surg, Los Angeles, CA 90073 USA. [Rhee, Connie M.] Univ Calif Irvine, Sch Med, Div Nephrol & Hypertens, Irvine, CA 92697 USA. [Casillas, Jacqueline] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Pediat Hematol & Oncol, Los Angeles, CA 90073 USA. [Iskander, Paul J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90073 USA. [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90073 USA. [Leung, Angela M.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA 90073 USA. RP Leung, AM (reprint author), 11301 Wilshire Blvd 111D, Los Angeles, CA 90073 USA. EM amleung@mednet.ucla.edu FU National Institutes of Health [K23HD068552]; University of California Los Angeles David Geffen School of Medicine FX This work was supported by the National Institutes of Health Grant K23HD068552 (to A.M.L.) and the University of California Los Angeles David Geffen School of Medicine Short-Term Training Project (M.L.B.). NR 27 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2016 VL 101 IS 6 BP 2366 EP 2370 DI 10.1210/jc.2016-1330 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9MU UT WOS:000378821100011 PM 27018967 ER PT J AU Ahearn, TU Tchrakian, N Wilson, KM Lis, R Nuttall, E Sesso, HD Loda, M Giovannucci, E Mucci, LA Finn, S Shui, IM AF Ahearn, Thomas U. Tchrakian, Nairi Wilson, Kathryn M. Lis, Rosina Nuttall, Elizabeth Sesso, Howard D. Loda, Massimo Giovannucci, Edward Mucci, Lorelei A. Finn, Stephen Shui, Irene M. TI Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN BREAST-CANCER; VITAMIN-D; EXTRACELLULAR CALCIUM; GENETIC-VARIATION; BONE METASTASIS; HEALTH-PROFESSIONALS; PROTEIN EXPRESSION; RISK; ACTIVATION; SECRETION AB Context: Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. Objective: We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. Design: Avalidated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. Setting: The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. Participants: We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Main Outcome: Participants were followed up or cancer-specific mortality or development of metastatic disease. Results: On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Conclusions: Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases. C1 [Ahearn, Thomas U.; Wilson, Kathryn M.; Nuttall, Elizabeth; Sesso, Howard D.; Giovannucci, Edward; Mucci, Lorelei A.; Shui, Irene M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Lis, Rosina; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Wilson, Kathryn M.; Giovannucci, Edward; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Tchrakian, Nairi; Finn, Stephen] Trinity Coll Dublin, Dept Histopathol Res, Dublin 8, Ireland. [Shui, Irene M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. RP Ahearn, TU (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,9th Floor, Boston, MA 02115 USA. EM tahearn@hsph.harvard.edu OI Finn, Stephen/0000-0002-8628-5814 FU National Institute of Health [R01CA136578, R01CA179129, UM1 CA167552, P50 CA090381, T32 CA09001]; Prostate Cancer Foundation; American Cancer Society-Ellison Foundation [PF-14-140-01-CCE]; Department of Defense; National Cancer Institute [CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute (Bethesda, Maryland) [HL-26490, HL-34595] FX This work was supported by National Institute of Health Grants R01CA136578, R01CA179129, UM1 CA167552, P50 CA090381, and T32 CA09001 (to T.U.A.); the Prostate Cancer Foundation Young Investigators Awards (to L.A.M. and K.M.W.); the American Cancer Society-Ellison Foundation Postdoctoral Fellowship PF-14-140-01-CCE (to T.U.A.); a Department of Defense Prostate Cancer Research Program Fellowship (to I.M.S.). The Physicians' Health Study is supported by Grants CA-34944 and CA-40360, Grant CA-097193 from the National Cancer Institute, and Grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute (Bethesda, Maryland). NR 38 TC 3 Z9 3 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2016 VL 101 IS 6 BP 2520 EP 2527 DI 10.1210/jc.2016-1082 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP9MU UT WOS:000378821100029 PM 27115058 ER PT J AU Huffman, JC DuBois, CM Mastromauro, CA Moore, SV Suarez, L Park, ER AF Huffman, Jeff C. DuBois, Christina M. Mastromauro, Carol A. Moore, Shannon V. Suarez, Laura Park, Elyse R. TI Positive psychological states and health behaviors in acute coronary syndrome patients: A qualitative study SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE adherence; coronary heart disease; health behavior; optimism; qualitative methods ID RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; PHYSICAL-ACTIVITY; CARDIAC REHABILITATION; DISPOSITIONAL OPTIMISM; CARDIOVASCULAR EVENTS; POSTTRAUMATIC GROWTH; UNSTABLE ANGINA; SELF-EFFICACY AB Positive psychological states are linked to superior cardiac outcomes, possibly mediated through increased participation in health behaviors. Trained study staff conducted in-depth semi-structured interviews in the hospital and 3months later for 34 patients diagnosed with an acute coronary syndrome. These interviews focused on positive psychological states, cardiac health behaviors, and their connection; the interviews were transcribed and independently coded using directed content analysis. Both optimism and positive affect were associated with completion of physical activity and healthy eating in a bidirectional manner. In contrast, gratitude, while common, was infrequently linked to completion of health behaviors. C1 [Huffman, Jeff C.; DuBois, Christina M.; Mastromauro, Carol A.; Moore, Shannon V.; Suarez, Laura; Park, Elyse R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Huffman, Jeff C.; Suarez, Laura; Park, Elyse R.] Harvard Med Sch, Boston, MA USA. [Park, Elyse R.] Benson Henry Inst Mind Body Med, Boston, MA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU National Institutes of Health-National Heart, Lung, and Blood Institute [R01HL113272] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health-National Heart, Lung, and Blood Institute (grant no. R01HL113272). NR 56 TC 2 Z9 2 U1 4 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 EI 1461-7277 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JUN PY 2016 VL 21 IS 6 BP 1026 EP 1036 DI 10.1177/1359105314544135 PG 11 WC Psychology, Clinical SC Psychology GA DP8JZ UT WOS:000378745700015 PM 25114026 ER PT J AU Adams, JM Bryant, DC AF Adams, Jeffrey M. Bryant, Debbie Chatman TI The Influence of Emerging Nursing Social and Community Partnership Leaders: An Interview With Dr Debbie Chatman Bryant SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB This department highlights emerging nursing leaders who have demonstrated leadership in advancing innovation and patient care in practice policy, research, education, and theory. This interview profiles Debbie Chatman Bryant, DNP, RN, director, Partnerships for Healthcare Quality Research, and director, Community Outreach, Hollings Cancer Center, Medical University of South Carolina. C1 [Bryant, Debbie Chatman] Partnerships Healthcare Qual Res, Charleston, SC USA. [Bryant, Debbie Chatman] Med Univ S Carolina, Hollings Canc Ctr, Community Outreach, Charleston, SC 29425 USA. [Adams, Jeffrey M.] Arizona State Univ, Coll Nursing & Hlth Innovat, WORLD Inst, Phoenix, AZ USA. [Adams, Jeffrey M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Adams, Jeffrey M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Adams, JM (reprint author), Brigham & Womens Hosp, Ctr Nursing Excellence BC 4 006A, 1620 Tremont St, Boston, MA 02120 USA. EM jeff.adams@world-institute.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2016 VL 46 IS 6 BP 297 EP 299 DI 10.1097/NNA.0000000000000348 PG 3 WC Nursing SC Nursing GA DP6LM UT WOS:000378608600004 PM 27214332 ER PT J AU Do, S AF Do, Synho TI The future of artificial intelligence for physicians SO JOURNAL OF THE KOREAN MEDICAL ASSOCIATION LA Korean DT Article DE Artificial Intelligence; Delivery of health care; Clinical decision support system AB Artificial Intelligence (AI) to support the medical decision-making process has long been both an interest and concern of physicians and the public. However, the introduction of open source software, supercomputers, and a variety of industry innovations has accelerated the progress of the development of AI in clinical decision support systems. This article summarizes the current trends and challenges in the medical field, and presents how AI can improve healthcare systems by increasing efficiency and decreasing costs. At the same time, it emphasizes the centrality of the role of physicians in utilizing AI as a tool to supplement their decisions as they provide patient-oriented care. C1 [Do, Synho] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Do, Synho] Harvard Univ, Sch Med, Boston, MA USA. RP Do, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Do, S (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM sdo@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 5 U2 6 PU KOREAN MEDICAL ASSOC PI SEOUL PA 302-75 INCHON-1 DONG, YONGSAN-GU, SEOUL, 140-721, SOUTH KOREA SN 1975-8456 EI 2093-5951 J9 J KOREAN MED ASSOC JI J. Korean Med. Assoc. PD JUN PY 2016 VL 59 IS 6 BP 410 EP 412 DI 10.5124/jkma.2016.59.6.410 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DP9JW UT WOS:000378813500001 ER PT J AU Bove, R Healy, BC Musallam, A Glanz, BI De Jager, PL Chitnis, T AF Bove, Riley Healy, Brian C. Musallam, Alexander Glanz, Bonnie I. De Jager, Philip L. Chitnis, Tanuja TI Exploration of changes in disability after menopause in a longitudinal multiple sclerosis cohort SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Clinically isolated syndrome; disability; disease progression; estrogen; hormone replacement therapy; menopause; multiple sclerosis; oophorectomy; patient reported outcome; quality of life ID WOMEN; DISEASE; SEX; AGE; IMPACT; ONSET; MS; SYMPTOMS; EXPOSURE; THERAPY AB Background: Onset of multiple sclerosis (MS) is typically in early adulthood. The impact, if any, of menopause on the MS course is unknown. Our objective was to determine whether menopause is associated with changes in MS severity in a longitudinal clinical cohort. Methods: Responses from an ongoing reproductive questionnaire deployed in all active female CLIMB observational study participants with a diagnosis of clinically isolated syndrome (CIS) or MS were analyzed when the response rate was 60%. Reproductive data were linked with clinical severity measures that were prospectively collected every six months, including our primary measure, the Expanded Disability Status Scale (EDSS). Results: Over one-half of the respondents (368 of 724 women) were postmenopausal. Median age at natural menopause was 51.5 years. In our primary analysis of 124 women who were followed longitudinally (mean duration 10.4 years) through their menopausal transition (natural or surgical), menopause represented an inflection point in their EDSS changes (difference of 0.076 units; 95% CI 0.010-0.14; p = 0.024). These findings were not explained by vitamin D levels, nor changes in treatment or smoking status over this period. There was no effect of hormone replacement therapy (HRT) exposure, but HRT use was low. Conclusions: We observed a possible worsening of MS disability after menopause. Larger cohorts are required to assess any HRT effects. C1 [Bove, Riley; Healy, Brian C.; Musallam, Alexander; Glanz, Bonnie I.; De Jager, Philip L.; Chitnis, Tanuja] Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. [Bove, Riley; Healy, Brian C.; Glanz, Bonnie I.; De Jager, Philip L.; Chitnis, Tanuja] Harvard Univ, Sch Med, Boston, MA USA. [Bove, Riley; Healy, Brian C.; De Jager, Philip L.; Chitnis, Tanuja] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA USA. [Healy, Brian C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM tchitnis@rics.bwh.harvard.edu FU National Multiple Sclerosis Society [RG-4256A4/2]; National Multiple Sclerosis Society/American Brain Foundation [FAN 1761-A-1]; NIH [5K12HD051959-09] FX This work was supported by the National Multiple Sclerosis Society (grant number RG-4256A4/2 to TC), the National Multiple Sclerosis Society/American Brain Foundation (Clinician Scientist Award FAN 1761-A-1 to RB) and the NIH (grant number 5K12HD051959-09 BIRCWH Scholar Award to RB). NR 34 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JUN PY 2016 VL 22 IS 7 BP 935 EP 943 DI 10.1177/1352458515606211 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP4EQ UT WOS:000378449400014 PM 26447063 ER PT J AU Wakeman, CA Moore, JL Noto, MJ Zhang, YF Singleton, MD Prentice, BM Gilston, BA Doster, RS Gaddy, JA Chazin, WJ Caprioli, RM Skaar, EP AF Wakeman, Catherine A. Moore, Jessica L. Noto, Michael J. Zhang, Yaofang Singleton, Marc D. Prentice, Boone M. Gilston, Benjamin A. Doster, Ryan S. Gaddy, Jennifer A. Chazin, Walter J. Caprioli, Richard M. Skaar, Eric P. TI The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction SO NATURE COMMUNICATIONS LA English DT Article ID IMAGING MASS-SPECTROMETRY; CYSTIC-FIBROSIS; BIOFILM FORMATION; MICROBIAL BIOFILMS; IRON HOMEOSTASIS; HUMAN-DISEASE; PATHOGENESIS; INFECTION; PYOVERDINE; ADAPTATION AB Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we herein visualize protein and metal distributions within Pseudomonas aeruginosa biofilms using imaging mass spectrometry. These in vitro experiments reveal correlations between differential protein distribution and metal abundance. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections. C1 [Wakeman, Catherine A.; Gaddy, Jennifer A.; Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Wakeman, Catherine A.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Moore, Jessica L.; Singleton, Marc D.; Chazin, Walter J.; Caprioli, Richard M.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Noto, Michael J.; Doster, Ryan S.; Gaddy, Jennifer A.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN 37232 USA. [Zhang, Yaofang; Prentice, Boone M.; Gilston, Benjamin A.; Chazin, Walter J.; Caprioli, Richard M.] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. RP Skaar, EP (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.; Skaar, EP (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA. EM r.caprioli@vanderbilt.edu; eric.skaar@vanderbilt.edu FU NIH/NIGMS [8P41 GM103391-05, S10 RR026742, P30 ES000267, R01 Al101171]; United States Department of Veterans Affairs Merit Award [INFB-024-13F]; Cystic Fibrosis Foundation; Department of Veterans Affairs [CDA-2 1IK2BX001701]; [T32 GM065086]; [T32AI007474-20]; [2T32HD060554-06A2] FX We thank Dr Hayes McDonald and Anna Felix of the Vanderbilt University Proteomics Core Laboratory for bottom-up proteomics analyses, Dr Nripesh Prasad from HudsonAlpha for analysis of RNA sequencing data, Dr Shannon Cornett of Bruker Daltonics for assistance with the rapifleX MALDI Tissuetyper, and members of the Caprioli and Skaar laboratories for critical reading of this manuscript. This work was supported by NIH/NIGMS grants 8P41 GM103391-05 to R.M.C., and by S10 RR026742, P30 ES000267 and R01 Al101171 to E.P.S., as well as the United States Department of Veterans Affairs Merit Award INFB-024-13F. J.L.M. is supported by grant number T32 GM065086. M.J.N. is supported by the Cystic Fibrosis Foundation. J.A.G. is supported by the Department of Veterans Affairs CDA-2 1IK2BX001701. R.S.D. has been supported by grants T32AI007474-20 and 2T32HD060554-06A2. Scanning electron imaging was performed in part through the use of the VUMC Cell Imaging Shared Resource. NR 67 TC 3 Z9 3 U1 6 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2016 VL 7 AR 11951 DI 10.1038/ncomms11951 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DP7NL UT WOS:000378686000001 PM 27301800 ER PT J AU Batalden, RP Weinstein, MM Foust-Wright, C Alperin, M Wakamatsu, MM Pulliam, SJ AF Batalden, Rebecca Posthuma Weinstein, Milena M. Foust-Wright, Caroline Alperin, Marianna Wakamatsu, May M. Pulliam, Samantha J. TI Clinical application of IUGA/ICS classification system for mesh erosion SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE CTS classification system; IUGA; ICS classification system; mesh erosion; surgery ID STRESS URINARY-INCONTINENCE; PELVIC ORGAN PROLAPSE; ICS JOINT TERMINOLOGY; FLOOR SURGERY; GRAFT INSERTION; COMPLICATIONS; PROSTHESES; OUTCOMES; WOMEN; RISK AB AimsOur aim was to assess the usability of the IUGA/ICS classification system for mesh erosion in a tertiary clinical practice and to determine if assigned classification is associated with patient symptoms, treatment, and outcome. MethodsWe retrospectively identified women who had mesh erosion after prolapse or incontinence surgery. Each erosion was classified using the IUGA/ICS category time site (CTS) system. Associations between classification and presenting symptom (asymptomatic, pain, bleeding, voiding, or defecatory dysfunction, infection, prolapse), treatment type, and outcome were evaluated with chi-squared test, student's t-test, and univariate logistic regression. ResultsWe identified 74 subjects with mesh erosion; only 70% were classifiable. Asymptomatic patients (n=19) (Category A) were more likely to be managed conservatively (P=0.001). Symptomatic patients (n=55) (Category B) were more likely to be managed surgically (P=0.003). Other variables had no association with treatment. No variables were associated with outcome. Presenting symptom was associated with both treatment (P=0.005) and outcome (P=0.03). Asymptomatic subjects were more likely to have satisfactory outcome (P=0.03). Urinary frequency and urgency were highly correlated with surgical management (P=0.02). ConclusionsOne third of mesh erosions could not be retrospectively coded using the IUGA/ICS classification. The components of the system were not predictive of treatment nor outcome with exception of the Category A (asymptomatic) and Category B (symptomatic). Asymptomatic women with mesh erosion can be successfully managed with conservative measures. Use of a classification system may be enhanced if the system is simplified by limiting the number of variables to those associated with interventions and patient outcome. Neurourol. Urodynam. 35:589-594, 2016. (c) 2015 Wiley Periodicals, Inc. C1 [Batalden, Rebecca Posthuma; Weinstein, Milena M.; Foust-Wright, Caroline; Wakamatsu, May M.; Pulliam, Samantha J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Alperin, Marianna] Univ Calif San Diego, San Diego, CA 92103 USA. RP Pulliam, SJ (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Female Pelv Med & Reconstruct Surg, 55 Fruit St,Founders 5, Boston, MA 02114 USA. EM spulliam@mgh.harvard.edu FU NICHD NIH HHS [K12 HD001259] NR 23 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD JUN PY 2016 VL 35 IS 5 BP 589 EP 594 DI 10.1002/nau.22756 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DP5HZ UT WOS:000378528200006 PM 25874639 ER PT J AU Homan, HD Dmochowski, R Cochran, JS Karsh, L Sherman, ND Yalla, S AF Homan, Harvey D. Dmochowski, Roger Cochran, James S. Karsh, Lawrence Sherman, Neil D. Yalla, Subbarao TI Safety and efficacy of a patient-controlled bladder management system for treating urinary retention in men SO NEUROUROLOGY AND URODYNAMICS LA English DT Article DE bladder outlet obstruction; quality of life; urinary bladder drainage; urinary bladder control; urinary catheters; urinary retention; urinary tract infections ID SPINAL-CORD-INJURY; TRACT-INFECTION; CATHETER AB AimsThe CymActive Bladder Management System (BMS) is a self-retaining, intraurethral catheter with a patient-controlled magnetic valve that allows cyclical bladder filling and emptying, without external appliances. We determined the safety and efficacy of the BMS in men with urinary retention who required catheterization for more than 7 days. MethodsMen requiring continuous drainage, bladder capacity less than 300ml, history of prostatic or urethral surgery, or urethral length outside of defined limits, were excluded. Data were collected from patient diaries and weekly visits during catheterization for up to 30 days. The primary composite endpoint assessed four outcomes: placement, post-void residual volume (PVR) of 75ml or less, adverse device-related events requiring early removal, and removal. ResultsNine of 23 patients met all four criteria: eight of 18 non-neurogenic (7/11 prior Foley users and 1/7 without Foley experience) and one of five neurogenic spinal cord injury (SCI) patients. Secondary outcomes in non-neurogenic patients included: 17/18 successful insertions; of these, 16/17 average PVR of 75ml; successful valve openings and closings 95% of more than 1,400 voids; and minimal leakage. Four of five SCI patients discontinued within 7 days. Cystourethroscopy after removal revealed no marked inflammation or mucosal changes. ConclusionsThis pilot study demonstrated the BMS is potentially useful, convenient, and safe for appropriate patients. A follow-up study will better define the characteristics of patients who benefit from this device and examine whether the use of antimuscarinic agents improves outcomes. Neurourol. Urodynam. 35:630-635, 2016. (c) 2015 Wiley Periodicals, Inc. C1 [Homan, Harvey D.] Ingen Med Ltd, 64 New Cavendish St, London W1G 8TB, England. [Dmochowski, Roger] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. [Cochran, James S.] Urol Clin North Texas, Dallas, TX USA. [Karsh, Lawrence] Urol Ctr Colorado, Denver, CO USA. [Sherman, Neil D.] Urol Surg Associates, Premier Urol Grp, Edison, NJ USA. [Yalla, Subbarao] Harvard Univ, Sch Med, Dept Urol, VA Boston Healthcare Syst, Boston, MA USA. RP Homan, HD (reprint author), Ingen Med Ltd, 64 New Cavendish St, London W1G 8TB, England. EM harveydhoman@ingenionmedical.com FU NIH [R44HD039566] FX Grant sponsor: NIH; Grant number: #R44HD039566 NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2467 EI 1520-6777 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PD JUN PY 2016 VL 35 IS 5 BP 630 EP 635 DI 10.1002/nau.22770 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DP5HZ UT WOS:000378528200014 PM 25856157 ER PT J AU Cairncross, C Grant, C Stonehouse, W Conlon, C McDonald, B Houghton, L Eyles, D Camargo, CA Coad, J von Hurst, P AF Cairncross, Carolyn Grant, Cameron Stonehouse, Welma Conlon, Cath McDonald, Barry Houghton, Lisa Eyles, Darryl Camargo, Carlos A., Jr. Coad, Jane von Hurst, Pamela TI The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children SO NUTRIENTS LA English DT Article DE vitamin D; children; allergic disease; New Zealand ID 25-HYDROXYVITAMIN D LEVELS; DRIED BLOOD SPOTS; ATOPIC-DERMATITIS; D DEFICIENCY; FOOD ALLERGY; D-RECEPTOR; D LEVEL; ASTHMA; SEVERITY; SENSITIZATION AB Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations >= 75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50-74.9 nmol/L (OR = 2.21, 1.33-3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children. C1 [Cairncross, Carolyn; Conlon, Cath; Coad, Jane; von Hurst, Pamela] Massey Univ, Sch Food & Nutr, Auckland 0632, New Zealand. [Grant, Cameron] Univ Auckland, Dept Paediat, Auckland 1010, New Zealand. [Grant, Cameron] Gen Paediat, Auckland 1010, New Zealand. [Grant, Cameron] Starship Childrens Hosp, Aucklan 1023, New Zealand. [Stonehouse, Welma] CSIRO Food & Nutr, Adelaide, SA 5000, Australia. [McDonald, Barry] Massey Univ, Inst Nat & Math Sci, Auckland 0632, New Zealand. [Houghton, Lisa] Univ Otago, Dept Human Nutr, Dunedin 9016, New Zealand. [Eyles, Darryl] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Eyles, Darryl] Queensland Ctr Mental Hlth Res, Brisbane, Qld 4072, Australia. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP von Hurst, P (reprint author), Massey Univ, Sch Food & Nutr, Auckland 0632, New Zealand. EM C.t.cairncross@massey.ac.nz; cc.grant@auckland.ac.nz; welma.stonehouse@csiro.au; c.conlon@massey.ac.nz; b.mcdonald@massey.ac.nz; lisa.houghton@otago.ac.nz; d.eyles@uq.edu.au; ccamargo@partners.org; j.coad@massey.ac.nz; p.r.vonhurst@massey.ac.nz RI Stonehouse, Welma/H-2316-2013; OI Camargo, Carlos/0000-0002-5071-7654; Grant, Cameron/0000-0002-4032-7230 NR 54 TC 0 Z9 0 U1 1 U2 6 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD JUN PY 2016 VL 8 IS 6 AR 326 DI 10.3390/nu8060326 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DP8YF UT WOS:000378783200011 ER PT J AU Chan, JK Brady, MF Penson, RT Huang, H Birrer, MJ Walker, JL DiSilvestro, PA Rubin, SC Martin, LP Davidson, SA Huh, WK O'Malley, DM Boente, MP Michael, H Monk, BJ AF Chan, John K. Brady, Mark F. Penson, Richard T. Huang, Helen Birrer, Michael J. Walker, Joan L. DiSilvestro, Paul A. Rubin, Stephen C. Martin, Lainie P. Davidson, Susan A. Huh, Warner K. O'Malley, David M. Boente, Matthew P. Michael, Helen Monk, Bradley J. TI Weekly Versus Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Meeting Abstract C1 [Chan, John K.] Calif Pacific Palo Alto Med Fdn, Sutter Canc Res Inst, San Francisco, CA USA. [Brady, Mark F.; Huang, Helen] Roswell Pk Canc Inst, NRG Oncol Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Penson, Richard T.; Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Joan L.] Univ Oklahoma, Oklahoma City, OK USA. [DiSilvestro, Paul A.] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Rubin, Stephen C.] Univ Penn, Philadelphia, PA 19104 USA. [Martin, Lainie P.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Davidson, Susan A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Huh, Warner K.] Univ Alabama Birmingham, Birmingham, AL USA. [O'Malley, David M.] Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA. [Boente, Matthew P.] Minnesota Oncol Hematol Oncol Serv, Edina, MN USA. [Michael, Helen] Indiana Univ Sch Med, Carmel, IN USA. [Monk, Bradley J.] Creighton Univ, Sch Med, Univ Arizona, Ctr Canc, Phoenix, AZ USA. [Monk, Bradley J.] St Josephs Hosp, Phoenix, AZ USA. NR 0 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 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JUN PY 2016 VL 71 IS 6 BP 344 EP 345 DI 10.1097/OGX.0000000000000328 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DP3XL UT WOS:000378429200013 ER PT J AU Jacobs, IJ Menon, U Ryan, A Gentry-Maharaj, A Burnell, M Kalsi, JK Amso, NN Apostolidou, S Benjamin, E Cruickshank, D Crump, DN Davies, SK Dawnay, A Dobbs, S Fletcher, G Ford, J Godfrey, K Gunu, R Habib, M Hallett, R Herod, J Jenkins, H Karpinskyj, C Leeson, S Lewis, SJ Liston, WR Lopes, A Mould, T Murdoch, J Oram, D Rabideau, DJ Reynolds, K Scott, I Seif, MW Sharma, A Singh, N Taylor, J Warburton, F Widschwendter, M Williamson, K Woolas, R Fallowfield, L McGuire, AJ Campbell, S Parmar, M Skates, SJ AF Jacobs, Ian J. Menon, Usha Ryan, Andy Gentry-Maharaj, Aleksandra Burnell, Matthew Kalsi, Jatinderpal K. Amso, Nazar N. Apostolidou, Sophia Benjamin, Elizabeth Cruickshank, Derek Crump, Danielle N. Davies, Susan K. Dawnay, Anne Dobbs, Stephen Fletcher, Gwendolen Ford, Jeremy Godfrey, Keith Gunu, Richard Habib, Mariam Hallett, Rachel Herod, Jonathan Jenkins, Howard Karpinskyj, Chloe Leeson, Simon Lewis, Sara J. Liston, William R. Lopes, Alberto Mould, Tim Murdoch, John Oram, David Rabideau, Dustin J. Reynolds, Karina Scott, Ian Seif, Mourad W. Sharma, Aarti Singh, Naveena Taylor, Julie Warburton, Fiona Widschwendter, Martin Williamson, Karin Woolas, Robert Fallowfield, Lesley McGuire, Alistair J. Campbell, Stuart Parmar, Mahesh Skates, Steven J. TI Ovarian Cancer Screening and Mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A Randomized Controlled Trial SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Meeting Abstract C1 [Jacobs, Ian J.; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K.; Apostolidou, Sophia; Crump, Danielle N.; Davies, Susan K.; Fletcher, Gwendolen; Ford, Jeremy; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Karpinskyj, Chloe; Lewis, Sara J.; Liston, William R.; Sharma, Aarti; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Woolas, Robert] UCL, Inst Womens Hlth, Dept Womens Canc, London, England. [Jacobs, Ian J.] Univ New S Wales, Sydney, NSW, Australia. [Jacobs, Ian J.] Univ Manchester, Ctr Womens Hlth, Inst Human Dev, Manchester, Lancs, England. [Amso, Nazar N.] Cardiff Univ, Coll Biomed & Life Sci, Sch Med, Obstet & Gynaecol, Cardiff CF10 3AX, S Glam, Wales. [Benjamin, Elizabeth] Univ Coll London Hosp, Dept Pathol Res, Inst Canc, London, England. [Dawnay, Anne] Univ Coll London Hosp, Clin Biochem, London, England. [Mould, Tim] Univ Coll London Hosp, Dept Gynaecol Oncol, London, England. [Cruickshank, Derek] James Cook Univ Hosp, Dept Gynaecol Oncol, Middlesbrough, Cleveland, England. [Dobbs, Stephen] Belfast City Hosp, Dept Gynaecol Oncol, Belfast BT9 7AD, Antrim, North Ireland. [Ford, Jeremy] Qatari Shareholding Co, Malomatia Informat Commun & Technol QATAR, Doha, Qatar. [Godfrey, Keith; Lopes, Alberto] Queen Elizabeth Hosp, Northern Gynaecol Oncol Ctr, Gateshead, Tyne & Wear, England. [Habib, Mariam] Natl Hosp Neurol & Neurosurg, MRC, Ctr Neuromuscular Dis, Queen Sq, London WC1N 3BG, England. [Hallett, Rachel] Bangor Univ, Sch Med Sci, Bangor, Gwynedd, Wales. [Herod, Jonathan] Liverpool Womens Hosp, Dept Gynaecol, Liverpool, Merseyside, England. [Herod, Jonathan] Hamad Med Corp, Womens Hosp, Doha, Qatar. [Jenkins, Howard; Scott, Ian] Royal Derby Hosp, Dept Gynaecol Oncol, Derby, England. [Leeson, Simon] Llandudno Hosp, Dept Gynaecol Oncol, Conwy, Gwynedd, Wales. [Lopes, Alberto] Derriford Hosp, Plymouth PL6 8DH, Devon, England. [Mould, Tim] Royal Free Hosp, Dept Gynaecol Oncol, Pond St, London NW3 2QG, England. [Murdoch, John] St Michaels Hosp, Dept Gynaecol Oncol, Bristol, Avon, England. [Oram, David; Reynolds, Karina] St Bartholomews Hosp, Dept Gynaecol Oncol, London, England. [Rabideau, Dustin J.; Skates, Steven J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Seif, Mourad W.] Univ Manchester, St Marys Hosp, Cent Manchester Fdn Trust, Manchester M13 0JH, Lancs, England. [Seif, Mourad W.] Univ Manchester, Inst Canc Sci, Manchester, Lancs, England. [Sharma, Aarti] Univ Wales Hosp, Dept Gynaecol Oncol, Heath Pk, Cardiff CF4 4XW, S Glam, Wales. [Singh, Naveena] Barts Hlth Natl Hlth Serv Trust, Dept Pathol, London, England. [Warburton, Fiona] Publ Hlth England, London, England. [Williamson, Karin] City Hosp Nottingham, Dept Gynaecol Oncol, Nottingham, England. [Woolas, Robert] Queen Alexandra Hosp, Dept Gynaecol Oncol, Portsmouth, Hants, England. [Fallowfield, Lesley] Univ Sussex, Brighton & Sussex Med Sch, Sussex Hlth Outcomes Res & Educ Canc, Brighton BN1 9RH, E Sussex, England. [McGuire, Alistair J.] London Sch Econ, Dept Social Policy, London WC2A 2AE, England. [Campbell, Stuart] Create Hlth Clin, London, England. [Parmar, Mahesh] UCL, MRC, Clin Trials Unit, London, England. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JUN PY 2016 VL 71 IS 6 BP 346 EP 348 DI 10.1097/01.ogx.0000483045.61136.eb PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DP3XL UT WOS:000378429200014 ER PT J AU Ahmad, NN Butsch, WS Aidarous, S AF Ahmad, Nadia N. Butsch, Winfield Scott Aidarous, Sabina TI Clinical Management of Obesity in Women Addressing a Lifecycle of Risk SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Weight loss; Overweight; Lifestyle; Antiobesity pharmacotherapy; Bariatric surgery; Energy regulation; Obesity treatment ID GESTATIONAL WEIGHT-GAIN; BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIALS; AMERICAN-HEART-ASSOCIATION; RESTING METABOLIC-RATE; FAT-FREE MASS; PHYSICAL-ACTIVITY; ENERGY-BALANCE; BARIATRIC SURGERY; UNITED-STATES AB The World Health Organization estimates that nearly 2 billion people worldwide are overweight, 600 million of whom are obese. The increasing prevalence of this condition in women is of particular concern given its impact on reproductive health and mortality. Burgeoning data implicating maternal obesity in fetal programming and the metabolic health of future generations further suggest that obesity in women is one of the most pressing public health concerns of the twenty-first century. However, health care professionals are infrequently engaged in obesity management. This article provides a conceptual understanding of obesity and a rational approach to treatment. C1 [Ahmad, Nadia N.; Aidarous, Sabina] Obes Med Inst, Armada Towers,P2,Floor 19,Jumeirah Lake Towers, Dubai, U Arab Emirates. [Ahmad, Nadia N.] Armada Med Ctr, Internal Med, Armada Towers,P2,Floor 19,Jumeirah Lake Towers, Dubai, U Arab Emirates. [Butsch, Winfield Scott] Massachusetts Gen Hosp, MGH Weight Ctr, 50 Staniford St, Boston, MA 02114 USA. RP Ahmad, NN (reprint author), Obes Med Inst, Armada Towers,P2,Floor 19,Jumeirah Lake Towers, Dubai, U Arab Emirates. EM drahmad@obesitymedicineinstitute.com NR 103 TC 0 Z9 0 U1 5 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 0889-8545 EI 1558-0474 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD JUN PY 2016 VL 43 IS 2 BP 201 EP + DI 10.1016/j.ogc.2016.01.007 PG 31 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DP4LE UT WOS:000378466600005 PM 27212089 ER PT J AU Amorocho, MC Fat, I AF Amorocho, Martha Cordoba Fat, Iuliu TI Anesthetic Techniques in Endoscopic Sinus and Skull Base Surgery SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Anesthesia for endoscopic sinus and skull base surgery; Anesthetic techniques; Anesthesia review; Endoscopic sinus surgery; Endoscopic skull base surgery; Endoscopic surgery ID OBSTRUCTIVE SLEEP-APNEA; LARYNGEAL MASK AIRWAY; CONTROLLED HYPOTENSION; SURGICAL FIELD; BLOOD-LOSS; PROPOFOL; SEVOFLURANE; PREMEDICATION; REMIFENTANIL; QUALITY AB Endoscopic sinus approach has become one of the most common surgical techniques for endoscopic sinus and skull base surgery. Anesthetic management has an important impact on the overall patient management, from the preoperative assessment and management to the quality of the surgical field and the postoperative recovery. Hemostasis is critical for adequate anatomical endoscopic visualization. Mild controlled hypotension seems to improve the visibility of the surgical field. Reduction of intraoperative bleeding should be considered during the treatment planning. Preoperative preparations include the optimization of comorbidities and cessation of drugs that may inhibit coagulation. C1 [Amorocho, Martha Cordoba] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Anesthesiol, 243 Charles St, Boston, MA 02114 USA. [Amorocho, Martha Cordoba] Brigham & Womens Hosp, Dept Anesthesiol & Crit Care, 75 Francis St, Boston, MA 02115 USA. [Fat, Iuliu] Harbor Hosp, Dept Anesthesiol, 3001 South Hanover St, Baltimore, MD 21225 USA. RP Amorocho, MC (reprint author), Brigham & Womens Hosp, Dept Anesthesiol & Crit Care, 75 Francis St, Boston, MA 02115 USA. EM mcordoba-amorocho@partners.org NR 30 TC 1 Z9 1 U1 1 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 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 2016 VL 49 IS 3 BP 531 EP + DI 10.1016/j.otc.2016.03.004 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA DP6BL UT WOS:000378581800003 PM 27267009 ER PT J AU Lin, G Bleier, B AF Lin, Giant Bleier, Benjamin TI Surgical Management of Severe Epistaxis SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Epistaxis; Sphenopalatine artery ligation; Anterior ethmoid artery ligation; Hemostasis; Endoscopic sinus surgery ID ENDOSCOPIC SINUS SURGERY; SPHENOPALATINE ARTERY LIGATION; RANDOMIZED CONTROLLED-TRIAL; ANTERIOR ETHMOID ARTERY; CLINICAL-TRIAL; EPINEPHRINE; ANATOMY; FORAMEN AB Many patients with severe epistaxis benefit from endoscopic intervention for control of bleeding. Critical maneuvers to improve endoscopic visualization during surgery include head-of-bed elevation, application of topical vasoconstrictors, and local injection of vasonstrictors. Controlled, hypotensive anesthesia may also decrease intraoperative blood loss and improve visualization during surgery. Intractable posterior epistaxis can be controlled with high rates of success with endoscopic sphenopalatine artery ligation. Although less common, intractable anterior epistaxis may be controlled by anterior ethmoid artery ligation once this artery is identified as the primary source. Less common sources of severe epistaxis are also discussed in this article. C1 [Lin, Giant] Advocare Aroesty Ear Nose & Throat Associates, 400 Valley Rd,Suite 105, Mt Arlington, NJ 07856 USA. [Bleier, Benjamin] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Bleier, B (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com NR 27 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 2016 VL 49 IS 3 BP 627 EP + DI 10.1016/j.otc.2016.01.003 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA DP6BL UT WOS:000378581800010 PM 27267015 ER PT J AU Gleysteen, J Clayburgh, D Cohen, J AF Gleysteen, John Clayburgh, Daniel Cohen, James TI Management of Carotid Blowout from Radiation Necrosis SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Carotid blowout; Endovascular; Radiation complication ID ARTERY RUPTURE; NECK CANCERS; HEAD; EXPERIENCE; OUTCOMES AB Although the incidence of carotid blowout has decreased with the advent of better reconstructive techniques, it remains a real risk after major head and neck surgery, especially in an irradiated field. A systematic, multidisciplinary approach incorporating appropriate history and physical examination, adequate resuscitation, diagnostic computed tomography, and diagnostic and therapeutic angiography can manage most of these patients in a safe and effective manner. Surgery has a limited role in acute management, although surgical techniques are useful both for prevention of this problem and for wound management after carotid blowout. C1 [Gleysteen, John; Clayburgh, Daniel] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Otolaryngol Head & Neck Surg, Portland, OR USA. [Cohen, James] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Otolaryngol Head & Neck Surg, ENT, P3-OC,3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. RP Cohen, J (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Otolaryngol Head & Neck Surg, ENT, P3-OC,3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. EM James.Cohen2@va.gov NR 15 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 2016 VL 49 IS 3 BP 829 EP + DI 10.1016/j.otc.2016.02.001 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA DP6BL UT WOS:000378581800024 PM 27267029 ER PT J AU Cheng, TL Johnson, SB Goodman, E AF Cheng, Tina L. Johnson, Sara B. Goodman, Elizabeth TI Breaking the Intergenerational Cycle of Disadvantage: The Three Generation Approach SO PEDIATRICS LA English DT Article ID THRIFTY PHENOTYPE HYPOTHESIS; LOW-BIRTH-WEIGHT; EXTERNALIZING BEHAVIOR; SOCIOECONOMIC-STATUS; UNITED-STATES; INDIVIDUAL-DIFFERENCES; DEVELOPMENTAL ORIGINS; ANTISOCIAL-BEHAVIOR; PARENTING PRACTICES; HEALTH DISPARITIES AB Health disparities in the United States related to socioeconomic status are persistent and pervasive. This review highlights how social disadvantage, particularly low socioeconomic status and the health burden it brings, is passed from 1 generation to the next. First, we review current frameworks for understanding the intergenerational transmission of health disparities and provide 4 illustrative examples relevant to child health, development, and well-being. Second, the leading strategy to break the cycle of poverty in young families in the United States, the 2-generation approach, is reviewed. Finally, we propose a new 3-generation approach that must combine with the 2-generation approach to interrupt the intergenerational cycle of disadvantage and eliminate health disparities. C1 [Cheng, Tina L.; Johnson, Sara B.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Cheng, Tina L.; Johnson, Sara B.] Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Goodman, Elizabeth] MassGen Hosp Children, Boston, MA USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Cheng, TL (reprint author), Johns Hopkins Univ, Gen Pediat & Adolescent Med, 200 N Wolfe St,Suite 2055, Baltimore, MD 21287 USA. EM tcheng2@jhmi.edu FU DC-Baltimore Research Center on Child Health Disparities from the National Institute on Minority Health and Health Disparities [P20 MD000198]; Centro SOL; Johns Hopkins Center for Salud/(Health) and Opportunity for Latinos; Rales Center on the Integration of Health and Education; National Institutes of Health (NIH) FX This publication was supported by the DC-Baltimore Research Center on Child Health Disparities (grant P20 MD000198) from the National Institute on Minority Health and Health Disparities (TLC), Centro SOL, Johns Hopkins Center for Salud/(Health) and Opportunity for Latinos (TLC), and the Rales Center on the Integration of Health and Education (SBJ, TLC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Funded by the National Institutes of Health (NIH). NR 101 TC 0 Z9 0 U1 12 U2 13 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 JUN PY 2016 VL 137 IS 6 AR e20152467 DI 10.1542/peds.2015-2467 PG 12 WC Pediatrics SC Pediatrics GA DP5EZ UT WOS:000378520100010 ER PT J AU Frazier, AL Krailo, M Poynter, J AF Frazier, A. Lindsay Krailo, Mark Poynter, Jen TI Can Big Data Shed Light on the Origins of Pediatric Cancer? SO PEDIATRICS LA English DT Editorial Material ID NEONATAL RISK-FACTORS; DNA-DAMAGE; PHOTOTHERAPY CAUSES; CHILDHOOD LEUKEMIA; INFANTS; US; HYPERBILIRUBINEMIA; CHILDREN; DISEASE; TRENDS C1 [Frazier, A. Lindsay] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. [Krailo, Mark] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Poynter, Jen] Univ Minnesota, Dept Pediat, Div Epidemiol & Clin Res, Minneapolis, MN 55455 USA. RP Frazier, AL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM lindsay_frazier@dfci.harvard.edu NR 19 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2016 VL 137 IS 6 AR e20160983 DI 10.1542/peds.2016-0983 PG 3 WC Pediatrics SC Pediatrics GA DP5EZ UT WOS:000378520100051 ER PT J AU Goldstein, RD Kinney, HC Willinger, M AF Goldstein, Richard D. Kinney, Hannah C. Willinger, Marian TI Sudden Unexpected Death in Fetal Life Through Early Childhood SO PEDIATRICS LA English DT Article ID HEALTHY TERM INFANTS; BRAIN-STEM ABNORMALITIES; MATERNAL SLEEP PRACTICES; NORTHERN PLAINS INDIANS; TEMPORAL-LOBE EPILEPSY; TRIPLE-RISK MODEL; HEART-RATE; SUBPLATE NEURONS; RAT PUPS; CEREBRAL OXYGENATION AB In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled "Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities." Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term "SIDS" in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and "omics" approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of "SIDS" as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. C1 [Goldstein, Richard D.] Harvard Univ, Sch Med, Dept Med, Dept Psychosocial Oncol & Palliat Care,Dana Farbe, Boston, MA 02115 USA. [Kinney, Hannah C.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Goldstein, RD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D2008, Boston, MA 02115 USA. EM richard_goldstein@dfci.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health (NIH) FX This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Funded by the National Institutes of Health (NIH). NR 108 TC 2 Z9 2 U1 6 U2 8 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 JUN PY 2016 VL 137 IS 6 AR e20154661 DI 10.1542/peds.2015-4661 PG 11 WC Pediatrics SC Pediatrics GA DP5EZ UT WOS:000378520100037 ER PT J AU Ramanadhan, S Nagler, RH McCauley, MP Lora, V Minsky, S Bruff, C Muneton, YF McCloud, RF Puleo, E Viswanath, K AF Ramanadhan, Shoba Nagler, Rebekah H. McCauley, Michael P. Lora, Vilma Minsky, Sara Bruff, Carmenza Muneton, Yudy F. McCloud, Rachel F. Puleo, Elaine Viswanath, Kasisomayajula TI Much Ventured, Much Gained: Community-Engaged Data Collection by Adolescents and Young Adults SO PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION LA English DT Article DE Community-engaged research; adolescents; young adults; youth; data collection; community-based participatory research; community health research; health disparities; health promotion; process issues; North America; socioeconomic factors; students; vulnerable populations ID FRAMEWORK; HEALTH AB Background: Community-engaged data collection offers an important opportunity to build community capacity to harness the power of data and create social change. Objectives: To share lessons learned from engaging 16 adolescents and young adults from a partner community to collect data for a public opinion survey as part of a broader community-based participatory research (CBPR) project. Methods: We conducted an analysis of archival documents, process data, and an assessment of survey assistants' experiences. Lessons Learned: High-quality data were collected from a hard-to-reach population. Survey assistants benefited from exposure to research and gained professional skills. Key challenges included conducting surveys in challenging environments and managing schedule constraints during the school year. The tremendous investment made by project partners was vital for success. Conclusions: Investments required to support engaged data collection were larger than anticipated, as were the rewards, prompting greater attention to the integration of adolescents and young adults in research efforts. C1 [Ramanadhan, Shoba; Minsky, Sara; Bruff, Carmenza; Muneton, Yudy F.; McCloud, Rachel F.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Ramanadhan, Shoba; Viswanath, Kasisomayajula] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Cambridge, MA 02138 USA. [Nagler, Rebekah H.] Univ Minnesota, Sch Journalism & Mass Commun, Minneapolis, MN 55455 USA. [McCauley, Michael P.] Med Coll Wisconsin, Program Genom & Eth, Milwaukee, WI 53226 USA. [Lora, Vilma] YWCA Greater Lawrence, Lawrence, MA USA. [Puleo, Elaine] Univ Massachusetts, Dept Biostat, Amherst, MA 01003 USA. RP Ramanadhan, S (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. FU National Cancer Institute [5 P50-CA148596, 3 R25-CA057711]; Building Interdisciplinary Research Careers in Women's Health Grant from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development [2 K12-HD055887]; Office of Research on Women's Health; National Institute on Aging FX The authors are grateful to the 16 survey assistants and 3 site supervisors who drove the success of this data collection effort. This research was supported by a grant from the National Cancer Institute (5 P50-CA148596, Viswanath, PI for Project 1). Funding support for R.H.N. and M.P.M. was provided through the National Cancer Institute to the Harvard Education Program in Cancer Prevention (3 R25-CA057711); R.H.N. also acknowledges support from the Building Interdisciplinary Research Careers in Women's Health Grant (2 K12-HD055887) from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development, the Office of Research on Women's Health, and the National Institute on Aging, administered by the University of Minnesota Deborah E. Powell Center for Women's Health. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 21 TC 0 Z9 0 U1 3 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1557-0541 EI 1557-055X J9 PROG COMM HLTH PARTN JI Prog. Community Health Partnersh. PD SUM PY 2016 VL 10 IS 2 BP 217 EP 224 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DP2ME UT WOS:000378322000007 PM 27346767 ER PT J AU Nipp, RD Zullig, LL Samsa, G Peppercorn, JM Schrag, D Taylor, DH Abernethy, AP Zafar, SY AF Nipp, Ryan D. Zullig, Leah L. Samsa, Gregory Peppercorn, Jeffrey M. Schrag, Deborah Taylor, Donald H., Jr. Abernethy, Amy P. Zafar, S. Yousuf TI Identifying cancer patients who alter care or lifestyle due to treatment-related financial distress SO PSYCHO-ONCOLOGY LA English DT Article ID OF-POCKET COSTS; CHRONIC MYELOID-LEUKEMIA; BREAST-CANCER; HEALTH-CARE; PHYSICIAN COMMUNICATION; NON-ATTENDANCE; US ADULTS; SURVIVORS; BURDEN; WOMEN AB BackgroundCancer patients may experience financial distress as a side effect of their care. Little is known about which patients are at greatest risk for altering their care or lifestyle due to treatment-related financial distress. MethodsWe conducted a cross-sectional survey study to determine which patients are at greatest risk for altering their care or lifestyle due to treatment-related financial distress. Eligible patients were adults receiving cancer treatment enrolled between June 2010 and May 2011. We grouped coping strategies as lifestyle altering or care altering. We assessed coping strategies and relationships between covariates using descriptive statistics and analysis of variance. ResultsAmong 174 participants, 89% used at least one lifestyle-altering coping strategy, while 39% used a care-altering strategy. Care-altering coping strategies adopted by patients included the following: not filling a prescription (28%) and taking less medication than prescribed (23%). Lifestyle-altering strategies included the following: spending less on leisure activities (77%), spending less on basics like food and clothing (57%), borrowing money (54%), and spending savings (50%). Younger patients were more likely than older patients to use coping strategies (p<0.001). Lower-income patients adopted care-altering strategies more than higher-income patients (p=0.03). Participants with more education and shorter duration of chemotherapy used lifestyle-altering strategies more than their counterparts (both p<0.05). ConclusionsAs a means of coping with treatment-related financial distress, patients were more likely to use lifestyle-altering approaches, but more than one-third adopted potentially harmful care-altering strategies. Younger age, lower income, higher education, and shorter duration of chemotherapy were characteristics associated with greater use of coping strategies. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Nipp, Ryan D.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Samsa, Gregory; Peppercorn, Jeffrey M.; Abernethy, Amy P.; Zafar, S. Yousuf] DUMC, Div Med Oncol, Dept Med, Durham, NC USA. [Taylor, Donald H., Jr.] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. [Zullig, Leah L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Zullig, Leah L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. RP Nipp, RD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM RyanD_Nipp@DFCI.harvard.edu FU HealthWell Foundation; VA Health Services Research and Development (HSR&D) Career Development Award [CDA 13-025]; American Cancer Society Mentored Research Scholar Grant; Greenwall Foundation; Novartis; US National Institutes of Health; US Agency for Healthcare Research and Quality; Robert Wood Johnson Foundation; Pfizer; Eli Lilly; Bristol Meyers Squibb; Helsinn Therapeutics; Amgen; Kanglaite; Alexion; Biovex; DARA Therapeutics; Mi-Co FX This study was funded by the HealthWell Foundation. Dr. Zullig is supported by a VA Health Services Research and Development (HSR&D) Career Development Award (CDA 13-025).; Dr. Zafar received research support from the HealthWell Foundation and the American Cancer Society Mentored Research Scholar Grant. Dr. Peppercorn received research support from the Greenwall Foundation and Novartis. Dr. Abernethy has research funding from the US National Institutes of Health, US Agency for Healthcare Research and Quality, Robert Wood Johnson Foundation, Pfizer, Eli Lilly, Bristol Meyers Squibb, Helsinn Therapeutics, Amgen, Kanglaite, Alexion, Biovex, DARA Therapeutics, Novartis, and Mi-Co; these funds are all distributed to Duke University Medical Center to support the research. NR 37 TC 1 Z9 1 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JUN PY 2016 VL 25 IS 6 BP 719 EP 725 DI 10.1002/pon.3911 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DP8DB UT WOS:000378727000015 PM 26149817 ER PT J AU Gradus, JL Marx, BP Sloan, DM AF Gradus, Jaimie L. Marx, Brian P. Sloan, Denise M. TI Investigating the Aftermath of Terror: Fundamental Outcomes, Methodological Choices, and Future Directions SO PSYCHOSOMATIC MEDICINE LA English DT Editorial Material DE ptsd; trauma; terrorism; public health ID NEW-YORK-CITY; SEPTEMBER 11; ATTACKS; STRESS; HEALTH; SYMPTOMS; SAMPLE; TRENDS AB Acts of terrorism are becoming increasingly common throughout the world. These events represent a significant public health concern given the associated health consequences. Although it is clear that terrorist attacks have mental and physical health sequelae, the exact nature and prevalence of these consequences are unclear. Epidemiological research can play an important role in better understanding the mental and physical impact of terrorist attacks. In this editorial, we highlight recent epidemiological research on these terrorism-related health outcomes. We also provide suggestions for how future studies can build on the existing literature and describe ways in which epidemiological methods can be harnessed to extend the current literature. Lastly, we offer recommendations on how to best prepare communities for the aftermath of terrorist attacks, highlighting secondary intervention and prevention strategies. Overall, multilevel strategies are needed to adequately cope with the growing rise of terrorist acts, and these strategies will have to be reassessed as the nature of terrorist attacks changes. C1 [Gradus, Jaimie L.; Marx, Brian P.; Sloan, Denise M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. [Gradus, Jaimie L.; Marx, Brian P.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM Jaimie.Gradus@va.gov NR 15 TC 0 Z9 0 U1 9 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUN PY 2016 VL 78 IS 5 BP 522 EP 524 DI 10.1097/PSY.0000000000000330 PG 3 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DP8AD UT WOS:000378719400001 PM 27136497 ER PT J AU Fung, CH Martin, JL Josephson, K Fiorentino, L Dzierzewski, JM Jouldjian, S Tapia, JCR Mitchell, MN Alessi, C AF Fung, Constance H. Martin, Jennifer L. Josephson, Karen Fiorentino, Lavinia Dzierzewski, Joseph M. Jouldjian, Stella Rodriguez Tapia, Juan Carlos Mitchell, Michael N. Alessi, Cathy TI Efficacy of Cognitive Behavioral Therapy for Insomnia in Older Adults With Occult Sleep-Disordered Breathing SO PSYCHOSOMATIC MEDICINE LA English DT Article DE aged; cognitive behavioral therapy; continuous positive airway pressure; sleep apnea syndromes ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE INSOMNIA; PLACEBO-CONTROLLED TRIAL; SYMPTOMS; VALIDITY; ISSUES; INDEX; APNEA AB Objectives The aims of the study were to determine whether mild, occult sleep-disordered breathing (SDB) moderates the efficacy of cognitive behavioral therapy for insomnia (CBTI) in older adults and to explore whether CBTI reduces the number of patients eligible for positive airway pressure (PAP) therapy. Methods Data were analyzed for 134 adults 60 years or older with insomnia and apnea-hypopnea index (AHI) of less than 15 who were randomized to a larger study of CBTI versus a sleep education control. Sleep outcomes (sleep onset latency, total wake time, wake after sleep onset, sleep efficiency, Pittsburgh Sleep Quality Index) were compared between CBTI and control at 6 months using repeated-measures analysis of variance adjusted for baseline values. AHI of 5 or greater versus less than 5 was included as an interaction term to evaluate changes in sleep outcomes. The number of participants at baseline and 6 months with mild SDB for whom insomnia was their only other indication for PAP was also compared between CBTI and control. Results AHI status (AHI 5 [75.5% of participants] versus AHI < 5) did not moderate improvements in sleep associated with CBTI (all p values .12). Nine (45.0%) of 20 participants with mild SDB for whom insomnia was their only other indication for PAP therapy at baseline no longer had another indication for PAP at 6 months, with no significant difference between CBTI and control. Conclusions CBTI improves sleep in older veterans with insomnia and untreated mild SDB. Larger trials are needed to assess whether CBTI reduces the number of patients with mild SDB eligible for PAP. C1 [Fung, Constance H.; Martin, Jennifer L.; Josephson, Karen; Dzierzewski, Joseph M.; Jouldjian, Stella; Rodriguez Tapia, Juan Carlos; Mitchell, Michael N.; Alessi, Cathy] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Fung, Constance H.; Martin, Jennifer L.; Dzierzewski, Joseph M.; Rodriguez Tapia, Juan Carlos; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Rodriguez Tapia, Juan Carlos] Pontificia Univ Catolica Chile, Dept Med, Alameda 340, Santiago, Region Metropol, Chile. RP Fung, CH (reprint author), 16111 Plummer St,11E, North Hills, CA 91343 USA. EM constance.fung@va.gov FU Veterans Administration Health Services Research and Development [08-295]; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center; American Federation for Aging Research; American SleepMedicine Foundation Physician Scientist Training Award; National Institute on Aging of the National Institutes of Health [K23AG045937]; National Institute on Aging, American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; UCLA Claude Pepper Older Americans Independence Center [5P30AG028748]; National Center for Advancing Translational Sciences UCLA Clinical and Translational Institute [UL1TR000124] FX This study was funded by Veterans Administration Health Services Research and Development (Alessi IIR 08-295), Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research (to Fung), American SleepMedicine Foundation Physician Scientist Training Award (to Fung), and National Institute on Aging of the National Institutes of Health under Award Number K23AG045937 (to Fung)/The Beeson Career Development in Aging Research Award Program (supported by National Institute on Aging, American Federation for Aging Research, The John A. Hartford Foundation, and The Atlantic Philanthropies; to Fung). Dzierzewski was supported by UCLA Claude Pepper Older Americans Independence Center (5P30AG028748) and National Center for Advancing Translational Sciences UCLA Clinical and Translational Institute (UL1TR000124). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, US Department of Veterans Affairs, or the United States Government. The authors report no conflicts of interest. This study did not involve any off-label or investigational use. NR 28 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 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUN PY 2016 VL 78 IS 5 BP 629 EP 639 DI 10.1097/PSY.0000000000000314 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DP8AD UT WOS:000378719400013 PM 27136498 ER PT J AU Richards, LK Shingleton, RM Goldman, R Siegel, D Thompson-Brenner, H AF Richards, Lauren K. Shingleton, Rebecca M. Goldman, Rachel Siegel, Deborah Thompson-Brenner, Heather TI Integrative Dynamic Therapy for Bulimia Nervosa: An Evidence-Based Case Study SO PSYCHOTHERAPY LA English DT Article DE bulimia nervosa; case report; cognitive behavioral therapy; integrative dynamic therapy; treatment outcome ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; EATING-DISORDERS; ANOREXIA-NERVOSA; PSYCHOANALYTIC PSYCHOTHERAPY; PSYCHODYNAMIC THERAPY AB Both cognitive-behavioral therapy (CBT) and psychodynamic psychotherapy are commonly used to treat eating disorders. To further investigate the effectiveness of integrative dynamic therapy (IDT) for bulimia nervosa (BN), our research group undertook a randomized, controlled pilot study comparing IDT with CBT for BN. The case described here was selected from a sample of N = 38 female patients with the symptoms of BN who enrolled in the study. IDT incorporated aspects of the first 4-week stage of CBT, including psychoeducation, self-monitoring, and regular eating. Subsequently, the treatment focused on emotional expression, emotion regulation (defenses), intrapsychic conflict, and interpersonal relationships. The objectives of the report are to demonstrate the effectiveness of an integrative approach to the treatment of eating disorders to address the symptoms of BN and personality issues using pre-, mid-, and posttreatment data, and to illustrate the patient and clinician reactions to each approach to treatment using excerpts from session transcripts and alliance data. C1 [Richards, Lauren K.; Shingleton, Rebecca M.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Goldman, Rachel; Siegel, Deborah] Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY USA. [Thompson-Brenner, Heather] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. RP Richards, LK (reprint author), Harvard Univ, Red Sox Fdn, Sch Med, 101 Merrimac St,Suite 250, Boston, MA 02114 USA.; Richards, LK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Home Base Program, Sch Med, 101 Merrimac St,Suite 250, Boston, MA 02114 USA. EM Lrichards3@mgh.harvard.edu NR 23 TC 2 Z9 2 U1 8 U2 9 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 EI 1939-1536 J9 PSYCHOTHERAPY JI Psychotherapy PD JUN PY 2016 VL 53 IS 2 BP 195 EP 205 DI 10.1037/pst0000054 PG 11 WC Psychology, Clinical SC Psychology GA DP5OS UT WOS:000378547500007 PM 27267504 ER PT J AU Brunstein, CG Cutler, CS DeFor, TE Kim, H Bejanyan, N Garfall, A Verneris, MR Chen, YB Warlick, ED Spitzer, T Miller, JS Antin, JH Weisdorf, DJ Soiffer, R Wagner, JE Ballen, KK AF Brunstein, Claudio G. Cutler, Corey S. DeFor, Todd E. Kim, Haesook Bejanyan, Nelli Garfall, Alfred Verneris, Michael R. Chen, Yi-Bin Warlick, Erica D. Spitzer, Thomas Miller, Jeffrey S. Antin, Joseph H. Weisdorf, Daniel J. Soiffer, Robert Wagner, John E. Ballen, Karen K. TI Antigen-Level Matching at HLA-C Improves Long-Term Outcomes After Double Umbilical Cord Blood Transplantation SO TRANSFUSION LA English DT Meeting Abstract CT 14th International Cord Blood Symposium CY JUN 09-11, 2016 CL San Francisco, CA C1 [Brunstein, Claudio G.; DeFor, Todd E.; Bejanyan, Nelli; Verneris, Michael R.; Warlick, Erica D.; Miller, Jeffrey S.; Weisdorf, Daniel J.; Wagner, John E.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Cutler, Corey S.; Kim, Haesook; Antin, Joseph H.; Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chen, Yi-Bin; Spitzer, Thomas; Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Garfall, Alfred] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD JUN PY 2016 VL 56 IS 6 MA ICBS1601 BP 2A EP 2A PG 1 WC Hematology SC Hematology GA DP5QU UT WOS:000378553200002 ER PT J AU Fisher, CE Alexander, J Bhattacharya, R Rakita, RM Kirby, KA Boeckh, M Limaye, AP AF Fisher, C. E. Alexander, J. Bhattacharya, R. Rakita, R. M. Kirby, K. A. Boeckh, M. Limaye, A. P. TI Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE solid organ transplant; cytomegalovirus disease; gastrointestinal; diagnosis; sensitivity ID CELL TRANSPLANTATION; ANTIGENEMIA ASSAY; CMV ANTIGENEMIA; INFECTION; PLASMA; DNA AB BackgroundGastrointestinal (GI) cytomegalovirus (CMV) disease is the most common manifestation of tissue-invasive CMV infection in solid organ transplant (SOT) recipients, but the diagnostic yields of blood and tissue testing have not been systematically assessed in a large patient cohort. MethodsWe retrospectively identified consecutive SOT recipients with biopsy-confirmed GI CMV disease who had both tissue and blood (CMV polymerase chain reaction or antigenemia) diagnostic testing performed within 14 days of diagnosis. Descriptive statistics and logistic regression were used to assess the association between patient factors and viremia and the diagnostic yield of tests performed on biopsy specimens. ResultsA total of 101 patients (73% donor seropositive/recipient seronegative [D+/R-], 22% recipient seropositive [R+]) had GI CMV disease (58% upper, 22% lower, and 20% both) at a median of 185 days (range, 21-6345 days) post transplant. In multivariate analysis, R+ CMV serostatus (odds ratio [OR] 0.1 [0.0-0.4], P < 0.001) and diagnosis >6 months post transplant (OR 0.3 [0.1-0.9], P = 0.03) were each independently associated with absence of CMV viremia at time of diagnosis. In the subset of patients (n = 29) in whom both histopathology and viral culture were performed on biopsy specimens, 11 (39%) had CMV detected only by culture and had similar clinical characteristics and outcomes to those with positive histopathology (P > 0.05 for all comparisons). ConclusionsThe sensitivity of viremia in SOT recipients with GI CMV disease is significantly lower in CMV-seropositive patients and in those >6 months post transplant. Addition of viral culture to endoscopic biopsy specimens significantly increases the diagnostic yield for GI CMV disease. C1 [Fisher, C. E.; Rakita, R. M.; Boeckh, M.; Limaye, A. P.] Univ Washington, Dept Med, Div Allergy, Seattle, WA USA. [Fisher, C. E.; Rakita, R. M.; Boeckh, M.; Limaye, A. P.] Univ Washington, Dept Med, Div Infect Dis, Seattle, WA USA. [Fisher, C. E.; Boeckh, M.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA. [Alexander, J.; Bhattacharya, R.] Univ Washington, Dept Med, Gastroenterol, Seattle, WA USA. [Kirby, K. A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Kirby, K. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Limaye, AP (reprint author), Univ Washington, Box 356174,1959 NE Pacific St, Seattle, WA 98195 USA. EM limaye@u.washington.edu FU National Institutes of Health [5 UO1 HL102547, AI NO1 272201100041C-0-0-1, K24 HL093294] FX This work was supported in part by National Institutes of Health grants 5 UO1 HL102547 and AI NO1 272201100041C-0-0-1 to A.P.L., and K24 HL093294 to M.B. NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 EI 1399-3062 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD JUN PY 2016 VL 18 IS 3 BP 372 EP 380 DI 10.1111/tid.12531 PG 9 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA DP8AX UT WOS:000378721400007 PM 27004439 ER PT J AU Baksh, SN Gellad, WF Alexander, GC AF Baksh, Sheriza N. Gellad, Walid F. Alexander, G. Caleb TI Maximizing the Post-Approval Safety of Flibanserin: A Role for Regulators, Clinicians, and Patients. SO ZEITSCHRIFT FUR SEXUALFORSCHUNG LA German DT Editorial Material DE Flibanserin; sexual dysfunction in women; sexual health ID SEXUAL DESIRE DISORDER; PREMENOPAUSAL WOMEN EFFICACY AB In August 2015, the US Food and Drug Administration (FDA) made the controversial decision to approve flibanserin (Addyi (R)) for women experiencing hypoactive sexual desire disorder. A number of factors contributed to disagreements regarding the FDA's decision, including the product's two prior failed FDA reviews, the unmet need of women with this disorder, extensive advocacy and politicization surrounding the product's relevance to women and sexual health, the potential for widespread off-label use, and the product's tenuous risk/benefit profile. Despite that, attention now shifts to maximizing the safe use of the product, including the optimal means to avoid numerous drug-drug interactions as well as the concomitant use of alcohol, both of which potentiate the risks of dizziness, hypotension, and syncope. Although the FDA has implemented a comprehensive Risk Evaluation and Mitigation Strategies program to maximize the product's safe use, patients, clinicians, and regulators must exhibit heightened vigilance early in the product's post-market life. C1 [Baksh, Sheriza N.; Alexander, G. Caleb] Johns Hopkins Univ, Ctr Drug Safety & Effectiveness, Baltimore, MD 21205 USA. [Baksh, Sheriza N.; Alexander, G. Caleb] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gellad, Walid F.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Alexander, G. Caleb] Johns Hopkins Med, Dept Med, Baltimore, MD USA. RP Baksh, SN (reprint author), Johns Hopkins Univ, Ctr Drug Safety & Effectiveness, Baltimore, MD 21205 USA. NR 22 TC 0 Z9 0 U1 4 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0932-8114 EI 1438-9460 J9 Z SEXUALFORSCH JI Z. Sex.forsch. PD JUN PY 2016 VL 29 IS 2 BP 176 EP + DI 10.1055/s-0042-108602 PG 13 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA DP5HV UT WOS:000378527800008 ER PT J AU Osier, ND Dixon, CE AF Osier, Nicole D. Dixon, C. Edward TI Catecholaminergic based therapies for functional recovery after TBI SO BRAIN RESEARCH LA English DT Review DE Traumatic brain injury; Catecholamine; Dopamine; Epinephrine; Norepinephrine; Therapy ID TRAUMATIC BRAIN-INJURY; CONTROLLED CORTICAL IMPACT; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; NUCLEUS-ACCUMBENS DOPAMINE; CONDITIONED FEAR RESPONSE; WATER MAZE PERFORMANCE; N-METHYL TRANSFERASE; CLOSED-HEAD-INJURY; METHYLPHENIDATE TREATMENT AB Among the many pathophysiologic consequences of traumatic brain injury are changes in catecholamines, including dopamine, epinephrine, and norepinephrine. In the context of TBI, dopamine is the one most extensively studied, though some research exploring epinephrine and norepinephrine have also been published. The purpose of this review is to summarize the evidence surrounding use of drugs that target the catecholaminergic system on pathophysiological and functional outcomes of TBI using published evidence from pre-clinical and clinical brain injury studies. Evidence of the effects of specific drugs that target catecholamines as agonists or antagonists will be discussed. Taken together, available evidence suggests that therapies targeting the catecholaminergic system may attenuate functional deficits after TBI. Notably, it is fairly common for TBI patients to be treated with catecholamine agonists for either physiological symptoms of TBI (e.g. altered cerebral perfusion pressures) or a co-occuring condition (e.g. shock), or cognitive symptoms (e.g. attentional and arousal deficits). Previous clinical trials are limited by methodological limitations, failure to replicate findings, challenges translating therapies to clinical practice, the complexity or lack of specificity of catecholamine receptors, as well as potentially counfounding effects of personal and genetic factors. Overall, there is a need for additional research evidence, along with a need for systematic dissemination of important study details and results as outlined in the common data elements published by the National Institute of Neurological Diseases and Stroke. Ultimately, a better understanding of catecholamines in the context of TBI may lead to therapeutic advancements. This article is part of a Special Issue entitled SI:Brain injury and recovery. Published by Elsevier B.V. C1 [Osier, Nicole D.; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15213 USA. [Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] VA Pittsburgh Healthcare, Pittsburgh, PA 15240 USA. [Osier, Nicole D.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15213 USA. RP Dixon, CE (reprint author), Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM dixonec@upmc.edu FU VA RRD [B1127-1, F31NR014957, T32NR009759]; Pittsburgh Foundation; Sigma Theta Tau International Eta Chapter; International Society for Nurses in Genetics; American Association of Neuroscience Nursing/Neuroscience Nursing Foundation; [R01NS079061]; [R01NS091062] FX This work was generously supported by several Grants, including: R01NS079061, R01NS091062, VA RR&D #B1127-1, F31NR014957 and T32NR009759. Additional support for this work was provided by Grants from the following foundations and professional societies: The Pittsburgh Foundation, Sigma Theta Tau International Eta Chapter, The International Society for Nurses in Genetics, and The American Association of Neuroscience Nursing/Neuroscience Nursing Foundation. The authors would like to thank Marilyn K. Farmer and Amanda Savarese for their continued editorial support and Michael D. Farmer for generously volunteering his time and talents to make the figures. NR 206 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUN 1 PY 2016 VL 1640 SI SI BP 15 EP 35 DI 10.1016/j.brainres.2015.12.026 PN A PG 21 WC Neurosciences SC Neurosciences & Neurology GA DP4DY UT WOS:000378447600003 PM 26711850 ER PT J AU Bhatnagar, S Iaccarino, MA Zafonte, R AF Bhatnagar, Saurabha Iaccarino, Mary Alexis Zafonte, Ross TI Pharmacotherapy in rehabilitation of post-acute traumatic brain injury SO BRAIN RESEARCH LA English DT Review DE Traumatic brain injury; Rehabilitation; Pharmacotherapy; Concussion; Medication ID RANDOMIZED CONTROLLED-TRIAL; SPINAL-CORD-INJURY; EXCESSIVE DAYTIME SLEEPINESS; INTRATHECAL BACLOFEN THERAPY; DOUBLE-BLIND CROSSOVER; UPPER-LIMB SPASTICITY; TOXIN TYPE-A; MULTIPLE-SCLEROSIS; ATTENTION DEFICITS; MILITARY PERSONNEL AB There are nearly 1.8 million annual emergency room visits and over 289,000 annual hospitalizations related to traumatic brain injury (TBI). The goal of this review article is to highlight pharmacotherapies that we often use in the clinic that have been shown to benefit various sequelae of TBI. We have decided to focus on sequelae that we commonly encounter in our practice in the post-acute phase after a TBI. These symptoms are hyper arousal, agitation, hypo-arousal, inattention, slow processing speed, memory impairment, sleep disturbance, depression, headaches, spasticity, and paroxysmal sympathetic hyperactivity. In this review article, the current literature for the pharmacological management of these symptoms are mentioned, including medications that have not had success and some ongoing trials. It is clear that the pharmacological management specific to those with TBI is often based on small studies and that often treatment is based on assumptions of how similar conditions are managed when not relating to TBI. As the body of the literature expands and targeted treatments start to emerge for TBI, the function of pharmacological management will need to be further defined. This article is part of a Special Issue entitled SI:Brain injury and recovery. Published by Elsevier B.V. C1 [Bhatnagar, Saurabha; Iaccarino, Mary Alexis; Zafonte, Ross] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp,Med Sch, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, Boston, MA 02115 USA. RP Bhatnagar, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp,Med Sch, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, Boston, MA 02115 USA. EM sbhatnagar1@partners.org; miaccarino@partners.org; rzafonte@partners.org NR 127 TC 1 Z9 1 U1 4 U2 11 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 JUN 1 PY 2016 VL 1640 SI SI BP 164 EP 179 DI 10.1016/j.brainres.2016.01.021 PN A PG 16 WC Neurosciences SC Neurosciences & Neurology GA DP4DY UT WOS:000378447600013 PM 26801831 ER PT J AU Calleja, LR Jacques, C Lamoureux, F Baud'huin, M Gabriel, MT Quillard, T Sahay, D Perrot, P Amiaud, J Charrier, C Brion, R Lecanda, F Verrecchia, F Heymann, D Ellisen, LW Ory, B AF Calleja, Lidia Rodriguez Jacques, Camille Lamoureux, Francois Baud'huin, Marc Gabriel, Marta Tellez Quillard, Thibaut Sahay, Debashish Perrot, Pierre Amiaud, Jerome Charrier, Celine Brion, Regis Lecanda, Fernando Verrecchia, Franck Heymann, Dominique Ellisen, Leif W. Ory, Benjamin TI Delta Np63 alpha Silences a miRNA Program to Aberrantly Initiate a Wound-Healing Program That Promotes TGF beta-Induced Metastasis SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EPITHELIAL-MESENCHYMAL TRANSITION; GROWTH-FACTOR-BETA; CANCER METASTASIS; UP-REGULATION; P63; EXPRESSION; P53; SUPPRESSOR; MIGRATION AB Primary cancer cell dissemination is a key event during the metastatic cascade, but context-specific determinants of this process remain largely undefined. Multiple reports have suggested that the p53 (TP53) family member p63 (TP63) plays an anti-metastatic role through its minor epithelial isoform containing the N-terminal transactivation domain (TAp63). However, the role and contribution of the major p63 isoform lacking this domain, Delta Np63 alpha, remain largely undefined. Here, we report a distinct and TAp63-independent mechanism by which Delta Np63 alpha-expressing cells within a TGF beta-rich microenvironment become positively selected for metastatic dissemination. Orthotopic transplantation of Delta Np63 alpha-expressing human osteosarcoma cells into athymic mice resulted in larger and more frequent lung metastases than transplantation of control cells. Mechanistic investigations revealed that Delta Np63 alpha repressed miR-527 and miR-665, leading to the upregulation of two TGF beta effectors, SMAD4 and T beta RII (TGFBR2). Furthermore, we provide evidence that this mechanism reflects a fundamental role for Delta Np63 alpha in the normal wound-healing response. We show that Delta Np63 alpha-mediated repression of miR-527/665 controls a TGF beta-dependent signaling node that switches off antimigratory miR-198 by suppressing the expression of the regulatory factor, KSRP (KHSRP). Collectively, these findings reveal that a novel miRNA network involved in the regulation of physiologic wound-healing responses is hijacked and suppressed by tumor cells to promote metastatic dissemination. (C)2016 AACR. C1 [Calleja, Lidia Rodriguez; Jacques, Camille; Lamoureux, Francois; Baud'huin, Marc; Gabriel, Marta Tellez; Quillard, Thibaut; Perrot, Pierre; Amiaud, Jerome; Charrier, Celine; Brion, Regis; Verrecchia, Franck; Heymann, Dominique; Ory, Benjamin] INSERM, UMR S 957, Equipe Labellisee LIGUE 2012, Nantes, France. [Calleja, Lidia Rodriguez; Jacques, Camille; Lamoureux, Francois; Baud'huin, Marc; Gabriel, Marta Tellez; Quillard, Thibaut; Perrot, Pierre; Amiaud, Jerome; Charrier, Celine; Brion, Regis; Verrecchia, Franck; Heymann, Dominique; Ory, Benjamin] Univ Nantes, Physiopathol Resorpt Osseuse & Therapie Tumeurs O, Nantes Atlantique Univ, Rue Gaston Veil, F-44035 Nantes, France. [Baud'huin, Marc; Perrot, Pierre; Heymann, Dominique] Nantes Univ Hosp, Nantes, France. [Sahay, Debashish] Univ Lyon 1, INSERM, Fac Med, Paris, France. [Lecanda, Fernando] Univ Navarra, Ctr Appl Med Res CIMA, Div Oncol, Adhes & Metastasis Lab, Navarra, Spain. [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. RP Ellisen, LW; Ory, B (reprint author), Univ Nantes, Fac Med, 1 Rue Gaston Veil, F-44035 Nantes, France. EM LELLISEN@mgh.harvard.edu; Benjamin.ory@univ-nantes.fr FU Seventh Framework Programme (FP7) [264817 - BONE-NET]; INSERM; Region Pays de la loire, Philippe Hulin, Nantes University, PICell; [RO1 DE-015945] FX This article was written as a part of research project which received funding from the Seventh Framework Programme (FP7/2007-2013) under grant agreement no264817 - BONE-NET.L.W. Ellisen was funded by RO1 DE-015945. C. Jacques was funded by INSERM and Region Pays de la loire, Philippe Hulin, Nantes University, PICell for time-lapse microscopy. NR 52 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2016 VL 76 IS 11 BP 3236 EP 3251 DI 10.1158/0008-5472.CAN-15-2317 PG 16 WC Oncology SC Oncology GA DO8UV UT WOS:000378060900015 ER PT J AU Steffel, J Varma, N Robertson, M Singh, JP Bax, JJ Borer, JS Dickstein, K Ford, I Gorcsan, J Gras, D Krum, H Sogaard, P Holzmeister, J Brugada, J Abraham, WT Ruschitzka, F AF Steffel, Jan Varma, Niraj Robertson, Michele Singh, Jagmeet P. Bax, Jeroen J. Borer, Jeffrey S. Dickstein, Kenneth Ford, Ian Gorcsan, John, III Gras, Daniel Krum, Henry Sogaard, Peter Holzmeister, Johannes Brugada, Josep Abraham, William T. Ruschitzka, Frank TI Effect of Gender on Outcomes After Cardiac Resynchronization Therapy in Patients With a Narrow QRS Complex A Subgroup Analysis of the EchoCRT Trial SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; cardiomyopathy; female gender; heart failure; risk factor ID DEFIBRILLATOR IMPLANTATION TRIAL; CHRONIC HEART-FAILURE; PREDICTORS; WOMEN; EVENTS; DEATH; SEX; MEN AB Background-In EchoCRT, a randomized controlled trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome (death from any cause or first hospitalization for worsening heart failure) occurred more frequently in the CRT-ON when compared with the control group. In this prespecified subgroup analysis, we evaluated the effect of sex on clinical outcome in EchoCRT. Methods and Results-In EchoCRT, 585 (72%) of included patients were men. At baseline, male patients had a higher incidence of ischemic cardiomyopathy and longer QRS duration. On uni- and multivariable analysis, no significant interaction was observed regarding sex for the primary or any of the secondary end points. Numerically, a higher all-cause mortality was observed in male patients randomized to CRT-ON versus CRT-OFF on univariable analysis (hazard ratio, 1.83; 95% confidence interval, 1.08-3.12); however, no statistically significant interaction compared with females randomized to CRT-ON versus CRT-OFF was noted (hazard ratio, 0.99; P interaction, 0.56). There was no difference in the primary safety end point of system-related complications, including CRT system-and implantation-related events. Conclusions-The largest hazard for all-cause mortality in EchoCRT was observed in men randomized to CRT-ON; the comparison with women did not reach statistical significance, which may be because of the premature termination of the trial and the limited data. These results suggest that male sex may be a risk factor for harm by CRT in patients with narrow QRS width, an observation which deserves further investigation. Clinical Trial Registration-URL: https://clinicaltrials.gov. Unique identifier: NCT00683696. C1 [Steffel, Jan; Holzmeister, Johannes; Ruschitzka, Frank] Univ Heart Ctr Zurich, Dept Cardiol, Ramistr 100, CH-8091 Zurich, Switzerland. [Varma, Niraj] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Robertson, Michele; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Bax, Jeroen J.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Borer, Jeffrey S.] SUNY, Coll Med, Div Cardiovasc Med, Howard Gilman Inst, Brooklyn, NY USA. [Borer, Jeffrey S.] SUNY, Coll Med, Div Cardiovasc Med, Ron & Jean Schiavone Inst, Brooklyn, NY USA. [Dickstein, Kenneth] Univ Bergen, Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway. [Gorcsan, John, III] Univ Pittsburgh, Div Cardiol, Pittsburgh, PA 15260 USA. [Gras, Daniel] Nouvelles Clin Nantaises, Serv Cardiol, Nantes, France. [Krum, Henry] Monash Univ, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Sogaard, Peter] Aalborg Univ Hosp, Dept Cardiol, Inst Clin, Aalborg, Denmark. [Brugada, Josep] Univ Barcelona, Hosp Clin, Thorax Inst, Dept Cardiol, Barcelona, Spain. [Abraham, William T.] Ohio State Univ, Med Ctr, Davis Heart & Lung Res Inst, Div Cardiovasc Med, Columbus, OH 43210 USA. RP Ruschitzka, F (reprint author), Univ Heart Ctr Zurich, Dept Cardiol, Heart Failure Clin & Transplantat, Ramistr 100, CH-8091 Zurich, Switzerland. EM frank.ruschitzka@gmail.com FU Amgen; Astra Zeneca; Boehringer Ingelheim; Boston Scientific; Cook Medical; Sanofi Aventis; Sorin; Bayer; Biotronik; Bristol-Myers Squibb; Daiichi-Sankyo; Medtronic; Pfizer; St. Jude Medical; Biosense Webster; St. Jude; RespiCardia Inc.; CardioInsight; GE Healthcare; Lantheus; Servier; Edwards Lifesciences; Cardiorentis; ARMGO; Novartis; Celladon; BioMARIN; EBR systems FX Dr Steffel reports research support to his institution by Bayer, Daiichi-Sankyo, Biotronik, Boston Scientific, Medtronic, St. Jude Medical; consultant/Advisory Board fees by Amgen, Astra Zeneca, Boehringer Ingelheim, Boston Scientific, Cook Medical, Sanofi Aventis, Sorin, Bayer, Biotronik, Bristol-Myers Squibb, Daiichi-Sankyo, Medtronic, Pfizer, St. Jude Medical, and Biosense Webster. He is a copresident of CorXL. Dr Varma reports consultant/Advisory Board fees from Biotronik, St. Jude, Sorin, and Medtronic. Dr Singh reports consultant/Advisory Fees by St. Jude Medical, Boston Scientific, Sorin, Medtronic, CardioInsight, and RespiCardia Inc. Dr Borer reports departmental grant support from GE Healthcare, Biotronik, Boston Scientific, Medtronic, Lantheus, Servier, and Edwards Lifesciences. Dr Borer reports consultant/Advisory fees from Cardiorentis, ARMGO, Novartis, Celladon, Amgen, Pfizer, Takeda, and BioMARIN. Dr Dickstein reports grant support from Medtronic, Boston Scientific, St. Jude, Biotronik, and Sorin. Dr Ford reports grant support from Biotronik, grant support and personal fees from Servier and Medtronic, and personal fees from RESMED. Dr Gorcsan reports research grant support from Biotronik, Medtronic, and GE. Dr Gras reports personal fees from Medtronic, St. Jude Medical, Boston Scientific, and Biotronik. Dr Krum reports personal fees from Biotronik. Dr Sogaard reports consultant fees from Biotronik, GE HealthCare, Bayer, and EBR systems. Dr Holzmeister reports direct employment, options, and member of the board of Cardiorentis. Dr Brugada reports consultant/Advisory Board fees from St. Jude, Biotronik, Boston Scientific, Sorin, and Boehringer Ingelheim. Dr Abraham reports grant support and personal fees from St. Jude Medical. Dr Ruschitzka reports personal fees from Biotronik, Servier, Cardiorentis. The other authors report no conflicts. 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 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2016 VL 9 IS 6 AR e003924 DI 10.1161/CIRCEP.115.003924 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9YG UT WOS:000378143300012 ER PT J AU deGoma, EM Ahmad, ZS O'Brien, EC Kindt, I Shrader, P Newman, CB Pokharel, Y Baum, SJ Hemphill, LC Hudgins, LC Ahmed, CD Gidding, SS Duffy, D Neal, W Wilemon, K Roe, MT Rader, DJ Ballantyne, CM Linton, MF Duell, PB Shapiro, MD Moriarty, PM Knowles, JW AF deGoma, Emil M. Ahmad, Zahid S. O'Brien, Emily C. Kindt, Iris Shrader, Peter Newman, Connie B. Pokharel, Yashashwi Baum, Seth J. Hemphill, Linda C. Hudgins, Lisa C. Ahmed, Catherine D. Gidding, Samuel S. Duffy, Danielle Neal, William Wilemon, Katherine Roe, Matthew T. Rader, Daniel J. Ballantyne, Christie M. Linton, MacRae F. Duell, P. Barton Shapiro, Michael D. Moriarty, Patrick M. Knowles, Joshua W. TI Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States Data From the CASCADE-FH Registry SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; familial hypercholesterolemia; genetic heart disease; low-density lipoprotein cholesterol; statin therapy ID ASSOCIATION EXPERT PANEL; CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; RISK-FACTORS; CARDIOVASCULAR-DISEASE; LOWERING TREATMENT; CHOLESTEROL LEVELS; BLOOD CHOLESTEROL; GUIDANCE; PREVALENCE AB Background-Cardiovascular disease burden and treatment patterns among patients with familial hypercholesterolemia (FH) in the United States remain poorly described. In 2013, the FH Foundation launched the Cascade Screening for Awareness and Detection (CASCADE) of FH Registry to address this knowledge gap. Methods and Results-We conducted a cross-sectional analysis of 1295 adults with heterozygous FH enrolled in the CASCADE-FH Registry from 11 US lipid clinics. Median age at initiation of lipid-lowering therapy was 39 years, and median age at FH diagnosis was 47 years. Prevalent coronary heart disease was reported in 36% of patients, and 61% exhibited 1 or more modifiable risk factors. Median untreated low-density lipoprotein cholesterol (LDL-C) was 239 mg/dL. At enrollment, median LDL-C was 141 mg/dL; 42% of patients were taking high-intensity statin therapy and 45% received > 1 LDL-lowering medication. Among FH patients receiving LDL-lowering medication(s), 25% achieved an LDL-C < 100 mg/dL and 41% achieved a >= 50% LDL-C reduction. Factors associated with prevalent coronary heart disease included diabetes mellitus (adjusted odds ratio 1.74; 95% confidence interval 1.08-2.82) and hypertension (2.48; 1.92-3.21). Factors associated with a >= 50% LDL-C reduction from untreated levels included high-intensity statin use (7.33; 1.86-28.86) and use of > 1 LDL-lowering medication (1.80; 1.34-2.41). Conclusions-FH patients in the CASCADE-FH Registry are diagnosed late in life and often do not achieve adequate LDL-C lowering, despite a high prevalence of coronary heart disease and risk factors. These findings highlight the need for earlier diagnosis of FH and initiation of lipid-lowering therapy, more consistent use of guideline-recommended LDL-lowering therapy, and comprehensive management of traditional coronary heart disease risk factors. C1 [deGoma, Emil M.; Rader, Daniel J.] Univ Penn, Philadelphia, PA 19104 USA. [Ahmad, Zahid S.] Univ Texas Southwestern, Dallas, TX USA. [O'Brien, Emily C.; Shrader, Peter; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. [Kindt, Iris; Ahmed, Catherine D.; Wilemon, Katherine] FH Fdn, South Pasadena, MO USA. [Newman, Connie B.] NYU, Sch Med, New York, NY 10003 USA. [Pokharel, Yashashwi] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Baum, Seth J.] Prevent Cardiol Inc, Boca Raton, FL USA. [Hemphill, Linda C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hudgins, Lisa C.] Rogosin Inst, New York, NY USA. [Gidding, Samuel S.] Nemours Cardiac Ctr, Wilmington, DE USA. [Duffy, Danielle] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Neal, William] W Virginia Univ, Morgantown, WV 26506 USA. [Ballantyne, Christie M.] Baylor Coll Med, Houston, TX 77030 USA. [Linton, MacRae F.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Duell, P. Barton; Shapiro, Michael D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Moriarty, Patrick M.] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. [Knowles, Joshua W.] Stanford Univ, Stanford, CA 94305 USA. RP Knowles, JW (reprint author), Stanford Univ, Cardiovasc Med, Falk CVRC, Room CV273,MC 5406,300 Pasteur Dr, Stanford, CA 94305 USA. EM knowlej@stanford.edu OI Newman, Connie/0000-0001-9144-056X FU Amgen; AstraZeneca; Pfizer; Regeneron; Sanofi; Aegerion; American Heart Association (AHA) National Innovative Research Grant [15IRG222930034]; National Institutes of Health [K23 HL114884] FX This study was supported by grants from Amgen, AstraZeneca, Pfizer, Regeneron, Sanofi, and Aegerion. Joshua W. Knowles is supported by an American Heart Association (AHA) National Innovative Research Grant 15IRG222930034. Zahid Ahmad is supported by an National Institutes of Health grant K23 HL114884. NR 43 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2016 VL 9 IS 3 BP 240 EP + DI 10.1161/CIRCGENETICS.116.001381 PG 24 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DO9UM UT WOS:000378133100007 PM 27013694 ER PT J AU Golbus, JR Stitziel, NO Zhao, W Xue, CY Farrall, M McPherson, R Erdmann, J Deloukas, P Watkins, H Schunkert, H Samani, NJ Saleheen, D Kathiresan, S Reilly, MP AF Golbus, Jessica R. Stitziel, Nathan O. Zhao, Wei Xue, Chenyi Farrall, Martin McPherson, Ruth Erdmann, Jeanette Deloukas, Panos Watkins, Hugh Schunkert, Heribert Samani, Nilesh J. Saleheen, Danish Kathiresan, Sekar Reilly, Muredach P. CA CARDIoGRAMplusC4D Myocardial Infarction Genetics ESP EOMI PROMIS Consortia TI Common and Rare Genetic Variation in CCR2, CCR5, or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atherosclerosis; diabetes mellitus; genetics; genome-wide association study; myocardial infarction ID GENOME-WIDE ASSOCIATION; ARTERY-DISEASE; CHEMOKINE RECEPTORS; FUNCTIONAL IMPACT; CODING VARIATION; IDENTIFIES 13; BLOOD-LIPIDS; LOCI; METAANALYSIS; MICE AB Background-The chemokine receptors CCR2, CCR5, and CX3CR1 coordinate monocyte trafficking in homeostatic and inflammatory states. Multiple small human genetic studies have variably linked single nucleotide polymorphisms in these genes to cardiometabolic disease. We interrogated genome-wide association, exome sequencing, and exome array genotyping studies to ascertain the relationship between variation in these genes and coronary artery disease (CAD), myocardial infarction (MI), and glucometabolic traits. Methods and Results-We interrogated the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) (60 801 cases and 123 504 controls), the MIGen and CARDIoGRAM Exome consortia (42 335 cases and 78 240 controls), and Exome Sequencing Project and Early-Onset Myocardial Infarction (ESP EOMI; 4703 cases and 5090 controls) data sets to ascertain the relationship between common, low frequency, and rare variation in CCR2, CCR5, or CX3CR1 with CAD and MI. We did not identify any variant associated with CAD or MI. We then explored common and low-frequency variation in South Asians through Pakistan Risk of Myocardial Infarction Study (PROMIS; 9058 cases and 8379 controls), identifying 6 variants associated with MI including CX3CR1 V249I. Finally, reanalysis of the European HapMap imputed Diabetes Genetics Replication and Meta-Analysis (DIAGRAM), Global Lipids Genetics Consortium (GLGC), Genetic Investigation of Anthropometric Traits (GIANT), and Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) data sets revealed no association with glucometabolic traits although 3 single nucleotide polymorphisms in PROMIS were associated with type II diabetes mellitus. Conclusions-No chemokine receptor variant was associated with CAD, MI, or glucometabolic traits in large European ancestry cohorts. In a South Asian cohort, we identified single nucleotide polymorphism associations with MI and type II diabetes mellitus but these did not meet significance in cohorts of European ancestry. These findings suggest the need for larger studies in South Asians but exclude clinically meaningful associations with CAD and glucometabolic traits in Europeans. C1 [Golbus, Jessica R.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Stitziel, Nathan O.] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA. [Zhao, Wei; Xue, Chenyi; Saleheen, Danish] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Farrall, Martin; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford, England. [McPherson, Ruth] Univ Ottawa Heart Inst, Div Cardiol, Ottawa, ON, Canada. [Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Schunkert, Heribert] Tech Univ Munich, DZHK, Munich Heart Alliance, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Gen Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.] Columbia Univ, Dept Med, 622 W 168th St,PH10-305, New York, NY 10032 USA. RP Golbus, JR (reprint author), Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.; Reilly, MP (reprint author), Columbia Univ, Dept Med, 622 W 168th St,PH10-305, New York, NY 10032 USA. EM jessica.golbus@uphs.upenn.edu; mpr2144@cumc.columbia.edu RI Erdmann, Jeanette/P-7513-2014; OI Erdmann, Jeanette/0000-0002-4486-6231; Stitziel, Nathan/0000-0002-4963-8211; Deloukas, Panos/0000-0001-9251-070X; Watkins, Hugh/0000-0002-5287-9016 FU Fondation Leducq (CADgenomics: Understanding CAD Genes) [12CVD02]; German Federal Ministry of Education and Research (BMBF) [01ZX1313A-2014]; European Union [601456]; DFG as a part of the Sonderforschungsbereich CRC [1123 (B2)]; British Heart Foundation; [R01-DK-090505]; [K24-HL-107643]; [R01-HL-111694]; [R01-HL-113147] FX This work was supported by R01-DK-090505 and K24-HL-107643 to M.P. Reilly. M.P. Reilly was also supported by R01-HL-111694 and R01-HL-113147. Dr Schunkert was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014), the European Union Seventh Framework Programme FP7/2007 to 2013 under grant agreement no HEALTH-F2-2013 to 601456 (CVgenes-at-target), and the DFG as a part of the Sonderforschungsbereich CRC 1123 (B2). Dr Samani holds a Chair funded by the British Heart Foundation and is a UK National Institute for Health Research Senior Investigator. NR 57 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 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2016 VL 9 IS 3 BP 250 EP + DI 10.1161/CIRCGENETICS.115.001374 PG 32 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DO9UM UT WOS:000378133100008 PM 27013693 ER PT J AU Karmpaliotis, D Karatasakis, A Alaswad, K Jaffer, FA Yeh, RW Wyman, RM Lombardi, WL Grantham, JA Kandzari, DE Lembo, NJ Doing, A Patel, M Bahadorani, JN Moses, JW Kirtane, AJ Parikh, M Ali, ZA Kalra, S Nguyen-Trong, PKJ Danek, BA Karacsonyi, J Rangan, BV Roesle, MK Thompson, CA Banerjee, S Brilakis, ES AF Karmpaliotis, Dimitri Karatasakis, Aris Alaswad, Khaldoon Jaffer, Farouc A. Yeh, Robert W. Wyman, R. Michael Lombardi, William L. Grantham, J. Aaron Kandzari, David E. Lembo, Nicholas J. Doing, Anthony Patel, Mitul Bahadorani, John N. Moses, Jeffrey W. Kirtane, Ajay J. Parikh, Manish Ali, Ziad A. Kalra, Sanjog Nguyen-Trong, Phuong-Khanh J. Danek, Barbara A. Karacsonyi, Judit Rangan, Bavana V. Roesle, Michele K. Thompson, Craig A. Banerjee, Subhash Brilakis, Emmanouil S. TI Outcomes With the Use of the Retrograde Approach for Coronary Chronic Total Occlusion Interventions in a Contemporary Multicenter US Registry SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE complication; coronary occlusion; outcome; percutaneous coronary intervention ID IN-HOSPITAL OUTCOMES; BYPASS GRAFT-SURGERY; LONG-TERM OUTCOMES; HYBRID APPROACH; PROCEDURAL OUTCOMES; PERCUTANEOUS INTERVENTION; UNITED-STATES; INSIGHTS; REVASCULARIZATION; RECANALIZATION AB Background-We sought to examine the efficacy and safety of chronic total occlusion percutaneous coronary intervention using the retrograde approach. Methods and Results-We compared the outcomes of the retrograde versus antegrade-only approach to chronic total occlusion percutaneous coronary intervention among 1301 procedures performed at 11 experienced US centers between 2012 and 2015. The mean age was 65.5 +/- 10 years, and 84% of the patients were men with a high prevalence of diabetes mellitus (45%) and previous coronary artery bypass graft surgery (34%). Overall technical and procedural success rates were 90% and 89%, respectively, and in-hospital major adverse cardiovascular events occurred in 31 patients (2.4%). The retrograde approach was used in 539 cases (41%), either as the initial strategy (46%) or after a failed antegrade attempt (54%). When compared with antegrade-only cases, retrograde cases were significantly more complex, both clinically (previous coronary artery bypass graft surgery prevalence, 48% versus 24%; P<0.001) and angiographically (mean Japan-chronic total occlusion score, 3.1 +/- 1.0 versus 2.1 +/- 1.2; P<0.001) and had lower technical success (85% versus 94%; P<0.001) and higher major adverse cardiovascular events (4.3% versus 1.1%; P<0.001) rates. On multivariable analysis, the presence of suitable collaterals, no smoking, no previous coronary artery bypass graft surgery, and left anterior descending artery target vessel were independently associated with technical success using the retrograde approach. Conclusions-The retrograde approach is commonly used in contemporary chronic total occlusion percutaneous coronary intervention, especially among more challenging lesions and patients. Although associated with lower success and higher major adverse cardiovascular event rates in comparison to antegrade-only crossing, retrograde percutaneous coronary intervention remains critical for achieving overall high success rates. C1 [Karmpaliotis, Dimitri; Moses, Jeffrey W.; Kirtane, Ajay J.; Ali, Ziad A.; Kalra, Sanjog] Columbia Univ, Ctr Intervent Vasc Therapy, New York Presbyterian Hosp, Med Ctr, New York, NY USA. [Karatasakis, Aris; Nguyen-Trong, Phuong-Khanh J.; Danek, Barbara A.; Karacsonyi, Judit; Rangan, Bavana V.; Roesle, Michele K.; Banerjee, Subhash; Brilakis, Emmanouil S.] VA North Texas Healthcare Syst, Dept Cardiol, Dallas, TX USA. [Karatasakis, Aris; Nguyen-Trong, Phuong-Khanh J.; Danek, Barbara A.; Karacsonyi, Judit; Rangan, Bavana V.; Roesle, Michele K.; Banerjee, Subhash; Brilakis, Emmanouil S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Alaswad, Khaldoon] Henry Ford Hosp, Dept Cardiol, Detroit, MI 48202 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Jaffer, Farouc A.; Yeh, Robert W.] Harvard Univ, Sch Med, Boston, MA USA. [Yeh, Robert W.] Beth Israel Deaconess Med Ctr, CardioVasc Inst, Boston, MA 02215 USA. [Wyman, R. Michael] Torrance Mem Med Ctr, Lundquist Cardiovasc Inst, Torrance, CA USA. [Lombardi, William L.] PeaceHlth St Joseph Med Ctr, Cardiovasc Ctr, Bellingham, WA USA. [Grantham, J. Aaron] St Lukes Hosp, Mid Amer Heart Inst, Dept Intervent Cardiol, Kansas City, MO 64111 USA. [Kandzari, David E.; Lembo, Nicholas J.] Piedmont Heart Inst, Dept Intervent Cardiol, Atlanta, GA USA. [Doing, Anthony] Med Ctr Rockies, Dept Cardiol, Loveland, CO USA. [Bahadorani, John N.] VA San Diego Healthcare Syst, Div Cardiovasc Med, San Diego, CA USA. [Bahadorani, John N.] Univ Calif, San Diego, CA USA. [Thompson, Craig A.] Boston Sci, Natick, MA USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 South Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@gmail.com OI Danek, Barbara/0000-0002-7607-4204; Parikh, Manish/0000-0002-8612-5407 FU National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1TR001105] FX Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 37 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD JUN PY 2016 VL 9 IS 6 AR e003434 DI 10.1161/CIRCINTERVENTIONS.115.003434 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9UU UT WOS:000378134200008 ER PT J AU Ho, JE Enserro, D Brouwers, FP Kizer, JR Shah, SJ Psaty, BM Bartz, TM Santhanakrishnan, R Lee, DS Chan, C Liu, K Blaha, MJ Hillege, HL van der Harst, P van Gilst, WH Kop, WJ Gansevoort, RT Vasan, RS Gardin, JM Levy, D Gottdiener, JS de Boer, RA Larson, MG AF Ho, Jennifer E. Enserro, Danielle Brouwers, Frank P. Kizer, Jorge R. Shah, Sanjiv J. Psaty, Bruce M. Bartz, Traci M. Santhanakrishnan, Rajalakshmi Lee, Douglas S. Chan, Cheeling Liu, Kiang Blaha, Michael J. Hillege, Hans L. van der Harst, Pim van Gilst, Wiek H. Kop, Willem J. Gansevoort, Ron T. Vasan, Ramachandran S. Gardin, Julius M. Levy, Daniel Gottdiener, John S. de Boer, Rudolf A. Larson, Martin G. TI Predicting Heart Failure With Preserved and Reduced Ejection Fraction The International Collaboration on Heart Failure Subtypes SO CIRCULATION-HEART FAILURE LA English DT Article DE diastolic heart failure; phenotype; primary prevention; risk factor; systolic heart failure ID LEFT-VENTRICULAR HYPERTROPHY; COMMUNITY-BASED COHORT; NATRIURETIC PEPTIDE; RISK PREDICTION; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; OUTCOMES RESEARCH; EUROPEAN-SOCIETY; LIFETIME RISK; OF-CARDIOLOGY AB Background-Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results-Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2: 1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78-0.82) and validation samples (internal: 0.79; 95% CI, 0.77-0.82 and external: 0.76; 95% CI: 0.71-0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80-0.84) and validation samples (internal: 0.80; 95% CI, 0.78-0.83 and external: 0.76; 95% CI, 0.71-0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison <= 0.02). Conclusions-We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes. C1 [Ho, Jennifer E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Santhanakrishnan, Rajalakshmi] Boston Univ, Cardiovasc Med Sect, Dept Med, Sch Med, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sect Prevent Med & Epidemiol, Sch Med, Boston, MA 02215 USA. [Ho, Jennifer E.; Vasan, Ramachandran S.; Levy, Daniel; Larson, Martin G.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Boston, MA USA. [Enserro, Danielle; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Brouwers, Frank P.; Hillege, Hans L.; van der Harst, Pim; van Gilst, Wiek H.; de Boer, Rudolf A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9713 AV Groningen, Netherlands. [Kizer, Jorge R.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. [Chan, Cheeling; Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Chan, Cheeling; Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Lee, Douglas S.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Lee, Douglas S.] Univ Toronto, Univ Hlth Network, Toronto, ON M5S 1A1, Canada. [Blaha, Michael J.] Johns Hopkins Univ, Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Gardin, Julius M.] Hackensack Univ, Med Ctr, Dept Med, Hackensack, NJ USA. [Gardin, Julius M.] Rutgers New Jersey Med Sch, Hackensack, NJ USA. [Kop, Willem J.] Tilburg Univ, Ctr Res Psychol Somat Dis, Dept Med & Clin Psychol, NL-5000 LE Tilburg, Netherlands. [Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. [Gottdiener, John S.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. RP Ho, JE (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,CPZN 3224, Boston, MA 02114 USA. FU National Heart, Lung, and Blood Institute [N01-HC25195, HHSN268201500001I, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083]; National Center for Research Resources [UL1-TR-000040, UL1-TR-001079]; Canadian Institutes of Health Research; The National Heart, Lung, and Blood Institute [N01HC85086, U01HL080295, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; [K23-HL116780] FX This work was partially supported by the National Heart, Lung, and Blood Institute (Framingham Heart Study, contract N01-HC25195 and HHSN268201500001I; Cardiovascular Health Study, contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant U01HL080295; and Multi-Ethnic Study of Atherosclerosis contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169) and the National Center for Research Resources (Multi-Ethnic Study of Atherosclerosis UL1-TR-000040 and UL1-TR-001079). The Cardiovascular Health Study received additional contribution from the National Institute of Neurological Disorders and Stroke, and R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Dr Ho is supported by K23-HL116780. Dr Lee is supported by a clinician-scientist award from the Canadian Institutes of Health Research. Dr Ho had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 51 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUN PY 2016 VL 9 IS 6 AR UNSP e003116 DI 10.1161/CIRCHEARTFAILURE.115.003116 PG 26 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9WP UT WOS:000378139000011 ER PT J AU Malhotra, R Dhakal, BP Eisman, AS Pappagianopoulos, PP Dress, A Weiner, RB Baggish, AL Semigran, MJ Lewis, GD AF Malhotra, Rajeev Dhakal, Bishnu P. Eisman, Aaron S. Pappagianopoulos, Paul P. Dress, Ashley Weiner, Rory B. Baggish, Aaron L. Semigran, Marc J. Lewis, Gregory D. TI Pulmonary Vascular Distensibility Predicts Pulmonary Hypertension Severity, Exercise Capacity, and Survival in Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; mortality; physiology; pulmonary heart disease; pulmonary hypertension ID PRESERVED EJECTION FRACTION; CARDIAC MAGNETIC-RESONANCE; ARTERY DISTENSIBILITY; HEMODYNAMIC-RESPONSE; PROGNOSTIC VALUE; OXYGEN-UPTAKE; PREVALENCE; STIFFNESS; PRESSURE; DISEASE AB Background-Pulmonary vascular (PV) distensibility, defined as the percent increase in pulmonary vessel diameter per mm Hg increase in pressure, permits the pulmonary vessels to increase in size to accommodate increased blood flow. We hypothesized that PV distensibility is abnormally low in patients with heart failure (HF) and serves as an important determinant of right ventricular performance and exercise capacity. Methods and Results-Patients with HF with preserved ejection fraction (n=48), HF with reduced ejection fraction (n=55), pulmonary arterial hypertension without left heart failure (n=18), and control subjects (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PV distensibility was derived from 1257 matched measurements (mean +/- SD, 8.3 +/- 2.8 per subject) of pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output. PV distensibility was lowest in the pulmonary arterial hypertension group (0.40 +/- 0.24% per mm Hg) and intermediate in the HF with preserved ejection fraction and HF with reduced ejection fraction groups (0.92 +/- 0.39 and 0.84 +/- 0.33% per mm Hg, respectively) compared to the control group (1.39 +/- 0.32% per mm Hg, P<0.0001 for all three). PV distensibility was associated with change in right ventricular ejection fraction (RVEF, rho=0.39, P<0.0001) with exercise and was an independent predictor of peak VO2. PV distensibility also predicted cardiovascular mortality independent of peak VO2 in HF patients (n=103; Cox hazard ratio, 0.30; 95% confidence interval, 0.10-0.93; P=0.036). In a subset of patients with HF with reduced ejection fraction (n=26), 12 weeks of treatment with the pulmonary vasodilator sildenafil or placebo led to a 24.6% increase in PV distensibility (P=0.015) in the sildenafil group only. Conclusions-PV distensibility is reduced in patients with HF and pulmonary arterial hypertension and is closely related to RV systolic function during exercise, maximal exercise capacity, and survival. Furthermore, PV distensibility is modifiable with selective pulmonary vasodilator therapy and may represent an important target for therapy in selected HF patients with pulmonary hypertension. C1 [Malhotra, Rajeev; Dhakal, Bishnu P.; Eisman, Aaron S.; Weiner, Rory B.; Baggish, Aaron L.; Semigran, Marc J.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Pappagianopoulos, Paul P.; Dress, Ashley; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Lewis, GD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM glewis@partners.org FU American Heart Association [11FTF7290032, 15GPSGC24800006]; Wild Family Foundation; National Heart, Lung, and Blood Institute [K08HL111210]; National Institutes of Health [R01-HL131029]; Hassenfeld Clinical Scholar Award FX Dr Malhotra was supported by the Fellow-to-Faculty Transition Award 11FTF7290032 from the American Heart Association, the Wild Family Foundation, and the K08HL111210 grant from the National Heart, Lung, and Blood Institute. Dr Lewis was supported by the American Heart Association Award 15GPSGC24800006, the National Institutes of Health grant R01-HL131029, and the Hassenfeld Clinical Scholar Award. Support for the sildenafil versus placebo trial was provided by Pfizer. NR 50 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUN PY 2016 VL 9 IS 6 AR e003011 DI 10.1161/CIRCHEARTFAILURE.115.003011 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9WP UT WOS:000378139000010 ER PT J AU ter Maaten, JM Valente, MAE Damman, K Cleland, JG Givertz, MM Metra, M O'Connor, CM Teerlink, JR Ponikowski, P Bloomfield, DM Cotter, G Davison, B Subacius, H van Veldhuisen, DJ van der Meer, P Hillege, HL Gheorghiade, M Voors, AA AF ter Maaten, Jozine M. Valente, Mattia A. E. Damman, Kevin Cleland, John G. Givertz, Michael M. Metra, Marco O'Connor, Christopher M. Teerlink, John R. Ponikowski, Piotr Bloomfield, Daniel M. Cotter, Gadi Davison, Beth Subacius, Haris van Veldhuisen, Dirk J. van der Meer, Peter Hillege, Hans L. Gheorghiade, Mihai Voors, Adriaan A. TI Combining Diuretic Response and Hemoconcentration to Predict Rehospitalization After Admission for Acute Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE diuretics; heart failure; hemoglobin; hospitalization ID ACUTE MYOCARDIAL-INFARCTION; RENAL-FUNCTION; POSTDISCHARGE OUTCOMES; AN ANALYSIS; DIAGNOSIS; DECONGESTION; ROLOFYLLINE; GUIDELINES; ANTAGONIST; PNEUMONIA AB Background-Both diuretic response and hemoconcentration are indicators of decongestion and have individually been found to predict rehospitalization after admission for acute heart failure (HF). This study examines the value of combining diuretic response and hemoconcentration to better predict patients at low risk for rehospitalization after admission for acute HF. Methods and Results-Diuretic response (defined as weight change per 40 mg of furosemide on day 4 after admission) and hemoconcentration (change in hemoglobin at discharge or day 7) were tested both individually and combined to predict the risk of HF and cardiovascular rehospitalization 60 days after hospitalization for acute HF. Analyses were performed in 1180 patients enrolled in the Placebo-Controlled Randomized Study of the Selective Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) trial and validated in 1776 patients enrolled in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Poor diuretic response was associated with low systolic blood pressure, high blood urea nitrogen, and history of coronary revascularization in both data sets (all P<0.05). Hemoconcentration was mainly associated with better renal function (P<0.05). Patients who displayed both favorable diuretic response and hemoconcentration had a markedly lower risk of rehospitalization for HF in PROTECT (multivariable HR, 0.41; 95% CI, 0.24 to 0.70; P<0.001) compared with all other patients. This finding was confirmed in EVEREST (multivariable HR, 0.52; 95% CI, 0.33 to 0.82; P=0.004) for patients with favorable diuretic response and hemoconcentration compared with all other patients. Conclusions-Combining 2 indicators of decongestion, hemoconcentration and diuretic response improves risk prediction for early rehospitalization after an admission for acute HF and may provide clinicians with an easily accessible tool to identify low-risk patients. C1 [ter Maaten, Jozine M.; Valente, Mattia A. E.; Damman, Kevin; van Veldhuisen, Dirk J.; van der Meer, Peter; Hillege, Hans L.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands. [Hillege, Hans L.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 AB Groningen, Netherlands. [Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Metra, Marco] Univ Brescia, I-25121 Brescia, Italy. [O'Connor, Christopher M.] Inova Heart & Vasc Inst, Falls Church, VA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Cotter, Gadi; Davison, Beth] Momentum Res, Durham, NC USA. [Subacius, Haris; Gheorghiade, Mihai] Univ Iowa, Carver Coll Med, Cardiovasc Res Ctr, Iowa City, IA USA. [Subacius, Haris; Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 FU Otsuka, Inc, Rockville, MD FX The PROTECT trial was supported by NovaCardia, a subsidiary of Merck. Financial and material support for the EVEREST trial was provided by Otsuka, Inc, Rockville, MD. NR 17 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUN PY 2016 VL 9 IS 6 AR e002845 DI 10.1161/CIRCHEARTFAILURE.115.002845 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9WP UT WOS:000378139000006 ER PT J AU Janne, PA Kim, G Shaw, AT Sridhara, R Pazdur, R McKee, AE AF Janne, Pasi A. Kim, Geoffrey Shaw, Alice T. Sridhara, Rajeshwari Pazdur, Richard McKee, Amy E. TI Dose Finding of Small-Molecule Oncology Drugs: Optimization throughout the Development Life Cycle SO CLINICAL CANCER RESEARCH LA English DT Article ID CONTINUAL REASSESSMENT METHOD; I CLINICAL-TRIALS; CANCER; DESIGN; TOXICITY; OUTCOMES AB In the current era of rapid marketing approval for promising new products in oncology, dose finding and optimization for small-molecule oncology drugs occurs throughout the development cycle and into the postmarketing setting. Many trials that support a regulatory application have high rates of dose reductions and discontinuations, which may result in postmarketing requirements (PMR) to study alternate doses or dosing schedules. Kinase inhibitors particularly have been susceptible to this problem, and among the 31 approved drugs of this class, the approvals of eight have included such PMRs and/or commitments. Thus, the current paradigm for dose finding and optimization could be improved. Newer strategies for dose finding rather than traditional 3 + 3 designs should be considered where feasible, and dose optimization should be continued after phase I and throughout development. Such strategies will increase the likelihood of a right dose for the right drug at the time of regulatory approval. (C) 2016 AACR. C1 [Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Geoffrey; Sridhara, Rajeshwari; Pazdur, Richard; McKee, Amy E.] US FDA, Silver Spring, MD USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McKee, AE (reprint author), US FDA, Off Hematol & Oncol Prod, 10903 New Hampshire Ave, White Oak, MD 20993 USA. EM amy.mckee@fda.hhs.gov FU Astellas Pharma; AstraZeneca FX P.A. Janne reports receiving commercial research grants from Astellas Pharma and AstraZeneca; royalties, through his institution, from LabCorp for intellectual property on EGFR mutations that is owned by Dana-Farber Cancer Institute and licensed to LabCorp; has ownership interest (including patents) in Gatekeeper Pharmaceuticals; and is a consultant/advisory board member for ARIAD Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Merrimack Pharmaceuticals, and Pfizer. A.T. Shaw is a consultant/advisory board member for ARIAD Pharmaceuticals, Daiichi Sankyo, EMD Serono, Genentech, Novartis, Pfizer, Roche, and Taiho Pharmaceutical. No potential conflicts of interest were disclosed by the other authors. NR 22 TC 3 Z9 3 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2016 VL 22 IS 11 BP 2613 EP 2617 DI 10.1158/1078-0432.CCR-15-2643 PG 5 WC Oncology SC Oncology GA DP2RN UT WOS:000378338200005 PM 27250931 ER PT J AU Meah, FA DiMeglio, LA Greenbaum, CJ Blum, JS Sosenko, JM Pugliese, A Geyer, S Xu, P Evans-Molina, C AF Meah, Farah A. DiMeglio, Linda A. Greenbaum, Carla J. Blum, Janice S. Sosenko, Jay M. Pugliese, Alberto Geyer, Susan Xu, Ping Evans-Molina, Carmella CA Type 1 Diabet TrialNet Study Grp TI The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants SO DIABETOLOGIA LA English DT Article DE Accelerator hypothesis; BMI; Diabetes in childhood; HOMA1-IR; Insulin sensitivity and resistance; Pancreatic autoantibodies; Pathway to Prevention; Prediction and prevention of type 1 diabetes; TrialNet; Type 1 diabetes ID 1 RISK SCORE; BETA-CELL FUNCTION; ACCELERATOR HYPOTHESIS; NATURAL-HISTORY; UNITED-STATES; INCIDENCE TRENDS; TOLERANCE-TEST; WEIGHT-GAIN; BODY-MASS; AUTOIMMUNITY AB Aims/hypothesis The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. Methods HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Results Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. Conclusions/interpretation Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue. C1 [Meah, Farah A.; Evans-Molina, Carmella] Indiana Univ Sch Med, Dept Med, 635 Barnhill Dr,MS 2031A, Indianapolis, IN 46202 USA. [Meah, Farah A.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Endocrinol, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [DiMeglio, Linda A.; Evans-Molina, Carmella] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. [Greenbaum, Carla J.] Benaroya Res Inst, Diabet Program, Seattle, WA USA. [Blum, Janice S.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Sosenko, Jay M.] Univ Miami, Leonard Miller Sch Med, Diabet Res Inst, Miami, FL USA. [Sosenko, Jay M.; Pugliese, Alberto] Univ Miami, Dept Med, Div Diabet Endocrinol & Metab, Leonard Miller Sch Med, Miami, FL USA. [Pugliese, Alberto] Univ Miami, Leonard Miller Sch Med, Dept Microbiol & Immunol, Miami, FL USA. [Geyer, Susan; Xu, Ping] Univ S Florida, Hlth Informat Inst, Tampa, FL USA. RP Evans-Molina, C (reprint author), Indiana Univ Sch Med, Dept Med, 635 Barnhill Dr,MS 2031A, Indianapolis, IN 46202 USA.; Evans-Molina, C (reprint author), Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. EM cevansmo@iu.edu FU National Institutes of Health (NIH) through National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK103180, U01-DK103153, U01-DK085476, U01-DK103266]; Juvenile Diabetes Research Foundation International (JDRF); NIH grants [R01 DK093954, UC4 DK 104166]; VA Merit Award [I01BX001733]; JDRF grant [SRA-2014-41] FX The sponsor of the trial was the Type 1 Diabetes TrialNet Pathway to Prevention Study Group. Type 1 Diabetes TrialNet Pathway to Prevention Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK103180, U01-DK103153, U01-DK085476, U01-DK103266 and the Juvenile Diabetes Research Foundation International (JDRF). This work was also partially supported by NIH grants R01 DK093954 and UC4 DK 104166 (to CEM), VA Merit Award I01BX001733 (to CEM) and JDRF grant SRA-2014-41 (to CEM, LAD and JSB). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, the US Department of Veterans Affairs or the United States Government, the JDRF or American Diabetes Association. NR 50 TC 1 Z9 1 U1 1 U2 1 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 JUN PY 2016 VL 59 IS 6 BP 1186 EP 1195 DI 10.1007/s00125-016-3924-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO8QN UT WOS:000378048500016 PM 26995649 ER PT J AU Dordea, AC Bray, MA Allen, K Logan, DJ Fei, F Malhotra, R Gregory, MS Carpenter, AE Buys, ES AF Dordea, Ana C. Bray, Mark-Anthony Allen, Kaitlin Logan, David J. Fei, Fei Malhotra, Rajeev Gregory, Meredith S. Carpenter, Anne E. Buys, Emmanuel S. TI An open-source computational tool to automatically quantify immunolabeled retinal ganglion cells SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Automated quantification; Retinal ganglion cell; CellProfiler; CellProfiler analyst ID IMAGE-ANALYSIS SOFTWARE; OPTIC-NERVE; INTRAOCULAR-PRESSURE; MOUSE MODEL; RGC LOSS; MICE; DEGENERATION; GLAUCOMA; CELLPROFILER; AXOTOMY AB A fully automated and robust method was developed to quantify beta-III-tubulin-stained retinal ganglion cells, combining computational recognition of individual cells by CellProfiler and a machine-learning tool to teach phenotypic classification of the retinal ganglion cells by CellProfiler Analyst. In animal models of glaucoma, quantification of immunolabeled retinal ganglion cells is currently performed manually and remains time-consuming. Using this automated method, quantifications of retinal ganglion cell images were accelerated tenfold: 1800 images were counted in 3 h using our automated method, while manual counting of the same images took 72 h. This new method was validated in an established murine model of microbead-induced optic neuropathy. The use of the publicly available software and the method's user-friendly design allows this technique to be easily implemented in any laboratory. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Dordea, Ana C.; Allen, Kaitlin; Buys, Emmanuel S.] Harvard Univ, Sch Med, Anesthesia Ctr Crit Care Res,Massachusetts Gen Ho, Dept Anesthesia Crit Care & Pain Med,Res Inst, Boston, MA USA. [Bray, Mark-Anthony; Logan, David J.; Carpenter, Anne E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Fei, Fei; Gregory, Meredith S.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA USA. [Malhotra, Rajeev] Harvard Univ, Sch Med, Div Cardiol, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. RP Buys, ES (reprint author), Harvard Univ, Sch Med, Anesthesia Ctr Crit Care Res,Massachusetts Gen Ho, Dept Anesthesia Crit Care & Pain Med,Res Inst, Boston, MA USA. EM ebuys@mgh.harvard.edu OI Malhotra, Rajeev/0000-0003-0120-4630 FU NIH [EY021543, EY022746-01, GM089652] FX This work was supported by NIH grants: [F.F. and M.G.K.] EY021543, [A.C.D., K.A. and E.S.B.] EY022746-01 and [M.A.B. and A.C.] GM089652. Jie Ma provided assistance with Brn3a staining. NR 24 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 2016 VL 147 BP 50 EP 56 DI 10.1016/j.exer.2016.04.012 PG 7 WC Ophthalmology SC Ophthalmology GA DP0NP UT WOS:000378186800006 PM 27119563 ER PT J AU Ramke, M Zhou, XH Materne, EC Rajaiya, J Chodosh, J AF Ramke, Mirja Zhou, Xiaohong Materne, Emma Caroline Rajaiya, Jaya Chodosh, James TI Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Epidemic keratoconjunctivitis; Adenovirus keratitis; Adenovirus; Macrophage; Dendritic cell; Neutrophil; Leukocyte; MaFIA mice; Host-pathogen interaction ID KERATOCONJUNCTIVITIS; ABLATION; MOUSE AB The cornea contains a heterogeneous population of antigen-presenting cells with the capacity to contribute to immune responses. Adenovirus keratitis is a severe corneal infection with acute and chronic phases. The role of resident corneal antigen-presenting cells in adenovirus keratitis has not been studied. We utilized transgenic MaFIA mice in which c-fins expressing macrophages and dendritic cells can be induced to undergo apoptosis, in a mouse model of adenovirus keratitis. Clinical keratitis and recruitment of myeloperoxidase and CD45(+) cells were diminished in c-fins depleted, adenovirus infected mice, as compared to controls, consistent with a role for myeloid-lineage cells in adenovirus keratitis. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Ramke, Mirja; Zhou, Xiaohong; Materne, Emma Caroline; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU National Institutes of Health (NIH) [EY013124, EY021558, P30 EY014104]; Research to Prevent Blindness, Inc., New York, NY; Falk Foundation; Massachusetts Lions Eye Research Fund FX This work was supported by National Institutes of Health (NIH) [EY013124, EY021558, and P30 EY014104], a Senior Scientific Investigator Award grant [to JC] from Research to Prevent Blindness, Inc., New York, NY, The Falk Foundation, and the Massachusetts Lions Eye Research Fund. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD JUN PY 2016 VL 147 BP 144 EP 147 DI 10.1016/j.exer.2016.05.016 PG 4 WC Ophthalmology SC Ophthalmology GA DP0NP UT WOS:000378186800017 PM 27185163 ER PT J AU Shepardson, RL Funderburk, JS Weisberg, RB AF Shepardson, Robyn L. Funderburk, Jennifer S. Weisberg, Risa B. TI Adapting Evidence-Based, Cognitive-Behavioral Interventions for Anxiety for Use With Adults in Integrated Primary Care Settings SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE anxiety; integrated primary care; integrated behavioral health; primary care behavioral health; cognitive-behavioral therapy ID RANDOMIZED CONTROLLED-TRIAL; PHARMACOLOGICAL-TREATMENT; ACTIVATION TREATMENTS; HEALTH-CARE; DISORDERS; DEPRESSION; THERAPY; METAANALYSIS; ACCEPTANCE; MINDFULNESS AB Evidence-based treatments for adult patients with anxiety are greatly needed within primary care settings. Psychotherapy protocols, including those for cognitive-behavioral therapy (CBT), are often disorder-specific and were developed for specialty mental health settings, rendering them infeasible in primary care. Behavioral health consultants (BHCs) integrated into primary care settings are uniquely positioned to provide anxiety treatment. However, due to the dearth of empirically supported brief treatments for anxiety, BHCs are tasked with adapting existing treatments for use in primary care, which is quite challenging due to the abbreviated format and population-based approach to care. CBT protocols are highly effective in the treatment of anxiety and fit well with the self-management emphasis of integrated primary care. We review the rationale and procedure for 6 evidence-based CBT intervention techniques (psycho-education, mindfulness and acceptance-based behavioral techniques, relaxation training, exposure, cognitive restructuring, and behavioral activation) that can be adapted for use in the brief format typical of integrated primary care. We offer tips based on our clinical experience, highlight resources (e.g., handouts, websites, apps), and discuss 2 case examples to aid BHCs in their everyday practice. Our goal is to provide BHCs with practical knowledge that will facilitate the use of evidence-based interventions to improve the treatment of anxiety in primary care settings. C1 [Shepardson, Robyn L.; Funderburk, Jennifer S.] Syracuse VA Med Ctr, VA Ctr Integrated Healthcare, 800 Irving Ave 116C, Syracuse, NY 13210 USA. [Shepardson, Robyn L.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. [Funderburk, Jennifer S.] Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. [Weisberg, Risa B.] VA Boston Healthcare Syst, Boston, MA USA. [Weisberg, Risa B.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Shepardson, RL (reprint author), Syracuse VA Med Ctr, VA Ctr Integrated Healthcare, 800 Irving Ave 116C, Syracuse, NY 13210 USA. EM robyn.shepardson@va.gov NR 57 TC 0 Z9 0 U1 2 U2 6 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD JUN PY 2016 VL 34 IS 2 BP 114 EP 127 DI 10.1037/fsh0000175 PG 14 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA DP0HH UT WOS:000378169700005 PM 27064434 ER PT J AU Abou Tayoun, AN Al Turki, SH Oza, AM Bowser, MJ Hernandez, AL Funke, BH Rehm, HL Amr, SS AF Abou Tayoun, Ahmad N. Al Turki, Saeed H. Oza, Andrea M. Bowser, Mark J. Hernandez, Amy L. Funke, Birgit H. Rehm, Heidi L. Amr, Sami S. TI Improving hearing loss gene testing: a systematic review of gene evidence toward more efficient next-generation sequencing-based diagnostic testing and interpretation SO GENETICS IN MEDICINE LA English DT Review DE clinical validity; gene disease association; hearing loss; next-generation sequencing ID ERYTHROKERATODERMIA VARIABILIS; PENDRED SYNDROME; ITALIAN FAMILY; INNER-EAR; MUTATIONS; DEAFNESS; PROTEIN; GJB3; IMPAIRMENT; COCHLEAR AB Purpose: With next generation sequencing technology improvement and cost reductions, it has become technically feasible to sequence a large number of genes in one diagnostic test. This is especially relevant for diseases with large genetic and/or phenotypic heterogeneity, such as hearing loss. However, variant interpretation remains the major bottleneck. This is further exacerbated by the lack in the clinical genetics community of consensus criteria for defining the evidence necessary to include genes on targeted disease panels or in genomic reports, and the consequent risk of reporting variants in genes with no relevance to disease. Methods: We describe a systematic evidence-based approach for assessing gene disease associations and for curating relevant genes for different disease aspects, including mode of inheritance, phenotypic severity, and mutation spectrum. Results: By applying this approach to clinically available hearing loss gene panels with a total of 163 genes, we show that a significant number (45%) of genes lack sufficient evidence of association with disease and thus are expected to increase uncertainty and patient anxiety, in addition to intensifying the interpretation burden. Information about all curated genes is summarized. Our retrospective analysis of 539 hearing loss cases tested by our previous OtoGenomeV2 panel demonstrates the impact of including genes with weak disease association in laboratory wet-bench and interpretation processes. Conclusion: Our study is, to our knowledge, the first to highlight the urgent need for defining the clinical validity of gene disease relationships for more efficient and accurate clinical testing and reporting. C1 [Abou Tayoun, Ahmad N.; Al Turki, Saeed H.] Harvard Univ, Sch Med, Genet Training Program, Cambridge, MA 02138 USA. [Abou Tayoun, Ahmad N.; Oza, Andrea M.; Bowser, Mark J.; Hernandez, Amy L.; Funke, Birgit H.; Rehm, Heidi L.; Amr, Sami S.] Partners Healthcare Personalized Med, Mol Med Lab, Cambridge, MA USA. [Abou Tayoun, Ahmad N.] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Genom Diagnost, Philadelphia, PA 19104 USA. [Funke, Birgit H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Rehm, Heidi L.; Amr, Sami S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Amr, SS (reprint author), Partners Healthcare Personalized Med, Mol Med Lab, Cambridge, MA USA.; Amr, SS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM samr@partners.org OI Amr, Sami/0000-0003-0927-6057; Rehm, Heidi/0000-0002-6025-0015 NR 46 TC 1 Z9 1 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2016 VL 18 IS 6 BP 545 EP 553 DI 10.1038/gim.2015.141 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DP0MQ UT WOS:000378184300002 PM 26562227 ER PT J AU Jenkinson, CP Goring, HHH Arya, R Blangero, J Duggirala, R DeFronzo, RA AF Jenkinson, Christopher P. Goring, Harald H. H. Arya, Rector Blangero, John Duggirala, Ravindranath DeFronzo, Ralph A. TI Transcriptomics in type 2 diabetes: Bridging the gap between genotype and phenotype SO GENOMICS DATA LA English DT Article DE Type 2 diabetes; Insulin resistance; Obesity; Gene expression; Mexican Americans; VAGES; ADH1B; Transcriptomics; GWAS; eQTL ID GENOME-WIDE ASSOCIATION; HUMAN SKELETAL-MUSCLE; LONG NONCODING RNAS; BETA-CELL FUNCTION; IN-VIVO; MITOCHONDRIAL-FUNCTION; INSULIN-RESISTANCE; FASTING GLUCOSE; RARE VARIANTS; GENETIC ARCHITECTURE AB Type 2 diabetes (T2D) is a common, multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits. Transcriptomic analysis bridges the gulf between GWAS and physiological studies. Recent GWAS studies have utilized very large population samples, numbering in the tens of thousands (or even hundreds of thousands) of individuals, yet establishing causal functional relationships between strongly associated genetic variants and disease remains elusive. In light of the findings described below, it is appropriate to consider how and why transcriptomic approaches in small samples might be capable of identifying complex disease-related genes which are not apparent using GWAS in large samples. (C) 2015 Published by Elsevier Inc. C1 [Jenkinson, Christopher P.; Goring, Harald H. H.; Arya, Rector; Blangero, John; Duggirala, Ravindranath] UTRGV, STDOI, Edinburg, TX USA. [DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX USA. [DeFronzo, Ralph A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Jenkinson, CP (reprint author), UTRGV, STDOI, ERAHC, 1214 W Schunior, Edinburg, TX 78541 USA. EM christopher.jenkinson@utrgv.edu NR 76 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-5960 J9 GENOM DATA JI Genom. Data PD JUN PY 2016 VL 8 BP 25 EP 36 DI 10.1016/j.gdata.2015.12.001 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA DO4OF UT WOS:000377761900006 PM 27114903 ER PT J AU Landegger, LD Cohen, MS AF Landegger, Lukas D. Cohen, Michael S. TI Use of the flexible fiber CO2 laser in pediatric transcanal endoscopic middle ear surgery SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Transcanal; Endoscopic ear surgery; Pediatric; Flexible fiber CO2 laser; Otology ID OUTCOMES AB We describe 4 pediatric patients (age 6-11 years) who underwent transcanal endoscopic ear surgery (TEES) with the assistance of a flexible fiber CO2 laser over a period of 6 months. Three of these individuals suffered from densely adherent cholesteatoma, where the laser permitted one-handed dissection while preserving endoscopic visualization by limiting bleeding. In the fourth patient, TEES ossiculoplasty was performed for a congenital stapes bar, with subsequent hearing improvement. Advantages and disadvantages of the flexible fiber CO2 laser in the setting of TEES are discussed. Use of the flexible fiber CO2 laser was found to expand the TEES toolkit. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Landegger, Lukas D.; Cohen, Michael S.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Landegger, Lukas D.; Cohen, Michael S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, 25 Shattuck St, Boston, MA 02115 USA. RP Cohen, MS (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM lukas_landegger@meei.harvard.edu; michael_cohen@meei.harvard.edu OI Landegger, Lukas D./0000-0002-9660-2625 NR 11 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUN PY 2016 VL 85 BP 154 EP 157 DI 10.1016/j.ijporl.2016.03.039 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA DP0MX UT WOS:000378185000030 PM 27240515 ER PT J AU Generoso, JR Latoures, RE Acar, Y Miller, DS Ciano, M Sandrei, R Vieira, M Luong, S Hirsch, J Fidler, RL AF Generoso, Jose Roberto, Jr. Latoures, Renee Elizabeth Acar, Yahya Miller, Dean Scott Ciano, Mark Sandrei, Renan Vieira, Marlon Luong, Sean Hirsch, Jan Fidler, Richard Lee TI Simulation Training in Early Emergency Response (STEER) SO JOURNAL OF CONTINUING EDUCATION IN NURSING LA English DT Article ID HOSPITAL CARDIAC-ARREST; INDUCED RESPIRATORY DEPRESSION; UNITED-STATES; OLDER-ADULTS; CARDIOPULMONARY-RESUSCITATION; DELIBERATE PRACTICE; 1ST 5; FALLS; TEAM; PERFORMANCE AB Little has been published about nurses' responses in the first 5 minutes of in-hospital emergencies. This study aimed to test a simulation curriculum based on institutional priorities using high-intensity, short-duration, frequent in situ content delivery based on deliberate practice. The study design was a prospective, single-center, mixed-methods quasi-experimental study. Scenarios used in this study were ventricular fibrillation, opiate-related respiratory depression, syncopal fall, and hemorrhagic stroke. The convenience sample included 41 teams (147 participants). Improvements were noted in initiating chest compressions (p = .018), time to check blood glucose (p = .046), and identification of heparin as a contributor to stroke (p = .043). Establishing in situ simulation-based teaching program is feasible and well received. This approach appears effective in increasing confidence, initiating life-saving measures, and empowering nurses to manage emergencies. Future studies should evaluate and improve on the curriculum, on data collection tools quantitatively, and on overcoming barriers to high-quality emergency care. C1 [Generoso, Jose Roberto, Jr.; Latoures, Renee Elizabeth; Acar, Yahya; Sandrei, Renan; Vieira, Marlon] Univ Calif San Francisco, 94150 Clement St, San Francisco, CA 94121 USA. [Hirsch, Jan] Univ Calif San Francisco, Anesthesia, San Francisco, CA 94121 USA. [Hirsch, Jan; Fidler, Richard Lee] San Francisco VA Med Ctr, Simulat Fellowship, San Francisco, CA USA. [Fidler, Richard Lee] Univ Calif San Francisco, Nursing, San Francisco, CA 94121 USA. [Miller, Dean Scott; Ciano, Mark; Luong, Sean] San Francisco VA Med Ctr, San Francisco, CA USA. [Luong, Sean] San Francisco VA Med Ctr, Adv Clin Simulat & Nurse Educ Informat, San Francisco, CA USA. RP Generoso, JR (reprint author), Univ Calif San Francisco, 94150 Clement St, San Francisco, CA 94121 USA. EM josegeneroso@va.gov NR 28 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-0124 EI 1938-2472 J9 J CONTIN EDUC NURS JI J. Contin. Educ. Nursing PD JUN PY 2016 VL 47 IS 6 BP 255 EP 265 DI 10.3928/00220124-20160518-06 PG 11 WC Nursing SC Nursing GA DP1FR UT WOS:000378236400006 PM 27232223 ER PT J AU Malow, BA Connolly, HV Weiss, SK Halbower, A Goldman, S Hyman, SL Katz, T Madduri, N Shui, A Macklin, E Reynolds, AM AF Malow, Beth A. Connolly, Heidi V. Weiss, Shelly K. Halbower, Ann Goldman, Suzanne Hyman, Susan L. Katz, Terry Madduri, Niru Shui, Amy Macklin, Eric Reynolds, Ann M. TI The Pediatric Sleep Clinical Global Impressions Scale-A New Tool to Measure Pediatric Insomnia in Autism Spectrum Disorders SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE sleep; autism; CGI; Children's Sleep Habits Questionnaire; actigraphy ID PERVASIVE DEVELOPMENTAL DISORDERS; SCHOOL-AGED CHILDREN; TYPICAL DEVELOPMENT; ACTIGRAPHY AB Objective: To pilot a clinician-based outcome measure that provides complementary information to objective measures and parent-based questionnaires for insomnia in children with autism spectrum, disorders (ASD). Method: The authors developed a Pediatric Sleep Clinical Global Impressions Scale (CGI). Questions included (1) the child's ability to fall asleep and remain sleeping independently (i.e., apart from parents); (2) bedtime resistance; (3) sleep onset delay; (4) night awakening; (5) parental satisfaction with their child's current sleep patterns; (6) family functioning as affected by their child's current sleep patterns; and (7) clinician's overall concern with the child's sleep. After refining the instrument through the evaluation of vignettes by ASD and sleep experts, the authors piloted the Pediatric Sleep CGI in a 12-week randomized trial of iron supplementation in children with ASD. Clinicians completed Pediatric Sleep CGIs and structured sleep histories, parents completed the Children's Sleep Habits Questionnaire (CSHQ), and children wore actigraphy watches. Results: In repeated measures models, the Pediatric Sleep CGI and CSHQ were correlated for sleep onset delay (r =.66, p <.001), night wakings (r =.40, p <.001), and total score (r =.29, p <.001). The CGI-S sleep onset delay and actigraphy sleep onset delay scores (r =.75, p =.0095) were also correlated. The overall CGI-S showed improvement with therapy (p =.047). Conclusion: The Pediatric Sleep CGI shows promise in measuring clinician-rated outcomes in pediatric insomnia in children with ASD. Larger samples will be necessary to examine reliability, validity, and measure to change, as well as applicability to other populations with pediatric insomnia. C1 [Malow, Beth A.; Goldman, Suzanne; Madduri, Niru] Vanderbilt Univ, Med Ctr, Dept Neurol, Sleep Disorders Div, 1161 21st Ave South,Room A-0116 MCN, Nashville, TN 37232 USA. [Connolly, Heidi V.; Hyman, Susan L.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Weiss, Shelly K.] Univ Toronto, Hosp Sick Children, Dept Neurol, Toronto, ON M5G 1X8, Canada. [Halbower, Ann; Katz, Terry; Reynolds, Ann M.] Univ Colorado, Dept Pediat, Denver, CO 80202 USA. [Shui, Amy; Macklin, Eric] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Malow, BA (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 1161 21st Ave South,Room A-0116 MCN, Nashville, TN 37232 USA. FU Autism Intervention Research Network on Physical Health (U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program) [UA3 MC 11054]; Autism Speaks Autism Treatment Network; CTSA from National Center for Advancing Translational Sciences [UL1TR000445, UL1 TR000042, UL1 TR001082] FX The authors report no conflicts of interest or financial relationships relevant to this article. This research was conducted as part of a multicenter trial funded through the Autism Intervention Research Network on Physical Health (Cooperative agreement UA3 MC 11054 from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital) and the Autism Speaks Autism Treatment Network. The views expressed in this publication do not necessarily reflect the views of Autism Speaks, Inc. Additional support was provided by CTSA award numbers UL1TR000445, UL1 TR000042, and UL1 TR001082 from the National Center for Advancing Translational Sciences. Contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. NR 18 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 2016 VL 37 IS 5 SI SI BP 370 EP 376 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA DP3CW UT WOS:000378371000003 PM 27244298 ER PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Dietary proanthocyanidins inhibit UV radiation-induced skin tumor development through functional activation of the immune system SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE Cyclobutane pyrimidine dimers; Dendritic cells; Skin cancer; T cells; Ultraviolet radiation ID ULTRAVIOLET-INDUCED CARCINOGENESIS; PRESENTING CELL-FUNCTION; DNA EXCISION-REPAIR; GRAPE SEED EXTRACT; CD8(+) T-CELLS; CONTACT HYPERSENSITIVITY; DENDRITIC CELLS; XERODERMA-PIGMENTOSUM; TRANSPLANT RECIPIENTS; MOLECULAR-MECHANISMS AB The incidence of skin cancer is equivalent to the incidence of malignancies in all other organs combined. The main risk factor for this disease is overexposure of the skin to solar ultraviolet (UV) radiation. UV irradiation induces inflammation, oxidative stress, DNA damage, and suppression of the immune system in the skin, which together contribute to carcinogenesis. The use of dietary phytochemicals shows great promise as a complementary and alternative strategy for skin cancer prevention. Grape seed proanthocyanidins (GSPs) have been tested extensively for their anti-skin cancer effect using in vivo animal models. Supplementation of an AIN76A control diet with GSPs (0.2 and 0.5%, w/w) significantly inhibits UV radiation-induced skin tumor development as well as malignant transformation of papillomas to carcinoma in mice. The inhibition of UVB-induced skin tumor development by GSPs is mediated through interrelated mechanisms of action including: (i) inhibition of inflammation, (ii) rapid repair of damaged DNA, and (iii) stimulation of immune system. Additionally, the chemopreventive effects of GSPs involve DNA repair-dependent functional activation of antigen-presenting cells and stimulation of CD8(+) effector T cells. These effects of GSPs could be useful in attenuation of the adverse effects of UV radiation and may have health benefits in humans. C1 [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Environm Hlth Sci, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.; Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Environm Hlth Sci, Birmingham, AL 35294 USA.; Katiyar, SK (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.; Katiyar, SK (reprint author), Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL 35294 USA.; Katiyar, SK (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. EM skatiyar@uab.edu FU National Cancer Institute/NIH [CA104428]; Veterans Administration Merit Review Award [1I01BX001410] FX The work reported from Dr. Katiyar's research laboratory was financially supported from the funds from National Cancer Institute/NIH (CA104428) and Veterans Administration Merit Review Award (1I01BX001410). Grateful thanks are due to our former and current research staff members for their outstanding contribution in the related studies. The content of this publication does not necessarily reflect the views or policies of the funding sources. NR 70 TC 0 Z9 0 U1 6 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUN PY 2016 VL 60 IS 6 SI SI BP 1374 EP 1382 DI 10.1002/mnfr.201501026 PG 9 WC Food Science & Technology SC Food Science & Technology GA DP5GE UT WOS:000378523500013 PM 26991736 ER PT J AU Poole, VN Robinson, ME Singleton, O DeGutis, J Milberg, WP McGlinchey, RE Salat, DH Esterman, M AF Poole, Victoria N. Robinson, Meghan E. Singleton, Omar DeGutis, Joseph Milberg, William P. McGlinchey, Regina E. Salat, David H. Esterman, Michael TI Intrinsic functional connectivity predicts individual differences in distractibility SO NEUROPSYCHOLOGIA LA English DT Article DE Attention; Distraction; Functional connectivity; Support vector regression; Resting-State fMRI ID DEFAULT-MODE NETWORK; TRANSCRANIAL MAGNETIC STIMULATION; TRAUMATIC BRAIN-INJURY; FRONTAL EYE FIELD; RESTING-STATE; ATTENTIONAL CAPTURE; VISUAL-ATTENTION; TOP-DOWN; PSYCHOLOGICAL SYMPTOMS; INTERFERENCE CONTROL AB Distractor suppression, the ability to filter and ignore task-irrelevant information, is critical for efficient task performance. While successful distractor suppression relies on a balance of activity in neural networks responsible for attention maintenance (dorsal attention network; DAN), reorientation (ventral attention network; VAN), and internal thought (default mode network, DMN), the degree to which intrinsic connectivity within and between these networks contributes to individual differences in distractor suppression ability is not well-characterized. For the purposes of understanding these interactions, the current study collected resting-state fMRI data from 32 Veterans and, several months later (7 5 months apart), performance on the additional singleton paradigm, a measure of distractor suppression. Using multivariate support vector regression models composed of resting state connectivity between regions of the DAN, VAN, and DMN, and a leave-one-subject-out cross-validation procedure, we were able to predict an individual's task performance, yielding a significant correlation between the actual and predicted distractor suppression (r=0.48, p=0.0053). Network-level analyses revealed that greater within-network DMN connectivity was predictive of better distractor suppression, while greater connectivity between the DMN and attention networks was predictive of poorer distractor suppression. The strongest connection hubs were determined to be the right frontal eye field and temporoparietal junction of the DAN and VAN, respectively, and medial (ventromedial prefrontal and posterior cingulate cortices) and bilateral prefrontal regions of the DMN. These results are amongst a small but growing number of studies demonstrating that resting state connectivity is related to stable individual differences in cognitive ability, and suggest that greater integrity and independence of the DMN is related to better attentional ability. Published by Elsevier Ltd. C1 [Poole, Victoria N.; Robinson, Meghan E.; DeGutis, Joseph; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.; Esterman, Michael] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, VA RR&D TBI Ctr Excellence, 150 S Huntington Ave, Boston, MA 02130 USA. [Poole, Victoria N.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Poole, Victoria N.; DeGutis, Joseph; Milberg, William P.; McGlinchey, Regina E.; Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA. [Poole, Victoria N.; Robinson, Meghan E.; Salat, David H.; Esterman, Michael] VA Boston Healthcare Syst, Neuroimaging Res Vet NeRVe Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. [Poole, Victoria N.; Singleton, Omar; DeGutis, Joseph; Esterman, Michael] VA Boston Healthcare Syst, Boston Attent & Learning Lab BAL1LAB, 150 S Huntington Ave, Boston, MA 02130 USA. [Robinson, Meghan E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Milberg, William P.; McGlinchey, Regina E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, 150 S Huntington Ave, Boston, MA 02130 USA. [Salat, David H.] AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Esterman, Michael] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Poole, VN (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM vpoole@bidmc.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU Translational Research Center for TBI and Stress Disorders (TRACTS); VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B9254-C]; Department of Veterans Affairs Clinical Sciences Research and Development [1IK2CX000706-01A2]; National Institutes of Health [5T32AG023480] FX This research was supported by the Translational Research Center for TBI and Stress Disorders (TRACTS), a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B9254-C), a Career Development award to M. E. from the Department of Veterans Affairs Clinical Sciences Research and Development (1IK2CX000706-01A2), and an institutional training award to V. P. from National Institutes of Health (T32 Grant 5T32AG023480). NR 72 TC 3 Z9 3 U1 8 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUN PY 2016 VL 86 BP 176 EP 182 DI 10.1016/j.neuropsychologia.2016.04.023 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DP4GC UT WOS:000378453400018 PM 27132070 ER PT J AU Seeganna, C Antai-Otong, D AF Seeganna, Carolyn Antai-Otong, Deborah TI Managing the Care of the Older Patient with Delirium and Dementia SO NURSING CLINICS OF NORTH AMERICA LA English DT Article DE Geriatric psychiatric emergencies; Delirium; Dementia; Cognitive disorders ID PREVALENCE; MANAGEMENT; PROGNOSIS; SUBTYPES; PROPHYLAXIS; PEOPLE; RISK AB As the population ages, nurses in various clinical settings must identify high-risk groups that are vulnerable to delirium and dementia. They also must be able to provide psychosocial and pharmacologic interventions that promote comfort and safety for patients and their families experiencing these distressful medical conditions. Efforts to facilitate health resolution and restore the patient and caregivers to an optimal level of functioning must be priorities. C1 [Seeganna, Carolyn] US Dept Vet Affairs, Mat Su Community Based Outpatient Clin, 865 North Seward Meridian Pkwy, Wasilla, AK 99654 USA. [Antai-Otong, Deborah] Vet Integrated Serv Networks VISN 17, Dept Vet Affairs, 2301 E Lamar Blvd, Arlington, TX 76006 USA. RP Seeganna, C (reprint author), US Dept Vet Affairs, Mat Su Community Based Outpatient Clin, 865 North Seward Meridian Pkwy, Wasilla, AK 99654 USA. EM Carolyn.Seeganna@va.gov NR 51 TC 0 Z9 0 U1 6 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0029-6465 EI 1558-1357 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2016 VL 51 IS 2 BP 261 EP + DI 10.1016/j.cnur.2016.01.009 PG 14 WC Nursing SC Nursing GA DP3BM UT WOS:000378367400011 PM 27229280 ER PT J AU Dagogo-Jack, I Shaw, AT AF Dagogo-Jack, Ibiayi Shaw, Alice T. TI Screening for ALK Rearrangements in Lung Cancer: Time for a New Generation of Diagnostics? SO ONCOLOGIST LA English DT Editorial Material ID EML4-ALK; IMMUNOHISTOCHEMISTRY; CRIZOTINIB; ADENOCARCINOMAS; CHEMOTHERAPY C1 [Dagogo-Jack, Ibiayi; Shaw, Alice T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org NR 15 TC 1 Z9 1 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2016 VL 21 IS 6 BP 662 EP 663 DI 10.1634/theoncologist.2016-0179 PG 2 WC Oncology SC Oncology GA DP2WB UT WOS:000378353100004 PM 27245570 ER PT J AU Truong, SR Barry, WT Moslehi, JJ Baker, EL Mayer, EL Partridge, AH AF Truong, Sandy R. Barry, William T. Moslehi, Javid J. Baker, Emily L. Mayer, Erica L. Partridge, Ann H. TI Evaluating the Utility of Baseline Cardiac Function Screening in Early-Stage Breast Cancer Treatment SO ONCOLOGIST LA English DT Article DE Cardiotoxicity; Cardiac function; Screening; Chemotherapy ID CARDIOTOXICITY; TRASTUZUMAB; DOXORUBICIN; THERAPIES AB Background. Cardiotoxicity can be a complication of anthracycline-or trastuzumab-based therapy for breast cancer patients. Screening echocardiograms (ECHOs) and radionuclide ventriculograms (RVGs) are often performed before administration of these agents to evaluate cardiac function. Limited evidence for the clinical utility of these screening tests is available. Methods. Early-stage breast cancer patients diagnosed from 2006 to 2011 (n = 1,067) with baseline ECHOs/RVGs were identified in a single institution prospective registry. Medical record review was performed to obtain pre- and post-ECHO/RVG treatment plans, baseline ECHO/RVG results, cardiac risk factors, and cardiac events. Patients with cardiac history were excluded. ECHO/RVG abnormalities were defined as ejection fraction (EF) <55%, valvular disease, left ventricular hypertrophy, and diastolic dysfunction. Cardiac events were defined as heart failure, myocardial infarction, arrhythmia, valvular disease, or angina during or after chemotherapy. Results. Among 600 eligible patients, abnormal ECHO/RVG results were observed in 13 (2.2%, 1.2%-3.7%), including 9 with baseline EF <55%. There were no detected changes in treatment plans, although more frequent cardiac monitoring was recommended for 2 patients. There were no significant differences in age, race, menopausal status, smoking history, alcohol use, body mass index, or medical comorbidities between patients with abnormal and normal results. In follow-up (mean, 4.0 years; range, 0-8.3), 15 patients developed cardiac events (none of whom had had abnormal baseline ECHOs/RVGs). Conclusion. Baseline ECHO/RVG in patients without prior cardiac history rarely yields an abnormality that prompts change in planned anthracycline- and/or trastuzumab-based treatment. Moreover, few cardiac events developed in this screened population in follow-up. C1 [Truong, Sandy R.; Barry, William T.; Mayer, Erica L.; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA. [Truong, Sandy R.; Barry, William T.; Baker, Emily L.; Mayer, Erica L.; Partridge, Ann H.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Moslehi, Javid J.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Moslehi, Javid J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Partridge, Ann H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu FU Pink Agenda; LIVESTRONG Foundation; Susan G. Komen Foundation FX This research was supported by the Pink Agenda, LIVESTRONG Foundation, and Susan G. Komen Foundation. These funding organizations had no involvement in the design and conduct of the study. Aportion of these data was previously presented as a poster at the 2014 American Society of Clinical Oncology annual meeting, Chicago, IL. NR 12 TC 1 Z9 1 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2016 VL 21 IS 6 BP 666 EP 670 DI 10.1634/theoncologist.2015-0449 PG 5 WC Oncology SC Oncology GA DP2WB UT WOS:000378353100006 PM 27107002 ER PT J AU Brown, CA Suneja, G Tapela, N Mapes, A Pusoentsi, M Mmalane, M Hodgeman, R Boyer, M Musimar, Z Ramogola-Masire, D Grover, S Nsingo-Bvochora, M Kayembe, M Efstathiou, J Lockman, S Dryden-Peterson, S AF Brown, Carolyn A. Suneja, Gita Tapela, Neo Mapes, Abigail Pusoentsi, Malebogo Mmalane, Mompati Hodgeman, Ryan Boyer, Matthew Musimar, Zola Ramogola-Masire, Doreen Grover, Surbhi Nsingo-Bvochora, Memory Kayembe, Mukendi Efstathiou, Jason Lockman, Shahin Dryden-Peterson, Scott TI Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting SO ONCOLOGIST LA English DT Article DE HIV; Botswana; Cancer; Timely oncology care; Advanced-stage cancer ID LUNG-CANCER; SOCIOECONOMIC-STATUS; BREAST-CANCER; DIAGNOSIS; SURVEILLANCE; MORTALITY; SURVIVAL; EPIDEMIOLOGY; CHALLENGES; CRITERIA AB Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom(aOR 1.39, 95% CI 1.03-1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. C1 [Brown, Carolyn A.; Mapes, Abigail; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Lockman, Shahin; Dryden-Peterson, Scott] Botswana Harvard AIDS Inst, Gaborone, Botswana. [Brown, Carolyn A.] Emory Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Suneja, Gita] Univ Utah, Dept Radiat Oncol, Salt Lake City, UT USA. [Tapela, Neo] Univ Botswana, Sch Med, Gaborone, Botswana. [Tapela, Neo; Musimar, Zola] Princess Marina Hosp, Dept Oncol, Gaborone, Botswana. [Pusoentsi, Malebogo] Minist Hlth Botswana, Gaborone, Botswana. [Boyer, Matthew] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA. [Ramogola-Masire, Doreen] Botswana UPenn Partnership Hlth Program, Gaborone, Botswana. [Grover, Surbhi] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Nsingo-Bvochora, Memory] Gaborone Private Hosp, Dept Oncol, Gaborone, Botswana. [Kayembe, Mukendi] Natl Hlth Lab, Anat Pathol, Gaborone, Botswana. [Efstathiou, Jason] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lockman, Shahin; Dryden-Peterson, Scott] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Lockman, Shahin; Dryden-Peterson, Scott] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Brown, CA (reprint author), Emory Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. EM carolyn.brown.a@gmail.com FU Harvard University [P30 AI060354]; University of Pennsylvania [P30 AI045008]; NIH; National Institute of Allergy and Infectious Diseases; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; National Institute of Mental Health; National Instituteon Aging; Fogarty International Center; Office of Regulatory Affairs; Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH) [8UL1TR000170-05]; Harvard University and its affiliated academic health care centers FX This article was made possible with help from the Harvard University (P30 AI060354) and University of Pennsylvania (P30 AI045008) Centers for AIDS Research (CFAR), an NIH funded program supported by the following NIH cofunding and participating institutes and centers: National Institute of Allergy and Infectious Diseases; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; National Institute of Mental Health; National Instituteon Aging; Fogarty International Center; and Office of Regulatory Affairs. The work was also 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, NIH Award 8UL1TR000170-05, 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 NIH. NR 36 TC 3 Z9 3 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2016 VL 21 IS 6 BP 731 EP 738 DI 10.1634/theoncologist.2015-0387 PG 8 WC Oncology SC Oncology GA DP2WB UT WOS:000378353100015 PM 27053501 ER PT J AU Feldman, AS AF Feldman, Adam S. TI Is Immediate Radical Cystectomy Justified When Non-Muscle-Invasive Bladder Cancer First Presents as High-Grade T1 Urothelial Carcinoma on Re-Resection? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BACILLUS-CALMETTE-GUERIN; RESTAGING TRANSURETHRAL RESECTION; DEFERRED CYSTECTOMY; NATURAL-HISTORY; RISK GROUPS; PROGRESSION; SURVIVAL; RECURRENCE; METAANALYSIS; OUTCOMES C1 [Feldman, Adam S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Feldman, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 32 TC 0 Z9 0 U1 1 U2 2 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2016 VL 30 IS 6 BP 541 EP 545 PG 5 WC Oncology SC Oncology GA DO8FG UT WOS:000378017400007 PM 27311841 ER PT J AU Chahine, LM Xie, SX Simuni, T Tran, B Postuma, R Amara, A Oertel, WH Iranzo, A Scordia, C Fullard, M Linder, C Purri, R Darin, A Rennert, L Videnovic, A Del Riva, P Weintraub, D AF Chahine, L. M. Xie, S. X. Simuni, T. Tran, B. Postuma, R. Amara, A. Oertel, W. H. Iranzo, A. Scordia, C. Fullard, M. Linder, C. Purri, R. Darin, A. Rennert, L. Videnovic, A. Del Riva, P. Weintraub, D. TI Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE REM sleep behavior disorder; Cognition; Dementia ID DEMENTIA; IMPAIRMENT; RISK AB Introduction: Cognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep behavior disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains. Methods: Parkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep behavior disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ >= 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates. Results: The baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (beta = -034, 95%CI -0.54, -0.13, p < 0.001), Symbol Digit Modalities Test (beta = -0.69, 95%CI -1.3, -0.09, p = 0.024), and Hopkins Verbal Learning Test Revised, delayed free recall (beta = -0.21, 95%CI -0.41, -0.013, p = 0.037). Conclusions: Possible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains. (C) 2016 Published by Elsevier Ltd. C1 [Chahine, L. M.; Xie, S. X.; Tran, B.; Scordia, C.; Fullard, M.; Linder, C.; Purri, R.; Darin, A.; Rennert, L.; Weintraub, D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Simuni, T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Postuma, R.] McGill Univ, Montreal, PQ, Canada. [Amara, A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Oertel, W. H.] Univ Marburg, Dept Neurol, Marburg, Germany. [Oertel, W. H.] Charitable Hertie Fdn, Frankfurt, Germany. [Iranzo, A.] Hosp Clin Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. [Videnovic, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Del Riva, P.] Univ Hosp Donostia, Dept Neurol, San Sebastian, Spain. RP Chahine, LM (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. EM lamachahine@hotmail.com OI Amara, Amy/0000-0003-0762-9656 FU Michael J. Fox Foundation for Parkinson's Research (MJFF); MJFF; Abbvie; Avid Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; Eli Lilly Co.; F. Hoffman-La Roche, Ltd.; GE Healthcare; Genentech; GlaxoSmithKline; Lundbeck; Merck; MesoScale; Piramal; Pfizer; UCB; NIH [P50 NS053488, AG10124, NS053488, T32MH065218, K23NS080912, K23 N705080912]; Michael J. Fox Foundation for Parkinson's Research; National Institutes of Health; Novartis Pharmaceuticals; Department of Veterans Affairs; Alzheimer's Disease Cooperative Study; University of Pennsylvania for the QUIP; QUIP-RS; GE Medical; TEVA; Acadia; Eli Lilly; Harbor; IMPAX; Merz, Inc.; Navidea; UCB Pharma US World Meds; National Parkinson Foundation; Auspex; Biotie; Civitas; Michael J. Fox Foundation; Fonds de la Recherche en Sante Quebec; Canadian Institute of Health Research; Parkinson Society; Weston-Garfield Foundation; Webster Foundation; Novartis Canada; Teva Neurosciences; German Research Foundation; International Parkinson Foundations; Michael J Fox Foundation; EU; Desitin; GE Health; Mundipharma; UCB- Amy FX P.P.M.I. is sponsored by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB.; Lama M. Chahine (i) receives support from the NIH (P50 NS053488) (ii) receives support as site Principal Investigator of the Parkinson's Progression Marker's Initiative and (iii) receives royalties from Wolters Kluwel (for book authorship).; Sharon Xie receives funding support from NIH AG10124 and NIH NS053488.; Lior Rennert receives funding support from NIH T32MH065218.; Daniel Weintraub has received research funding or support from Michael J. Fox Foundation for Parkinson's Research, National Institutes of Health, Novartis Pharmaceuticals, Department of Veterans Affairs, Avid Radiopharmaceuticals, and Alzheimer's Disease Cooperative Study; honoraria from AbbVie, Biotie, Teva Pharmaceuticals, Otsuka, UCB, Clintrex LLC, and the CHDI Foundation; license fee payments from the University of Pennsylvania for the QUIP and QUIP-RS; royalties from Wolters Kluweland; and fees for legal consultation for lawsuit related to antipsychotic prescribing in a patient with Parkinson's disease.; Tanya Simuni has received consulting fees as a speaker and/or consultant from GE Medical, TEVA, Acadia, Abbvie, Eli Lilly, Harbor, IMPAX, Lundbeck, Merz, Inc., Navidea, Pfizer, UCB Pharma US World Meds. The National Parkinson Foundation has provided Dr. Simuni with research funding for studies and she is a consultant for the foundation. Dr. Simuni has received research funding from TEVA, Auspex, Biotie, and Civitas. The NIH and the Michael J. Fox Foundation have provided research funding.; Ron Postuma received grants from the Fonds de la Recherche en Sante Quebec, the Canadian Institute of Health Research, the Parkinson Society, the Weston-Garfield Foundation, and the Webster Foundation, as well as funding for consultancy from Biotie and speaker fees from Novartis Canada and Teva Neurosciences.; Wolfgang H Oertel is Hertie Senior Research Professor of the Charitable Hertie Foundation, Frankfurt/Main, Germany. He received research grants form the German Research Foundation, International Parkinson Foundations, the Michael J Fox Foundation and the EU- Research Program Horizon 2020 (JPND). He is consultant of the Novartis Foundation. He received consulting fees as a speaker and/or consultant from AbbVie, Desitin, GE Health, Mundipharma and UCB- Amy W. Amara, MD, PhD receives research funding from NIH K23NS080912 and the Michael J. Fox Foundation and has served as an investigator for studies funded by Abbvie.; Aleksander Videnovic receives research funding from NIH K23 N705080912. NR 12 TC 3 Z9 3 U1 5 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUN PY 2016 VL 27 BP 102 EP 106 DI 10.1016/j.parkreldis.2016.03.006 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DP0PN UT WOS:000378191800016 PM 27010070 ER PT J AU Schoenfeld, AJ Wang, XH Wang, YY Hornicek, FJ Nielsen, GP Duan, ZF Ferrone, S Schwab, JH AF Schoenfeld, Andrew J. Wang, Xinhui Wang, Yangyang Hornicek, Francis J. Nielsen, G. Petur Duan, Zhenfeng Ferrone, Soldano Schwab, Joseph H. TI CSPG4 as a prognostic biomarker in chordoma SO SPINE JOURNAL LA English DT Article DE Biomarkers; Chordoma; CSPG4; Metastases; Outcomes; Survival ID ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES; PRIMARY BONE-TUMORS; ANTIGEN HMW-MAA; MOBILE SPINE; MALIGNANT-MELANOMA; SACRAL CHORDOMAS; CANCER; SURVIVAL; EXPERIENCE; MIMICRY AB BACKGROUND: There are currently no generally accepted biomarkers used in the clinical treatment of chordoma tumors. CSPG4 has been associated with disease severity in other tumors. PURPOSE: This study aimed to characterize the frequency of CSPG4 expression in chordoma tumors and to correlate it with disease severity and clinical outcome. STUDY DESIGN: A retrospective review of clinical outcomes and immunohistochemical staining using tissue micro-array was carried out. PATIENT SAMPLE: The sample comprised 86 patients treated for chordoma at a single center (1985-2007). OUTCOME MEASURES: Survival and incidence of metastases were the outcome measures. METHODS: Pathologic specimens of chordoma tumors were evaluated for the expression of CSPG4 by immunohistochemical staining with mAbs. Chi-square testing and Cox proportional hazard regression analysis were used to evaluate the impact of CSPG4 expression on survival and incidence of metastases, while controlling for patient age, sex, and surgical margins. RESULTS: Average patient age at the time of presentation was 59.8 years (standard deviation [SD] 13.7). Average follow-up was 6.5 years (SD 4.8). Twenty (23%) patients developed metastatic disease. At the time of final follow-up, 57 patients (66%) had died. Chordoma tumors from 62 patients (72%) stained positive for CSPG4. CSPG4 expression more than doubled the risk of death (hazard ratio [HR] 2.3; 95% CI 1.04, 5.17). CSPG4 positive tumors were also associated with an increased risk of metastatic disease (31% for CSPG4 positive tumors vs. 0% in CSPG4 negative, p=.02). CONCLUSIONS: Results presented here support the consideration of using CSPG4 as a biomarker establishing the prognosis for chordoma tumors. A positive CSPG4 stain may be associated with an increased risk of metastasis and mortality from disease. (C) 2015 Elsevier Inc. All rights reserved. C1 [Schoenfeld, Andrew J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. [Wang, Xinhui; Wang, Yangyang; Nielsen, G. Petur; Ferrone, Soldano] Harvard Univ, Dept Surg, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Hornicek, Francis J.; Duan, Zhenfeng; Ferrone, Soldano; Schwab, Joseph H.] Harvard Univ, Dept Orthopaed Surg, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. RP Schoenfeld, AJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. EM ajschoen@neomed.edu OI Schoenfeld, Andrew/0000-0002-3691-1215 FU K12 MeRIT; Harvard Catalyst, Harvard Medical School (K12 MeRIT; Medical Research Investigator Training Program); Robert Wood Johnson Foundation FX AJS: Grant: Robert Wood Johnson Foundation (F; Paid directly to institution/employer); Royalties: Wolters Kluwer Health (A); Consulting: Arbormetrix (B); Deputy Editor: The Spine Journal (A), outside the submitted work. XW: Nothing to disclose. YW: Nothing to disclose. FJH: Nothing to disclose. GPN: Nothing to disclose. ZD: Nothing to disclose. SF: Nothing to disclose. JHS: Grant: K12 MeRIT (F); Medical Research Investigator Training Program Sponsored by the Harvard Catalyst, Harvard Medical School (K12 MeRIT; Medical Research Investigator Training Program 2008-2010), pertaining to the submitted work. NR 30 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD JUN PY 2016 VL 16 IS 6 BP 722 EP 727 DI 10.1016/j.spinee.2015.11.059 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DP0TC UT WOS:000378201100029 PM 26689475 ER PT J AU Ritterhouse, LL Wirth, LJ Randolph, GW Sadow, PM Ross, DS Liddy, W Lennerz, JK AF Ritterhouse, Lauren L. Wirth, Lori J. Randolph, Gregory W. Sadow, Peter M. Ross, Douglas S. Liddy, Whitney Lennerz, Jochen K. TI ROS1 Rearrangement in Thyroid Cancer SO THYROID LA English DT Article ID CARCINOMA; VARIANT; FUSIONS AB Background: Aberrations involving the ROS1 gene have not been reported in thyroid cancer. Here, a case of ROS1-associated thyroid cancer with unique and aggressive characteristics is presented. Patient findings: A 24-year-old athlete presented with a 3.5 cm left paramedian upper neck mass. Open biopsy demonstrated a papillary thyroid carcinoma arising in the pyramidal lobe. Additional imaging revealed involvement of her cricothyroid membrane, thyroid laryngeal cartilage, and left vocal cord. Complete en bloc surgical resection of the thyroid with cricothyroid membrane and endolarynx was performed with negative surgical margins. Microscopically, the tumor was largely solid with microfollicular architecture with focal cytoplasmic clearing and nodular invasion with rare true papillae, extending posteriorly through the cricothyroid membrane into the deep soft tissue of the left anterior vocal cord (pT4a). Metastases were present in 5/11 lateral neck and pretracheal lymph nodes with a size up to 0.4 cm (pN1b) with perinodal lymphatic involvement. She was staged according to her age (<45 years) as stage I. The solid-variant histology and locally aggressive behavior triggered oncologic genotyping, which was performed using massive parallel sequencing and anchored multiplexed next-generation sequencing for gene fusion detection on formalin-fixed paraffin embedded tissue. Targeted genotyping did not reveal a panel-specific point mutation. However, gene fusion assessment demonstrated a gene fusion involving ROS1. Mapping of the fusion and sequence analysis identified CCDC30 as the ROS1 fusion partner. Sequence-based prediction of the fusion product revealed the coiled-coil domain 30 (CCDC30) gene fused to the N-terminal ROS1 kinase domain, with CCDC30 as the postulated driver of ROS1-kinase constitutive activation. ROS1 rearrangement was confirmed using fluorescent in situ hybridization as an orthogonal method. A review of all currently reported ROS1 fusions in >7000 samples (The Cancer Genome Atlas) showed no prior report of ROS1-CCDC30, ROS1 fusions, or presence of ROS1 aberrations in thyroid cancer. Summary: Herein, the first case of a ROS1 rearrangement in a papillary thyroid carcinoma with a locally aggressive presentation is reported. Conclusion: A review of additional patients with solid-variant papillary thyroid carcinoma and similar clinical characteristics with undetermined tumor genetics is needed, especially in light of the availability of ROS1-targeted therapeutics. C1 [Ritterhouse, Lauren L.; Sadow, Peter M.; Lennerz, Jochen K.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wirth, Lori J.; Ross, Douglas S.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Randolph, Gregory W.; Sadow, Peter M.; Liddy, Whitney] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Randolph, Gregory W.; Sadow, Peter M.; Liddy, Whitney] Harvard Univ, Sch Med, Boston, MA USA. RP Ritterhouse, LL (reprint author), Massachusetts Gen Hosp, Ctr Integrated Diagnost, Jackson Bldg,Floor 10,Mailstop GRJ 1015, Boston, MA 02114 USA. EM lritterhouse@partners.org NR 13 TC 1 Z9 1 U1 0 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 JUN PY 2016 VL 26 IS 6 BP 794 EP 797 DI 10.1089/thy.2016.0101 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO8UH UT WOS:000378059100006 PM 27089969 ER PT J AU Du, E Wenig, BM Su, HK Rowe, ME Haser, GC Asa, SL Baloch, Z Faquin, WC Fellegara, G Giordano, T Ghossein, R LiVolsi, VA Lloyd, R Mete, O Ozbek, U Rosai, J Suster, S Thompson, LD Turk, AT Urken, ML AF Du, Eugenie Wenig, Bruce M. Su, Henry K. Rowe, Meghan E. Haser, Grace C. Asa, Sylvia L. Baloch, Zubair Faquin, William C. Fellegara, Giovanni Giordano, Thomas Ghossein, Ronald LiVolsi, Virginia A. Lloyd, Ricardo Mete, Ozgur Ozbek, Umut Rosai, Juan Suster, Saul Thompson, Lester D. Turk, Andrew T. Urken, Mark L. TI Inter-Observer Variation in the Pathologic Identification of Extranodal Extension in Nodal Metastasis from Papillary Thyroid Carcinoma SO THYROID LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; LYMPH-NODES; CANCER; DISEASE; NUMBER AB Background: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases. Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE. Results: The overall strength of agreement in identifying ENE was only fair (kappa = 0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997. Conclusions: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists' identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified. C1 [Du, Eugenie] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Bronx, NY 10467 USA. [Wenig, Bruce M.] Mt Sinai Beth Israel, Dept Pathol, New York, NY USA. [Urken, Mark L.] Mt Sinai Beth Israel, Dept Otolaryngol Head & Neck Surg, New York, NY USA. [Su, Henry K.; Rowe, Meghan E.; Haser, Grace C.] Thyroid Head & Neck Canc THANC Fdn, 10 Union Sq East,Suite 5B, New York, NY 10003 USA. [Asa, Sylvia L.; Mete, Ozgur] Toronto Gen Hosp, Dept Pathol, Lab Med Program, Toronto, ON, Canada. [Baloch, Zubair; LiVolsi, Virginia A.] Hosp Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fellegara, Giovanni; Rosai, Juan] Ctr Diagnost Italiano, Ctr Consulenze Anat Patol Oncol, Milan, Italy. [Giordano, Thomas] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Ghossein, Ronald] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Lloyd, Ricardo] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. [Ozbek, Umut] Mt Sinai Hosp, Populat Hlth Sci & Policy, New York, NY 10029 USA. [Suster, Saul] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Thompson, Lester D.] Woodland Hills Med Ctr, Dept Pathol, Woodland Hills, CA USA. [Turk, Andrew T.] New York Presbyterian Columbia, Dept Pathol, New York, NY USA. RP Rowe, ME (reprint author), Thyroid Head & Neck Canc THANC Fdn, 10 Union Sq East,Suite 5B, New York, NY 10003 USA. EM mrowe@thancfoundation.org FU THANC Foundation; Mount Sinai Health System FX We would like to acknowledge the generous support of the THANC Foundation and the Mount Sinai Health System. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JUN PY 2016 VL 26 IS 6 BP 816 EP 819 DI 10.1089/thy.2015.0551 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO8UH UT WOS:000378059100009 PM 27089928 ER PT J AU Barbesino, G AF Barbesino, Giuseppe TI Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient Taking Biotin Megadoses SO THYROID LA English DT Article ID INTERFERENCE; TSH AB Background: Accurate immunoassays measuring minute quantities of hormones are the cornerstone of the practice of endocrinology. Despite tremendous advances in this field, novel pitfalls in these tests emerge from time to time. Oral biotin can interfere with immunoassays of several hormones. The purpose of this report is to relate an extreme case of such interference. Patient findings: Apatient with progressivemultiple sclerosiswas found to have extremely elevated free thyroxine, triiodothyronine, and suppressed thyrotropin (TSH) levels. His TSH receptor binding inhibiting antibody level was also elevated. This constellation of laboratory findings suggested a diagnosis of severe Graves' disease. All of the assays yielding abnormal results employed the biotin-streptavidin affinity in their design. The patient had no symptoms of hyperthyroidism, and detailed review of his medications revealed intake of megadoses of biotin. Temporary discontinuation of biotin treatment resulted in complete resolution of the biochemical abnormalities. Conclusions: Non-physiologic biotin supplementation may interfere with several immunoassays, including thyroid hormones, TSH, thyroglobulin, and TSH receptor binding inhibiting antibody, leading to erroneous diagnoses. Questioning for biotin intake should be part of the evaluation for patients undergoing endocrine tests. Interruption of biotin supplementation for at least two days prior to biotin-sensitive tests should be sufficient to avoid major misdiagnoses. C1 [Barbesino, Giuseppe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA USA. RP Barbesino, G (reprint author), Massachusetts Gen Hosp, Thyroid Unit, WACC 730S,55 Fruit St, Boston, MA 02114 USA. EM gbarbesino@mgh.harvard.edu NR 8 TC 8 Z9 8 U1 2 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JUN PY 2016 VL 26 IS 6 BP 860 EP 863 DI 10.1089/thy.2015.0664 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO8UH UT WOS:000378059100016 PM 27043844 ER PT J AU Bhosale, PR Javitt, MC Atri, M Harris, RD Kang, SK Meyer, BJ Pandharipande, PV Reinhold, C Salazar, GM Shipp, TD Simpson, L Sussman, BL Uyeda, J Wall, DJ Zelop, CM Glanc, P AF Bhosale, Priyadarshani R. Javitt, Marcia C. Atri, Mostafa Harris, Robert D. Kang, Stella K. Meyer, Benjamin J. Pandharipande, Pari V. Reinhold, Caroline Salazar, Gloria M. Shipp, Thomas D. Simpson, Lynn Sussman, Betsy L. Uyeda, Jennifer Wall, Darci J. Zelop, Carolyn M. Glanc, Phyllis TI ACR Appropriateness Criteria (R) Acute Pelvic Pain in the Reproductive Age Group SO ULTRASOUND QUARTERLY LA English DT Article DE acute pelvic pain; pregnancy; premenopausal; ultrasound; computed tomography; Appropriateness Criteria ID DEEP VENOUS THROMBOSIS; MAGNETIC-RESONANCE UROGRAPHY; HELICAL COMPUTED-TOMOGRAPHY; LOWER-QUADRANT PAIN; ACUTE APPENDICITIS; ADNEXAL TORSION; SUSPECTED APPENDICITIS; DIAGNOSTIC PERFORMANCE; ECTOPIC PREGNANCY; OVARIAN TORSION AB Acute pelvic pain in premenopausal women frequently poses a diagnostic dilemma. These patients may exhibit nonspecific signs and symptoms such as nausea, vomiting and leukocytosis. The cause of pelvic pain includes a myriad of diagnostic possibilities such as obstetric, gynecologic, urologic, gastrointestinal, and vascular etiologies. The choice of the imaging modality is usually determined by a suspected clinical differential diagnosis. Thus the patient should undergo careful evaluation and the suspected differential diagnosis should be narrowed before an optimal imaging modality is chosen. Transvaginal and transabdominal pelvic sonography is the modality of choice, to assess for pelvic pain, when an obstetric or gynecologic etiology is suspected and computed tomography is often more useful when gastrointestinal or genitourinary pathology is thought to be more likely. Magnetic resonance imaging, when available in the acute setting, is favored over computed tomography for assessing pregnant patients for nongynecologic etiologies owing to its lack of ionizing radiation. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Bhosale, Priyadarshani R.] Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd Ste 1473, Houston, TX 77030 USA. [Javitt, Marcia C.] Rambam Healthcare Campus, Haifa, Israel. [Atri, Mostafa] Toronto Gen Hosp, Toronto, ON, Canada. [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Kang, Stella K.] NYU, Med Ctr, New York, NY 10016 USA. [Meyer, Benjamin J.] Northwestern Univ, Prentice Womens Hosp, Chicago, IL 60611 USA. [Pandharipande, Pari V.; Salazar, Gloria M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reinhold, Caroline] McGill Univ, Montreal, PQ, Canada. [Shipp, Thomas D.; Uyeda, Jennifer] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Shipp, Thomas D.; Simpson, Lynn; Zelop, Carolyn M.] Amer Coll Obstetricians & Gynecologists, New York, NY USA. [Simpson, Lynn] Columbia Presbyterian Med Ctr, New York, NY 10032 USA. [Sussman, Betsy L.] Univ Vermont, Med Ctr, Burlington, VT USA. [Wall, Darci J.] Mayo Clin, Rochester, MN USA. [Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA. [Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Bayview Campus, Toronto, ON M4N 3M5, Canada. RP Bhosale, PR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiol, 1515 Holcombe Blvd Ste 1473, Houston, TX 77030 USA. EM priya.bhosale@di.mdacc.tmc.edu FU Medical Imaging and Technology Alliance, a Division of the National Electrical Manufacturers Association FX Dr Pandharipande received research funding from the Medical Imaging and Technology Alliance, a Division of the National Electrical Manufacturers Association. No other conflicts of interests were reported by authors. NR 92 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD JUN PY 2016 VL 32 IS 2 BP 108 EP 115 DI 10.1097/RUQ.0000000000000200 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP3RR UT WOS:000378413100003 PM 26588104 ER PT J AU Clark, TJT Pokharel, S Meier, J Wang, C Maximin, S AF Clark, Toshimasa J. T. Pokharel, Sajal Meier, Jeffrey Wang, Carolyn Maximin, Suresh TI Thyroid Nodule Doubling Time is Not a Reliable Indicator of Benign or Malignant Nature SO ULTRASOUND QUARTERLY LA English DT Article DE thyroid nodules; doubling time; papillary thyroid carcinoma ID INTEROBSERVER VARIATION; TUMOR-GROWTH; ULTRASOUND; HISTORY; US AB Thyroid nodules are often followed up with serial ultrasound imaging. Doubling time is well established in the evaluation of lung nodules. We examined whether benign and malignant thyroid nodules exhibit differences in doubling time. This retrospective, IRB-approved study included patients with nodules aspirated between January and June 2012 (benign), and January 2012 to December 2014 (suspicious or malignant), no interval thyroidectomy, and two ultrasound examinations longer than 180 days apart. Diameters and morphology were assessed by a single observer, demographics recorded, and doubling time calculated. Area under the receiver operating characteristic curve was derived. Society of Radiologists in Ultrasound criteria were used to determine aspiration appropriateness initially and after follow-up. 59 patients with 61 nodules were included. Statistically significant between-group differences exist for sex, solidity, echogenicity, and microcalcifications, with no significant differences in doubling time, age, days between studies, vascularity, or mean diameter. Benign nodules' doubling time was 340 to 7134 days (mean, 2196; median, 1593), with 9 nodules that decreased in size. Malignant nodules' doubling time was 451 to 17182 days (mean, 3940; median, 2137), with 7 nodules that decreased in size. Using a threshold of 1100 days, sensitivity and specificity of doubling time to predict malignancy are 19.0% and 86.7%, respectively. Area under the receiver operating characteristic curve is 0.39. Follow-up imaging resulted in 6 additional benign and 0 additional malignant nodules meeting criteria. There is no significant difference in benign or malignant nodules' doubling times, and a decrease in nodule size is nonspecific. These findings challenge the underlying rationale for routine imaging follow-up of thyroid nodules. C1 [Clark, Toshimasa J. T.; Pokharel, Sajal; Meier, Jeffrey] Univ Colorado Denver, Dept Radiol, Abdominal Imaging Sect, 12401 E 17th Ave,Mail Stop L-954, Aurora, CO 80045 USA. [Wang, Carolyn; Maximin, Suresh] Univ Washington, Dept Radiol, Body Imaging Sect, Seattle, WA 98195 USA. [Maximin, Suresh] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Clark, TJT (reprint author), Univ Colorado Denver, 12401 E 17th Ave,Mail Stop L-954, Aurora, CO 80045 USA. EM toshimasa.clark@ucdenver.edu NR 14 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 0894-8771 EI 1536-0253 J9 ULTRASOUND Q JI Ultrasound Q. PD JUN PY 2016 VL 32 IS 2 BP 132 EP 135 DI 10.1097/RUQ.0000000000000190 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP3RR UT WOS:000378413100006 PM 26441381 ER PT J AU Chidi, AP Bryce, CL Donohue, JM Fine, MJ Landsittel, DP Myaskovsky, L Rogal, SS Switzer, GE Tsung, A Smith, KJ AF Chidi, Alexis P. Bryce, Cindy L. Donohue, Julie M. Fine, Michael J. Landsittel, Douglas P. Myaskovsky, Larissa Rogal, Shari S. Switzer, Galen E. Tsung, Allan Smith, Kenneth J. TI Economic and Public Health Impacts of Policies Restricting Access to Hepatitis C Treatment for Medicaid Patients SO VALUE IN HEALTH LA English DT Article DE cost-effectiveness; hepatitis C; interferon-free; Medicaid; Medicare ID INTERFERON-FREE REGIMENS; ADVANCED LIVER-DISEASE; GENOTYPE 1 INFECTION; ALL-CAUSE MORTALITY; UNITED-STATES; VIRUS-INFECTION; COST-EFFECTIVENESS; COMPENSATED CIRRHOSIS; ANTIVIRAL THERAPY; TREATMENT-NAIVE AB Background: Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. Objectives: To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C. Methods: Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice only advanced disease is treated before Medicare eligibility and 2) Full Access both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. Results: Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from $5,369 to $11,960 and in effectiveness from 0.82 to 3.01 quality-adjusted life-years. In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared with Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients. Conclusions: Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full-access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment. C1 [Chidi, Alexis P.; Fine, Michael J.; Landsittel, Douglas P.; Myaskovsky, Larissa; Rogal, Shari S.; Switzer, Galen E.; Tsung, Allan; Smith, Kenneth J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chidi, Alexis P.; Fine, Michael J.; Myaskovsky, Larissa; Rogal, Shari S.; Switzer, Galen E.; Tsung, Allan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bryce, Cindy L.; Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Chidi, AP (reprint author), 3471 Fifth Ave,Suite 300, Pittsburgh, PA 15213 USA. EM apc10@pitt.edu FU Gilead Sciences FX S. Rogal receives research funding for unrelated projects from Gilead Sciences. The rest of the authors report no potential conflicts of interest. NR 79 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD JUN PY 2016 VL 19 IS 4 BP 326 EP 334 DI 10.1016/j.jval.2016.01.010 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA DO9GU UT WOS:000378094200006 PM 27325324 ER PT J AU Chaukos, D Vestal, HS Bernstein, C AF Chaukos, Deanna Vestal, Heather S. Bernstein, Carol TI Responding to the Call for Improving Resident Wellness SO ACADEMIC MEDICINE LA English DT Letter C1 [Chaukos, Deanna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chaukos, Deanna] McLean Hosp, Adult Psychiat Residency Training Program, Boston, MA USA. [Vestal, Heather S.] Massachusetts Gen Hosp, Belmont, MA USA. [Vestal, Heather S.] McLean Hosp, Adult Psychiat Residency Training Program, 115 Mill St, Belmont, MA 02178 USA. [Bernstein, Carol] NYU, Sch Med, Psychiat, New York, NY USA. [Bernstein, Carol] NYU, Sch Med, Educ, New York, NY USA. [Bernstein, Carol] NYU, Sch Med, Residency Training, New York, NY USA. RP Chaukos, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Chaukos, D (reprint author), McLean Hosp, Adult Psychiat Residency Training Program, Boston, MA USA. EM dchaukos@partners.org NR 2 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 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2016 VL 91 IS 6 BP 750 EP 750 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DO8OB UT WOS:000378041800002 PM 27218898 ER PT J AU Hashimoto, DA Bynum, WE Lillemoe, KD Sachdeva, AK AF Hashimoto, Daniel A. Bynum, William E. Lillemoe, Keith D. Sachdeva, Ajit K. TI See More, Do More, Teach More: Surgical Resident Autonomy and the Transition to Independent Practice SO ACADEMIC MEDICINE LA English DT Editorial Material ID OPERATIVE EXPERIENCE; SURGERY RESIDENTS; CHALLENGES; EDUCATION AB The graduate medical education system is tasked with training competent and autonomous health care providers while also improving patient safety, delivering more efficient care, and cutting costs. Concerns about resident autonomy and preparation for independent and safe practice appear to be growing, and the field of surgery faces unique challenges in preparing graduates for independent practice. Multiple factors are contributing to an erosion of resident autonomy and decreased operative experience, including differing views of autonomy, financial forces, duty hours regulations, and diverse community health care needs. Identifying these barriers and developing solutions to overcome them are vital first steps in reversing the trend of diminishing autonomy in surgical residency training. This Commentary highlights the problem of decreasing autonomy, outlines specific threats to resident autonomy, and discusses potential solutions to mitigate their impact on the successful transition to independent practice. C1 [Hashimoto, Daniel A.; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. [Bynum, William E.] Natl Capital Consortium Family Med Residency, Ft Belvoir, VA USA. [Sachdeva, Ajit K.] Amer Coll Surg, Div Educ, Chicago, IL USA. RP Hashimoto, DA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM dahashimoto@partners.org NR 17 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2016 VL 91 IS 6 BP 757 EP 760 DI 10.1097/ACM.0000000000001142 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DO8OB UT WOS:000378041800011 PM 26934694 ER PT J AU Weppner, WG Davis, K Sordahl, J Willis, J Fisher, A Brotman, A Tivis, R Gordon, T Smith, CS AF Weppner, William G. Davis, Kyle Sordahl, Jeffrey Willis, Janet Fisher, Amber Brotman, Adam Tivis, Rick Gordon, Tim Smith, C. Scott TI Interprofessional Care Conferences for High-Risk Primary Care Patients SO ACADEMIC MEDICINE LA English DT Article ID EDUCATION AB Problem As health care systems convert to team-based care, the need to improve interprofessional education is tremendous. In addition to formal instruction, trainees need authentic team-based workplace learning experiences. Approach The authors designed the PACTICU (Patient-Aligned Care Team Interprofessional Care Update) conference to provide team-based care to high-risk patients while teaching trainees principles of interprofessionalism and modeling relevant behaviors. Trainees, supervisors, and affiliated support staff from the fields of internal medicine, nurse practitioner, pharmacy, psychology, and nursing all participate in this conference. During the conference, each participant focuses on the narrative of the patient's illness from his/ her own professional perspective. A multifaceted care plan with specific action items is the product of the conference. To evaluate this workplace learning opportunity, the authors recorded patient characteristics, plus trainees' participation and satisfaction. Outcomes Over the first 16 months (2013-2014) of the PACT-ICU, 33 trainees presented 79 patients. Each trainee presented two or three times each academic year. Patients were 90% male; their mean age was 64.5 years (SD 9.3, range 28-92), and their mean calculated 90-day risk of death or hospitalization was 22% (SD 14%, range 1%-45%). Overall, all surveyed trainees (n = 32; 97% response rate) expressed satisfaction, reporting that the conference was "helpful" or "very helpful" in developing treatment plans. Next Steps Further assessment of change in trainee behavior related to interprofessional team care, patient-level outcomes (e.g., quality of care and utilization), and factors facilitating dissemination of the model to other academic clinic settings is necessary. C1 [Weppner, William G.; Willis, Janet; Fisher, Amber; Brotman, Adam; Tivis, Rick; Gordon, Tim] Boise VA Ctr Excellence Primary Care Educ, Boise, ID USA. [Weppner, William G.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Davis, Kyle] St Lukes Mt States Tumor Inst, Boise, ID USA. [Sordahl, Jeffrey] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Smith, C. Scott] VA Ctr Excellence Primary Care Educ, Seattle, WA USA. [Smith, C. Scott] Univ Washington, Div Gen Internal Med & Med Educ, Seattle, WA 98195 USA. RP Weppner, WG (reprint author), Boise VA Med Ctr, Med Serv Off 111, Boise, ID 83702 USA. EM William.weppner@va.gov FU VA Centers of Excellence in Primary Care Education, Office of Academic Affairs FX VA Centers of Excellence in Primary Care Education, Office of Academic Affairs. NR 10 TC 1 Z9 1 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2016 VL 91 IS 6 BP 798 EP 802 DI 10.1097/ACM.0000000000001151 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA DO8OB UT WOS:000378041800020 PM 27008359 ER PT J AU Cho, CF Lee, K Speranza, MC Bononi, FC Viapiano, MS Luyt, LG Weissleder, R Chiocca, EA Lee, H Lawler, SE AF Cho, Choi-Fong Lee, Kyungheon Speranza, Maria-Carmela Bononi, Fernanda C. Viapiano, Mariano S. Luyt, Leonard G. Weissleder, Ralph Chiocca, E. Antonio Lee, Hakho Lawler, Sean E. TI Design of a Microfluidic Chip for Magnetic-Activated Sorting of One Bead-One-Compound Libraries SO ACS COMBINATORIAL SCIENCE LA English DT Article DE one-bead-one-compound combinatorial library; microfluidics; magnetic-activated sorting ID LARGE COMBINATORIAL LIBRARIES; CONTINUOUS-FLOW; PEPTIDE LIBRARIES; IDENTIFICATION; LIGANDS; BIOMARKERS; SEPARATION; DISCOVERY; CELLS AB Molecular targeting using ligands specific to disease markers has shown great promise for early detection and directed therapy. Bead-based combinatorial libraries have served as powerful tools for the discovery of novel targeting agents. Screening platforms employing magnetic capture have been used to achieve rapid and efficient identification of high affinity ligands from one-bead-one-compound (OBOC) libraries. Traditional manual methodologies to isolate magnetized "hit" beads are tedious and lack accuracy, and existing instruments to expedite bead sorting tend to be costly and complex. Here, we describe the design and construction of a simple and inexpensive microfluidic magnetic sorting device using standard photolithography and soft lithography approaches to facilitate high-throughput isolation of magnetized positive hit beads from combinatorial libraries. We have demonstrated that the device is able to sort magnetized beads with superior accuracy compared to conventional manual sorting approaches. This chip offers a very convenient yet inexpensive alternative-for screening OBOC libraries. C1 [Cho, Choi-Fong; Speranza, Maria-Carmela; Viapiano, Mariano S.; Chiocca, E. Antonio; Lawler, Sean E.] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Sch Med,Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA. [Lee, Kyungheon; Weissleder, Ralph; Lee, Hakho] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Bononi, Fernanda C.; Luyt, Leonard G.] Univ Western Ontario, Dept Chem, London, ON N6A 3K7, Canada. [Bononi, Fernanda C.; Luyt, Leonard G.] Univ Western Ontario, Dept Oncol, London, ON N6A 3K7, Canada. [Cho, Choi-Fong] Brigham & Womens Hosp, Dept Neurosurg, 4 Blackfan Circle,HIM 9-07, Boston, MA 02115 USA. RP Cho, CF (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Sch Med,Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA.; Cho, CF (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 4 Blackfan Circle,HIM 9-07, Boston, MA 02115 USA. EM ccho@bwh.harvard.edu OI Viapiano, Mariano/0000-0002-8756-388X; Speranza, Maria Carmela/0000-0001-8531-9739 FU Department of Neurosurgery; Brigham and Women's Hospital; Canadian Institute of Health Research (CIHR); Natural Sciences and Engineering Research Council of Canada (NSERC) FX This study was supported by institutional funds from the Department of Neurosurgery, Brigham and Women's Hospital (E.A.C.), fellowship funds from the Canadian Institute of Health Research (CIHR) (C.-F.C.), Natural Sciences and Engineering Research Council of Canada (NSERC) (L.G.L.) and B*Cured funds (S.E.L.). We acknowledge Calixto Saenz (Harvard Medical School) for providing us with access to the microfluidics facility. We thank Bradley Pentelute for his support and Emily Avery (Princeton University) for her technical assistance. NR 28 TC 0 Z9 0 U1 18 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2156-8952 EI 2156-8944 J9 ACS COMB SCI JI ACS Comb. Sci. PD JUN PY 2016 VL 18 IS 6 BP 271 EP 278 DI 10.1021/acscombsci.5b00180 PG 8 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA DO6WZ UT WOS:000377925500001 PM 27124678 ER PT J AU Brody, LR Jack, DC Bruck-Segal, DL Ruffing, EG Firpo-Perretti, YM Dale, SK Weber, KM Cohen, MH AF Brody, Leslie R. Jack, Dana C. Bruck-Segal, Dana L. Ruffing, Elizabeth G. Firpo-Perretti, Yudelki M. Dale, Sannisha K. Weber, Kathleen M. Cohen, Mardge H. TI Life Lessons from Women with HIV: Mutuality, Self-Awareness, and Self-Efficacy SO AIDS PATIENT CARE AND STDS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; AFRICAN-AMERICAN WOMEN; PHYSICIAN-PATIENT RELATIONSHIPS; CHILDHOOD SEXUAL-ABUSE; CD4 CELL COUNT; MEDICATION ADHERENCE; ANTIRETROVIRAL THERAPY; POSITIVE WOMEN; MENTAL-HEALTH; REPORTED ADHERENCE AB Women with HIV in the United States cope with multiple traumas that influence adherence to antiretroviral therapy (ART) and well-being. Narrative themes from three life turning points and a projective story task were compared for two groups of women with HIV (HIV well-managed vs. HIV not well-managed, matched on demographics and narrative word count) to understand predictors of successful outcomes. The well-managed group (n = 10) was virally suppressed and reported >= 95% ART adherence; the not well-managed group (n = 10) had detectable viral load and reported <95% ART adherence. Women were predominantly African American with low socioeconomic status and averaged 46.51 years. A three-stage coding process (with coders blind to group status in stages 1 and 2) involved (1) line by line thematic analyses that generated 155 subthemes reflecting six content areas (interpersonal relationships; culture and community; sense of self; relationship to past, present, and future experiences; self-care; and motivators for change); (2) absence/presence of the 155 subthemes was compared for the two groups; the frequency of 37 subthemes was found to significantly differ; and (3) the 37 differentiating subthemes were conceptually integrated, revealing that the well-managed group's narratives more frequently reflected (a) mutuality (growth-fostering relationships involving reciprocal care and empathy); (b) self-awareness (recognition of personal strengths and weaknesses and multiple factors contributing to life choices and trajectories); and (c) self-efficacy (active coping, self-advocacy, and utilizing resources). Implications for treatment and interconnections among themes are discussed, emphasizing the factors that enable women to care for themselves and others. C1 [Brody, Leslie R.; Bruck-Segal, Dana L.; Ruffing, Elizabeth G.; Firpo-Perretti, Yudelki M.] Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,2nd Floor, Boston, MA 02215 USA. [Jack, Dana C.] Western Washington Univ, Fairhaven Coll Interdisciplinary Studies, Bellingham, WA 98225 USA. [Dale, Sannisha K.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Weber, Kathleen M.] Hektoen Inst Med, Cook Cty Hlth & Hosp Syst, Chicago, IL USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Cook Cty Hlth & Hosp Syst, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. RP Brody, LR (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,2nd Floor, Boston, MA 02215 USA. EM lrbrody@gmail.com FU National Institute of Allergy and Infectious Diseases [U01-AI-34994]; National Cancer Institute; National Institute of Drug Abuse FX Data were collected by the Chicago site of the Women's Interagency HIV Study (WIHS), which is funded by the National Institute of Allergy and Infectious Diseases Grant U01-AI-34994 (PIs, Dr. Mardge Cohen and Dr. Audrey French) and cofunded by the National Cancer Institute and National Institute of Drug Abuse. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the views of the National Institutes of Health. The authors thank the WIHS participants and WIHS staff, especially Sally Urwin, Cheryl Watson, and Karlene Schowalter, who collected and managed data, and Gwendolyn Kelso and Ruth Cruise who transcribed and coded data. NR 85 TC 1 Z9 1 U1 5 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JUN PY 2016 VL 30 IS 6 BP 261 EP 273 DI 10.1089/apc.2016.0031 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DO8JK UT WOS:000378029400004 PM 27214648 ER PT J AU Allen, GI Amoroso, N Anghel, C Balagurusamy, V Bare, CJ Beaton, D Bellotti, R Bennett, DA Boehme, KL Boutros, PC Caberlotto, L Caloian, C Campbell, F Neto, EC Chang, YC Chen, BB Chen, CY Chien, TY Clark, T Das, S Davatzikos, C Deng, JY Dillenberger, D Dobson, RJB Dong, QL Doshi, J Duma, D Errico, R Erus, G Everett, E Fardo, DW Friend, SH Frohlich, H Gan, J St George-Hyslop, P Ghosh, SS Glaab, E Green, RC Guan, YF Hong, MY Huang, C Hwang, J Ibrahim, J Inglese, P Iyappan, A Jiang, QJ Katsumata, Y Kauwe, JSK Klein, A Kong, D Krause, R Lalonde, E Lauria, M Lee, E Lin, XH Liu, ZD Livingstone, J Logsdon, BA Lovestone, S Ma, TW Malhotra, A Mangravite, LM Maxwell, TJ Merrill, E Nagorski, J Namasivayam, A Narayan, M Naz, M Newhouse, SJ Norman, TC Nurtdinov, RN Oyang, YJ Pawitan, Y Peng, SW Peters, MA Piccolo, SR Praveen, P Priami, C Sabelnykova, VY Senger, P Shen, X Simmons, A Sotiras, A Stolovitzky, G Tangaro, S Tateo, A Tung, YA Tustison, NJ Varol, E Vradenburg, G Weiner, MW Xiao, GH Xie, L Xie, Y Xu, J Yang, HJ Zhan, XW Zhou, YY Zhu, F Zhu, HT Zhu, SF AF Allen, Genevera I. Amoroso, Nicola Anghel, Catalina Balagurusamy, Venkat Bare, Christopher J. Beaton, Derek Bellotti, Roberto Bennett, David A. Boehme, Kevin L. Boutros, Paul C. Caberlotto, Laura Caloian, Cristian Campbell, Frederick Chaibub Neto, Elias Chang, Yu-Chuan Chen, Beibei Chen, Chien-Yu Chien, Ting-Ying Clark, Tim Das, Sudeshna Davatzikos, Christos Deng, Jieyao Dillenberger, Donna Dobson, Richard J. B. Dong, Qilin Doshi, Jimit Duma, Denise Errico, Rosangela Erus, Guray Everett, Evan Fardo, David W. Friend, Stephen H. Froehlich, Holger Gan, Jessica St George-Hyslop, Peter Ghosh, Satrajit S. Glaab, Enrico Green, Robert C. Guan, Yuanfang Hong, Ming-Yi Huang, Chao Hwang, Jinseub Ibrahim, Joseph Inglese, Paolo Iyappan, Anandhi Jiang, Qijia Katsumata, Yuriko Kauwe, John S. K. Klein, Arno Kong, Dehan Krause, Roland Lalonde, Emilie Lauria, Mario Lee, Eunjee Lin, Xihui Liu, Zhandong Livingstone, Julie Logsdon, Benjamin A. Lovestone, Simon Ma, Tsung-wei Malhotra, Ashutosh Mangravite, Lara M. Maxwell, Taylor J. Merrill, Emily Nagorski, John Namasivayam, Aishwarya Narayan, Manjari Naz, Mufassra Newhouse, Stephen J. Norman, Thea C. Nurtdinov, Ramil N. Oyang, Yen-Jen Pawitan, Yudi Peng, Shengwen Peters, Mette A. Piccolo, Stephen R. Praveen, Paurush Priami, Corrado Sabelnykova, Veronica Y. Senger, Philipp Shen, Xia Simmons, Andrew Sotiras, Aristeidis Stolovitzky, Gustavo Tangaro, Sabina Tateo, Andrea Tung, Yi-An Tustison, Nicholas J. Varol, Erdem Vradenburg, George Weiner, Michael W. Xiao, Guanghua Xie, Lei Xie, Yang Xu, Jia Yang, Hojin Zhan, Xiaowei Zhou, Yunyun Zhu, Fan Zhu, Hongtu Zhu, Shanfeng CA Alzheimer's Dis Neuroimaging Initi TI Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Azheimer's disease; Biomarkers; Crowdsource; Big data; Bioinformatics; Cognitive decline; Imaging; Genetics ID GENOME-WIDE ASSOCIATION; RISK PREDICTION; IMPAIRMENT; BIOMARKERS; DEMENTIA; PATTERNS; ATROPHY; PROJECT; HEALTH; MEMORY AB Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license. C1 [Allen, Genevera I.; Campbell, Frederick; Everett, Evan; Gan, Jessica; Jiang, Qijia; Liu, Zhandong; Nagorski, John; Narayan, Manjari] Rice Univ, Dept Stat & Elect & Comp Engn, Houston, TX USA. [Amoroso, Nicola; Bellotti, Roberto; Tateo, Andrea] Univ Bari A Moro, Dipartimento Fis M Merlin, Bari, Italy. [Amoroso, Nicola; Bellotti, Roberto; Tangaro, Sabina] Ist Nazl Fis Nucl, Sez Bari, I-70126 Bari, Italy. [Anghel, Catalina; Boutros, Paul C.; Caloian, Cristian; Lalonde, Emilie; Lin, Xihui; Livingstone, Julie; Sabelnykova, Veronica Y.] Ontario Inst Canc Res, Informat & Biocomp Program, MaRS Ctr, Toronto, ON, Canada. [Balagurusamy, Venkat; Dillenberger, Donna; Stolovitzky, Gustavo] IBM Res, IBM Computat Biol Ctr, Yorktown Hts, NY USA. [Bare, Christopher J.; Chaibub Neto, Elias; Friend, Stephen H.; Klein, Arno; Logsdon, Benjamin A.; Mangravite, Lara M.; Norman, Thea C.; Peters, Mette A.] Sage Bionetworks, Seattle, WA USA. [Beaton, Derek] Univ Texas Dallas, Sch Behav & Brain Sci, Richardson, TX 75083 USA. [Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA. [Boehme, Kevin L.; Kauwe, John S. K.; Piccolo, Stephen R.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Boutros, Paul C.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Boutros, Paul C.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada. [Caberlotto, Laura; Lauria, Mario; Praveen, Paurush; Priami, Corrado] Microsoft Res, Univ Trento Ctr Computat & Syst Biol COSBI, Rovereto, Italy. [Chang, Yu-Chuan; Oyang, Yen-Jen] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan. [Chen, Beibei; Ma, Tsung-wei; Xiao, Guanghua; Xie, Yang; Xu, Jia; Zhan, Xiaowei; Zhou, Yunyun] Univ Texas SW Med Ctr Dallas, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA. [Chen, Chien-Yu; Hong, Ming-Yi] Natl Taiwan Univ, Dept Bioind Mechatron Engn, Taipei 10764, Taiwan. [Chien, Ting-Ying] Yuan Ze Univ, Innovat Ctr Big Data & Digital Convergence, Taoyuan, Taiwan. [Clark, Tim; Das, Sudeshna; Merrill, Emily] Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA USA. [Clark, Tim; Das, Sudeshna] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Davatzikos, Christos; Doshi, Jimit; Erus, Guray; Sotiras, Aristeidis; Varol, Erdem] Univ Penn, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA. [Deng, Jieyao; Dong, Qilin; Peng, Shengwen; Zhu, Shanfeng] Fudan Univ, Sch Comp Sci, Shanghai 200433, Peoples R China. [Deng, Jieyao; Dong, Qilin; Peng, Shengwen; Zhu, Shanfeng] Fudan Univ, Shanghai Key Lab Intelligent Informat Proc, Shanghai 200433, Peoples R China. [Dobson, Richard J. B.; Newhouse, Stephen J.; Simmons, Andrew] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, London WC2R 2LS, England. [Dobson, Richard J. B.] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Duma, Denise] Baylor Coll Med, Dept Pediat Neurol, Houston, TX 77030 USA. [Errico, Rosangela] Univ Genoa, Genoa, Italy. [Fardo, David W.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Fardo, David W.; Katsumata, Yuriko; Shen, Xia] Univ Kentucky, Dept Biostat, Lexington, KY USA. [Froehlich, Holger; Iyappan, Anandhi; Malhotra, Ashutosh; Naz, Mufassra; Praveen, Paurush] Univ Bonn, Bonn Aachen Int Ctr IT, Bonn, Germany. [St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2, England. [St George-Hyslop, Peter] Univ Toronto, Cambridge CB2, England. [Ghosh, Satrajit S.] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Ghosh, Satrajit S.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Glaab, Enrico; Krause, Roland; Namasivayam, Aishwarya] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg. [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Broad Inst, 75 Francis St, Boston, MA 02115 USA. [Green, Robert C.] Harvard Univ, Sch Med, Boston, MA USA. [Guan, Yuanfang; Zhu, Fan] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Guan, Yuanfang] Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. [Guan, Yuanfang] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Huang, Chao; Ibrahim, Joseph; Kong, Dehan; Lee, Eunjee; Yang, Hojin; Zhu, Hongtu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Hwang, Jinseub] Daegu Univ, Dept Comp Sci & Stat, Gyongsan, Gyeongsangbuk D, South Korea. [Inglese, Paolo] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Fac Med, London, England. [Lovestone, Simon] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Iyappan, Anandhi; Malhotra, Ashutosh; Naz, Mufassra; Senger, Philipp] Schloss Birlinghoven, Dept Bioinformat, Fraunhofer Inst Algorithms & Sci Comp SCAI, St Augustin, Germany. [Maxwell, Taylor J.] George Washington Univ, Computat Biol Inst, Ashburn, VA USA. [Newhouse, Stephen J.] Kings Coll London, Dept Biostat, London WC2R 2LS, England. [Nurtdinov, Ramil N.] Hosp Univ Vall dHebron, Dept Neuroimmunol, Fdn Inst Recerca, Barcelona, Spain. [Pawitan, Yudi; Shen, Xia] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Stolovitzky, Gustavo] Icahn Sch Med Mt Sinai, Genet & Genom Sci Dept, New York, NY 10029 USA. [Tung, Yi-An] Natl Taiwan Univ, Genome & Syst Biol Degree Program, Taipei 10764, Taiwan. [Tustison, Nicholas J.] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA USA. [Vradenburg, George] Global CEO Initiat Alzheimers Dis, Washington, DC USA. [Weiner, Michael W.] UCSF, SFVAMC, Radiol Med Psychiat & Neurol, San Francisco, CA USA. [Xie, Lei] CUNY Hunter Coll, Dept Comp Sci, New York, NY 10021 USA. [Zhu, Shanfeng] Fudan Univ, Ctr Computat Syst Biol, Shanghai 200433, Peoples R China. [Shen, Xia] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. [Shen, Xia] Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Dobson, Richard J. B.] UCL, Farr Inst Hlth Informat Res, UCL Inst Hlth Informat, London WC1E 6BT, England. RP Kauwe, JSK (reprint author), Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. RI Simmons, Andrew/B-8848-2008; OI Simmons, Andrew/0000-0003-2306-5811; Lauria, Mario/0000-0001-5983-7292; Bare, J. Christopher/0000-0003-1006-1491; Tangaro, Sabina/0000-0002-1372-3916; Amoroso, Nicola/0000-0003-0211-0783; Livingstone, Julie/0000-0002-8424-3768; Inglese, Paolo/0000-0001-6179-9643; Clark, Timothy/0000-0003-4060-7360; Frohlich, Holger/0000-0002-5328-1243; Glaab, Enrico/0000-0003-3977-7469 FU National Institutes of Health [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; NIH grants [P30 AG010129, K01 AG030514, P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152]; Rush Alzheimer's Disease Center; Rush University Medical Center; Illinois Department of Public Health; Translational Genomics Research Institute; EFPIA companies; EU under the FP6 programme; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd; Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; SMEs; McGill University; MSSM; UCSF; Goteborg University; EMA; University of Washington; UCLA; BrightFocus Foundation; NIA; Alzheimer's Research UK; European Medicines Agency; Global CEO Initiative on Alzheimer's Disease; Pfizer, Inc; Ray and Dagmar Dolby Family Fund; Rosenberg Alzheimer's Project; Sanofi S.A; Takeda Pharmaceutical Company Ltd; USA gainst Alzheimer's FX This study was supported by the following individuals and organizations: Alan Evans (McGill University), Gaurav Pandey (MSSM), Gil Rabinovici (UCSF), Kaj Blennow (Goteborg University), Kristine Yaffe (UCSF), Maria Isaac (EMA), Nolan Nichols (University of Washington), Paul Thompson (UCLA), Reisa Sperling (Harvard), Scott Small (Columbia), Guy Eakin (BrightFocus Foundation), Maria Carillo (Alzheimer's Association), Neil Buckholz (NIA), Alzheimer's Research UK, European Medicines Agency, Global CEO Initiative on Alzheimer's Disease, Pfizer, Inc, Ray and Dagmar Dolby Family Fund, Rosenberg Alzheimer's Project, Sanofi S.A, and Takeda Pharmaceutical Company Ltd, USA gainst Alzheimer's.; Study data were provided by the following groups: (1) The Alzheimer's Disease Neuroimaging Initiative (ADNI)-ADNI is funded by the National Institutes of Health (U01 AG024904), 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; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; 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 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. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. (2) The Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago-Data collection was supported through funding by NIA grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, and U01AG46152, the Illinois Department of Public Health, and the Translational Genomics Research Institute. (3) Euro-pean AddNeuroMed study-The AddNeuroMed data are from a public-private partnership supported by EFPIA companies, SMEs and the EU under the FP6 programme. Clinical leads responsible for data collection are Iwona Kloszewska (Lodz), Simon Lovestone (London), Patrizia Mecocci (Perugia), Hilkka Soininen (Kuopio), Magda Tsolaki (Thessaloniki), and Bruno Vellas (Toulouse). NR 33 TC 6 Z9 6 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2016 VL 12 IS 6 BP 645 EP 653 DI 10.1016/j.jalz.2016.02.006 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA DO3TW UT WOS:000377705600002 PM 27079753 ER PT J AU Denburg, A Rodriguez-Galindo, C Joffe, S AF Denburg, Avram Rodriguez-Galindo, Carlos Joffe, Steven TI Clinical Trials Infrastructure as a Quality Improvement Intervention in Low- and Middle-Income Countries SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE global health; learning health system; research ethics; trial effect; trial benefits ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; LEARNING HEALTH-CARE; PEDIATRIC-ONCOLOGY; RANDOMIZED-TRIALS; BURKITTS-LYMPHOMA; WILMS-TUMOR; OUTCOMES; MEMBERSHIP; MANAGEMENT AB Mounting evidence suggests that participation in clinical trials confers neither advantage nor disadvantage on those enrolled. Narrow focus on the question of a "trial effect," however, distracts from a broader mechanism by which patients may benefit from ongoing clinical research. We hypothesize that the existence of clinical trials infrastructure-the organizational culture, systems, and expertise that develop as a product of sustained participation in cooperative clinical trials research-may function as a quality improvement lever, improving the quality of care and outcomes of all patients within an institution or region independent of their individual participation in trials. We further contend that this "infrastructure effect" can yield particular benefits for patients in low-and middle-income countries (LMICs). The hypothesis of an infrastructure effect as a quality improvement intervention, if correct, justifies enhanced research capacity in LMIC as a pillar of health system development. C1 [Denburg, Avram] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Denburg, Avram] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA USA. [Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Boston, MA USA. [Joffe, Steven] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Denburg, A (reprint author), Hosp Sick Children, Div Haematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM avram.denburg@sickkids.ca OI Denburg, Avram/0000-0003-0039-0742 FU Sick Kids Foundation; Paediatric Chairs of Canada; Canadian Institutes of Health Research; Pierre Elliott Trudeau Foundation; Greenwall Foundation through the Greenwall Faculty Scholars Program FX During the period of this research, Dr. Denburg was a Fellow of the Pediatric Scientist Development Program, supported by grants from Sick Kids Foundation and the Paediatric Chairs of Canada; a Knowledge Translation Fellow of the Canadian Institutes of Health Research; and a Pierre Elliott Trudeau Foundation Doctoral Scholar. Dr. Joffe was supported by a grant from the Greenwall Foundation through the Greenwall Faculty Scholars Program. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. NR 40 TC 8 Z9 8 U1 4 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUN PY 2016 VL 16 IS 6 BP 3 EP 11 DI 10.1080/15265161.2016.1170230 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DO3KU UT WOS:000377681300006 PM 27216089 ER PT J AU Karp, JF Dew, MA Wahed, AS Fitzgerald, K Bolon, CA Weiner, DK Morse, JQ Albert, S Butters, M Gildengers, A Reynolds, CF AF Karp, Jordan F. Dew, Mary Amanda Wahed, Abdus S. Fitzgerald, Kelley Bolon, Chloe A. Weiner, Debra K. Morse, Jennifer Q. Albert, Steve Butters, Meryl Gildengers, Ariel Reynolds, Charles F., III TI Challenges and Solutions for Depression Prevention Research: Methodology for a Depression Prevention Trial for Older Adults with Knee Arthritis and Emotional Distress SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; prevention; pain; anxiety; late life ID LATE-LIFE DEPRESSION; ADAPTIVE TREATMENT STRATEGIES; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; CHRONIC PAIN; MACULAR DEGENERATION; COLLABORATIVE CARE; PHYSICAL-THERAPY; MANUAL THERAPY AB Objective: To describe the methodology, challenges, and baseline characteristics of a prevention development trial entitled" Reducing Pain, Preventing Depression." Methods: A sequential multiple assignment randomized trial (SMART) compared sequences of cognitive behavioral therapy (CBT) and physical therapy for knee pain and prevention of depression and anxiety. Participants were randomized to CBT, physical therapy, or enhanced usual care and followed for 12 months for new-episode depression or anxiety. Participants were age >= 60 with knee osteoarthritis and subsyndromal depression, defined as 9-item Patient Health Questionnaire (PHQ-9) score >= 1 (which included the endorsement of one of the cardinal symptoms of depression How mood or anhedonia]) and no diagnosis of major depressive disorder per the Structured Clinical Interview for DSM-IV. Depression and anxiety severity and characterization of new episodes were assessed with the PHQ-9, Generalized Anxiety Disorder-7, and the PRIME-MD. Knee pain was characterized with the Western Ontario McMaster Arthritis Index. Response was defined as at least "Very Much Better" on a Patient Global Impression of Change. Results: At baseline there were 99 patients with an average age of 71; 61.62% were women and 81.8% white. The average PHQ-9 was 5.6 and average Generalized Anxiety Disorder-7, was 3.2. Most were satisfied with the interventions and study procedures. The challenges and solutions described here will also be used in a confirmatory clinical trial of efficacy. Conclusion: A SMART design for depression and anxiety prevention, using both CBT and physical therapy, appears to be feasible and acceptable to participants. The methodologic innovations of this project may advance the field of late-life depression and anxiety prevention. C1 [Karp, Jordan F.; Dew, Mary Amanda; Bolon, Chloe A.; Weiner, Debra K.; Butters, Meryl; Gildengers, Ariel; Reynolds, Charles F., III] Univ Pittsburgh, Dept Psychiat, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Fitzgerald, Kelley] Univ Pittsburgh, Dept Phys Therapy, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Dew, Mary Amanda; Albert, Steve] Univ Pittsburgh, Sch Publ Hlth, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Wahed, Abdus S.] Univ Pittsburgh, Dept Biostat, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. [Karp, Jordan F.; Weiner, Debra K.] Geriatr Res Educ & Clin Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Morse, Jennifer Q.] Chatham Univ, Dept Psychol, Pittsburgh, PA USA. RP Reynolds, CF (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, 758 Bellefield Towers,3811 OHara St, Pittsburgh, PA 15213 USA. EM reynoldscf@upmc.edu OI Wahed, Abdus/0000-0001-6911-7221; Albert, Steven/0000-0001-6786-9956 FU National Institutes of Health [P30 MH090333, AG033575, UL1RR024153, UL1TR000005] FX This study was funded by National Institutes of Health grants P30 MH090333, AG033575, UL1RR024153, and UL1TR000005. NR 33 TC 1 Z9 1 U1 6 U2 6 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 JUN PY 2016 VL 24 IS 6 BP 433 EP 443 DI 10.1016/j.jagp.2015.10.012 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DO6AZ UT WOS:000377865900003 PM 26809601 ER PT J AU Kekre, N Mak, KS Stopsack, KH Binder, M Ishii, K Branvall, E Cutler, CS AF Kekre, Natasha Mak, Kimberley S. Stopsack, Konrad H. Binder, Moritz Ishii, Kazusa Branvall, Elsa Cutler, Corey S. TI Impact of HLA-Mismatch in Unrelated Donor Hematopoietic Stem Cell Transplantation: A Meta-Analysis SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CLASS-I; SINGLE-CENTER; HLA-DPB1; MALIGNANCIES; SURVIVAL; LEUKEMIA; OUTCOMES; ALLELES; DISEASE AB The magnitude of risk associated with 9/10 mismatched unrelated donor (MMURD) hematopoietic stem cell transplantation and that of mismatches at the individual HLA loci remain unclear. We performed a meta-analysis to assess the difference in clinical outcomes between matched unrelated donor (MUD) and MMURD transplantation. A comprehensive search of Medline and Embase for manuscripts regarding transplantation outcomes in primarily adult patients with hematologic malignancies was performed. The pooled effect estimates were calculated using DerSimonian-Laird random effects models. A total of 13 studies were included, reporting on 13,446 transplants. 9/10 MMURD transplantation was associated with worse overall survival compared to 10/10 MUD transplantation (pooled HR: 1.27, 95% CI: 1.12-1.45; n=7 studies). Mismatch at HLA-A, -B, or -C was associated with significantly worse overall survival compared to MUD transplantation, while there was no significant difference associated with -DQ or -DPB1 mismatch. Inferior survival associated with HLA-DRB1 mismatch could not be ruled out. Data on acute and chronic graft-versus-host disease were scarce but favored MUD transplantation. In summary, this meta-analysis of the available literature favored MUD over MMURD transplantation in hematologic malignancies and further quantifies the risks associated with specific HLA-allele mismatches.(C) 2016 Wiley Periodicals, Inc. C1 [Kekre, Natasha] Ottawa Hosp Res Inst, Div Hematol, Ottawa, ON, Canada. [Mak, Kimberley S.] Boston Univ, Sch Med, Dept Radiat Oncol, Boston Med Ctr, Boston, MA 02118 USA. [Stopsack, Konrad H.; Binder, Moritz] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Ishii, Kazusa] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Branvall, Elsa] Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden. [Cutler, Corey S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Kekre, N (reprint author), Univ Ottawa, Blood & Marrow Transplant Program, Ottawa Hosp Res Inst, Ottawa, ON, Canada. EM nkekre@toh.on.ca OI Binder, Moritz/0000-0001-9014-9658 NR 28 TC 0 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2016 VL 91 IS 6 BP 551 EP 555 DI 10.1002/ajh.24342 PG 5 WC Hematology SC Hematology GA DO2CE UT WOS:000377586400012 PM 26927727 ER PT J AU Jurczyszyn, A Grzasko, N Gozzetti, A Czepiel, J Cerase, A Hungria, V Crusoe, E Dias, ALMS Vij, R Fiala, MA Caers, J Rasche, L Nooka, AK Lonial, S Vesole, DH Philip, S Gangatharan, S Druzd-Sitek, A Walewski, J Corso, A Cocito, F Vekemans, MCM Atilla, E Beksac, M Leleu, X Davila, J Badros, A Aneja, E Abildgaard, N Kastritis, E Fantl, D Schutz, N Pika, T Butrym, A Olszewska-Szopa, M Usnarska-Zubkiewicz, L Usmani, SZ Nahi, H Chim, CS Shustik, C Madry, K Lentzsch, S Swiderska, A Helbig, G Guzicka-Kazimierczak, R Lendvai, N Waage, A Andersen, KT Murakami, H Zweegman, S Castillo, JJ AF Jurczyszyn, Artur Grzasko, Norbert Gozzetti, Alessandro Czepiel, Jacek Cerase, Alfonso Hungria, Vania Crusoe, Edvan Miranda Silva Dias, Ana Luiza Vij, Ravi Fiala, Mark A. Caers, Jo Rasche, Leo Nooka, Ajay K. Lonial, Sagar Vesole, David H. Philip, Sandhya Gangatharan, Shane Druzd-Sitek, Agnieszka Walewski, Jan Corso, Alessandro Cocito, Federica Vekemans, Marie-Christine M. Atilla, Erden Beksac, Meral Leleu, Xavier Davila, Julio Badros, Ashraf Aneja, Ekta Abildgaard, Niels Kastritis, Efstathios Fantl, Dorotea Schutz, Natalia Pika, Tomas Butrym, Aleksandra Olszewska-Szopa, Magdalena Usnarska-Zubkiewicz, Lidia Usmani, Saad Z. Nahi, Hareth Chim, Chor S. Shustik, Chaim Madry, Krzysztof Lentzsch, Suzanne Swiderska, Alina Helbig, Grzegorz Guzicka-Kazimierczak, Renata Lendvai, Nikoletta Waage, Anders Andersen, Kristian T. Murakami, Hirokazu Zweegman, Sonja Castillo, Jorge J. TI Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID OF-THE-LITERATURE; CHROMOSOMAL-ABNORMALITIES; INTRATHECAL CHEMOTHERAPY; MENINGEAL MYELOMA; AGENTS; MANIFESTATIONS; BENDAMUSTINE; ASSOCIATION; THALIDOMIDE; INVASION AB The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and > 1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. (C) 2016 Wiley Periodicals, Inc. C1 [Jurczyszyn, Artur; Czepiel, Jacek] Jagiellonian Univ, Coll Med, Krakow, Poland. [Grzasko, Norbert] Med Univ Lublin, Dept Hematooncol & Bone Marrow Transplantat, Lublin, Poland. [Grzasko, Norbert] St Johns Canc Ctr, Dept Hematol, Lublin, Poland. [Gozzetti, Alessandro; Cerase, Alfonso] Azienda Osped Univ Senese, Siena, Italy. [Hungria, Vania; Crusoe, Edvan; Miranda Silva Dias, Ana Luiza] Santa Casa Med Sch, Sao Paulo, Brazil. [Vij, Ravi; Fiala, Mark A.] Washington Univ, Sch Med, St Louis, MO USA. [Caers, Jo] Ctr Hosp Univ Liege, Liege, Belgium. [Rasche, Leo] Univ Hosp Wurzburg, Wurzburg, Germany. [Nooka, Ajay K.; Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Vesole, David H.; Philip, Sandhya] Hackensack UMC, John Theurer Canc Ctr, Hackensack, NJ USA. [Vesole, David H.; Philip, Sandhya] Georgetown Univ, Washington, DC USA. [Gangatharan, Shane] Fremantle Hosp, Fremantle, WA, Australia. [Druzd-Sitek, Agnieszka; Walewski, Jan] Maria Sklodowska Curie Inst, Oncol Ctr, Warsaw, Poland. [Corso, Alessandro; Cocito, Federica] Univ Pavia, Fdn IRCCS Policlin San Matteo, Via Palestro 3, I-27100 Pavia, Italy. [Vekemans, Marie-Christine M.] Clin Univ St Luc, B-1200 Brussels, Belgium. [Atilla, Erden; Beksac, Meral] Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. [Leleu, Xavier] CHU Poitiers, Hop La Miletrie, Poitiers, France. [Davila, Julio] Hosp Univ Salamanca, Salamanca, Spain. [Badros, Ashraf] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Aneja, Ekta] Weill Cornell Med Coll, New York, NY USA. [Abildgaard, Niels] Odense Univ Hosp, DK-5000 Odense, Denmark. [Kastritis, Efstathios] Univ Athens, Athens 11528, Greece. [Fantl, Dorotea; Schutz, Natalia] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. [Pika, Tomas] Univ Hosp Olomouc, Olomouc, Czech Republic. [Butrym, Aleksandra; Olszewska-Szopa, Magdalena; Usnarska-Zubkiewicz, Lidia] Wroclaw Med Univ, Wroclaw, Poland. [Usmani, Saad Z.] Levine Canc Inst Carolinas HealthCare Syst, Charlotte, NC USA. [Nahi, Hareth] Karolinska Univ Hosp, Stockholm, Sweden. [Chim, Chor S.] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. [Shustik, Chaim] McGill Univ, Royal Victoria Hosp, Montreal, PQ, Canada. [Madry, Krzysztof] Med Univ Warsaw, Warsaw, Poland. [Lentzsch, Suzanne] Columbia Univ, Med Ctr, New York, NY USA. [Swiderska, Alina] Prov Hosp, Zielona Gora, Poland. [Helbig, Grzegorz] Silesian Med Univ, Katowice, Poland. [Guzicka-Kazimierczak, Renata] Pomeranian Med Univ, Szczecin, Poland. [Lendvai, Nikoletta] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Waage, Anders] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. [Andersen, Kristian T.] Vejle Hosp, Vejle, Denmark. [Murakami, Hirokazu] Gunma Univ, Grad Sch Hlth Sci, Maebashi, Gunma, Japan. [Zweegman, Sonja] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Castillo, Jorge J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RP Jurczyszyn, A (reprint author), Jagiellonian Univ, Coll Med, Dept Hematol, 17 Kopernika Str, PL-31501 Krakow, Poland. EM mmjurczy@cyf-kr.edu.pl RI gozzetti, alessandro/D-9055-2014; OI gozzetti, alessandro/0000-0003-0769-6891; Andersen, Kristian Thidemann/0000-0002-8077-7113; nahi, hareth/0000-0003-4711-5094; Castillo, Jorge/0000-0001-9490-7532 FU NCI NIH HHS [P30 CA008748] NR 33 TC 0 Z9 1 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2016 VL 91 IS 6 BP 575 EP 580 DI 10.1002/ajh.24351 PG 6 WC Hematology SC Hematology GA DO2CE UT WOS:000377586400017 PM 26955792 ER PT J AU Gustine, JN Meid, K Dubeau, TE Treon, SP Castillo, JJ AF Gustine, Joshua N. Meid, Kirsten Dubeau, Toni E. Treon, Steven P. Castillo, Jorge J. TI Atrial fibrillation associated with ibrutinib in Waldenstrom macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID LEUKEMIA; RISK C1 [Gustine, Joshua N.; Meid, Kirsten; Dubeau, Toni E.; Treon, Steven P.; Castillo, Jorge J.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M221,450 Brookline Ave, Boston, MA 02115 USA. [Treon, Steven P.; Castillo, Jorge J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Castillo, JJ (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M221,450 Brookline Ave, Boston, MA 02115 USA. EM jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 6 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2016 VL 91 IS 6 BP E312 EP E313 DI 10.1002/ajh.24366 PG 3 WC Hematology SC Hematology GA DO2CE UT WOS:000377586400008 PM 26994323 ER PT J AU Chokshi, FH Tu, RK Nicola, GN Hirsch, JA AF Chokshi, F. H. Tu, R. K. Nicola, G. N. Hirsch, J. A. TI Myelography CPT Coding Updates: Effects of 4 Mew Codes and Unintended Consequences SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article AB The Current Procedural Terminology of the American Medical Association has recently introduced coding changes for myelography with the introduction of new bundled codes. The aim of this review was to help neuroradiologists understand these code changes and their unintended consequences and to discuss various scenarios in which permutations of various codes could occur in clinical practice. C1 [Chokshi, F. H.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Div Neuroradiol, 1364 Clifton Rd NE, Atlanta, GA 30068 USA. [Tu, R. K.] NFPHC United Med Ctr, Progress Radiol, Dept Radiol, Washington, DC USA. [Tu, R. K.] BridgePoint Hosp Capitol Hill, Bridge Point Subacute & Rehabil Hadley, BridgePoint Hosp Hadley, Dept Radiol, Washington, DC USA. [Tu, R. K.] George Washington Univ, Dept Radiol, Washington, DC USA. [Nicola, G. N.] Hackensack Univ, Med Ctr, Hackensack Radiol Grp, River Edge, NJ USA. [Hirsch, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc Div, Boston, MA USA. RP Chokshi, FH (reprint author), Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Div Neuroradiol, 1364 Clifton Rd NE, Atlanta, GA 30068 USA. EM falgun.chokshi@emory.edu FU Association of University Radiologists GE Radiology Research Academic Fellowship Award FX Falgun H. Chokshi, MD, MS, is an Association of University Radiologists GE Radiology Research Academic Fellow (2015-2017). This investigation was supported, in part, by the Association of University Radiologists GE Radiology Research Academic Fellowship Award. NR 9 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN PY 2016 VL 37 IS 6 BP 997 EP 999 DI 10.3174/ajnr.A4666 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DO2TN UT WOS:000377633100004 PM 26744447 ER PT J AU Jakobiec, FA Syed, ZA Stagner, AM Harris, GJ Rootman, J Yoon, MK Mombaerts, I AF Jakobiec, Frederick A. Syed, Zeba A. Stagner, Anna M. Harris, Gerald J. Rootman, Jack Yoon, Michael K. Mombaerts, Ilse TI Orbital Inflammation in Pregnant Women SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RECTUS MUSCLE INVOLVEMENT; EUTHYROID GRAVES-DISEASE; RABBIT LACRIMAL GLAND; PRESENTING SIGN; CROHNS-DISEASE; ULCERATIVE-COLITIS; IMMUNE CELLS; MYOSITIS; DACRYOADENITIS AB OBJECTIVE: To analyze overlaps between pregnancy and orbital inflammation (OI). DESIGN: Retrospective observational case series. METHODS: Eight new cases from 1997 to 2015 and 2 previously published cases were identified for inclusion in this investigation to provide the fullest clinical picture. Medical records, imaging studies, and the results of biopsies were reviewed. RESULTS: Three categories of association were discovered: (1) OI arising for the first time during pregnancy (5 cases); (2) OI arising within 3 months of delivery (2 cases); and (3) previously diagnosed OI reactivated or exacerbated by pregnancy (3 cases). One patient had a preexistent systemic autoimmune disease and another's was later diagnosed. One patient had attacks during sequential pregnancies. Findings included eyelid swelling and erythema, conjunctival chemosis, pain on eye movement, minimal diplopia, the usual absence of proptosis, and general preservation of visual acuity. Imaging studies disclosed extraoculai muscle swelling (8 cases), most frequently of a single lateral rectus muscle. There were 2 cases of dacryoadenitis; 1 of these and an additional case displayed inflammation of the retrobulbar fat. Corticosteroids effected resolution of most symptoms. Singleton births were normal with the exceptions of an intrauterine fetal demise owing to acrania and a molar pregnancy. CONCLUSION: CH usually affects a single rectus muscle (typically the lateral) and, less often, the lacrimal gland and is often mild when it arises during or after pregnancy. Independent systemic autoimmune disease is an uncommon feature. Corticosteroids were efficacious except in 1 case with severe orbital scarring. No definitive causal relationships between pregnancy and OI could be established based on the clinical data. (C) 2016 Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Syed, Zeba A.; Stagner, Anna M.; Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Harris, Gerald J.] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA. [Rootman, Jack] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Mombaerts, Ilse] Univ Hosp Leuven, Dept Ophthalmol, Leuven, Belgium. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 60 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2016 VL 166 BP 91 EP 102 DI 10.1016/j.ajo.2016.03.029 PG 12 WC Ophthalmology SC Ophthalmology GA DO2QD UT WOS:000377624000015 PM 27038895 ER PT J AU Navarro-Alvarez, N Shah, JA Zhu, A Ligocka, J Yeh, H Elias, N Rosales, I Colvin, R Cosimi, AB Markmann, JF Hertl, M Sachs, DH Vagefi, PA AF Navarro-Alvarez, N. Shah, J. A. Zhu, A. Ligocka, J. Yeh, H. Elias, N. Rosales, I. Colvin, R. Cosimi, A. B. Markmann, J. F. Hertl, M. Sachs, D. H. Vagefi, P. A. TI The Effects of Exogenous Administration of Human Coagulation Factors Following Pig-to-Baboon Liver Xenotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID RECOMBINANT FACTOR VIIA; THROMBOTIC MICROANGIOPATHY; TRANSPLANTATION; SURVIVAL; THROMBOCYTOPENIA; HEMOSTASIS; XENOGRAFTS; PLATELETS; KIDNEY AB We sought to determine the effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation (LXT) using GaIT-KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor Vila (1 mu g/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large-vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor Vila. Further studies are warranted because this regimen may allow for prolonged survival following LXT. C1 [Navarro-Alvarez, N.; Shah, J. A.; Zhu, A.; Ligocka, J.; Yeh, H.; Elias, N.; Rosales, I.; Colvin, R.; Cosimi, A. B.; Markmann, J. F.; Hertl, M.; Sachs, D. H.; Vagefi, P. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA USA. RP Navarro-Alvarez, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA USA. EM pvagefi@mgh.harvard.edu OI Shah, Jigesh/0000-0003-2097-0656 FU National Institute of Allergy and Infectious Disease, NIAID [2T32AI007529-16A1] FX The authors would like to thank Christian Schuetz for his assistance in the organization of data and review of the manuscript. J.A.S. is supported by a National Institute of Allergy and Infectious Disease, NIAID, 2T32AI007529-16A1 Training Grant. NR 28 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 IS 6 BP 1715 EP 1725 DI 10.1111/ajt.13647 PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA DO2EO UT WOS:000377592900012 PM 26613235 ER PT J AU Shankar, J Nguyen, MH Crespo, MM Kwak, EJ Lucas, SK McHugh, KJ Mounaud, S Alcorn, JF Pilewski, JM Shigemura, N Kolls, JK Nierman, WC Clancy, CJ AF Shankar, J. Nguyen, M. H. Crespo, M. M. Kwak, E. J. Lucas, S. K. McHugh, K. J. Mounaud, S. Alcorn, J. F. Pilewski, J. M. Shigemura, N. Kolls, J. K. Nierman, W. C. Clancy, C. J. TI Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID VENTILATOR-ASSOCIATED TRACHEOBRONCHITIS; CARE-ASSOCIATED PNEUMONIA; REGULATORY T-CELLS; ANTIMICROBIAL TREATMENT; BRONCHOALVEOLAR LAVAGE; GENETIC ASSOCIATION; ANTIBIOTIC-THERAPY; TRIAL DESIGN; INFECTIONS; DIVERSITY AB Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia colonization comparisons. The dissimilar micro biomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. C1 [Shankar, J.; Lucas, S. K.; Mounaud, S.; Nierman, W. C.] J Craig Venter Inst, Rockville, MD 20850 USA. [Nguyen, M. H.; Kwak, E. J.; Clancy, C. J.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Crespo, M. M.; Pilewski, J. M.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [McHugh, K. J.; Alcorn, J. F.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15213 USA. [Shigemura, N.] Univ Pittsburgh, Dept Cardiothorac Surg, Pittsburgh, PA USA. [Kolls, J. K.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Richard King Mellon Fdn,Inst Pediat Res, Pittsburgh, PA 15213 USA. [Clancy, C. J.] VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA USA. RP Shankar, J (reprint author), J Craig Venter Inst, Rockville, MD 20850 USA.; Nguyen, MH (reprint author), Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. EM jyoti.shankar@gmail.com; mhn5@pitt.edu FU National Institutes of Health [R21AI107290, R21AI111037, R01HL107380]; Bill and Melinda Gates Foundation [OPP1017579] FX We express our gratitude to the patients and families in the University of Pittsburgh Medical Center (UPMC) Lung Transplantation Program who consented to participate in this project and to the health care providers and coordinators for their excellent patient care and ongoing support of translational research, We thank Ellen Press and Lloyd Clarke of the UPMC Infectious Diseases Division for maintaining our biorepository and providing detailed data on the usage of antimicrobials and other therapeutic agents. We thank Sebastian Szpakowski and Andrey Tovchigrechko for contributing the open source bioinformatics workflow for taxonomic classification of microbiome sequences and the authors of BoomSpikeSlab, ggplot2, scales, tidyr, reshape2, data.table, Hmisc and R Studio and the R Core Development Team for their statistical packages, We thank Karla Stucker for constructive comments that greatly improved our manuscript, We gratefully acknowledge the collaborative platforms from Google Docs, Paperpile, and GitHub. This work was supported in part by awards from the National Institutes of Health (R21AI107290, R21AI111037, R01HL107380) and the Bill and Melinda Gates Foundation (OPP1017579). NR 81 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 IS 6 BP 1766 EP 1778 DI 10.1111/ajt.13676 PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA DO2EO UT WOS:000377592900016 PM 26693965 ER PT J AU Buhler, L Illigens, BMW Nadazdin, O Tena, A Lee, S Sachs, DH Cooper, DKC Benichou, G AF Buhler, L. Illigens, B. M. -W. Nadazdin, O. Tena, A. Lee, S. Sachs, D. H. Cooper, D. K. C. Benichou, G. TI Persistence of Indirect but Not Direct T Cell Xenoresponses in Baboon Recipients of Pig Cell and Organ Transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; HUMORAL XENOGRAFT REJECTION; ALLOGRAFT-REJECTION; CD154 BLOCKADE; RECOGNITION; PATHWAYS; MOUSE; ALLOREACTIVITY; ALLORESPONSE; TOLERANCE AB We investigated the contributions of direct and indirect T cell antigen recognition pathways to the immune response to porcine antigens in naive baboons and baboon recipients of pig xenografts. In naive baboons, in vitro culture of peripheral blood T cells with intact pig cells (direct xenorecognition pathway) or pig cell sonicates and baboon antigen-presenting cells (indirect xenorecognition pathway) induced the activation and expansion of xenoreactive T cells producing proinflammatory cytokines, interleukin-2 and interferon-7. Primary indirect xenoresponses were mediated by preexisting memory T cells, whose presence is not typically observed in primary alloresponses. Next, baboons were conditioned with a nonmyeloablative regimen before short-term immunosuppression and transplantation of xenogeneic peripheral blood progenitor cells and a kidney, heart, or pancreatic islets from a miniature swine. All transplants were rejected acutely within 30 days after their placement. Posttransplantation, we observed an inhibition of the direct xenoresponse but a significant expansion of indirectly activated proinflammatory T cells. These results suggest that additional treatment to suppress indirect T cell immunity in primates may be required to achieve tolerance of pig xenografts through hematopoietic chimerism. C1 [Buhler, L.; Tena, A.; Sachs, D. H.; Cooper, D. K. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA USA. [Illigens, B. M. -W.; Nadazdin, O.; Lee, S.; Benichou, G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Unit, Boston, MA 02115 USA. [Cooper, D. K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. RP Benichou, G (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Transplantat Unit, Boston, MA 02115 USA. EM gbenichou@partners.org FU National Institutes of Health (NIH) [U01 AI068642, R21 AI074844, U19 AI090959, P01AI045897, R21AI100278, R03AI094235] FX This work was supported by National Institutes of Health (NIH) grants U01 AI068642, R21 AI074844, and U19 AI090959 to D.K.C.C., NIH P01AI045897 to D.H.S., and R21AI100278 and R03AI094235 to G.B. NR 30 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2016 VL 16 IS 6 BP 1917 EP 1922 DI 10.1111/ajt.13695 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA DO2EO UT WOS:000377592900031 PM 26718119 ER PT J AU Haerter, F Eikermann, M AF Haerter, Friederike Eikermann, Matthias TI Effectiveness versus Efficacy of Calabadion and Sugammadex for Nondepolarizing Neuromuscular Blocking Agent Reversal Reply SO ANESTHESIOLOGY LA English DT Letter ID RISK C1 [Haerter, Friederike; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Eikermann, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM meikermann@partners.org NR 7 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 2016 VL 124 IS 6 BP 1417 EP 1418 DI 10.1097/ALN.0000000000001098 PG 3 WC Anesthesiology SC Anesthesiology GA DO3NB UT WOS:000377687200036 PM 27187130 ER PT J AU Shah, JA Navarro-Alvarez, N DeFazio, M Rosales, IA Elias, N Yeh, H Colvin, RB Cosimi, AB Markmann, JF Hertl, M Sachs, DH Vagefi, PA AF Shah, Jigesh A. Navarro-Alvarez, Nalu DeFazio, Matthew Rosales, Ivy A. Elias, Nahel Yeh, Heidi Colvin, Robert B. Cosimi, A. Benedict Markmann, James F. Hertl, Martin Sachs, David H. Vagefi, Parsia A. TI A Bridge to Somewhere: 25-day Survival After Pig-to-Baboon Liver Xenotransplantation SO ANNALS OF SURGERY LA English DT Letter ID TRANSPLANTATION; MODEL C1 [Shah, Jigesh A.; Navarro-Alvarez, Nalu; DeFazio, Matthew; Rosales, Ivy A.; Elias, Nahel; Yeh, Heidi; Colvin, Robert B.; Cosimi, A. Benedict; Markmann, James F.; Hertl, Martin; Sachs, David H.; Vagefi, Parsia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02114 USA. RP Vagefi, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02114 USA. EM pvagefi@mgh.harvard.edu NR 7 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JUN PY 2016 VL 263 IS 6 BP 1069 EP 1071 DI 10.1097/SLA.0000000000001659 PG 3 WC Surgery SC Surgery GA DO4PO UT WOS:000377765400012 PM 26825261 ER PT J AU Dwyer, MK Lewis, CL Hanmer, AW McCarthy, JC AF Dwyer, Maureen K. Lewis, Cara L. Hanmer, Alfred W. McCarthy, Joseph C. TI Do Neuromuscular Alterations Exist for Patients With Acetabular Labral Tears During Function? SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID SYMPTOMATIC FEMOROACETABULAR IMPINGEMENT; HIP ARTHROSCOPY; OUTCOME SCORE; FOLLOW-UP; VALIDITY; JOINT AB Purpose: To determine if contact forces and electromyography (EMG) muscle amplitudes were altered during the lunge for patients with symptomatic labral tears compared with asymptomatic control subjects. Methods: Surface electromyography electrodes were placed over the gluteus medius, gluteus maximus, adductor longus, and rectus femoris muscles of the patients' involved limb and matched limb of asymptomatic controls. Subjects performed 3 trials of the lunge on a clinical force platform. An electrogoniometer tracked knee flexion motion during testing. Average root mean squared EMG muscle amplitudes for each muscle were calculated for the descent and ascent phases of the lunge, represented as a percentage of maximum activity (%MVIC). Peak knee flexion was calculated from the goniometer (degrees). The dependent variables from the force platform were lunge distance (%height), contact time (seconds), vertical impact force (%BW), and force impulse (%BW(star)s). Dependent variables were compared between groups using either independent samples t tests or Mann-Whitney U tests. Relations between dependent variables were assessed with Spearman Rho correlation coefficients. The level of significance was set at P <= .05. Results: Twenty-one patients with symptomatic unilateral labral tears (14 females, 7 males) and 17 asymptomatic control subjects (11 females, 6 males) participated in this study. Average gluteus maximus EMG muscle amplitudes were reduced for symptomatic labral patients compared with asymptomatic controls during lunge ascent (51.6 +/- 31.1 v 71.7 +/- 36.3 [mean difference (MD): 20.1% (-2.4%, 42.6%)], P = .042). Average vertical impact force was reduced (21.8 +/- 5.5 v 26.8 +/- 7.3 [MD: 5.1%BW (0.84%BW, 9.3%BW)], P = .02) and average contact time (1.8 +/- 0.4 v 1.5 +/- 0.4 [MD: 0.27 seconds (0.006 seconds, 0.54 seconds)], P = .045) and force impulse (188.4 +/- 42.4 v 162.6 +/- 33.3 [MD: 25.8%BW*s (0.3%BW*s, 51.4%BW*s)], P = .042) were increased for symptomatic labral patients compared with asymptomatic controls. Vertical impact force was inversely correlated with gluteus medius muscle amplitudes during lunge descent for symptomatic labral patients (r = -0.452, P = .045). Conclusions: Our study shows that contact forces and EMG muscle amplitudes are altered during the lunge for patients with symptomatic labral tears. The presence of a relation between muscle amplitudes and contact forces suggests that targeting muscle impairments may restore function in these patients. Level of Evidence: Level III, case-control study. C1 [Dwyer, Maureen K.; Hanmer, Alfred W.; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Joint Ctr, Newton, MA 02462 USA. [Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lewis, Cara L.] Boston Univ, Boston, MA 02215 USA. RP Dwyer, MK (reprint author), Newton Wellesley Hosp, 2014 Washington St,Green Bldg Ste 361, Newton, MA 02462 USA. EM mkdwyer@partners.org NR 30 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD JUN PY 2016 VL 32 IS 6 BP 1045 EP 1052 DI 10.1016/j.arthro.2016.03.016 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DO1UF UT WOS:000377563900017 PM 27129378 ER PT J AU Dooley, K Devalliere, J Uygun, BE Yarmush, ML AF Dooley, Kevin Devalliere, Julie Uygun, Basak E. Yarmush, Martin L. TI Functionalized Biopolymer Particles Enhance Performance of a Tissue-Protective Peptide under Proteolytic and Thermal Stress SO BIOMACROMOLECULES LA English DT Article ID ELASTIN-LIKE POLYPEPTIDES; MATRIX METALLOPROTEINASES MMP-2; BETA ROLL PEPTIDE; HYDROGEL FORMATION; ENGINEERED SKIN; CHRONIC WOUNDS; DRUG-DELIVERY; PROTEIN; ERYTHROPOIETIN; NANOPARTICLES AB Cutaneous burns are often exacerbated by poor perfusimi and subsequent necrosis of the miCrovaSculature surrounding the primary injury. Preservation of these vessels canjechice necrotic tissue expansion and increase successrates of skin graft procedures. Recent work has identified a peptide derived from- erythropoietin, ARA290, with the ability to mediate-tissue protection in a variety of cell types. Here we demonstrate the advantages of fusing ARA290 to ail elastinlike polyPepticle (ELP) to salvage microvascular endothelial cells in harsh proteolytic conditions following thermal shock. These fusion proteins were expressed recombinantly in bacterial hosts and rapidly purified by inverse transition-cycling. They were shown to spontaneously aggregate into particles at subphysiological. temperatures. The bifunctional submicron particles were resistant to digestion in enzymes upregulated after burn injury. Furthermore; the data strongly suggest these ARA290-functionalized particles were superior to treatment with the peptide alone in preventing microvascular cell death in these conditions. The results bring to light an efficient and cost-effective strategy for the delivery therapeutic peptides to" protanlytically active wound sites. C1 [Dooley, Kevin; Devalliere, Julie; Uygun, Basak E.; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02114 USA.; Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM ireis@sbi.org FU Shriners Hospitals for Children; Shriners Hospital for Children FX This work was funded by the Shriners Hospitals for Children. J.D. was supported by a Shriners Hospital for Children postdoctoral fellowship award. NR 49 TC 0 Z9 0 U1 8 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 EI 1526-4602 J9 BIOMACROMOLECULES JI Biomacromolecules PD JUN PY 2016 VL 17 IS 6 BP 2073 EP 2079 DI 10.1021/acs.biomac.6b00280 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA DO6WS UT WOS:000377924800017 PM 27219509 ER PT J AU Wilhelm, S Greenberg, JL Rosenfield, E Kasarskis, I Blashill, AJ AF Wilhelm, Sabine Greenberg, Jennifer L. Rosenfield, Elizabeth Kasarskis, Irina Blashill, Aaron J. TI The Body Dysmorphic Disorder Symptom Scale: Development and preliminary validation of a self-report scale of symptom specific dysfunction SO BODY IMAGE LA English DT Article DE Body dysmorphic disorder; Self-report; Symptom subtypes; Symptom severity; Psychometric properties ID OBSESSIVE-COMPULSIVE SCALE; RELIABILITY; VALIDITY; QUESTIONNAIRE AB The Body Dysmorphic Disorder Symptom Scale (BDD-SS) is a new self-report measure used to examine the severity of a wide variety of symptoms associated with body dysmorphic disorder (BDD). The BDD-SS was designed to differentiate, for each group of symptoms, the number of symptoms endorsed and their severity. This report evaluates and compares the psychometric characteristics of the BDD-SS in relation to other measures of BDD, body image, and depression in 99 adult participants diagnosed with BDD. Total scores of the BDD-SS showed good reliability and convergent validity and moderate discriminant validity. Analyses of the individual BDD-SS symptom groups confirmed the reliability of the checking, grooming, weight/shape, and cognition groups. The current findings indicate that the BDD-SS can be quickly administered and used to examine the severity of heterogeneous BDD symptoms for research and clinical purposes. (C) 2016 Published by Elsevier Ltd. C1 [Wilhelm, Sabine; Greenberg, Jennifer L.; Rosenfield, Elizabeth; Kasarskis, Irina; Blashill, Aaron J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine; Greenberg, Jennifer L.; Rosenfield, Elizabeth; Kasarskis, Irina; Blashill, Aaron J.] Harvard Univ, Sch Med, Boston, MA USA. [Blashill, Aaron J.] San Diego State Univ, SDSU UCSD Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM swilhelm@mgh.harvard.edu FU Neil and Anna Rasmussen Research Fund; International Obsessive Compulsive Disorder Foundation; National Institute of Mental Health [MH070490, MH091078] FX The present study was supported by the Neil and Anna Rasmussen Research Fund, and in part by the International Obsessive Compulsive Disorder Foundation and the National Institute of Mental Health (MH070490; MH091078). NR 25 TC 1 Z9 1 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 EI 1873-6807 J9 BODY IMAGE JI Body Image PD JUN PY 2016 VL 17 BP 82 EP 87 DI 10.1016/j.bodyim.2016.02.006 PG 6 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA DO4CD UT WOS:000377728500011 PM 26971118 ER PT J AU Drucker, AM Li, WQ Lin, L Cho, E Li, T Camargo, CA Qureshi, AA AF Drucker, A. M. Li, W. -Q. Lin, L. Cho, E. Li, T. Camargo, C. A., Jr. Qureshi, A. A. TI Atopic dermatitis (eczema) in US female nurses: lifestyle risk factors and atopic comorbidities SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID ADULT C1 [Drucker, A. M.] Univ Hlth Network, Div Dermatol, Toronto, ON, Canada. [Drucker, A. M.; Li, W. -Q.; Lin, L.; Cho, E.; Qureshi, A. A.] Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02903 USA. [Li, W. -Q.; Cho, E.; Qureshi, A. A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Cho, E.; Li, T.; Camargo, C. A., Jr.; Qureshi, A. A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Cho, E.; Li, T.; Camargo, C. A., Jr.; Qureshi, A. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, C. A., Jr.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Qureshi, A. A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. RP Qureshi, AA (reprint author), Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02903 USA.; Qureshi, AA (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.; Qureshi, AA (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Qureshi, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Qureshi, AA (reprint author), Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. EM abrar_qureshi@brown.edu OI Drucker, Aaron/0000-0002-7388-9475 FU NCI NIH HHS [UM1 CA176726] NR 6 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUN PY 2016 VL 174 IS 6 BP 1395 EP 1397 DI 10.1111/bjd.14373 PG 3 WC Dermatology SC Dermatology GA DO8QA UT WOS:000378047100041 PM 26707970 ER PT J AU Siegel, DS Dimopoulos, M Jagannath, S Goldschmidt, H Durrant, S Kaufman, JL Leleu, X Nagler, A Offner, F Graef, T Eid, JE Houp, J Gause, C Vuocolo, S Anderson, KC AF Siegel, David S. Dimopoulos, Meletios Jagannath, Sundar Goldschmidt, Hartmut Durrant, Simon Kaufman, Jonathan L. Leleu, Xavier Nagler, Arnon Offner, Fritz Graef, Thorsten Eid, Joseph E. Houp, Jennifer Gause, Christine Vuocolo, Scott Anderson, Kenneth C. TI VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE Combination therapy; Efficacy; Histone deacetylase inhibitor; Proteasome inhibitor; Safety ID HISTONE DEACETYLASE INHIBITORS; HIGH-DOSE DEXAMETHASONE; PANOBINOSTAT; ACETYLATION; CARFILZOMIB; PROGRESSION; PROTEASOME; THERAPY AB The present study was designed to determine the efficacy and tolerability of vorinostat combined with bortezomib in patients with multiple myeloma. Patients received 21-day cycles of bortezomib plus vorinostat. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). Vorinostat plus bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities. Background: The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Patients and Methods: Eligible patients were age > 18 years, had received >= 2 previous regimens, had disease refractory to >= 1 previous bortezomib-containing regimen, and had received >= 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. Results: The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. Conclusion: The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population. (C) 2016 Elsevier Inc. All rights reserved. C1 [Siegel, David S.] Hackensack Univ, Med Ctr, Myeloma Div, Hackensack, NJ USA. [Dimopoulos, Meletios] Univ Athens, Dept Therapeut, Athens, Greece. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Goldschmidt, Hartmut] Univ Klinikum Heidelberg, Heidelberg, Germany. [Durrant, Simon] Royal Brisbane & Womens Hosp, Bone Marrow Transplant Clin Hematol Unit, Brisbane, Qld, Australia. [Kaufman, Jonathan L.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Leleu, Xavier] Univ Lille, Serv Malad Sang, Lille, France. [Nagler, Arnon] Chaim Sheba Med Ctr, Div Hematol, IL-52621 Tel Hashomer, Israel. [Offner, Fritz] Univ Ziekenhuis Gent, Ghent, Belgium. [Graef, Thorsten; Eid, Joseph E.; Houp, Jennifer; Gause, Christine; Vuocolo, Scott] Merck & Co Inc, Kenilworth, NJ USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Siegel, DS (reprint author), Hackensack Univ, John Theurer Canc Ctr, Med Ctr, Myeloma Div, 92 Second St,Third Floor, Hackensack, NJ 07601 USA. EM dsiegel@hackensackumc.org FU Merck & Co., Inc. (Kenilworth, NJ) FX This study was funded by Merck & Co., Inc. (Kenilworth, NJ) in its entirety. Merck & Co., Inc., participated in the collection and analysis of data, preparation of clinical reports from the data, and the writing of the report, along with external authors. The authors wish to thank Martha Carroll Vollmer, Kristen Lewis, and Alan Meehan of Merck & Co., Inc., for editorial assistance. NR 21 TC 3 Z9 3 U1 3 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2016 VL 16 IS 6 BP 329 EP + DI 10.1016/j.clml.2016.02.042 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA DO8JI UT WOS:000378029200007 PM 27025160 ER PT J AU Khoury, HJ Goldberg, SL Mauro, MJ Stone, RM Deininger, MW Bradley-Garelik, MB Mohamed, H Guilhot, F AF Khoury, Hanna J. Goldberg, Stuart L. Mauro, Michael J. Stone, Richard M. Deininger, Michael W. Bradley-Garelik, M. Brigid Mohamed, Hesham Guilhot, Francois TI Cross-Intolerance With Dasatinib Among Imatinib-Intolerant Patients With Chronic Phase Chronic Myeloid Leukemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE BCR-ABL; Drug toxicity; Recurrent adverse event; Treatment discontinuation; Tyrosine kinase inhibitor ID CHRONIC MYELOGENOUS LEUKEMIA; DURABLE CYTOGENETIC RESPONSES; ADVANCED SOLID TUMORS; YOUNG-ADULTS; FOLLOW-UP; TRIAL DASISION; BCR-ABL; FAILURE; INHIBITION; RESISTANCE AB Some patients with chronic myeloid leukemia (CML) are intolerant to first-line imatinib treatment. Our retrospective data analysis of 271 CML imatinib-intolerant patients from phase II and III studies examined the extent of cross-intolerance between imatinib and dasatinib. Our results have confirmed the clinical safety and efficacy of dasatinib in imatinib-intolerant CML patients, suggesting that dasatinib could be a suitable treatment choice for this population. Background: BCR-ABL inhibitors have improved the prognosis of patients with chronic myeloid leukemia (CML). However, imatinib, the first approved BCR-ABL inhibitor, must be discontinued in many patients because of resistance or intolerance. Patients and Methods: The present retrospective, pooled analysis of phase II and III data explored the extent of cross-intolerance between imatinib and dasatinib, a second-generation BCR-ABL inhibitor, in 271 CML imatinib-intolerant patients. Results: Overall, 47 patients (17%) had cross-intolerance to dasatinib, determined by recurrence of grade 3 or 4 adverse events (AEs). Of the 228 patients who discontinued imatinib because of non-hematologic intolerance, 10 (4%) experienced the same severe non-hematologic AEs with dasatinib, with 4 of these patients (2%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients who discontinued imatinib because of hematologic intolerance, 37 (86%) experienced a recurrence of grade 3 or 4 hematologic AEs with dasatinib, with 8 patients (19%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients taking dasatinib at the optimized dose of 100 mg/d, 1 (2%) discontinued therapy because of recurrence of nonhematologic AEs and 3 (7%) because of recurrence of hematologic AEs. With a median treatment duration of 22 months, the estimated rates of progression-free survival and overall survival at 2 years were greater for patients with nonhematologic versus hematologic intolerance to imatinib who switched to dasatinib (progression-free survival, 94% vs. 68%, respectively; overall survival, 98% vs. 88%, respectively). Conclusion: Dasatinib could be an appropriate treatment option for imatinib-intolerant patients with CML, with cross-intolerance resulting in discontinuation in a few patients. (C) 2016 Elsevier Inc. All rights reserved. C1 [Khoury, Hanna J.] Emory Univ, Winship Canc Ctr, Dept Hematol & Med Oncol, Div Hematol, 1365 Clifton Rd,Suite C1152, Atlanta, GA 30322 USA. [Goldberg, Stuart L.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Mauro, Michael J.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Deininger, Michael W.] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bradley-Garelik, M. Brigid; Mohamed, Hesham] Bristol Myers Squibb Co, Princeton, NJ USA. [Guilhot, Francois] Ctr Hosp Univ Poitiers, Clin Invest Ctr, Dept Oncol Hematol & Cell Therapy, Inserm 0802, Poitiers, France. RP Khoury, HJ (reprint author), Emory Univ, Winship Canc Ctr, Dept Hematol & Med Oncol, Div Hematol, 1365 Clifton Rd,Suite C1152, Atlanta, GA 30322 USA. EM hkhoury@emory.edu FU Bristol-Myers Squibb (BMS); BMS FX The present analysis was supported by research funding from Bristol-Myers Squibb (BMS). Professional medical writing support and editorial assistance was provided by Ami P. Modi, PhD, of StemScientific, an Ashfield Company, a part of UDG Healthcare Plc, funded by BMS. We did not receive financial compensation for writing the report. NR 29 TC 0 Z9 0 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2016 VL 16 IS 6 BP 341 EP + DI 10.1016/j.clml.2016.03.004 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DO8JI UT WOS:000378029200009 PM 27133948 ER PT J AU Perez, DL LaFrance, WC AF Perez, David L. LaFrance, W. Curt, Jr. TI Nonepileptic seizures: an updated review SO CNS SPECTRUMS LA English DT Review DE cognitive behavioral therapy; conversion disorder; fMRI; neuroimaging; functional neurological disorder; psychogenic nonepileptic seizures; sertraline ID PERSONALITY-ASSESSMENT INVENTORY; RANDOMIZED CONTROLLED-TRIAL; FUNCTIONAL CONNECTIVITY; EPILEPTIC SEIZURES; PSYCHOGENIC SEIZURES; CONVERSION DISORDER; DIAGNOSIS; TRAUMA; DISSOCIATION; OUTCOMES AB Psychogenic nonepileptic seizures (PNES) are a functional neurological disorder/conversion disorder subtype, which are neurobehavioral conditions at the interface of neurology and psychiatry. Significant advancements over the past decade have been made in the diagnosis, management, and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions, and outcome studies. Epidemiology and healthcare utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid in the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES; these should be assessed in diagnostic evaluations and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot, multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy-informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control, and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders. C1 [Perez, David L.] Harvard Univ, Sch Med, Dept Neurol, Cognit Behav Neurol Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Perez, David L.] Harvard Univ, Sch Med, Dept Psychiat, Neuropsychiat Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Rhode Isl Hosp, Dept Psychiat, Neuropsychiatry & Behav Neurol Div,Alpert Med Sch, Providence, RI 02903 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA. RP LaFrance, WC (reprint author), Rhode Isl Hosp, 593 Eddy St,Potter 3, Providence, RI 02903 USA. EM William_LaFrance_Jr@Brown.edu FU NINDS [R25NS065743-05S1] FX This work was supported by the NINDS (D.L.P., R25NS065743-05S1) NR 75 TC 1 Z9 1 U1 10 U2 20 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2016 VL 21 IS 3 BP 239 EP 246 DI 10.1017/S109285291600002X PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DO9BY UT WOS:000378080500006 PM 26996600 ER PT J AU Zhukovsky, EA Morse, RJ Maus, MV AF Zhukovsky, Eugene A. Morse, Richard J. Maus, Marcela V. TI Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CHIMERIC-ANTIGEN-RECEPTOR; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; SINGLE-CHAIN ANTIBODY; TARGETED CANCER-IMMUNOTHERAPY; CHRONIC LYMPHOCYTIC-LEUKEMIA; LIGAND FUSION PROTEINS; MALIGNANT B-CELLS; CD19 X CD3; TUMOR-CELLS AB To realize the full potential of cancer immunotherapy, the latest generation immunotherapeutics are designed to harness the potent tumor-killing capacity of T cells. Thus, to mobilize T cells, new optimized bispecific antibody (BsAb) designs, enabling efficient polyclonal redirection of cytotoxic activity through binding to CD3 and a Tumor Associated Antigen (TAA) and refined genetically modified T cells have recently expanded the arsenal of available options for cancer treatment. This review presents the current understanding of the parameters crucial to the design of optimal T cell redirecting BsAb and chimeric antigen receptor (CAR)-modified T cells. However, there are additional questions that require thorough elucidation. Both modalities will benefit from design changes that may increase the therapeutic window. One such approach could employ the discrimination afforded by multiple TAA to significantly increase selectivity. C1 [Zhukovsky, Eugene A.] Biomunex Pharmaceut, F-75116 Paris, France. [Morse, Richard J.] Morse Consulting, F-75016 Paris, France. [Maus, Marcela V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. RP Zhukovsky, EA (reprint author), Biomunex Pharmaceut, F-75116 Paris, France.; Maus, MV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM ezhukovsky@biomunex.com; mvmaus@mgh.harvard.edu OI Maus, Marcela/0000-0002-7578-0393 FU National Cancer Institute [K08 CA1669039] FX Dr Marcela V Maus is supported by the National Cancer Institute (K08 CA1669039). The authors wish to thank Joost Bakker (Scicomvisuals) for help in preparation of the figures. NR 111 TC 7 Z9 7 U1 9 U2 29 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2016 VL 40 BP 24 EP 35 DI 10.1016/j.coi.2016.02.006 PG 12 WC Immunology SC Immunology GA DO5QA UT WOS:000377836700006 PM 26963133 ER PT J AU Tran, NT Su, HR Khodadadi-Jamayran, A Lin, S Zhang, L Zhou, DW Pawlik, KM Townes, TM Chen, YB Mulloy, JC Zhao, XY AF Ngoc-Tung Tran Su, Hairui Khodadadi-Jamayran, Alireza Lin, Shan Zhang, Li Zhou, Dewang Pawlik, Kevin M. Townes, Tim M. Chen, Yabing Mulloy, James C. Zhao, Xinyang TI The AS-RBM15 lncRNA enhances RBM15 protein translation during megakaryocyte differentiation SO EMBO REPORTS LA English DT Article DE antisense RNA; hematopoiesis; RBM15 ID LONG NONCODING RNAS; HEMATOPOIETIC STEM-CELLS; NATURAL ANTISENSE TRANSCRIPT; GENOME-WIDE ANALYSIS; MEGAKARYOBLASTIC LEUKEMIA; ADULT HEMATOPOIESIS; MESSENGER-RNA; C-MYC; GENE; RUNX1 AB Antisense RNAs regulate the transcription and translation of the corresponding sense genes. Here, we report that an antisense RNA, AS-RBM15, is transcribed in the opposite direction within exon 1 of RBM15. RBM15 is a regulator of megakaryocyte (MK) differentiation and is also involved in a chromosome translocation t(1; 22) in acute megakaryocytic leukemia. MK terminal differentiation is enhanced by up-regulation of AS-RBM15 expression and attenuated by AS-RBM15 knockdown. At the molecular level, AS-RBM15 enhances RBM15 protein translation in a CAP-dependent manner. The region of the antisense AS-RBM15 RNA, which overlaps with the 5'UTR of RBM15, is sufficient for the up-regulation of RBM15 protein translation. In addition, we find that transcription of both RBM15 and AS-RBM15 is activated by the transcription factor RUNX1 and repressed by RUNX1-ETO, a leukemic fusion protein. Therefore, AS-RBM15 is a regulator of megakaryocyte differentiation and may play a regulatory role in leukemogenesis. C1 [Ngoc-Tung Tran; Su, Hairui; Khodadadi-Jamayran, Alireza; Zhang, Li; Zhou, Dewang; Pawlik, Kevin M.; Townes, Tim M.; Zhao, Xinyang] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35233 USA. [Lin, Shan; Mulloy, James C.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Chen, Yabing] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Chen, Yabing] Birmingham Vet Affairs Med Ctr, Res Dept, Birmingham, AL USA. RP Zhao, XY (reprint author), Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35233 USA. EM Zhaox88@uab.edu OI Zhao, Xinyang/0000-0001-6677-7072 FU UAB new investigator start-up fund; NIH [HL092215, DK100847]; VA [BX000369, BX001591] FX We would like to thank Drs. Yinfeng Zhang, Sunnie Thompson, and David Schneider for valuable advice and Dr. Qingbai She at the University of Kentucky for reagents. The project is funded by a UAB new investigator start-up fund (XZ). YC is supported by NIH grants HL092215 and DK100847 and VA grants BX000369 and BX001591. We would like to thank the UAB Comprehensive Flow Cytometry Core as part of RDCC (P30AR048311 and P30AI027767) for technical support. NR 59 TC 2 Z9 2 U1 6 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD JUN PY 2016 VL 17 IS 6 BP 887 EP 900 DI 10.15252/embr.201541970 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DO3UM UT WOS:000377707400013 PM 27118388 ER PT J AU Mehta, SN Goldfine, AB Abrahamson, MJ McMullen, W Laffel, LMB AF Mehta, Sanjeev N. Goldfine, Allison B. Abrahamson, Martin J. McMullen, William Laffel, Lori M. B. TI IMPROVEMENTS IN METABOLIC CONTROL IN ADULTS WITH TYPE 2 DIABETES FOLLOWING REFERRAL TO A DIABETES CENTER, 2005-2010 SO ENDOCRINE PRACTICE LA English DT Article ID NUTRITION EXAMINATION SURVEY; PRIMARY-CARE PHYSICIANS; UNITED-STATES; RETROSPECTIVE COHORT; CLINICAL INERTIA; NATIONAL-HEALTH; SPECIALTY CARE; MELLITUS; OUTCOMES; INSULIN AB Objective: We aimed to compare metabolic control in adults with diabetes in the general population to those newly referred to a diabetes center and after 1 year of specialty care. Methods: We performed a retrospective comparison of adults with diabetes aged >= 20 years data from the National Health and Nutrition Examination Survey (NHANES, n = 1,674) and a diabetes center (n = 3,128) from 2005-2010. NHANES participants represented the civilian, non institutionalized U.S. population. Diabetes center referrals lived primarily around eastern Massachusetts. The proportion attaining targets for glycated hemoglobin A1c (A1c), blood pressure (BP), low-density lipoprotein (LDL) cholesterol, or all 3 (ABC control) and the proportion prescribed medications to lower A1c, BP, or cholesterol were evaluated. Results: Compared to the general sample, a smaller proportion of new diabetes center referrals had A1c <7% (<53 mmol/mol, 24% vs. 53%, P<.001), BP <130/80 mm Hg (38% vs. 50%, P<.001), and ABC control (5.6% vs. 17%, P<.001) but not LDL<100 mg/dL (<2.6 mmol/L, 54% vs. 53%, P = .65). After 1 year, more diabetes center referrals attained targets for A1c (40%), BP (38%), LDL (67%), and ABC control (15%) (P<.001 for all versus baseline). ABC control was not different between the general sample and diabetes center referrals at 1 year (P = .16). After 1 year, a greater percentage of diabetes center referrals compared to the general sample were prescribed medications to lower glucose (95% vs. 72%), BP (79% vs. 64%), and cholesterol (77% vs. 54%)(all P<.001). Conclusion: Compared to the general population, glycemic control was significantly worse for adults newly referred to the diabetes center. Within 1 year of specialty care, ABC control increased 270% in the setting of significant therapy escalation. C1 [Mehta, Sanjeev N.; Goldfine, Allison B.; McMullen, William; Laffel, Lori M. B.] Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, One Joslin Pl, Boston, MA 02215 USA. [Abrahamson, Martin J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrine, Boston, MA 02215 USA. RP Mehta, SN (reprint author), Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, One Joslin Pl, Boston, MA 02215 USA. EM sanjeev.mehta@joslin.harvard.edu FU Joslin Diabetes Center's Diabetes and Endocrinology Research Center [NIH P30DK036836] FX This research was supported by the Joslin Diabetes Center's Diabetes and Endocrinology Research Center (NIH P30DK036836). An abstract from the preliminary analysis was presented at the 73rd Scientific Sessions of the American Diabetes Association held June 21-25, 2013 in Chicago, Illinois. NR 40 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD JUN PY 2016 VL 22 IS 6 BP 689 EP 698 DI 10.4158/EP151080.OR PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7NQ UT WOS:000377969700005 PM 27176141 ER PT J AU Le, KT Sawicki, MP Wang, MB Hershman, JM Leung, AM AF Le, Karen T. Sawicki, Mark P. Wang, Marilene B. Hershman, Jerome M. Leung, Angela M. TI HIGH PREVALENCE OF AGENT ORANGE EXPOSURE AMONG THYROID CANCER PATIENTS IN THE NATIONAL VA HEALTHCARE SYSTEM SO ENDOCRINE PRACTICE LA English DT Article ID KOREAN VIETNAM VETERANS; ARYL-HYDROCARBON RECEPTOR; HORMONE LEVELS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; ASSOCIATION; FORCE; TCDD; RISK AB Objective: Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S. Little is known regarding the epidemiology and characteristics of patients with thyroid cancer within the national Veterans Health Administration (VHA) integrated healthcare system. The aim of this study was to further understand the characteristics of thyroid cancer patients in the VHA population, particularly in relation to Agent Orange exposure. Methods: This is a descriptive analysis of the VA (Veterans Affairs) Corporate Data Warehouse database from all U.S. VHA healthcare sites from October1, 1999, to December 31, 2013. Information was extracted for all thyroid cancer patients based on International Classification of Diseases ninth revision diagnosis codes; histologic subtypes of thyroid cancer were not available. Results: There were 19,592 patients (86% men, 76% white, 58% married, 42% Vietnam-era Veteran) in the VHA system with a diagnosis of thyroid cancer within this 14-year study period. The gender-stratified prevalence rates of thyroid cancer among the Veteran population during the study period were 1:1,114 (women) and 1:1,023 (men), which were lower for women but similar for men, when compared to the U.S. general population in 2011 (1:350 for women and 1:1,219 for men). There was a significantly higher proportion of self-reported Agent Orange exposure among thyroid cancer patients (10.0%), compared to the general VHA population (6.2%) (P<.0001). Conclusion: Thyroid cancer patients, in this sample, have a higher prevalence of self-reported Agent Orange exposure compared to the overall national VA patient population. C1 [Le, Karen T.; Hershman, Jerome M.; Leung, Angela M.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Endocrinol, Los Angeles, CA USA. [Le, Karen T.] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Sawicki, Mark P.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Sawicki, Mark P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Wang, Marilene B.] VA Greater Los Angeles Healthcare Syst, Dept Otolaryngol, Los Angeles, CA USA. [Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Hershman, Jerome M.; Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90095 USA. RP Leung, AM (reprint author), VA Greater Los Angeles Healthcare Syst, Div Endocrinol, 11301 Wilshire Blvd 111D, Los Angeles, CA 90073 USA. EM angela.leung@va.gov FU National Institutes of Health [K23HD068552] FX This work was supported in part by National Institutes of Health grant K23HD068552 (to A.M.L.). NR 24 TC 0 Z9 0 U1 3 U2 4 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD JUN PY 2016 VL 22 IS 6 BP 699 EP 702 DI 10.4158/EP151108.OR PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7NQ UT WOS:000377969700006 PM 27176142 ER PT J AU Alvarez, RD Matulonis, UA Herzog, TJ Coleman, RL Monk, BJ Markman, M AF Alvarez, Ronald D. Matulonis, Ursula A. Herzog, Thomas J. Coleman, Robert L. Monk, Bradley J. Markman, Maurie TI Moving beyond the platinum sensitive/resistant paradigm for patients with recurrent ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material DE Recurrent ovarian cancer; Platinum sensitive/resistant ID PEGYLATED LIPOSOMAL DOXORUBICIN; BRCA2 MUTATIONS; PHASE-II; CHEMOTHERAPY; CARCINOMA; THERAPY; CA-125; WOMEN; CISPLATIN; OLAPARIB C1 [Alvarez, Ronald D.] Univ Alabama Birmingham, Birmingham, AL USA. [Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Herzog, Thomas J.] Univ Cincinnati, UC Canc Inst, Cincinnati, OH USA. [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Monk, Bradley J.] Univ Arizona, Ctr Canc, St Josephs Hosp & Med Ctr, Phoenix, AZ USA. [Markman, Maurie] Canc Treatment Ctr Amer, Philadelphia, PA USA. RP Alvarez, RD (reprint author), 176F RM 10250,619 19th St South, Birmingham, AL 35233 USA. EM rdalvarez@uab.edu FU NCI NIH HHS [P30 CA008748] NR 27 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 JUN PY 2016 VL 141 IS 3 BP 405 EP 409 DI 10.1016/j.ygyno.2016.03.005 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DO2RB UT WOS:000377626500002 PM 27049967 ER PT J AU Hernandez, SF Chisholm, S Borger, D Foster, R Rueda, BR Growdon, WB AF Hernandez, Silvia F. Chisholm, Sarah Borger, Darrell Foster, Rosemary Rueda, Bo R. Growdon, Whitfield B. TI Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Uterine serous carcinoma; HER2; Ridaforolimus; Trastuzumab resistance; mTOR inhibition; Rapalog ID HER2-OVEREXPRESSING BREAST-CANCER; METASTATIC ENDOMETRIAL CANCER; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II; TRASTUZUMAB RESISTANCE; PI3K PATHWAY; CELL LINES; INHIBITION; GROWTH; THERAPY AB Objective. Uterine serous carcinomas (USC) harbor simultaneous HER2 (ERBB2) over-expression and gain of function mutations in PIK3CA. These concurrent alterations may uncouple single agent anti-HER2 therapeutic efficacy making inhibition of the mammalian target of rapamycin (mTOR) a promising option to heighten antitumor response. Methods. Both in vitro and in vivo experiments were conducted to assess proliferation, cell death and antitumor activity of ridaforolimus, lapatinib and combination lapatinib, trastuzumab (L/T) and ridaforolimus. With institutional approval, NOD/SCID mice beating xenografts of non-immortalized, HER2 gene amplified cell lines (ARK1, ARK2) with and without PIK3CA gene mutations were divided into four arm cohorts. Ridaforolimus was administered alone and in combination with L/T. Tumor volumes were assessed and posttreatment analysis was performed. Results. We observed dose dependent in vitro abrogation of downstream target proteins including phospho-AKT and phospho-S6. In both in vivo models, single agent ridaforolimus impaired xenograft tumor growth. Combination ridaforolimus and L/T, however, further improved the observed anti-tumor activity only in the ARK1 model with the PIK3CA gene mutation (E542K). The addition of mTOR inhibition to dual HER2 blockade added no additional anti-tumor effects in the ARK2 xenografts. Western blot and immunohistochemical analysis of downstream pathway alterations following in vivo treatment revealed dual HER2 blockade with ridaforolimus was necessary to induce apoptosis, decrease proliferation and abrogate phospho-S6 protein expression in the PIK3CA mutated model. Conclusions. These pilot data suggest that PIK3CA gene mutation may be an effective biomarker for selecting those HER2 over-expressing USC tumors most likely to benefit from mTOR inhibition. (C) 2016 Elsevier Inc. All rights reserved. C1 [Hernandez, Silvia F.; Chisholm, Sarah; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Hernandez, Silvia F.; Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Harvard Univ, Sch Med, Boston, MA USA. [Foster, Rosemary; Rueda, Bo R.; Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Borger, Darrell] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, THR 901,55 Fruit St, Boston, MA 02114 USA. EM wgrowdon@partners.org FU institutional K12 Proton Share NCI Grant [C06 CA059267]; Advanced Medical Research Foundation; Vincent Department of Obstetrics and Gynecology Research Funds FX We gratefully acknowledge Dr. Alessandro Santin for donating the ARK1 and ARK2 cells. We also would like to acknowledge Dr. Nile Albright and the Advanced Medical Research Foundation for their continued insights that guide our work. We are also grateful to Meredith Weglarz of the FACS core facility, Harvard Stem Cell Institute. This research was funded by an institutional K12 Proton Share NCI Grant C06 CA059267 (WBG), and funding from the Advanced Medical Research Foundation (BRR) and Vincent Department of Obstetrics and Gynecology Research Funds (BRR). NR 41 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2016 VL 141 IS 3 BP 570 EP 579 DI 10.1016/j.ygyno.2016.03.027 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DO2RB UT WOS:000377626500030 PM 27017985 ER PT J AU Simone, CG Markham, MJ Dizon, DS AF Simone, Christine G. Markham, Merry Jennifer Dizon, Don S. TI Chemotherapy in ovarian germ cell tumors: A systematic review SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Ovarian cancer; Ovarian germ cell tumors; Malignant germ cell tumors ID GYNECOLOGIC-ONCOLOGY-GROUP; BLEOMYCIN-INDUCED PNEUMONITIS; PLATINUM-BASED CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; ADJUVANT THERAPY; STAGE-I; ETOPOSIDE; CISPLATIN; CARBOPLATIN AB Objective. Ovarian germ cell tumors (OGCTs) are rare tumors that comprise a diverse group of histologic subtypes that can either be benign or malignant. Malignant ovarian germ cell tumors (OGCTs) historically carried a poor prognosis, especially among those diagnosed with advanced disease. With the advent of combination chemotherapy, risk of relapse has markedly decreased. There is limited prospective data on the efficacy of specific chemotherapy regimens in the treatment of malignant OGCTs. This article critically reviews the literature pertinent to the treatment of OGCTs with chemotherapy. Methods. MEDLINE was searched for English language literature on prospective studies on the treatment of malignant OGCTs, focusing on publications since 1995. Results. As modern chemotherapy regimens have evolved, risk of relapse has decreased with implementation of platinum based regimens in the adjuvant setting. However, the role of neoadjuvant platinum based regimens and treatment of metastatic or recurrent malignant OGCTs remains poorly understood due to lack of randomized control trials. Conclusions. Malignant OGCTs represent a rare subset of ovarian neoplasms for which focused, prospective clinical trials are needed to determine the most effective therapies. (C) 2016 Elsevier Inc. All rights reserved. C1 [Simone, Christine G.; Markham, Merry Jennifer] Univ Florida, Dept Med, Div Hematol & Oncol, POB 100278, Gainesville, FL 32610 USA. [Dizon, Don S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Med,Med Sch, Boston, MA 02114 USA. RP Markham, MJ (reprint author), Univ Florida, Dept Med, Div Hematol & Oncol, POB 100278, Gainesville, FL 32610 USA. EM merry.markham@medicine.ufl.edu OI Markham, Merry/0000-0003-3567-3494 NR 31 TC 1 Z9 1 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2016 VL 141 IS 3 BP 602 EP 607 DI 10.1016/j.ygyno.2016.02.007 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DO2RB UT WOS:000377626500034 PM 26873864 ER PT J AU Boruta, DM AF Boruta, David M. TI Laparoendoscopic single-site surgery in gynecologic oncology: An update SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Laparoendoscopic single-site surgery; Single-incision laparoscopy; Single-port surgery ID ASSISTED VAGINAL HYSTERECTOMY; RANDOMIZED-CONTROLLED-TRIAL; CONVENTIONAL LAPAROSCOPY; ENDOMETRIAL CANCER; CERVICAL-CANCER; RADICAL HYSTERECTOMY; SURGICAL OUTCOMES; LESS PAINFUL; HERNIA; COMPLICATIONS AB The preferred surgical approach for many gynecologic oncology procedures is now laparoscopy. Reduced morbidity, shorter hospitalization and a more rapid recovery have been associated with minimally invasive surgical approaches when compared to laparotomy. Incisional morbidity, including vascular and viscous injury, postoperative hernia, infection, and pain remain significant concerns. Use of fewer and smaller incisions during laparoscopy may be expected to further minimize these risks. Laparoendoscopic single-site surgery (LESS), or single incision laparoscopy, describes the use of one small skin incision to complete laparoscopic surgical procedures. Recent advances in instrumentation have allowed increasingly complex procedures in gynecologic cancer patients to be completed. This review will serve as an update in regards to implementation of LESS in gynecologic oncology. Technical challenges encountered during performance of LESS as well as strategies to overcome these challenges will be discussed. (C) 2016 Elsevier Inc. All rights reserved. C1 [Boruta, David M.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Yawkey Suite 9E,55 Fruit St, Boston, MA 02114 USA. RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Yawkey Suite 9E,55 Fruit St, Boston, MA 02114 USA. EM dboruta@mgh.harvard.edu NR 46 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2016 VL 141 IS 3 BP 616 EP 623 DI 10.1016/j.ygyno.2016.03.014 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DO2RB UT WOS:000377626500036 PM 26980644 ER PT J AU Nose, V AF Nose, Vania TI Genodermatosis Affecting the Skin and Mucosa of the Head and Neck: Clinicopathologic, Genetic, and Molecular Aspect-PTEN-Hamartoma Tumor Syndrome/Cowden Syndrome SO HEAD & NECK PATHOLOGY LA English DT Article DE PTEN hamartoma tumor syndrome (PHTS); Phosphatase and tensin homolog (PTEN) gene; Cowden syndrome (CS); Multiple neoplasms; Hamartomas; Mucosal papillomatosis; Trichilemmomas; Thyroid adenomatous nodules; Thyroid carcinoma; Adult Lhermitte-Duclos disease ID COWDEN-SYNDROME; IMMUNOHISTOCHEMICAL ANALYSIS; DIAGNOSTIC-CRITERIA; CANCER; POLYPOSIS; MUTATIONS; DISEASE; LESIONS AB PTEN hamartoma tumor syndrome refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Cowden syndrome, the principal PTEN-related disorder is characterized by multiple neoplasms and hamartomas, mucosal papillomatosis, and skin lesions, trichilemmomas. Trichilemmomas and mucocutaneous papillomatous papules are one of the first signs of the disease. Early recognition of these skin lesions may help on diagnosing an underlying malignancy and early cancer screening. C1 [Nose, Vania] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nose, Vania] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nose, V (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Nose, V (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM vnose@mgh.harvard.edu NR 25 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-055X EI 1936-0568 J9 HEAD NECK PATHOL JI Head Neck Pathol. PD JUN PY 2016 VL 10 IS 2 BP 131 EP 138 DI 10.1007/s12105-016-0708-7 PG 8 WC Pathology SC Pathology GA DO6KJ UT WOS:000377891800003 PM 26975628 ER PT J AU Radkay-Gonzalez, L Faquin, W McHugh, JB Lewis, JS Tuluc, M Seethala, RR AF Radkay-Gonzalez, Lisa Faquin, William McHugh, Jonathan B. Lewis, James S., Jr. Tuluc, Madalina Seethala, Raja R. TI Ciliated Adenosquamous Carcinoma: Expanding the Phenotypic Diversity of Human Papillomavirus-Associated Tumors SO HEAD & NECK PATHOLOGY LA English DT Article DE Adenosquamous; Non-keratinizing; Ciliated; Human papillomavirus; MAML2 ID MUCOEPIDERMOID CARCINOMA; SALIVARY-GLANDS; NECK-CANCER; HEAD; ADENOCARCINOMA; TRANSLOCATION AB This study describes a unique subset of ciliated, human papillomavirus (HPV) related, adenosquamous carcinomas (AsqCA) of the head and neck that in contrast to most AsqCA, often show areas with lower grade cytonuclear features. They are comprised of largely non-keratinizing squamous cell carcinoma components with cystic change, gland formation, mucin production, and cilia in tumor cells. Seven cases of ciliated AsqCA were retrieved. Site distribution was as follows: palatine tonsil-3/7, base of tongue-1/7, and neck (unknown primary site)-3/7. Despite the occasional resemblance to mucoepidermoid carcinoma (MEC), the tumors showed focal keratinizing morphology and atypia, and all tumors were negative for MAML2 rearrangements. Oropharyngeal and neck tumors were uniformly p16 positive and showed punctate staining by in situ hybridization for high risk HPV DNA. There were two distant metastases (lung), and one tumor related death. Thus, ciliated AsqCA are HPV-associated lesions that pose unique pitfalls, closely mimicking MEC and other salivary gland tumors. These tumors add to the list of those which defy the dogma that ciliated epithelium always equates to a benign process. C1 [Radkay-Gonzalez, Lisa; Seethala, Raja R.] Univ Pittsburgh, Presbyterian Shadyside Hosp, Dept Pathol & Lab Med, Med Ctr, Pittsburgh, PA 15232 USA. [Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [McHugh, Jonathan B.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. [Lewis, James S., Jr.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Lewis, James S., Jr.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. [Tuluc, Madalina] Thomas Jefferson Univ Hosp, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Seethala, Raja R.] A614 X Presbyterian Univ Hosp, 200 Lothrop St, Pittsburgh, PA 15213 USA. RP Seethala, RR (reprint author), Univ Pittsburgh, Presbyterian Shadyside Hosp, Dept Pathol & Lab Med, Med Ctr, Pittsburgh, PA 15232 USA.; Seethala, RR (reprint author), A614 X Presbyterian Univ Hosp, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM seethalarr@upmc.edu NR 25 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-055X EI 1936-0568 J9 HEAD NECK PATHOL JI Head Neck Pathol. PD JUN PY 2016 VL 10 IS 2 BP 167 EP 175 DI 10.1007/s12105-015-0653-x PG 9 WC Pathology SC Pathology GA DO6KJ UT WOS:000377891800008 PM 26411881 ER PT J AU Bernstein, SN Sailer, DN Catov, JM Canavan, TP AF Bernstein, Sarah N. Sailer, Devereux N. Catov, Janet M. Canavan, Timothy P. TI Ultrasonography estimates of fetal growth in fetuses affected by trisomy 21 SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Down syndrome; Fetal growth curves; Trisomy 21; Ultrasonography ID DOWN-SYNDROME; AGE; LENGTH; CHARTS AB Objective: To construct growth curves specific for fetuses with trisomy 21 (121) and to compare them with the reference-based standard. Methods: A retrospective cohort study was conducted of ultrasonography examinations from women with singleton pregnancies with a confirmed diagnosis of T21 who sought care at an academic tertiary-care center in the USA between January 1, 2003, and December 31, 2013. Growth curves were constructed using linear regression and compared with the Hadlock standard. Results: The study included 425 ultrasonography examinations from 235 women. The head circumference and femur length were smaller than the reference standards at all gestational ages (head circumference: P = 0.017; femur length: P < 0.001). The abdominal circumference was larger than the reference standard from 29 weeks onward (P < 0.001). The biparietal diameter was smaller in the second trimester and in the late third trimester (P < 0.001). The overall estimated fetal weight was not different from the reference standard. Conclusion: The T21-specific growth curves indicate anthropometric differences between T21 fetuses and the general population. Once validated, such individual growth curves could allow for more accurate prenatal assessment and management of fetuses affected by T21. (C) 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Bernstein, Sarah N.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Sailer, Devereux N.; Catov, Janet M.; Canavan, Timothy P.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Catov, Janet M.] Magee Womens Res Inst, Pittsburgh, PA USA. RP Bernstein, SN (reprint author), 8 Lamartine Terrace, Boston, MA 02130 USA. EM snbernstein@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 EI 1879-3479 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JUN PY 2016 VL 133 IS 3 BP 287 EP 290 DI 10.1016/j.ijgo.2015.09.034 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DO5OZ UT WOS:000377833800008 PM 26969147 ER PT J AU Kaliannan, K Wang, B Li, XY Bhan, AK Kang, JX AF Kaliannan, K. Wang, B. Li, X-Y Bhan, A. K. Kang, J. X. TI Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID DIETARY FATTY-ACIDS; METABOLIC ENDOTOXEMIA; MICE; INFLAMMATION AB Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics. C1 [Kaliannan, K.; Wang, B.; Li, X-Y; Kang, J. X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, 149-13th St, Boston, MA 02129 USA. [Kaliannan, K.; Wang, B.; Li, X-Y; Bhan, A. K.; Kang, J. X.] Harvard Univ, Sch Med, 149-13th St, Boston, MA 02129 USA. [Bhan, A. K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, 149-13th St, Boston, MA 02129 USA.; Kang, JX (reprint author), Harvard Univ, Sch Med, 149-13th St, Boston, MA 02129 USA. EM kang.jing@mgh.harvard.edu FU Sansun Life Sciences; Fortune Education Foundation FX This study was supported by the generous funding from Sansun Life Sciences and the Fortune Education Foundation. We are also grateful to Marina Kang for her editorial assistance and Amy Goodale for her experimental assistance. NR 16 TC 3 Z9 3 U1 6 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2016 VL 40 IS 6 BP 1039 EP 1042 DI 10.1038/ijo.2016.27 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DO2NQ UT WOS:000377617100021 PM 26876435 ER PT J AU So-Armah, KA Tate, JP Chang, CCH Butt, AA Gerschenson, M Gibert, CL Leaf, D Rimland, D Rodriguez-Barradas, MC Budoff, MJ Samet, JH Kuller, LH Deeks, SG Crothers, K Tracy, RP Crane, HM Sajadi, MM Tindle, HA Justice, AC Freiberg, MS AF So-Armah, Kaku A. Tate, Janet P. Chang, Chung-Chou H. Butt, Adeel A. Gerschenson, Mariana Gibert, Cynthia L. Leaf, David Rimland, David Rodriguez-Barradas, Maria C. Budoff, Matthew J. Samet, Jeffrey H. Kuller, Lewis H. Deeks, Steven G. Crothers, Kristina Tracy, Russell P. Crane, Heidi M. Sajadi, Mohammad M. Tindle, Hilary A. Justice, Amy C. Freiberg, Matthew S. CA VACS Project Team TI Do Biomarkers of Inflammation, Monocyte Activation, and Altered Coagulation Explain Excess Mortality Between HIV Infected and Uninfected People? SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; mortality; inflammation; monocyte activation; coagulation ID VETERANS AGING COHORT; ALL-CAUSE MORTALITY; ANTIRETROVIRAL THERAPY; GENERAL-POPULATION; HEPATITIS-C; RISK; INDEX; ASSOCIATION; DISEASE; ADULTS AB Background: HIV infection and biomarkers of inflammation [measured by interleukin-6 (IL-6)], monocyte activation [soluble CD14 (sCD14)], and coagulation (D-dimer) are associated with morbidity and mortality. We hypothesized that these immunologic processes mediate (explain) some of the excess risk of mortality among HIV infected (HIV+) versus uninfected people independently of comorbid diseases. Methods: Among 2350 (1521 HIV+) participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS BC), we investigated whether the association between HIV and mortality was altered by adjustment for IL-6, sCD14, and D-dimer, accounting for confounders. Participants were followed from date of blood draw for biomarker assays (baseline) until death or July 25, 2013. Analyses included ordered logistic regression and Cox Proportional Hazards regression. Results: During 6.9 years (median), 414 deaths occurred. The proportional odds of being in a higher quartile of IL-6, sCD14, or D-dimer were 2-3 fold higher for viremic HIV+ versus uninfected people. Mortality rates were higher among HIV+ compared with uninfected people [incidence rate ratio (95% CI): 1.31 (1.06 to 1.62)]. Mortality risk increased with increasing quartiles of IL-6, sCD14, and D-dimer regardless of HIV status. Adjustment for IL-6, sCD14, and D-dimer partially attenuated mortality risk among HIV+ people with unsuppressed viremia (HIV-1 RNA >= 10,000 copies per milliliter) compared with uninfected people-hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people. milliliter) compared with uninfected people-hazard ratio (95% CI) decreased from 2.18 (1.60 to 2.99) to 2.00 (1.45 to 2.76). Conclusions: HIV infection is associated with elevated IL-6, sCD14, and D-dimer, which are in turn associated with mortality. Baseline measures of these biomarkers partially mediate excess mortality risk among HIV+ versus uninfected people. C1 [So-Armah, Kaku A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, Gen Internal Med Sect, West Haven, CT USA. [Tate, Janet P.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Chang, Chung-Chou H.; Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Butt, Adeel A.] Hamad Med Corp, Hamad Healthcare Qual Inst, Doha, Qatar. [Butt, Adeel A.] Weill Cornell Med Coll, Dept Med, Doha, Qatar. [Butt, Adeel A.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Gerschenson, Mariana] Univ Hawaii Manoa, Cell & Mol Biol Dept, John A Burns Sch Med, Honolulu, HI 96822 USA. [Gibert, Cynthia L.] VA Med Ctr, Med Serv Infect Dis, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. [Leaf, David] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rimland, David] VA Med Ctr, Med Serv, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Med Serv, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. [Budoff, Matthew J.] Los Angeles Biomed Res Inst, Dept Med, Torrance, CA USA. [Samet, Jeffrey H.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Samet, Jeffrey H.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Samet, Jeffrey H.] Boston Med Ctr, Dept Gen Internal Med, Boston, MA USA. [Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA. [Crothers, Kristina] Univ Washington, Div Pulm & Crit Care, Dept Internal Med, Seattle, WA 98195 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Burlington, VT USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. [Crane, Heidi M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Sajadi, Mohammad M.] Baltimore VA Med Ctr, Dept Med, Baltimore, MD USA. [Sajadi, Mohammad M.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Tindle, Hilary A.; Freiberg, Matthew S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Freiberg, Matthew S.] VA Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP So-Armah, KA (reprint author), Boston Univ, Sch Med, 801 Massachusetts Ave, Boston, MA 02118 USA. EM kaku@bu.edu OI Crothers, Kristina/0000-0001-9702-0371 FU National Institute on Alcohol Abuse and Alcoholism; National Heart Lung and Blood Institute at the National Institutes of Health [R01HC095136-04 5R01HC095126-04, R01AI110259-01A1, 1I01BX002358-01A1]; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; Gilead; AbbVie FX Supported by National Institute on Alcohol Abuse and Alcoholism and National Heart Lung and Blood Institute at the National Institutes of Health (Grant Number R01HC095136-04 5R01HC095126-04 to M.F; R01AI110259-01A1 and 1I01BX002358-01A1 to MMS). Veterans Aging Cohort Study funded by: National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566). The authors would also like to acknowledge the substantial in-kind support we receive from the Veterans Affairs Healthcare System. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. And also supported by Gilead and AbbVie (Adeel Butt). NR 25 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2016 VL 72 IS 2 BP 206 EP 213 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DO8UI UT WOS:000378059300022 PM 26885807 ER PT J AU Al-Qurayshi, Z Randolph, GW Alshehri, M Kandil, E AF Al-Qurayshi, Zaid Randolph, Gregory W. Alshehri, Mohammed Kandil, Emad TI Analysis of Variations in the Use of Intraoperative Nerve Monitoring in Thyroid Surgery SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID RECURRENT LARYNGEAL NERVE; PARATHYROID SURGERY; PALSY; METAANALYSIS; INJURY; RISK; IDENTIFICATION; MANAGEMENT; OPERATIONS; PARALYSIS AB IMPORTANCE Intraoperative nerve monitoring (IONM) is increasingly performed during thyroid surgery. OBJECTIVE To examine the use of IONM and its association with patient demographic characteristics and surgeon volume. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional analysis used the State Inpatient Databases from January 1, 2010, to December 31, 2011, to assess patient demographic characteristics and surgeon volume. Available 30-day readmission data for all adult patients (aged >= 18 years) who underwent thyroidectomy in Florida, New York, and Washington were included. Follow-up was completed on December 31, 2011, and data were analyzed from March 11, 2015, to February 17, 2016. MAIN OUTCOMES AND MEASURES Use of IONM and incidence of postoperative vocal cord paralysis. RESULTS A total of 17 268 patients undergoing thyroidectomy were included (20.3% men; 79.7% women; mean [SD] age, 53.0 [15.1] years), of whom 1433 patients (8.3%) had IONM. Patients who were significantly less likely to undergo IONM included black patients (185 [7.9%]; adjusted odds ratio [AOR], 0.79; 95% CI, 0.65-0.97) and those with Medicare (382 [8.4%]; AOR, 0.81; 95% CI, 0.69-0.94) or Medicaid (125 [5.5%]; AOR, 0.59; 95% CI, 0.48, 0.74) health coverage. Black patients had a higher prevalence of vocal cord paralysis compared with white patients (37 [1.6%] vs 138 [1.3%]; AOR, 1.64; 95% CI, 1.11-2.43) in a multivariate model that also controlled for IONM use. Low-volume surgeons were more likely to use IONM (1199 [9.2%] vs 234 [5.5%]; AOR, 1.76; 95% CI, 1.48-2.09). However, patients treated by low-volume surgeons had a higher risk for vocal cord paralysis compared with those treated by high-volume surgeons (187 [1.4%] vs 26 [0.6%]; AOR, 2.47; 95% CI, 1.61-3.80). The risk for vocal cord paralysis was not associated with the performance of IONM (AOR, 0.74; 95% CI, 0.48-1.16) or the type of thyroidectomy (AOR, 1.04; 95% CI, 0.75-1.44). CONCLUSIONS AND RELEVANCE Disparities in the use of IONM are based on demographic factors of the patients and surgeon volume. Intraoperative nerve monitoring appears to be used less in black patients or those with Medicare health coverage and is not associated with the risk for vocal cord paralysis. C1 [Al-Qurayshi, Zaid; Alshehri, Mohammed; Kandil, Emad] Tulane Univ, Sch Med, Dept Surg, 1430 Tulane Ave,Mail Stop SL 22, New Orleans, LA 70112 USA. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Div Thyroid & Parathyroid Endocrine Surg, Boston, MA 02114 USA. RP Kandil, E (reprint author), Tulane Univ, Sch Med, Dept Surg, 1430 Tulane Ave,Mail Stop SL 22, New Orleans, LA 70112 USA. EM ekandil@tulane.edu OI Al-Qurayshi, Zaid/0000-0002-3534-7253 NR 30 TC 0 Z9 0 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD JUN PY 2016 VL 142 IS 6 BP 584 EP 589 DI 10.1001/jamaoto.2016.0412 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DO6ZU UT WOS:000377932800012 PM 27101092 ER PT J AU Spence, RT Mueller, JL Chang, DC AF Spence, Richard T. Mueller, Jessica L. Chang, David C. TI A Novel Approach to Global Benchmarking of Risk-Adjusted Surgical Outcomes Beyond Perioperative Mortality Rate SO JAMA SURGERY LA English DT Editorial Material C1 [Spence, Richard T.] Univ Cape Town, Dept Surg, ZA-7925 Cape Town, South Africa. [Spence, Richard T.; Mueller, Jessica L.; Chang, David C.] Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr Clin Effectiveness Surg, 165 Cambridge St, Boston, MA 02114 USA. [Mueller, Jessica L.; Chang, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Spence, RT (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr Clin Effectiveness Surg, 165 Cambridge St, Boston, MA 02114 USA. EM rtspence@mgh.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JUN PY 2016 VL 151 IS 6 BP 501 EP 502 DI 10.1001/jamasurg.2016.0091 PG 2 WC Surgery SC Surgery GA DO6ZT UT WOS:000377932700006 PM 27050769 ER PT J AU Johanning, JM Hall, D Arya, S AF Johanning, Jason M. Hall, Daniel Arya, Shipra TI Frailty and Mortality After Noncardiac Surgery in Elderly Individuals Metrics, Systems, and the Elephant SO JAMA SURGERY LA English DT Editorial Material ID CARE C1 [Johanning, Jason M.] Nebraska Western Iowa VA Med Ctr, Dept Surg, 4101 Woolworth Ave, Omaha, NE 68105 USA. [Hall, Daniel] VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA USA. [Arya, Shipra] Emory Univ, Div Vasc Surg & Endovasc Therapy, Surg Res, Atlanta, GA 30322 USA. RP Johanning, JM (reprint author), Nebraska Western Iowa VA Med Ctr, Dept Surg, 4101 Woolworth Ave, Omaha, NE 68105 USA. EM jason.johanning@va.gov OI Hall, Daniel/0000-0001-6382-0522 NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JUN PY 2016 VL 151 IS 6 BP 545 EP 546 DI 10.1001/jamasurg.2015.5235 PG 3 WC Surgery SC Surgery GA DO6ZT UT WOS:000377932700014 PM 26790639 ER PT J AU Dizon, DS Birrer, MJ AF Dizon, Don S. Birrer, Michael J. TI Making a Difference: Distinguishing Two Primaries From Metastasis in Synchronous Tumors of the Ovary and Uterus SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOMETRIAL; CANCERS; CARCINOMAS; DIAGNOSIS C1 [Dizon, Don S.; Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dizon, Don S.; Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Birrer, MJ (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM mbirrer@partners.org NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2016 VL 108 IS 6 AR djv442 DI 10.1093/jnci/djv442 PG 2 WC Oncology SC Oncology GA DP2CS UT WOS:000378296300014 PM 26832772 ER PT J AU Yuan, C Clish, CB Wu, C Mayers, JR Kraft, P Townsend, MK Zhang, MF Tworoger, SS Bao, Y Qian, ZR Rubinson, DA Ng, K Giovannucci, EL Ogino, S Stampfer, MJ Gaziano, JM Ma, J Sesso, HD Anderson, GL Cochrane, BB Manson, JE Torrence, ME Kimmelman, AC Amundadottir, LT Heiden, MGV Fuchs, CS Wolpin, BM AF Yuan, Chen Clish, Clary B. Wu, Chen Mayers, Jared R. Kraft, Peter Townsend, Mary K. Zhang, Mingfeng Tworoger, Shelley S. Bao, Ying Qian, Zhi Rong Rubinson, Douglas A. Ng, Kimmie Giovannucci, Edward L. Ogino, Shuji Stampfer, Meir J. Gaziano, John Michael Ma, Jing Sesso, Howard D. Anderson, Garnet L. Cochrane, Barbara B. Manson, JoAnn E. Torrence, Margaret E. Kimmelman, Alec C. Amundadottir, Laufey T. Heiden, Matthew G. Vander Fuchs, Charles S. Wolpin, Brian M. TI Circulating Metabolites and Survival Among Patients With Pancreatic Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ASSOCIATIONS; COHORT; HEALTH; 2-HYDROXYGLUTARATE; ADENOCARCINOMA; IDENTIFICATION; GEMCITABINE; MUTATIONS; CARCINOMA; VARIANTS AB Background: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. Methods: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. Results: Two metabolites in the tricarboxylic acid (TCA) cycle-isocitrate and aconitate-were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, P-trend <.001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, P-trend <.001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P-trend <.001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. Conclusions: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer. C1 [Yuan, Chen; Qian, Zhi Rong; Rubinson, Douglas A.; Ng, Kimmie; Ogino, Shuji; Heiden, Matthew G. Vander; Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yuan, Chen; Qian, Zhi Rong; Rubinson, Douglas A.; Ng, Kimmie; Ogino, Shuji; Heiden, Matthew G. Vander; Fuchs, Charles S.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA. [Clish, Clary B.; Heiden, Matthew G. Vander] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China. [Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China. [Mayers, Jared R.; Torrence, Margaret E.; Heiden, Matthew G. Vander] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Mayers, Jared R.; Torrence, Margaret E.; Heiden, Matthew G. Vander] MIT, Dept Biol, Cambridge, MA USA. [Kraft, Peter; Tworoger, Shelley S.; Giovannucci, Edward L.; Ogino, Shuji; Stampfer, Meir J.; Ma, Jing; Sesso, Howard D.; Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Townsend, Mary K.; Tworoger, Shelley S.; Bao, Ying; Giovannucci, Edward L.; Stampfer, Meir J.; Ma, Jing; Manson, JoAnn E.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Gaziano, John Michael; Sesso, Howard D.; Manson, JoAnn E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Zhang, Mingfeng; Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gaziano, John Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org OI Mayers, Jared/0000-0002-8607-1787 FU National Institutes of Health (NIH) [UM1 CA167552]; NIH [UM1 CA186107, P01 CA87969, R01 CA49449, CA 97193, CA 34944, CA 40360, HL 26490, HL 34595, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221, R01 CA124908, P50 CA127003]; Nestle Research Center award NIH; Robert T. and Judith B. Hale Fund for Pancreatic Cancer; Perry S. Levy Fund for Gastrointestinal Cancer Research; Pappas Family Research Fund for Pancreatic Cancer; Department of Defense [CA130288]; Howard Hughes Medical Institute; Lustgarten Foundation; Promises for Purple FX HPFS is supported by National Institutes of Health (NIH) grant UM1 CA167552. NHS is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449. PHS is supported by NIH grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595. The Women's Health Initiative (WHI) program is funded by the NIH through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.; Additional support came from a Nestle Research Center award to the Broad Institute; from the Robert T. and Judith B. Hale Fund for Pancreatic Cancer, Perry S. Levy Fund for Gastrointestinal Cancer Research, Pappas Family Research Fund for Pancreatic Cancer, NIH R01 CA124908, and NIH P50 CA127003 to CSF; and from Department of Defense CA130288, Howard Hughes Medical Institute, Lustgarten Foundation, and Promises for Purple to BMW. NR 45 TC 3 Z9 3 U1 4 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN PY 2016 VL 108 IS 6 AR djv409 DI 10.1093/jnci/djv409 PG 8 WC Oncology SC Oncology GA DP2CS UT WOS:000378296300006 PM 26755275 ER PT J AU Westover, MB Gaspard, N AF Westover, M. Brandon Gaspard, Nicolas TI Not a Simple Plumbing Problem: Updating Our Understanding of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Editorial Material C1 [Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gaspard, Nicolas] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, Brussels, Belgium. [Gaspard, Nicolas] Univ Libre Bruxelles, Comprehens Epilepsy Ctr, Hop Erasme, Brussels, Belgium. [Gaspard, Nicolas] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Gaspard, Nicolas] Yale Univ, Sch Med, Comprehens Epilepsy Ctr, New Haven, CT USA. RP Westover, MB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. FU NINDS NIH HHS [K23 NS090900] NR 12 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2016 VL 33 IS 3 BP 171 EP 173 DI 10.1097/WNP.0000000000000269 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO5LQ UT WOS:000377825000002 PM 27258439 ER PT J AU Chung, DY Oka, F Ayata, C AF Chung, David Y. Oka, Fumiaki Ayata, Cenk TI Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE cortical spreading depression; peri-infarct depolarization; ischemia; secondary brain injury; neurovascular coupling; stroke; neurocritical care ID REDUCES INFARCT SIZE; PERIINFARCT DEPOLARIZATIONS; BLOOD-FLOW; MIGRAINE PROPHYLAXIS; NORMOBARIC HYPEROXIA; BRAIN-INJURY; DEPRESSION; STROKE; CORTEX; TRIAL AB Delayed cerebral ischemia is the most feared cause of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggests that delayed cerebral ischemia represents multiple concurrent and synergistic mechanisms, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SDs) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. We now know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. In this review, we discuss the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage, or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression in subarachnoid hemorrhage and other forms of acute brain injury. C1 [Chung, David Y.; Oka, Fumiaki; Ayata, Cenk] Harvard Univ, Sch Med, Neurovasc Res Unit, Dept Radiol,Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. [Chung, David Y.; Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chung, David Y.; Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Neurosci Intens Care Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oka, Fumiaki] Yamaguchi Univ, Sch Med, Dept Neurosurg, Ube, Yamaguchi 755, Japan. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Neurovasc Res Unit, Dept Radiol,Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org FU NINDS NIH HHS [P01 NS055104, R25 NS065743] NR 53 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2016 VL 33 IS 3 BP 196 EP 202 DI 10.1097/WNP.0000000000000275 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO5LQ UT WOS:000377825000005 PM 27258442 ER PT J AU Muniz, CF Shenoy, AV O'Connor, KL Bechek, SC Boyle, EJ Guanci, MM Tehan, TM Zafar, SF Cole, AJ Patel, AB Westover, MB Rosenthal, ES AF Muniz, Carlos F. Shenoy, Apeksha V. O'Connor, Kathryn L. Bechek, Sophia C. Boyle, Emily J. Guanci, Mary M. Tehan, Tara M. Zafar, Sahar F. Cole, Andrew J. Patel, Aman B. Westover, Michael B. Rosenthal, Eric S. TI Clinical Development and Implementation of an Institutional Guideline for Prospective EEG Monitoring and Reporting of Delayed Cerebral Ischemia SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE delayed cerebral ischemia; continuous EEG; subarachnoid hemorrhage ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; CORTICAL SPREADING ISCHEMIA; EARLY MICROVASOSPASM; VASOSPASM; DEPOLARIZATION; OUTCOMES; ABSENCE AB Delayed cerebral ischemia (DCI) is the most common and disabling complication among patients admitted to the hospital for subarachnoid hemorrhage (SAH). Clinical and radiographic methods often fail to detect DCI early enough to avert irreversible injury. We assessed the clinical feasibility of implementing a continuous EEG (cEEG) ischemia monitoring service for early DCI detection as part of an institutional guideline. An institutional neuromonitoring guideline was designed by an interdisciplinary team of neurocritical care, clinical neurophysiology, and neurosurgery physicians and nursing staff and cEEG technologists. The interdisciplinary team focused on (1) selection criteria of high-risk patients, (2) minimization of safety concerns related to prolonged monitoring, (3) technical selection of quantitative and qualitative neurophysiologic parameters based on expert consensus and review of the literature, (4) a structured interpretation and reporting methodology, prompting direct patient evaluation and iterative neurocritical care, and (5) a two-layered quality assurance process including structured clinician interviews assessing events of neurologic worsening and an adjudicated consensus review of neuroimaging and medical records. The resulting guideline's clinical feasibility was then prospectively evaluated. The institutional SAH monitoring guideline used transcranial Doppler ultrasound and cEEG monitoring for vasospasm and ischemia monitoring in patients with either Fisher group 3 or Hunt-Hess grade IV or V SAH. Safety criteria focused on prevention of skin breakdown and agitation. Technical components included monitoring of transcranial Doppler ultrasound velocities and cEEG features, including quantitative alpha:delta ratio and percent alpha variability, qualitative evidence of new focal slowing, late-onset epileptiform activity, or overall worsening of background. Structured cEEG reports were introduced including verbal communication for findings concerning neurologic decline. The guideline was successfully implemented over 27 months, during which neurocritical care physicians referred 71 SAH patients for combined transcranial Doppler ultrasound and cEEG monitoring. The quality assurance process determined a DCI rate of 48% among the monitored population, more than 90% of which occurred during the duration of cEEG monitoring (mean 6.9 days) beginning 2.7 days after symptom onset. An institutional guideline implementing cEEG for SAH ischemia monitoring and reporting is feasible to implement and efficiently identify patients at high baseline risk of DCI during the period of monitoring. C1 [Muniz, Carlos F.; Shenoy, Apeksha V.; Boyle, Emily J.; Zafar, Sahar F.; Cole, Andrew J.; Westover, Michael B.; Rosenthal, Eric S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [O'Connor, Kathryn L.] Univ Michigan, Sch Kinesiol, Ann Arbor, MI 48109 USA. [Bechek, Sophia C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Guanci, Mary M.; Tehan, Tara M.] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. [Patel, Aman B.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Rosenthal, ES (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM erosenthal@mgh.harvard.edu OI O'Connor, Kathryn/0000-0002-5494-2357 FU NINDS NIH HHS [K23 NS090900] NR 29 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2016 VL 33 IS 3 BP 217 EP 226 DI 10.1097/WNP.0000000000000281 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO5LQ UT WOS:000377825000008 PM 27258445 ER PT J AU Wickering, E Gaspard, N Zafar, S Moura, VJ Biswal, S Bechek, S O'Connor, K Rosenthal, ES Westover, MB AF Wickering, Ellis Gaspard, Nicolas Zafar, Sahar Moura, Valdery J. Biswal, Siddharth Bechek, Sophia O'Connor, Kathryn Rosenthal, Eric S. Westover, M. Brandon TI Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE subarachnoid hemorrhage; SAH; delayed cerebral ischemia; DCI; continuous EEG monitoring; ICU EEG ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; CONTINUOUS EEG; INFARCTION; VASOSPASM; FREQUENCY; BLOOD; RISK AB The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha-delta ratio and relative alpha variability are needed before an automated EEG-based early delayed cerebral ischemia detection system is ready for clinical use. C1 [Wickering, Ellis] Univ Twente, Dept Tech Med, POB 217, NL-7500 AE Enschede, Netherlands. [Gaspard, Nicolas] Univ Libre Bruxelles, Dept Neurol, Comprehens Epilepsy Ctr, Hop Erasme, Brussels, Belgium. [Gaspard, Nicolas] Yale Univ, Sch Med, Dept Neurol, Comprehens Epilepsy Ctr, New Haven, CT 06510 USA. [Zafar, Sahar; Moura, Valdery J.; Biswal, Siddharth; Bechek, Sophia; O'Connor, Kathryn; Rosenthal, Eric S.; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM mwestover@mgh.harvard.edu OI O'Connor, Kathryn/0000-0002-5494-2357 FU NINDS NIH HHS [K23 NS090900] NR 17 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2016 VL 33 IS 3 BP 227 EP 234 DI 10.1097/WNP.0000000000000278 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO5LQ UT WOS:000377825000009 PM 27258446 ER PT J AU Zafar, SF Westover, MB Gaspard, N Gilmore, EJ Foreman, BP O'Connor, KL Rosenthal, ES AF Zafar, Sahar F. Westover, M. Brandon Gaspard, Nicolas Gilmore, Emily J. Foreman, Brandon P. O'Connor, Kathryn L. Rosenthal, Eric S. TI Interrater Agreement for Consensus Definitions of Delayed Ischemic Events After Aneurysmal Subarachnoid Hemorrhage SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Subarachnoid hemorrhage; Ischemia; Vasospasm; Critical care; Nomenclature ID CEREBRAL-ISCHEMIA; CLINICAL-TRIALS; OUTCOME EVENT; VASOSPASM; PROPOSAL AB Background:Thirty percent of patients with subarachnoid hemorrhage experience delayed cerebral ischemia or delayed ischemic neurologic decline (DIND). Variability in the definitions of delayed ischemia makes outcome studies difficult to compare. A recent consensus statement advocates standardized definitions for delayed ischemia in clinical trials of subarachnoid hemorrhage. We sought to evaluate the interrater agreement of these definitions.Methods:Based on consensus definitions, we assessed for: (1) delayed cerebral infarction, defined as radiographic cerebral infarction; (2) DIND type 1 (DIND1), defined as focal neurologic decline; and (3) DIND2, defined as a global decline in arousal. Five neurologists retrospectively reviewed electronic records of 58 patients with subarachnoid hemorrhage. Three reviewers had access to and reviewed neuroradiology imaging. We assessed interrater agreement using the Gwet kappa statistic.Results:Interrater agreement statistics were excellent (95.83%) for overall agreement on the presence or absence of any delayed ischemic event (DIND1, DIND2, or delayed cerebral infarction). Agreement was moderate for specifically identifying DIND1 (56.58%) and DIND2 (48.66%) events. We observed greater agreement for DIND1 when there was a significant focal motor decline of at least 1 point in the motor score. There was fair agreement (39.20%) for identifying delayed cerebral infarction; CT imaging was the predominant modality.Conclusions:Consensus definitions for delayed cerebral ischemia yielded near-perfect overall agreement and can thus be applied in future large-scale studies. However, a strict process of adjudication, explicit thresholds for determining focal neurologic decline, and MRI techniques that better discriminate edema from infarction seem critical for reproducibility of determination of specific outcome phenotypes, and will be important for successful clinical trials. C1 [Zafar, Sahar F.; Westover, M. Brandon; O'Connor, Kathryn L.; Rosenthal, Eric S.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gaspard, Nicolas] Univ Libre Bruxelles, Dept Neurol, Brussels, Belgium. [Gilmore, Emily J.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Foreman, Brandon P.] UC Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH USA. RP Rosenthal, ES (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM erosenthal@mgh.harvard.edu OI O'Connor, Kathryn/0000-0002-5494-2357 FU Andrew David Heitman Neuroendovascular Research Foundation; National Institute of Health (NIH-NINDS) [1K23NS090900-01]; Phyllis & Jerome Lyle Rappaport Foundation; Fonds Erasme pour la Recherche Medicale FX E.S.R. received research support from the Andrew David Heitman Neuroendovascular Research Foundation. M.B.W. received research support from the National Institute of Health (NIH-NINDS, 1K23NS090900-01), the Phyllis & Jerome Lyle Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Foundation. N.G. is a clinical master specialist of the Fonds de la Recherche Scientifique (FNRS) and received research support from the Fonds Erasme pour la Recherche Medicale. NR 18 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2016 VL 33 IS 3 BP 235 EP 240 DI 10.1097/WNP.0000000000000276 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO5LQ UT WOS:000377825000010 PM 27258447 ER PT J AU Welsh, L Binder, W Miller, ES AF Welsh, Laura Binder, William Miller, Emily S. TI UNSTEADY GAIT AND DIZZINESS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID SPINAL-CORD COMPRESSION; TUMORAL CALCINOSIS; EMERGENCY-DEPARTMENT; EPIDURAL ABSCESS; PATHOGENESIS; DIAGNOSIS; ATAXIA; DELAYS C1 [Welsh, Laura; Miller, Emily S.] Harvard Univ, Sch Med, Dept Emergency Med, Zero Emerson Pl,Ste 3B, Boston, MA 02114 USA. [Welsh, Laura; Miller, Emily S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Welsh, Laura] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. [Binder, William] Brown Univ, Dept Emergency Med, Alpert Sch Med, Providence, RI 02912 USA. [Binder, William] Miriam Hosp, Dept Emergency Med, Rhode Isl Hosp, Providence, RI 02906 USA. RP Miller, ES (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Zero Emerson Pl,Ste 3B, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD JUN PY 2016 VL 50 IS 6 BP 887 EP 890 PG 4 WC Emergency Medicine SC Emergency Medicine GA DO7VF UT WOS:000377990400012 PM 27221016 ER PT J AU van Leeuwen, WF Janssen, SJ Ring, D AF van Leeuwen, Wouter F. Janssen, Stein J. Ring, David TI Radiographic Progression of Kienbock Disease: Radial Shortening Versus No Surgery SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Kienbock disease; lunatomalacia; progression; radial shortening; natural course ID NEGATIVE ULNAR VARIANCE; CARPAL BONE ANGLES; LATERAL WRIST RADIOGRAPHS; FOLLOW-UP; WEDGE OSTEOTOMY; CLASSIFICATION; POPULATION; KINEMATICS; OUTCOMES AB Purpose The natural course of the pathophysiology of Kienbock disease is uncertain. Shortening of the radius is believed to modify the pathophysiology by addressing mechanical influences on the lunate. The aim of this study was to compare the radiographic progression of Kienbock disease among patients who had radial shortening osteotomy and patients who had no surgical treatment, with a minimum 1-year interval between radiographs. Methods Among 207 patients with Kienbock disease, we included all 48 eligible patients who had either radial shortening osteotomy or nonsurgical treatment and 2 sets of wrist radiographs available a minimum of 1 year apart. We compared changes in carpal height ratio, Stahl index, and carpal angles between the 2 sets of radiographs and between radial shortening osteotomy and nonsurgical treatment. Results We found, on average, a small decrease in the carpal height ratio and the Stahl index in patients who did and did not have surgery, with no differences between the 2 groups. Nearly half of the patients had no decrease in the carpal height ratio and/or the Stahl index. Conclusions Radiographic progression of Kienbock over 1 year or more seems slight on average regardless of treatment. Future research might address the probability of and factors associated with radiographic progression of Kienbock disease. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved. C1 [van Leeuwen, Wouter F.; Janssen, Stein J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA USA. [Ring, David] Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd,Ste 1-114AC MC R1800, Austin, TX 78723 USA. RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd,Ste 1-114AC MC R1800, Austin, TX 78723 USA. EM david.ring@austin.utexas.edu OI Ring, David/0000-0002-6506-4879 NR 52 TC 0 Z9 0 U1 0 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUN PY 2016 VL 41 IS 6 BP 681 EP 688 DI 10.1016/j.jhsa.2016.02.016 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DO5TV UT WOS:000377846600003 PM 27068002 ER PT J AU VanEpps, EM Downs, JS Loewenstein, G AF VanEpps, Eric M. Downs, Julie S. Loewenstein, George TI Advance Ordering for Healthier Eating? Field Experiments on the Relationship Between the Meal Order-Consumption Time Delay and Meal Content SO JOURNAL OF MARKETING RESEARCH LA English DT Article DE time delay; field experiment; eating ID DECISION-MAKING; CHOICES; FUTURE; FOOD; INCONSISTENCY; PATERNALISM; PREFERENCE; IMMEDIATE; REWARD; STATES AB Encouraging consumers to select meals in advance rather than at mealtime has been proposed as a strategy to promote healthier eating decisions, taking advantage of the improved self-control that is thought to accompany decisions about the future. In two field studies at an employee cafeteria and a third in a university setting, we examine how time delays between placing a lunch order and picking it up affect the healthfulness of that lunch. The first study, a secondary data analysis, finds that longer delays between placing an order and picking up the meal are associated with reductions in calorie content. The second study tests the causality of this relationship by exogenously restricting some lunch orders to be substantially delayed, leading to a marginally significant (approximately 5%) reduction in calories among delayed orders. The third study compares orders for truly immediate consumption versus orders placed in advance and demonstrates a significant (100 calorie, or approximately 10%) reduction in lunch calories. We discuss evidence regarding possible theoretical mechanisms underlying this effect, as well as practical implications of our findings. C1 [VanEpps, Eric M.] Univ Penn, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Downs, Julie S.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Loewenstein, George] Carnegie Mellon Univ, Econ & Psychol, Pittsburgh, PA 15213 USA. RP VanEpps, EM (reprint author), Univ Penn, VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. EM vanepps@mail.med.upenn.edu; downs@andrew.cmu.edu; gl20@andrew.cmu.edu NR 51 TC 2 Z9 2 U1 14 U2 20 PU AMER MARKETING ASSOC PI CHICAGO PA 311S WACKER DR, STE 5800, CHICAGO, IL 60606-6629 USA SN 0022-2437 EI 1547-7193 J9 J MARKETING RES JI J. Mark. Res. PD JUN PY 2016 VL 53 IS 3 BP 369 EP 380 DI 10.1509/jmr.14.0234 PG 12 WC Business SC Business & Economics GA DO7SM UT WOS:000377983300005 ER PT J AU Albuquerque, FC Fiorella, D Hirsch, JA Pretigiacomo, C Tarr, RW AF Albuquerque, Felipe C. Fiorella, David Hirsch, Joshua A. Pretigiacomo, Charles Tarr, Robert W. TI Tribulations of stroke trials SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Letter C1 [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, 350 W Thomas Rd, Phoenix, AZ 85013 USA. [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Pretigiacomo, Charles] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, 185 S Orange Ave, Newark, NJ 07103 USA. [Tarr, Robert W.] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH USA. RP Albuquerque, FC (reprint author), Barrow Neurol Inst, Div Neurol Surg, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM felipe.albuquerque@bnaneuro.net NR 1 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2016 VL 8 IS E1 BP E13 EP + DI 10.1136/neurintsurg-2013-010978 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DO9PC UT WOS:000378117800014 PM 24101741 ER PT J AU Hirsch, JA Mehta, BP Chandra, RV Leslie-Mazwi, TM Rost, NS Yoo, AJ AF Hirsch, Joshua A. Mehta, Brijesh P. Chandra, Ronil V. Leslie-Mazwi, Thabele M. Rost, Natalia S. Yoo, Albert J. TI Efficacy of intra-arterial therapy in the elderly requires further study SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Letter ID ACUTE ISCHEMIC-STROKE; MECHANICAL THROMBECTOMY; THROMBOLYSIS; OLDER C1 [Hirsch, Joshua A.; Mehta, Brijesh P.; Chandra, Ronil V.; Leslie-Mazwi, Thabele M.; Rost, Natalia S.; Yoo, Albert J.] Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, 55 Fruit St,Gray 2, Boston, MA 02114 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM hirsch@snisonline.org NR 10 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2016 VL 8 IS E1 BP E6 EP + DI 10.1136/neurintsurg-2012-010524 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DO9PC UT WOS:000378117800005 PM 22993244 ER PT J AU Mehta, BP Leslie-Mazwi, TM Simonsen, CZ Rabinov, JD Hirsch, JA Gupta, R Yoo, AJ AF Mehta, Brijesh P. Leslie-Mazwi, Thabele M. Simonsen, Claus Z. Rabinov, James D. Hirsch, Joshua A. Gupta, Rishi Yoo, Albert J. TI ADAPT FAST Study: third-generation stroke thrombectomy devices place renewed focus on the elusive relationship between revascularization and good outcomes SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Letter ID ACUTE ISCHEMIC-STROKE; ENDOVASCULAR THERAPY; SELECTION; TRIAL; MRI; REPERFUSION; IMPACT; ONSET; TIMES C1 [Mehta, Brijesh P.] Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, 55 Fruit St Gray 241, Boston, MA 02114 USA. [Leslie-Mazwi, Thabele M.] Massachusetts Gen Hosp, Dept Neurointervent Serv, Boston, MA 02114 USA. [Simonsen, Claus Z.; Rabinov, James D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept NeuroEndovasc Program, Boston, MA 02114 USA. [Gupta, Rishi] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Yoo, Albert J.] Massachusetts Gen Hosp, Dept Intervent & Diagnost Neuroradiol, Boston, MA 02114 USA. RP Mehta, BP (reprint author), Massachusetts Gen Hosp, Dept NeuroIntervent Radiol, 55 Fruit St Gray 241, Boston, MA 02114 USA. EM brijesh.mehta@icloud.com NR 16 TC 0 Z9 0 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2016 VL 8 IS E1 BP E21 EP + DI 10.1136/neurintsurg-2014-011507 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DO9PC UT WOS:000378117800021 PM 25335791 ER PT J AU Serrano-Pozo, A Qian, J Muzikansky, A Monsell, SE Montine, TJ Frosch, MP Betensky, RA Hyman, BT AF Serrano-Pozo, Alberto Qian, Jing Muzikansky, Alona Monsell, Sarah E. Montine, Thomas J. Frosch, Matthew P. Betensky, Rebecca A. Hyman, Bradley T. TI Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ABC score; Alzheimer disease; Amyloid plaques; National Alzheimer's Coordinating Center; Neuritic plaques; Neurofibrillary tangles; Thal stages ID UNIFORM DATA SET; ASSOCIATION GUIDELINES; COORDINATING-CENTER; NATIONAL INSTITUTE; CEREBELLAR PLAQUES; SENILE PLAQUES; HUMAN BRAIN; DEMENTIA; MICROGLIA; PATHOLOGY AB The 2012 neuropathological criteria for the diagnosis of Alzheimer disease (AD) summarize the extent of AD neuropathological change with an ABC score, which is a composite of the Thal stage of amyloid deposition (A), the Braak stage of neurofibrillary tangles (NFTs) (B), and the CERAD neuritic plaque score (C). NFTs and neuritic plaques are well-established contributors to cognitive impairment, but whether the Thal amyloid stage independently predicts antemortem cognition remains unknown. We used the National Alzheimer's Coordinating Center autopsy data set to build adjacent-categories logit regression models with CDR-SOB and Mini-Mental State Examination (MMSE) scores as cognitive outcome variables. Increasing CERAD scores were independently associated with higher CDR-SOB scores, whereas increasing Braak NFT stages predicted both higher CDR-SOB and lower MMSE scores. Increasing Thal amyloid stages were not significantly independently associated with either outcome measure. Increasing ABC scores predicted higher CDR-SOB and lower MMSE scores. These results raise the possibility that Thal amyloid stages do not substantially contribute to predicting antemortem cognition compared to CERAD neuritic plaque scores and Braak NFT stages, and suggest that the diffuse amyloid deposits participating in the assignment of Thal amyloid stages are neutral with respect to clinically detectable cognitive and functional changes. C1 [Serrano-Pozo, Alberto] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. [Qian, Jing] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Monsell, Sarah E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.; Betensky, Rebecca A.; Hyman, Bradley T.] Massachusetts Alzheimer Dis Res Ctr, 16th St,Bldg 114, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Alzheimer Dis Res Ctr, 16th St,Bldg 114, Charlestown, MA 02129 USA. EM bhyman@mgh.harvard.edu FU NIA NIH HHS [U01 AG016976, P50 AG005134] NR 41 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 BP 516 EP 526 DI 10.1093/jnen/nlw026 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000004 PM 27105663 ER PT J AU Tirosh, I Venteicher, AS Hebert, C Escalante, L Neftel, C Nahed, BV Curry, WT Cahill, DP Frosch, MP Louis, DN Regev, A Suva, ML AF Tirosh, Itay Venteicher, Andrew S. Hebert, Christine Escalante, Leah Neftel, Cyril Nahed, Brian V. Curry, Will T. Cahill, Dan P. Frosch, Matthew P. Louis, David N. Regev, Aviv Suva, Mario L. TI Large-scale single-cell RNA-seq reveals a developmental hierarchy in oligodendrogliomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah; Neftel, Cyril; Nahed, Brian V.; Curry, Will T.; Cahill, Dan P.; Frosch, Matthew P.; Louis, David N.; Suva, Mario L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Tirosh, Itay; Venteicher, Andrew S.; Hebert, Christine; Escalante, Leah; Neftel, Cyril; Regev, Aviv; Suva, Mario L.] Broad Inst MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 14 BP 571 EP 571 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000023 ER PT J AU Abedalthagafi, M Abedalthagafi, M Bi, WL Horowitz, PH Agarwalla, P Gibson, W Laws, E Beroukhim, R Santagata, S AF Abedalthagafi, Malak Abedalthagafi, Malak Bi, Wenya Linda Horowitz, Peleg Horowitz Agarwalla, Pankaj Gibson, William Laws, Edward, Jr. Beroukhim, Rameen Santagata, Sandro TI Molecular Genetics Pathology of Pituitary Adenomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Abedalthagafi, Malak] King Fahad Med City, Dept Pathol, Riyadh, Saudi Arabia. [Abedalthagafi, Malak] Brigham & Womens Hosp, Boston, MA 02115 USA. [Abedalthagafi, Malak] KACST, Riyadh, Saudi Arabia. [Abedalthagafi, Malak] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Abedalthagafi, Malak] KFMC, Riyadh, Saudi Arabia. [Abedalthagafi, Malak] King Abdulaziz Sci & Technol, Riyadh, Saudi Arabia. [Bi, Wenya Linda; Horowitz, Peleg Horowitz; Laws, Edward, Jr.; Santagata, Sandro] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Agarwalla, Pankaj; Gibson, William; Beroukhim, Rameen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 25 BP 574 EP 574 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000034 ER PT J AU Williams, E Kim, J Muzikansky, A Iafrate, J Plotkin, S Stemmer-Rachamimov, A AF Williams, Erik Kim, James Muzikansky, Alona Iafrate, John Plotkin, Scott Stemmer-Rachamimov, Anat TI Molecular and histologic features of a series of sporadic and familial schwannomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Williams, Erik; Kim, James; Muzikansky, Alona; Iafrate, John; Plotkin, Scott; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 27 BP 574 EP 575 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000036 ER PT J AU Williams, E McGuone, D Frosch, M Hyman, B Stemmer-Rachamimov, A AF Williams, Erik McGuone, Declan Frosch, Matthew Hyman, Brad Stemmer-Rachamimov, Anat TI Absence of Alzheimer disease neuropathologic changes in eyes of subjects with Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Williams, Erik; McGuone, Declan; Frosch, Matthew; Hyman, Brad; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 33 BP 576 EP 576 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000042 ER PT J AU Nasrallah, M Martinez-Lage, M O'Rourke, D Desai, A Morrissette, J Brem, S Maloney, E Shen, A Mansfield, K Mohan, S Wang, SM Verma, G Lacey, S Melenhorst, J Navenot, JM Zheng, ZH Levine, B Okada, H June, C Maus, M AF Nasrallah, MacLean Martinez-Lage, Maria O'Rourke, Donald Desai, Arati Morrissette, Jennifer Brem, Steven Maloney, Eileen Shen, Angela Mansfield, Keith Mohan, Suyash Wang, Sumei Verma, Gaurav Lacey, Simon Melenhorst, Jan Navenot, Jean-Marc Zheng, Zhaohui Levine, Bruce Okada, Hideho June, Carl Maus, Marcela TI T Cells Redirected to EGFRvIII with a Chimeric Antigen Receptor Engraft, Traffic and Mediate Antigen Loss in Patients with EGFRvIII plus Glioblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Nasrallah, MacLean; Martinez-Lage, Maria; Morrissette, Jennifer] Hosp Univ Penn, Dept Path & Lab Med, Philadelphia, PA 19104 USA. [O'Rourke, Donald; Brem, Steven; Maloney, Eileen] Hosp Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Desai, Arati] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Shen, Angela; Mansfield, Keith] Novartis Pharmaceut, Macquarie Park, NSW, Australia. [Mohan, Suyash; Wang, Sumei; Verma, Gaurav] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Lacey, Simon; Melenhorst, Jan; Navenot, Jean-Marc; Zheng, Zhaohui; Levine, Bruce; June, Carl] Univ Penn, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA. [Okada, Hideho] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Maus, Marcela] Massachusetts Gen Hosp, Ctr Canc Immunol, Boston, MA 02114 USA. [Maus, Marcela] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 62 BP 584 EP 584 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000071 ER PT J AU Juric-Sekhar, G Flanagan, M Keene, C Louis, D AF Juric-Sekhar, Gordana Flanagan, Margaret Keene, Christopher Louis, David TI Intracerebellar Crystal-Storing Histiocytosis SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Juric-Sekhar, Gordana; Flanagan, Margaret; Keene, Christopher] Univ Washington, Seattle, WA 98195 USA. [Louis, David] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 66 BP 585 EP 585 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000075 ER PT J AU Solomon, D Raleigh, D Lloyd, S Lazar, A Garcia, M Sneed, P Clarke, J McDermott, M Berger, M Haas-Kogan, D Tihan, T AF Solomon, David Raleigh, David Lloyd, Shane Lazar, Ann Garcia, Michael Sneed, Penny Clarke, Jennifer McDermott, Michael Berger, Mitchel Haas-Kogan, Daphne Tihan, Tarik TI Histopathologic Review of Pineal Parenchymal Tumors Identifies Novel Morphologic Subtypes and Prognostic Factors for Outcome SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Solomon, David; Tihan, Tarik] Univ Calif San Francisco, Div Neuropathol, San Francisco, CA 94143 USA. [Raleigh, David; Lloyd, Shane; Lazar, Ann; Garcia, Michael; Sneed, Penny] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Clarke, Jennifer] Univ Calif San Francisco, Neurooncol Div, San Francisco, CA 94143 USA. [McDermott, Michael; Berger, Mitchel] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Haas-Kogan, Daphne] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 72 BP 586 EP 587 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000081 ER PT J AU Solomon, I De Girolami, U Chettimada, S Misra, V Singer, E Gabuzda, D AF Solomon, Isaac De Girolami, Umberto Chettimada, Sukrutha Misra, Vikas Singer, Elyse Gabuzda, Dana TI Brain and liver pathology and amyloid deposition among older HIV-positive patients in the late HAART era SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Solomon, Isaac; De Girolami, Umberto] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chettimada, Sukrutha; Misra, Vikas] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Singer, Elyse] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 88 BP 591 EP 591 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000097 ER PT J AU Marshall, D Rose, S Rice, S Beller, A Peskind, E Keene, C AF Marshall, Desiree Rose, Shannon Rice, Samantha Beller, Allison Peskind, Elaine Keene, C. TI Results of NINDS/NIBIB CTE neuropathology screening in an ADRC cohort. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Marshall, Desiree; Rose, Shannon; Rice, Samantha; Beller, Allison; Keene, C.] Univ Washington Pathol, Seattle, WA USA. [Peskind, Elaine] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 133 BP 604 EP 604 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000142 ER PT J AU Huber, B Cormier, K Babcock, K Alvarez, V Stein, T McKee, A AF Huber, Bertrand Cormier, Kerry Babcock, Katharine Alvarez, Victor Stein, Thor McKee, Ann TI Structural characterization of perivascular lesions in chronic traumatic encephalopathy SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [Huber, Bertrand] Boston Univ, VA Boston Healthcare, Boston, MA 02215 USA. [Cormier, Kerry] VA Boston Healthcare, Brockton, MA USA. [Babcock, Katharine; Alvarez, Victor] Bedford Vet Affairs Med Ctr, Bedford, MA USA. [Stein, Thor; McKee, Ann] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 140 BP 606 EP 606 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000149 ER PT J AU DeWitt, J Louis, D Lennerz, J AF DeWitt, John Louis, David Lennerz, Jochen TI Modeling Cost-Effectiveness of IDH1 Testing in Glioma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 92nd Annual Meeting of the American-Association-of-Neuropathologist-Inc CY JUN 16-19, 2016 CL Baltimore, MD SP Amer Assoc Neuropathologist Inc C1 [DeWitt, John; Louis, David; Lennerz, Jochen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2016 VL 75 IS 6 MA 152 BP 609 EP 609 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DO3FC UT WOS:000377665000161 ER PT J AU Chukwueke, U Batchelor, T Brastianos, P AF Chukwueke, Ugonma Batchelor, Tracy Brastianos, Priscilla TI Management of Brain Metastases in Patients With Melanoma SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Review ID GRADED PROGNOSTIC ASSESSMENT; OPEN-LABEL; PHASE-2 TRIAL; MALIGNANT-MELANOMA; IPILIMUMAB; SURVIVAL; THERAPY; DABRAFENIB; RADIOTHERAPY; VEMURAFENIB AB Melanoma is the third most common systemic cancer that leads to brain metastases. The annual incidence of melanoma has increased over time, with brain metastases developing in 40% to 50% of patients with advanced melanoma. Traditional management of melanoma-related brain metastases has focused on symptom control as a result of the significant neurologic morbidity associated with the disease. Median overall survival for these patients, if untreated, is approximately 3 months. As with other brain metastases, a multidisciplinary treatment approach that includes surgery and radiation therapy is typically used, with historically little role for systemic, cytotoxic therapy. During the past decade, advancement within the field of genomics has led to the identification of melanoma-specific mutations, namely, v-Raf murine sarcoma viral oncogene homolog B and neuroblastoma RAS viral oncogene homolog, as well as to the development of agents that target these driver mutations. In addition, the advent of immunotherapies, specifically, agents that target cytotoxic T-lymphocyte antigen-4, anti-programmed death-1, and programmed death ligand-1, has increased the potential therapeutic options available to patients with both systemic and brain disease. With these advances, early trials have demonstrated improved overall survival in patients with brain metastases who receive these therapies either as single agents or as part of multimodality treatment regimens. C1 [Brastianos, Priscilla] Massachusetts Gen Hosp, 55 Fruit St,YAW 9E, Boston, MA 02114 USA. [Brastianos, Priscilla] Harvard Univ, Sch Med, 55 Fruit St,YAW 9E, Boston, MA 02114 USA. RP Brastianos, P (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 9E, Boston, MA 02114 USA.; Brastianos, P (reprint author), Harvard Univ, Sch Med, 55 Fruit St,YAW 9E, Boston, MA 02114 USA. EM pbrastianos@mgh.harvard.edu NR 33 TC 3 Z9 3 U1 4 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JUN PY 2016 VL 12 IS 6 BP 536 EP U285 DI 10.1200/JOP.2016.011882 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO5KD UT WOS:000377821100023 PM 27288470 ER PT J AU Freedman, RA Kouri, EM West, DW Lii, J Keating, NL AF Freedman, Rachel A. Kouri, Elena M. West, Dee W. Lii, Joyce Keating, Nancy L. TI Association of Breast Cancer Knowledge With Receipt of Guideline-Recommended Breast Cancer Treatment SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID TREATMENT DECISION-MAKING; ADJUVANT CHEMOTHERAPY; OLDER WOMEN; HEALTH LITERACY; RACIAL/ETHNIC DISPARITIES; INCREASING MAMMOGRAPHY; RACIAL DISPARITIES; KEY TREATMENT; REGISTRY DATA; POPULATION AB Purpose Knowledge about one's breast cancer characteristics is poor, but whether this knowledge affects treatment is uncertain. Among women with breast cancer, we examined whether tumor knowledge was associated with adjuvant treatment receipt. Methods We surveyed a population-based sample of women in Northern California with stage 0 to III breast cancer diagnosed during 2010 to 2011 (participation rate, 68.5%). Interviews were conducted between 4 months and 3 years after diagnosis. Among 414 respondents with stage I to III disease, we examined receipt of guideline-recommended chemotherapy, radiation, and hormonal therapy by reporting correct information about one's tumor, including stage, estrogen receptor, human epidermal growth factor receptor 2 (HER2), and grade (using registry data for confirmation). We performed multivariate logistic regression to assess the probability of receiving each treatment in relevant patient groups, adjusting for patient and tumor characteristics, and examined the impact of reporting correct tumor information on treatment receipt. Results Among relevant treatment-eligible groups, 81% received chemotherapy, 91% received radiation, and 83% received hormonal therapy. In adjusted analyses, having correct (v incorrect) information for stage and HER2 were associated with chemotherapy receipt (odds ratio [OR], 4.45; 95% CI, 1.50 to 12.50 for stage; OR, 2.70; 95% CI, 1.02 to 7.18 for HER2). Correctly reporting estrogen receptor status was associated with hormonal therapy receipt (OR, 3.91; 95% CI, 1.73 to 8.86), and correctly reporting stage was associated with radiation receipt (OR, 2.76; 95% CI, 1.03 to 7.40). Conclusion Knowledge about one's tumor characteristics was strongly associated with receipt of recommended therapies. Interventions to improve patients' knowledge and understanding of their cancers should be tested as a strategy for improving receipt of care. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Inst Publ Hlth, Sacramento, CA USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org NR 45 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JUN PY 2016 VL 12 IS 6 BP 547 EP E625 DI 10.1200/JOP.2015.008508 PG 15 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO5KD UT WOS:000377821100001 ER PT J AU Rocque, GB Partridge, EE Pisu, M Martin, MY Demark-Wahnefried, W Acemgil, A Kenzik, K Kvale, EA Meneses, K Li, XL Li, YF Halilova, KI Jackson, BE Chambless, C Lisovicz, N Fouad, M Taylor, RA AF Rocque, Gabrielle B. Partridge, Edward E. Pisu, Maria Martin, Michelle Y. Demark-Wahnefried, Wendy Acemgil, Aras Kenzik, Kelly Kvale, Elizabeth A. Meneses, Karen Li, Xuelin Li, Yufeng Halilova, Karina I. Jackson, Bradford E. Chambless, Carol Lisovicz, Nedra Fouad, Mona Taylor, Richard A. TI The Patient Care Connect Program: Transforming Health Care Through Lay Navigation SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID DEEP SOUTH NETWORK; CANCER CONTROL; UNITED-STATES; COMMUNITY; DISTRESS; THERMOMETER; DISPARITIES; COST AB The Patient Care Connect Program (PCCP) is a lay patient navigation program, implemented by the University of Alabama at Birmingham Health System Cancer Community Network. The PCCP's goal is to provide better health and health care, as well as to lower overall expenditures. The program focuses on enhancing the health of patients, with emphasis on patient empowerment and promoting proactive participation in health care. Navigator training emphasizes palliative care principles and includes development of skills to facilitate advance care planning conversations. Lay navigators are integrated into the health care team, with the support of a nurse supervisor, physician medical director, and administrative champion. The intervention focuses on patients with high needs to reach those with the greatest potential for benefit from supportive services. Navigator activities are guided by frequent distress assessments, which help to identify patient concerns across multiple domains, triage patients to appropriate resources, and ultimately overcome barriers to health care. In this article, we describe the PCCP's development, infrastructure, selection and training of lay navigators, and program operations. C1 [Rocque, Gabrielle B.] Univ Alabama Birmingham, 1824 6th Ave S,WTI 240E, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Rocque, GB (reprint author), Univ Alabama Birmingham, 1824 6th Ave S,WTI 240E, Birmingham, AL 35294 USA. EM grocque@uabmc.edu NR 36 TC 2 Z9 2 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JUN PY 2016 VL 12 IS 6 BP 551 EP E642 DI 10.1200/JOP.2015.008896 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO5KD UT WOS:000377821100003 ER PT J AU Walling, AM Keating, NL Kahn, KL Dy, S Mack, JW Malin, J Arora, NK Adams, JL Antonio, ALM Tisnado, D AF Walling, Anne M. Keating, Nancy L. Kahn, Katherine L. Dy, Sydney Mack, Jennifer W. Malin, Jennifer Arora, Neeraj K. Adams, John L. Antonio, Anna Liza M. Tisnado, Diana TI Lower Patient Ratings of Physician Communication Are Associated With Unmet Need for Symptom Management in Patients With Lung and Colorectal Cancer SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CARE OUTCOMES RESEARCH; QUALITY-OF-LIFE; SURVEILLANCE CONSORTIUM; PSYCHOMETRIC PROPERTIES; CONSUMER ASSESSMENT; DYSPNEA; QUESTIONNAIRES; CHEMOTHERAPY; ASSESSMENTS; EXPERIENCE AB Purpose Little is known about factors associated with unmet needs for symptom management in patients with cancer. Methods Patients with a new diagnosis of lung and colorectal cancer from the diverse nationally representative Cancer Care Outcomes Research and Surveillance cohort completed a survey approximately 5 months after diagnosis (N = 5,422). We estimated the prevalence of unmet need for symptom management, defined as patients who report that they wanted help for at least one common symptom (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, diarrhea) during the 4 weeks before the survey but did not receive it. We identified patient factors associated with unmet need by using logistic regression with random effects to account for clustering within study sites. Results Overall, 15% (791 of 5,422) of patients had at least one unmet need for symptom management. Adjusting for sociodemographic and clinical factors, African American race, being uninsured or poor, having early-stage lung cancer, and the presence of moderate to severe symptoms were associated with unmet need (all P < .05). Furthermore, patients who rated their physician's communication score, 80 (on a 0 to 100 scale) had adjusted rates of an unmet need for symptom management that were more than twice as high as patients who rated their physicians with a perfect communication score (23.1% v 10.0%; P < .001). Conclusion A significant minority of patients with newly diagnosed lung and colorectal cancer report unmet needs for symptom management. Interventions to improve symptom management should consider the importance of physician communication to the patient's experience of disease. C1 Univ Calif Los Angeles, David Geffen Sch Med, 911 Broxton Ave, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Fielding Sch Publ Hlth, Vet Affairs Greater Los Angeles Healthcare Syst, 911 Broxton Ave, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Kaiser Permanente, Ctr Effectiveness & Safety Res, Pasadena, CA USA. Calif State Univ Fullerton, Fullerton, CA 92634 USA. Harvard Univ, Brigham & Womens Hosp, Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. Patient Ctr Outcomes Res Inst, Washington, DC USA. RP Walling, AM (reprint author), Univ Calif Los Angeles, Div Gen Internal Med, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM awalling@mednet.ucla.edu NR 36 TC 1 Z9 1 U1 5 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JUN PY 2016 VL 12 IS 6 BP 564 EP E669 DI 10.1200/JOP.2015.005538 PG 18 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO5KD UT WOS:000377821100005 ER PT J AU Rugo, HS Rumble, RB Burstein, HJ AF Rugo, Hope S. Rumble, R. Bryan Burstein, Harold J. TI Endocrine Therapy for Hormone Receptor Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline Summary SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID SUBTYPES C1 [Rugo, Hope S.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rugo, HS (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JUN PY 2016 VL 12 IS 6 BP 583 EP U246 DI 10.1200/JOP.2016.012914 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO5KD UT WOS:000377821100027 PM 27221996 ER PT J AU Chow, ET Otis, JD Simons, LE AF Chow, Erika T. Otis, John D. Simons, Laura E. TI The Longitudinal Impact of Parent Distress and Behavior on Functional Outcomes Among Youth With Chronic Pain SO JOURNAL OF PAIN LA English DT Article DE Pediatrics; fear avoidance; pain catastrophizing; parenting; child ID QUALITY-OF-LIFE; COMMITMENT THERAPY ACT; PEDIATRIC CHRONIC PAIN; RANDOMIZED CONTROLLED-TRIAL; FEAR-AVOIDANCE MODEL; GENERIC CORE SCALES; CHILDS PAIN; PRELIMINARY VALIDATION; EMOTIONAL DISTRESS; POSTSURGICAL PAIN AB Accumulating evidence supports the concurrent association between parent distress and behavior and child functioning in the context of chronic pain, with existing longitudinal studies limited to a pediatric surgical context that identify parent catastrophizing as influential. In this study, we examined how parent factors assessed at a multidisciplinary pediatric pain clinic evaluation affect child psychological and functional outcomes over time. A cohort of 195 patients with chronic pain (ages 8-17 years) and their parents who presented for a multidisciplinary evaluation completed measures at baseline and at 4-month follow-up. Patients completed measures of pain catastrophizing, pain-related fear and avoidance, generalized anxiety, depressive symptoms, and functional disability. Parents completed measures of pain catastrophizing, pain-related fear and avoidance, and protective responses to child pain. Parent-reported child school functioning was also collected. Parent distress and behavior was concurrently associated with child distress and functioning at evaluation. After controlling for baseline child functioning, baseline parent avoidance and protective behavior emerged as significant predictors of child functioning at 4-month follow-up. Parent distress and behavior influence child distress and functioning over time and these findings identify key parent domains to target in the context of a child's pain treatment. Perspective: Parent behavior, specifically avoidance and protective responses, influence child distress and functioning over time. Child pain treatment interventions should include influential parent factors to ensure successful outcomes. (C) 2016 by the American Pain Society C1 [Chow, Erika T.; Simons, Laura E.] Boston Childrens Hosp, Div Pain Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02215 USA. [Chow, Erika T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Otis, John D.] VA Boston Healthcare Syst, Div Res, Boston, MA USA. [Otis, John D.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Otis, John D.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Simons, Laura E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Simons, Laura E.] Boston Childrens Hosp, PAIN Grp, Boston, MA 02215 USA. [Simons, Laura E.] Ctr Pain & Brain, Boston, MA USA. RP Simons, LE (reprint author), Boston Childrens Hosp, 21 Autumn St, Boston, MA 02215 USA. EM laura.simons@childrens.harvard.edu OI Simons, Laura/0000-0002-3395-9483 FU K23 award [HD067202]; Harvard Catalyst Clinical and Translational Research Center (NCATS) [8ULTR000170]; Sara Page Mayo Endowment for Pediatric Pain Research and Treatment; Department of Anesthesiology, Perioperative and Pain Medicine at Boston Children's Hospital FX This investigation was supported by a K23 award (HD067202), the Harvard Catalyst Clinical and Translational Research Center (NCATS grant #8ULTR000170), the Sara Page Mayo Endowment for Pediatric Pain Research and Treatment, and the Department of Anesthesiology, Perioperative and Pain Medicine at Boston Children's Hospital. No conflicts of interest exist for any of the authors. NR 51 TC 4 Z9 4 U1 4 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUN PY 2016 VL 17 IS 6 BP 729 EP 738 DI 10.1016/j.jpain.2016.02.014 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO2RQ UT WOS:000377628000010 PM 26993960 ER PT J AU Nyborn, JA Olcese, M Nickerson, T Mack, JW AF Nyborn, Justin A. Olcese, Maura Nickerson, Taylor Mack, Jennifer W. TI "Don't Try to Cover the Sky with Your Hands": Parents' Experiences with Prognosis Communication About Their Children with Advanced Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID HOPE; PREFERENCES; DISCLOSURE; CARE; INFORMATION; ONCOLOGY; IMPACT AB Background: Physicians worry that disclosure of prognostic information can be distressing and deprive families of hope. Retrospective studies have shown that prognostic disclosure does not abrogate hope, but prospective data are lacking. Objective: The study objective was to prospectively evaluate responses to prognosis communication among parents of children with advanced cancer. Design: For this qualitative study we audiotaped conversations between clinicians and parents of children with newly relapsed or refractory cancer, and then interviewed parents about experiences with prognosis communication. Parents were asked to reflect on physician statements about prognosis. Setting/subjects: Subjects were 32 pairs of parents and clinicians of children with relapsed or refractory cancer treated at Dana-Farber/Boston Children's Center for Cancer and Blood Disorders, Boston, Massachusetts. Results: Prognosis was discussed in 28/32 conversations (88%). Although most parents (N=22, 69%) found prognostic information upsetting, most also valued honest communication about prognosis (N=22, 69%.) Parents noted that frank disclosure fostered hope by relieving uncertainty and allowing them to make the best possible decisions for their children. Excessive optimism or a lack of information, in contrast, was sometimes experienced as a threat to hope and the parent-clinician relationship. A minority of parents were upset by clinician communication about prognosis (N=4, 12%), but most did not consider the clinician responsible for their distress. Rather, parents attributed distress to the difficult situation. Conclusions: Many parents consider prognosis communication to be both difficult and necessary. While upsetting, prognostic information engenders hope by helping parents feel prepared to do their best for their children in the difficult days to come. C1 [Nyborn, Justin A.; Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Nyborn, Justin A.; Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02115 USA. [Olcese, Maura] Oregon Hlth & Sci Univ, Portland, OR USA. [Nickerson, Taylor] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA. RP Nyborn, JA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM justin.nyborn@gmail.com FU National Palliative Care Research Center; Hyundai Hope on Wheels Grant FX This study was funded by the National Palliative Care Research Center, and by a Hyundai Hope on Wheels Grant. NR 19 TC 2 Z9 2 U1 2 U2 2 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 JUN PY 2016 VL 19 IS 6 BP 626 EP 631 DI 10.1089/jpm.2015.0472 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO8OY UT WOS:000378044100011 PM 27115314 ER PT J AU Lakin, JR Isaacs, E Sullivan, E Harris, HA McMahan, RD Sudore, RL AF Lakin, Joshua R. Isaacs, Eric Sullivan, Erin Harris, Heather A. McMahan, Ryan D. Sudore, Rebecca L. TI Emergency Physicians' Experience with Advance Care Planning Documentation in the Electronic Medical Record: Useful, Needed, and Elusive SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ELDERLY-PATIENTS; DECISION-MAKING; END; DIRECTIVES; FAILURE; DEATH AB Objective: For patients' preferences to be honored, emergency department (ED) physicians must be able to find and use advance care planning (ACP) information in the electronic medical record (EMR). ED physicians' experiences with ACP EMR documentation and their documentation needs are unknown. Methods: We surveyed 70 ED physicians (81% response rate) from a tertiary and county ED. Our primary outcome was confidence finding and using ACP EMR documentation (percentage reporting very/extremely on a five-point Likert scale). Secondary outcomes included frequency of use and perceived usefulness of types of ACP documentation. Suggestions for improvement were analyzed using thematic content analysis. Results: Participants' mean age was 36 years (+/- 9) and 54% were women. Thirty-one percent reported being very/extremely confident they could find ACP EMR documentation, and 55% felt very/extremely confident they could use it to care for patients. Yet 74% needed it >= 1 time/week and 43% >= 5 times/week. Participants reported code status orders (90%), Physician Orders for Life Sustaining Treatment (POLST) (86%), and durable power of attorney for health care (78%) as very/extremely useful, followed by values statements (31%), oral directives (34%), and living wills (37%). ED physicians wanted highly visible ACP information, "on the main screen." Conclusions: EMR systems are not optimized to provide critical ACP information to ED physicians who lack confidence finding or using ACP EMR documentation to care for patients. Dedicated ACP information on the EMR home screen and tailored training may be needed to help ED providers find, use, and discuss ACP documentation to provide care aligned with patients' goals. C1 [Lakin, Joshua R.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Adult Palliat Care, Boston, MA 02115 USA. [Lakin, Joshua R.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Isaacs, Eric; Sullivan, Erin] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. [Harris, Heather A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [McMahan, Ryan D.; Sudore, Rebecca L.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Harris, Heather A.] San Francisco Gen Hosp, Support & Palliat Care Serv, Div Hosp Med, San Francisco, CA 94110 USA. [McMahan, Ryan D.; Sudore, Rebecca L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Lakin, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D-216A, Boston, MA 02215 USA. EM jlakin@partners.org NR 10 TC 0 Z9 0 U1 3 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2016 VL 19 IS 6 BP 632 EP 638 DI 10.1089/jpm.2015.0486 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DO8OY UT WOS:000378044100012 PM 27203483 ER PT J AU Nobles, CJ Valentine, SE Borba, CPC Gerber, MW Shtasel, DL Marques, L AF Nobles, Carrie J. Valentine, Sarah E. Borba, Christina P. C. Gerber, Monica W. Shtasel, Derri L. Marques, Luana TI Black-white disparities in the association between posttraumatic stress disorder and chronic illness SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Chronic illness; Health disparities; Heart disease; Posttraumatic stress disorder; Race/ethnicity; Type 2 diabetes ID NATIONAL COMORBIDITY SURVEY; CORONARY-HEART-DISEASE; NUTRITION EXAMINATION SURVEY; DIAGNOSTIC INTERVIEW CIDI; UNITED-STATES; SURVEY REPLICATION; CARDIOVASCULAR EVENTS; DEPRESSIVE SYMPTOMS; REGRESSION APPROACH; TRAUMATIC STRESS AB Objective: Non-Latino blacks experience a higher proportion of chronic illness and associated disabilities than non-Latino whites. Posttraumatic stress disorder (PTSD) is associated with a greater risk of chronic illness, although few studies have investigated whether the interaction of PTSD with racial disparities may lead to a greater risk of chronic illness among blacks with PTSD than among whites with PTSD. Methods: We evaluated data from the population-based National Survey of American Life and the National Comorbidity Survey Replication to investigate the association between race, lifetime PTSD and self-reported chronic illness. Weighted linear and Poisson regression models assessed differences in the magnitude of association between PTSD and chronic illness by race on both the additive and multiplicative scales. Results: The magnitude of the association between lifetime PTSD and diabetes was greater among blacks (RD 0.07, 95% CI 0.02, 0.11; RR 1.9, 95% CI 1.4, 2.5) than whites (RD 0.004, 95% CI -0.02, 0.03; RR 1.2, 95% CI 0.7, 1.9) on the additive (p = 0.017) scale. The magnitude of the association between lifetime PTSD and heart disease was greater among blacks (RD 0.09, 95% CI 0.05, 0.13) than whites (RD 0.04, 95% CI 0.01, 0.07) on the additive scale at a level approaching significance (p = 0.051). Conclusion: A lifetime history of PTSD was associated with a significantly greater risk of diabetes among blacks as compared to whites. These findings suggest that continuous exposure to racial inequalities may be associated with a greater risk of PTSD-related health sequela. (c) 2016 Elsevier Inc. All rights reserved. C1 [Nobles, Carrie J.; Valentine, Sarah E.; Borba, Christina P. C.; Gerber, Monica W.; Shtasel, Derri L.; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, 70 Everett Ave Suite 516, Chelsea, MA 02150 USA. [Nobles, Carrie J.; Valentine, Sarah E.; Borba, Christina P. C.; Shtasel, Derri L.; Marques, Luana] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nobles, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 70 Everett Ave Suite 516, Chelsea, MA 02150 USA. EM cnobles@mgh.harvard.edu OI Nobles, Carrie/0000-0002-2182-8486 FU National Institute of Mental Health [NIMH K23 MH096029-01A1] FX Time for this manuscript was funded in part by a grant from the National Institute of Mental Health (NIMH K23 MH096029-01A1) awarded to Dr. Luana Marques. NR 68 TC 0 Z9 0 U1 6 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2016 VL 85 BP 19 EP 25 DI 10.1016/j.jpsychores.2016.03.126 PG 7 WC Psychiatry SC Psychiatry GA DO2RI UT WOS:000377627200004 PM 27212665 ER PT J AU Denlinger, CS Ligibel, JA Are, M Baker, KS Broderick, G Demark-Wahnefried, W Friedman, DL Goldman, M Jones, LW King, A Ku, GH Kvale, E Langbaum, TS McCabe, MS Melisko, M Montoya, JG Mooney, K Morgan, MA Moslehi, JJ O'Connor, T Overholser, L Paskett, ED Peppercorn, J Rodriguez, MA Ruddy, KJ Sanft, T Silverman, P Smith, S Syrjala, KL Urba, SG Wakabayashi, MT Zee, P McMillian, NR Freedman-Cass, DA AF Denlinger, Crystal S. Ligibel, Jennifer A. Are, Madhuri Baker, K. Scott Broderick, Gregory Demark-Wahnefried, Wendy Friedman, Debra L. Goldman, Mindy Jones, Lee W. King, Allison Ku, Grace H. Kvale, Elizabeth Langbaum, Terry S. McCabe, Mary S. Melisko, Michelle Montoya, Jose G. Mooney, Kathi Morgan, Mary Ann Moslehi, Javid J. O'Connor, Tracey Overholser, Linda Paskett, Electra D. Peppercorn, Jeffrey Rodriguez, M. Alma Ruddy, Kathryn J. Sanft, Tara Silverman, Paula Smith, Sophia Syrjala, Karen L. Urba, Susan G. Wakabayashi, Mark T. Zee, Phyllis McMillian, Nicole R. Freedman-Cass, Deborah A. TI NCCN Guidelines (R) Insights Survivorship, Version 1.2016 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID NON-HODGKINS-LYMPHOMA; LONG-TERM SURVIVORS; QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; SUPPORTIVE CARE NEEDS; CANCER SURVIVORS; DISTRESS THERMOMETER; PSYCHOLOGICAL DISTRESS; ADULT SURVIVORS; PSYCHOSOCIAL OUTCOMES AB The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment. They are intended to aid health care professionals who work with survivors of adult-onset cancer in the posttreatment period, including those in general oncology, specialty cancer survivor clinics, and primary care practices. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors. This article summarizes the NCCN Survivorship panel's discussions for the 2016 update of the guidelines regarding the management of anxiety, depression, posttraumatic stress disorder-related symptoms, and emotional distress in survivors. C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Ligibel, Jennifer A.] Dana Farber Brigham & Womens Canc Ctr, Milford, MA 01757 USA. [Are, Madhuri] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Baker, K. Scott; Syrjala, Karen L.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Broderick, Gregory; Ruddy, Kathryn J.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Demark-Wahnefried, Wendy; Kvale, Elizabeth] Univ Alabama Birmingham, Comprehens Canc Ctr, Birmingham, AL USA. [Friedman, Debra L.; Moslehi, Javid J.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Goldman, Mindy; Melisko, Michelle] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Jones, Lee W.; McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [King, Allison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Ku, Grace H.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Langbaum, Terry S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Montoya, Jose G.] Stanford Canc Inst, Palo Alto, CA USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Morgan, Mary Ann] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY USA. [Overholser, Linda] Univ Colorado, Canc Ctr, Boulder, CO 80309 USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Paskett, Electra D.] Solove Res Inst, Columbus, OH USA. [Peppercorn, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rodriguez, M. Alma] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Sanft, Tara] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Silverman, Paula] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Silverman, Paula] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [Smith, Sophia] Duke Canc Inst, Durham, NC USA. [Urba, Susan G.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA. [Wakabayashi, Mark T.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Zee, Phyllis] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [McMillian, Nicole R.; Freedman-Cass, Deborah A.] Natl Comprehens Canc Network, Ft Washington, MD USA. RP Denlinger, CS (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. FU Merck Co., Inc.; GlaxoSmithKline; Pfizer Inc. FX Electra D. Paskett, PhD, Panel Member, has disclosed that she has equity interest/stock options from Pfizer Inc, and receives grant/research support from Merck & Co., Inc.; Jeffrey Peppercorn, MD, MPH, Panel Member, has disclosed that he has equity interest/stock options and receives salary from GlaxoSmithKline, and receives grant/research support from Pfizer Inc. NR 50 TC 2 Z9 2 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2016 VL 14 IS 6 BP 715 EP 724 PG 10 WC Oncology SC Oncology GA DO3OE UT WOS:000377690100004 PM 27283164 ER PT J AU Redig, AJ Janne, PA AF Redig, Amanda J. Janne, Pasi A. TI No Target Left Behind: Improving Therapeutic Options for ERBB2-Mutant Non-Small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID HER2 KINASE DOMAIN; PHASE-II; MUTATION; TUMORS; ADENOCARCINOMA; CHEMOTHERAPY; COMBINATION; MUTANT; EGFR C1 [Redig, Amanda J.; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Redig, Amanda J.; Janne, Pasi A.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Redig, Amanda J.; Janne, Pasi A.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Janne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02215 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,LC 4118, Boston, MA 02215 USA. EM Pasi_Janne@dfci.harvard.edu NR 14 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2016 VL 11 IS 6 BP 784 EP 786 DI 10.1016/j.jtho.2016.04.009 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DO2WM UT WOS:000377641700001 PM 27211578 ER PT J AU Ma, XL Le Teuff, G Lacas, B Tsao, MS Graziano, S Pignon, JP Douillard, JY Le Chevalier, T Seymour, L Filipits, M Pirker, R Janne, PA Shepherd, FA Brambilla, E Soria, JC Hainaut, P AF Ma, Xiaoli Le Teuff, Gwenael Lacas, Benjamin Tsao, Ming Sound Graziano, Stephen Pignon, Jean-Pierre Douillard, Jean-Yves Le Chevalier, Thierry Seymour, Lesley Filipits, Martin Pirker, Robert Janne, Pasi A. Shepherd, Frances A. Brambilla, Elisabeth Soria, Jean-Charles Hainaut, Pierre CA LACE-Bio Collaborative Grp TI Prognostic and Predictive Effect of TP53 Mutations in Patients with Non-Small Cell Lung Cancer from Adjuvant Cisplatin-Based Therapy Randomized Trials: A LACE-Bio Pooled Analysis SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE TP53 mutations; Lung cancer; Prognostic; Predictive ID VINORELBINE PLUS CISPLATIN; MUTANT P53; TOBACCO-SMOKE; SOMATIC MUTATIONS; DNA-DAMAGE; CHEMOTHERAPY; PATTERNS; TISSUE; GENES; RAS AB Introduction: Tumor protein p53 gene (TP53) mutations are common in stage I through III non-small cell lung cancer, but clinical trials have shown inconsistent results regarding their relationship to the effects of adjuvant therapy. The objective is to clarify their putative prognostic and predictive effects. Methods: A pooled analysis of TP53 mutations (exons 5-8) was conducted in four randomized trials (the International Adjuvant Lung Cancer Trial, J BRonchus 10, Cancer and Leukemia Group B-9633, and Adjuvant Navelbine International Trialist Association trial) of platinum-based adjuvant chemotherapy (ACT) versus observation (OBS). Hazard ratios (HRs) and 95% confidence intervals (CIs) of mutant versus wild-type (WT) TP53 for overall survival (OS) and disease-free survival (DFS) were estimated using a multi variable Cox model stratified on trial and adjusted on sex, age, and clinicopathological variables. Predictive value was evaluated with an interaction between treatment and TP53. Results: A total of 1209 patients (median follow-up 5.5 years) were included. There were 573 deaths (47%) and 653 DFS events (54%). Mutations (434 [36%]) had no prognostic effect (OBS HROS = 0.99, 95% CI: 0.77-1.28, p = 0.95; HRDFS = 0.99, 95% CI: 0.78-1.25, p = 0.92) but were marginally predictive of benefit from ACT for OS (test for interaction: OS, p = 0.06; DFS, p = 0.11). Patients with WT TP53 had a tendency toward better outcomes with ACT than did those in the OBS group (HROS = 0.77, 95% CI: 0.62-0.95, p = 0.02; HRDFS = 0.75, 95% CI: 0.62-0.92, p = 0.005). In the ACT arm, a deleterious effect of mutant versus WT TP53 was observed (HROS = 1.40, 950/6 CI: 1.10-1.78, p = 0.006; HRDFS = 1.31, 95% CI: 1.04-1.64, p = 0.02). Conclusions: TP53 mutation had no prognostic effect but was marginally predictive for survival from ACT. In patients who received ACT, TP53 mutation tended to be associated with shorter survival than wild-type TP53. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Ma, Xiaoli; Hainaut, Pierre] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. [Ma, Xiaoli] Jinan Cent Hosp, Cent Lab, Jinan, Peoples R China. [Le Teuff, Gwenael; Lacas, Benjamin; Pignon, Jean-Pierre] Gustave Roussy, Dept Biostat, Paris, France. [Le Teuff, Gwenael; Lacas, Benjamin; Pignon, Jean-Pierre] Paris Sud & Paris Saclay Univ, CESP, INSERM, U1018, Villejuif, France. [Le Teuff, Gwenael; Lacas, Benjamin; Pignon, Jean-Pierre] Ligue Canc, Paris, France. [Tsao, Ming Sound] Univ Toronto, Dept Pathol, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON, Canada. [Graziano, Stephen] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. [Douillard, Jean-Yves; Le Chevalier, Thierry] Inst Cancerol Ouest, Dept Med Oncol, R Gauducheau, St Herblain, France. [Seymour, Lesley] Queens Univ, Natl Canc Inst Canada Clin Trials Grp, Kingston, ON, Canada. [Filipits, Martin] Med Univ Vienna, Inst Canc Res, Vienna, Austria. [Pirker, Robert] Med Univ Vienna, Dept Med 1, Vienna, Austria. [Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Janne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. [Shepherd, Frances A.; Hainaut, Pierre] Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Brambilla, Elisabeth] Univ Grenoble Alpes, Inst Albert Bonniot, INSERM, U1209,CNRS 5309, Grenoble, France. [Brambilla, Elisabeth; Hainaut, Pierre] CHU Grenoble, Dept Pathol, F-38043 Grenoble, France. [Soria, Jean-Charles] Gustave Roussy, Dept Med, Paris, France. [Hainaut, Pierre] Int Prevent Res Inst, Lyon, France. RP Hainaut, P (reprint author), Univ Grenoble Alpes, Inst Albert Bonniot, Inserm 1209, CNRS 5309, Allee Alpes, F-38700 La Tronche, France. EM pierre.hainaut@univ-grenoble-alpes.fr FU la Ligue Nationale Contre le Cancer (France); le Programme National d'Excellence Specialise Cancer du Poumon de l'Institut National du Cancer (France); National Cancer Institute (United States); Canadian Cancer Society Research Institute; Sanofi; Chair of Excellence in Translational Research of Canceropole Rhone Alpes/Grenoble Metro/Conseil General du Department de l'Isere, France FX This work was supported by la Ligue Nationale Contre le Cancer (France), le Programme National d'Excellence Specialise Cancer du Poumon de l'Institut National du Cancer (France), the National Cancer Institute (United States), the Canadian Cancer Society Research Institute, and an unrestricted grant from Sanofi. Dr. Hainaut is the recipient of the Chair of Excellence in Translational Research of Canceropole Rhone Alpes/Grenoble Metro/Conseil General du Department de l'Isere, France. NR 45 TC 4 Z9 4 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2016 VL 11 IS 6 BP 850 EP 861 DI 10.1016/j.jtho.2016.02.002 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DO2WM UT WOS:000377641700009 PM 26899019 ER PT J AU Chang, DC Williams, M Sangji, NF Britt, LD Rogers, SO AF Chang, David C. Williams, Mallory Sangji, Naveen F. Britt, L. D. Rogers, Selwyn O., Jr. TI Pattern of law enforcement-related injuries in the United States SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Law enforcement; civilian; pattern of injuries AB BACKGROUND The pattern of law enforcement-related injuries of police and civilians in the United States is unknown. METHODS Data were aggregated from the Federal Bureau of Investigations, the Bureau of Justice Statistics, the Centers for Disease Control (CDC) Web-based Injury Statistics Query and Reporting System, and the Nationwide Inpatient Sample (NIS) from 2003 to 2011. Law enforcement-related injuries in the CDC Web-based Injury Statistics Query and Reporting System and the NIS were identified using E-codes 970-976, which are meant to identify injuries inflicted by the police or other law-enforcing agents, including military on duty, in the course of arresting or attempting to arrest lawbreakers, suppressing disturbances, maintaining order, and other legal action. RESULTS The CDC reported a total of 715,118 nonfatal injuries and 3,156 fatal injuries from 2003 to 2011. In contrast, for the same period, the NIS identified a total of 3,958 patients, ranging from 348 to 572 per year. Among the injured, 1,548 (48.0%) were white, 866 were black (26.8%), and 605 were Hispanic (18.8%); 1,011 patients (25.5%) were injured by firearms, while 2,304 (58.2%) experienced blows or manhandling. Firearm-injured hospitalized patients are more likely to be male, black or Hispanics, and in the age group of 18 years to 39 years. CONCLUSION The majority of law enforcement-related injuries are among white or black young men. Hispanic patients are more likely to be injured by a firearm than struck. When injured by firearm, white and black patients are more likely to die compared with Hispanic patients. Unfortunately, data about these injuries are scattered across multiple data systems. A uniform national system to aggregate these data sources is needed to better understand the scope of the problem, for both law enforcement personnel and civilians. LEVEL OF EVIDENCE Epidemiologic study, level III. C1 [Chang, David C.; Sangji, Naveen F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 403, Boston, MA 02114 USA. [Britt, L. D.] Eastern Virginia Med Sch, Dept Surg, Norfolk, VA 23501 USA. [Rogers, Selwyn O., Jr.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Williams, Mallory] Soto Cano Air Base, Dept Surg, Med Element, Comayagua, Honduras. RP Chang, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 403, Boston, MA 02114 USA. EM dchang8@mgh.harvard.edu NR 13 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JUN PY 2016 VL 80 IS 6 BP 870 EP 875 DI 10.1097/TA.0000000000001000 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA DO5MX UT WOS:000377828300006 PM 26886001 ER PT J AU Sista, AK Goldhaber, SZ Vedantham, S Kline, JA Kuo, WT Kahn, SR Kabrhel, C McLaughlin, VV White, SB Kim, NH Gray, M Simon, MA Benenati, JF Misra, S Sterling, KM Kee, ST Konstantinides, SV Jaff, MR Kearon, C AF Sista, Akhilesh K. Goldhaber, Samuel Z. Vedantham, Suresh Kline, Jeffrey A. Kuo, William T. Kahn, Susan R. Kabrhel, Christopher McLaughlin, Vallerie V. White, Sarah B. Kim, Nick H. Gray, Michael Simon, Marc A. Benenati, James F. Misra, Sanjay Sterling, Keith M. Kee, Stephen T. Konstantinides, Stavros V. Jaff, Michael R. Kearon, Clive TI Research Priorities in Submassive Pulmonary Embolism: Proceedings from a Multidisciplinary Research Consensus Panel SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; VENOUS THROMBOEMBOLISM; THROMBOLYTIC THERAPY; CONTROLLED-TRIAL; 6-MIN WALK; PEMB-QOL; METAANALYSIS; MULTICENTER; QUESTIONNAIRE C1 [Sista, Akhilesh K.] NYU, Langone Sch Med, Dept Radiol, Div Intervent Radiol, 660 First Ave,Room 318, New York, NY 10016 USA. [Goldhaber, Samuel Z.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Vedantham, Suresh] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Kline, Jeffrey A.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Kuo, William T.] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Kahn, Susan R.] McGill Univ, Dept Med, Jewish Gen Hosp, Ctr Clin Epidemiol, Montreal, PQ, Canada. [Kabrhel, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Jaff, Michael R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [McLaughlin, Vallerie V.] Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA. [White, Sarah B.] Med Coll Wisconsin, Dept Radiol, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA. [Kim, Nick H.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. [Gray, Michael] Pulm Hypertens Assoc, Silver Spring, MD USA. [Simon, Marc A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Benenati, James F.] Baptist Hosp Miami, Miami Cardiac & Vasc Inst, Dept Radiol, Miami, FL USA. [Misra, Sanjay] Mayo Clin, Dept Radiol, Minneapolis, MN USA. [Sterling, Keith M.] INOVA Alexandria Hosp, Cardiovascular & Intervent Associates, Dept Radiol, Alexandria, VA USA. [Kee, Stephen T.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. [Konstantinides, Stavros V.] Univ Med Ctr Mainz, Dept Med, Ctr Thrombosis & Hemostasis, Mainz, Germany. [Kearon, Clive] McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Sista, AK (reprint author), NYU, Langone Sch Med, Dept Radiol, Div Intervent Radiol, 660 First Ave,Room 318, New York, NY 10016 USA. EM asista@gmail.com OI Kabrhel, Christopher/0000-0002-8699-7176; Sista, Akhilesh/0000-0001-5582-796X FU SIR Foundation FX The authors thank the SIR Foundation and its staff for financially and organizationally supporting this Research Consensus Panel. NR 37 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2016 VL 27 IS 6 BP 787 EP 794 DI 10.1016/j.jvir.2016.03.035 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DO2QY UT WOS:000377626200001 PM 27287967 ER PT J AU Sheth, R Balesh, ER Zhang, YS Hirsch, JA Khademhosseini, A Oklu, R AF Sheth, Rahul Balesh, Elie R. Zhang, Yu Shrike Hirsch, Joshua A. Khademhosseini, Ali Oklu, Rahmi TI Three-Dimensional Printing: An Enabling Technology for IR SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review ID TISSUE ENGINEERING SCAFFOLDS; PROJECTION STEREOLITHOGRAPHY; BONE REGENERATION; LIVER-ABSCESS; MODELS; COMPLEX; FABRICATION; MICROFABRICATION; RECANALIZATION; ARCHITECTURES AB Rapid prototyping, also known as three-dimensional (3D) printing, is a recent technologic advancement with tremendous potential for advancing medical device design. A wide range of raw materials can be incorporated into complex 3D structures, including plastics, metals, biocompatible polymers, and even living cells. With its promise of highly customized, adaptable, and personalized device design at the point of care, 3D printing stands to revolutionize medical care. The present review summarizes the methods for 3D printing and their current and potential roles in medical device design, with an emphasis on their potential relevance to interventional radiology. C1 [Sheth, Rahul] Univ Texas Houston, MD Anderson Canc Ctr, Dept Intervent Radiol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Balesh, Elie R.] Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Div Neurointervent Radiol, Boston, MA 02114 USA. [Zhang, Yu Shrike; Khademhosseini, Ali; Oklu, Rahmi] Harvard Univ, Brigham & Womens Hosp, Sch Med, Biomat Innovat Res Ctr,Div Biomed Engn,Dept Med, Boston, MA 02115 USA. [Zhang, Yu Shrike; Khademhosseini, Ali] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Zhang, Yu Shrike; Khademhosseini, Ali] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Oklu, Rahmi] Mayo Clin, Div Intervent Radiol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. RP Oklu, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Biomat Innovat Res Ctr,Div Biomed Engn,Dept Med, Boston, MA 02115 USA.; Oklu, R (reprint author), Mayo Clin, Div Intervent Radiol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM oklu.rahmi@mayo.edu OI Khademhosseini, Ali/0000-0001-6322-8852; Oklu, Rahmi/0000-0003-4984-1778 NR 53 TC 2 Z9 2 U1 19 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2016 VL 27 IS 6 BP 859 EP 865 DI 10.1016/j.jvir.2016.02.029 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DO2QY UT WOS:000377626200011 PM 27117948 ER PT J AU Hsu, MC Weber, CN Mohammed, MA Gade, TP Hunt, S Nadolski, GJ Clark, TWI AF Hsu, Michael C. Weber, Charles N. Mohammed, Mustafa A. Gade, Terence P. Hunt, Stephen Nadolski, Gregory J. Clark, Timothy W. I. TI Thermal Changes during Rheolytic Mechanical Thrombectomy SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; PERCUTANEOUS THROMBOLYTIC DEVICE; VASCULAR INJURY; HSP90; THERMOTOLERANCE; EXPRESSION; MODEL; CD31 AB Purpose: To characterize thermal changes induced by rheolytic thrombectomy (RT) within an ex vivo venous model and evaluate resultant changes of endothelial and vessel wall injury. Materials and Methods: Patent human saphenous vein segments without thrombus were mounted in an ex vivo perfusion system with a temperature probe apposed to the adventitial surface. RT was performed over a guide wire to, facilitate device centering. Continuous RT was performed for 4 minutes with temperature recorded every 10 seconds. Pulsed RT was performed for eight cycles of 30 seconds followed by 10 seconds of deactivation. Mean temperature increase, maximum temperature (T-max), intimal/medial thickness, endothelial cell staining (CD31), and heat shock protein 90 (HSP90) expression were compared between untreated and RT-treated venous segments. Results: Continuous RT produced a mean 7.6 degrees C increase in temperature above baseline with mean T-max of 44.1 degrees C. Pulsed RT produced a mean 7.3 degrees C increase in temperature and mean T-max of 43.8 degrees C. Differences in mean temperature increase (P = .66) and T-max (P =.71) between the two groups were not statistically significant. RT-treated segments showed intima/media thinning (0.32 mm before RT and 0.18 mm after RT; P = .004) and reduction in intact endothelium (38.8% before RT and 13.8% after RT; P = .002). Staining for HSP90 showed a 3.1% increase in expression after RT (P = .31). Conclusions: RT in this venous model showed reproducible increases in vessel temperature and evidence of endothelial and vessel wall injury. Avoiding prolonged RT application to a focal vascular segment during clinical use may be beneficial. C1 [Hsu, Michael C.; Weber, Charles N.; Gade, Terence P.; Hunt, Stephen; Nadolski, Gregory J.; Clark, Timothy W. I.] Univ Penn, Perelman Sch Med, Sect Intervent Radiol, Philadelphia, PA 19104 USA. [Hsu, Michael C.; Weber, Charles N.; Gade, Terence P.; Hunt, Stephen; Nadolski, Gregory J.; Clark, Timothy W. I.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hsu, Michael C.; Weber, Charles N.; Mohammed, Mustafa A.; Gade, Terence P.; Hunt, Stephen; Nadolski, Gregory J.] Philadelphia Vet Affairs Med Ctr, Penn Image Guided Intervent Lab, Philadelphia, PA USA. RP Clark, TWI (reprint author), Penn Presbyterian Med Ctr, Sect Intervent Radiol, 51 North 39 St, Philadelphia, PA 19104 USA. EM timothy.clark@uphs.upenn.edu FU Guerbet LLC (Bloomington, Indiana); Velano Vascular (San Francisco, California); Teleflex (Morrisville, North Carolina); C.R. Bard, Inc (Murray Hill, New Jersey); Guerbet LLC; Teleflex; Merit Medical Systems, Inc (South Jordan, Utah) FX T.P.G. received grants from Guerbet LLC (Bloomington, Indiana) and Velano Vascular (San Francisco, California). G J N. received grants from Teleflex (Morrisville, North Carolina), C.R. Bard, Inc (Murray Hill, New Jersey), and Guerbet LLC and is a consultant for Teleflex. T W.I C. is a consultant for and receives personal fees from Teleflex and Merit Medical Systems, Inc (South Jordan, Utah). None of the other authors have identified a conflict of interest. NR 32 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2016 VL 27 IS 6 BP 905 EP 912 DI 10.1016/j.jvir.2016.02.008 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DO2QY UT WOS:000377626200019 PM 27103145 ER PT J AU Blosnich, JR Hanmer, J Yu, L Matthews, DD Kavalieratos, D AF Blosnich, John R. Hanmer, Janel Yu, Lan Matthews, Derrick D. Kavalieratos, Dio TI Health Care Use, Health Behaviors, and Medical Conditions Among Individuals in Same-Sex and Opposite-Sex Partnerships A Cross-Sectional Observational Analysis of the Medical Expenditures Panel Survey (MEPS), 2003-2011 SO MEDICAL CARE LA English DT Article DE sexual orientation; health disparities; health care utilization; minority health ID YOUNG-ADULTS; LIFE SURVEY; HETEROSEXUAL INDIVIDUALS; CARDIOVASCULAR-DISEASE; MENTAL-DISORDERS; UNITED-STATES; HELP-SEEKING; ORIENTATION; GAY; DISPARITIES AB Background: Prior research documents disparities between sexual minority and nonsexual minority individuals regarding health behaviors and health services utilization. However, little is known regarding differences in the prevalence of medical conditions. Objectives: To examine associations between sexual minority status and medical conditions. Research Design: We conducted multiple logistic regression analyses of the Medical Expenditure Panel Survey (2003-2011). We identified individuals who reported being partnered with an individual of the same sex, and constructed a matched cohort of individuals in opposite-sex partnerships. Subjects: A total of 494 individuals in same-sex partnerships and 494 individuals in opposite-sex partnerships. Measures: Measures of health risk (eg, smoking status), health services utilization (eg, physician office visits), and presence of 15 medical conditions (eg, cancer, diabetes, arthritis, HIV, alcohol disorders). Results: Same-sex partnered men had nearly 4 times the odds of reporting a mood disorder than did opposite-sex partnered men [ adjusted odds ratio (aOR) = 3.96; 95% confidence interval (CI), 1.85-8.48]. Compared with opposite-sex partnered women, samesex partnered women had greater odds of heart disease (aOR = 2.59; 95% CI, 1.19-5.62), diabetes (aOR = 2.75; 95% CI, 1.10-6.90), obesity (aOR = 1.92; 95% CI, 1.26-2.94), high cholesterol (aOR = 1.89; 95% CI, 1.03-3.50), and asthma (aOR = 1.90; 95% CI, 1.02-1.19). Even after adjusting for sociodemographics, health risk behaviors, and health conditions, individuals in same-sex partnerships had 67% increased odds of past-year emergency department utilization and 51% greater odds of Z3 physician visits in the last year compared with opposite-sex partnered individuals. Conclusions: A combination of individual-level, provider-level, and system-level approaches are needed to reduce disparities in medical conditions and health care utilization among sexual minority individuals. C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Hanmer, Janel; Yu, Lan; Kavalieratos, Dio] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Matthews, Derrick D.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM john.blosnich@va.gov FU Department of Veterans Affairs (VA) Office of Academic Affiliations; Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System; National Institute of Mental Health [T32MH094174]; National Institutes of Health [KL2 TR000146]; Agency for Healthcare Research and Quality [K12HS022989]; Junior Faculty Career Development Award from the National Palliative Care Research Center FX Supported by a postdoctoral fellowship to J.R.B. through the Department of Veterans Affairs (VA) Office of Academic Affiliations and the Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System. D.D.M. was supported by the National Institute of Mental Health Training Program to Address HIV-Related Health Disparities in MSM (T32MH094174). J.H. was supported by the National Institutes of Health through Grant Number KL2 TR000146. D.K. was supported by supported by K12HS022989 from the Agency for Healthcare Research and Quality, and a Junior Faculty Career Development Award from the National Palliative Care Research Center. NR 50 TC 0 Z9 0 U1 4 U2 8 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 JUN PY 2016 VL 54 IS 6 BP 547 EP 554 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UR UT WOS:000378060400002 PM 26974678 ER PT J AU Brewster, AL Cherlin, EJ Ndumele, CD Collins, D Burgess, JF Charns, MP Bradley, EH Curry, LA AF Brewster, Amanda L. Cherlin, Emily J. Ndumele, Chima D. Collins, Diane Burgess, James F., Jr. Charns, Martin P. Bradley, Elizabeth H. Curry, Leslie A. TI What Works in Readmissions Reduction How Hospitals Improve Performance SO MEDICAL CARE LA English DT Article DE readmissions; hospital management; quality improvement; organizational practices ID ACUTE MYOCARDIAL-INFARCTION; CARE TRANSITIONS INTERVENTION; STANDARDIZED MORTALITY-RATES; RANDOMIZED CONTROLLED-TRIAL; HEART-FAILURE READMISSIONS; HEALTH-SERVICES RESEARCH; QUALITY-OF-CARE; MEDICARE BENEFICIARIES; 30-DAY READMISSION; FOLLOW-UP AB Background: Hospitals across the United States are pursuing strategies to reduce avoidable readmissions but the evidence on how best to accomplish this goal is mixed, with no specific clinical practice shown to reduce readmissions consistently. Changes to hospital organizational practices, a key component of context, also may be critical to improving performance on readmissions, but this has not been studied. Objective: The aim of this study was to understand how high-performing hospitals improved risk-stratified readmission rates, and whether their changes to clinical practices and organizational practices differed from low-performing hospitals. Design: This was a qualitative study of 10 hospitals in which readmission rates had decreased (n = 7) or increased (n = 3). Participants: A total of 82 hospital staff drawn from hospitals that had participated in the State Action on Avoidable Readmissions quality improvement initiative. Results: High-performing hospitals were distinguished by several organizational practices that facilitated readmissions reduction, that is, collective habits of action or interpretation shared by organization members. First, high-performing hospitals reported focused efforts to improve collaboration across hospital departments. Second, they helped postacute providers improve care by sharing the hospital's clinical and quality improvement expertise and data. Third, high performers enthusiastically engaged in trial and error learning to reduce readmissions. Fourth, they emphasized that re-admissions represented bad outcomes for patients, de-emphasizing the role of financial penalties. Both high-performing and low-performing hospitals had implemented most clinical practice changes commonly recommended to reduce readmissions. Conclusions: Our findings highlight several organizational practices that hospitals may be able to use to enhance the effectiveness of their readmissions reduction efforts. C1 [Brewster, Amanda L.; Cherlin, Emily J.; Ndumele, Chima D.; Bradley, Elizabeth H.; Curry, Leslie A.] Yale Univ, Dept Hlth Policy & Management, Sch Publ Hlth, POB 208364, New Haven, CT 06520 USA. [Collins, Diane] Yale New Haven Med Ctr, 20 York St, New Haven, CT 06504 USA. [Burgess, James F., Jr.; Charns, Martin P.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Burgess, James F., Jr.; Charns, Martin P.] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA USA. RP Brewster, AL (reprint author), Yale Univ, Dept Hlth Policy & Management, Sch Publ Hlth, POB 208364, New Haven, CT 06520 USA. EM amanda.brewster@yale.edu FU Commonwealth Fund; Medicines Company through the Yale University FX Supported by The Commonwealth Fund, One East 75th Street, New York, NY 10021.; L.A.C. and E.H.B. report that they are recipients of a research grant from The Medicines Company through the Yale University to fund a different study. The remaining authors declare no conflict of interest. NR 51 TC 3 Z9 3 U1 9 U2 13 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 JUN PY 2016 VL 54 IS 6 BP 600 EP 607 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UR UT WOS:000378060400009 PM 27050446 ER PT J AU Elwy, AR Glickman, ME Bokhour, BG Dell, NS Mueller, NM Zhao, SB Osei-Bonsu, PE Rodrigues, S Coldwell, CM Ngo, TA Schlosser, J Vielhauer, MJ Pirraglia, PA Eisen, SV AF Elwy, A. Rani Glickman, Mark E. Bokhour, Barbara G. Dell, Natalie S. Mueller, Nora M. Zhao, Shibei Osei-Bonsu, Princess E. Rodrigues, Stephanie Coldwell, Craig M. Ngo, Tu A. Schlosser, James Vielhauer, Melanie J. Pirraglia, Paul A. Eisen, Susan V. TI Using Mixed Methods to Examine the Role of Veterans' Illness Perceptions on Depression Treatment Utilization and HEDIS Concordance SO MEDICAL CARE LA English DT Article DE mental health; mixed methods; illness perceptions; veterans; primary care; treatment-seeking ID PRIMARY-CARE PATIENTS; MENTAL-HEALTH-CARE; BEHAVIOR; BARRIERS; VALIDITY; SERVICES; BELIEFS; SEEKING; MODEL AB Background: Although depression screening occurs annually in the Department of Veterans Affairs (VA) primary care, many veterans may not be receiving guideline-concordant depression treatment. Objectives: To determine whether veterans' illness perceptions of depression may be serving as barriers to guideline-concordant treatment. Research Design: We used a prospective, observational design involving a mailed questionnaire and chart review data collection to assess depression treatment utilization and concordance with Healthcare Effectiveness Data and Information Set guidelines adopted by the VA. The Self-Regulation Model of Illness Behavior guided the study. Subjects: Veterans who screened positive for a new episode of depression at 3 VA primary care clinics in the US northeast. Measures: The Illness Perceptions Questionnaire-Revised, measuring patients' perceptions of their symptoms, cause, timeline, consequences, cure or controllability, and coherence of depression and its symptoms, was our primary measure to calculate veterans' illness perceptions. Treatment utilization was assessed 3 months after the positive depression screen through chart review. Healthcare Effectiveness Data and Information Set (HEDIS) guidelineconcordant treatment was determined according to a checklist created for the study. Results: A total of 839 veterans screened positive for a new episode of depression from May 2009-June 2011;275 (32.8%) completed the survey. Ninety-two (33.9%) received HEDIS guideline-concordant depression treatment. Veterans' illness perceptions of their symptoms, cause, timeline, and controllability of depression predicted receiving guideline-concordant treatment. Conclusions: Many veterans are not receiving guideline-concordant treatment for depression. HEDIS guideline measures may not be assessing all aspects of quality depression care. Conversations about veterans' illness perceptions and their specific needs are encouraged to ensure that appropriate treatment is achieved. C1 [Elwy, A. Rani; Glickman, Mark E.; Bokhour, Barbara G.; Dell, Natalie S.; Mueller, Nora M.; Zhao, Shibei; Osei-Bonsu, Princess E.; Eisen, Susan V.] Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd 152, Bedford, MA 01730 USA. [Elwy, A. Rani; Glickman, Mark E.; Bokhour, Barbara G.; Eisen, Susan V.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Rodrigues, Stephanie] UMass Mem Med Ctr, Dept Psychiat, Univ Campus, Worcester, MA USA. [Coldwell, Craig M.] Boston Univ, Dept Psychiat, Sch Med, VA New England Healthcare Syst, Bedford, MA USA. [Ngo, Tu A.] Edith Nourse Rogers Mem VA Hosp, Psychol Serv, Bedford, MA USA. [Vielhauer, Melanie J.] VA Boston Healthcare Syst, Gen Mental Hlth Serv, Boston, MA USA. [Vielhauer, Melanie J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Pirraglia, Paul A.] Providence VA Med Ctr, Primary Care Serv, Boston, MA USA. RP Elwy, AR (reprint author), Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd 152, Bedford, MA 01730 USA. EM rani.elwy@va.gov FU Department of Veterans Affairs, Health Services Research and Development Service [IAC 07-087]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative FX This study was funded by the Department of Veterans Affairs, Health Services Research and Development Service (Grant IAC 07-087 to A.R.E.).; A.R.E. is an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative. The remaining authors declare no conflict of interest. NR 27 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 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUN PY 2016 VL 54 IS 6 BP E35 EP E42 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UR UT WOS:000378060400001 PM 24374425 ER PT J AU Boada-Romero, E Serramito-Gomez, I Sacristan, MP Boone, DL Xavier, RJ Pimentel-Muinos, FX AF Boada-Romero, Emilio Serramito-Gomez, Inmaculada Sacristan, Maria P. Boone, David L. Xavier, Ramnik J. Pimentel-Muinos, Felipe X. TI The T300A Crohn's disease risk polymorphism impairs function of the WD40 domain of ATG16L1 SO NATURE COMMUNICATIONS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; AUTOPHAGY GENE ATG16L1; SELECTIVE AUTOPHAGY; ISOLATION MEMBRANE; DENDRITIC CELLS; PROTEIN; SUSCEPTIBILITY; NOD2; VARIANT AB A coding polymorphism of human ATG16L1 (rs2241880; T300A) increases the risk of Crohn's disease and it has been shown to enhance susceptibility of ATG16L1 to caspase cleavage. Here we show that T300A also alters the ability of the C-terminal WD40-repeat domain of ATG16L1 to interact with an amino acid motif that recognizes this region. Such alteration impairs the unconventional autophagic activity of TMEM59, a transmembrane protein that contains the WD40 domain-binding motif, and disrupts its normal intracellular trafficking and its ability to engage ATG16L1 in response to bacterial infection. TMEM59-induced autophagy is blunted in cells expressing the fragments generated by caspase processing of the ATG16L1-T300A risk allele, whereas canonical autophagy remains unaffected. These results suggest that the T300A polymorphism alters the function of motif-containing molecules that engage ATG16L1 through the WD40 domain, either by influencing this interaction under non-stressful conditions or by inhibiting their downstream autophagic signalling after caspase-mediated cleavage. C1 [Boada-Romero, Emilio; Serramito-Gomez, Inmaculada; Sacristan, Maria P.; Pimentel-Muinos, Felipe X.] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Ctr Invest Canc, Campus Miguel de Unamuno, Salamanca 37007, Spain. [Boone, David L.] Indiana Univ Sch Med, Dept Microbiol, South Bend, IN 46617 USA. [Boone, David L.] Indiana Univ Sch Med, Dept Immunol, South Bend, IN 46617 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Pimentel-Muinos, FX (reprint author), Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Ctr Invest Canc, Campus Miguel de Unamuno, Salamanca 37007, Spain. EM fxp@usal.es FU Ministerio de Ciencia e Innovacion of the Spanish Government [SAF2011-23714]; Ministerio de Economia y Competitividad of the Spanish Government [SAF2014-53320-R]; Broad Medical Research Program at Crohn's and Colitis Foundation of America (CCFA) [IBD-0369]; Junta de Castilla y Leon local government (Department of Education) [CSI001A10-2, FIC016U14]; Junta de Castilla y Leon local government (Department of Health) [SAN11-FXP]; Fundacion Solorzano [FS/1-2009, FS/18-2014]; NIH [R01DK097485, P30DK043351, U19AI109725]; Helmsley Trust; FEDER programme of the European Union; FPU programme (Ministerio de Educacion, MEC, Spanish Government); Fundacion Moraza FX We thank members of the CIC for support. This work was funded by grants from the Ministerio de Ciencia e Innovacion (Ref. SAF2011-23714) and the Ministerio de Economia y Competitividad (Ref. SAF2014-53320-R) of the Spanish Government, the Broad Medical Research Program at Crohn's and Colitis Foundation of America (CCFA; Ref. IBD-0369), the Junta de Castilla y Leon local government (Department of Education (Refs. CSI001A10-2, FIC016U14) and Department of Health (Ref. SAN11-FXP)) and the Fundacion Solorzano (Refs. FS/1-2009 and FS/18-2014). R.J.X. is funded by the NIH (grants R01DK097485, P30DK043351 and U19AI109725) and the Helmsley Trust. Additional funding comes from the FEDER programme of the European Union. E.B.R. and I.S.G. are graduate students funded by predoctoral fellowships from the FPU programme (Ministerio de Educacion, MEC, Spanish Government) and the Fundacion Moraza, respectively. F.X.P. holds a tenured position at the CSIC. NR 65 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 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2016 VL 7 AR 11821 DI 10.1038/ncomms11821 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO6NW UT WOS:000377901400001 PM 27273576 ER PT J AU Chabon, JJ Simmons, AD Lovejoy, AF Esfahani, MS Newman, AM Haringsma, HJ Kurtz, DM Stehr, H Scherer, F Karlovich, CA Harding, TC Durkin, KA Otterson, GA Purcell, WT Camidge, DR Goldman, JW Sequist, LV Piotrowska, Z Wakelee, HA Neal, JW Alizadeh, AA Diehn, M AF Chabon, Jacob J. Simmons, Andrew D. Lovejoy, Alexander F. Esfahani, Mohammad S. Newman, Aaron M. Haringsma, Henry J. Kurtz, David M. Stehr, Henning Scherer, Florian Karlovich, Chris A. Harding, Thomas C. Durkin, Kathleen A. Otterson, Gregory A. Purcell, W. Thomas Camidge, D. Ross Goldman, Jonathan W. Sequist, Lecia V. Piotrowska, Zofia Wakelee, Heather A. Neal, Joel W. Alizadeh, Ash A. Diehn, Maximilian TI Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients SO NATURE COMMUNICATIONS LA English DT Article ID TYROSINE KINASE INHIBITORS; RECEPTOR GENE-MUTATIONS; ACQUIRED-RESISTANCE; NSCLC PATIENTS; MET AMPLIFICATION; KRAS MUTATIONS; INTRATUMOR HETEROGENEITY; GEFITINIB SENSITIVITY; COLORECTAL-CANCER; PLASMA DNA AB Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in similar to 33% of patients after osimertinib treatment, occurs in < 3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. C1 [Chabon, Jacob J.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Stehr, Henning; Alizadeh, Ash A.; Diehn, Maximilian] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. [Chabon, Jacob J.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Stehr, Henning; Scherer, Florian; Alizadeh, Ash A.; Diehn, Maximilian] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA. [Simmons, Andrew D.; Haringsma, Henry J.; Karlovich, Chris A.; Harding, Thomas C.] Clovis Oncol Inc, San Francisco, CA 94158 USA. [Kurtz, David M.; Scherer, Florian; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Kurtz, David M.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Durkin, Kathleen A.] Univ Calif Berkeley, Coll Chem, Mol Graph & Computat Facil, Berkeley, CA 94720 USA. [Otterson, Gregory A.] Ohio State Univ, Columbus, OH 43210 USA. [Purcell, W. Thomas; Camidge, D. Ross] Univ Colorado, Sch Med, Dept Med, Div Med Oncol, Aurora, CO 80045 USA. [Goldman, Jonathan W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sequist, Lecia V.; Piotrowska, Zofia] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sequist, Lecia V.; Piotrowska, Zofia] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alizadeh, Ash A.] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA. [Diehn, Maximilian] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Alizadeh, AA; Diehn, M (reprint author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.; Alizadeh, AA; Diehn, M (reprint author), Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA.; Alizadeh, AA (reprint author), Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA.; Alizadeh, AA (reprint author), Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA.; Diehn, M (reprint author), Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. EM arasha@stanford.edu; diehn@stanford.edu OI Newman, Aaron/0000-0002-1857-8172 FU National Science Foundation [DGE-114747]; Department of Defense; National Cancer Institute [R01CA188298]; US National Institutes of Health Director's New Innovator Award [1-DP2-CA186569]; Ludwig Institute for Cancer Research; Stanford Cancer Institute-Developmental Cancer Research Award; CRK Faculty Scholar Fund FX We thank Marileila Garcia for FISH analysis and Asuragen for NGS analysis of tumours collected from in vivo studies. We are grateful to the patients, investigators, and members of Clovis Oncology involved in these clinical studies. This work was supported with grants from the National Science Foundation (J.J.C.; DGE-114747), the Department of Defense (M.D., A.A.A. and A.M.N.), the National Cancer Institute (M.D., A.A.; R01CA188298), the US National Institutes of Health Director's New Innovator Award Program (M.D.; 1-DP2-CA186569), the Ludwig Institute for Cancer Research (M.D. and A.A.A.), a Stanford Cancer Institute-Developmental Cancer Research Award (M.D. and A.A.A.), and the CRK Faculty Scholar Fund (M.D.). NR 66 TC 26 Z9 27 U1 14 U2 21 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 JUN PY 2016 VL 7 AR 11815 DI 10.1038/ncomms11815 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DO8BN UT WOS:000378007200001 PM 27283993 ER PT J AU Wilson, MN Vila, PM Cohen, DS Carter, JM Lawlor, CM Davis, KS Raol, NP AF Wilson, Meghan N. Vila, Peter M. Cohen, David S. Carter, John M. Lawlor, Claire M. Davis, Kara S. Raol, Nikhila P. TI The Pursuit of Otolaryngology Subspecialty Fellowships SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE fellowship; residency ID LONG-RANGE TRENDS; NECK-SURGERY; RESIDENTS; PROLIFERATION; IMPACT; HEAD AB Objectives To examine otolaryngology resident interest in subspecialty fellowship training and factors affecting interest over time and over the course of residency training Study Design Cross-sectional study of anonymous online survey data. Setting Residents and fellows registered as members-in-training through the American Academy of Otolaryngology-Head and Neck Surgery. Subjects and Methods Data regarding fellowship interest and influencing factors, including demographics, were extracted from the Section for Residents and Fellows Annual Survey response database from 2008 to 2014. Results Over 6 years, there were 2422 resident and fellow responses to the survey. Senior residents showed a statistically significant decrease in fellowship interest compared with junior residents, with 79% of those in postgraduate year (PGY) 1, 73% in PGY-2 and PGY-3, and 64% in PGY-4 and PGY-5 planning to pursue subspecialty training (P < .0001). Educational debt, age, and intended practice setting significantly predicted interest in fellowship training. Sex was not predictive. The most important factors cited by residents in choosing a subspecialty were consistently type of surgical cases and nature of clinical problems. Conclusions In this study, interest in pursuing fellowship training decreased with increased residency training. This decision is multifactorial in nature and also influenced by age, educational debt, and intended practice setting. C1 [Wilson, Meghan N.] Louisiana State Univ, Dept Otolaryngol, Hlth Sci Ctr, 533 Bolivar St,Ste 566, New Orleans, LA 70112 USA. [Vila, Peter M.] Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. [Cohen, David S.] Wayne State Univ, Dept Otolaryngol, Detroit, MI 48201 USA. [Carter, John M.; Lawlor, Claire M.] Tulane Univ, Dept Otolaryngol, New Orleans, LA 70118 USA. [Davis, Kara S.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA USA. [Raol, Nikhila P.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Wilson, MN (reprint author), Louisiana State Univ, Dept Otolaryngol, Hlth Sci Ctr, 533 Bolivar St,Ste 566, New Orleans, LA 70112 USA. EM mnw326@gmail.com NR 17 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2016 VL 154 IS 6 BP 1027 EP 1033 DI 10.1177/0194599816639038 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DO5KY UT WOS:000377823200008 PM 27026739 ER PT J AU Moriarty, H Winter, L Robinson, K Piersol, CV Vause-Earland, T Iacovone, DB Newhart, B True, G Fishman, D Hodgson, N Gitlin, LN AF Moriarty, Helene Winter, Laraine Robinson, Keith Piersol, Catherine Verrier Vause-Earland, Tracey Iacovone, Delores Blazer Newhart, Brian True, Gala Fishman, Deborah Hodgson, Nancy Gitlin, Laura N. TI A Randomized Controlled Trial to Evaluate the Veterans' In-home Program for Military Veterans With Traumatic Brain Injury and Their Families: Report on Impact for Family Members SO PM&R LA English DT Article ID CAREGIVER BURDEN; NEUROPSYCHIATRIC SEQUELAE; SOCIAL SUPPORT; OLDER-ADULTS; HEALTH-CARE; INTERVENTION; REHABILITATION; DEPRESSION; INDIVIDUALS; DEMENTIA AB Background: Traumatic brain injury (TBI) creates many challenges for families as well as for patients. Few intervention studies have considered both the needs of the person with TBI and his or her family and included both in the intervention process. To address this gap, we designed an innovative intervention for veterans with TBI and families-the Veterans' In-home Program (VIP)-targeting veterans' environment, delivered in veterans' homes, and involving their families. Objectives: To determine whether the VIP is more effective than standard outpatient clinic care in improving family members' well-being in 3 domains (depressive symptoms, burden, and satisfaction) and to assess its acceptability to family members. Design: In this randomized controlled trial, 81 dyads (veteran/family member) were randomly assigned to VIP or an enhanced usual care control condition. Randomization occurred after the baseline interview. Follow-up interviews occurred 3-4 months after baseline, and the interviewer was blinded to group assignment. Setting: Interviews and intervention sessions were conducted in veterans' homes or by telephone. Participants: A total of 81 veterans with TBI recruited from a Veterans Affairs (VA) polytrauma program and a key family member for each participated. Of the 81 family members, 63 completed the follow-up interview. Intervention: The VIP, guided by the person-environment fit model, consisted of 6 home visits and 2 telephone calls delivered by occupational therapists over a 3- to 4-month period. Family members were invited to participate in the 6 home sessions. Main Outcome Measures: Family member well-being was operationally defined as depressive symptomatology, caregiver burden, and caregiver satisfaction 3- 4 months after baseline. Acceptability was operationally defined through 3 indicators. Results: Family members in the VIP showed significantly lower depressive symptom scores and lower burden scores when compared to controls at follow-up. Satisfaction with caregiving did not differ between groups. Family members' acceptance of the intervention was high. Conclusions: VIP represents the first evidence-based intervention that considers both the veteran with TBI and the family. VIP had a significant impact on family member well-being and thus addresses a large gap in previous research and services for families of veterans with TBI. C1 [Moriarty, Helene] Villanova Univ, Coll Nursing, 800 Lancaster Ave,Driscoll Hall, Villanova, PA 19085 USA. [Moriarty, Helene; Winter, Laraine; Fishman, Deborah] Corporal Michael J Crescenz Vet Affairs Med Ctr, Nursing Serv, Philadelphia, PA USA. [Winter, Laraine] Corporal Michael J Crescenz Vet Affairs Med Ctr, Philadelphia Res & Educ Fdn, Philadelphia, PA USA. [Robinson, Keith; Iacovone, Delores Blazer; Newhart, Brian] Corporal Michael J Crescenz Vet Affairs Med Ctr, Rehabil Med Serv, Polytrauma Network Site Vet Integrated Serv Netwo, Philadelphia, PA USA. [Robinson, Keith; True, Gala] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Piersol, Catherine Verrier; Vause-Earland, Tracey] Thomas Jefferson Univ, Jefferson Coll Hlth Profess, Philadelphia, PA 19107 USA. [True, Gala] Corporal Michael J Crescenz Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Hodgson, Nancy; Gitlin, Laura N.] Johns Hopkins Univ, Ctr Innovat Care Aging, Sch Nursing, Baltimore, MD USA. RP Moriarty, H (reprint author), Villanova Univ, Coll Nursing, 800 Lancaster Ave,Driscoll Hall, Villanova, PA 19085 USA.; Moriarty, H (reprint author), Corporal Michael J Crescenz Vet Affairs Med Ctr, Nursing Serv, Philadelphia, PA USA. EM helene.moriarty@villanova.edu FU Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health [R21 HD068857-01] FX The project described was supported by Award Number R21 HD068857-01 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health & Human Development or the National Institutes of Health. NR 90 TC 0 Z9 0 U1 9 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD JUN PY 2016 VL 8 IS 6 BP 495 EP 509 DI 10.1016/j.pmrj.2015.10.008 PG 15 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DO6OX UT WOS:000377904100001 PM 26514790 ER PT J AU Marino, C Child, B Krasinski, VC AF Marino, Casadi Khaki Child, Beckie Krasinski, Vanessa Campbell TI Sharing Experience Learned Firsthand (SELF): Self-Disclosure of Lived Experience in Mental Health Services and Supports SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE self-disclosure; stigma; peer-delivered services; recovery ID STIGMA; ILLNESS AB Objective: Self-disclosure of lived experiences with mental health challenges is a central method for challenging stigma and promoting empowerment. Individuals are encouraged to share their stories yet little is known about the process of self-disclosure in this context. This article presents the results of an investigation of the role of lived experience in professional training and work. Method: A mixed methods design was used in a sequential exploratory manner. A purposive sample of 35 individuals participated in interviews and focus groups. Based on their reports and a literature review, an anonymous online survey (N = 117) was developed and distributed through consumer networks and the SAMHSA funded Consumer Technical Assistance Centers. The qualitative data was subjected to thematic analysis. The survey data were statistically analyzed for differences in levels of disclosure and factors regarding risks, benefits, and guidance regarding self-disclosure. Results: Participants valued their lived experience as a resource through which they could assist others and service delivery. Lived experience was foundational to building relationships with individuals in recovery. Disclosure was dependent on social context and perceptions of safety. Individuals expressed concerns regarding exclusion and discrimination. Conclusions and Implications for Practice: Project participants maintained that their lived experience was their greatest strengths in helping others. At the same time, decisions about disclosure were made in complex social contexts featuring power differentials. Sharing lived experience is essential to peer-delivered services and further exploration is needed to support service development. C1 [Marino, Casadi Khaki; Child, Beckie] Portland State Univ, Sch Social Work, POB 751, Portland, OR 97202 USA. [Krasinski, Vanessa Campbell] Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, Boston, MA 02114 USA. RP Marino, C (reprint author), Portland State Univ, Sch Social Work, POB 751, Portland, OR 97202 USA. EM casadi@pdx.edu FU Bringing Recovery Supports to Scale Technical Assistance Center Strategy (BRSS TACS) Peer-Run Organization/Recovery Community Organization Award FX The SELF project was funded by Bringing Recovery Supports to Scale Technical Assistance Center Strategy (BRSS TACS) Peer-Run Organization/Recovery Community Organization Award. Any opinions expressed are those of the authors and do not represent those of BRSS TACS. We thank PhD candidates Timothy Kelly and Stephania Hayes for their contributions to the SELF project. NR 21 TC 0 Z9 0 U1 6 U2 11 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X EI 1559-3126 J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD JUN PY 2016 VL 39 IS 2 BP 154 EP 160 DI 10.1037/prj0000171 PG 7 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA DO2TS UT WOS:000377633600010 PM 26653777 ER PT J AU Gao, N Dolce, J Rio, J Heitzmann, C Loving, S AF Gao, Ni Dolce, Joni Rio, John Heitzmann, Carma Loving, Samantha TI In-Vivo Job Development Training Among Peer Providers of Homeless Veterans Supported Employment Programs SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE Department of Veterans Affairs; homeless veterans; supported employment; in vivo training; job development AB Topic: This column describes a goal-oriented, time-limited in vivo coaching/training approach for skills building among peer veterans vocational rehabilitation specialists of the Homeless Veteran Supported Employment Program (HVSEP). Purpose: Planning, implementing, and evaluating the training approach for peer providers was intended, ultimately, to support veterans in their goal of returning to community competitive employment. Sources Used: The description draws from the training experience that aimed to improve the ability of peer providers to increase both rates of employment and wages of the homeless veterans using their services. Conclusions and Implications for Practice: Training peers using an in vivo training approach provided a unique opportunity for the veterans to improve their job development skills with a focus to support employment outcomes for the service users. Peers who received training also expressed that learning skills through an in vivo training approach was more engaging than typical classroom trainings. C1 [Gao, Ni; Dolce, Joni] Rutgers State Univ, Dept Psychiat Rehabil & Counseling Profess, Stratford, NJ USA. [Rio, John] Advocates Human Potential, Albany, NY USA. [Heitzmann, Carma] US Dept Vet Affairs, Menlo Pk, CA USA. [Loving, Samantha] US Dept Vet Affairs, Richmond, VA USA. RP Gao, N (reprint author), Rutgers State Univ, Dept Psychiat Rehabil & Counseling Profess, Stratford, NJ USA. EM gaoni@rutgers.edu NR 9 TC 0 Z9 0 U1 3 U2 4 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X EI 1559-3126 J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD JUN PY 2016 VL 39 IS 2 BP 191 EP 192 DI 10.1037/prj0000196 PG 2 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA DO2TS UT WOS:000377633600017 PM 27281042 ER PT J AU Stanley, B Chaudhury, SR Chesin, M Pontoski, K Bush, AM Knox, KL Brown, GK AF Stanley, Barbara Chaudhury, Sadia R. Chesin, Megan Pontoski, Kristin Bush, Ashley Mahler Knox, Kerry L. Brown, Gregory K. TI An Emergency Department Intervention and Follow-Up to Reduce Suicide Risk in the VA: Acceptability and Effectiveness SO PSYCHIATRIC SERVICES LA English DT Article ID VETERANS; PREVENTION AB Objective: Emergency departments (EDs) are often the primary contact point for suicidal individuals. The post-ED visit period is a high suicide risk time. To address the need for support during this time, a novel intervention was implemented in five Department of Veterans Affairs medical center EDs. The intervention combined the Safety Planning Intervention (SPI) with structured follow-up and monitoring (SFU) by telephone for suicidal individuals who did not require hospitalization. This study assessed the intervention's acceptability and perceived usefulness. Methods: A selected sample of 100 intervention participants completed a semistructured interview consisting of open-ended questions about the intervention's acceptability, usefulness, and helpfulness. Satisfaction with the SPI and SFU was separately evaluated. Results: Nearly all participants found the SAFE VET intervention to be acceptable, reporting that it was helpful in preventing further suicidal behavior and fostering treatment engagement. Conclusions: The SAFE VET intervention showed promise as an ED intervention for suicidal patients. C1 [Stanley, Barbara; Chaudhury, Sadia R.] Columbia Univ, Dept Psychiat, New York, NY USA. [Stanley, Barbara; Chaudhury, Sadia R.; Chesin, Megan] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Chesin, Megan] William Paterson Univ, Dept Psychol, Wayne, NJ USA. [Pontoski, Kristin; Bush, Ashley Mahler; Brown, Gregory K.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Brown, Gregory K.] US Dept Vet Affairs, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Knox, Kerry L.] Univ Rochester, Dept Psychiat, Rochester, NY USA. RP Stanley, B (reprint author), Columbia Univ, Dept Psychiat, New York, NY USA. EM bhs2@cumc.columbia.edu FU Mental Health Services and Quality Enhancement Research Initiative, U.S. Department of Veterans Affairs; VISN 2 Center of Excellence for Suicide Prevention FX The SAFE VET project was supported by the Mental Health Services and Quality Enhancement Research Initiative, U.S. Department of Veterans Affairs, and the VISN 2 Center of Excellence for Suicide Prevention. Ira Katz, M.D., Ph.D., and Jan Kemp, Ph.D., provided valuable insight into the project design. Coordination of the SAFE VET project was provided by site leaders Lisa Brenner, Ph.D., Joan Chips, L.C.S.W., Joshua Hooberman, Ph.D., Christine Jackson, Ph.D., Mitchel Kling, M.D., and Keith Rogers, M.D., and by acute services coordinators Patricia Alexander, Ph.D., Laura Blandy, Psy. D., Aimee Coughlin, M.S.W., John Dennis, Ph.D., Michael Miello, Ph.D., Katherine Mostkoff, L.C.S.W., and Jarrod Reisweber, Psy. D. The authors also acknowledge project interviewers Emily Biggs, M.A., Jason Cha, M. Phil. Ed., Maryanne McGinn, M. A., and Laura Mowery, Psy. D. Essential guidance and support were provided by Lauren Denneson, Ph.D., Steven Dobscha, M.D., Walter Matweychuk, Ph.D., Gerd Naydock, M.S.W., Keith Rogers, M.D., Donald Tavakoli, M.D., and Adam Wolkin, M.D. NR 12 TC 0 Z9 0 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2016 VL 67 IS 6 BP 679 EP 682 DI 10.1176/appi.ps.201500082 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DO4UK UT WOS:000377779900019 ER PT J AU Rudmikl, L Soler, ZM Hopkins, C Schlosser, RJ Peters, A White, AA Orlandi, RR Fokkens, WJ Douglas, R Smith, TL AF Rudmikl, Luke Soler, Zachary M. Hopkins, Claire Schlosser, Rodney J. Peters, Anju White, Andrew A. Orlandi, Richard R. Fokkens, Wytske J. Douglas, Richard Smith, Timothy L. TI Defining appropriateness criteria for endoscopic sinus surgery during management of uncomplicated adult chronic rhinosinusitis: a RAND/UCLA appropriateness study SO RHINOLOGY LA English DT Article DE sinusitis; patient selection; criteria selection; sinus surgery; quality of health care ID REFRACTORY CHRONIC RHINOSINUSITIS; CONTINUED MEDICAL THERAPY; SMALL-AREA VARIATION; COMPUTED-TOMOGRAPHY; UNITED-STATES; GEOGRAPHIC-VARIATION; SYMPTOM OUTCOMES; IMPACT OUTCOMES; NASAL POLYPOSIS; HEALTH-CARE AB Introduction: Appropriate indications for endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) are currently poorly defined. The lack of clear surgical indications for ESS likely contributes to the large geographic variation in surgical rates and contributes to reduced quality of care. The objective of this study was to define appropriateness criteria for ESS during management of adult patients with uncomplicated CRS. Methods:The RAND/UCLA appropriateness methodology was performed. An international, multi-disciplinary panel of 10 experts in CRS was formed and completed two rounds of a modified Delphi ranking process along with a face-to-face meeting. Results: A total of 624 clinical scenarios were ranked, 312 scenarios each for CRS with and CRS without nasal polyps. For adult patients with uncomplicated CRS with nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is 1 and there has been a minimum trial of a topical intranasal corticosteroid plus a short-course of systemic corticosteroid with a post-treatment total SNOT-22 score >= 20. For adult patients with uncomplicated CRS without nasal polyps, ESS can be appropriately offered when the CT Lund-Mackay score is >= 1 and there has been a minimum trial of a topical intranasal corticosteroid plus either a short-course of a broad spectrum/culture-directed systemic antibiotic or the use of a prolonged course of systemic low-dose anti-inflammatory antibiotic with a post-treatment total SNOT-22 score >= 20. Conclusion:This study has developed and reported of list of appropriateness criteria to offer ESS as a treatment'option'during management of uncomplicated adult CRS. The extent or technique of ESS was not addressed in this study and will depend on surgeon and patient factors. Furthermore, these criteria are the minimal threshold to make ESS a treatment'option'and do not imply that all patients meeting these criteria require surgery. The decision to perform ESS should be made after an informed patient makes a preference-sensitive decision to proceed with surgery. Applying these appropriateness criteria for ESS may optimize patient selection, reduce the incidence of unwarranted surgery, and assist clinicians in providing high quality, patient-centered care to patients with CRS. C1 [Rudmikl, Luke] Univ Calgary, Dept Surg, Div Otolaryngol Head & Neck Surg, Calgary, AB, Canada. [Soler, Zachary M.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Charleston, SC 29425 USA. [Hopkins, Claire] Guys & St Thomas NHS Trust, Dept ENT, London, England. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Peters, Anju] Northwestern Univ, Div Allergy, Dept Internal Med, Chicago, IL 60611 USA. [White, Andrew A.] Scripps Clin, Div Allergy & Immunol, La Jolla, CA 92037 USA. [Orlandi, Richard R.] Univ Utah, Div Otolaryngol Head & Neck Surg, Salt Lake City, UT USA. [Fokkens, Wytske J.] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Douglas, Richard] Univ Auckland, Dept Surg, Auckland 1, New Zealand. [Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Oregon Sinus Ctr, Div Rhinol & Sinus Surg, Portland, OR 97201 USA. RP Rudmikl, L (reprint author), Univ Calgary, Dept Surg, Div Otolaryngol Head & Neck Surg, Richmond Rd Diagnost & Treatment Ctr, 1820 Richmond Rd SW, Calgary, AB T2T 5C7, Canada. EM Lukerudmik@gmail.com FU MSI Foundation FX The authors would like to thank the MSI Foundation for their grant to support this project. NR 70 TC 4 Z9 4 U1 1 U2 1 PU INT RHINOLOGIC SOC PI UTRECHT PA UNIV MEDICAL CENTER UTRECHT, RM G05 127, DEPT OTORHINOL, HEIDELBERGLAAN 100, 3584 CX UTRECHT, NETHERLANDS SN 0300-0729 J9 RHINOLOGY JI Rhinology PD JUN PY 2016 VL 54 IS 2 BP 117 EP 128 DI 10.4193/Rhino16.023 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA DO8EM UT WOS:000378015400005 PM 26934470 ER PT J AU Zou, L Feng, Y Xu, G Jian, W Chao, W AF Zou, L. Feng, Y. Xu, G. Jian, W. Chao, W. TI SPLENIC RNA AND SYNTHETIC MICRORNAS INDUCE COMPLEMENT ACTIVATION VIA TLR SIGNALING SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Zou, L.; Feng, Y.; Chao, W.] Univ Maryland, Sch Med, Anesthesiol, Baltimore, MD 21201 USA. [Zou, L.; Feng, Y.; Xu, G.; Jian, W.; Chao, W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 6 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA 11 BP 17 EP 17 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000012 ER PT J AU Kashiwagi, S Mohammed, K Yasuhara, S Kaneki, M Jeevendra, M AF Kashiwagi, S. Mohammed, K. Yasuhara, S. Kaneki, M. Jeevendra, M. TI INFLAMMATORY RESPONSES, PROTEOLYSIS AND MUSCLE WASTING (MW) REVERSAL IN BURN INJURED (BI) MICE WITH GTS-21, A SPECIFIC AGONIST FOR NICOTINIC ACETYLCHOLINE RECEPTORS (alpha 7ACHRS) SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Kashiwagi, S.; Mohammed, K.; Yasuhara, S.; Jeevendra, M.] Shriners Hosp Children Boston, Boston, MA USA. [Kashiwagi, S.; Mohammed, K.; Yasuhara, S.; Kaneki, M.; Jeevendra, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA 19 BP 20 EP 21 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000020 ER PT J AU Nakazawa, H Tanaka, T Kuriyama, N Kaneki, M AF Nakazawa, H. Tanaka, T. Kuriyama, N. Kaneki, M. TI FARNESYLTRANSFERASE INHIBITOR PREVENTS BURN-INDUCED HIF-1 alpha EXPRESSION, BASAL MTORC1 ACTIVATION AND MITOCHONDRIAL DYSFUNCTION IN MOUSE SKELETAL MUSCLE SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Nakazawa, H.; Tanaka, T.; Kuriyama, N.; Kaneki, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Nakazawa, H.; Kuriyama, N.; Kaneki, M.] Shriners Hosp Children, Boston, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P10 BP 46 EP 46 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000103 ER PT J AU Nakazawa, H Tanaka, T Kuriyama, N Kaneki, M AF Nakazawa, H. Tanaka, T. Kuriyama, N. Kaneki, M. TI COENZYME Q10 PREVENTS BURN-INDUCED MUSCLE MITOCHONDRIAL DYSFUNCTION/DISINTEGRITY AND INSULIN RESISTANCE IN MOUSE SKELETAL MUSCLE. SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Nakazawa, H.; Tanaka, T.; Kuriyama, N.; Kaneki, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Nakazawa, H.; Tanaka, T.; Kuriyama, N.; Kaneki, M.] Shriners Hosp Children, Boston, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P13 BP 47 EP 48 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000106 ER PT J AU Kuriyama, N Shimomura, Y Nishida, O Bittner, EA Goverman, J Kaneki, M AF Kuriyama, N. Shimomura, Y. Nishida, O. Bittner, E. A. Goverman, J. Kaneki, M. TI FARNESYLTRANSFERASE INHIBITOR AMELIORATES IMPAIRED DIRECTIONALITY IN CHEMOTAXIS AND SPONTANEOUS MOTILITY OF NEUTROPHILS FROM BURN PATIENTS SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Kuriyama, N.; Bittner, E. A.; Kaneki, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Kuriyama, N.; Shimomura, Y.; Nishida, O.] Fujita Hlth Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Toyoake, Aichi 47011, Japan. [Goverman, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Kaneki, M.] Shriners Hosp Children, Boston, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P16 BP 48 EP 49 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000109 ER PT J AU Feng, Y Zou, L Yan, D Chen, H Xu, G Jian, W Chao, W AF Feng, Y. Zou, L. Yan, D. Chen, H. Xu, G. Jian, W. Chao, W. TI CARDIAC RNA AND MIRNA MIMICS INDUCES LEUKOCYTE RECRUITMENT IN VIVO AND MAP KINASE ACTIVATION VIA TLR7 SIGNALING SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Feng, Y.; Zou, L.; Chao, W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Feng, Y.; Zou, L.; Yan, D.; Chen, H.; Xu, G.; Jian, W.; Chao, W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P53 BP 63 EP 63 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000146 ER PT J AU Voigt, CD Herndon, DN Toliver-Kinsky, T Tompkins, RG Moldawer, L Gibran, N Gamelli, RL Miller-Graziano, C Jeschke, M Andersen, CR Finnerty, C AF Voigt, C. D. Herndon, D. N. Toliver-Kinsky, T. Tompkins, R. G. Moldawer, L. Gibran, N. Gamelli, R. L. Miller-Graziano, C. Jeschke, M. Andersen, C. R. Finnerty, C. TI CHARACTERIZATION OF ALTERATIONS IN CELL SURFACE MARKERS OF T CELL POPULATIONS AS A RESULT OF BURN INJURY SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Voigt, C. D.; Herndon, D. N.; Toliver-Kinsky, T.; Andersen, C. R.; Finnerty, C.] Univ Texas Med Branch, Surg, Galveston, TX 77555 USA. [Voigt, C. D.; Herndon, D. N.; Toliver-Kinsky, T.; Andersen, C. R.; Finnerty, C.] Shriners Hosp Children, Galveston, TX 77550 USA. [Moldawer, L.] Univ Florida, Gainesville, FL USA. [Gibran, N.] Univ Washington, Seattle, WA 98195 USA. [Gamelli, R. L.] Loyola Univ, Chicago, IL 60611 USA. [Jeschke, M.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Miller-Graziano, C.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Tompkins, R. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tompkins, R. G.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P93 BP 80 EP 80 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000186 ER PT J AU Hobai, IA Siwik, D Valentine, C Remick, D Colucci, WS AF Hobai, I. A. Siwik, D. Valentine, C. Remick, D. Colucci, W. S. TI REDOX-DEPENDENT AND -INDEPENDENT MECHANISMS UNDERLIE CARDIAC DYSFUNCTION IN A MOUSE MODEL OF POLYMICROBIAL SEPSIS SO SHOCK LA English DT Meeting Abstract CT 39th Annual Conference of the Shock-Society on Shock CY JUN 11-14, 2016 CL Austin, TX SP Shock Soc C1 [Hobai, I. A.] Massachusetts Gen Hosp, Anesthesia, Boston, MA 02114 USA. [Hobai, I. A.; Siwik, D.; Valentine, C.; Remick, D.; Colucci, W. S.] Boston Univ, Med Ctr, Boston, MA USA. NR 0 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2016 VL 45 IS 6 SU 1 MA P214 BP 126 EP 126 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA DO3OX UT WOS:000377692000306 ER PT J AU Sarantopoulos, J Mita, MM Birrer, MJ Cranmer, LD Campos, LT Zhang, XP Bristow, P Kaito, H Strout, V Camacho, LH AF Sarantopoulos, John Mita, Monica M. Birrer, Michael J. Cranmer, Lee D. Campos, Luis T. Zhang, Xiaoping Bristow, Penelope Kaito, Hidekuni Strout, Vincent Camacho, Luis H. TI Phase 1 Study of Monotherapy with KHK2866, an Anti-Heparin-Binding Epidermal Growth Factor-Like Growth Factor Monoclonal Antibody, in Patients with Advanced Cancer SO TARGETED ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; HB-EGF; OVARIAN-CANCER; PLUS IRINOTECAN; BREAST-CANCER; EXPRESSION; CARCINOMA; CHEMOTHERAPY; BEVACIZUMAB AB Background KHK2866 is a recombinant, humanized, non-fucosylated, monoclonal antibody directed at heparinbinding epidermal growth factor-like growth factor (HBEGF). Objective To determine the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, potential immunogenicity, and preliminary clinical efficacy of KHK2866 monotherapy in patients with advanced and refractory cancer in a first- in- human, phase 1 study. Materials and Methods Using a standard 3+ 3 dose-escalation design, 20 patients received KHK2866 (0.3, 1, and 3 mg/kg) intravenously once weekly. Two additional patients received 0.1 mg/kg in a cohort which was subsequently added following protocol amendment. Results The first three patients enrolled experienced grade 2 hypersensitivity (acute infusion reactions) after the first dose of KHK2866. After prophylactic treatment with an H1blocker and corticosteroids in subsequently recruited patients, two grade 2 hypersensitivity reactions were observed in the remaining 19 patients. Grade 2/3 neurotoxicity appeared to be dose- limiting at 3 mg/kg in the original dose- escalation cohorts (n= 2), at 1 mg/kg in the MTD dose expansion cohort (n= 1), and at 0.1 mg/kg (n= 1). Neurotoxicity was manifested as complex partial seizure activity, aphasia, and confusion after first-dose administration. Pharmacokinetic exposure to KHK2866 increased proportionally to dose. Mean elimination half-life was 71.9-118 h over the dose range from 0.3 to 3 mg/kg. All KHK2866 doses decreased serum free HBEGF levels, generally below the lower limit of quantification. Conclusions The study was terminated because of neuropsychiatric toxicity. The only predictive factor for neuropsychiatric toxicity was administration of KHK2866. These effects were reversible, but were not predictable. Their etiology is not presently understood. [Study registered at ClinicalTrials.gov#NCT0179291] C1 [Sarantopoulos, John] Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, 4th Floor,Zeller Bldg,7979 Wurzbach Rd, San Antonio, TX 78229 USA. [Mita, Monica M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Gynecol Oncol, Boston, MA USA. [Cranmer, Lee D.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Campos, Luis T.; Camacho, Luis H.] Oncol Consultants, Houston, TX USA. [Zhang, Xiaoping; Bristow, Penelope; Kaito, Hidekuni; Strout, Vincent] Kyowa Hakko Kirin Pharma Inc, Princeton, NJ USA. RP Sarantopoulos, J (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, 4th Floor,Zeller Bldg,7979 Wurzbach Rd, San Antonio, TX 78229 USA. EM sarantopoulo@uthscsa.edu; Monica.Mita@cshs.org; mbirrer@partners.org; Lcranmer@uacc.arizona.edu; Lcampos@oncologyconsultants.com; azhang@kyowa-kirin-pharma.com; penny@coreclinicalsolutions.com; hidekuni.kaito@fujifilmkyowakirin-biologics.com; vstrout@kyowa-kirin-pharma.com; lhcamacho@mac.com FU Kyowa Hakko Kirin, Inc. FX Kyowa Hakko Kirin, Inc. NR 42 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1776-2596 EI 1776-260X J9 TARGET ONCOL JI Target. Oncol. PD JUN PY 2016 VL 11 IS 3 BP 317 EP 327 DI 10.1007/s11523-015-0394-5 PG 11 WC Oncology SC Oncology GA DO6TV UT WOS:000377917300005 PM 26507836 ER PT J AU Bu, X Mahoney, KM Freeman, GJ AF Bu, Xia Mahoney, Kathleen M. Freeman, Gordon J. TI Learning from PD-1 Resistance: New Combination Strategies SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material ID IMMUNE CHECKPOINTS; MELANOMA; BLOCKADE; CELL AB Only a minority of cancer patients respond to anti PD-1 immunotherapy. A recent study demonstrates that PD-1 therapy-resistant melanoma patients present distinct signatures of upregulated genes involved in immunosuppression, angiogenesis, monocyte and macrophage chemotaxis, extracellular matrix remodeling, and epithelial-mesenchymal transition (EMT). Combination targeting of these pathways with PD-1 may help overcome PD-1 resistance, thus producing effective antitumor immunity. C1 [Bu, Xia; Mahoney, Kathleen M.; Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Mahoney, Kathleen M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfcl.harvard.edu NR 10 TC 2 Z9 2 U1 6 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 EI 1471-499X J9 TRENDS MOL MED JI Trends Mol. Med PD JUN PY 2016 VL 22 IS 6 BP 448 EP 451 DI 10.1016/j.molmed.2016.04.008 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DO4BZ UT WOS:000377728100002 PM 27174038 ER PT J AU Masch, WR Ellis, JH Wang, CL Cohan, RH Davenport, MS AF Masch, William R. Ellis, James H. Wang, Carolyn L. Cohan, Richard H. Davenport, Matthew S. TI Effect of available intravenous access on accuracy and timeliness of epinephrine administration SO ABDOMINAL RADIOLOGY LA English DT Article DE Contrast reaction; Simulation; Training; High-fidelity; Epinephrine ID CONTRAST-MEDIA; ANAPHYLACTIC REACTIONS; POSTMORTEM FINDINGS; ALLERGIC REACTIONS; MANAGEMENT; RADIOLOGY; PREPAREDNESS; SIMULATION; FREQUENCY; SAFETY AB To evaluate the effect of available intravenous (IV) access on the accuracy and timeliness of epinephrine administration during a surprise mock severe contrast reaction. Informed consent was waived for this prospective randomized IRB-approved study. Radiology trainees with previous annual hands-on contrast reaction training (n = 46) were randomized to one of two surprise mock contrast reactions over a 23-month period: Group 1-severe laryngeal edema with IV access present (n = 27) or Group 2-severe laryngeal edema without IV access present (n = 19). Both intramuscular (IM, Epi-Pen(A (R))) and IV epinephrine were available in both scenarios. Time-to-treat and epinephrine administration error rates were compared by study group and by route of administration using two-tailed Student's t test or chi (2) test. Epinephrine administration errors were correlated with training experience using Pearson's correlation. Mean time to epinephrine administration was significantly faster for scenarios without IV access (Group 2: 35 +/- 16 s vs. Group 1: 62 +/- 49 s, p = 0.03), and for intramuscular administrations overall (IM: 42 +/- 34 s vs. IV: 98 +/- 46 s, p < 0.001). Epinephrine administration errors were common: (63% [17/27, Group 1] vs. 61% [11/18, Group 2], p = 1.00), had no relationship with time to most recent hands-on training (r = 0.24, p = 0.11), and were not predicted by year of post-graduate training (r = 0.04, p = 0.79). Lack of IV access is associated with a faster epinephrine administration time but no improvement in epinephrine administration error rate among radiology trainees responding to a surprise mock severe contrast reaction. Annual hands-on training appears to have little effect on epinephrine administration accuracy. C1 [Masch, William R.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. [Masch, William R.; Ellis, James H.; Wang, Carolyn L.; Cohan, Richard H.; Davenport, Matthew S.] Univ Michigan Hlth Syst, Dept Radiol, Div Abdominal Imaging, 1500 E Med Ctr Dr,B1-D502H, Ann Arbor, MI 48109 USA. [Ellis, James H.; Cohan, Richard H.; Davenport, Matthew S.] Univ Michigan Hlth Syst, Dept Radiol, 1500 E Med Ctr Dr,B1-D502G, Ann Arbor, MI 48109 USA. [Wang, Carolyn L.] Univ Washington, Dept Radiol, 1959 NE Pacific St, Seattle, WA 98195 USA. [Davenport, Matthew S.] Univ Michigan Hlth Syst, Dept Radiol, 1500 E Med Ctr Dr,B2-A209P, Ann Arbor, MI 48108 USA. [Davenport, Matthew S.] Michigan Radiol Qual Collaborat, Ann Arbor, MI USA. RP Davenport, MS (reprint author), Univ Michigan Hlth Syst, Dept Radiol, Div Abdominal Imaging, 1500 E Med Ctr Dr,B1-D502H, Ann Arbor, MI 48109 USA.; Davenport, MS (reprint author), Univ Michigan Hlth Syst, Dept Radiol, 1500 E Med Ctr Dr,B1-D502G, Ann Arbor, MI 48109 USA.; Davenport, MS (reprint author), Univ Michigan Hlth Syst, Dept Radiol, 1500 E Med Ctr Dr,B2-A209P, Ann Arbor, MI 48108 USA.; Davenport, MS (reprint author), Michigan Radiol Qual Collaborat, Ann Arbor, MI USA. EM matdaven@med.umich.edu NR 19 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JUN PY 2016 VL 41 IS 6 BP 1133 EP 1141 DI 10.1007/s00261-016-0660-8 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DO0EV UT WOS:000377453100012 PM 26880173 ER PT J AU Bossone, E Pyeritz, RE Braverman, AC Peterson, MD Ehrlich, M O'Gara, P Suzuki, T Trimarchi, S Gilon, D Greason, K Desai, ND Montgomery, DG Isselbacher, EM Nienaber, CA Eagle, KA AF Bossone, Eduardo Pyeritz, Reed E. Braverman, Alan C. Peterson, Mark D. Ehrlich, Marek O'Gara, Patrick Suzuki, Toru Trimarchi, Santi Gilon, Dan Greason, Kevin Desai, Nimesh D. Montgomery, Daniel G. Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. CA IRAD Investigators TI Shock complicating type A acute aortic dissection: Clinical correlates, management, and outcomes SO AMERICAN HEART JOURNAL LA English DT Article ID RISK-FACTORS; INSIGHTS AB Aims Shock is among the most dreaded and common complications of type A acute aortic dissection (TAAAD). However, clinical correlates, management, and short- and long-term outcomes of TAAAD patients presenting with shock in real-world clinical practice are not known. Methods and Results We evaluated 2,704 patients with TAAAD enrolled in the International Registry of Acute Aortic Dissection between January 1, 1996, and August 18, 2012. On admission, 407 (15.1%) TAAAD patients presented with shock. Most in-hospital complications (coma, myocardial or mesenteric ischemia or infarction, and cardiac tamponade) were more frequent in shock patients. In-hospital mortality was significantly higher in TAAAD patients with than without shock (30.2% vs 23.9%, P = .007), regardless of surgical or medical treatment. Most shock patients underwent surgical repair, with medically managed patients demonstrating older age and more complications at presentation. Estimates using Kaplan-Meier survival analysis indicated that most (89%) TAAAD patients with shock discharged alive from the hospital survived 5 years, a rate similar to that of TAAAD patients without shock (82%, P = .609). Conclusions Shock occurred in 1 of 7 TAAAD patients and was associated with higher rates of in-hospital adverse events and mortality. However, TAAAD survivors with or without shock showed similar long-term mortality. Successful early and aggressive management of shock in TAAAD patients has the potential for improving long-term survival in this patient population. C1 [Bossone, Eduardo] Univ Salerno, Div Cardiol, I-84100 Salerno, Italy. [Pyeritz, Reed E.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pyeritz, Reed E.] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Braverman, Alan C.] Washington Univ, Div Cardiovasc, St Louis, MO USA. [Peterson, Mark D.] St Michaels Hosp, Div Cardiac Surg, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Ehrlich, Marek] Univ Vienna, Dept Cardiothorac Surg, Vienna, Austria. [O'Gara, Patrick] Brigham & Womens Hosp, Dept Cardiol, 75 Francis St, Boston, MA 02115 USA. [Suzuki, Toru] Univ Tokyo, Cardiovasc Med, Tokyo, Japan. [Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy. [Gilon, Dan] Hadassah Hebrew Univ, Med Ctr, Inst Heart, Jerusalem, Israel. [Greason, Kevin] Mayo Clin, Dept Cardiovasc Surg, Rochester, MN USA. [Desai, Nimesh D.] Univ Penn, Dept Cardiovasc Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Rostock, Dept Internal Med, D-18055 Rostock, Germany. RP Bossone, E (reprint author), Univ Salerno Italy, Cava de Tirreni & Amalfi Coast Hosp, Div Cardiol, Heart Dept, Via Pr Amedeo 36, I-83023 Lauro, VA, Italy. EM ebossone@hotmail.com RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 14 TC 3 Z9 3 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUN PY 2016 VL 176 BP 93 EP 99 DI 10.1016/j.ahj.2016.02.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO0MC UT WOS:000377472000016 PM 27264225 ER PT J AU Schnabel, RB Maas, R Wang, N Yin, XY Larson, MG Levy, D Ellinor, PT Lubitz, SA McManus, D Magnani, JW Atzler, D Boger, RH Schwedhelm, E Vasan, RS Benjamin, EJ AF Schnabel, Renate B. Maas, Renke Wang, Na Yin, Xiaoyan Larson, Martin G. Levy, Daniel Ellinor, Patrick T. Lubitz, Steven A. McManus, DavidD. Magnani, Jared W. Atzler, Dorothee Boeger, Rainer H. Schwedhelm, Edzard Vasan, Ramachandran S. Benjamin, Emelia J. TI Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation SO AMERICAN HEART JOURNAL LA English DT Article ID CONGESTIVE-HEART-FAILURE; OXIDE SYNTHASE INHIBITOR; COMMUNITY-BASED COHORT; CARDIOVASCULAR EVENTS; PLASMA-CONCENTRATIONS; ARTERIAL STIFFNESS; RISK PREDICTION; DISEASE; BIOMARKERS; MARKERS AB Background Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. Methods and Results In 3,310 individuals (mean age 58 +/- 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, L-arginine, symmetric dimethylarginine (SDMA), and the ratio of L-arginine/ADMAto incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age-and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither L-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755-0.809). Conclusions Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement. C1 [Schnabel, Renate B.; Yin, Xiaoyan; Larson, Martin G.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBIs & Boston Univ Framingham Study, Framingham, MA USA. [Schnabel, Renate B.] Partner Site Hamburg Kiel Lubeck, DZHK German Ctr Cardiovasc Res, Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Maas, Renke] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany. [Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Ellinor, Patrick T.] Univ Massachusetts, Sch Med, Cardiovasc Res Ctr, Worcester, MA USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Broad Inst Harvard & Massachusetts Inst Technol, Program inMed Populat Genet, Cambridge, MA USA. [Ellinor, Patrick T.; Lubitz, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [McManus, DavidD.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA. [Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Atzler, Dorothee] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Boeger, Rainer H.; Schwedhelm, Edzard] Univ Med Ctr Hamburg Eppendorf, Inst Clin Pharmacol & Toxicol, Hamburg, Germany. [Boeger, Rainer H.; Schwedhelm, Edzard] Univ Ctr Hamburg Eppendorf, Cardiovasc Res Ctr, Hamburg, Germany. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovascular Inst, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Schnabel, RB (reprint author), Univ Heart Ctr, Dept Gen & Intervent Cardiol, Martinistr 52, D-20246 Hamburg, Germany. EM r.schnabel@uke.de OI Ramachandran, Vasan/0000-0001-7357-5970 FU Bayer HealthCare FX Dr Ellinor is the principal investigator on a grant from Bayer HealthCare to the Broad Institute related to AF genetics and therapeutics. NR 50 TC 0 Z9 0 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JUN PY 2016 VL 176 BP 100 EP 106 DI 10.1016/j.ahj.2016.03.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO0MC UT WOS:000377472000017 PM 27264226 ER PT J AU Karas, MG Yee, LM Biggs, ML Djousse, L Mukamal, KJ Ix, JH Zieman, SJ Siscovick, DS Gottdiener, JS Rosenberg, MA Kronmal, RA Heckbert, SR Kizer, JR AF Karas, Maria G. Yee, Laura M. Biggs, Mary L. Djousse, Luc Mukamal, Kenneth J. Ix, Joachim H. Zieman, Susan J. Siscovick, David S. Gottdiener, John S. Rosenberg, Michael A. Kronmal, Richard A. Heckbert, Susan R. Kizer, Jorge R. TI Measures of Body Size and Composition and Risk of Incident Atrial Fibrillation in Older People SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; atrial fibrillation; body size; obesity ID CARDIOVASCULAR HEALTH; HEART-FAILURE; ATHEROSCLEROSIS RISK; MASS INDEX; OBESITY; DISEASE; FAT; DETERMINANTS; COHORT; ADULTS AB Various anthropometric measures, including height, have been associated with atrial fibrillation (AF). This raises questions about the appropriateness of using ratio measures such as body mass index (BMI), which contains height squared in its denominator, in the evaluation of AF risk. Among older adults, the optimal anthropometric approach to risk stratification of AF remains uncertain. Anthropometric and bioelectrical impedance measures were obtained from 4,276 participants (mean age = 72.4 years) free of cardiovascular disease in the Cardiovascular Health Study. During follow-up (1989-2008), 1,050 cases of AF occurred. BMI showed a U-shaped association, whereas height, weight, waist circumference, hip circumference, fat mass, and fat-free mass were linearly related to incident AF. The strongest adjusted association occurred for height (per each 1-standard-deviation increment, hazard ratio = 1.38, 95% confidence interval: 1.25, 1.51), which exceeded all other measures, including weight (hazard ratio = 1.21, 95% confidence interval: 1.13, 1.29). Combined assessment of log-transformed weight and height showed regression coefficients that departed from the 1 to -2 ratio inherent in BMI, indicating a loss of predictive information. Risk estimates for AF tended to be stronger for hip circumference than for waist circumference and for fat-free mass than for fat mass, which was explained largely by height. These findings highlight the prominent role of body size and the inadequacy of BMI as determinants of AF in older adults. C1 [Karas, Maria G.] Weill Cornell Med Coll, Dept Med, Div Cardiol, New York, NY USA. [Yee, Laura M.; Biggs, Mary L.; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Djousse, Luc; Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Gottdiener, John S.] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA. [Rosenberg, Michael A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Div Cardiol, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Kizer, JR (reprint author), Albert Einstein Coll Med, Dept Med, Cardiovasc Clin Res Unit, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jorge.kizer@einstein.yu.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [R01 HL094555, K23 HL127296, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG023629] FX This study was supported by grant R01 HL094555 from the National Heart, Lung, and Blood Institute to L. D., K. J. M, J. H. I, S. J. Z., and J. R. K. M. A. R. was supported by grant K23 HL127296 from the National Heart, Lung, and Blood Institute. The Cardiovascular Health Study was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by grant AG023629 from the National Institute on Aging. NR 46 TC 2 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2016 VL 183 IS 11 BP 998 EP 1007 DI 10.1093/aje/kwv278 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DN9RK UT WOS:000377417600005 PM 27188936 ER PT J AU Akiba, Y Kaunitz, JD Montrose, MH AF Akiba, Yasutada Kaunitz, Jonathan D. Montrose, Marshall H. TI CFTR and pH(i) regulation SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Letter ID CYSTIC-FIBROSIS; PH C1 [Akiba, Yasutada; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Montrose, Marshall H.] Univ Cincinnati, Dept Mol & Cellular Physiol, Cincinnati, OH USA. RP Kaunitz, JD (reprint author), VAGLAHS, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 8 TC 1 Z9 1 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN 1 PY 2016 VL 310 IS 11 BP G1183 EP G1183 DI 10.1152/ajpgi.00133.2016 PG 1 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA DN9XE UT WOS:000377433200031 PM 27281734 ER PT J AU Dordea, AC Vandenwijngaert, S Garcia, V Tainsh, RET Nathan, DI Allen, K Raher, MJ Tainsh, LT Zhang, F Lieb, WS Mikelman, S Kirby, A Stevens, C Thoonen, R Hindle, AG Sips, PY Falck, JR Daly, MJ Brouckaert, P Bloch, KD Bloch, DB Malhotra, R Schwartzman, ML Buys, ES AF Dordea, Ana C. Vandenwijngaert, Sara Garcia, Victor Tainsh, Robert E. T. Nathan, Daniel I. Allen, Kaitlin Raher, Michael J. Tainsh, Laurel T. Zhang, Fan Lieb, Wolfgang S. Mikelman, Sarah Kirby, Andrew Stevens, Christine Thoonen, Robrecht Hindle, Allyson G. Sips, Patrick Y. Falck, John R. Daly, Mark J. Brouckaert, Peter Bloch, Kenneth D. Bloch, Donald B. Malhotra, Rajeev Schwartzman, Michal L. Buys, Emmanuel S. TI Androgen-sensitive hypertension associated with soluble guanylate cyclase-alpha(1) deficiency is mediated by 20-HETE SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE 20-HETE; nitric oxide; soluble guanylate cyclase; hypertension; vascular function; cytochrome P450 ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; 20-HYDROXYEICOSATETRAENOIC ACID; ENDOTHELIAL DYSFUNCTION; GENDER-DIFFERENCES; COMMON VARIANTS; KNOCKOUT MICE; CYP4A11 GENE; SYNTHASE; POLYMORPHISMS AB Dysregulated nitric oxide (NO) signaling contributes to the pathogenesis of hypertension, a prevalent and often sex-specific risk factor for cardiovascular disease. We previously reported that mice deficient in the alpha(1)-subunit of the NO receptor soluble guanylate cyclase (sGC(alpha 1)(-/-) mice) display sex-and strain-specific hypertension: male but not female sGC(alpha 1)(-/-) mice are hypertensive on an 129S6 (S6) but not a C57BL6/J (B6) background. We aimed to uncover the genetic and molecular basis of the observed sex-and strain-specific blood pressure phenotype. Via linkage analysis, we identified a suggestive quantitative trait locus associated with elevated blood pressure in male sGC(alpha 1)(-/-) S6 mice. This locus encompasses Cyp4a12a, encoding the predominant murine synthase of the vasoconstrictor 20-hydroxy5,8,11,14- eicosatetraenoic acid (20-HETE). Renal expression of Cyp4a12a in mice was associated with genetic background, sex, and testosterone levels. In addition, 20-HETE levels were higher in renal preglomerular microvessels of male sGC(alpha 1)(-/-) S6 than of male sGC(alpha 1)(-/-) B6 mice. Furthermore, treating male sGC(alpha 1)(-/-) S6 mice with the 20-HETE antagonist 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid (20-HEDE) lowered blood pressure. Finally, 20-HEDE rescued the genetic background-and testosterone-dependent impairment of acetylcholine-induced relaxation in renal interlobar arteries associated with sGC(alpha 1)(-/-) deficiency. Elevated Cyp4a12a expression and 20-HETE levels render mice susceptible to hypertension and vascular dysfunction in a setting of sGC(alpha 1)(-/-) deficiency. Our data identify Cyp4a12a as a candidate sex-specific blood pressure-modifying gene in the context of deficient NO-sGC signaling. C1 [Dordea, Ana C.; Vandenwijngaert, Sara; Tainsh, Robert E. T.; Nathan, Daniel I.; Allen, Kaitlin; Raher, Michael J.; Tainsh, Laurel T.; Lieb, Wolfgang S.; Mikelman, Sarah; Thoonen, Robrecht; Hindle, Allyson G.; Bloch, Kenneth D.; Bloch, Donald B.; Malhotra, Rajeev; Buys, Emmanuel S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Anesthesia Ctr Critical Care Res, Dept Anesthesia Crit Care & Pain Med,Res Inst, Boston, MA USA. [Garcia, Victor; Zhang, Fan; Schwartzman, Michal L.] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA. [Kirby, Andrew; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, 55 Fruit St,Thier 511B, Boston, MA 02114 USA. [Kirby, Andrew; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Stevens, Christine; Daly, Mark J.] Broad Inst Harvard & Massachusetts Inst Techonol, Program Med & Populat Genet, Cambridge, MA USA. [Sips, Patrick Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Bloch, Kenneth D.; Bloch, Donald B.; Malhotra, Rajeev] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen, Boston, MA USA. RP Buys, ES (reprint author), Massachusetts Gen Hosp, Res Inst, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 55 Fruit St,Thier 511B, Boston, MA USA. EM ebuys@mgh.harvard.edu FU American Heart Association [10SDG2610313]; Eleanor and Miles Shore 50th Anniversary Fellowship program for Scholars in Medicine from Harvard Medical School; National Institutes of Health [P01-HL-034300, K08-HL-111210, R01-HL-74352, HL-111392, HL-34300-26A1S1, 5R01-EY-022746]; Foundation Leducq; FWO-Vlaanderen [FWOG093810N]; UGent-GOA Programs [BOF10/GOA/024]; Belgian American Education Foundation FX This work was supported by the American Heart Association (10SDG2610313 to E. S. Buys, Philips Resuscitation Fellowship Award to P. Y. Sips), an Eleanor and Miles Shore 50th Anniversary Fellowship program for Scholars in Medicine from Harvard Medical School (to E. S. Buys), National Institutes of Health (P01-HL-034300 to M. L. Schwartzman, K08-HL-111210 to R. Malhotra, R01-HL-74352 to K. D. Bloch, HL-111392 to J. R. Falck, HL-34300-26A1S1 to V. Garcia, and 5R01-EY-022746 to E. S. Buys), a grant from the Foundation Leducq [to K. D. Bloch], grants from the FWO-Vlaanderen and the UGent-GOA Programs (FWOG093810N and BOF10/GOA/024, respectively, to P. Bloch), and a fellowship from the Belgian American Education Foundation (to S. Vandenwijngaert). NR 43 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN 1 PY 2016 VL 310 IS 11 BP H1790 EP H1800 DI 10.1152/ajpheart.00877.2015 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA DN9XQ UT WOS:000377434400040 PM 27199131 ER PT J AU Thoonen, R Hindle, AG Scherrer-Crosbie, M AF Thoonen, Robrecht Hindle, Allyson G. Scherrer-Crosbie, Marielle TI Brown adipose tissue: The heat is on the heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE cardiovascular; diabetes; endocrine function; obesity ID DIET-INDUCED OBESITY; NERVE GROWTH-FACTOR; MAMMALIAN NONSHIVERING THERMOGENESIS; MITOCHONDRIAL UNCOUPLING PROTEIN; INCREASES ENERGY-EXPENDITURE; IMPROVES INSULIN SENSITIVITY; AGE-RELATED-CHANGES; HIGH-FAT DIETS; ADAPTIVE THERMOGENESIS; GLUCOSE-HOMEOSTASIS AB The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. C1 [Thoonen, Robrecht; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Hindle, Allyson G.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Pain Med, Boston, MA 02114 USA. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com FU National Institute of Diabetes and Digestive and Kidney Diseases [R21-DK-092909]; Tosteson Fund for Medical Discovery FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R21-DK-092909 (to M. Scherrer-Crosbie) and the Tosteson Fund for Medical Discovery (to R. Thoonen). NR 202 TC 2 Z9 2 U1 6 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN 1 PY 2016 VL 310 IS 11 BP H1592 EP H1605 DI 10.1152/ajpheart.00698.2015 PG 14 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA DN9XQ UT WOS:000377434400023 PM 27084389 ER PT J AU Minhas, JS Wickner, PG Long, AA Banerji, A Blumenthal, KG AF Minhas, Jasmit S. Wickner, Paige G. Long, Aidan A. Banerji, Aleena Blumenthal, Kimberly G. TI Immune-mediated reactions to vancomycin A systematic case review and analysis SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID IGA BULLOUS DERMATOSIS; TOXIC EPIDERMAL NECROLYSIS; ACUTE INTERSTITIAL NEPHRITIS; RED-MAN SYNDROME; OF-THE-LITERATURE; DRESS-SYNDROME; DRUG REACTION; HYPERSENSITIVITY REACTION; TUBULOINTERSTITIAL NEPHRITIS; STAPHYLOCOCCUS-AUREUS AB Background: Vancomycin is a broad-spectrum antibiotic whose use may be limited by adverse drug reactions (ADRs). Although vancomycin toxic effects are known, there are limited data on vancomycin hypersensitivity reactions (HSRs). Objective: To understand the most commonly reported vancomycin HSRs through systematic case review. Methods: We performed a literature search for English-language case reports and series from 1982 through 2015 (last search July 31, 2015) on Ovid MEDLINE and PubMed. The search included the subject heading vancomycin with the subheading adverse effects and separate text searches for vancomycin with a list of specified HSRs. References of identified articles were reviewed to find additional articles. Clinical data were collected and summarized. Results: Of 201 identified articles, 84 were screened and 57 fully assessed; these 57 articles contained 71 vancomycin HSR cases that were included in analysis. Vancomycin HSRs were immediate (anaphylaxis, n = 7) and nonimmediate (n = 64). Nonimmediate HSRs included linear IgA bullous dermatosis (LABD, n = 34), drug rash eosinophilia and systemic symptoms (DRESS) syndrome (n = 16), acute interstitial nephritis (AIN, n = 8), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN, n = 6). Median times of vancomycin therapy before HSR onset was 7 days (interquartile range [IQR], 4-10 days) for LABD, 9 days (IQR, 9-22 days) for SJS/TEN, 21 days (IQR, 17-28 days) for DRESS syndrome, and 26 days (IQR, 7-29 days) for AIN. Overall, 11 patients (16%) died, and 4 (6%) had deaths attributed to the HSR. Conclusion: Vancomycin causes a variety of HSRs; the most commonly identified were nonimmediate HSRs, with LABD being most frequent. We observed a high frequency of HSR mortality. Further data are needed to understand the frequency and severity of vancomycin HSRs. (C) 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Minhas, Jasmit S.] Lahey Clin Fdn, Dept Med, 41 Burlington Mall Rd, Burlington, MA 01805 USA. [Wickner, Paige G.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA. [Wickner, Paige G.; Long, Aidan A.; Banerji, Aleena; Blumenthal, Kimberly G.] Harvard Univ, Sch Med, Boston, MA USA. [Long, Aidan A.; Banerji, Aleena; Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Edward P Lawrence Ctr Qual & Safety, Boston, MA 02114 USA. RP Minhas, JS (reprint author), Lahey Clin Fdn, Dept Med, 41 Burlington Mall Rd, Burlington, MA 01805 USA. EM jasmit.minhas@lahey.org FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health) [UL1 TR001102]; Harvard University and its affiliated academic healthcare centers; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102] FX This work was conducted with the support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. NR 88 TC 4 Z9 4 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUN PY 2016 VL 116 IS 6 BP 544 EP 553 DI 10.1016/j.anai.2016.03.030 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DN9AX UT WOS:000377372500013 PM 27156746 ER PT J AU Greenwood-Ericksen, MB Poon, SJ Nelson, LS Weiner, SG Schuur, JD AF Greenwood-Ericksen, Margaret B. Poon, Sabrina J. Nelson, Lewis S. Weiner, Scott G. Schuur, Jeremiah D. TI Best Practices for Prescription Drug Monitoring Programs in the Emergency Department Setting: Results of an Expert Panel SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Scientific Assembly of the American-College-of-Emergency-Physicians CY OCT, 2015 CL Boston, MA SP Amer Coll Emergency Phys ID OVERDOSE; OPIOIDS; TRENDS; IMPACT; POLICY; CARE; PAIN AB Prescription drug monitoring programs are generally underused in emergency departments (ED) and nationwide enrollment is low among emergency physicians. We aimed to develop consensus recommendations for prescription drug monitoring program policy and design to optimize their functionality and use in the ED. We assembled a technical expert panel with key stakeholders in emergency medicine, public health, and public policy. The panel included academic and community-based emergency physicians, a pediatric fellowship-trained emergency physician, a medical toxicologist, a public health expert, a patient advocate, a legal expert, and two state prescription drug monitoring program administrators. We compiled prescription drug monitoring program policies and characteristics and organized them into domains based on user-prescription drug monitoring program interaction. The panel convened for 3 rounds in which the policies and characteristics were introduced, discussed, and modified in an iterative fashion to achieve consensus. The process yielded policy recommendations and design features, with majority agreement. The panel made 18 policy recommendations within these main themes: enrollment should be mandatory, with an automatic process to mitigate the workload; registration should be open to all prescribers; delegates should have access to prescription drug monitoring program to alleviate work flow burdens; prescription drug monitoring program data should be pushed into hospital electronic health records; prescription drug monitoring program review should be mandatory for patients receiving opioid prescriptions and based on objective criteria; the prescription drug monitoring program content should be standardized and updated in a timely manner; and states should encourage interstate data sharing. An expert panel identified 18 recommendations that can be used by states and policymakers to improve prescription drug monitoring program design to increase use in the ED setting. C1 [Greenwood-Ericksen, Margaret B.; Poon, Sabrina J.; Weiner, Scott G.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. [Greenwood-Ericksen, Margaret B.; Poon, Sabrina J.; Weiner, Scott G.; Schuur, Jeremiah D.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02163 USA. [Greenwood-Ericksen, Margaret B.; Poon, Sabrina J.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nelson, Lewis S.] NYU, Sch Med, Ronald O Perelman Dept Emergency Med, New York, NY USA. RP Greenwood-Ericksen, MB (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA.; Greenwood-Ericksen, MB (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02163 USA.; Greenwood-Ericksen, MB (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM mgreenwood-ericksen@partners.org OI Nelson, Lewis/0000-0001-9551-3922 NR 40 TC 2 Z9 2 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUN PY 2016 VL 67 IS 6 BP 755 EP 764 DI 10.1016/j.annemergmed.2015.10.019 PG 10 WC Emergency Medicine SC Emergency Medicine GA DN9TU UT WOS:000377424400014 PM 26619757 ER PT J AU Yun, BJ Prabhakar, AM Warsh, J Kaplan, R Brennan, J Dempsey, KE Raja, AS AF Yun, Brian J. Prabhakar, Anand M. Warsh, Jonathan Kaplan, Robert Brennan, John Dempsey, Kyle E. Raja, Ali S. TI Time-Driven Activity-Based Costing in Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Article AB Value in emergency medicine is determined by both patient-important outcomes and the costs associated with achieving them. However, measuring true costs is challenging. Without an understanding of costs, emergency department (ED) leaders will be unable to determine which interventions might improve value for their patients. Although ongoing research may determine which outcomes are meaningful, an accurate costing system is also needed. This article reviews current costing mechanisms in the ED and their pitfalls. It then describes how time-driven activity-based costing may be superior to these current costing systems. Time-driven activity-based costing, in addition to being a more accurate costing system, can be used for process improvements in the ED. C1 [Yun, Brian J.; Brennan, John; Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Prabhakar, Anand M.] Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging, Boston, MA 02114 USA. [Prabhakar, Anand M.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Imaging, Boston, MA 02114 USA. [Warsh, Jonathan; Kaplan, Robert; Dempsey, Kyle E.] Harvard Univ, Sch Business, Cambridge, MA 02138 USA. [Yun, Brian J.; Prabhakar, Anand M.; Dempsey, Kyle E.; Raja, Ali S.] Harvard Univ, Sch Med, Boston, MA 02163 USA. RP Yun, BJ (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.; Yun, BJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM byun@partners.org NR 19 TC 4 Z9 4 U1 7 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUN PY 2016 VL 67 IS 6 BP 765 EP 772 DI 10.1016/j.annemergmed.2015.08.004 PG 8 WC Emergency Medicine SC Emergency Medicine GA DN9TU UT WOS:000377424400015 PM 26365921 ER PT J AU Matulonis, UA Penson, RT Domchek, SM Kaufman, B Shapira-Frommer, R Audeh, MW Kaye, S Molife, LR Gelmon, KA Robertson, JD Mann, H Ho, TW Coleman, RL AF Matulonis, U. A. Penson, R. T. Domchek, S. M. Kaufman, B. Shapira-Frommer, R. Audeh, M. W. Kaye, S. Molife, L. R. Gelmon, K. A. Robertson, J. D. Mann, H. Ho, T. W. Coleman, R. L. TI Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety SO ANNALS OF ONCOLOGY LA English DT Article DE olaparib; monotherapy; ovarian cancer; BRCA1; 2 mutation; pooled analysis ID OPEN-LABEL; PHASE-2; MULTICENTER; POLYMERASE; INHIBITOR; THERAPY AB Background: The PARP inhibitor olaparib (Lynparza (TM)) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. This analysis evaluated pooled data from two phase I trials [NCT00516373 (study 2); NCT00777582 (study 24)] and four phase II trials [NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42)] that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline. Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received a parts per thousand yen3 lines of prior chemotherapy. In the pooled population, the ORR was 36% [95% confidence interval (CI) 30-42] and the median DoR was 7.4 months (95% CI 5.7-9.1). The ORR among patients who had received a parts per thousand yen3 lines of prior chemotherapy was 31% (95% CI 25-38), with a DoR of 7.8 months (95% CI 5.6-9.5). The safety profile of olaparib was similar in patients who had received a parts per thousand yen3 lines of prior chemotherapy compared with the pooled population; grade a parts per thousand yen3 adverse events were reported in 54% and 50% of patients, respectively. Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received a parts per thousand yen3 lines of prior chemotherapy. NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662. C1 [Matulonis, U. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Penson, R. T.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Domchek, S. M.] Basser Res Ctr, Dept Med, Philadelphia, PA USA. [Domchek, S. M.] Abramson Canc Ctr, Philadelphia, PA USA. [Kaufman, B.; Shapira-Frommer, R.] Chaim Sheba Med Ctr, Div Oncol, IL-52621 Tel Hashomer, Israel. [Audeh, M. W.] Cedars Sinai Med Ctr, Div Med Oncol, Los Angeles, CA 90048 USA. [Kaye, S.; Molife, L. R.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England. [Kaye, S.; Molife, L. R.] Inst Canc Res, Sutton, Surrey, England. [Gelmon, K. A.] BC Canc Agcy, Dept Med Oncol, Vancouver, BC, Canada. [Robertson, J. D.; Mann, H.] AstraZeneca, Global Med Dev, Macclesfield, Cheshire, England. [Ho, T. W.] AstraZeneca, Global Med Dev, Wilmington, DE USA. [Coleman, R. L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Susan Smith Ctr Womens Canc, 450 Brookline Ave,Y1421, Boston, MA 02215 USA. EM ursula_matulonis@dfci.harvard.edu FU AstraZeneca FX This work was supported by AstraZeneca. No grants were received. NR 18 TC 4 Z9 5 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2016 VL 27 IS 6 BP 1013 EP 1019 DI 10.1093/annonc/mdw133 PG 7 WC Oncology SC Oncology GA DN9VD UT WOS:000377427900008 PM 26961146 ER PT J AU Dinh, KT Mahal, BA Ziehr, DR Muralidhar, V Chen, YW Viswanathan, VB Nezolosky, MD Beard, CJ Choueiri, TK Martin, NE Orio, PF Sweeney, CJ Trinh, QD Nguyen, PL AF Dinh, Kathryn T. Mahal, Brandon A. Ziehr, David R. Muralidhar, Vinayak Chen, Yu-Wei Viswanathan, Vidya B. Nezolosky, Michelle D. Beard, Clair J. Choueiri, Toni K. Martin, Neil E. Orio, Peter F. Sweeney, Christopher J. Quoc-Dien Trinh Nguyen, Paul L. TI Risk of prostate cancer mortality in men with a history of prior cancer SO BJU INTERNATIONAL LA English DT Article DE prostate; prostatic neoplasm; second malignancy; treatment; survival ID UNITED-STATES; SURVIVORS; NETHERLANDS AB Objectives To describe outcomes of patients with prostate cancer diagnosed after another malignancy and identify factors associated with prostate cancer death in this population, as little is known about the clinical significance of prostate cancer as a subsequent malignancy. Patients and Methods We studied 18 225 men diagnosed with prostate cancer after another malignancy from 1973 to 2006. We compared demographic and clinical variables, and the proportion of death from prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine and Gray's regression was used to consider the effect of treatment on prostate cancer death. We then studied a second cohort of 88 013 men with prostate cancer as a first or second malignancy to describe current diagnostic and treatment patterns. Results One in seven men died from prostate cancer in our first cohort. More died from prostate cancer following colorectal cancer (16.8% vs 13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly 50% lower risk of death when high-grade or high-stage (adjusted hazard ratio 0.55, 95% confidence interval [CI] 0.47-0.64). Patients who died from prostate cancer had higher grade and stage disease, and received less treatment than patients who died from prior malignancy. The second cohort showed subsequent prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818-0.930) than primary prostate cancer. Conclusions Prostate cancer remains a significant cause of mortality when diagnosed as a subsequent cancer. These results suggest prostate cancer treatment should be seriously considered in patients with prior malignancies, especially those with high-grade or locally advanced prostate cancer. C1 [Dinh, Kathryn T.; Mahal, Brandon A.; Ziehr, David R.; Muralidhar, Vinayak; Beard, Clair J.; Choueiri, Toni K.; Martin, Neil E.; Orio, Peter F.; Sweeney, Christopher J.; Quoc-Dien Trinh; Nguyen, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Wei] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Viswanathan, Vidya B.; Nezolosky, Michelle D.; Beard, Clair J.; Martin, Neil E.; Orio, Peter F.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Viswanathan, Vidya B.; Nezolosky, Michelle D.; Beard, Clair J.; Choueiri, Toni K.; Martin, Neil E.; Orio, Peter F.; Sweeney, Christopher J.; Quoc-Dien Trinh; Nguyen, Paul L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Dana Farber Canc Inst, Div Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), 75 Francis St,ASB-1 L1, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD JUN PY 2016 VL 117 IS 6B BP E20 EP E28 DI 10.1111/bju.13144 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA DO2DE UT WOS:000377589100002 PM 25845283 ER PT J AU Eichler, FS Li, JK Guo, YR Caruso, PA Bjonnes, AC Pan, J Booker, JK Lane, JM Tare, A Vlasac, I Hakonarson, H Gusella, JF Zhang, JG Keating, BJ Saxena, R AF Eichler, Florian S. Li, Jiankang Guo, Yiran Caruso, Paul A. Bjonnes, Andrew C. Pan, Jessica Booker, Jessica K. Lane, Jacqueline M. Tare, Archana Vlasac, Irma Hakonarson, Hakon Gusella, James F. Zhang, Jianguo Keating, Brendan J. Saxena, Richa TI CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids SO BRAIN LA English DT Article DE leukodystrophy; whole exome sequencing; dementia; neuroinflammation; neurodegeneration ID COLONY-STIMULATING FACTOR; GENETIC-VARIATION; FACTOR-I; MICROGLIA; RECEPTOR; DISEASE; EXPRESSION; MUTATIONS; VARIANTS; DATABASE AB Mutations in CSF1R, which encodes colony stimulating factor 1 receptor, cause hereditary diffuse leukoencephalopathy with axonal spheroids. Eichler et al. describe a family in which the mother is unaffected despite carrying a CSF1R mutation in 20% of blood cells. Haematopoietic stem cell transplantation halted disease progression in her affected daughter.Mutations in CSF1R, which encodes colony stimulating factor 1 receptor, cause hereditary diffuse leukoencephalopathy with axonal spheroids. Eichler et al. describe a family in which the mother is unaffected despite carrying a CSF1R mutation in 20% of blood cells. Haematopoietic stem cell transplantation halted disease progression in her affected daughter.Mutations in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hereditary diffuse leukoencephalopathy with axonal spheroids. We identified a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.(E664K)] by exome sequencing in five members of a family with hereditary diffuse leukoencephalopathy with axonal spheroids. Three affected siblings had characteristic white matter abnormalities and presented with progressive neurological decline. In the fourth affected sibling, early progression halted after allogeneic haematopoietic stem cell transplantation from a related donor. Blood spot DNA from this subject displayed chimerism in CSF1R acquired after haematopoietic stem cell transplantation. Interestingly, both parents were unaffected but the mother's blood and saliva were mosaic for the CSF1R mutation. Our findings suggest that expression of wild-type CSF1R in some cells, whether achieved by mosaicism or chimerism, may confer benefit in hereditary diffuse leukoencephalopathy with axonal spheroids and suggest that haematopoietic stem cell transplantation might have a therapeutic role for this disorder. C1 [Eichler, Florian S.; Pan, Jessica; Gusella, James F.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eichler, Florian S.; Caruso, Paul A.; Pan, Jessica; Lane, Jacqueline M.; Gusella, James F.; Saxena, Richa] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Eichler, Florian S.; Bjonnes, Andrew C.; Lane, Jacqueline M.; Tare, Archana; Vlasac, Irma; Gusella, James F.; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Eichler, Florian S.; Pan, Jessica] Massachusetts Gen Hosp, Ctr Rare Neurol Dis, Boston, MA 02114 USA. [Li, Jiankang; Zhang, Jianguo] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Li, Jiankang; Zhang, Jianguo] BGI Shenzhen, Shenzhen Key Lab Neurogen, Shenzhen 518083, Peoples R China. [Guo, Yiran; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Guo, Yiran; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Guo, Yiran; Hakonarson, Hakon; Keating, Brendan J.] Univ Penn, Perelman Sch Med, Dept Paediat, Philadelphia, PA 19104 USA. [Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bjonnes, Andrew C.; Lane, Jacqueline M.; Tare, Archana; Vlasac, Irma; Gusella, James F.; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Booker, Jessica K.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27514 USA. [Lane, Jacqueline M.; Saxena, Richa] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Eichler, FS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 55 Fruit St,VBK 731, Boston, MA 02114 USA. EM feichler@partners.org FU Children's Hospital of Philadelphia and Massachusetts General Hospital Department of Anaesthesia, Critical Care and Pain Medicine Institutional funds; NIH [R01 NS072446, R01FD004127, R01NS082331, F32DK102323, R21HL121728, R01DK102696, R01 HL113338]; PCORI FX This work was supported by an Institutional Development Award to the Center for Applied Genomics from The Children's Hospital of Philadelphia and Massachusetts General Hospital Department of Anaesthesia, Critical Care and Pain Medicine Institutional funds. F.S.E received funding from NIH (R01 NS072446, R01FD004127, R01NS082331) and PCORI; J.M.L received funding from NIH (F32DK102323) and R.S. received funding from NIH (R21HL121728, R01DK102696, R01 HL113338). NR 21 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JUN PY 2016 VL 139 BP 1666 EP 1672 DI 10.1093/brain/aww066 PN 6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DN9WA UT WOS:000377430200014 PM 27190017 ER PT J AU de Vries, YA de Jonge, P van den Heuvel, E Turner, EH Roest, AM AF de Vries, Ymkje Anna de Jonge, Peter van den Heuvel, Edwin Turner, Erick H. Roest, Annelieke M. TI Influence of baseline severity on antidepressant efficacy for anxiety disorders: meta-analysis and meta-regression SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; VENLAFAXINE EXTENDED-RELEASE; PLACEBO-CONTROLLED TRIAL; COMORBIDITY SURVEY REPLICATION; RANDOMIZED CONTROLLED-TRIAL; DSM-IV DISORDERS; DOUBLE-BLIND; PANIC DISORDER; SOCIAL PHOBIA AB Background Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range. Aims To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) and panic disorder. Method Fifty-six trials of second-generation antidepressants for the short-term treatment of an anxiety disorder were included. Baseline and change scores were extracted for placebo and treatment groups in each trial. Mixed effects meta-regression was used to investigate the effects of treatment group, baseline severity and their interaction. Results Increased baseline severity did not predict greater improvement in drug groups compared with placebo groups. Standardised regression coefficients of the interaction term between baseline severity and treatment group were 0.04 (95% CI -0.13 to 0.20, P = 0.65) for GAD, 70.06 (95% CI -0.20 to 0.09, P = 0.43) for SAD, 0.04 (95% CI -0.07 to 0.16, P = 0.46) for OCD, 0.16 (95% CI -0.22 to 0.53, P = 0.37) for PTSD and 0.002 (95% CI -0.10 to 0.10, P = 0.96) for panic disorder. For OCD, baseline severity did predict improvement in both placebo and drug groups equally (b = 0.11, 95% CI 0.05 to 0.17, P = 0.001). Conclusions No relationship between baseline severity and drug-placebo difference was found for anxiety disorders. These results suggest that if the efficacy of antidepressants is considered clinically relevant, they may be prescribed to patients with anxiety regardless of symptom severity. C1 [de Vries, Ymkje Anna; de Jonge, Peter; Roest, Annelieke M.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Interdisciplinary Ctr Psychopathol & Emot Regulat, NL-9700 AB Groningen, Netherlands. [van den Heuvel, Edwin] Tech Univ Eindhoven, Dept Math & Comp Sci, POB 513, NL-5600 MB Eindhoven, Netherlands. [Turner, Erick H.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Behav Hlth & Neurosci Div, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP de Vries, YA (reprint author), Univ Med Ctr Groningen, Dept Psychiat, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM y.a.de.vries@umcg.nl FU Dutch Brain Foundation [KS2011(1)-120] FX The study was supported by grant KS2011(1)-120 from the Dutch Brain Foundation to P.J. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 74 TC 3 Z9 3 U1 5 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 2016 VL 208 IS 6 BP 515 EP + DI 10.1192/bjp.bp.115.173450 PG 19 WC Psychiatry SC Psychiatry GA DO1HV UT WOS:000377530000004 PM 26989093 ER PT J AU Rosenblau, G Kliemann, D Lemme, B Walter, H Heekeren, HR Dziobek, I AF Rosenblau, Gabriela Kliemann, Dorit Lemme, Benjamin Walter, Henrik Heekeren, Hauke R. Dziobek, Isabel TI The role of the amygdala in naturalistic mentalising in typical development and in autism spectrum disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID SOCIAL COGNITION; PERSONALITY-DISORDER; DIAGNOSTIC INTERVIEW; EMOTION RECOGNITION; ASPERGER-SYNDROME; BRAIN; SCHIZOPHRENIA; MIND; METACOGNITION; NEUROSCIENCE AB Background The substantial discrepancy between mentalising in experimental settings v. real-life social interactions hinders the understanding of the neural basis of real-life social cognition and of social impairments in psychiatric disorders. Aims To determine the neural mechanisms underlying naturalistic mentalising in individuals with and without autism spectrum disorder. Method We investigated mentalising with a new video-based functional magnetic resonance imaging task in 20 individuals with autism spectrum disorder and 22 matched healthy controls. Results Naturalistic mentalising implicated regions of the traditional mentalising network (medial prefrontal cortex, temporoparietal junction), and additionally the insula and amygdala. Moreover, amygdala activity predicted implicit mentalising performance on an independent behavioural task. Compared with controls, the autism spectrum disorder group did not show differences in neural activity within classical mentalising regions. They did, however, show reduced amygdala activity and a reduced correlation between amygdala activity and mentalising accuracy on the behavioural task, compared with controls. Conclusions These findings highlight the crucial role of the amygdala in making accurate implicit mental state inferences in typical development and in the social cognitive impairments of individuals with autism spectrum disorder. C1 [Rosenblau, Gabriela; Kliemann, Dorit; Dziobek, Isabel] Free Univ Berlin, Cluster Excellence Languages Emot, Berlin, Germany. [Rosenblau, Gabriela; Kliemann, Dorit; Lemme, Benjamin] Free Univ Berlin, Dept Educ & Psychol, Berlin, Germany. [Rosenblau, Gabriela] Yale Univ, Yale Child Study Ctr, Ctr Translat Dev Neurosci, New Haven, CT USA. [Kliemann, Dorit] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Kliemann, Dorit] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Walter, Henrik] Charite, Dept Psychiat, Div Mind & Brain Res, D-13353 Berlin, Germany. [Heekeren, Hauke R.] Free Univ Berlin, Cluster Excellence Languages Emot, Dept Educ & Psychol, Berlin, Germany. [Heekeren, Hauke R.] Free Univ Berlin, Dahlem Inst Neuroimaging Emot, Berlin, Germany. [Dziobek, Isabel] Humboldt Univ, Sch Mind & Brain, D-10099 Berlin, Germany. RP Rosenblau, G (reprint author), Yale Child Study Ctr, 230 S Frontage Rd, New Haven, CT 06519 USA. EM gabriela.rosenblau@yale.edu RI Walter, Henrik/O-2612-2013 FU German Research Foundation (DFG) [EXC 302] FX The study was funded by a grant from the German Research Foundation (DFG; EXC 302). NR 46 TC 1 Z9 1 U1 10 U2 15 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 2016 VL 208 IS 6 BP 556 EP + DI 10.1192/bjp.bp.114.159269 PG 12 WC Psychiatry SC Psychiatry GA DO1HV UT WOS:000377530000009 PM 26585095 ER PT J AU Spiegel, A Brooks, MW Houshyar, S Reinhardt, F Ardolino, M Fessler, E Chen, MB Krall, JA DeCock, J Zervantonakis, IK Iannello, A Iwamoto, Y Cortez-Retamozo, V Kamm, RD Pittet, MJ Raulet, DH Weinberg, RA AF Spiegel, Asaf Brooks, Mary W. Houshyar, Samin Reinhardt, Ferenc Ardolino, Michele Fessler, Evelyn Chen, Michelle B. Krall, Jordan A. DeCock, Jasmine Zervantonakis, Ioannis K. Iannello, Alexandre Iwamoto, Yoshiko Cortez-Retamozo, Virna Kamm, Roger D. Pittet, Mikael J. Raulet, David H. Weinberg, Robert A. TI Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells SO CANCER DISCOVERY LA English DT Article ID COLONY-STIMULATING-FACTOR; NATURAL-KILLER-CELLS; MYELOID CELLS; MATRIX METALLOPROTEINASES; BONE-MARROW; CANCER-PATIENTS; HEPATOCELLULAR-CARCINOMA; PREMETASTATIC LUNG; PREDICTS SURVIVAL; ANGIOGENIC SWITCH AB Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b(+)/Ly6G(+) neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL1 beta and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their cross-talk with host cells and disseminating carcinoma cells. SIGNIFICANCE: This study provides important insights into the systemic contributions of neutrophils to cancer metastasis by identifying how neutrophils facilitate intermediate steps of the invasion-metastasis cascade. We demonstrate that neutrophils suppress natural killer cell activity and increase extravasation of tumor cells. (C) 2016 AACR. C1 [Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Fessler, Evelyn; Krall, Jordan A.; DeCock, Jasmine; Weinberg, Robert A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Ardolino, Michele; Iannello, Alexandre; Raulet, David H.] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA. [Ardolino, Michele; Iannello, Alexandre; Raulet, David H.] Univ Calif Berkeley, Canc Res Lab, Div Immunol, Berkeley, CA 94720 USA. [Chen, Michelle B.; Zervantonakis, Ioannis K.; Kamm, Roger D.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA USA. [Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA USA. [Weinberg, Robert A.] MIT, Ludwig Ctr Mol Oncol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU Human Frontier Science Program [LT00728/2008-L]; Charles King Trust Foundation; Ludwig Fund for Cancer Research; Cancer Research Institute Irvington Fellowship; Leukemia and Lymphoma Society; Sofie-Wallner-Preis; Dr. Ernst und Anita Bauer-Stiftung; NIH [P01 CA080111, U54 CA163109, R01 CA093678, R01 AI084880]; Breast Cancer Research Foundation; Ludwig Center for Molecular Oncology FX A. Spiegel was supported by fellowships from the Human Frontier Science Program (LT00728/2008-L), the Charles King Trust Foundation, and the Ludwig Fund for Cancer Research. M. Ardolino was supported by a Cancer Research Institute Irvington Fellowship. A. Iannello holds a Special Fellow Award from the Leukemia and Lymphoma Society. E. Fessler was supported by the Sofie-Wallner-Preis and the Dr. Ernst und Anita Bauer-Stiftung. This work was supported by NIH P01 CA080111 (R.A. Weinberg), U54 CA163109 (R.A. Weinberg), R01 CA093678 (D.H. Raulet), and R01 AI084880 (M.J. Pittet); the Breast Cancer Research Foundation (R.A. Weinberg); and the Ludwig Center for Molecular Oncology (R.A. Weinberg). NR 74 TC 12 Z9 13 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JUN PY 2016 VL 6 IS 6 BP 630 EP 649 DI 10.1158/2159-8290.CD-15-1157 PG 20 WC Oncology SC Oncology GA DN9US UT WOS:000377426800016 PM 27072748 ER PT J AU Kelly, RS Heiden, MGV Giovannucci, E Mucci, LA AF Kelly, Rachel S. Heiden, Matthew G. Vander Giovannucci, Edward Mucci, Lorelei A. TI Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID MAGNETIC-RESONANCE-SPECTROSCOPY; CHROMATOGRAPHY-MASS SPECTROMETRY; COLORECTAL-CANCER; BREAST-CANCER; AMINO-ACIDS; PROFILES; TISSUE; METABOLITES; SIGNATURES; DISCOVERY AB Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer. (C)2016 AACR. C1 [Kelly, Rachel S.; Giovannucci, Edward; Mucci, Lorelei A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kelly, Rachel S.; Giovannucci, Edward; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Kelly, Rachel S.; Giovannucci, Edward; Mucci, Lorelei A.] Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA. [Heiden, Matthew G. Vander] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Heiden, Matthew G. Vander] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Heiden, Matthew G. Vander] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Giovannucci, Edward] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Kelly, RS (reprint author), Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA.; Kelly, RS (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM hprke@channing.harvard.edu FU DF/HCC Specialized Programs in Research Excellence (SPORE) in Prostate Cancer - NCI/NIH [2P50CA090381-11A1, P01 CA055075, CA133891, CA141298, CA136578, UM1 CA167552] FX This work is supported by the DF/HCC Specialized Programs in Research Excellence (SPORE) in Prostate Cancer funded by the NCI/NIH (grant number: 2P50CA090381-11A1; Principal Investigator: Philip Kantoff), P01 CA055075, CA133891, CA141298, CA136578, and UM1 CA167552 (to M.G. Vander Heiden, E. Giovannucci, and L.A Mucci). L.A. Mucci is a Young Investigator of the Prostate Cancer Foundation. NR 109 TC 2 Z9 2 U1 5 U2 20 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2016 VL 25 IS 6 BP 887 EP 906 DI 10.1158/1055-9965.EPI-15-1223 PG 20 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DO1HC UT WOS:000377528100002 PM 27197278 ER PT J AU Giorgi, EE Li, YQ Caberto, CP Beckman, KB Lum-Jones, A Haiman, CA Le Marchand, L Stram, DO Saxena, R Cheng, IN AF Giorgi, Elena E. Li, Yuqing Caberto, Christian P. Beckman, Kenneth B. Lum-Jones, Annette Haiman, Christopher A. Le Marchand, Loic Stram, Daniel O. Saxena, Richa Cheng, Iona TI No Association between the Mitochondrial Genome and Prostate Cancer Risk: The Multiethnic Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MUTATIONS AB Background: Mitochondria are involved in many processes that are central to the life and death of a cell. Oxidative phosphorylation (OXPHOS), in particular, is known to be altered in carcinogenesis, leading to an increase in the production of reactive oxidative species and glycolysis, one of the hallmarks of cancer cells. Because of this, genetic variation in the mitochondrial genome, which encodes for part of the OXPHOS pathway, has been suggested to play a role in many cancers, including prostate cancer. Methods: We comprehensively examined the role of the mitochondrial genome and prostate cancer risk in 4,086 prostate cancer cases and 3,698 controls from the Multiethnic Cohort (MEC), testing 350 mitochondrial SNPs (mtSNPs) in five racial/ethnic populations-Africans, Asian Americans, Europeans, Latinos, and Native Hawaiians. Logistic regression was conducted to examine single mitochondrial SNP and haplogroup associations. The sequence kernel association test was conducted for gene and pathway analysis. Results: Eleven mtSNPs and haplogroup N were nominally associated with overall prostate cancer risk at P < 0.05. The mitochondrial DNA-encoded OXPHOS pathway, complexes, and genes were not associated with prostate cancer risk. No significant associations were identified after multiple testing corrections (all FDR q > 0.20). Conclusions: The mitochondrial genome was not associated with prostate cancer risk in our study of 7,784 subjects from the MEC. Impact: Our comprehensive study does not support the role of the mitochondrial genome in the risk of prostate cancer. (C) 2016 AACR. C1 [Giorgi, Elena E.] Los Alamos Natl Lab, Theoret Biol & Biophys, Los Alamos, NM USA. [Li, Yuqing; Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA. [Li, Yuqing; Cheng, Iona] Stanford Canc Inst, Palo Alto, CA USA. [Caberto, Christian P.; Lum-Jones, Annette; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Beckman, Kenneth B.] Univ Minnesota, Genom Ctr, Minneapolis, MN USA. [Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Giorgi, EE (reprint author), Los Alamos Natl Lab, MS K710, Los Alamos, NM 87544 USA. EM egiorgi@lanl.gov FU NCI [CA140636, CA173782, CA63464, CA54281, CA33619, CA164973, CA98758] FX This work was funded through NCI grants CA140636 (to I. Cheng), CA173782 (to I. Cheng), CA63464 (to B.E. Henderson), CA54281 (to L.N. Kolonel), CA33619 (to L.N. Kolonel), CA164973 (to L. Le Merchand, C. Haiman, L. Wilkens), and CA98758 (to B.E. Henderson). NR 8 TC 1 Z9 1 U1 3 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2016 VL 25 IS 6 BP 1001 EP 1003 DI 10.1158/1055-9965.EPI-16-0111 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DO1HC UT WOS:000377528100014 PM 27021046 ER PT J AU Foster, CL Badlam, J De Groote, MA Chan, ED AF Foster, Clayton L. Badlam, Jessica De Groote, Mary Ann Chan, Edward D. TI A 65-Year-Old Groundskeeper With High Fever, Pulmonary Nodules, and Thoracic Lymphadenopathy Typhoidal tularemia with secondary pulmonary involvement SO CHEST LA English DT Editorial Material ID FRANCISELLA-TULARENSIS; UNITED-STATES AB A 65-year-old man with treated latent tuberculous infection presented with 1 week of fevers (up to 39.6 degrees C), chills, headache, lightheadedness, and malaise. He reported a chronic, nonproductive cough without hemoptysis but denied other localizing symptoms, sick contacts, or recent travel. He lived in an urban area in eastern Colorado and owned one healthy dog but otherwise denied known animal exposures. He was a retired oil driller who had worked in southern Arizona, New Mexico, and northern Mexico (Sonora region). Other travel included 3 years in the early 1970s working as a military aircraft mechanic in Vietnam, Laos, and Thailand. Six weeks prior to admission, he began work as a groundskeeper on a golf course that had experienced recent flooding, using a riding mower and exposing himself to airborne dust and organic debris. He smoked a pipe daily for 30 years but quit 2 months prior to presentation, although he continued to smoke marijuana weekly. He denied intravenous drug use. C1 [Foster, Clayton L.] Univ Colorado Anschutz Med Campus, Div Infect Dis, Aurora, CO USA. [Badlam, Jessica; Chan, Edward D.] Univ Colorado Anschutz Med Campus, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [De Groote, Mary Ann] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO 80206 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509 Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 8 TC 0 Z9 0 U1 2 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2016 VL 149 IS 6 BP E191 EP E194 DI 10.1016/j.chest.2015.12.035 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN7YL UT WOS:000377296000007 PM 27287596 ER PT J AU Heffron, R Pintye, J Matthews, LT Weber, S Mugo, N AF Heffron, Renee Pintye, Jillian Matthews, Lynn T. Weber, Shannon Mugo, Nelly TI PrEP as Peri-conception HIV Prevention for Women and Men SO CURRENT HIV/AIDS REPORTS LA English DT Article DE Pre-exposure prophylaxis; PrEP; HIV prevention; Pregnancy; Peri-conception; Safer conception; Science of prevention; Review ID TENOFOVIR DISOPROXIL FUMARATE; ANTIRETROVIRAL PREEXPOSURE PROPHYLAXIS; HEPATITIS-B-VIRUS; SERODISCORDANT COUPLES; RANDOMIZED-TRIAL; INFECTED ADULTS; HARM REDUCTION; CLINICAL-TRIAL; AFRICAN WOMEN; MALE PARTNER AB Daily oral tenofovir (TDF)-based pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy and recommended for men and women with substantial risk of HIV acquisition. The peri-conception period, the stage prior to pregnancy when condom use is necessarily reduced, has elevated HIV risk that can be mitigated by PrEP use. Data from a randomized trial suggest that peri-conception PrEP use by HIV-seronegative women does not increase the risk of pregnancy loss, birth defects or congenital anomalies, preterm birth, or infant growth faltering. Women considering PrEP use throughout pregnancy must weigh the known increased risk of HIV acquisition with unknown risks of drug effects on infant growth. PrEP has been used safely by HIV-seronegative men with HIV-seropositive female partners who have become pregnant. As an effective user-controlled HIV prevention strategy, PrEP offers autonomy and empowerment for HIV prevention and can be recommended alongside antiretroviral therapy, fertility screening, vaginal self-insemination, intercourse timed to peak fertility, medically assisted reproduction, and other safer conception strategies to provide multiple options. The integration of PrEP into safer conception programs is warranted and will safely reduce HIV transmission to women, men, and children during the peri-conception period. C1 [Heffron, Renee] Univ Washington, Dept Global Hlth, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA. [Heffron, Renee] Univ Washington, Dept Epidemiol, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA. [Pintye, Jillian] Univ Washington, Sch Nursing, 325 Ninth Ave,Box 359909, Seattle, WA 98104 USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, 125 Nashua St,Suite 722, Boston, MA 02114 USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Suite 722, Boston, MA 02114 USA. [Weber, Shannon] Univ Calif San Francisco, 1001 Potrero Ave,6D-33, San Francisco, CA 94110 USA. [Mugo, Nelly] Kenya Govt Med Res Ctr, Clin Res Ctr, Nairobi, Kenya. RP Heffron, R (reprint author), Univ Washington, Dept Global Hlth, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA.; Heffron, R (reprint author), Univ Washington, Dept Epidemiol, 325 Ninth Ave,Box 359927, Seattle, WA 98104 USA. EM rheffron@uw.edu; jpintye@uw.edu; ltmatthews@mgh.harvard.edu; shannon.weber@ucsf.edu; rwamba@csrtkenya.org FU [R00 HD 076679]; [K23 MH095655] FX RH was supported by R00 HD 076679 and LTM was supported by K23 MH095655. NR 78 TC 5 Z9 5 U1 4 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD JUN PY 2016 VL 13 IS 3 BP 131 EP 139 DI 10.1007/s11904-016-0312-1 PG 9 WC Infectious Diseases SC Infectious Diseases GA DN9WL UT WOS:000377431300001 PM 26993627 ER PT J AU Luzak, A Schnell-Inderst, P Buhn, S Mayer-Zitarosa, A Siebert, U AF Luzak, Agnes Schnell-Inderst, Petra Buehn, Stefanie Mayer-Zitarosa, Anja Siebert, Uwe TI Clinical effectiveness of cancer screening biomarker tests offered as self-pay health service: a systematic review SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID OVARIAN-CANCER; BREAST-CANCER; TUMOR-MARKERS; RECOMMENDATIONS; PROSTATE; TRIAL; LUNG; METAANALYSIS; MORTALITY; PROGRAMS AB Background: Biomarker tests are increasingly being offered by laboratories and clinicians as self-pay health services to screen asymptomatic individuals; however, sufficient evidence may not be available to support this practice. We investigated the benefit-harm tradeoffs associated with 11 biomarkers currently offered in Germany as self-pay tests to screen for cancer. Methods: We systematically searched bibliographic databases for health technology assessments, systematic reviews and randomized-controlled trials (RCTs) through September 2015. We included publications that analysed cancer screening biomarkers and reported patient-relevant outcomes (mortality, morbidity, quality of life), and potential harms of screening, among asymptomatic individuals in screening and non-screening arms. Language was restricted to English and German. Two reviewers independently screened references; data were extracted and quality of included studies was evaluated by a reviewer and validated by a second reviewer. Results: Six publications of secondary literature and four publications reporting results from two RCTs were included. For 10 cancer screening biomarkers, no direct evidence on patient-relevant outcomes was available. Only one trial, which simultaneously assessed cancer antigen 125 (CA125) and vaginal ultrasound for ovarian cancer screening, provided the outcome of interest. Screening compared with usual care did not reduce ovarian cancer mortality. Patient harms included overdiagnosis and false-positive results. Conclusion: Although ovarian cancer screening with CA125 showed no benefit, false-positive tests, overdiagnosis and overtreatment were reported. Physicians and laboratories should provide patients with comprehensive information about the lack of evidence and potential harms caused by biomarker screening tests offered as a self-pay health service. C1 [Luzak, Agnes; Schnell-Inderst, Petra; Buehn, Stefanie; Mayer-Zitarosa, Anja; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth, Hlth Serv Res & Hlth Technol Assessment, A-6060 Hall In Tirol, Austria. [Luzak, Agnes; Schnell-Inderst, Petra; Buehn, Stefanie; Mayer-Zitarosa, Anja; Siebert, Uwe] Oncotyrol Ctr Personalized Canc Med, Div Hlth Technol Assessment & Bioinformat, Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Hlth Serv Res & Hlth Technol Assessment, Dept Publ Hlth,Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.at FU COMET Center Oncotyrol; Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tyrolean Future Foundation/Standortagentur Tirol (SAT) FX This work was supported by the COMET Center Oncotyrol, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tyrolean Future Foundation/Standortagentur Tirol (SAT). The funding agreement ensured the authors' independence in designing studies, data interpretation, writing and publishing results. NR 38 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 EI 1464-360X J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD JUN PY 2016 VL 26 IS 3 BP 498 EP 505 DI 10.1093/eurpub/ckv227 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO0LQ UT WOS:000377470800028 PM 26733629 ER PT J AU Lin, AE Karnis, MF Calderwood, L Crenshaw, M Bhatt, A Souter, I Silberbach, M Reindollar, RH AF Lin, Angela E. Karnis, Megan F. Calderwood, Laurel Crenshaw, Melissa Bhatt, Ami Souter, Irene Silberbach, Michael Reindollar, Richard H. TI Proposal for a national registry to monitor women with Turner syndrome seeking assisted reproductive technology SO FERTILITY AND STERILITY LA English DT Editorial Material C1 [Lin, Angela E.] Harvard Univ, Sch Med, MassGen Hosp Children, Med Genet, Boston, MA USA. [Karnis, Megan F.] Ontario Network Experts Fertil, Burlington, ON, Canada. [Karnis, Megan F.] McMaster Univ, Gynecol Reprod Endocrinol & Infertil, Hamilton, ON, Canada. [Calderwood, Laurel] Boston Univ, Sch Med, Boston, MA 02118 USA. [Crenshaw, Melissa] Johns Hopkins Med, All Childrens Hosp, Med Genet, St Petersburg, FL USA. [Bhatt, Ami] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Adult Congenital Heart Defect Serv,Dept Med, Boston, MA USA. [Souter, Irene] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Reprod Endocrinol & Infertil,Dept Obstet & Gy, Boston, MA USA. [Silberbach, Michael] Oregon Hlth & Sci Univ, Doernbecher Mem Hosp Children, Pediat Cardiol, Portland, OR 97201 USA. [Reindollar, Richard H.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Geisel Sch Med, Hanover, NH 03756 USA. RP Lin, AE (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Med Genet, Boston, MA USA. NR 6 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2016 VL 105 IS 6 BP 1446 EP 1448 DI 10.1016/j.fertnstert.2016.01.042 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DN7WM UT WOS:000377290900009 PM 26878093 ER PT J AU Gaskins, AJ Chiu, YH Williams, PL Keller, MG Toth, TL Hauser, R Chavarro, JE AF Gaskins, Audrey J. Chiu, Yu-Han Williams, Paige L. Keller, Myra G. Toth, Thomas L. Hauser, Russ Chavarro, Jorge E. CA EARTH Study Team TI Maternal whole grain intake and outcomes of in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article DE Whole grains; in vitro fertilization; female infertility; assisted reproductive technology ID POLYCYSTIC-OVARY-SYNDROME; HORMONE-BINDING GLOBULIN; INSULIN-RESISTANCE; FEMALE REPRODUCTION; OXIDATIVE STRESS; FREE-RADICALS; WOMEN; PREGNANCY; PHYTOESTROGENS; METAANALYSIS AB Objective: To evaluate the relationship between pretreatment intake of whole grains and outcomes of IVF. Design: Prospective cohort study. Setting: Academic medical center. Patient(s): A total of 273 women who collectively underwent 438 IVF cycles. Intervention(s): Whole grain intake was assessed with a validated food frequency questionnaire at enrollment. Main Outcome Measure(s): Intermediate and clinical end points of IVF were abstracted from medical records. Result(s): Women had a median whole grain intake of 34.2 g per day (similar to 1.2 servings/day). Higher pretreatment whole grain intake was associated with higher probability of implantation and live birth. The adjusted percentage of cycles resulting in live birth for women in the highest quartile of whole grain intake (>52.4 g/day) was 53% (95% confidence interval [CI] 41%, 65%) compared with 35% (95% CI 25%, 46%) for women in the lowest quartile (<21.4 g/day). This association was largely driven by intake of bran as opposed to germ. When intermediate end points of IVF were examined, only endometrial thickness on the day of ET was associated with whole grain intake. A 28-g per day (similar to 1 serving/day) increase in whole grain intake was associated with a 0.4-mm (95% CI 0.1, 0.7 mm) increase in endometrial thickness. Conclusion(s): Higher pretreatment whole grain intake was related to higher probability of live birth among women undergoing IVF. The higher probability of live birth may result from increased endometrial thickness on the day of ET and improved embryo receptivity manifested in a higher probability of implantation. (C) 2016 by American Society for Reproductive Medicine.) C1 [Gaskins, Audrey J.; Chiu, Yu-Han; Chavarro, Jorge E.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Keller, Myra G.; Hauser, Russ] Harvard Univ, Dept Environm Hlth, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Keller, Myra G.; Toth, Thomas L.; Hauser, Russ] Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. [Keller, Myra G.; Toth, Thomas L.; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. RP Gaskins, AJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Bldg 2,3rd Floor,655 Huntington Ave, Boston, MA 02115 USA. EM agaskins@hsph.harvard.edu FU National Institutes of Health from National Institute of Environmental Health Sciences [R01-ES009718]; National Institutes of Health from National Institute of Diabetes and Digestive and Kidney Diseases [P30-DK046200, T32-DK007703-16]; National Institutes of Health from National Institute of Child Health and Human Development [L50-HD085359] FX Supported by National Institutes of Health grants R01-ES009718 from National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development. NR 40 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2016 VL 105 IS 6 BP 1503 EP U170 DI 10.1016/j.fertnstert.2016.02.015 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DN7WM UT WOS:000377290900022 PM 26926253 ER PT J AU Hansen, KR He, ALW Styer, AK Wild, RA Butts, S Engmann, L Diamond, MP Legro, RS Coutifaris, C Alvero, R Robinson, RD Casson, P Christman, GM Huang, H Santoro, N Eisenberg, E Zhang, HP AF Hansen, Karl R. He, Amy Linnea W. Styer, Aaron K. Wild, Robert A. Butts, Samantha Engmann, Lawrence Diamond, Michael P. Legro, Richard S. Coutifaris, Christos Alvero, Ruben Robinson, Randal D. Casson, Peter Christman, Gregory M. Huang, Hao Santoro, Nanette Eisenberg, Esther Zhang, Heping CA Eunice Kennedy Shriver Natl Inst TI Predictors of pregnancy and live-birth in couples with unexplained infertility after ovarian stimulation intrauterine insemination SO FERTILITY AND STERILITY LA English DT Article DE Unexplained infertility; predictors; ovarian stimulation; intrauterine inseminate pregnancy ID FUNCTIONAL HYPOTHALAMIC AMENORRHEA; REPRODUCTIVE TECHNOLOGY ART; IN-VITRO FERTILIZATION; QUALITY-OF-LIFE; UNITED-STATES; WOMEN; EFFICACY; OUTCOMES; SUPEROVULATION; GONADOTROPIN AB Objective: To identify baseline characteristics of couples that are likely to predict conception, clinical pregnancy, and live birth after up to four cycles of ovarian stimulation with IUI in couples with unexplained infertility. Design: Secondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live birth, and multiple pregnancy rates after ovarian stimulation-IUI with clomiphene citrate, letrozole, or gonadotropins. Setting: Outpatient clinical units. Patient(s): Nine-hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial. Intervention(s): As part of the clinical trial, treatment was randomized equally to one of three arms and continued for up to four cycles or until pregnancy was achieved. Main Outcome Measure(s): Conception, clinical pregnancy, and live-birth rates. Result(s): In a multivariable logistic regression analysis, after adjustment for other covariates, age, waist circumference, income level, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Other baseline demographic and lifestyle characteristics including smoking, alcohol use, and serum levels of antimilllerian hormone were not significantly associated with pregnancy outcomes. Conclusion(s): While age duration of infertility were significant independent ofrace and educationreflect. differences in the underlying etiologie plained infertility or cOOldrevealdmispayarities in access to fertility and/or obstetrical care. Clinical Trial Registration.. NCT01044862. (Fertil Steril 2016,105:1575_83. (C) 2016 byAni ican Society for Reproductive Medicine.) C1 [Hansen, Karl R.; Wild, Robert A.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, 920 Stanton L Young Blvd,WP 2410, Oklahoma City, OK 73104 USA. [He, Amy Linnea W.; Huang, Hao; Zhang, Heping] Yale Univ, Dept Biostat, Sch Publ Hlth, New Haven, CT USA. [Styer, Aaron K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. [Butts, Samantha; Coutifaris, Christos] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Engmann, Lawrence] Univ Connecticut, Sch Med, Dept Obstet & Gynecol, Farmington, CT USA. [Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Dept Obstet & Gynecol, Aurora, CO USA. [Robinson, Randal D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Casson, Peter] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT USA. [Christman, Gregory M.] Univ Florida, Shands Hosp, Dept Obstet & Gynecol, Gainesville, FL USA. [Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Hansen, KR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, 920 Stanton L Young Blvd,WP 2410, Oklahoma City, OK 73104 USA. EM karl-hansen@ouhsc.edu OI Alvero, Ruben/0000-0001-6542-710X; Diamond, Michael/0000-0001-6353-4489 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, U10HD055925, U10HD077680]; American Recovery and Reinvestment Act FX This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) grants for Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, U10HD055925, and U10HD077680. This research was made possible by the funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the National Institutes of Health. NR 38 TC 2 Z9 2 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2016 VL 105 IS 6 BP 1575 EP U262 DI 10.1016/j.fertnstert.2016.02.020 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DN7WM UT WOS:000377290900032 PM 26949110 ER PT J AU Caballero-Franco, C Kissler, S AF Caballero-Franco, C. Kissler, S. TI The autoimmunity-associated gene RGS1 affects the frequency of T follicular helper cells SO GENES AND IMMUNITY LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIPLE-SCLEROSIS; B-LYMPHOCYTES; RISK; NOD; ORGANIZATION; EXPRESSION; CHEMOKINES; DISEASE; MOUSE AB RGS1 (regulator of G-protein signaling 1) has been associated with multiple autoimmune disorders including type I diabetes. RGS1 desensitizes the chemokine receptors CCR7 and CXCR4 that are critical to the localization of T and B cells in lymphoid organs. To explore how RGS1 variation contributes to autoimmunity, we generated Rgs1 knockdown (KD) mice in the nonobese diabetic (NOD) model for type I diabetes. We found that Rgs1 KD increased the size of germinal centers, but decreased the frequency of T follicular helper (TFH) cells. We show that loss of Rgs1 in T cells had both a T cell-intrinsic effect on migration and TFH cell frequency, and an indirect effect on B-cell migration and germinal center formation. Notably, several recent publications described an increase in circulating TFH cells in patients with type I diabetes, suggesting this cell population is involved in pathogenesis. Though Rgs1 KD was insufficient to alter diabetes frequency in the NOD model, our findings raise the possibility that RGS1 plays a role in autoimmunity owing to its function in TFH cells. This mechanistic link, although speculative at this time, would lend support to the notion that TFH cells are key participants in autoimmunity and could explain the association of RGS1 with several immune-mediated diseases. C1 [Caballero-Franco, C.; Kissler, S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. RP Kissler, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM stephan.kissler@joslin.harvard.edu FU Joslin DRC Flow Cytometry Core facility; JDRF [2-2010-383, 1-INO-2014-169-A-V]; DRC award (NIH) [P30DK036836] FX We acknowledge support from the Joslin DRC Flow Cytometry Core facility. This work was supported in part by a Career Development Award (2-2010-383) and an Innovative Award (1-INO-2014-169-A-V) from JDRF to SK, and by a DRC award (NIH Award Number P30DK036836) to the Joslin Diabetes Center. NR 30 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2016 VL 17 IS 4 BP 228 EP 238 DI 10.1038/gene.2016.16 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA DO0EF UT WOS:000377451500004 PM 27029527 ER PT J AU Alegria, M Alvarez, K Ishikawa, RZ DiMarzio, K McPeck, S AF Alegria, Margarita Alvarez, Kiara Ishikawa, Rachel Zack DiMarzio, Karissa McPeck, Samantha TI Removing Obstacles To Eliminating Racial And Ethnic Disparities In Behavioral Health Care SO HEALTH AFFAIRS LA English DT Article ID MENTAL-HEALTH; ACCOUNTABLE CARE; UNITED-STATES; VULNERABLE POPULATIONS; DEPRESSION TREATMENT; CULTURAL COMPETENCE; MINORITY-GROUPS; SERVICES; ENGAGEMENT; BARRIERS AB Despite decades of research, racial and ethnic disparities in behavioral health care persist. The Affordable Care Act expanded access to behavioral health care, but many reform initiatives fail to consider research about racial/ethnic minorities. Mistaken assumptions that underlie the expansion of behavioral health care run the risk of replicating existing service disparities. Based on a review of relevant literature and numerous observational and field studies with minority populations, we identified the following three mistaken assumptions: Improvement in health care access alone will reduce disparities, current service planning addresses minority patients' preferences, and evidence-based interventions are readily available for diverse populations. We propose tailoring the provision of care to remove obstacles that minority patients face in accessing treatment, promoting innovative services that respond to patients' needs and preferences, and allowing flexibility in evidence-based practice and the expansion of the behavioral health workforce. These proposals should help meet the health care needs of a growing racial/ethnic minority population. C1 [Alegria, Margarita] Harvard Univ, Sch Med, Dept Psychiat, Psychol, Boston, MA 02115 USA. [Alegria, Margarita; Alvarez, Kiara; Ishikawa, Rachel Zack; DiMarzio, Karissa; McPeck, Samantha] Massachusetts Gen Hosp, Dispar Res Unit, Dept Med, Boston, MA 02114 USA. RP Alegria, M (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Psychol, Boston, MA 02115 USA.; Alegria, M (reprint author), Massachusetts Gen Hosp, Dispar Res Unit, Dept Med, Boston, MA 02114 USA. EM malegria@mgh.harvard.edu FU National Institute on Minority Health and Health Disparities (NIMHD) [P60 MD002261]; National Institute of Mental Health (NIMH) [1 P50 MH 073469]; National Institute on Drug Abuse [R01DA034952]; Patient-Centered Outcomes Research Institute [CD-12-11-4187]; National Institute on Aging (NIA) [1R01AG046149]; NIMH [R01MH098374-03S1]; Substance Abuse and Mental Health Services Administration's Center for Mental Health Services; Office of Behavioral and Social Sciences Research [U01 MH62209] FX This study was supported by the National Institute on Minority Health and Health Disparities (NIMHD) (Research Grant and Supplement No. P60 MD002261); the National Institute of Mental Health (NIMH) (Research Grant No. 1 P50 MH 073469); the National Institute on Drug Abuse (Research Grant No. R01DA034952); the Patient-Centered Outcomes Research Institute (Contract No. CD-12-11-4187); the National Institute on Aging (NIA) (Research Grant No. 1R01AG046149); and the NIMH, the Substance Abuse and Mental Health Services Administration's Center for Mental Health Services, and the Office of Behavioral and Social Sciences Research (Research Grant No. U01 MH62209). Kiara Alvarez was supported by the NIMH (Research Grant No. R01MH098374-03S1). The content of the article is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding institutions. NR 55 TC 1 Z9 1 U1 6 U2 11 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2016 VL 35 IS 6 BP 991 EP 999 DI 10.1377/hlthaff.2016.0029 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DO1HF UT WOS:000377528400006 PM 27269014 ER PT J AU Danielson, CK McCauley, JL Gros, KS Jones, AM Barr, SC Borkman, AL Bryant, BG Ruggiero, KJ AF Danielson, Carla Kmett McCauley, Jenna L. Gros, Kirstin Stauffacher Jones, Andrea M. Barr, Simone C. Borkman, April L. Bryant, Brittany G. Ruggiero, Kenneth J. TI SiHLEWeb.com: Development and usability testing of an evidence-based HIV prevention website for female African-American adolescents SO HEALTH INFORMATICS JOURNAL LA English DT Article DE adolescents; African-American; e-Health; prevention; mixed-methods ID COMMUNITY-BASED ORGANIZATIONS; RANDOMIZED CONTROLLED-TRIAL; HEALTH INTERVENTIONS; PRELIMINARY EFFICACY; COMPUTER-TECHNOLOGY; STRATEGIES; INTERNET; PROGRAMS; DELIVERY; WOMEN AB African-American adolescent girls are at disproportionate risk for HIV infection. Although numerous evidence-based risk-reduction interventions exist, dissemination and implementation resources remain limited, and prevention services remain notably inaccessible to the very populations at highest risk for HIV infection. Internet delivery of HIV risk-reduction programming has promise as a mechanism for extending the reach of existing prevention efforts and overcoming barriers associated with traditional service delivery. This article (1) details the development process for the creation of SiHLEWeb, a web-adapted version of an evidence-based, culturally informed HIV prevention program traditionally delivered to female African-American adolescents via an in-person group format, and (2) presents findings from quantitative and qualitative usability testing conducted among 18 African-American girls (13-18 years). Results suggest that users found the website improved knowledge and learning, was helpful, efficient to use, and generally attractive. Users reported some concerns about website navigation. Implications for Internet delivery of health prevention programming are discussed. C1 [Danielson, Carla Kmett; McCauley, Jenna L.; Jones, Andrea M.; Ruggiero, Kenneth J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Jones, Andrea M.] Univ Georgia, Athens, GA 30602 USA. [Barr, Simone C.] Univ Texas Houston, Sch Med, Houston, TX USA. [Bryant, Brittany G.] Communities Sch, Arlington, VA USA. RP Danielson, CK (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 67 President St,MSC 861, Charleston, SC 29425 USA. EM danielso@musc.edu FU South Carolina Clinical & Translational Research (SCTR) Institute; National Center for Research Resources (NCRR) at the National Institutes of Health (NIH) [UL1 RR029882, UL1 TR000062]; Substance Abuse and Mental Health Services Administration [1U79SP015156]; [R01DA031285]; [K12DA031794] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by a Pilot Health Disparities Research Grant (PI: Danielson) from the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, funded through the National Center for Research Resources (NCRR) at the National Institutes of Health (NIH) Grant Numbers UL1 RR029882 and UL1 TR000062 (PI: Brady) and by a grant from the Substance Abuse and Mental Health Services Administration (1U79SP015156; PI: Danielson). The preparation of this manuscript was supported by R01DA031285 (PI: Danielson) and K12DA031794 (PI: Brady; McCauley). NR 45 TC 0 Z9 0 U1 5 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1460-4582 EI 1741-2811 J9 HEALTH INFORM J JI Health Inform. J. PD JUN PY 2016 VL 22 IS 2 BP 194 EP 208 DI 10.1177/1460458214544048 PG 15 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA DN6RM UT WOS:000377203500010 PM 25167865 ER PT J AU Shapiro, JM Zoega, H Shah, SA Bright, RM Mallette, M Moniz, H Grabert, SA Bancroft, B Merrick, M Flowers, NT Samad, Z Lidofsky, S LeLeiko, NS Sands, BE AF Shapiro, Jason M. Zoega, Helga Shah, Samir A. Bright, Renee M. Mallette, Meaghan Moniz, Heather Grabert, Stacey A. Bancroft, Barbara Merrick, Marjorie Flowers, Nicole T. Samad, Zahid Lidofsky, Sheldon LeLeiko, Neal S. Sands, Bruce E. TI Incidence of Crohn's Disease and Ulcerative Colitis in Rhode Island: Report from the Ocean State Crohn's and Colitis Area Registry SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; Crohn's disease; ulcerative colitis; epidemiology; incidence ID INFLAMMATORY-BOWEL-DISEASE; EPIDEMIOLOGY; PREVALENCE; SMOKING; LIFE; IBD AB Background:Studies describing the incidence of Crohn's disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island.Methods:The Ocean State Crohn's and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010.Results:A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3-32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohn's and Colitis Area Registry for follow-up.Conclusions:The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohn's and Colitis Area Registry cohort is ongoing. C1 [Shapiro, Jason M.; Bancroft, Barbara; LeLeiko, Neal S.] Hasbro Childrens Hosp, Div Pediat Gastroenterol Nutr & Liver Dis, Providence, RI USA. [Shapiro, Jason M.; Shah, Samir A.; LeLeiko, Neal S.] Brown Univ, Alpert Med Sch, Providence, RI 02903 USA. [Zoega, Helga; Sands, Bruce E.] Icahn Sch Med Mt Sinai, Dr Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA. [Zoega, Helga] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, IS-101 Reykjavik, Iceland. [Shah, Samir A.; Bright, Renee M.; Mallette, Meaghan; Moniz, Heather; Lidofsky, Sheldon] Rhode Isl Hosp, Div Gastroenterol, Providence, RI USA. [Grabert, Stacey A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merrick, Marjorie] Crohns & Colitis Fdn Amer, New York, NY USA. [Flowers, Nicole T.; Samad, Zahid] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Shapiro, JM (reprint author), Brown Univ, Div Pediat Gastroenterol Nutr & Liver Dis, Hasbro Childrens Hospital, Alpert Med Sch,Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. EM jshapiro@lifespan.org FU CCFA/CDC [5U01DP004785-02] FX This work was supported by CCFA/CDC 5U01DP004785-02. NR 27 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2016 VL 22 IS 6 BP 1456 EP 1461 DI 10.1097/MIB.0000000000000745 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DN9DM UT WOS:000377379500030 PM 26926039 ER PT J AU Rieder, F Cohen, BL Dotson, JL Bewtra, M Ananthakrishnan, AN Falaiye, TO Ha, CY AF Rieder, Florian Cohen, Benjamin L. Dotson, Jennifer L. Bewtra, Meenakshi Ananthakrishnan, Ashwin N. Falaiye, Tolulope O. Ha, Christina Y. TI Rising Educators, Academicians, and Clinicians Helping Inflammatory Bowel Disease (REACH-IBD)Promoting Improvement of Inflammatory Bowel Disease Education in the United States SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material C1 [Rieder, Florian] Cleveland Clin Fdn, Dept Gastroenterol Hepatol & Nutr, Inst Digest Dis, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Cohen, Benjamin L.] Icahn Sch Med Mt Sinai, Div Gastroenterol, New York, NY 10029 USA. [Dotson, Jennifer L.] Nationwide Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Columbus, OH USA. [Dotson, Jennifer L.] Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, Columbus, OH USA. [Bewtra, Meenakshi] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Falaiye, Tolulope O.] Penn State Milton S Hershey Med Ctr, Div Pediat Gastroenterol & Nutr, Hershey, PA USA. [Ha, Christina Y.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. RP Rieder, F (reprint author), Cleveland Clin Fdn, Dept Gastroenterol Hepatol & Nutr, Inst Digest Dis, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIDDK NIH HHS [P30 DK097948, P30 DK043351, T32 DK083251] NR 7 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 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2016 VL 22 IS 6 BP 1531 EP 1532 DI 10.1097/MIB.0000000000000814 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DN9DM UT WOS:000377379500038 PM 27167574 ER PT J AU Long, MD Onyiah, JC Miller, M Herfarth, HH AF Long, Millie D. Onyiah, Joseph C. Miller, Melissa Herfarth, Hans H. TI Cytomegalovirus Viral Load in the Colon and Risk of Colectomy in Hospitalized Patients With Inflammatory Bowel Diseases SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID ULCERATIVE-COLITIS C1 [Long, Millie D.; Onyiah, Joseph C.; Herfarth, Hans H.] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Onyiah, Joseph C.] Univ Colorado, Dept Med, Div Gastroenterol & Hepatol, Aurora, CO USA. [Onyiah, Joseph C.] Denver VA Med Ctr, Denver, CO USA. [Miller, Melissa] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. RP Long, MD (reprint author), Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2016 VL 22 IS 6 BP E21 EP E22 DI 10.1097/MIB.0000000000000799 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DN9DM UT WOS:000377379500007 PM 27120572 ER PT J AU Wang, CH Charlton, B Kohlwes, J AF Wang, Christina Hao Charlton, Blake Kohlwes, Jeffrey TI The Horrible Taste of Nectar and Honey-Inappropriate Use of Thickened Liquids in Dementia A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ASPIRATION; INTERVENTIONS; PNEUMONIA C1 [Wang, Christina Hao; Charlton, Blake; Kohlwes, Jeffrey] Univ Calif San Francisco, PRIME Residency Program, Dept Internal Med, 4150 Clement St, San Francisco, CA 94121 USA. [Wang, Christina Hao; Charlton, Blake; Kohlwes, Jeffrey] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. RP Wang, CH (reprint author), Univ Calif San Francisco, PRIME Residency Program, Dept Internal Med, 4150 Clement St, San Francisco, CA 94121 USA.; Wang, CH (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM hao.wang@ucsf.edu NR 6 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 JUN PY 2016 VL 176 IS 6 BP 735 EP 736 DI 10.1001/jamainternmed.2016.1384 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KU UT WOS:000377184000004 PM 27135181 ER PT J AU Kepes, JA Wilhite, JB Markland, AD AF Kepes, Jeffrey A. Wilhite, James B., Jr. Markland, Alayne D. TI Complications of Indwelling Urinary Catheter Care and Care Transitions A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Kepes, Jeffrey A.] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, BDB 327,1720 Second Ave S, Birmingham, AL 35294 USA. [Wilhite, James B., Jr.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Markland, Alayne D.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Clin Programs, Birmingham, AL USA. [Markland, Alayne D.] Birmingham VA Med Ctr, Birmingham, AL USA. [Markland, Alayne D.] Univ Alabama Birmingham, Dept Gerontol Geriatr & Palliat Care, Birmingham, AL USA. RP Kepes, JA (reprint author), Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, BDB 327,1720 Second Ave S, Birmingham, AL 35294 USA. EM jkepes@uabmc.edu OI Markland, Alayne/0000-0002-6567-6744 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN PY 2016 VL 176 IS 6 BP 737 EP 738 DI 10.1001/jamainternmed.2016.0606 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KU UT WOS:000377184000005 PM 27088441 ER PT J AU Moin, T AF Moin, Tannaz TI Obesity Management and Prevention More Questions Than Answers SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Moin, Tannaz] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Moin, T (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 911 Broxton Ave,Off 302, Los Angeles, CA 90024 USA. EM tmoin@mednet.ucla.edu NR 6 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 JUN PY 2016 VL 176 IS 6 BP 753 EP 754 DI 10.1001/jamainternmed.2016.1211 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KU UT WOS:000377184000009 PM 27135966 ER PT J AU Kesselheim, AS Gagne, JJ Eddings, W Franklin, JM Ross, KM Fulchino, LA Campbell, EG AF Kesselheim, Aaron S. Gagne, Joshua J. Eddings, Wesley Franklin, Jessica M. Ross, Kathryn M. Fulchino, Lisa A. Campbell, Eric G. TI Prevalence and Predictors of Generic Drug Skepticism Among Physicians: Results of a National Survey SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Kesselheim, Aaron S.; Gagne, Joshua J.; Eddings, Wesley; Franklin, Jessica M.; Fulchino, Lisa A.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, PORTAL, 75 Francis St, Boston, MA 02115 USA. [Kesselheim, Aaron S.; Gagne, Joshua J.; Eddings, Wesley; Franklin, Jessica M.; Fulchino, Lisa A.; Campbell, Eric G.] Harvard Univ, Sch Med, Boston, MA USA. [Ross, Kathryn M.] Amer Board Internal Med, Philadelphia, PA USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Kesselheim, AS (reprint author), Brigham & Womens Hosp, Dept Med, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM akesselheim@partners.org NR 5 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 JUN PY 2016 VL 176 IS 6 BP 845 EP 847 DI 10.1001/jamainternmed.2016.1688 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DN6KU UT WOS:000377184000028 PM 27158897 ER PT J AU Greenblatt, EE Winkler, T Harris, RS Kelly, VJ Kone, M Katz, I Martin, A Caillibotte, G Hess, DR Venegas, JG AF Greenblatt, Elliot Eliyahu Winkler, Tilo Harris, Robert Scott Kelly, Vanessa Jane Kone, Mamary Katz, Ira Martin, Andrew Caillibotte, George Hess, Dean R. Venegas, Jose G. TI Regional Ventilation and Aerosol Deposition with Helium-Oxygen in Bronchoconstricted Asthmatic Lungs SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Article DE aerosol concentration; aerosol deposition; branching factor; breathing frequency; carrier gas; escape fraction; helium-oxygen; lobar; lung expansion; peripheral deposition; retention fraction; ventilation ID INHALED PARTICLES; CONTROLLED-TRIAL; FLOW-RATES; AIR; DELIVERY; DRIVEN; NEBULIZER; THERAPY; BRONCHODILATOR; EXACERBATIONS AB Background: Theoretical models suggest that He-O-2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributions from subjects with asthma inhaling He-O-2 as carrier gas. The data are compared with those that we previously obtained from a similar group of subjects inhaling air. Methods: Subjects with mild-to-moderate asthma were bronchoconstricted with methacholine and imaged with PET-CT while inhaling aerosol carried with He-O-2. Mean-normalized-values of lobar specific ventilation sV* and deposition sD* were derived and the factors affecting the distribution of sD* were evaluated along with the effects of breathing frequency (f) and regional expansion (F-VOL). Results: Lobar distributions of sD* and sV* with He-O-2 were not statistically different from those previously measured with air. However, with He-O-2 there was a larger number of lobes having sV* and sD* closer to unity and, in those subjects with uneven deposition distributions, the correlation of sD* with sV* was on average higher (p < 0.05) in He-O-2 (0.84 +/- 0.8) compared with air (0.55 +/- 0.28). In contrast with air, where the frequency of breathing during nebulization was associated with the degree of sD*-sV* correlation, with He-O-2 there was no association. Also, the modulation of f on the correlation between F-VOL and sD*/sV* in air, was not observed in He-O-2. Conclusion: There were no differences in the inter-lobar heterogeneity of sD* or sV* in this group of mild asthmatic subjects breathing He-O-2 compared with patients previously breathing air. Future studies, using these personalized 3D data sets as input to CFD models, are needed to understand if, and for whom, breathing He-O-2 during aerosol inhalation may be beneficial. C1 [Greenblatt, Elliot Eliyahu] MIT, Boston, MA USA. [Greenblatt, Elliot Eliyahu; Winkler, Tilo; Harris, Robert Scott; Kelly, Vanessa Jane; Kone, Mamary; Hess, Dean R.; Venegas, Jose G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, Elliot Eliyahu; Winkler, Tilo; Harris, Robert Scott; Kelly, Vanessa Jane; Kone, Mamary; Hess, Dean R.; Venegas, Jose G.] Harvard Univ, Sch Med, 2 Hawthorne Pl, Boston, MA 02114 USA. [Katz, Ira; Caillibotte, George] Air Liquide Sante Int, R&D Med, Les Loges En Josas, France. [Katz, Ira] Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA. [Martin, Andrew] Amer Air Liquide, Delaware Res & Technol Ctr, Newark, DE USA. [Martin, Andrew] Univ Alberta, Dept Mech Engn, Edmonton, AB, Canada. RP Venegas, JG (reprint author), Harvard Univ, Sch Med, 2 Hawthorne Pl, Boston, MA 02114 USA.; Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Bioengn, 2 Hawthorne Pl, Boston, MA 02114 USA. EM jvenegas@habanero.mgh.harvard.edu FU National Institutes of Health [R01HL68011]; American Air Liquide Inc. FX Research reported in this publication was supported by the National Institutes of Health under award number R01HL68011. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by American Air Liquide Inc., and Aerogen is thanked for providing the vibrating mesh nebulizers at no cost. NR 38 TC 2 Z9 2 U1 5 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 EI 1941-2703 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD JUN PY 2016 VL 29 IS 3 BP 260 EP 272 DI 10.1089/jamp.2014.1204 PG 13 WC Respiratory System SC Respiratory System GA DN9CZ UT WOS:000377378100086 PM 26824777 ER PT J AU Balekian, DS Banerji, A Blumenthal, KG Camargo, CA Long, AA AF Balekian, Diana S. Banerji, Aleena Blumenthal, Kimberly G. Camargo, Carlos A., Jr. Long, Aidan A. TI Allergen immunotherapy: No evidence of infectious risk SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID RHINITIS C1 [Balekian, Diana S.; Banerji, Aleena; Blumenthal, Kimberly G.; Camargo, Carlos A., Jr.; Long, Aidan A.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Balekian, Diana S.; Banerji, Aleena; Blumenthal, Kimberly G.; Camargo, Carlos A., Jr.; Long, Aidan A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Long, AA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.; Long, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM aalong@partners.org FU NHLBI NIH HHS [T32 HL116275] NR 15 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2016 VL 137 IS 6 BP 1887 EP + DI 10.1016/j.jaci.2016.03.021 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DO1GT UT WOS:000377527200032 PM 27090935 ER PT J AU Mansbach, JM Hasegawa, K Henke, DM Ajami, NJ Petrosino, JF Shaw, CA Piedra, PA Sullivan, AF Espinola, JA Camargo, CA AF Mansbach, Jonathan M. Hasegawa, Kohei Henke, David M. Ajami, Nadim J. Petrosino, Joseph F. Shaw, Chad A. Piedra, Pedro A. Sullivan, Ashley F. Espinola, Janice A. Camargo, Carlos A., Jr. TI Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID ASTHMA; INFECTIONS; SYMPTOMS C1 [Mansbach, Jonathan M.] Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Hasegawa, Kohei; Sullivan, Ashley F.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Henke, David M.; Shaw, Chad A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Ajami, Nadim J.; Petrosino, Joseph F.; Piedra, Pedro A.] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol & Pediat, Houston, TX 77030 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Mansbach, JM (reprint author), Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu FU NHLBI NIH HHS [R21 HL129909]; NIAID NIH HHS [R01 AI108588, U01 AI067693, U01 AI087881] NR 9 TC 4 Z9 4 U1 3 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2016 VL 137 IS 6 BP 1909 EP 1913 DI 10.1016/j.jaci.2016.01.036 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA DO1GT UT WOS:000377527200041 PM 27061249 ER PT J AU Eda, H Santo, L Wein, MN Hu, DZ Cirstea, DD Nemani, N Tai, YT Raines, SE Kuhstoss, SA Munshi, NC Kronenberg, HM Raje, NS AF Eda, Homare Santo, Loredana Wein, Marc N. Hu, Dorothy Z. Cirstea, Diana D. Nemani, Neeharika Tai, Yu-Tzu Raines, Sarah E. Kuhstoss, Stuart Allen Munshi, Nikhil C. Kronenberg, Henry M. Raje, Noopur S. TI Regulation of Sclerostin Expression in Multiple Myeloma by Dkk-1: A Potential Therapeutic Strategy for Myeloma Bone Disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE TUMOR-INDUCED BONE DISEASE; CYTOKINES; OSTEOBLASTS; STROMAL; STEM CELLS; THERAPEUTICS ID SINGLE-AGENT CARFILZOMIB; POSTMENOPAUSAL OSTEOPOROSIS; NEUTRALIZING ANTIBODY; PRECLINICAL ACTIVITY; KINASE INHIBITOR; BMP ANTAGONIST; STEM-CELLS; IN-VIVO; COMBINATION; TARGET AB Sclerostin is a potent inhibitor of osteoblastogenesis. Interestingly, newly diagnosed multiple myeloma (MM) patients have high levels of circulating sclerostin that correlate with disease stage and fractures. However, the source and impact of sclerostin in MM remains to be defined. Our goal was to determine the role of sclerostin in the biology of MM and its bone microenvironment as well as investigate the effect of targeting sclerostin with a neutralizing antibody (scl-Ab) in MM bone disease. Here we confirm increased sclerostin levels in MM compared with precursor disease states like monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM. Furthermore, we found that a humanized MM xenograft mouse model bearing human MM cells (NOD-SCID.CB17 male mice injected intravenously with 2.5 million of MM1.S-Luc-GFP cells) demonstrated significantly higher concentrations of mouse-derived sclerostin, suggesting a microenvironmental source of sclerostin. Associated with the increased sclerostin levels, activated -catenin expression levels were lower than normal in MM mouse bone marrow. Importantly, a high-affinity grade scl-Ab reversed osteolytic bone disease in this animal model. Because scl-Ab did not demonstrate significant in vitro anti-MM activity, we combined it with the proteasome inhibitor carfilzomib. Our data demonstrated that this combination therapy significantly inhibited tumor burden and improved bone disease in our in vivo MM mouse model. In agreement with our in vivo data, sclerostin expression was noted in marrow stromal cells and osteoblasts of MM patient bone marrow samples. Moreover, MM cells stimulated sclerostin expression in immature osteoblasts while inhibiting osteoblast differentiation in vitro. This was in part regulated by Dkk-1 secreted by MM cells and is a potential mechanism contributing to the osteoblast dysfunction noted in MM. Our data confirm the role of sclerostin as a potential therapeutic target in MM bone disease and provides the rationale for studying scl-Ab combined with proteasome inhibitors in MM. (c) 2016 American Society for Bone and Mineral Research. C1 [Eda, Homare; Santo, Loredana; Cirstea, Diana D.; Nemani, Neeharika; Raje, Noopur S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Wein, Marc N.; Hu, Dorothy Z.; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Tai, Yu-Tzu; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA. [Tai, Yu-Tzu; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, 44 Binney St, Boston, MA 02115 USA. [Raines, Sarah E.; Kuhstoss, Stuart Allen] Lilly Res Labs, Regenerat Biol, Indianapolis, IN USA. RP Raje, NS (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU LLS Clinical Scholar Award; NIH NRSA [DK100215]; NIH [P01 DK011794] FX We thank the Center for Skeletal Research Histology Core (NIH P30 AR 066261) for performing IHC on MM patients and mouse samples. This work was supported by a LLS Clinical Scholar Award (to NSR), NIH NRSA DK100215 (to MNW), and NIH P01 DK011794 (to HMK). NR 47 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2016 VL 31 IS 6 BP 1225 EP 1234 DI 10.1002/jbmr.2789 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN7PL UT WOS:000377269200013 PM 26763740 ER PT J AU Lenz, M Wahl, D Zderic, I Gueorguiev, B Jupiter, JB Perren, SM AF Lenz, Mark Wahl, Dieter Zderic, Ivan Gueorguiev, Boyko Jupiter, Jesse B. Perren, Stephan M. TI Head-locking durability of fixed and variable angle locking screws under repetitive loading SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE polyaxial locking; variable angle locking; screw removal torque; locking durability; fixed angle locking ID PLATE; FRACTURES.; STABILITY; INSERTION; REMOVAL AB Polyaxial locking screws are increasingly applied in fracture fixation. To investigate the durability of the head-locking mechanism, the removal torque of variable angle (VA) and fixed angle (FA) stainless steel and titanium locking screws was investigated without and after a cyclic loading test. Stainless steel (St) and titanium (Ti) 2.4mm orthogonally inserted FA screws and 2.4mm VA screws inserted in different inclinations (0 degrees-15 degrees) (n=6 per group) were locked at 0.8Nm. Removal torque was determined without (W) and after (A) cyclic loading (sinusoidal load, 5Hz, constant amplitude of 25N, up to 10000 cycles, or failure). Significant differences in-between the groups were detected by Student's t-test (p<0.05). Except VA Ti in 0deg and FA, all groups exhibited a drop in removal torque below the insertion torque without and after cyclic testing. The removal torque was (St: FA W:0.81Nm +/- 0.04 A:0.72Nm +/- 0.04; VA0deg W:0.73Nm +/- 0.04 A:0.65Nm +/- 0.05; VA15deg W:0.51Nm +/- 0.05 A:0.50Nm +/- 0.08; Ti: FA W:0.82Nm +/- 0.03 A:0.70Nm +/- 0.04; VA0deg W:0.80Nm +/- 0.02 A:0.72Nm +/- 0.05; VA15deg W:0.55Nm +/- 0.03 A:0.54Nm +/- 0.06). In all groups, the removal torque after cyclic testing did not drop below 16% of the removal torque without cyclic testing. No head loosening was observed after cyclic testing. Stainless steel and titanium 2.4mm fixed and variable angle locking screws provide a stable and lasting head-locking mechanism. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:949-952, 2016. C1 [Lenz, Mark; Wahl, Dieter; Zderic, Ivan; Gueorguiev, Boyko; Perren, Stephan M.] AO Res Inst Davos, Clavadelerstr 8, CH-7270 Davos, Switzerland. [Lenz, Mark] Univ Hosp Jena, Dept Trauma Hand & Reconstruct Surg, Jena, Germany. [Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Perren, Stephan M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. RP Lenz, M (reprint author), AO Res Inst Davos, Clavadelerstr 8, CH-7270 Davos, Switzerland.; Lenz, M (reprint author), Univ Hosp Jena, Dept Trauma Hand & Reconstruct Surg, Jena, Germany. EM lenzmar@web.de FU AO Foundation via the AOTK System [AR2012_10] FX The authors are not compensated and there are no other institutional subsidies, corporate affiliations, or funding sources supporting this work unless clearly documented and disclosed. This investigation was performed with the assistance of the AO Foundation via the AOTK System (grant no. AR2012_10). DePuy Synthes is acknowledged for the delivery of all implants. Funding had no influence on the investigation including the results. NR 12 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JUN PY 2016 VL 34 IS 6 BP 949 EP 952 DI 10.1002/jor.23108 PG 4 WC Orthopedics SC Orthopedics GA DN9GN UT WOS:000377387600006 PM 26580296 ER PT J AU Lozano-Calderon, SA Swaim, SO Federico, A Anderson, ME Gebhardt, MC AF Lozano-Calderon, Santiago A. Swaim, Sara O. Federico, Amy Anderson, Megan E. Gebhardt, Mark C. TI Predictors of Soft-Tissue Complications and Deep Infection in Allograft Reconstruction of the Proximal Tibia SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE sarcoma; nutritional optimization; immunologic optimization; proximal tibia; osteoarticular allograft ID LIMB-SALVAGE SURGERY; BONE-TUMORS; OSTEOARTICULAR ALLOGRAFTS; BIOLOGICAL RECONSTRUCTION; RESECTION; SARCOMA; KNEE; OSTEOSARCOMA; CHILDREN AB Background and Objectives: Reconstruction of the proximal tibia after wide resection of malignant tumors in the pediatric population is very challenging. Advocates of allograft reconstruction argue as advantages bone preservation, biological reconstruction that facilitates reattachment of the extensor mechanism and other soft-tissue structures, delay of metallic prosthesis use and preservation of the distal femoral growth plate. However, complications are significant, infection being very common. Methods: Under IRB-approved protocol, 32 patients (17 males, 15 females), 13 years old in average (2-20), who underwent 33 allograft reconstructions of the proximal tibia, were evaluated for the occurrence of soft-tissue complications and/or deep infection (infection affecting the allograft). Potential predictors of soft-tissue complications and deep infection, categorized as pre- and perioperative variables, were analyzed in relation to the risk for developing a soft -tissue complication or a deep infection. Results: The prevalence of soft -tissue complications was 48% (16/33). However, we were not able to identify any significant predictors. The prevalence of deep (allograft) infection was 15% (5/33). Multivariate logistic regression determined higher BMI at the index surgical procedure and lower pre-operative WBC to be independent predictors of deep infection. For each unit of increase in BMI, the odds of deep infection increased by 40% (OR = 1.40; CI = 1.07-3.06; P < 0.05). For each one unit (1,000) of increase in the pre-operative white cell-count, the odds of deep infection decreased by 70% (OR = 0.30; 95%CI = 0.01-0.89; P < 0.05). Four of the five deep infections were in patients with soft -tissue complications, mainly wound dehiscence. However, wound dehiscence or soft -tissue complications were not predictive of deep infection. Conclusion: Soft-tissue complications are prevalent in allograft reconstruction of the proximal tibia. Prevention is important as these may progress to deep infection. Careful attention to nutritional (BMI) and immunological status may help in patient selection for allograft reconstruction. If allograft reconstruction is opted for, efforts should focus on optimization of these factors as they proved to be independent predictors of subsequent deep infection. (C) 2016 Wiley Periodicals, Inc. C1 [Lozano-Calderon, Santiago A.; Anderson, Megan E.; Gebhardt, Mark C.] Harvard Univ, Massachusetts Gen Hosp,Childrens Hosp Boston, Sch Med,Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg,Musculoskeletal Oncol Serv, Boston, MA 02114 USA. [Swaim, Sara O.] Childrens Hosp, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, 300 Longwood Ave, Boston, MA 02115 USA. [Federico, Amy] Childrens Hosp, Dept Pediat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. RP Lozano-Calderon, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Musculoskeletal Oncol Serv, YAW 3B Suite 3700,55 Fruit St, Boston, MA 02114 USA. EM slozanocalderon@partners.org NR 18 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 1 PY 2016 VL 113 IS 7 BP 811 EP 817 DI 10.1002/jso.24234 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA DN9IJ UT WOS:000377392600016 PM 27126893 ER PT J AU McCabe, SE Dickinson, K West, BT Wilens, TE AF McCabe, Sean Esteban Dickinson, Kara West, Brady T. Wilens, Timothy E. TI Age of Onset, Duration, and Type of Medication Therapy for Attention-Deficit/Hyperactivity Disorder and Substance Use During Adolescence: A Multi-Cohort National Study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; stimulant medication therapy; nonstimulant medication therapy; epidemiology; adolescent substance use ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; STIMULANT MEDICATION; CIGARETTE-SMOKING; LONG-TERM; DRUG-USE; METHYLPHENIDATE TREATMENT; YOUNG-ADULTS; ILLICIT USE; ADHD AB Objective: To examine whether age of onset, duration, or type of medication therapy for attention-deficit/hyperactivity disorder (ADHD) is associated with substance use during adolescence. Method: Nationally representative samples of high school seniors were surveyed via self-administered questionnaires. The sample consisted of 40,358 individuals from 10 independent cohorts (2005-2014) and represented a population that was 52% female, 62% white, 10% African American, 14% Hispanic, and 14% other race/ethnicity. Design-based logistic regression analyses were used to test the associations between age of onset, duration, and type of ADHD medication therapy and recent substance use, controlling for potential confounding factors. Results: Individuals who initiated stimulant medication therapy for ADHD later (aged 10-14 years and 15 years and older) and for shorter duration (2 years or less and 3-5 years) as well as those who reported only nonstimulant medication therapy for ADHD had significantly greater odds of substance use in adolescence relative to individuals who initiated stimulant medication therapy for ADHD earlier (aged 9 years or less) and for longer duration (6 or more years). The odds of substance use generally did not differ between population controls (youth without ADHD and unmedicated youth with ADHD) and individuals who initiated stimulant medication for ADHD early (aged 9 years or less) and for longer duration (aged 6 or more years). Conclusion: Relative to later onset and shorter duration of stimulant treatment for ADHD, early onset and longer duration of stimulant treatment for ADHD was associated with a risk of substance use during adolescence that is lower than and similar to that in the general population. C1 Univ Michigan, Ann Arbor, MI USA. [McCabe, Sean Esteban; Dickinson, Kara] Univ Michigan, Inst Res Women & Gender, 204 S State St, Ann Arbor, MI 48109 USA. [McCabe, Sean Esteban] Univ Michigan, Subst Abuse Res Ctr, 204 S State St, Ann Arbor, MI 48109 USA. [West, Brady T.] Univ Michigan, Inst Social Res, Survey Res Ctr, 204 S State St, Ann Arbor, MI 48109 USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Pediat Unit, Boston, MA 02114 USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Adult Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. RP McCabe, SE (reprint author), Univ Michigan, Inst Res Women & Gender, 204 S State St, Ann Arbor, MI 48109 USA.; McCabe, SE (reprint author), Univ Michigan, Subst Abuse Res Ctr, 204 S State St, Ann Arbor, MI 48109 USA. FU National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH) [R01DA031160, R01DA036541] FX The development of this manuscript was supported by research grants R01DA031160 and R01DA036541 from the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or NIH. NR 42 TC 2 Z9 2 U1 8 U2 8 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 JUN PY 2016 VL 55 IS 6 BP 479 EP 486 DI 10.1016/j.jaac.2016.03.011 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA DN9TT UT WOS:000377424300007 PM 27238066 ER PT J AU Beijers, RJHCG van den Borst, B Newman, AB Yende, S Kritchevsky, SB Cassano, PA Bauer, DC Harris, TB Schols, AMWJ AF Beijers, Rosanne J. H. C. G. van den Borst, Bram Newman, Anne B. Yende, Sachin Kritchevsky, Stephen B. Cassano, Patricia A. Bauer, Douglas C. Harris, Tamara B. Schols, Annemie M. W. J. CA Hlth ABC Study TI A Multidimensional Risk Score to Predict All-Cause Hospitalization in Community-Dwelling Older Individuals With Obstructive Lung Disease SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE COPD; pulmonary disease; older age persons; Cox proportional hazards modeling ID PULMONARY-DISEASE; PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; ELDERLY SUBJECTS; COPD; MORTALITY; PERFORMANCE; COMORBIDITIES; POPULATION; TIOTROPIUM AB Background: Both respiratory and nonrespiratory hospitalizations are common and costly events in older individuals with obstructive lung disease. Prevention of any hospitalization in these individuals is essential. We aimed to construct a prediction model for all-cause hospitalization risk in community-dwelling older individuals with obstructive lung disease. Methods: We studied 268 community-dwelling individuals with obstructive lung disease (defined as FEV1/FVC-/- MEFs; and W. Massefski (Dana-Farber Cancer Institute) for technical assistance with MAIM1 characterization by NMR. This research was supported by NIH grant 1R35CA197583, a Leukemia and Lymphoma Society (LLS) Marshall A. Lichtman Specialized Center of Research project grant, the Todd J. Schwartz Memorial Fund, the Wolpoff Family Foundation and an LLS Scholar Award (L.D.W.); NIH grant R01GM101135 and a Waters Corporation research collaboration (J.R.E.); and NIH grant T32GM007753 (J.L.). NR 37 TC 5 Z9 5 U1 4 U2 9 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 JUN PY 2016 VL 23 IS 6 BP 600 EP 607 DI 10.1038/nsmb.3223 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA DN9SU UT WOS:000377421800023 PM 27159560 ER PT J AU Ho, L Bloom, PA Vega, JG Yemul, S Zhao, W Ward, L Savage, E Rooney, R Patel, DH Pasinetti, GM AF Ho, Lap Bloom, Patricia A. Vega, Joan G. Yemul, Shrishailam Zhao, Wei Ward, Libby Savage, Evan Rooney, Robert Patel, Divyen H. Pasinetti, Giulio Maria TI Biomarkers of Resilience in Stress Reduction for Caregivers of Alzheimer's Patients SO NEUROMOLECULAR MEDICINE LA English DT Article DE Family caregiver; Mindfulness-based stress reduction; Emotional distress; Depression; Dementia ID PERIPHERAL-BLOOD; MINDFULNESS MEDITATION; CANCER-PATIENTS; PROGRAM; RISK; DEMENTIA; LEVEL; WOMEN; TRIAL AB Caregiving for a dementia patient is associated with increased risk of psychological and physical health problems. We investigated whether a mindfulness-based stress reduction (MBSR) training course for caregivers that closely models the MBSR curriculum originally established by the Center of Mindfulness at the University of Massachusetts may improve the psychological resilience of non-professional caregivers of Alzheimer's disease patients. Twenty adult non-professional caregivers of dementia patients participated in an 8-week MBSR training course. Caregiver stress, depression, burden, grief, and gene expression profiles of blood mononuclear cells were assessed at baseline and following MBSR. MBSR training significantly improved the psychological resilience of some of the caregivers. We identified predictive biomarkers whose expression is associated with the likelihood of caregivers to benefit from MBSR, and biomarkers whose expression is associated with MBSR psychological benefits. Our biomarker studies provide insight into the mechanisms of health benefits of MBSR and a basis for developing a personalized medicine approach for applying MBSR for promoting psychological and cognitive resilience in caregivers of dementia patients. C1 [Ho, Lap; Yemul, Shrishailam; Zhao, Wei; Ward, Libby; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Room 20-02, New York, NY 10029 USA. [Bloom, Patricia A.; Vega, Joan G.] Icahn Sch Med Mt Sinai, Dept Geriatr, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Savage, Evan; Rooney, Robert; Patel, Divyen H.] Genome Explorat Inc, Memphis, TN 38105 USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Room 20-02, New York, NY 10029 USA.; Pasinetti, GM (reprint author), James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. EM Giulio.Pasinetti@mssm.edu FU Icahn School of Medicine at Mount Sinai; Geriatric Research Education and Clinical Centers (GRECC) of the James J. Peters Veterans Affairs Medical Center; Career Scientist Award in the Research and Development unit FX This study was supported by discretionary funding from the Icahn School of Medicine at Mount Sinai to Dr. Giulio Maria Pasinetti and by the Geriatric Research Education and Clinical Centers (GRECC) of the James J. Peters Veterans Affairs Medical Center. In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We acknowledge that the contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 41 TC 0 Z9 0 U1 9 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD JUN PY 2016 VL 18 IS 2 BP 177 EP 189 DI 10.1007/s12017-016-8388-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA DN9XZ UT WOS:000377435300005 PM 26984114 ER PT J AU Zhang, SZ You, ZR Wang, SX Yang, JS Yang, LJ Sun, Y Mi, WL Yang, LL McCabe, MF Shen, SQ Chen, L Mao, JR AF Zhang, Shuzhuo You, Zerong Wang, Shuxing Yang, Jinsheng Yang, Lujia Sun, Yan Mi, Wenli Yang, Liling McCabe, Michael F. Shen, Shiqian Chen, Lucy Mao, Jianren TI Neuropeptide S modulates the amygdaloidal HCN activities (I-h) in rats: Implication in chronic pain SO NEUROPHARMACOLOGY LA English DT Article DE NPS; HCN; Amygdala; GABA; Pain ID ACTIVATED PACEMAKER CHANNELS; CORTICOTROPIN-RELEASING-FACTOR; NEUROPATHIC PAIN; CATION CHANNELS; FUNCTIONAL-CHARACTERIZATION; MOLECULAR CHARACTERIZATION; PERIPHERAL MONONEUROPATHY; EXPRESSING NEURONS; PYRAMIDAL NEURONS; THALAMIC NEURONS AB Neuropeptide S (NPS), an endogenous anxiolytic, has been shown to protect against chronic pain through interacting with its cognate NPS receptor (NPSR) in the brain. However, the cellular mechanism of this NPS action remains unclear. We report that NPS inhibits hyperpolarization-activated cyclic nucleotide gated (HCN) channel current (Ih) in the rat's amygdala through activation of NPSR. This NPS effect is mediated through ERK1/2 phosphorylation in a subset of pyramidal-like neurons located in the medial amygdala. The characters of the recorded Ih suggest a major role for HCN1 activity in this process. Inhibition of I-h by NPS stimulates the glutamatergic drive onto fast spiking intra-amygdalolidal GABAergic interneurons, which in turn facilitates GABA release onto pyramidal-like neurons. Moreover, the HCN1 expression is increased in the amygdala of rats with peripheral nerve injury and intra-amygdaloidal administration of the HCN channel inhibitor ZD7288 attenuates nociceptive behavior in these rats. These results suggest that NPS-mediated modulation of intra-amygdaloidal HCN channel activities may be an important central inhibitory mechanism for regulation of chronic pain. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Zhang, Shuzhuo; You, Zerong; Wang, Shuxing; Yang, Jinsheng; Mi, Wenli; Yang, Liling; McCabe, Michael F.; Shen, Shiqian; Chen, Lucy; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. [Zhang, Shuzhuo; Yang, Lujia; Sun, Yan] Beijing Inst Pharmacol & Toxicol, 27 Tai Ping Rd, Beijing 100850, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM jmao@mgh.harvard.edu FU NIH [R01 DE022901, R01 DE018214] FX This work was supported by NIH grants R01 DE022901 and R01 DE018214 (J.M.). NR 74 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2016 VL 105 BP 420 EP 433 DI 10.1016/j.neuropharm.2016.02.004 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA DN8EF UT WOS:000377311300039 PM 26855147 ER PT J AU Goldfine, AB Patti, ME AF Goldfine, Allison B. Patti, Mary Elizabeth TI How common is hypoglycemia after gastric bypass? SO OBESITY LA English DT Editorial Material ID SURGERY; NEUROGLYCOPENIA C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu FU NIDDK NIH HHS [RC1 DK086918, R56 DK095451, P30 DK036836] NR 6 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2016 VL 24 IS 6 BP 1210 EP 1211 DI 10.1002/oby.21520 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DO1EK UT WOS:000377521100005 PM 27225595 ER PT J AU Al-kindi, H Fletcher, CDM Khan, Y AF Al-kindi, Hunaina Fletcher, Christopher D. M. Khan, Yasmeen TI Chondrolipoma of the tonsil SO PATHOLOGY LA English DT Letter ID LIPOMA C1 [Al-kindi, Hunaina] Directorate Gen Khoula Hosp, Hi Tech Med Lab, Dept Histopathol, Muscat, Oman. [Fletcher, Christopher D. M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Fletcher, Christopher D. M.] Brigham & Womens Hosp, Anat Pathol, 75 Francis St, Boston, MA 02115 USA. [Khan, Yasmeen] Al Raffah Hosp, Muscat, Oman. RP Al-kindi, H (reprint author), Directorate Gen Khoula Hosp, Hi Tech Med Lab, Dept Histopathol, Muscat, Oman. EM alkindihunaina@hotmail.com NR 12 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 0031-3025 EI 1465-3931 J9 PATHOLOGY JI Pathology PD JUN PY 2016 VL 48 IS 4 BP 386 EP 388 DI 10.1016/j.pathol.2016.03.010 PG 3 WC Pathology SC Pathology GA DN7CS UT WOS:000377233500018 PM 27136706 ER PT J AU Maguire, EM Bokhour, BG Asch, SM Wagner, TH Gifford, AL Gallagher, TH Durfee, JM Martinello, RA Elwy, AR AF Maguire, E. M. Bokhour, B. G. Asch, S. M. Wagner, T. H. Gifford, A. L. Gallagher, T. H. Durfee, J. M. Martinello, R. A. Elwy, A. R. TI Disclosing large scale adverse events in the US Veterans Health Administration: lessons from media responses SO PUBLIC HEALTH LA English DT Article DE Crisis and risk communication; Media analysis; Disclosures of large scale adverse events ID CRISIS; RISK; COMMUNICATION; POLICY AB Objectives: We examined print, broadcast and social media reports about health care systems' disclosures of large scale adverse events to develop future effective messaging. Study design: Directed content analysis. Methods: We systematically searched four communication databases, YouTube and Really Simple Syndication (RSS) feeds relating to six disclosures of lapses in infection control practices in the Department of Veterans Affairs occurring between 2009 and 2012. We assessed these with a coding frame derived from effective crisis and risk communication models. Results: We identified 148 unique media reports. Some components of effective communication (discussion of cause, reassurance, self-efficacy) were more present than others (apology, lessons learned). Media about 'promoting secrecy ' and 'slow response ' appeared in reports when time from event discovery to patient notification was over 75 days. Elected officials' quotes (n = 115) were often negative (83%). Hospital officials' comments (n = 165) were predominantly neutral (92%), and focused on information sharing. Conclusions: Health care systems should work to ensure that they develop clear messages focused on what is not well covered by the media, including authentic apologies, remedial actions taken, and shorten the timeframe between event identification and disclosure to patients. Published by Elsevier Ltd on behalf of The Royal Society for Public Health. C1 [Maguire, E. M.; Bokhour, B. G.; Gifford, A. L.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd, Bedford, MA USA. [Elwy, A. R.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 South Huntington Ave,Jamaica Plain Campus, Boston, MA 02130 USA. [Bokhour, B. G.; Gifford, A. L.; Elwy, A. R.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 715 Albany St, Boston, MA USA. [Asch, S. M.; Wagner, T. H.] VA Palo Alto Healthcare Syst, Ctr Innovat Implementat, 3801 Miranda Ave, Menlo Pk, CA USA. [Wagner, T. H.] VA Palo Alto Healthcare Syst, Hlth Econ Resource Ctr, 3801 Miranda Ave, Menlo Pk, CA USA. [Asch, S. M.; Wagner, T. H.] Stanford Univ, Sch Med, 291 Campus Dr, Stanford, CA 94305 USA. [Gallagher, T. H.] Univ Washington, Sch Med, 1959 NE Pacific St, Seattle, WA USA. [Durfee, J. M.; Martinello, R. A.] Vet Hlth Adm, Clin Publ Hlth Program, Off Publ Hlth, 810 Vermont Ave NW, Washington, DC USA. [Martinello, R. A.] Yale Univ, Sch Med, Cedar St, New Haven, CT USA. RP Maguire, EM (reprint author), 200 Springs Rd 152, Bedford, MA 01730 USA. EM Elizabeth.maguire@va.gov FU VA Health Services Research and Development Service [SDR 11-440] FX VA Health Services Research and Development Service (SDR 11-440). Funding source has no role in study design, analysis or writing of this article NR 33 TC 1 Z9 1 U1 1 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0033-3506 EI 1476-5616 J9 PUBLIC HEALTH JI Public Health PD JUN PY 2016 VL 135 BP 75 EP 82 DI 10.1016/j.puhe.2015.10.016 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DN9QH UT WOS:000377414200010 PM 27026251 ER PT J AU Wallace, B Khanna, D Aquino-Beaton, C Singh, JA Duffy, E Elashoff, D Khanna, PP AF Wallace, Beth Khanna, Dinesh Aquino-Beaton, Cleopatra Singh, Jasvinder A. Duffy, Erin Elashoff, David Khanna, Puja P. TI Performance of Gout Impact Scale in a longitudinal observational study of patients with gout SO RHEUMATOLOGY LA English DT Article DE gout; validated measure; outcomes ID QUALITY-OF-LIFE; HEALTH; DISEASE AB Objective. The aim was to evaluate the reliability, validity and responsiveness to change of the Gout Impact Scale (GIS), a disease-specific measure of patient-reported outcomes, in a multicentre longitudinal prospective cohort of gout patients. Methods. Subjects completed the GIS, a 24-item instrument with five scales: Concern Overall, Medication Side Effects, Unmet Treatment Need, Well-Being during Attack, and Concern Over Attack. The total GIS score was calculated by averaging the GIS scale scores. HAQ-Disability Index (HAQ-DI), Short Form (SF)-36 physical and mental component summaries (PCS and MCS) and physician and patient gout severity assessments were also completed. Reliability was assessed with Cronbach's alpha. Baseline GIS scores were compared in subjects with and without gout attacks in the past 3 months using Wilcoxon rank sum tests. Multivariate linear regression was used to evaluate predictors of total GIS. Pearson's correlation coefficients 0.24-0.36 were considered moderate and > 0.37 considered large. The effect size for responsiveness to change was interpreted as follows: 0.20-0.49 small, 0.50-0.79 medium and > 0.79 large. Results. In 147 subjects, reliability was acceptable for total GIS (0.93) and all GIS scales (0.82-0.94) except Medication Side Effects and Unmet Treatment Need. Total GIS and all scales except Medication Side Effects discriminated between subjects with and without recent gout attacks (P < 0.05). Total GIS showed moderate-to-large correlations with HAQ-DI, SF-36 PCS and MCS (0.33-0.46). Improvement in total GIS tracked with improved physician and patient severity scores. Worsening physician severity score and recent gout attack predicted worsening total GIS. Conclusion. Total GIS score is reliable, valid and responsive to change in patients with gout, and differentiates between subjects with and without recent gout attacks. C1 [Wallace, Beth; Khanna, Dinesh; Khanna, Puja P.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Aquino-Beaton, Cleopatra] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Rheumatol, Los Angeles, CA USA. [Singh, Jasvinder A.] Univ Alabama & Birmingham VA, Div Rheumatol, Dept Med, Birmingham, AL USA. [Duffy, Erin; Elashoff, David] Univ Calif Los Angeles, Dept Med Stat Core, Los Angeles, CA USA. [Khanna, Puja P.] Ann Arbor VA Med Ctr, Div Rheumatol, Dept Med, Ann Arbor, MI USA. RP Khanna, PP (reprint author), Dept Internal Med, Div Rheumatol, 300 North Ingalls,Ste 7C27, Ann Arbor, MI 48109 USA. EM pkhanna@med.umich.edu NR 24 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2016 VL 55 IS 6 BP 982 EP 990 DI 10.1093/rheumatology/kew007 PG 9 WC Rheumatology SC Rheumatology GA DN9WU UT WOS:000377432200004 PM 26888852 ER PT J AU Wallace, ZS Mattoo, H Mahajan, VS Kulikova, M Lu, L Deshpande, V Choi, HK Pillai, S Stone, JH AF Wallace, Zachary S. Mattoo, Hamid Mahajan, Vinay S. Kulikova, Maria Lu, Leo Deshpande, Vikram Choi, Hyon K. Pillai, Shiv Stone, John H. TI Predictors of disease relapse in IgG4-related disease following rituximab SO RHEUMATOLOGY LA English DT Article DE IgG4-related disease; rituximab; IgG4; IgE; eosinophil; biomarker; relapse; remission; IgG4RD Responder Index ID SERUM IGG4; AUTOIMMUNE PANCREATITIS; SYSTEMIC-DISEASE; EVENTS AB Objective. IgG4-related disease (IgG4-RD) is a relapsing-remitting condition responsible for fibroinflammatory lesions that can lead to organ damage and life-threatening complications at nearly any anatomical site. The duration of remission following treatment varies and predictors of relapse are unclear. The objectives of this study were to review our experience with rituximab as remission induction in IgG4RD, to clarify the duration of efficacy and to identify predictors of flare following treatment. Methods. In this retrospective cohort study, all patients were treated with two doses of rituximab (1 g) separated by 15 days. Clinical, radiographic and laboratory data pertaining to rituximab response and disease relapse were collected from the electronic medical record. Kaplan-Meier curves were constructed to estimate the time to disease relapse. Log-rank analyses were performed to compare times to relapse among subgroups. Potential relapse predictors were evaluated with Cox regression analysis. Results. Fifty-seven of 60 patients (95%) had clinical responses to rituximab. Forty-one patients (68%) were treated without glucocorticoids. Twenty-one patients (37%) experienced relapses following treatment at a median time from the first infusion of 244 days. Baseline concentrations of serum IgG4, IgE and circulating eosinophils predicted subsequent relapses, with hazard ratios of 6.2 (95% CI: 1.2, 32.0), 8.2 (95% CI: 1.4, 50.0) and 7.9 (95% CI: 1.8, 34.7), respectively. The higher the baseline values, the greater the risk of relapse and the shorter the time to relapse. Only 10% of the patients had elevations of all three major risk factors, underscoring the importance of measuring all three at baseline. Conclusion. Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently. C1 [Wallace, Zachary S.; Lu, Leo; Choi, Hyon K.; Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Mattoo, Hamid; Mahajan, Vinay S.; Kulikova, Maria; Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mattoo, Hamid; Mahajan, Vinay S.; Kulikova, Maria; Pillai, Shiv] Massachusetts Gen Hosp, Massachusetts Inst Technol, Ragon Inst, Boston, MA 02114 USA. [Mattoo, Hamid; Mahajan, Vinay S.; Kulikova, Maria; Pillai, Shiv] Harvard Univ, Boston, MA 02115 USA. [Lu, Leo] Boston Univ, Sch Med, Boston, MA 02118 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram; Choi, Hyon K.; Pillai, Shiv; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU NIAID NIH HHS [K08 AI113163, U19 AI110495]; NIAMS NIH HHS [T32 AR007258] NR 28 TC 9 Z9 9 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2016 VL 55 IS 6 BP 1000 EP 1008 DI 10.1093/rheumatology/kev438 PG 9 WC Rheumatology SC Rheumatology GA DN9WU UT WOS:000377432200006 PM 26888853 ER PT J AU Lee, T Lu, N Felson, DT Choi, HK Dalal, DS Zhang, YQ Dubreuil, M AF Lee, Taeyeon Lu, Na Felson, David T. Choi, Hyon K. Dalal, Deepan S. Zhang, Yuqing Dubreuil, Maureen TI Use of non-steroidal anti-inflammatory drugs correlates with the risk of venous thromboembolism in knee osteoarthritis patients: a UK population-based case-control study SO RHEUMATOLOGY LA English DT Article DE NSAIDs; VTE; knee osteoarthritis ID ACUTE MYOCARDIAL-INFARCTION; SELECTIVE CYCLOOXYGENASE-2 INHIBITORS; BODY-MASS INDEX; RHEUMATOID-ARTHRITIS; GASTROINTESTINAL TOXICITY; PULMONARY-EMBOLISM; RANDOMIZED-TRIALS; METAANALYSIS; THROMBOSIS; CELECOXIB AB Objective. We aimed to examine whether the current users of specific NSAIDs have an increased risk of venous thromboembolism (VTE) among knee OA patients. Methods. We conducted a population-based case-control study using The Health Improvement Network, a database of patient records from general practices in the UK. For every VTE case, we identified five controls matched on age, sex and calendar year of study enrolment. We used conditional logistic regression to assess the association between current use of specific NSAIDs and risk of VTE relative to remote NSAID users. Results. Among knee OA patients with at least one NSAID prescription, we identified 4020 incident cases of VTE and 20 059 matched controls. Adjusted odd ratios (ORs) relative to the remote users were 1.38 (95% CI: 1.32, 1.44) for recent users and 1.43 (95% CI: 1.36, 1.49) for current users. Among the current NSAID users, the risk of VTE was increased with diclofenac [OR 1.63 (95% CI: 1.53, 1.74)], ibuprofen [OR = 1.49 (95% CI: 1.38, 1.62)], meloxicam [OR = 1.29 (95% CI: 1.11, 1.50)] and coxibs [celecoxib, OR = 1.30 (95% CI: 1.11, 1.51); rofecoxib, OR = 1.44 (95% CI: 1.18, 1.76)]; naproxen did not increase VTE risk [OR = 1.00 (95% CI: 0.89, 1.12)]. Conclusion. Compared with the remote users of NSAIDs, the risk of VTE increased for current users of diclofenac, ibuprofen, meloxicam, and coxibs, but not for naproxen, in the knee OA population. Clinicians should consider the risk profile for specific NSAIDs when recommending their use. C1 [Lee, Taeyeon; Lu, Na; Felson, David T.; Zhang, Yuqing] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Lu, Na; Choi, Hyon K.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Felson, David T.; Dalal, Deepan S.; Dubreuil, Maureen] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Dubreuil, Maureen] VA Boston Healthcare Syst, USA Rheumatol Div, Boston, MA USA. RP Dubreuil, M (reprint author), Boston Univ, Sch Med, Rheumatol Sect, Med, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM mdubreui@bu.edu FU NIAMS NIH HHS [P60 AR047785] NR 38 TC 1 Z9 1 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2016 VL 55 IS 6 BP 1099 EP 1105 DI 10.1093/rheumatology/kew036 PG 7 WC Rheumatology SC Rheumatology GA DN9WU UT WOS:000377432200019 PM 26983451 ER PT J AU Keer, N Hershfield, M Caskey, T Unizony, S AF Keer, Nikky Hershfield, Michael Caskey, Thomas Unizony, Sebastian TI Novel compound heterozygous variants in CECR1 gene associated with childhood onset polyarteritis nodosa and deficiency of ADA2 SO RHEUMATOLOGY LA English DT Letter ID ADENOSINE-DEAMINASE 2; CLASSIFICATION; VASCULOPATHY; CRITERIA C1 [Keer, Nikky] St Vincent Hosp, Dept Med, 123 Summer St, Worcester, MA 01608 USA. [Hershfield, Michael] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Hershfield, Michael] Duke Univ, Sch Med, Dept Biochem, Durham, NC USA. [Caskey, Thomas] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Unizony, Sebastian] Massachusetts Gen Hosp, Div Rheumatol, Boston, MA 02114 USA. RP Keer, N (reprint author), St Vincent Hosp, Dept Med, 123 Summer St, Worcester, MA 01608 USA. EM nikkyke@pcom.edu NR 6 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2016 VL 55 IS 6 BP 1145 EP 1147 DI 10.1093/rheumatology/kew050 PG 3 WC Rheumatology SC Rheumatology GA DN9WU UT WOS:000377432200029 PM 27069017 ER PT J AU Scott, RA Freitag, DF Li, L Chu, AY Surendran, P Young, R Grarup, N Stancakova, A Chen, YN Varga, TV Yaghootkar, H Luan, JA Zhao, JH Willems, SM Wessel, J Wang, S Maruthur, N Michailidou, K Pirie, A van der Lee, SJ Gillson, C Al Olama, AA Amouyel, P Arriola, L Arveiler, D Aviles-Olmos, I Balkau, B Barricarte, A Barroso, I Garcia, SB Bis, JC Blankenberg, S Boehnke, M Boeing, H Boerwinkle, E Borecki, IB Bork-Jensen, J Bowden, S Caldas, C Caslake, M Cupples, LA Cruchaga, C Czajkowski, J den Hoed, M Dunn, JA Earl, HM Ehret, GB Ferrannini, E Ferrieres, J Foltynie, T Ford, I Forouhi, NG Gianfagna, F Gonzalez, C Grioni, S Hiller, L Jansson, JH Jorgensen, ME Jukema, JW Kaaks, R Kee, F Kerrison, ND Key, TJ Kontto, J Kote-Jarai, Z Kraja, AT Kuulasmaa, K Kuusisto, J Linneberg, A Liu, CY Marenne, G Mohlke, KL Morris, AP Muir, K Muller-Nurasyid, M Munroe, PB Navarro, C Nielsen, SF Nilsson, PM Nordestgaard, BG Packard, CJ Palli, D Panico, S Peloso, GM Perola, M Peters, A Poole, CJ Quiros, JR Rolandsson, O Sacerdote, C Salomaa, V Sanchez, MJ Sattar, N Sharp, SJ Sims, R Slimani, N Smith, JA Thompson, DJ Trompet, S Tumino, R van der A, DL van der Schouw, YT Virtamo, J Walker, M Walter, K Abraham, JE Amundadottir, LT Aponte, JL Butterworth, A Dupuis, J Easton, DF Eeles, RA Erdmann, J Franks, PW Frayling, TM Hansen, T Howson, JMM Jorgensen, T Kooner, J Laakso, M Langenberg, C McCarthy, MI Pankow, JS Pedersen, O Riboli, E Rotter, JI Saleheen, D Samani, NJ Schunkert, H Vollenweider, P O'Rahilly, S Deloukas, P Danesh, J Goodarzi, MO Kathiresan, S Meigs, JB Ehm, MG Wareham, NJ Waterworth, DM AF Scott, Robert A. Freitag, Daniel F. Li, Li Chu, Audrey Y. Surendran, Praveen Young, Robin Grarup, Niels Stancakova, Alena Chen, Yuning Varga, Tibor V. Yaghootkar, Hanieh Luan, Jian'an Zhao, Jing Hua Willems, Sara M. Wessel, Jennifer Wang, Shuai Maruthur, Nisa Michailidou, Kyriaki Pirie, Ailith van der Lee, Sven J. Gillson, Christopher Al Olama, Ali Amin Amouyel, Philippe Arriola, Larraitz Arveiler, Dominique Aviles-Olmos, Iciar Balkau, Beverley Barricarte, Aurelio Barroso, Ines Garcia, Sara Benlloch Bis, Joshua C. Blankenberg, Stefan Boehnke, Michael Boeing, Heiner Boerwinkle, Eric Borecki, Ingrid B. Bork-Jensen, Jette Bowden, Sarah Caldas, Carlos Caslake, Muriel Cupples, L. Adrienne Cruchaga, Carlos Czajkowski, Jacek den Hoed, Marcel Dunn, Janet A. Earl, Helena M. Ehret, Georg B. Ferrannini, Ele Ferrieres, Jean Foltynie, Thomas Ford, Ian Forouhi, Nita G. Gianfagna, Francesco Gonzalez, Carlos Grioni, Sara Hiller, Louise Jansson, Jan-Hakan Jorgensen, Marit E. Jukema, J. Wouter Kaaks, Rudolf Kee, Frank Kerrison, Nicola D. Key, Timothy J. Kontto, Jukka Kote-Jarai, Zsofia Kraja, Aldi T. Kuulasmaa, Kari Kuusisto, Johanna Linneberg, Allan Liu, Chunyu Marenne, Galle Mohlke, Karen L. Morris, Andrew P. Muir, Kenneth Mueller-Nurasyid, Martina Munroe, Patricia B. Navarro, Carmen Nielsen, Sune F. Nilsson, Peter M. Nordestgaard, Borge G. Packard, Chris J. Palli, Domenico Panico, Salvatore Peloso, Gina M. Perola, Markus Peters, Annette Poole, Christopher J. Quiros, J. Ramn Rolandsson, Olov Sacerdote, Carlotta Salomaa, Veikko Sanchez, Mara-Jose Sattar, Naveed Sharp, Stephen J. Sims, Rebecca Slimani, Nadia Smith, Jennifer A. Thompson, Deborah J. Trompet, Stella Tumino, Rosario van der A, Daphne L. van der Schouw, Yvonne T. Virtamo, Jarmo Walker, Mark Walter, Klaudia Abraham, Jean E. Amundadottir, Laufey T. Aponte, Jennifer L. Butterworth, Adams. Dupuis, Josee Easton, Douglas F. Eeles, Rosalind A. Erdmann, Jeanette Franks, Paul W. Frayling, Timothy M. Hansen, Torben Howson, Joanna M. M. Jorgensen, Torben Kooner, Jaspal Laakso, Markku Langenberg, Claudia McCarthy, Mark I. Pankow, James S. Pedersen, Oluf Riboli, Elio Rotter, Jerome I. Saleheen, Danish Samani, Nilesh J. Schunkert, Heribert Vollenweider, Peter O'Rahilly, Stephen Deloukas, Panos Danesh, John Goodarzi, Mark O. Kathiresan, Sekar Meigs, James B. Ehm, Margaret G. Wareham, Nicholas J. Waterworth, Dawn M. CA CVD50 Consortium GERAD-EC Consortium Neurology Working Grp CHARGE Alzheimer's Dis Genetics Consortiu Pancreatic Canc Cohort Consortium European Prospective Invest Into C EPIC-InterAct CHARGE Consortium CHD Exome Consortium CARDIOGRAM Exome Consortium TI A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; TYPE-2 DIABETES-MELLITUS; PLACEBO-CONTROLLED TRIAL; RECEPTOR AGONIST LIXISENATIDE; ONCE-DAILY LIXISENATIDE; RANDOMIZED CONTROLLED-TRIAL; INCRETIN-BASED THERAPIES; BETA-CELL FUNCTION; BODY-MASS INDEX; DOUBLE-BLIND AB Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. C1 [Scott, Robert A.; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Gillson, Christopher; Forouhi, Nita G.; Kerrison, Nicola D.; Sharp, Stephen J.; Langenberg, Claudia; Wareham, Nicholas J.] Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England. [Freitag, Daniel F.; Surendran, Praveen; Young, Robin; Butterworth, Adams.; Howson, Joanna M. M.; Danesh, John] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Freitag, Daniel F.; Barroso, Ines; Marenne, Galle; Walter, Klaudia; Danesh, John] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Li, Li] GlaxoSmithKline, Stat Genet Projects Clin Platforms & Sci PCPS, Res Triangle Pk, NC 27709 USA. [Chu, Audrey Y.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Grarup, Niels; Bork-Jensen, Jette; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, NovoNordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark. [Stancakova, Alena] Univ Eastern Finland, Inst Clin Med, Internal Med, FI-70211 Kuopio, Finland. [Chen, Yuning; Wang, Shuai; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Varga, Tibor V.; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-205 Malmo, Sweden. [Yaghootkar, Hanieh; Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX1 2LU, Devon, England. [Willems, Sara M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CE Rotterdam, Netherlands. [Wessel, Jennifer] Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA. [Wessel, Jennifer] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Maruthur, Nisa] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Maruthur, Nisa] Johns Hopkins Univ, Welch Ctr Prevent Epidemol & Clin Res, Baltimore, MD 21205 USA. [Maruthur, Nisa] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Michailidou, Kyriaki; Pirie, Ailith; Al Olama, Ali Amin; Garcia, Sara Benlloch; Thompson, Deborah J.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England. [van der Lee, Sven J.] Erasmus Univ, Dept Epidemiol, Med Ctr, NL-3000 CA Rotterdam, Netherlands. [Amouyel, Philippe] Univ Lille, Ctr Hosp Reg Univ Lille, INSERM, Inst Pasteur Lille,UMR 1167,RID AGE, F-59000 Lille, France. [Arriola, Larraitz] Publ Hlth Div Gipuzkoa, San Sebastian 20013, Spain. [Arriola, Larraitz] Basque Govt, Inst BIOdonostia, San Sebastian 20014, Spain. [Arriola, Larraitz; Barricarte, Aurelio; Navarro, Carmen; Sanchez, Mara-Jose] CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain. [Arveiler, Dominique] Univ Strasbourg, Dept Epidemiol & Publ Hlth EA3430, F-67085 Strasbourg, France. [Aviles-Olmos, Iciar; Foltynie, Thomas] UCL Inst Neurol, Sobell Partment Motor Neurosci, London WC1N 3BG, England. [Balkau, Beverley] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, F-94807 Villejuif, France. [Balkau, Beverley; Barroso, Ines] Univ Paris 11, F-94805 Villejuif, France. [Barricarte, Aurelio] Navarre Publ Hlth Inst ISPN, Pamplona 31003, Spain. [O'Rahilly, Stephen] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England. [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. [Blankenberg, Stefan] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany. [Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Boeing, Heiner] German Inst Human Nutr, Potsdam Rehbruecke, D-14558 Nuthetal, Germany. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77025 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA. [Bowden, Sarah] Univ Birmingham, Inst Canc Studies, Canc Res UK Clin Trials Unit, Birmingham B15 2TT, W Midlands, England. [Caldas, Carlos] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England. [Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Dept Oncol, Cambridge CB2 0RE, England. [Caslake, Muriel; Ford, Ian; Packard, Chris J.; Sattar, Naveed] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. [Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Cruchaga, Carlos] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Czajkowski, Jacek; Kraja, Aldi T.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA. [Czajkowski, Jacek; Kraja, Aldi T.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA. [den Hoed, Marcel] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75237 Uppsala, Sweden. [Dunn, Janet A.; Hiller, Louise] Univ Warwick, Warwick Clin Trials Unit, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. [Earl, Helena M.] Univ Cambridge, Cambridge CB2 0QQ, England. [Earl, Helena M.] Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England. [Ehret, Georg B.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Ferrannini, Ele] CNR, Inst Clin Physiol, I-56124 Pisa, Italy. [Ferrieres, Jean] Ctr Hosp Univ CHU Toulouse, Dept Epidemiol, INSERM, UMR 1027, F-31000 Toulouse, France. [Gianfagna, Francesco] Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy. [Gianfagna, Francesco] IRCCS, Dept Epidemiol & Prevent, Ist Neurol Mediterraneo Neuromed, I-86077 Pozzilli, Italy. [Gonzalez, Carlos] Catalan Inst Oncol ICO, Barcelona 08908, Spain. [Grioni, Sara] Epidemiol & Prevent Unit, I-20133 Milan, Italy. [Jansson, Jan-Hakan] Res Unit, S-93141 Skelleftea, Sweden. [Jansson, Jan-Hakan; Jukema, J. Wouter; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. [Jorgensen, Marit E.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Jorgensen, Marit E.] Southern Denmark Univ, Natl Inst Publ Hlth, DK-1353 Odense, Denmark. [Trompet, Stella] Leiden Univ, Med Ctr, NL-2333 AA Leiden, Netherlands. [Kaaks, Rudolf] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Kee, Frank] Queens Univ Belfast, UK Clin Res Collaborat UKCRC, Ctr Excellence Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland. [Key, Timothy J.] Univ Oxford, S Parks Rd, Oxford OX1 2JD, England. [Kontto, Jukka; Kuulasmaa, Kari; Salomaa, Veikko; Virtamo, Jarmo] Natl Inst Hlth & Welfare, FI-00271 Helsinki, Finland. [Kote-Jarai, Zsofia; Eeles, Rosalind A.] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Kuusisto, Johanna] Univ Eastern Finland, Inst Clin Med, Internal Med, FI-70211 Kuopio, Finland. [Linneberg, Allan] Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark. [Linneberg, Allan] Rigshosp, Dept Clin Expt, DK-2100 Copenhagen, Denmark. 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[Mueller-Nurasyid, Martina; Peters, Annette; Schunkert, Heribert] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany. [Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London EC1M 6BQ, England. [Navarro, Carmen] Murcia Reg Hlth Council, Dept Epidemiol, IMIB Arrixaca, Murcia 30008, Spain. [Nielsen, Sune F.; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Copenhagen, Denmark. [Nilsson, Peter M.] Lund Univ, S-20502 Malmo, Sweden. [Palli, Domenico; Perola, Markus] Canc Res & Prevent Inst ISPO, I-50141 Florence, Italy. [Panico, Salvatore] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, I-80131 Naples, Italy. [Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Peloso, Gina M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland. [Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany. [Poole, Christopher J.] Univ Hosp Coventry & Warwickshire, Arden Canc Ctr, Dept Med Oncol, Coventry CV2 2DX, W Midlands, England. [Quiros, J. Ramn] Publ Hlth Directorate, Oviedo 33006, Asturias, Spain. [Rolandsson, Olov] Umea Univ, S-90187 Umea, Sweden. [Sacerdote, Carlotta] Univ Turin, Citta Salute & Sci Hosp, Unit Canc Epidemiol, I-10126 Turin, Italy. [Sacerdote, Carlotta] Ctr Canc Prevent CPO, I-10126 Turin, Italy. [Sacerdote, Carlotta] Human Genet Fdn, I-10126 Turin, Italy. [Sanchez, Mara-Jose] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada 18012, Spain. [Sims, Rebecca] Cardiff Univ, MRC Ctr, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales. [Slimani, Nadia] Int Agcy Res Canc, F-69372 Lyon, France. [Smith, Jennifer A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Tumino, Rosario] ASP Ragusa, Civ MP Arezzo Hosp, Canc Registry & Histopathol Unit, I-97100 Ragusa, Italy. [van der A, Daphne L.] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands. [van der Schouw, Yvonne T.] Univ Med Ctr Utrecht, NL-3508 GA Utrecht, Netherlands. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Abraham, Jean E.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Strangeways Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge CB1 8RN, England. [Amundadottir, Laufey T.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Aponte, Jennifer L.; Ehm, Margaret G.] GlaxoSmithKline, PCPS, Genet, Res Triangle Pk, NC 27709 USA. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Surrey SW3 6JJ, England. [Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany. [Franks, Paul W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jorgensen, Torben] Res Ctr Prevent & Hlth, DK-2600 Capital Region, Denmark. [Jorgensen, Torben] Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, DK-1014 Copenhagen, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, DK-9220 Aalborg, Denmark. [Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England. [Kooner, Jaspal] Imperial Coll Healthcare NHS Trust, London W2 1NY, England. [Kooner, Jaspal] Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England. [Laakso, Markku] Univ Kuopio, Dept Med, FI-70211 Kuopio, Finland. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab OCDEM, Oxford OX3 7LE, England. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London W2 1PG, England. [Rotter, Jerome I.] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA. [Saleheen, Danish] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England. [Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany. [Vollenweider, Peter] Lausanne Univ Hosp CHUV, Dept Internal Med, Internal Med, BH10-462, CH-1011 Lausanne, Switzerland. [O'Rahilly, Stephen] MRC Metab Dis Unit, Cambridge CB2 0QQ, England. [O'Rahilly, Stephen] Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England. [Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiol Div, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Waterworth, Dawn M.] GlaxoSmithKline, PCPS, Genet, Philadelphia, PA 19104 USA. RP Waterworth, DM (reprint author), Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England. EM robert.scott@mrc-epid.cam.ac.uk; nick.wareham@mrc-epid.cam.ac.uk; dawn.m.waterworth@gsk.com RI Gianfagna, Francesco/K-4561-2016; van der Schouw, Yvonne/F-8327-2014; Peters, Annette/A-6117-2011; Deloukas, Panos/B-2922-2013; Colaus, PsyColaus/K-6607-2013; Grarup, Niels/K-2807-2015; Grioni, Sara/K-5320-2016; Erdmann, Jeanette/P-7513-2014; OI Gianfagna, Francesco/0000-0003-4615-0816; van der Schouw, Yvonne/0000-0002-4605-435X; Deloukas, Panos/0000-0001-9251-070X; Grarup, Niels/0000-0001-5526-1070; PALLI, Domenico/0000-0002-5558-2437; Grioni, Sara/0000-0002-5891-8426; Erdmann, Jeanette/0000-0002-4486-6231; Caldas, Carlos/0000-0003-3547-1489; Earl, Helena/0000-0003-1549-8094; Wessel, Jennifer/0000-0002-7031-0085; Sacerdote, Carlotta/0000-0002-8008-5096; Kuulasmaa, Kari/0000-0003-2165-1411; Forouhi, Nita/0000-0002-5041-248X; Jorgensen, Torben/0000-0001-9453-2830; Varga, Tibor/0000-0002-2383-699X; Kontto, Jukka/0000-0003-3899-9852; Smith, Jennifer/0000-0002-3575-5468; Pankow, James/0000-0001-7076-483X; Ewing, Ailith/0000-0002-2272-1277; Linneberg, Allan/0000-0002-0994-0184; Peters, Annette/0000-0001-6645-0985 FU GSK; Medical Research Council [MC_UU_12015/1]; [R01 AG033193]; [UO1AG032984] FX The work described in this manuscript was funded, in part, by GSK and, in part, by the Medical Research Council (MC_UU_12015/1). CHARGE (Cohorts for Health and Aging Research in Genetic Epidemiology) AD analyses were funded by R01 AG033193 (P. I. Seshadri). ADGC (Alzheimer's Disease Genetics Consortium) AD analyses were funded by UO1AG032984 (P. I. Schellenberg). Additional funding sources are outlined in the Supplementary Materials. NR 115 TC 10 Z9 10 U1 5 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 1 PY 2016 VL 8 IS 341 AR 341ra76 DI 10.1126/scitranslmed.aad3744 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA DO0AY UT WOS:000377443000003 PM 27252175 ER PT J AU Krupic, F Rolfson, O Nemes, S Karrholm, J AF Krupic, Ferid Rolfson, Ola Nemes, Szilard Karrholm, Johan TI Poor patient-reported outcome after hip replacement, related to poor perception of perioperative information, commoner in immigrants than in non-immigrants SO ACTA ORTHOPAEDICA LA English DT Article ID TOTAL KNEE ARTHROPLASTY; PATIENTS EXPECTATIONS; ANXIETY; SATISFACTION; ANESTHESIA AB Background and purpose - In preparing patients for total hip replacement surgery, providing thorough information helps to reduce anxiety, manage postoperative pain, prevent complications, and better engage patients in their rehabilitation. However, patient characteristics may have an influence on the ability to comprehend and assimilate the information given. We investigated differences in patients born in Sweden and those born outside Sweden regarding how they perceived the information given before THR, and if this was associated with different patient-reported outcomes one year after surgery. Patients and methods - From Sahlgrenska University Hospital, we recruited 150 patients born in Sweden and 50 patients born outside Sweden who were to undergo THR. We retrieved routinely collected data from the Swedish Hip Arthroplasty Register including basic demographic variables and patient-reported outcome measures, both preoperatively and at 1-year follow-up. In a separate survey carried out 1-2 weeks after surgery, patients were asked about the information provided in connection with the operation. Results - Patients born outside Sweden more frequently reported that they were poorly informed about possibilities to treat pain and about the operation itself. 1 year after the operation, patients born outside Sweden who, 1-2 weeks after the operation, had reported that they were poorly informed also reported having worse outcomes. Poorer results were found for the questions self-care and anxiety/depression in the EQ-5D questionnaire, pain on a visual analog scale (VAS), EQVAS, and EQ-5D index compared to those patients born in Sweden who had received at least some information of acceptable quality. Interpretation - One quarter of the patients were not satisfied with the information provided before and after THR. These patients more commonly reported perioperative anxiety and they were more often born outside Sweden. Poorly informed patients who had come from countries outside Sweden were more likely to report inferior outcome 1 year after the operation. C1 [Krupic, Ferid; Rolfson, Ola; Karrholm, Johan] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. [Krupic, Ferid; Rolfson, Ola; Nemes, Szilard; Karrholm, Johan] Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Rolfson, Ola] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, Boston, MA USA. RP Krupic, F (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. EM ferid.krupic@gu.se OI Rolfson, Ola/0000-0001-6534-1242 NR 26 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD JUN PY 2016 VL 87 IS 3 BP 218 EP 224 DI 10.3109/17453674.2015.1135664 PG 7 WC Orthopedics SC Orthopedics GA DN5IA UT WOS:000377098700002 PM 26848766 ER PT J AU Francis, K AF Francis, Kim TI What Is Best Practice for Providing Pain Relief During Retinopathy of Prematurity Eye Examinations? SO ADVANCES IN NEONATAL CARE LA English DT Article DE evidence-based practice; eye examination; neonates; nonpharmacological pain management; nursing; pain; pain assessment; pain management; pharmacologic pain management; premature infants; preterm infants; retinopathy of prematurity ID INDIRECT OPHTHALMOSCOPY; SCREENING EXAMINATION; NONNUTRITIVE SUCKING; TOPICAL ANESTHESIA; CONTROLLED-TRIAL; PROCEDURAL PAIN; REDUCE PAIN; INFANTS; SUCROSE; STRESS AB Background: Retinopathy of prematurity screenings is considered a painful procedure. Yet, preterm infants 30 weeks of gestation or less or weighing 1500 g or less or between 1500 and 2000 g or greater than 30 weeks of gestation with an unstable course are required to have these examinations until their eyes reach maturity. Purpose: A systematic search of the literature was conducted to answer the question "For premature infants undergoing retinal eye examinations, what interventions are the most effective for pain reduction?" Methods/Search Strategy: CINAHL Plus and MEDLINE were searched using the key words: retinopathy of prematurity and pain. The search was limited to the last 10 years and experimental or quasi-experimental studies attempting to reduce pain during eye examinations. Findings/Results: The search criteria yielded 14 studies that addressed interventions to decrease pain during examinations. Three strategies were noted for pain relief including nonpharmacological interventions (n = 9), topical anesthetics (n = 3), and examination techniques (n = 2). The findings indicate that these 3 strategies provided varying results for pain relief but could be beneficial if provided in a consistent protocol. Implications for Practice: Consequently, policies for pain management during retinopathy of prematurity examinations need to be used consistently. It is important for clinicians to consider using a combination of strategies that maximize comfort and provide pain relief. Implications for Research: There remains a need to continue to examine pain-relieving techniques for retinopathy of prematurity examinations. Further investigation is needed to evaluate effective strategies that mitigate pain and the pathways causing pain. In addition, investigating the clinical feasibility of examinations without speculum use may be worthwhile. C1 [Francis, Kim] Massachusetts Gen Hosp, 55 Fruit St Blake 13, Boston, MA 02114 USA. RP Francis, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St Blake 13, Boston, MA 02114 USA. EM KFrancis2@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 1536-0903 EI 1536-0911 J9 ADV NEONAT CARE JI Adv. Neonatal Care PD JUN PY 2016 VL 16 IS 3 BP 220 EP 228 DI 10.1097/ANC.0000000000000267 PG 9 WC Nursing SC Nursing GA DN5YH UT WOS:000377147100029 PM 27195471 ER PT J AU Metra, M Mentz, RJ Hernandez, AF Heizer, GM Armstrong, PW Clausell, N Corbalan, R Costanzo, MR Dickstein, K Dunlap, ME Ezekowitz, JA Howlett, JG Komajda, M Krum, H Lombardi, C Fonarow, GC McMurray, JJV Nieminen, MS Swedberg, K Voors, AA Starling, RC Teerlink, JR O'Connor, CM AF Metra, Marco Mentz, Robert J. Hernandez, Adrian F. Heizer, Gretchen M. Armstrong, Paul W. Clausell, Nadine Corbalan, Ramon Costanzo, Maria Rosa Dickstein, Kenneth Dunlap, Mark E. Ezekowitz, Justin A. Howlett, Jonathan G. Komajda, Michel Krum, Henry Lombardi, Carlo Fonarow, Gregg C. McMurray, John J. V. Nieminen, Markku S. Swedberg, Karl Voors, Adriaan A. Starling, Randall C. Teerlink, John R. O'Connor, Christopher M. TI Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; INTERNATIONAL DIFFERENCES; READMISSION RATES; OUTCOMES; MANAGEMENT; NESIRITIDE; GLOBALIZATION; CLOPIDOGREL; TICAGRELOR; COUNTRIES AB A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical, areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0:79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different, geographical areas. (C) 2016 Elsevier Inc. All rights reserved. C1 [Metra, Marco; Lombardi, Carlo] Univ Brescia, Dept Med & Surg Specialties, Div Cardiol, Brescia, Italy. [Mentz, Robert J.; Hernandez, Adrian F.; Heizer, Gretchen M.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Dept Med, Duke Clin Res Inst,Div Cardiol, Durham, NC 27710 USA. [Armstrong, Paul W.; Ezekowitz, Justin A.] Univ Alberta, Div Cardiol, Edmonton, AB, Canada. [Clausell, Nadine] Hosp Clin Porto Alegre, Serv Cardiol, Porto Alegre, RS, Brazil. [Corbalan, Ramon] Pontificia Univ Catolica Chile, Cardiovasc Div, Alameda 340, Santiago, Chile. [Costanzo, Maria Rosa] Advocate Heart Inst, Naperville, IL USA. [Dickstein, Kenneth] Univ Bergen, Stavenger Univ Hosp, Div Cardiol, Bergen, Norway. [Dunlap, Mark E.] Metrohlth Med Ctr, Heart & Vasc Ctr, Cleveland, OH USA. [Howlett, Jonathan G.] Univ Calgary, Libin Cardiovasc Inst, Calgary, AB, Canada. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [Krum, Henry] Monash Univ, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [McMurray, John J. V.] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Nieminen, Markku S.] Meilahti Hosp, Heart & Lung Ctr, Helsinki, Finland. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Emergency & Cardiovasc Med, Gothenburg, Sweden. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Starling, Randall C.] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Teerlink, John R.] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metra, M (reprint author), Univ Brescia, Dept Med & Surg Specialties, Div Cardiol, Brescia, Italy. EM metramarco@libero.it OI mcmurray, john/0000-0002-6317-3975 FU National Institutes of Health [U10HL110312]; Amgen; Gilead; Novartis; Otsuka; ResMed; Respicardia; Cardikinetix; Impulse Dynamics; St. Jude; Lung LLC; ARCA FX Dr. Metra has received consulting honoraria from Bayer, Novartis, Servier. Dr. Mentz receives research support with the grant U10HL110312 from National Institutes of Health, Amgen, Gilead, Novartis, Otsuka, and ResMed; and honoraria from HeartWare, Luitpold, Novartis, ResMed, and Thoratec. Dr. Costanzo has received consulting honoraria from Metronic, St. Jude, Respicardia, and ZS Pharma; and grants to Advocate Heart Institute from Respicardia, Cardikinetix, Impulse Dynamics, St. Jude, Novartis, Lung LLC, and ARCA. Dr. Fonarow reports consulting for Abbot, Amgen, Bayer, Baxter, Janssen, Novartis, Medtronic. The other authors have no conflicts of interest to disclose. NR 30 TC 1 Z9 1 U1 2 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2016 VL 117 IS 11 BP 1771 EP 1778 DI 10.1016/j.amjcard.2016.03.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN4RH UT WOS:000377054400011 PM 27108685 ER PT J AU Maki, KC Kaspar, KL Khoo, C Derrig, LH Schild, AL Gupta, K AF Maki, Kevin C. Kaspar, Kerrie L. Khoo, Christina Derrig, Linda H. Schild, Arianne L. Gupta, Kalpana TI Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE antibiotics; bacteria; cranberry; inflammation; proanthocyanidin; urinary tract infection; women ID PLACEBO-CONTROLLED TRIAL; ESCHERICHIA-COLI; IN-VITRO; PROANTHOCYANIDINS; PREVENTION; EPIDEMIOLOGY; VALIDATION; CYSTITIS; DISEASES; PRODUCTS AB Background: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption. Objective: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs. Design: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time. Results: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914). Conclusion: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. C1 [Maki, Kevin C.; Derrig, Linda H.; Schild, Arianne L.] Biofortis Clin Res, Addison, IL USA. [Maki, Kevin C.] MB Clin Res, Glen Ellyn, IL USA. [Kaspar, Kerrie L.; Khoo, Christina] Ocean Spray Cranberries, Lakeville Middleboro, MA USA. [Gupta, Kalpana] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gupta, Kalpana] VA Boston Healthcare Syst, Boston, MA USA. RP Maki, KC (reprint author), Biofortis Clin Res, Addison, IL USA.; Maki, KC (reprint author), MB Clin Res, Glen Ellyn, IL USA. EM kmaki@mbclinicalresearch.com FU Ocean Spray Cranberries Inc. FX Supported by Ocean Spray Cranberries Inc. Beverages were-provided by Ocean Spray Cranberries Inc. This is a free access article, distributed under terms (http://www.nutrition.org/publications/guidelines-and-Policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. NR 50 TC 5 Z9 5 U1 20 U2 23 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2016 VL 103 IS 6 BP 1434 EP 1442 DI 10.3945/ajcn.116.130542 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DN4RD UT WOS:000377054000010 PM 27251185 ER PT J AU Schoenfeld, JD Wo, JY Mamon, HJ Kwak, EL Mullen, JT Enzinger, PZ Blaskowsky, LS Ryan, DP Hong, TS AF Schoenfeld, Jonathan D. Wo, Jennifer Y. Mamon, Harvey J. Kwak, Eunice L. Mullen, John T. Enzinger, Peter Z. Blaskowsky, Lawrence S. Ryan, David P. Hong, Theodore S. TI The Impact of Positive Margins on Outcome Among Patients With Gastric Cancer Treated With Radiation SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology (ASCO) CY JAN 24-26, 2013 CL San Francisco, CA SP Amer Soc Clin Oncol DE gastric cancer; radiotherapy; chemotherapy; margins; multimodality ID POSTOPERATIVE CHEMORADIOTHERAPY; PREOPERATIVE RADIOTHERAPY; PATHOLOGICAL RESPONSE; RANDOMIZED-TRIAL; RECTAL-CANCER; FOLLOW-UP; ADENOCARCINOMA; SURGERY; CHEMOTHERAPY; THERAPY AB Objectives: Positive surgical margins have been associated with worse outcomes in gastric cancer patients. We evaluated the impact of positive margins in a modern cohort treated with radiotherapy. Methods: We performed a multi-institutional retrospective analysis of patients treated from 1998 through 2010. All underwent definitive surgery and were followed up for recurrence and survival. We assessed associations with positive margins using the log-rank tests and Cox proportional hazard models. Results: We identified 91 patients with a median follow-up of 42 months. Seven received radiation before surgery; the remainder were treated postoperatively. Epirubicin-based chemotherapy was given to 8 patients perioperatively and 25 postoperatively. Nineteen had positive margins (21%), including 25% of patients who received chemotherapy perioperatively. All patients who received neoadjuvant radiotherapy had negative margins. There were 41 recurrences and 44 deaths. Positive margins were associated with increased recurrence risk after adjusting for other factors (hazard ratio = 2.8, P = 0.01). In addition, median survival with positive margins was 31 months as compared with 77 months after complete resection (P = 0.13). Conclusions: Positive margins were associated with recurrence despite aggressive multimodality therapy including radiotherapy and the selective use of chemotherapy. Thus, additional consideration is warranted for strategies such as neoadjuvant chemoradiation intended to facilitate complete resection. C1 [Schoenfeld, Jonathan D.; Mamon, Harvey J.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Enzinger, Peter Z.] Brigham & Womens Hosp, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. [Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kwak, Eunice L.; Blaskowsky, Lawrence S.; Ryan, David P.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Schoenfeld, JD (reprint author), Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave,DAL257, Boston, MA 02114 USA. EM jdschoenfeld@partners.org NR 24 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2016 VL 39 IS 3 BP 243 EP 247 DI 10.1097/COC.0000000000000047 PG 5 WC Oncology SC Oncology GA DN5XZ UT WOS:000377146300005 PM 24577163 ER PT J AU Decker, BK Clancy, CJ AF Decker, Brooke K. Clancy, Cornelius J. TI Culture positivity and bacterial burden thresholds for Legionella in hospital water: Proceed with caution SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Letter ID LEGIONNAIRES-DISEASE C1 [Decker, Brooke K.; Clancy, Cornelius J.] Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C,Med IIIE U, Pittsburgh, PA 15240 USA. [Decker, Brooke K.; Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Decker, BK (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C,Med IIIE U, Pittsburgh, PA 15240 USA. EM brooke.decker@va.gov NR 7 TC 1 Z9 1 U1 2 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JUN 1 PY 2016 VL 44 IS 6 BP 730 EP 730 DI 10.1016/j.ajic.2015.11.038 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DN0IK UT WOS:000376747400029 PM 26851195 ER PT J AU Temming, LA Cahill, AG Riley, LE AF Temming, Lorene A. Cahill, Alison G. Riley, Laura E. TI Clinical management of medications in pregnancy and lactation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE medications in lactation; medications in pregnancy; psychiatric medications in pregnancy ID SEROTONIN-REUPTAKE INHIBITORS; PERSISTENT PULMONARY-HYPERTENSION; ANTIDEPRESSANT USE; BIRTH-DEFECTS; RISK; DRUGS; CITALOPRAM; NEWBORN AB Prescription and over-the-counter medication use during pregnancy and lactation is exceedingly common. There are many available resources to gather information and guide patient counseling. These include primary literature, online resources, professional society recommendations, and drug labels. One must consider both disease and drug characteristics when making decisions on medication use during pregnancy and lactation. Providers can then use this information to balance the risks of fetal or neonatal exposure against the potential benefits of maternal treatment and the risks of untreated disease. C1 [Temming, Lorene A.; Cahill, Alison G.] Washington Univ, Dept Obstet & Gynecol, St Louis, MO USA. [Riley, Laura E.] Massachusetts Gen Hosp, Obstet & Gynecol, Boston, MA 02114 USA. RP Temming, LA (reprint author), Washington Univ, Dept Obstet & Gynecol, St Louis, MO USA. EM temmingl@wudosis.wustl.edu OI Temming, Lorene/0000-0002-0676-0081 FU National Institutes of Health (NIH) [5T32HD055172-07]; NIH National Center for Advancing Translational Sciences (NCATS), components of the NIH [UL1 TR000448]; NIH Roadmap for Medical Research FX Dr Temming is supported by a National Institutes of Health (NIH) T32 training grant (5T32HD055172-07). This publication was also made possible by Grant Number UL1 TR000448 from the NIH National Center for Advancing Translational Sciences (NCATS), components of the NIH, and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCATS or NIH. NR 23 TC 0 Z9 0 U1 8 U2 10 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 JUN PY 2016 VL 214 IS 6 BP 698 EP 702 DI 10.1016/j.ajog.2016.01.187 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DN6YP UT WOS:000377222800007 PM 26844758 ER PT J AU Leffert, LR Clancy, CR Bateman, BT Cox, M Schulte, PJ Smith, EE Fonarow, GC Kuklina, EV George, MG Schwamm, LH AF Leffert, Lisa R. Clancy, Caitlin R. Bateman, Brian T. Cox, Margueritte Schulte, Phillip J. Smith, Eric E. Fonarow, Gregg C. Kuklina, Elena V. George, Mary G. Schwamm, Lee H. TI Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ischemic; pregnancy; stroke ID TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; INTRAVENOUS THROMBOLYSIS; RISK-FACTORS; GUIDELINES-STROKE; ALTEPLASE; TRENDS; WOMEN; PREECLAMPSIA; THROMBECTOMY AB BACKGROUND: Stroke, which is a rare but devastating event during pregnancy, occurs in 34 of every 100,000 deliveries; obstetricians are often the first providers to be contacted by symptomatic patients. At least one-half of pregnancy-related strokes are likely to be of the ischemic stroke subtype. Most pregnant or newly postpartum women with ischemic stroke do not receive acute stroke reperfusion therapy, although this is the recommended treatment for adults. Little is known about these therapies in pregnant or postpartum women because pregnancy has been an exclusion criterion for all reperfusion trials. Until recently, pregnancy and obstetric delivery were specifically identified as warnings to intravenous alteplase tissue plasminogen activator in Federal Drug Administration labeling. OBJECTIVE: The primary study objective was to compare the characteristics and outcomes of pregnant or postpartum vs nonpregnant women with ischemic stroke who received acute reperfusion therapy. STUDY DESIGN: Pregnant or postpartum (<6 weeks; n = 338) and nonpregnant (n = 24,303) women 18-44 years old with ischemic stroke from 1991 hospitals that participated in the American Heart Association's Get With the Guidelines-Stroke Registry from 2008-2013 were identified by medical history or International Classification of Diseases, Ninth Revision, codes. Acute stroke reperfusion therapy was defined as intravenous tissue plasminogen activator, catheter-based thrombolysis, or thrombectomy or any combination thereof. A sensitivity analysis was done on patients who received intravenous tissue plasminogen activator monotherapy only. Chi-square tests were used for categoric variables, and Wilcoxon Rank-Sum was used for continuous variables. Conditional logistic regression was used to assess the association of pregnancy with short-term outcomes. RESULTS: Baseline characteristics of the pregnant or postpartum vs nonpregnant women with ischemic stroke revealed a younger group who, despite greater stroke severity, were less likely to have a history of hypertension or to arrive via emergency medical services. There were similar rates of acute stroke reperfusion therapy in the pregnant or postpartum vs nonpregnant women (11.8% vs 10.5%; P =.42). Pregnant or postpartum women were less likely to receive intravenous tissue plasminogen activator monotherapy (4.4% vs 7.9%; P =.03), primarily because of pregnancy and recent surgery. There was a trend toward increased symptomatic intracranial hemorrhage in the pregnant or postpartum patients who were treated with tissue plasminogen activator, yet no cases of major systemic bleeding or in-hospital death occurred, and there were similar rates of discharge to home. Data on the timing of pregnancy, which were available in 145 of 338 cases, showed that 44.8% of pregnancy-related strokes were antepartum, that 2.8% occurred during delivery, and that 52.4% were during the postpartum period. CONCLUSIONS: Using data from the Get With the Guidelines-Stroke Registry to assemble the largest cohort of pregnant or postpartum ischemic stroke patients who had been treated with reperfusion therapy, we observed that pregnant or postpartum women had similarly favorable short-term outcomes and equal rates of total reperfusion therapy to nonpregnant women, despite lower rates of intravenous tissue plasminogen activator use. Future studies should identify the characteristics of pregnant and postpartum ischemic stroke patients who are most likely to safely benefit from reperfusion therapy. C1 [Leffert, Lisa R.; Clancy, Caitlin R.; Bateman, Brian T.] Massachusetts Gen Hosp, Obstet Anesthesia Div, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Cox, Margueritte] Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC USA. [Schulte, Phillip J.] Duke Clin Res Inst, Clin Trials Stat Grp, Outcomes Res & Assessment Grp, Durham, NC USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Fonarow, Gregg C.] Ronald Reagan Univ Calif Los Angeles Med Ctr, Ahmanson Univ Calif Los Angeles Cardiomyopathy Ct, Dept Med, Los Angeles, CA USA. [Kuklina, Elena V.] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Reprod Hlth, Atlanta, GA 30333 USA. [George, Mary G.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA USA. RP Leffert, LR (reprint author), Massachusetts Gen Hosp, Obstet Anesthesia Div, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM lleffert@partners.org OI Fonarow, Gregg/0000-0002-3192-8093 FU Get With The Guidelines (GWTG)-Stroke Young Investigator Database Research Seed Grant, by the American Heart Association/American Stroke Association; Medtronic; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janseen Pharmaceutical Companies of Johnson Johnson; AHA Pharmaceutical Roundtable; NINDS; Patient-Centered Outcomes Research Institute (PCORI) FX Supported by a Get With The Guidelines (GWTG)-Stroke Young Investigator Database Research Seed Grant, which is provided by the American Heart Association/American Stroke Association and is sponsored, in part, by Medtronic and has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, Janseen Pharmaceutical Companies of Johnson & Johnson and the AHA Pharmaceutical Roundtable.; L.H.S. serves as a volunteer for the American Heart Association as chair of the stroke clinical workgroup for Get with the Guideline-Stroke and chair of the Healthcare Accreditation Science Committee; he serves as the PI of an NINDS funded SPOTRIAS network trial, MR WITNESS, which is a Phase 2 safety study of alteplase delivered in an extended time window with MR-guided patient selection (NCT01282242). The study is funded primarily by NINDS, and alteplase is provided by Genentech to MGH for distribution to sites; there are modest per patient supplemental site payments. Genentech has no control over study design, analysis or publication. L.H.S. reports receiving significant research support from the Patient-Centered Outcomes Research Institute (PCORI), serving as a stroke systems consultant to the Massachusetts Department of Public Health, and serving as a scientific consultant regarding trial design and conduct to Lundbeck (international steering committee, DIAS3, 4 trial); and Penumbra (data and safety monitoring committee, Separator 3D trial). All other authors report no conflicts of interest. NR 45 TC 2 Z9 2 U1 2 U2 5 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 JUN PY 2016 VL 214 IS 6 AR 723.e1-e11 DI 10.1016/j.ajog.2015.12.016 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DN6YP UT WOS:000377222800016 PM 26709084 ER PT J AU Sima, C Aboodi, GM Lakschevitz, FS Sun, CX Goldberg, MB Glogauer, M AF Sima, Corneliu Aboodi, Guy M. Lakschevitz, Flavia S. Sun, Chunxiang Goldberg, Michael B. Glogauer, Michael TI Nuclear Factor Erythroid 2-Related Factor 2 Down-Regulation in Oral Neutrophils Is Associated with Periodontal Oxidative Damage and Severe Chronic Periodontitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TOTAL ANTIOXIDANT CAPACITY; GINGIVAL CREVICULAR FLUID; ALVEOLAR BONE LOSS; REACTIVE OXYGEN; LEUKOCYTE MIGRATION; LIPID-PEROXIDATION; RESPONSE PATHWAY; IL-8 EXPRESSION; STRESS; NRF2 AB The balance between reactive oxygen species and antioxidants plays an important role in periodontal health. We previously demonstrated that high reactive oxygen species production by oral polymorphonuclear neutrophils (oPMNs) in chronic periodontitis (CP) refractory to conventional therapy is associated with severe destruction of periodontium. Herein, we show that inhibition of antioxidant production through down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oPMN, despite enhanced recruitment in the oral cavity, is associated with severe CP. Twenty-four genes in the Nrf2-mediated oxidative stress response pathway were down-regulated in PMNs of diseased patients. Downstream of Nrf2, levels of oPMN superoxide dismutase 1 and catalase were decreased in severe CP, despite increased recruitment. Nrf2(-/-) mice had more severe loss of periodontium in response to periodontitis-inducing subgingival ligatures compared with wild-types. Levels of 8-hydroxy-deoxyguanosine were increased in periodontal Lesions of Nrf2(-/-) mice, indicating high oxidative damage. We report, for the first time, Nrf2 pathway down-regulation in oPMNs of patients with severe CP. PMNs of CP patients may be primed for low antioxidant response in the context of high recruitment in the oral cavity, resulting in increased oxidative tissue damage. C1 [Sima, Corneliu] Forsyth Inst, Dept Appl Oral Sci, 245 First St,Room 5145, Cambridge, MA 02142 USA. [Sima, Corneliu] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. [Aboodi, Guy M.; Lakschevitz, Flavia S.; Goldberg, Michael B.; Glogauer, Michael] Univ Toronto, Fac Dent, Dept Periodontol, Toronto, ON, Canada. [Aboodi, Guy M.; Lakschevitz, Flavia S.; Sun, Chunxiang; Glogauer, Michael] Univ Toronto, Fac Dent, Matrix Dynam Grp, Toronto, ON, Canada. RP Sima, C (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St,Room 5145, Cambridge, MA 02142 USA. EM csima@forsyth.org FU Canadian Institute of Health Research grant [TBO-122068]; National Institute of Dental and Craniofacial Research Award [K99DE024575] FX Supported by Canadian Institute of Health Research grant TBO-122068 (M.G.) and National Institute of Dental and Craniofacial Research Award K99DE024575 (C.S.). NR 46 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 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2016 VL 186 IS 6 BP 1417 EP 1426 DI 10.1016/j.ajpath.2016.01.013 PG 10 WC Pathology SC Pathology GA DN7DZ UT WOS:000377236800002 PM 27070823 ER PT J AU Sarris, J Murphy, J Mischoulon, D Papakostas, GI Fava, M Berk, M Ng, CH AF Sarris, Jerome Murphy, Jenifer Mischoulon, David Papakostas, George I. Fava, Maurizio Berk, Michael Ng, Chee H. TI Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; FOLIC-ACID SUPPLEMENTATION; ADENOSYL-L-METHIONINE; DOUBLE-BLIND; MAJOR DEPRESSION; EICOSAPENTAENOIC ACID; S-ADENOSYLMETHIONINE; PROSTATE-CANCER AB Objective: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta analysis) has been conducted. Method: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean "difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. Results: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic add, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias). Conclusions: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms. C1 [Sarris, Jerome] Univ Melbourne, Dept Psychiat, Melbourne Clin, ARCADIA Mental Hlth Res Grp,Professorial Unit, Melbourne, Vic, Australia. Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic, Australia. Harvard Univ, Sch Med, Dept Psychiat, Depress Clin & Res Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. Deakin Univ, Sch Med, Barwon Hlth, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia. Orygen, Melbourne, Vic, Australia. Ctr Youth Mental Hlth, Melbourne, Vic, Australia. Florey Inst Neurosci & Mental Hlth, Melbourne, Australia. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne Clin, ARCADIA Mental Hlth Res Grp,Professorial Unit, Melbourne, Vic, Australia. EM jsarris@unimelb.edu.au FU C.R. Roper Fellowship at the University of Melbourne; NHMRC Senior Principal Research Fellowship [1059660]; Integria Healthcare; MediHerb; Pfizer; Taki Mai; Pepsico; BioCeuticals; Blackmores; Soho-Flordis; Elsevier; HealthEd; National Health and Medical Research Council; FisherWallace; Nordic Naturals; Methylation Sciences; PharmoRx Therapeutics; AstraZeneca; Bristol-Myers Squibb; Forest; National Institute of Mental Health; Neuralstem; PAMLAB; Ridge Diagnostics; Sunovion; Tal Medical; Theracos; Acadia; Alkermes; Avanir; AXSOME Therapeutics; Biogen; Cerecor; Dinippon Sumitomo; Eli Lilly; EnVivo; Euthymics Bioscience; FORUM; GenOmind; GlaxoSmithKline; Intracellular; Janssen RD; Johnson&Johnson Pharmaceutical Research and Development Lundbeck; Merck; MSI Methylation Sciences; National Center for Complementary and Alternative Medicine; National Coordinating Center for Integrative Medicine; NIDA; NIMH; Naurex; Nestle Health Sciences; Novartis; Nutrition 21; Osmotica; Otsuka; Photothera; PPD; Puretech Ventures; PsychoGenics; RCT Logic; Reckitt Benckiser; Roche; Sanofi-Aventis; Servier Laboratories; Stanley Medical Research Institute; Taisho; Takeda; VistaGen; Stanley Medical Research Foundation; MBF; NHMRC; Cooperative Research Centre; Simons Autism Foundation; Cancer Council of Victoria; Rotary Health; Meat and Livestock Board; Woolworths; BeyondBlue; Geelong Medical Research Foundation; Organon; Mayne Pharma; Servier; Wyeth; Lundbeck FX Dr. Sarris is supported by a C.R. Roper Fellowship at the University of Melbourne Dr. Berk is supported by NHMRC Senior Principal Research Fellowship 1059660; All authors except Dr. Murphy disclose having been provided previous or current research funding to study pharmaceuticals and nutraceuticals for mood disorders, including but not restricted to omega 3, folinic acid, 5-MTHF, tryptophan, and S-adenosylmethionine. Dr. Sarris reports no specific direct conflict of interest; general disclosures involve presentation honoraria, travel support, clinical trial grants, or book royalties from Integria Healthcare, MediHerb, Pfizer, Taki Mai, Pepsico, BioCeuticals, Blackmores, Soho-Flordis, Elsevier, HealthEd, and the National Health and Medical Research Council. Dr. Mischoulon has received research support from FisherWallace, Nordic Naturals, Methylation Sciences, and PharmoRx Therapeutics; he has received honoraria for consulting, speaking, and writing from the Massachusetts General Hospital Psychiatry Academy; and he has received royalties from Lippincott Williams & Wilkins for the book Natural Medications for Psychiatric Disorders: Considering the Alternatives. Dr Papakostas has served as a consultant for Abbott, AstraZeneca, Avanir, Axsome (on behalf of Massachusetts General Hospital [MGH)], Brainsway, Bristol-Myers Squibb, Cephalon, Dey, Eli Lilly, Genentech (on behalf of MGH), GlaxoSmithKline, Evotec, H. Lundbeck, Inflabloc, Janssen Global Services (on behalf of MGH), Jazz Pharmaceuticals, Johnson Er Johnson (on behalf of MGH), Methylation Sciences, Novartis, One Carbon Therapeutics (on behalf of MGH), Osmotica (on behalf of MGH), Otsuka, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire, Sunovion, Taisho, Takeda, Theracos, and Wyeth; he has received honoraria (for lectures or consultancy) from Abbott, AstraZeneca, Avanir, Bristol-Myers Squibb, Brainsway, Cephalon, Dey, Eli Lilly, Evotec, Forest, GlaxoSmithKline, Inflabloc, Jazz, H. Lundbeck, Medichem, Meiji Seika, Novartis, Otsuka, PAMLAB, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire, Sunovion, Takeda, Theracos, Titan, and Wyeth; he has received research support (paid to hospital) from AstraZeneca, Bristol-Myers Squibb, Forest, the National Institute of Mental Health, Neuralstem, PAMLAB, Pfizer, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Sunovion, Tal Medical, and Theracos; he has also served (not currently) on the speaker's bureau for Bristol-Myers Squibb and Pfizer. Dr.; Fava has received research support from and/or served as an adviser or consultant to Acadia, Alkermes, AstraZeneca, Avanir, AXSOME Therapeutics, Biogen, Bristol-Myers Squibb, Cerecor, Dinippon Sumitomo, Eli Lilly, EnVivo, Euthymics Bioscience, Forest, FORUM, GenOmind, GlaxoSmithKline, Intracellular, Janssen R&D, Johnson&Johnson Pharmaceutical Research and Development Lundbeck, Merck, Methylation Sciences, MSI Methylation Sciences, the National Center for Complementary and Alternative Medicine, the National Coordinating Center for Integrative Medicine, NIDA, NIMH, Naurex, Nestle Health Sciences, Neuralstem, Novartis, Nutrition 21, Osmotica, Otsuka, PamLab, Pfizer, PharmoRx Therapeutics, Photothera, PPD, Puretech Ventures, PsychoGenics, RCT Logic (formerly Clinical Trials Solutions), Reckitt Benckiser, Ridge Diagnostics, Roche, Sanofi-Aventis, Servier Laboratories, the Stanley Medical Research Institute, Sunovion, Taisho, Takeda, Tal Medical, and VistaGen, he has had speaking or publishing rotes for the American Society of Clinical Psychopharmacology, Belvoir Media Group, CME Institute/Physicians Postgraduate Press, and MGH Psychiatry Academy; he has equity holdings in Compellis and PsyBrain; he is named on patents for sequential parallel comparison design, licensed by MGH to Pharmaceutical Product Development, and a patent application for a combination of ketamine plus scopolamine in major depressive disorder, licensed by MGH to Biohaven; and he is a copyright holder for the MGH Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, the Symptoms of Depression Questionnaire, and SAFER and has publications with Lippincott Williams & Wilkins, Wolkers Kluwer, and World Scientific Publishing. Dr. Berk has received grant/research support from Stanley Medical Research Foundation, MBF, NHMRC, NHMRC Senior Principal Research Fellowship (1059660), Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Rotary Health, Meat and Livestock Board, Woolworths, BeyondBlue, Geelong Medical Research Foundation, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, and Servier; he has been a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth; he has been a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Bioadvantex, Merck, Glaxo SmithKline, Lundbeck, Janssen Cilag, and Servier; and he is a co-inventor of two provisional patents regarding the use of NAC and related compounds for psychiatric indications, which, while assigned to the Mental Health Research Institute, could lead to personal remuneration upon a commercialization event Dr. Ng has served on advisory boards for Servier, Wyeth, and Eli Lilly, has received research grant support from Wyeth and Lundbeck; and has received honoraria from Servier, Bristol-Myers Squibb, Organon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Astra-Zeneca, Wyeth, and Pfizer. Dr. Murphy reports no financial relationships with commercial interests. NR 91 TC 15 Z9 15 U1 19 U2 24 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2016 VL 173 IS 6 BP 575 EP 587 DI 10.1176/appi.ajp.2016.15091228 PG 13 WC Psychiatry SC Psychiatry GA DN3FT UT WOS:000376948500009 PM 27113121 ER PT J AU Ackman, JB AF Ackman, Jeanne B. TI Reply to "Quantitative MRI of the Thymus: Chemical-Shift Ratio, Signal Intensity Index, and Apparent Diffusion Coefficient Value" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID HYPERPLASIA C1 [Ackman, Jeanne B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ackman, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2016 VL 206 IS 6 BP W98 EP W98 DI 10.2214/AJR.16.16162 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN2XW UT WOS:000376927300008 PM 27042958 ER PT J AU Petranovic, M Gilman, MD Shepard, JAO AF Petranovic, Milena Gilman, Matthew D. Shepard, Jo-Anne O. TI Reply to "Is It Time for a Nonionizing Radiation Technique for Biopsy of Anterior Mediastinal Masses?" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID NEEDLE-BIOPSY; PROTOCOL C1 [Petranovic, Milena; Gilman, Matthew D.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Petranovic, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 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 JUN PY 2016 VL 206 IS 6 BP W96 EP W96 DI 10.2214/AJR.16.16314 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN2XW UT WOS:000376927300006 PM 27214161 ER PT J AU Garey, L Bakhshaie, J Brandt, CP Langdon, KJ Kauffman, BY Schmidt, NB Leventhal, AM Zvolensky, MJ AF Garey, Lorra Bakhshaie, Jafar Brandt, Charles P. Langdon, Kirsten J. Kauffman, Brooke Y. Schmidt, Norman B. Leventhal, Adam M. Zvolensky, Michael J. TI Interplay of Dysphoria and Anxiety Sensitivity in Relation to Emotion Regulatory Cognitions of Smoking Among Treatment-Seeking Smokers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; PSYCHIATRIC-DISORDERS; NICOTINE DEPENDENCE; DEPRESSIVE SYMPTOMS; CESSATION TREATMENT; TOBACCO DEPENDENCE; CIGARETTE-SMOKING; VALIDATION; DIMENSIONS; PREDICTION AB Background and Objectives: There is evidence that anxiety sensitivity (AS) plays a role in the maintenance of smoking, yet there is little understanding of how AS interplays with other affective symptomatology variables that are also related to smoking, such as dysphoria. Therefore, the current cross-sectional study evaluated the interactive effects of AS and dysphoria on emotion regulatory cognitions, including smoking negative affect reduction expectancies, perceived barriers for cessation, and smoking-specific experiential avoidance. Method: A total of 448 adult treatment-seeking daily smokers, who responded to study advertisements, were recruited to participate in a smoking cessation treatment trial (47.8% female; M-age = 37.2, SD = 13.5). The current study utilized self-report baseline data from trial participants. Results: After accounting for covariates, simple slope analyses revealed that AS was positively related to negative affect reduction expectancies (beta = .03, p = .01), perceived barriers to cessation (beta = .22, p = .002), and smoking avoidance and inflexibility (beta = .07, p = .04), among smokers with lower (vs. higher) levels of dysphoria. Conclusions: The current findings suggest that higher levels of dysphoria may mitigate the relation between AS and emotion regulatory cognitions of smoking. Scientific Significance: The current findings highlight the unique and additive clinical relevance of AS and dysphoria regarding emotion regulatory smoking cognitions that may impede quit success. C1 [Garey, Lorra; Bakhshaie, Jafar; Brandt, Charles P.; Kauffman, Brooke Y.; Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Langdon, Kirsten J.] VA Boston Healthcare Ctr, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Langdon, Kirsten J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Schmidt, Norman B.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Leventhal, Adam M.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Leventhal, Adam M.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. RP Garey, L; Zvolensky, MJ (reprint author), Univ Houston, Dept Psychol, Subst Use Treatment Clin, Anxiety & Hlth Res Lab, 126 Fred J Heyne Bldg,Suite 104, Houston, TX 77204 USA. EM llgarey@uh.edu; mjzvolen@central.uh.edu FU National Institute of Mental Health [RO1-MH076629-01A1]; Florida State University, Tallahassee, FL FX This study was funded by National Institute of Mental Health Grant (RO1-MH076629-01A1) awarded to Michael J. Zvolensky at the University of Houston, Houston, TX, and Norman B. Schmidt at Florida State University, Tallahassee, FL. NR 36 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 267 EP 274 DI 10.1111/ajad.12379 PG 8 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500005 PM 27122303 ER PT J AU Flanagan, JC Hakes, JK McClure, EA Snead, AL Back, SE AF Flanagan, Julianne C. Hakes, Jahn K. McClure, Erin A. Snead, Alexandra L. Back, Sudie E. TI Effects of Intimate Partner Violence, PTSD, and Alcohol Use on Cigarette Smoking in a Nationally Representative Sample SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; GENDER-DIFFERENCES; UNITED-STATES; TOBACCO USE; EPIDEMIOLOGIC SURVEY; NICOTINE DEPENDENCE; ANXIETY DISORDERS; RANDOMIZED-TRIAL AB Background and Objectives: Separate literatures indicate that intimate partner violence (IPV), posttraumatic stress disorder (PTSD), and alcohol use are independently associated with increased risk for cigarette smoking. No previous studies have examined the cooccurrence of these problems on smoking quantity and potential gender-specific relationships. This study will address this gap in the literature. Methods: Data from Wave 2 of the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) were examined. Variables were assessed during the past year. Individuals (N = 25,604) who reported being married, dating, or involved in a romantic relationship were included. Results: Among men, PTSD and alcohol use were associated with more cigarettes smoked per day. Among women, PTSD, alcohol use, and IPV victimization were associated with more cigarettes smoked per day. Women who experienced IPV victimization smoked approximately three additional cigarettes per day. Discussion and Conclusions: IPV victimization, PTSD, and alcohol use were associated with cigarettes smoked among women, while IPV experiences were not associated with smoking risk among men. Scientific Significance: These findings represent an important contribution to the existing literature in that it elucidates the compounding relationship between a common and complex comorbidity and cigarette smoking. Findings indicate a critical need to implement routine smoking screening and intervention in venueswhere intimate partner violence is commonly encountered, such as advocacy and substance use treatment settings. C1 [Flanagan, Julianne C.; McClure, Erin A.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 5 Charleston Ctr Dr,Suite 151, Charleston, SC 29455 USA. [Hakes, Jahn K.] US Bur Census, Suitland, MD USA. [Snead, Alexandra L.] Univ Houston, Dept Psychol, Houston, TX USA. [Back, Sudie E.] Ralph H Johnson VAMC, Charleston, SC USA. RP Flanagan, JC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 5 Charleston Ctr Dr,Suite 151, Charleston, SC 29455 USA. EM hellmuth@musc.edu FU National Institute on Child Health and Human Development; Office of Research on Women's Health [K12HD055885]; National Institute on Drug Abuse in Bethesda, Maryland [K01DA036739] FX This manuscript is the result of work supported, in part, by the National Institute on Child Health and Human Development and the Office of Research on Women's Health (K12HD055885; PI: Kathleen T. Brady, Medical University of South Carolina) and National Institute on Drug Abuse (K01DA036739; PI: Erin McClure) in Bethesda, Maryland. NR 42 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 283 EP 290 DI 10.1111/ajad.12381 PG 8 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500007 PM 27196699 ER PT J AU Fuehrlein, B Mota, N Kachadourian, L Arias, A Trevisan, L Krystal, J Southwick, S Pietrzak, R AF Fuehrlein, Brian Mota, Natalie Kachadourian, Lorig Arias, Albert Trevisan, Louis Krystal, John Southwick, Steven Pietrzak, Robert TI High Burden of Alcohol Use Disorders in the US Veteran Population: Results from the National Health and Resilience in Veterans Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Fuehrlein, Brian; Kachadourian, Lorig; Arias, Albert; Trevisan, Louis; Krystal, John; Southwick, Steven; Pietrzak, Robert] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Mota, Natalie] US Dept Vet Affairs, Washington, DC USA. FU Department of Veterans Affairs (VA National Center for PTSD); National Institute on Alcohol Abuse and Alcoholism [P50AA12870, M01RR00125]; Yale Center for Clinical Investigation [UL1 RR024139] FX Department of Veterans Affairs (VA National Center for PTSD), the National Institute on Alcohol Abuse and Alcoholism (P50AA12870, M01RR00125), and the Yale Center for Clinical Investigation (UL1 RR024139). NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 314 EP 314 PG 1 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500024 ER PT J AU Insler, J Ping, S Feman, C Suzuki, J AF Insler, Joseph Ping, Siu Feman, Chin Suzuki, Joji TI Gabapentin: The Potential for Nonmedical Use and Negative Sequelae SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Insler, Joseph] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Ping, Siu; Feman, Chin] Harvard Univ, Sch Med, McLean Hosp, Cambridge, MA 02138 USA. [Suzuki, Joji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 327 EP 328 PG 2 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500054 ER PT J AU Insler, J Rodriguez, C Desai, N Pugh, K AF Insler, Joseph Rodriguez, Claudia Desai, Nitigna Pugh, Kendra TI Treatment Resistant Alcohol Use Disorder: Expanding the Role of Extended Release Naltrexone SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Insler, Joseph] VA Boston Healthcare Syst, Boston, MA USA. [Rodriguez, Claudia] Boston Univ Med, Boston, MA USA. [Pugh, Kendra] MA Bedford VA Med Ctr, Bedford, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 328 EP 328 PG 1 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500055 ER PT J AU Seth, A Ajagbe, T Wang, DL Middleton, F Batki, SL Meszaros, ZS AF Seth, Amit Ajagbe, Tolani Wang, Dongliang Middleton, Frank Batki, Steven L. Meszaros, Zsuzsa Szombathyne TI A Retrospective Study of Prenatal, Childhood, and Adolescent Nicotine, Alcohol, and Drug Exposure in Schizophrenia SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Seth, Amit; Ajagbe, Tolani; Batki, Steven L.; Meszaros, Zsuzsa Szombathyne] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Wang, Dongliang] Dept Publ Hlth & Prevent Med, Syracuse, NY USA. [Middleton, Frank] SUNY Upstate Med Univ, Dept Neurosci Physiol, Syracuse, NY 13210 USA. [Batki, Steven L.] UCSF, Dept Psychiat, San Francisco, CA USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. FU Brain and Behavior Research Foundation FX This research was supported by the Brain and Behavior Research Foundation ( PI: Dr. Meszaros). NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 337 EP 337 PG 1 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500075 ER PT J AU Wong, T Pennington, D Schmeling, B Lasher, B Schrodek, E Yohannes, S McDonald, J Batki, SL AF Wong, Tiffany Pennington, David Schmeling, Brandi Lasher, Brooke Schrodek, Emily Yohannes, Seghel McDonald, Jordan Batki, Steven L. TI Relationships between Alcohol Use and Cognitive Reserve, Complaints, and Function in Veterans with Traumatic Injury SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wong, Tiffany; Pennington, David; Schmeling, Brandi; Lasher, Brooke; Schrodek, Emily; Yohannes, Seghel; McDonald, Jordan] San Francisco VA Med Ctr, San Francisco, CA USA. [Wong, Tiffany; Schmeling, Brandi] Palo Alto Univ, Palo Alto, CA USA. [Pennington, David; Lasher, Brooke; Schrodek, Emily; Yohannes, Seghel; McDonald, Jordan; Batki, Steven L.] NCIRE, Palo Alto, CA USA. [Batki, Steven L.] UCSF, San Francisco VA Med Ctr, San Francisco, CA USA. FU Department of Defense [W81XWH-12-2-0137, W81XWH-11-2-0245] FX Department of Defense W81XWH-12-2-0137 and W81XWH-11-2-0245 (SLB), administered by the Northern California Institute for Research and Education. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 341 EP 341 PG 1 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500085 ER PT J AU Yule, A Wilens, T Carrellas, N AF Yule, Amy Wilens, Timothy Carrellas, Nicholas TI Attention Deficit Hyperactivity Disorder (ADHD) and Overdose (OD) Risk in Transitional Age Youth (TAY) with Substance Use Disorders (SUD) SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Yule, Amy; Wilens, Timothy; Carrellas, Nicholas] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. FU Louis V. Gerstner III Research Scholar Award FX Louis V. Gerstner III Research Scholar Award NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUN PY 2016 VL 25 IS 4 BP 341 EP 341 PG 1 WC Substance Abuse SC Substance Abuse GA DN6YC UT WOS:000377221500084 ER PT J AU Hohloch, K Zeynalova, S Chapuy, B Pfreundschuh, M Loeffler, M Ziepert, M Feller, AC Trumper, L Hasenclever, D Wulf, G Schmitz, N AF Hohloch, Karin Zeynalova, Samira Chapuy, Bjoern Pfreundschuh, Michael Loeffler, Markus Ziepert, Marita Feller, Alfred C. Truemper, Lorenz Hasenclever, Dirk Wulf, Gerald Schmitz, Norbert TI Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma SO ANNALS OF HEMATOLOGY LA English DT Article DE Aggressive lymphoma; Relapse; Triple transplant approach ID BONE-MARROW TRANSPLANTATION; CONTINUAL REASSESSMENT METHOD; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE THERAPY; CONVENTIONAL CHEMOTHERAPY; RITUXIMAB ERA; OPEN-LABEL; DEXA-BEAM; ETOPOSIDE; CARMUSTINE AB Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity. C1 [Hohloch, Karin] Kantonsspital Graubunden, Hematol & Oncol, Chur, Switzerland. [Hohloch, Karin; Chapuy, Bjoern; Truemper, Lorenz; Wulf, Gerald] Univ Gottingen, Univ Med, Dept Hematol & Med Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany. [Zeynalova, Samira; Loeffler, Markus; Ziepert, Marita; Hasenclever, Dirk] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany. [Chapuy, Bjoern] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pfreundschuh, Michael] Univ Clin Saarland, Dept Internal Med 1, Homburg, Germany. [Feller, Alfred C.] Univ Schleswig Holstein, Dept Pathol, Campus Lubeck, Lubeck, Germany. [Schmitz, Norbert] Asklepios Klin St Georg, Dept Hematol Oncol & Stem Cell Transplantat, Hamburg, Germany. RP Hohloch, K (reprint author), Kantonsspital Graubunden, Hematol & Oncol, Chur, Switzerland.; Hohloch, K (reprint author), Univ Gottingen, Univ Med, Dept Hematol & Med Oncol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM karin.hohloch@med.uni-goettingen.de NR 29 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD JUN PY 2016 VL 95 IS 7 BP 1121 EP 1128 DI 10.1007/s00277-016-2671-5 PG 8 WC Hematology SC Hematology GA DN6LG UT WOS:000377185400011 PM 27165090 ER PT J AU Stahl, M Xu, ML Steensma, DP Rampal, R Much, M Zeidan, AM AF Stahl, Maximilian Xu, Mina L. Steensma, David P. Rampal, Raajit Much, Melissa Zeidan, Amer M. TI Clinical response to ruxolitinib in CSF3R T618-mutated chronic neutrophilic leukemia SO ANNALS OF HEMATOLOGY LA English DT Letter ID SETBP1 MUTATIONS; ATYPICAL CML; CSF3R; DIAGNOSIS C1 [Stahl, Maximilian; Xu, Mina L.; Much, Melissa; Zeidan, Amer M.] Yale Univ, Sch Med, Dept Pathol, Brady Mem Lab, 310 Cedar St, New Haven, CT 06510 USA. [Steensma, David P.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Rampal, Raajit] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. RP Stahl, M (reprint author), Yale Univ, Sch Med, Dept Pathol, Brady Mem Lab, 310 Cedar St, New Haven, CT 06510 USA. EM maximilian.stahl@yale.edu NR 9 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD JUN PY 2016 VL 95 IS 7 BP 1197 EP 1200 DI 10.1007/s00277-016-2664-4 PG 4 WC Hematology SC Hematology GA DN6LG UT WOS:000377185400022 PM 27068405 ER PT J AU Badrane, H Nguyen, MH Clancy, CJ AF Badrane, Hassan Nguyen, M. Hong Clancy, Cornelius J. TI Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TRANSCRIPTIONAL REGULATOR CAS5; BUDDING YEAST; SACCHAROMYCES-CEREVISIAE; FILAMENTOUS GROWTH; HYPHAL FORMATION; DAMAGE RESPONSE; CYTOKINESIS; VIRULENCE; CANDIDA-ALBICANS-IRS4; PHOSPHOINOSITIDES AB Phosphatidylinositol 4,5-bisphosphate [PI(4,5) P-2] activates the yeast cell wall integrity pathway. Candida albicans exposure to caspofungin results in the rapid redistribution of PI(4,5) P-2 and septins to plasma membrane foci and subsequent fungicidal effects. We studied C. albicans PI(4,5) P-2 and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5) P-2 and septins were visualized by live imaging of C. albicans cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5) P-2 was also visualized in GFP-PH domain-expressing C. albicans mkc1 mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5) P-2 and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5) P-2 levels increased in a dose-response manner at caspofungin concentrations of <= 4x MIC and progressively decreased at concentrations of >= 8x MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5) P-2 and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4x MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5) P-2 redistribution remained apparent in mkc1 mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at <= 4x and >= 8x MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H2O2 did not impact the PI(4,5) P-2 or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5) P-2-septin and PKC-Mkc1 responses that correlate with the extent of C. albicans killing, and the responses are not induced by other antifungal agents. PI(4,5) P-2-septin regulation is crucial in early caspofungin responses and PKC-Mkc1 activation. C1 [Badrane, Hassan; Nguyen, M. Hong; Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Dept Med, Pittsburgh, PA USA. [Clancy, Cornelius J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Badrane, H (reprint author), Univ Pittsburgh, Div Infect Dis, Dept Med, Pittsburgh, PA USA. EM hab42@pitt.edu FU U.S. Department of Veterans Affairs (VA) [1IO1BX001955] FX This work, including the efforts of Cornelius J. Clancy, was funded by U.S. Department of Veterans Affairs (VA) (1IO1BX001955). NR 48 TC 1 Z9 1 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2016 VL 60 IS 6 BP 3591 EP 3600 DI 10.1128/AAC.02711-15 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DN4PE UT WOS:000377048900040 PM 27021331 ER PT J AU Padrez, KA Ungar, L Schwartz, HA Smith, RJ Hill, S Antanavicius, T Brown, DM Crutchley, P Asch, DA Merchant, RM AF Padrez, Kevin A. Ungar, Lyle Schwartz, Hansen Andrew Smith, Robert J. Hill, Shawndra Antanavicius, Tadas Brown, Dana M. Crutchley, Patrick Asch, David A. Merchant, Raina M. TI Linking social media and medical record data: a study of adults presenting to an academic, urban emergency department SO BMJ QUALITY & SAFETY LA English DT Article ID BEHAVIOR-CHANGE INTERVENTIONS; ALZHEIMERS-DISEASE; HEALTH INFORMATION; FACEBOOK; TWITTER; CARE; COMMUNICATION; NETWORKS; INTERNET; QUALITY AB Background Social media may offer insight into the relationship between an individual's health and their everyday life, as well as attitudes towards health and the perceived quality of healthcare services. Objective To determine the acceptability to patients and potential utility to researchers of a database linking patients' social media content with their electronic medical record (EMR) data. Methods Adult Facebook/Twitter users who presented to an emergency department were queried about their willingness to share their social media data and EMR data with health researchers for the purpose of building a databank for research purposes. Shared posts were searched for select terms about health and healthcare. Results Of the 5256 patients approached, 2717 (52%) were Facebook and/or Twitter users. 1432 (53%) of those patients agreed to participate in the study. Of these participants, 1008 (71%) consented to share their social media data for the purposes of comparing it with their EMR. Social media data consisted of 1 395 720 posts/tweets to Facebook and Twitter. Participants sharing social media data were slightly younger (29.1 +/- 9.8 vs 31.9 +/- 10.4 years old; p<0.001), more likely to post at least once a day (42% vs 29%; p=0.003) and more likely to present to the emergency room via self-arrival mode and have private insurance. Of Facebook posts, 7.5% (95% CI 4.8% to 10.2%) were related to health. Individuals with a given diagnosis in their EMR were significantly more likely to use terms related to that diagnosis on Facebook than patients without that diagnosis in their EMR (p<0.0008). Conclusions Many patients are willing to share and link their social media data with EMR data. Sharing patients have several demographic and clinical differences compared with non-sharers. A database that merges social media with EMR data has the potential to provide insights about individuals' health and health outcomes. C1 [Padrez, Kevin A.] Univ Calif San Francisco, Emergency Med, San Francisco, CA 94143 USA. [Padrez, Kevin A.; Ungar, Lyle; Schwartz, Hansen Andrew; Smith, Robert J.; Hill, Shawndra; Antanavicius, Tadas; Brown, Dana M.; Crutchley, Patrick; Asch, David A.; Merchant, Raina M.] Univ Penn, Penn Med Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Ungar, Lyle; Schwartz, Hansen Andrew] Univ Penn, Comp & Informat Sci, Philadelphia, PA 19104 USA. [Ungar, Lyle; Schwartz, Hansen Andrew; Smith, Robert J.; Antanavicius, Tadas; Crutchley, Patrick] Univ Penn, Posit Psychol Ctr, Philadelphia, PA 19104 USA. [Smith, Robert J.; Brown, Dana M.; Merchant, Raina M.] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hill, Shawndra] Univ Penn, Operat & Informat Management Dept, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Merchant, RM (reprint author), Univ Penn, Dept Emergency Med, Penn Med Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. EM Raina.merchant@uphs.upenn.edu OI Crutchley, Patrick/0000-0003-4400-9309; Smith, Robert James/0000-0001-9746-1230 FU Leonard Davis Institute of Health Economics; NIH [HL122457-01A1, 109083-01] FX Leonard Davis Institute of Health Economics. RMM received funding support from NIH, R01, and (HL122457-01A1) and NIH, K23 (109083-01). NR 45 TC 5 Z9 5 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUN PY 2016 VL 25 IS 6 BP 414 EP 423 DI 10.1136/bmjqs-2015-004489 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DN2WT UT WOS:000376924400006 PM 26464519 ER PT J AU Reid, AT Bzdok, D Langner, R Fox, PT Laird, AR Amunts, K Eickhoff, SB Eickhoff, CR AF Reid, Andrew T. Bzdok, Danilo Langner, Robert Fox, Peter T. Laird, Angela R. Amunts, Katrin Eickhoff, Simon B. Eickhoff, Claudia R. TI Multimodal connectivity mapping of the human left anterior and posterior lateral prefrontal cortex SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Meta-analytic connectivity modeling; Functional connectivity; Structural covariance; Working memory; Anterior lateral prefrontal cortex; Posterior lateral prefrontal cortex ID SPATIAL WORKING-MEMORY; TRANSCRANIAL MAGNETIC STIMULATION; CENTRAL EXECUTIVE FUNCTIONS; GLOBAL SIGNAL REGRESSION; HUMAN CEREBRAL-CORTEX; FUNCTIONAL CONNECTIVITY; DEFAULT-MODE; HUMAN BRAIN; COGNITIVE CONTROL; FRONTAL LOBES AB Working memory is essential for many of our distinctly human abilities, including reasoning, problem solving, and planning. Research spanning many decades has helped to refine our understanding of this high-level function as comprising several hierarchically organized components, some which maintain information in the conscious mind, and others which manipulate and reorganize this information in useful ways. In the neocortex, these processes are likely implemented by a distributed frontoparietal network, with more posterior regions serving to maintain volatile information, and more anterior regions subserving the manipulation of this information. Recent meta-analytic findings have identified the anterior lateral prefrontal cortex, in particular, as being generally engaged by working memory tasks, while the posterior lateral prefrontal cortex was more strongly associated with the cognitive load required by these tasks. These findings suggest specific roles for these regions in the cognitive control processes underlying working memory. To further characterize these regions, we applied three distinct seed-based methods for determining cortical connectivity. Specifically, we employed meta-analytic connectivity mapping across task-based fMRI experiments, resting-state BOLD correlations, and VBM-based structural covariance. We found a frontoparietal pattern of convergence which strongly resembled the working memory networks identified in previous research. A contrast between anterior and posterior parts of the lateral prefrontal cortex revealed distinct connectivity patterns consistent with the idea of a hierarchical organization of frontoparietal networks. Moreover, we found a distributed network that was anticorrelated with the anterior seed region, which included most of the default mode network and a subcomponent related to social and emotional processing. These findings fit well with the internal attention model of working memory, in which representation of information is processed according to an anteroposterior gradient of abstract-to-concrete representations. C1 [Reid, Andrew T.; Bzdok, Danilo; Langner, Robert; Amunts, Katrin; Eickhoff, Simon B.; Eickhoff, Claudia R.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Bzdok, Danilo; Langner, Robert; Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Claudia R.] Univ Hosp Aachen, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Laird, Angela R.] Florida Int Univ, Miami, FL 33199 USA. [Amunts, Katrin] Univ Dusseldorf, C&O Vogt Inst Brain Res, Dusseldorf, Germany. [Bzdok, Danilo] CEA Saclay, Parietal Team, INRIA, Neurospin,Bat 145, F-91191 Gif Sur Yvette, France. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Reid, AT (reprint author), Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. EM a.reid@fz-juelich.de RI Reid, Andrew/O-4359-2015; OI Reid, Andrew/0000-0002-0523-926X; Langner, Robert/0000-0002-3237-001X; Amunts, Katrin/0000-0001-5828-0867 FU Deutsche Forschungsgemeinschaft (DFG) [EI 816/4-1, LA 3071/3-1, EI 816/6-1]; National Institute of Mental Health [R01-MH074457]; Helmholtz-Portfolio Project on "Supercomputing and Modeling for the Human Brain"; European Union [604102] FX This study was supported by the Deutsche Forschungsgemeinschaft (DFG, EI 816/4-1, LA 3071/3-1; EI 816/6-1.), the National Institute of Mental Health (R01-MH074457), the Helmholtz-Portfolio Project on "Supercomputing and Modeling for the Human Brain" and the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 604102 (Human Brain Project). NR 104 TC 3 Z9 3 U1 7 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUN PY 2016 VL 221 IS 5 BP 2589 EP 2605 DI 10.1007/s00429-015-1060-5 PG 17 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DN4DB UT WOS:000377012100013 PM 25982222 ER PT J AU Hackett, TA Clause, AR Takahata, T Hackett, NJ Polley, DB AF Hackett, Troy A. Clause, Amanda R. Takahata, Toru Hackett, Nicholas J. Polley, Daniel B. TI Differential maturation of vesicular glutamate and GABA transporter expression in the mouse auditory forebrain during the first weeks of hearing SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Glutamate; GABA; Fox-3; Protein; RNA; Development; Sequencing; Cortex; Thalamus; Geniculate; A1; Juvenile; Critical period; Homeostatic plasticity; BDNF; MeCP2 ID MEDIAL GENICULATE-BODY; PRIMARY VISUAL-CORTEX; CRITICAL-PERIOD PLASTICITY; EXPERIENCE-DEPENDENT PLASTICITY; PARALAMINAR THALAMIC NUCLEI; FREQUENCY-MODULATED SWEEPS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; RAT CEREBRAL-CORTEX; POSTNATAL-DEVELOPMENT AB Vesicular transporter proteins are an essential component of the presynaptic machinery that regulates neurotransmitter storage and release. They also provide a key point of control for homeostatic signaling pathways that maintain balanced excitation and inhibition following changes in activity levels, including the onset of sensory experience. To advance understanding of their roles in the developing auditory forebrain, we tracked the expression of the vesicular transporters of glutamate (VGluT1, VGluT2) and GABA (VGAT) in primary auditory cortex (A1) and medial geniculate body (MGB) of developing mice (P7, P11, P14, P21, adult) before and after ear canal opening (similar to P11-P13). RNA sequencing, in situ hybridization, and immunohistochemistry were combined to track changes in transporter expression and document regional patterns of transcript and protein localization. Overall, vesicular transporter expression changed the most between P7 and P21. The expression patterns and maturational trajectories of each marker varied by brain region, cortical layer, and MGB subdivision. VGluT1 expression was highest in A1, moderate in MGB, and increased with age in both regions. VGluT2 mRNA levels were low in A1 at all ages, but high in MGB, where adult levels were reached by P14. VGluT2 immunoreactivity was prominent in both regions. VGluT1 (+) and VGluT2 (+) transcripts were co-expressed in MGB and A1 somata, but co-localization of immunoreactive puncta was not detected. In A1, VGAT mRNA levels were relatively stable from P7 to adult, while immunoreactivity increased steadily. VGAT (+) transcripts were rare in MGB neurons, whereas VGAT immunoreactivity was robust at all ages. Morphological changes in immunoreactive puncta were found in two regions after ear canal opening. In the ventral MGB, a decrease in VGluT2 puncta density was accompanied by an increase in puncta size. In A1, perisomatic VGAT and VGluT1 terminals became prominent around the neuronal somata. Overall, the observed changes in gene and protein expression, regional architecture, and morphology relate to-and to some extent may enable-the emergence of mature sound-evoked activity patterns. In that regard, the findings of this study expand our understanding of the presynaptic mechanisms that regulate critical period formation associated with experience-dependent refinement of sound processing in auditory forebrain circuits. C1 [Hackett, Troy A.; Takahata, Toru] Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, 465 21st Ave South,MRB 3 Suite 7110, Nashville, TN 37232 USA. [Clause, Amanda R.; Polley, Daniel B.] Harvard Univ, Sch Med, Eaton Peabody Labs, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, Boston, MA USA. [Hackett, Nicholas J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Hackett, TA (reprint author), Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, 465 21st Ave South,MRB 3 Suite 7110, Nashville, TN 37232 USA. EM troy.a.hackett@vanderbilt.edu FU NIH/NIDCD [K18 DC012527, R01 DC009836] FX Special thanks to Tia Hughes and Cara Sutcliffe in the VANTAGE core at Vanderbilt University for expert assistance with RNA isolation and sample quality assessment; Dr. Holli Hutcheson Dilks in the VANTAGE core for design and supervision of RNA sequencing; Dr. Yan Guo in the VANGARD core for expertise and implementation of bioinformatics analyses. The authors gratefully acknowledge the support of NIH/NIDCD grants K18 DC012527 to T.A.H. and R01 DC009836 to D.P. NR 301 TC 2 Z9 2 U1 4 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUN PY 2016 VL 221 IS 5 BP 2619 EP 2673 DI 10.1007/s00429-015-1062-3 PG 55 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DN4DB UT WOS:000377012100015 PM 26159773 ER PT J AU Baek, K Shim, WH Jeong, J Radhakrishnan, H Rosen, BR Boas, D Franceschini, M Biswal, BB Kim, YR AF Baek, Kwangyeol Shim, Woo Hyun Jeong, Jaeseung Radhakrishnan, Harsha Rosen, Bruce R. Boas, David Franceschini, Maria Biswal, Bharat B. Kim, Young R. TI Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Interhemispheric connectivity; Spontaneous activity; Resting state fMRI; Local field potential; Cortical layers ID INDEPENDENT COMPONENT ANALYSIS; LOW-FREQUENCY FLUCTUATIONS; MONKEY VISUAL-CORTEX; CORPUS-CALLOSUM; BARREL CORTEX; BOLD FMRI; LAMINAR SPECIFICITY; BRAIN ACTIVITY; MRI SIGNAL; DYNAMICS AB The spontaneous cerebral hemodynamic fluctuations observed during the resting state have been frequently visualized using functional magnetic resonance imaging (rsfMRI). However, the neuronal populations and neuroelectric characteristics underlying the functional connectivity of cerebrohemodynamic activities are poorly understood. We investigated the characteristics of bi-hemispheric functional connectivity via electrophysiology and rsfMRI in the primary sensory cortex of rats anesthetized by alpha-chloralose. Unlike the evoked responses, the spontaneous electrophysiological activity was concentrated in the infragranular layers and could be classified into subtypes with distinctive current sources and sinks. Both neuroelectric and rsfMRI signals were interhemispherically correlated in a layer-specific manner, suggesting that there are independent neural inputs to infragranular and granular/supragranular layers. The majority of spontaneous electrophysiological activities were bilaterally paired with delays of up to similar to 50 ms between each pair. The variable interhemispheric delay implies the involvement of indirect, multi-neural pathways. Our findings demonstrated the diverse activity patterns of layer-specific electrophysiological substrates and suggest the recruitment of multiple, non-specific brain regions in construction of interhemispheric functional connectivity. C1 [Baek, Kwangyeol; Shim, Woo Hyun; Jeong, Jaeseung] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Baek, Kwangyeol; Shim, Woo Hyun; Rosen, Bruce R.; Boas, David; Franceschini, Maria; Kim, Young R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. [Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA. [Rosen, Bruce R.; Boas, David; Franceschini, Maria; Kim, Young R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Biswal, Bharat B.] New Jersey Inst Technol, Dept Biomed Engn, Newark, NJ 07102 USA. [Kim, Young R.] Ulsan Natl Inst Sci & Technol, Ulsan, South Korea. RP Jeong, J (reprint author), Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea.; Kim, YR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.; Kim, YR (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Kim, YR (reprint author), Ulsan Natl Inst Sci & Technol, Ulsan, South Korea. EM jsjeong@kaist.ac.kr; spmn@nmr.mgh.harvard.edu RI Jeong, Jaeseung /C-1620-2011 FU National Institutes of Health [5R01EB002066, R01 EB001954]; Korea Science and Engineering Foundation (KOSEF) - Korean government [NRF-2006-2005399, M10644000028-06N4400-02810] FX The authors thank Drs. Jitendra Sharma and Robert Haslinger for their valuable comments on this manuscript. This work was supported by grants from the National Institutes of Health (Grant Number 5R01EB002066, R01 EB001954) and a Korea Science and Engineering Foundation (KOSEF) grant that was funded by the Korean government (Grant number NRF-2006-2005399, M10644000028-06N4400-02810). NR 55 TC 2 Z9 2 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUN PY 2016 VL 221 IS 5 BP 2801 EP 2815 DI 10.1007/s00429-015-1073-0 PG 15 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA DN4DB UT WOS:000377012100024 PM 26077581 ER PT J AU Abel, GA Cronin, AM Odejide, OO Uno, H Stone, RM Steensma, DP AF Abel, Gregory A. Cronin, Angel M. Odejide, Oreofe O. Uno, Hajime Stone, Richard M. Steensma, David P. TI Influence of patient and provider characteristics on quality of care for the myelodysplastic syndromes SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Myelodysplastic syndromes; quality of care; diagnosis; treatment; disparities ID STIMULATING AGENT USE; UNITED-STATES; COMORBIDITY INDEX; CANCER; POPULATION; VALIDATION; MANAGEMENT; PATTERNS; SURVIVAL; MDS AB Little is known about quality of care for patients with myelodysplastic syndromes (MDS), or patient and provider factors that influence quality. We identified Medicare enrollees diagnosed with MDS between 2006 and 2011, and analysed linked claims for performance on two widely-accepted quality measures: diagnostic bone marrow cytogenetic testing (diagnostic quality) and pre-treatment iron assessment for patients receiving an erythropoiesis-stimulating agent (ESA; treatment quality). A total of 4575 patients met the criteria for diagnostic quality measurement, and 3379 for treatment quality measurement. In the diagnostic cohort, 74% had a claim for marrow cytogenetic testing 3months before to 3months after diagnosis. In multivariate models, younger age (P<0001), treatment at a higher-volume MDS centre (P<0001), and claims for pancytopenia (P<0001) were all associated with higher levels of testing. A borderline result was observed for diagnostic year, with improvement over time (P=006). In the treatment cohort, 56% had evidence of pre-ESA iron assessment, with higher rates for later years of diagnosis (P<0001), higher household income (P=003), and those treated at higher-volume centres (P=001). In this large cohort of patients with MDS, quality of care was suboptimal overall, but worse in several specific subgroups. These data suggest that targeted educational and/or process-focused interventions are warranted. C1 [Abel, Gregory A.; Cronin, Angel M.; Odejide, Oreofe O.; Uno, Hajime] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02215 USA. [Abel, Gregory A.; Stone, Richard M.; Steensma, David P.] Dana Farber Canc Inst, Ctr Leukemia, Dept Med Oncol, Boston, MA 02215 USA. [Odejide, Oreofe O.] Dana Farber Canc Inst, Ctr Lymphoma, Dept Med Oncol, Boston, MA 02215 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu FU American Cancer Society; Edward P. Evans Foundation FX American Cancer Society Research Scholar Grant; Edward P. Evans Foundation. NR 34 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2016 VL 173 IS 5 BP 713 EP 721 DI 10.1111/bjh.13987 PG 9 WC Hematology SC Hematology GA DN7KA UT WOS:000377253000006 PM 26913376 ER PT J AU Le, HG Saeed, H Mantagos, IS Mitchell, CM Goverman, J Chodosh, J AF Le, Hong-Gam Saeed, Hajirah Mantagos, Iason S. Mitchell, Caroline M. Goverman, Jeremy Chodosh, James TI Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey SO BURNS LA English DT Article DE Stevens-Johnson syndrome; Toxic epidermal necrolysis; Survey; Burn intensive care unit ID ERYTHEMA MULTIFORME; MANAGEMENT; GUIDELINES; PROGNOSIS; DRUGS AB Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated. (C) 2015 Elsevier Ltd and ISBI. All rights reserved. C1 [Le, Hong-Gam] Univ Michigan, Sch Med, 1125 Freesia St, Ann Arbor, MI 48105 USA. [Saeed, Hajirah; Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Mantagos, Iason S.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. [Mitchell, Caroline M.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. [Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Div Burns, 55 Fruit St, Boston, MA 02114 USA. RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM hgle@med.umich.edu; Hajirah_Saeed@meei.harvard.edu; Jason.Mantagos@childrens.harvard.edu; Caroline.Mitchell@mgh.harvard.edu; JGoverman@mgh.harvard.edu; James_Chodosh@meei.harvard.edu OI Mantagos, Iason/0000-0002-3510-5465 NR 48 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 EI 1879-1409 J9 BURNS JI Burns PD JUN PY 2016 VL 42 IS 4 BP 830 EP 835 DI 10.1016/j.burns.2015.12.001 PG 6 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA DN2IC UT WOS:000376886300025 PM 26810444 ER PT J AU Baudhuin, LM Funke, BH Bean, LH Deignan, JL Hofherr, S Miller, DT Nagani, N Santani, A Saunders, C AF Baudhuin, Linnea M. Funke, Birgit H. Bean, Lora H. Deignan, Joshua L. Hofherr, Sean Miller, David T. Nagani, Narasimhan Santani, Avni Saunders, Carol TI Classifying Germline Sequence Variants in the Era of Next-Generation Sequencing SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Baudhuin, Linnea M.] Mayo Clin, Dept Lab Med & Pathol, Lab Med & Pathol, Rochester, MN 55905 USA. [Baudhuin, Linnea M.] Mayo Clin, Dept Lab Med & Pathol, Personalized Genom Lab, Rochester, MN 55905 USA. [Baudhuin, Linnea M.] Mayo Clin, Dept Lab Med & Pathol, Clin Genome Sequencing Lab, Rochester, MN 55905 USA. [Funke, Birgit H.] Partners HealthCare Personalized Med, Mol Med Lab, Cambridge, MA USA. [Funke, Birgit H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol, Boston, MA USA. [Bean, Lora H.] Emory Genet Lab, Mol Lab, Decatur, GA USA. [Deignan, Joshua L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, UCLA Mol Diagnost Labs, Los Angeles, CA 90095 USA. [Hofherr, Sean] Childrens Natl Med Ctr, Div Lab Med, Mol Diagnost & Biochem Genet, Washington, DC 20010 USA. [Miller, David T.] Claritas Genom, Cambridge, MA USA. [Miller, David T.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Miller, David T.] Harvard Univ, Sch Med, Pediat, Boston, MA USA. [Nagani, Narasimhan] Lab Corp Amer Holdings, Integrated Genet, Westborough, MA USA. [Santani, Avni] Childrens Hosp Philadelphia, Div Genom Diagnost, Philadelphia, PA 19104 USA. [Santani, Avni] Univ Penn, Perelman Sch Med, Clin Pathol, Philadelphia, PA 19104 USA. [Saunders, Carol] Childrens Mercy, Dept Pathol & Lab Med, Mol Genet Lab, Kansas City, MO USA. RP Baudhuin, LM (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM baudhuin.linnea@mayo.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2016 VL 62 IS 6 BP 799 EP 806 DI 10.1373/clinchem.2015.247874 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DN4QI UT WOS:000377051900004 PM 26861553 ER PT J AU Salvador-Culla, B Kolovou, PE Arzeno, L Martinez, S Lopez, MA AF Salvador-Culla, Borja Kolovou, Paraskevi E. Arzeno, Linnette Martinez, Santiago Lopez, Miguel A. TI Boston Keratoprosthesis Type 1 in Chemical Burns SO CORNEA LA English DT Review DE Boston keratoprosthesis; ocular chemical burns; artificial cornea; keratoprosthesis; corneal transplantation ID REPEATED CORNEAL TRANSPLANTATION; I KERATOPROSTHESIS; MULTICENTER; GLAUCOMA; OUTCOMES; IMPLANTATION; ENDOPHTHALMITIS; PREVENTION; RETENTION; TITANIUM AB Purpose:To describe and further analyze the long-term results in visual acuity (VA), anatomical retention, and rate of complications from patients who underwent Boston keratoprosthesis (B-Kpro) type 1 after ocular chemical burns in the Dominican Republic.Methods:A retrospective review of 42 eyes (22 OD:20 OS) of 36 patients who underwent B-Kpro type 1 implantation after severe ocular burn at Hospital Elias Santana in Santo Domingo, Dominican Republic, between April 2006 and October 2014, were included.Results:Demographics, VA, anatomical retention, and the rates of postoperative complications and concurrent surgeries were evaluated.Conclusions:The excellent anatomical retention rates and visual outcomes presented in this study support the remarkable capability of B-Kpro type 1 to restore functional VA in eyes with severe chemical injuries. However, strict control of the postoperative complications is necessary for long-term success. In conclusion, the use of a B-Kpro type 1 after severe chemical burn is a viable option in patients otherwise condemned to the high risk of failure associated with conventional corneal grafts. C1 [Salvador-Culla, Borja; Kolovou, Paraskevi E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Arzeno, Linnette; Martinez, Santiago; Lopez, Miguel A.] Hosp Elias Santana, Dept Ophthalmol, Santo Domingo, Dominican Rep. RP Salvador-Culla, B (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM salvaculla@gmail.com FU Massachusetts Eye and Ear Infirmary, Boston, MA FX Supported by Keratoprosthesis Fund, Massachusetts Eye and Ear Infirmary, Boston, MA (to B.S.-C. and P.E.K. were). The other authors have no funding to report. The sponsor or funding organization had no role in the design or conduct of this research. NR 37 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JUN PY 2016 VL 35 IS 6 BP 911 EP 916 DI 10.1097/ICO.0000000000000837 PG 6 WC Ophthalmology SC Ophthalmology GA DN3DM UT WOS:000376942600041 PM 27078002 ER PT J AU Auerbach, JS Schott, CK AF Auerbach, Jonathan S. Schott, Christopher K. TI Solid-Organ Graft-Versus-Host Disease After Liver Transplant: A Case Report SO CRITICAL CARE NURSE LA English DT Article ID LUNG; MACROCHIMERISM AB Solid-organ transplant graft-versus-host disease (SOT-GVHD) is a rare complication of organ transplant that is associated with high mortality. The initial signs and symptoms are vague, so this disease is easily confused with other posttransplant complications. A case of SOT-GVHD occurred after ortho-topic liver transplant for liver failure due to hepatitis C in a patient in a Veterans Affairs intensive care unit. The patient had dehydration, acute kidney injuries, rashes, diarrhea, and pancytopenia. Results of skin biopsy, bone marrow biopsy, and cytogenetic studies were consistent with SOT-GVHD. Despite supportive care including antibiotics, antiviral and antifungal therapy, high-dose steroids, antithymoglobulin and neupogen, the patient died of overwhelming sepsis. Owing to the rarity of SOT-GVHD, no evidence-based guidelines or recommendations for treatment exist. Treatment includes high-dose corticosteroids and antibiotic, antifungal, and antiviral prophylaxis. Treatment of liver transplant-related GVHD with anti-tumor necrosis factor a agents has been successful. C1 [Auerbach, Jonathan S.] Boca Raton Reg Hosp, Boca Raton, FL USA. [Auerbach, Jonathan S.] Bethesda Hosp, Boca Raton, FL USA. [Auerbach, Jonathan S.] Florida Atlantic Univ, Charles E Schmidt Coll Med, Boca Raton, FL 33431 USA. [Schott, Christopher K.] VA Pittsburgh Hlth Care Syst, Mail Route 124-U,Univ Dr C, Pittsburgh, PA 15240 USA. [Schott, Christopher K.] Univ Pittsburgh, Med Ctr, Crit Care & Emergency Med, Pittsburgh, PA USA. [Schott, Christopher K.] Univ Pittsburgh, Med Ctr, Crit Care Ultrasonog, Pittsburgh, PA USA. [Schott, Christopher K.] Univ Pittsburgh, Med Ctr, Med Student Crit Care Elect, Pittsburgh, PA USA. RP Schott, CK (reprint author), VA Pittsburgh Hlth Care Syst, Mail Route 124-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM schottck@upmc.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 EI 1940-8250 J9 CRIT CARE NURSE JI Crit. Care Nurse PD JUN PY 2016 VL 36 IS 3 BP E7 EP E11 DI 10.4037/ccn2016988 PG 5 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA DN5BZ UT WOS:000377082500002 PM 27252108 ER PT J AU Cefalu, WT Rubino, F Cummings, DE AF Cefalu, William T. Rubino, Francesco Cummings, David E. TI Metabolic Surgery for Type 2 Diabetes: Changing the Landscape of Diabetes Care SO DIABETES CARE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; Y GASTRIC BYPASS; INTENSIVE MEDICAL-MANAGEMENT; LIFE-STYLE INTERVENTION; SWEDISH OBESE SUBJECTS; BARIATRIC SURGERY; CLINICAL-TRIAL; GASTROINTESTINAL SURGERY; SYSTEMATIC ANALYSIS; GLUCOSE-METABOLISM C1 [Cefalu, William T.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Rubino, Francesco] Kings Coll London, Div Diabet & Nutr Sci, London WC2R 2LS, England. [Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. EM cefaluwt@pbrc.edu FU NCCIH NIH HHS [P50 AT002776]; NIDDK NIH HHS [U34 DK107917, R01 DK084324, R01 DK103842, R01 DK089528]; NIGMS NIH HHS [U54 GM104940] NR 52 TC 4 Z9 4 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 857 EP 860 DI 10.2337/dc16-0686 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500010 PM 27222543 ER PT J AU Batterham, RL Cummings, DE AF Batterham, Rachel L. Cummings, David E. TI Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery SO DIABETES CARE LA English DT Article ID Y GASTRIC BYPASS; VERTICAL SLEEVE GASTRECTOMY; BETA-CELL FUNCTION; OUTCOMES LONGITUDINAL DATABASE; DUODENAL-JEJUNAL BYPASS; BARIATRIC SURGERY; WEIGHT-LOSS; BILE-ACIDS; INSULIN SENSITIVITY; HYPERINSULINEMIC HYPOGLYCEMIA AB More than 20 years ago, Pories et al. published a seminal article, Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus. This was based on their observation that bariatric surgery rapidly normalized blood glucose levels in obese people with type 2 diabetes mellitus (T2DM), and 10 years later, almost 90% remained diabetes free. Pories et al. suggested that caloric restriction played a key role and that the relative contributions of proximal intestinal nutrient exclusion, rapid distal gut nutrient delivery, and the role of gut hormones required further investigation. These findings of T2DM improvement/remission after bariatric surgery have been widely replicated, together with the observation that bariatric surgery prevents or delays incident T2DM. Over the ensuing two decades, important glucoregulatory roles of the gastrointestinal (GI) tract have been firmly established. However, the physiological and molecular mechanisms underlying the beneficial glycemic effects of bariatric surgery remain incompletely understood. In addition to the mechanisms proposed by Pories et al., changes in bile acid metabolism, GI tract nutrient sensing and glucose utilization, incretins, possible anti-incretin(s), and the intestinal microbiome are implicated. These changes, acting through peripheral and/or central pathways, lead to reduced hepatic glucose production, increased tissue glucose uptake, improved insulin sensitivity, and enhanced -cell function. A constellation of factors, rather than a single overarching mechanism, likely mediate postoperative glycemic improvement, with the contributing factors varying according to the surgical procedure. Thus, different bariatric/metabolic procedures provide us with experimental tools to probe GI tract physiology. Embracing this approach through the application of detailed phenotyping, genomics, metabolomics, and gut microbiome studies will enhance our understanding of metabolic regulation and help identify novel therapeutic targets. C1 [Batterham, Rachel L.] UCL, Dept Med, Obes Res Ctr, London, England. [Batterham, Rachel L.] Univ Coll London Hosp, Bariatr Ctr Weight Management & Metab Surg, London, England. [Batterham, Rachel L.] Univ Coll London Hosp, Natl Inst Hlth Res, Biomed Res Ctr, London, England. [Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. RP Batterham, RL (reprint author), UCL, Dept Med, Obes Res Ctr, London, England.; Batterham, RL (reprint author), Univ Coll London Hosp, Bariatr Ctr Weight Management & Metab Surg, London, England.; Batterham, RL (reprint author), Univ Coll London Hosp, Natl Inst Hlth Res, Biomed Res Ctr, London, England. EM r.batterham@ucl.ac.uk FU Rosetrees Trust; Stoneygate Trust; National Institute of Diabetes and Digestive and Kidney Diseases [RO1-DK-103842, RO1-DK-084324, RO1-DK-089528, U34-DK-107917] FX R.L.B. is supported by grants from the Rosetrees Trust and Stoneygate Trust. D.E.C. is supported by National Institute of Diabetes and Digestive and Kidney Diseases grants RO1-DK-103842, RO1-DK-084324, RO1-DK-089528, and U34-DK-107917. NR 67 TC 9 Z9 10 U1 5 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 893 EP 901 DI 10.2337/dc16-0145 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500014 PM 27222547 ER PT J AU Adams, TD Arterburn, DE Nathan, DM Eckel, RH AF Adams, Ted D. Arterburn, David E. Nathan, David M. Eckel, Robert H. TI Clinical Outcomes of Metabolic Surgery: Microvascular and Macrovascular Complications SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; Y GASTRIC BYPASS; TERM-FOLLOW-UP; MAJOR CARDIOVASCULAR EVENTS; AFFAIRS MEDICAL-CENTERS; MORBIDLY OBESE-PATIENTS; CHRONIC KIDNEY-DISEASE; BLOOD-GLUCOSE CONTROL; BARIATRIC SURGERY; WEIGHT-LOSS AB Understanding of the long-term clinical outcomes associated with bariatric surgery has recently been advanced. Research related to the sequelae of diabetesin particular, long-term microvascular and macrovascular complicationsin patients who undergo weight-loss surgery is imperative to this pursuit. While numerous randomized control trials have assessed glucose control with bariatric surgery compared with intensive medical therapy, bariatric surgery outcome data relating to microvascular and macrovascular complications have been limited to observational studies and nonrandomized clinical trials. As a result, whether bariatric surgery is associated with a long-term reduction in microvascular and macrovascular complications when compared with current intensive glycemic control therapy cannot be determined because the evidence is insufficient. However, the consistent salutary effects of bariatric surgery on diabetes remission and glycemic improvement support the opportunity (and need) to conduct high-quality studies of bariatric surgery versus intensive glucose control. This review provides relevant background information related to the treatment of diabetes, hyperglycemia, and long-term complications; reports clinical findings (to date) with bariatric surgery; and identifies ongoing research focusing on long-term vascular outcomes associated with bariatric surgery. C1 [Adams, Ted D.] Univ Utah, Intermt Healthcare, Intermt LiVe Well Ctr, Salt Lake City, UT USA. [Adams, Ted D.] Univ Utah, Div Cardiovasc Genet, Salt Lake City, UT USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. [Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA. [Eckel, Robert H.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA. RP Adams, TD (reprint author), Univ Utah, Intermt Healthcare, Intermt LiVe Well Ctr, Salt Lake City, UT USA.; Adams, TD (reprint author), Univ Utah, Div Cardiovasc Genet, Salt Lake City, UT USA. EM ted.adams@imail.org FU National Institutes of Health; NIDDK; Patient-Centered Outcomes Research Institute; Department of Veterans Affairs; division of Healthwise FX T.D.A. has received research funding from the National Institutes of Health and the NIDDK. D.E.A. has received institutional research grants and payments for travel expenses related to bariatric surgery from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, the Department of Veterans Affairs, and the Informed Medical Decisions Foundation (now a division of Healthwise). NR 101 TC 4 Z9 4 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 912 EP 923 DI 10.2337/dc16-0157 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500016 PM 27222549 ER PT J AU Cummings, DE Cohen, RV AF Cummings, David E. Cohen, Ricardo V. TI Bariatric/Metabolic Surgery to Treat Type 2 Diabetes in Patients With a BMI < 35 kg/m(2) SO DIABETES CARE LA English DT Article ID SWEDISH OBESE SUBJECTS; GASTRIC BYPASS-SURGERY; BODY-MASS INDEX; RANDOMIZED CONTROLLED-TRIAL; INTENSIVE MEDICAL THERAPY; LONG-TERM REMISSION; BARIATRIC SURGERY; METABOLIC SURGERY; GASTROINTESTINAL SURGERY; CONTROLLED INTERVENTION AB OBJECTIVEGlobal usage of bariatric surgery has been dictated for the past quarter century by National Institutes of Health recommendations restricting these operations to individuals with a BMI 35 kg/m(2). Strong evidence now demonstrates that bariatric procedures markedly improve or cause remission of type 2 diabetes mellitus (T2DM), in part through weight-independent mechanisms, and that baseline BMI does not predict surgical benefits on glycemic or cardiovascular outcomes. This impels consideration of such operations as metabolic surgery, which is used expressly to treat T2DM, including among patients with a BMI <35 kg/m(2) who constitute the majority of people with diabetes worldwide. Here, we review available evidence to inform that consideration.RESULTSA meta-analysis of the 11 published randomized clinical trials (RCTs) directly comparing bariatric/metabolic surgery versus a variety of medical/lifestyle interventions for T2DM provides level 1A evidence that surgery is superior for T2DM remission, glycemic control, and HbA(1c) lowering. Importantly, this is equally true for patients whose baseline BMI is below or above 35 kg/m(2). Similar conclusions derive from meta-analyses of high-quality nonrandomized prospective comparisons. Meta-analysis of all pertinent published studies indicates that T2DM remission rates following bariatric/metabolic surgery are comparable above and below the 35 kg/m(2) BMI threshold. The safety, antidiabetes durability, and benefits on other cardiovascular risk factors from bariatric/metabolic surgery appear roughly comparable among patients with a BMI below or above 35 kg/m(2). Further studies are needed to extend long-term findings and measure hard macrovascular/microvascular outcomes and mortality in RCTs.CONCLUSIONSExtant data, including level 1A evidence from numerous RCTs, support new guidelines from the 2nd Diabetes Surgery Summit that advocate for the consideration of bariatric/metabolic surgery as one option, along with lifestyle and medical therapy, to treat T2DM among patients with a BMI <35 kg/m(2). C1 [Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Cohen, Ricardo V.] Oswaldo Cruz Hosp, Ctr Diabet & Obes, Sao Paulo, Brazil. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.; Cummings, DE (reprint author), Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. EM davidec@u.washington.edu FU NIH [RO1 DK103842, RO1 DK084324, RO1 DK089528, U34 DK107917] FX D.E.C. is supported by NIH grants RO1 DK103842, RO1 DK084324, RO1 DK089528, and U34 DK107917. NR 45 TC 3 Z9 3 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 924 EP 933 DI 10.2337/dc16-0350 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500017 PM 27222550 ER PT J AU Powe, CE Allard, C Battista, MC Doyon, M Bouchard, L Ecker, JL Perron, P Florez, JC Thadhani, R Hivert, MF AF Powe, Camille E. Allard, Catherine Battista, Marie-Claude Doyon, Myriam Bouchard, Luigi Ecker, Jeffrey L. Perron, Patrice Florez, Jose C. Thadhani, Ravi Hivert, Marie-France TI Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus SO DIABETES CARE LA English DT Article ID GLUCOSE-TOLERANCE TEST; RESISTANCE; PREGNANCY; HYPERGLYCEMIA; INDEXES; GROWTH AB OBJECTIVETo characterize physiologic subtypes of gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODSInsulin sensitivity and secretion were estimated in 809 women at 24-30 weeks' gestation, using oral glucose tolerance test-based indices. In women with GDM (8.3%), defects in insulin sensitivity or secretion were defined below the 25th percentile in women with normal glucose tolerance (NGT). GDM subtypes were defined based on the defect(s) present.RESULTSRelative to women with NGT, women with predominant insulin sensitivity defects (51% of GDM) had higher BMI and fasting glucose, larger infants (birth weight z score 0.57 [-0.01 to 1.37] vs. 0.03 [-0.53 to 0.52], P = 0.001), and greater risk of GDM-associated adverse outcomes (57.6 vs. 28.2%, P = 0.003); differences were independent of BMI. Women with predominant insulin secretion defects (30% of GDM) had BMI, fasting glucose, infant birth weights, and risk of adverse outcomes similar to those in women with NGT.CONCLUSIONSHeterogeneity of physiologic processes underlying hyperglycemia exists among women with GDM. GDM with impaired insulin sensitivity confers a greater risk of adverse outcomes. C1 [Powe, Camille E.; Florez, Jose C.; Hivert, Marie-France] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Powe, Camille E.; Ecker, Jeffrey L.; Florez, Jose C.; Thadhani, Ravi; Hivert, Marie-France] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Allard, Catherine; Battista, Marie-Claude; Doyon, Myriam; Bouchard, Luigi; Perron, Patrice; Hivert, Marie-France] Univ Sherbrooke, Quebec City, PQ, Canada. [Allard, Catherine; Battista, Marie-Claude; Doyon, Myriam; Bouchard, Luigi; Perron, Patrice; Hivert, Marie-France] Ctr Hosp Univ Sherbrooke, Ctr Rech Clin Etienne Le Bel, Quebec City, PQ, Canada. [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. RP Hivert, MF (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.; Hivert, MF (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Hivert, MF (reprint author), Univ Sherbrooke, Quebec City, PQ, Canada.; Hivert, MF (reprint author), Ctr Hosp Univ Sherbrooke, Ctr Rech Clin Etienne Le Bel, Quebec City, PQ, Canada.; Hivert, MF (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. EM mhivert@partners.org OI Allard, Catherine/0000-0002-8829-4984 FU National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK007028-41, K24 DK094872-03]; Diabete Quebec; Fonds de Recherche du Quebec - Sante [20697]; Canadian Institutes of Health Research [MOP 115071]; American Diabetes Association [1-15-ACE-26] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007028-41 to C.E.P. and K24 DK094872-03 to R.T.), Diabete Quebec (P.P.), Fonds de Recherche du Quebec - Sante (20697 to M.-F.H.), the Canadian Institutes of Health Research (MOP 115071 to M.-F.H.), and the American Diabetes Association (Accelerator Award 1-15-ACE-26 to M.-F.H.). NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 1052 EP 1055 DI 10.2337/dc15-2672 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500033 PM 27208340 ER PT J AU Livny, A Ravona-Springer, R Heymann, A Priess, R Kushnir, T Tsarfaty, G Rabinov, L Moran, R Hoffman, H Cooper, I Greenbaum, L Silverman, J Sano, M Johnson, SC Bendlin, BB Beeri, MS AF Livny, Abigail Ravona-Springer, Ramit Heymann, Anthony Priess, Rachel Kushnir, Tammar Tsarfaty, Galia Rabinov, Leeron Moran, Reut Hoffman, Hadass Cooper, Itzik Greenbaum, Lior Silverman, Jeremy Sano, Mary Johnson, Sterling C. Bendlin, Barbara B. Beeri, Michal Schnaider TI Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID VASCULAR RISK-FACTORS; COGNITIVE DECLINE; APOLIPOPROTEIN-E; DISEASE; BRAIN; METAANALYSIS; EPSILON-4; DEMENTIA; MELLITUS; PEOPLE AB OBJECTIVEWe assessed whether the apolipoprotein epsilon 4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA(1c) SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSWMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles.RESULTSHbA(1c) variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA(1c), number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050).CONCLUSIONSThe results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control. C1 [Livny, Abigail; Kushnir, Tammar; Tsarfaty, Galia; Rabinov, Leeron; Moran, Reut] Chaim Sheba Med Ctr, Dept Diagnost Imaging, IL-52621 Tel Hashomer, Israel. [Livny, Abigail; Ravona-Springer, Ramit; Hoffman, Hadass; Cooper, Itzik; Greenbaum, Lior; Beeri, Michal Schnaider] Chaim Sheba Med Ctr, Josef Sagol Neurosci Ctr, IL-52621 Tel Hashomer, Israel. [Ravona-Springer, Ramit] Chaim Sheba Med Ctr, Memory Clin, IL-52621 Tel Hashomer, Israel. [Heymann, Anthony; Priess, Rachel] Maccabi Healthcare Serv, Tel Aviv, Israel. [Heymann, Anthony; Kushnir, Tammar; Tsarfaty, Galia] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Cooper, Itzik; Sano, Mary; Beeri, Michal Schnaider] Interdisciplinary Ctr Herzliya, Sch Psychol, Herzliyya, Israel. [Silverman, Jeremy] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Silverman, Jeremy] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Johnson, Sterling C.; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Johnson, Sterling C.; Bendlin, Barbara B.] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. RP Livny, A (reprint author), Chaim Sheba Med Ctr, Dept Diagnost Imaging, IL-52621 Tel Hashomer, Israel.; Livny, A (reprint author), Chaim Sheba Med Ctr, Josef Sagol Neurosci Ctr, IL-52621 Tel Hashomer, Israel. EM abigail.livnyezer@gmail.com FU American Federation for Aging Research; National Institute on Aging [P50-AG-05138, R01-AG-034087, R21-AG-043878]; Helen Bader Foundation; Leroy Schecter Foundation; Irma T. Hirschl Scholar Award FX This research was conducted while I.C. was a New Investigator Award in Alzheimer Disease recipient from the American Federation for Aging Research and was supported by National Institute on Aging grants P50-AG-05138 (to M.S.) and R01-AG-034087 and R21-AG-043878 (to M.S.B.) as well as the Helen Bader Foundation, the Leroy Schecter Foundation, and the Irma T. Hirschl Scholar Award (to M.S.B.). NR 17 TC 0 Z9 0 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2016 VL 39 IS 6 BP 1056 EP 1059 DI 10.2337/dc15-2331 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN3RJ UT WOS:000376980500034 PM 27208321 ER PT J AU Rinke, ML Singh, H Ruberman, S Adelman, J Choi, SJ O'Donnell, H Stein, REK Brady, TM Heo, M Lehmann, CU Kairys, S Rice-Conboy, E Theissen, K Bundy, DG AF Rinke, Michael L. Singh, Hardeep Ruberman, Sarah Adelman, Jason Choi, Steven J. O'Donnell, Heather Stein, Ruth E. K. Brady, Tammy M. Heo, Moonseong Lehmann, Christoph U. Kairys, Steven Rice-Conboy, Elizabeth Theissen, Keri Bundy, David G. TI Primary care pediatricians' interest in diagnostic error reduction SO DIAGNOSIS LA English DT Article DE diagnostic error; pediatrics; primary care AB Background: Diagnostic errors causing harm in children are understudied, resulting in a knowledge gap regarding pediatricians' interest in reducing their incidence. Methods: Electronic survey of general pediatricians focusing on diagnostic error incidence, errors they were interested in trying to improve, and errors reduced by their electronic health record (EHR). Results: Of 300 contacted pediatricians, 77 (26%) responded, 58 (19%) served ambulatory patients, and 48 (16%) completed the entire questionnaire. Of these 48, 17 (35%) reported making a diagnostic error at least monthly, and 16 (33%) reported making a diagnostic error resulting in an adverse event at least annually. Pediatricians were "most" interested in "trying to improve" missed diagnosis of hypertension (17%), delayed diagnosis due to missed subspecialty referral (15%), and errors associated with delayed follow-up of abnormal laboratory values (13%). Among the 44 pediatricians with an EHR, 16 (36%) said it reduced the likelihood of missing obesity and 14 (32%) said it reduced the likelihood of missing hypertension. Also, 15 (34%) said it helped avoid delays in follow-up of abnormal laboratory values. A third (36%) reported no help in diagnostic error reduction from their EHR. Conclusions: Pediatricians self-report an appreciable number of diagnostic errors and were most interested in preventing high frequency, non-life-threatening errors. There exists a need to leverage EHRs to support error reduction efforts. C1 [Rinke, Michael L.; Choi, Steven J.; O'Donnell, Heather; Stein, Ruth E. K.] Childrens Hosp Montefiore, Dept Pediat, Bronx, NY USA. [Rinke, Michael L.; Ruberman, Sarah; Choi, Steven J.; O'Donnell, Heather; Stein, Ruth E. K.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Singh, Hardeep] Baylor Coll Med, Dept Med, Michael E Debakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston, TX 77030 USA. [Adelman, Jason] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Brady, Tammy M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Heo, Moonseong] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Lehmann, Christoph U.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Kairys, Steven] Jersey Shore Univ, Med Ctr, Neptune, NJ USA. [Kairys, Steven; Rice-Conboy, Elizabeth; Theissen, Keri] Amer Acad Pediat, Div Qual, Qual Improvement Innovat Networks, Elk Grove Village, IL USA. [Bundy, David G.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Rinke, ML (reprint author), Childrens Hosp Montefiore, Dept Pediat, Bronx, NY USA.; Rinke, ML (reprint author), Albert Einstein Coll Med, Bronx, NY 10467 USA. EM mrinke@montefiore.org FU NCATS NIH HHS [UL1 TR001073] NR 13 TC 0 Z9 0 U1 0 U2 0 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-8011 EI 2194-802X J9 DIAGNOSIS JI Diagnosis PD JUN PY 2016 VL 3 IS 2 BP 65 EP 69 DI 10.1515/dx-2015-0033 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DN7FU UT WOS:000377241500005 PM 28111611 ER PT J AU Zon, L AF Zon, Leonard TI Modeling human diseases: an education in interactions and interdisciplinary approaches SO DISEASE MODELS & MECHANISMS LA English DT Editorial Material ID ZEBRAFISH; TRANSPLANTATION; CANCER AB Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic. C1 [Zon, Leonard] Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Stem Cell Program,Boston C, 44 Binney St, Boston, MA 02115 USA. [Zon, Leonard] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Boston Childrens Hosp, 44 Binney St, Boston, MA 02115 USA. [Zon, Leonard] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Zon, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Stem Cell Program,Boston C, 44 Binney St, Boston, MA 02115 USA.; Zon, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Hematol Oncol,Boston Childrens Hosp, 44 Binney St, Boston, MA 02115 USA.; Zon, L (reprint author), Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM zon@enders.tch.harvard.edu NR 18 TC 0 Z9 0 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JUN 1 PY 2016 VL 9 IS 6 BP 597 EP 600 DI 10.1242/dmm.025882 PG 4 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DN5EG UT WOS:000377088600001 PM 27483497 ER PT J AU Hauser, R Gaskins, AJ Souter, I Smith, KW Dodge, LE Ehrlich, S Meeker, JD Calafat, AM Williams, PL AF Hauser, Russ Gaskins, Audrey J. Souter, Irene Smith, Kristen W. Dodge, Laura E. Ehrlich, Shelley Meeker, John D. Calafat, Antonia M. Williams, Paige L. CA EARTH Study Team TI Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BISPHENOL-A CONCENTRATIONS; DI(2-ETHYLHEXYL) PHTHALATE; GRANULOSA-CELLS; UNITED-STATES; IVF TREATMENT; DNA-DAMAGE; PREGNANCY; EXPOSURE; SPERM; VARIABILITY AB Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [ mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, Sigma DEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of Sigma DEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. C1 [Hauser, Russ; Smith, Kristen W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ; Gaskins, Audrey J.; Dodge, Laura E.; Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ; Souter, Irene] Harvard Univ, Dept Obstet & Gynecol, Sch Med, Massachusetts Gen Hosp,Fertil Ctr, Boston, MA 02115 USA. [Gaskins, Audrey J.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Ehrlich, Shelley] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Bldg 1,Room 1409,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES009718, ES022955, ES000002, T32ES007069]; National Institute of Child Health and Human Development (NICHD), National Institutes of Health [T32HD060454] FX This work was supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32HD060454 from the National Institute of Child Health and Human Development (NICHD), National Institutes of Health. NR 52 TC 8 Z9 8 U1 8 U2 20 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2016 VL 124 IS 6 BP 831 EP 839 DI 10.1289/ehp.1509760 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DN5BO UT WOS:000377081300027 PM 26545148 ER PT J AU Christiansen, JS Backeljauw, PF Bidlingmaier, M Biller, BMK Boguszewski, MCS Casanueva, FF Chanson, P Chatelain, P Choong, CS Clemmons, DR Cohen, LE Cohen, P Frystyk, J Grimberg, A Hasegawa, Y Haymond, MW Ho, K Hoffman, AR Holly, JMP Horikawa, R Hoybye, C Jorgensen, JOL Johannsson, G Juul, A Katznelson, L Kopchick, JJ Lee, KO Lee, KW Luo, XP Melmed, S Miller, BS Misra, M Popovic, V Rosenfeld, RG Ross, J Ross, RJ Saenger, P Strasburger, CJ Thorner, MO Werner, H Yuen, K AF Christiansen, Jens Sandahl Backeljauw, Philippe F. Bidlingmaier, Martin Biller, Beverly M. K. Boguszewski, Margaret C. S. Casanueva, Felipe F. Chanson, Philippe Chatelain, Pierre Choong, Catherine S. Clemmons, David R. Cohen, Laurie E. Cohen, Pinchas Frystyk, Jan Grimberg, Adda Hasegawa, Yukihiro Haymond, Morey W. Ho, Ken Hoffman, Andrew R. Holly, Jeff M. P. Horikawa, Reiko Hoeybye, Charlotte Jorgensen, Jens Otto L. Johannsson, Gudmundur Juul, Anders Katznelson, Laurence Kopchick, John J. Lee, K. O. Lee, Kuk-Wha Luo, Xiaoping Melmed, Shlomo Miller, Bradley S. Misra, Madhusmita Popovic, Vera Rosenfeld, Ron G. Ross, Judith Ross, Richard J. Saenger, Paul Strasburger, Christian J. Thorner, Michael O. Werner, Haim Yuen, Kevin TI Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GH-DEFICIENT ADULTS; CONTINUOUS-INFUSION; PEDIATRIC-PATIENTS; DAILY INJECTIONS; THERAPY; CHILDREN; LIPOPROTEIN; SYSTEM; RISK AB Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations. C1 [Christiansen, Jens Sandahl; Frystyk, Jan; Jorgensen, Jens Otto L.] Aarhus Univ, Aarhus, Denmark. [Backeljauw, Philippe F.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Bidlingmaier, Martin] Klinikum Univ Munchen, Munich, Germany. [Biller, Beverly M. K.; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boguszewski, Margaret C. S.] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Casanueva, Felipe F.] Univ Santiago de Compostela, Santiago De Compostela, Spain. [Chanson, Philippe] Univ Paris Saclay, Le Kremlin Bicetre, France. [Chatelain, Pierre] Univ Lyon 1, F-69365 Lyon, France. [Choong, Catherine S.] Univ Western Australia, Subiaco, WA, Australia. [Clemmons, David R.] Univ N Carolina, Chapel Hill, NC USA. [Cohen, Laurie E.] Boston Childrens Hosp, Boston, MA USA. [Cohen, Pinchas] Univ So Calif, Los Angeles, CA USA. [Grimberg, Adda] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hasegawa, Yukihiro] Tokyo Metropolitan Childrens Med Ctr, Tokyo, Japan. [Haymond, Morey W.] Baylor Coll Med, Houston, TX 77030 USA. [Ho, Ken] Univ Queensland, Brisbane, Qld, Australia. [Hoffman, Andrew R.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Hoffman, Andrew R.] Stanford Univ, Palo Alto, CA 94304 USA. [Holly, Jeff M. P.] Univ Bristol, Bristol, Avon, England. [Horikawa, Reiko] Natl Ctr Child Hlth & Dev, Tokyo, Japan. [Hoeybye, Charlotte] Karolinska Univ Hosp, Stockholm, Sweden. [Johannsson, Gudmundur] Univ Gothenburg, Gothenburg, Sweden. [Juul, Anders] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Katznelson, Laurence] Stanford Univ, Stanford, CA 94305 USA. [Kopchick, John J.] Ohio Univ, Athens, OH 45701 USA. [Lee, K. O.] Natl Univ Singapore, Singapore 117548, Singapore. [Lee, Kuk-Wha] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Luo, Xiaoping] Tongji Hosp, Wuhan, Peoples R China. [Melmed, Shlomo] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Miller, Bradley S.] Masonic Childrens Hosp, Minneapolis, MN USA. [Popovic, Vera] Univ Belgrade, Belgrade, Serbia. [Rosenfeld, Ron G.] Stat5 Consulting, Los Altos, CA USA. [Ross, Judith] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Ross, Richard J.] Univ Sheffield, Sheffield, S Yorkshire, England. [Saenger, Paul] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Strasburger, Christian J.] Charite, D-13353 Berlin, Germany. [Thorner, Michael O.] Univ Virginia, Charlottesville, VA USA. [Werner, Haim] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Yuen, Kevin] Swedish Neurosci Inst, Seattle, WA USA. RP Hoffman, AR (reprint author), VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.; Hoffman, AR (reprint author), Stanford Univ, Palo Alto, CA 94304 USA. EM arhoffman@stanford.edu FU Growth Hormone Research Society FX This work was supported by the Growth Hormone Research Society. NR 28 TC 2 Z9 2 U1 1 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUN PY 2016 VL 174 IS 6 BP C1 EP C8 DI 10.1530/EJE-16-0111 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN5NB UT WOS:000377114700001 PM 27009113 ER PT J AU Black, KE Berdyshev, E Bain, G Castelino, FV Shea, BS Probst, CK Fontaine, BA Bronova, I Goulet, L Lagares, D Ahluwalia, N Knipe, RS Natarajan, V Tager, AM AF Black, Katharine E. Berdyshev, Evgeny Bain, Gretchen Castelino, Flavia V. Shea, Barry S. Probst, Clemens K. Fontaine, Benjamin A. Bronova, Irina Goulet, Lance Lagares, David Ahluwalia, Neil Knipe, Rachel S. Natarajan, Viswanathan Tager, Andrew M. TI Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis SO FASEB JOURNAL LA English DT Article DE ectonucleotide pyrophosphatase; phosphodiesterase 2; lysophospholipase D; lysophosphatidylcholine; bleomycin; mouse model ID LYSOPHOSPHOLIPASE-D; SPHINGOSINE 1-PHOSPHATE; LIPID MEDIATORS; VASCULAR LEAK; HAIR-GROWTH; LPA; ENZYME; EXPRESSION; IDENTIFICATION; INFLAMMATION AB Lysophosphatidic acid (LPA) is an important mediator of pulmonary fibrosis. In blood and multiple tumor types, autotaxin produces LPA from lysophosphatidylcholine (LPC) via lysophospholipase D activity, but alternative enzymatic pathways also exist for LPA production. We examined the role of autotaxin (ATX) in pulmonary LPA production during fibrogenesis in a bleomycin mouse model. We found that bleomycin injury increases the bronchoalveolar lavage (BAL) fluid levels of ATX protein 17-fold. However, the LPA and LPC species that increase in BAL of bleomycin-injured mice were discordant, inconsistent with a substrate-product relationship between LPC and LPA in pulmonary fibrosis. LPA species with longer chain polyunsaturated acyl groups predominated in BAL fluid after bleomycin injury, with 22:5 and 22:6 species accounting for 55 and 16% of the total, whereas the predominant BAL LPC species contained shorter chain, saturated acyl groups, with 16:0 and 18:0 species accounting for 56 and 14% of the total. Further, administration of the potent ATX inhibitor PAT-048 to bleomycin-challenged mice markedly decreased ATX activity systemically and in the lung, without effect on pulmonary LPA or fibrosis. Therefore, alternative ATX-independent pathways are likely responsible for local generation of LPA in the injured lung. These pathways will require identification to therapeutically target LPA production in pulmonary fibrosis.Black, K. E., Berdyshev, E., Bain, G., Castelino, F. V., Shea, B. S., Probst, C. K., Fontaine, B. A., Bronova, I., Goulet, L., Lagares, D., Ahluwalia, N., Knipe, R. S., Natarajan, V., Tager, A. M. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. C1 [Black, Katharine E.; Shea, Barry S.; Probst, Clemens K.; Fontaine, Benjamin A.; Lagares, David; Ahluwalia, Neil; Knipe, Rachel S.; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA USA. [Black, Katharine E.; Castelino, Flavia V.; Shea, Barry S.; Probst, Clemens K.; Fontaine, Benjamin A.; Lagares, David; Ahluwalia, Neil; Knipe, Rachel S.; Tager, Andrew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Castelino, Flavia V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Berdyshev, Evgeny; Bronova, Irina; Natarajan, Viswanathan] Univ Illinois, Dept Med, Chicago, IL USA. [Natarajan, Viswanathan] Univ Illinois, Dept Pharmacol, Chicago, IL USA. [Berdyshev, Evgeny; Bronova, Irina] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Bain, Gretchen; Goulet, Lance] PharmAkea Inc, San Diego, CA USA. [Shea, Barry S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Tager, AM (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Pulm & Crit Care Med, CNY149-8301,149 Thirteenth St, Charlestown, MA 02129 USA. EM amtager@partners.org FU U.S. National Institutes of Health (NIH), National Heart, Lung, and Blood Institute [R01HL108975]; Office of the Director [P01HL098050, S10OD010660]; National Center for Research Resources; National Center for Advancing Translational Sciences, NIH National Center for Advancing Translational Sciences [UL1TR001102]; Harvard University FX The authors acknowledge the support of U.S. National Institutes of Health (NIH), National Heart, Lung, and Blood Institute Grant R01HL108975 (to A. M. T.); Grant P01HL098050 and Grant S10OD010660 from the Office of the Director (for ESI-LC/MS/MS equipment) (to V. N. and E. B.). The authors also gratefully acknowledge assistance with the analyses performed by the Harvard Clinical and Translational Science Center (Harvard Catalyst), which is supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH National Center for Advancing Translational Sciences Grant UL1TR001102, and financial contributions from Harvard University and its affiliated academic healthcare centers. The content of this manuscript 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 NIH. K. E. B. and A. M. T. conceived the project, designed the studies, and wrote the manuscript. K. E. B. performed and analyzed experiments investigating ATX or phospholipase activity, concentration, and expression. G. B. and L. G. designed and analyzed PAT-048 pharmacodynamic and pharmacokinetic analyses. E. B., I. B., and V. N. performed the LC/MS analysis of LPA and LPC. F. V. C. and B. S. S assisted with experimental design and data acquisition. R. S. K., C. K. P., and B. A. F. performed the animal experiments and assisted with data acquisition; D. L. and N. A. performed the FTY720 animal experiments and assisted with the experimental design. E. B., G. B., B. S. S., N. A., and V. N. also reviewed and intellectually contributed to the manuscript. G. B. and L. G. receive income and own equity in PharmAkea, Inc., and A. M. T. is a member of the PharmAkea scientific advisory board. NR 46 TC 2 Z9 2 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JUN PY 2016 VL 30 IS 6 BP 2435 EP 2450 DI 10.1096/fj.201500197R PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DN2FA UT WOS:000376878300031 PM 27006447 ER PT J AU Hurley, BP Pirzai, W Eaton, AD Harper, M Roper, J Zimmermann, C Ladics, GS Layton, RJ Delaney, B AF Hurley, Bryan P. Pirzai, Waheed Eaton, Alex D. Harper, Marc Roper, Jason Zimmermann, Cindi Ladics, Gregory S. Layton, Raymond J. Delaney, Bryan TI An experimental platform using human intestinal epithelial cell lines to differentiate between hazardous and non-hazardous proteins SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Protein toxins; Intestinal epithelial cells; Cytotoxicity ID CLOSTRIDIUM-DIFFICILE TOXIN; PHASEOLUS-VULGARIS LECTINS; HEAT-LABILE ENTEROTOXIN; WHEAT-GERM-AGGLUTININ; STREPTOLYSIN-O; CACO-2 CELLS; IN-VITRO; BETA-LACTOGLOBULIN; ESCHERICHIA-COLI; BARRIER FUNCTION AB Human intestinal epithelial cell lines (T84, Caco-2, and HCT-8) grown on permeable Transwell (TM) filters serve as models of the gastrointestinal barrier. In this study, this in vitro model system was evaluated for effectiveness at distinguishing between hazardous and non-hazardous proteins. Indicators of cytotoxicity (LDH release, MTT conversion), monolayer barrier integrity ([H-3]-inulin flux, horseradish peroxidase flux, trans-epithelial electrical resistance [TEER]), and inflammation (IL-8, IL-6 release) were monitored following exposure to hazardous or non-hazardous proteins. The hazardous proteins examined include streptolysin 0 (from Streptococcus pyogenes), Clostridium difficile Toxins A and B, heat-labile toxin from enterotoxigenic Escherichia coli, listeriolysin 0 (from Listeria monocytogenes), melittin (from bee venom), and mastoparan (from wasp venom). Non-hazardous proteins included bovine and porcine serum albumin, bovine fibronectin, and ribulose bisphosphate carboxylase/oxygenase (RuBisco) from spinach. Food allergenic proteins bovine milk beta-lactoglobulin and peanut Ara h 2 were also tested as was the anti nutritive food protein wheat germ agglutinin. Results demonstrated that this model system effectively distinguished between hazardous and non-hazardous proteins through combined analysis of multiple cells lines and assays. This experimental strategy may represent a useful adjunct to multi-component analysis of proteins with unknown hazard profiles. (C) 2016 DuPont Pioneer. Published by Elsevier Ltd. C1 [Hurley, Bryan P.; Pirzai, Waheed; Eaton, Alex D.] Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, CNY 114 114-3503, Charlestown, MA 02129 USA. [Hurley, Bryan P.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02129 USA. [Harper, Marc; Zimmermann, Cindi; Layton, Raymond J.; Delaney, Bryan] DuPont Pioneer, 8325 NW 62nd Ave, Johnston, IA 50131 USA. [Roper, Jason; Ladics, Gregory S.] DuPont Haskell, 1090 Elkton Rd, Newark, DE 19714 USA. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, CNY 114 114-3503, Charlestown, MA 02129 USA. EM bphurley@partners.org FU DuPont Pioneer FX These studies were conducted at MGH under contract research that was funded by DuPont Pioneer. BPH, WP, and AE are employees of MGH and MH, JR, CZ, GSL, RJL, and BD are employees of DuPont Pioneer. NR 72 TC 1 Z9 1 U1 7 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2016 VL 92 BP 75 EP 87 DI 10.1016/j.fct.2016.04.003 PG 13 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA DN1CR UT WOS:000376804400009 PM 27060235 ER PT J AU Corral-Frias, NS Pizzagalli, DA Carre, JM Michalski, LJ Nikolova, YS Perlis, RH Fagerness, J Lee, MR Conley, ED Lancaster, TM Haddad, S Wolf, A Smoller, JW Hariri, AR Bogdan, R AF Corral-Frias, N. S. Pizzagalli, D. A. Carre, J. M. Michalski, L. J. Nikolova, Y. S. Perlis, R. H. Fagerness, J. Lee, M. R. Conley, E. Drabant Lancaster, T. M. Haddad, S. Wolf, A. Smoller, J. W. Hariri, A. R. Bogdan, R. TI COMT Val(158)Met genotype is associated with reward learning: a replication study and meta-analysis SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Anhedonia; COMT; dopamine; meta-analysis; response bias; reward ID METHYLTRANSFERASE VAL(108/158)MET POLYMORPHISM; VENTRAL STRIATUM REACTIVITY; MAJOR DEPRESSIVE DISORDER; GENETIC ASSOCIATION; TREATMENT RESPONSE; PREFRONTAL CORTEX; HUMAN BRAIN; VAL158MET POLYMORPHISM; MIDBRAIN DOPAMINE; NUCLEUS-ACCUMBENS AB Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val(158)Met) has been linked to reward learning, where homozygosity for the Met allele (linked to heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across three separate samples that were combined for analyses (age: 21.80 +/- 3.95; n = 392; 268 female; European-American: n = 208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants ( = 0.20, t = 2.75, P < 0.01; R-2 = 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI -0.11 to -0.03; z = 3.2; P < 0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. C1 [Corral-Frias, N. S.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Corral-Frias, N. S.; Michalski, L. J.; Bogdan, R.] Washington Univ, Dept Psychol, BRAIN Lab, St Louis, MO 63130 USA. [Pizzagalli, D. A.] McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02178 USA. [Pizzagalli, D. A.] McLean Hosp, Neuroimaging Ctr, 115 Mill St, Belmont, MA 02178 USA. [Pizzagalli, D. A.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Carre, J. M.] Nipissing Univ, North Bay, ON, Canada. [Nikolova, Y. S.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Perlis, R. H.; Smoller, J. W.] Massachusetts Gen Hosp, Cambridge, MA USA. [Perlis, R. H.; Smoller, J. W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Perlis, R. H.; Fagerness, J.; Haddad, S.; Smoller, J. W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Lee, M. R.] NIDA, Intramural Res Program, Baltimore, MD USA. [Conley, E. Drabant] 23 & Me, Cardiff, S Glam, Wales. [Lancaster, T. M.] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. [Wolf, A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wolf, A.] Harvard Univ, Sch Med, Boston, MA USA. [Hariri, A. R.] Duke Univ, Neurogenet Lab, Dept Psychol & Neurosci, Durham, NC USA. [Bogdan, R.] Washington Univ, Div Biol & Biomed Sci, St Louis, MO USA. RP Corral-Frias, NS (reprint author), Washington Univ, Campus Box 1125,Psychol Bldg,One Brookings Dr, St Louis, MO 63130 USA. EM corraln@psychiatry.wustl.edu FU NIMH [R01-MH068376, MH101521, T32-MH014677]; Sackler Scholar in Psychobiology; Duke University; National Institutes of Health [NIDA R01-DA033369, NIDA R01-DA031579, NIA R01-AG045231, T32-GM081739]; Klingenstein Third Generation Foundation; Otsuka America Pharmaceutical; Pfizer FX We are thankful to the Duke Neurogenetics Study (DNS) and Center for Depression, Anxiety and Stress Research (CDASR) participants and staff. Studies conducted at Harvard University were supported by NIMH Grant R01-MH068376 (awarded to D.A.P.), and a Sackler Scholar in Psychobiology (awarded to R.B.). D.A.P. was also partially supported by NIMH grant MH101521. The Duke Neurogenetics Study is supported by Duke University and the National Institutes of Health (NIDA R01-DA033369). A.R.H. receives additional support from the National Institutes of Health (NIDA R01-DA031579). N.C.S. was supported by NIMH (T32-MH014677). R.B. was supported by the Klingenstein Third Generation Foundation and receives additional support from the National Institutes of Health (NIA R01-AG045231). L.J.M. was supported by the National Institutes of Health (T32-GM081739). In the past three years, Dr. Pizzagalli has received honoraria/consulting fees from Otsuka America Pharmaceutical and Pfizer for activities unrelated to this project. All other authors report no conflict of interest. NR 91 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 EI 1601-183X J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUN PY 2016 VL 15 IS 5 BP 503 EP 513 DI 10.1111/gbb.12296 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DN6VV UT WOS:000377215500006 PM 27138112 ER PT J AU Kosmicki, JA Churchhouse, CL Rivas, MA Neale, BM AF Kosmicki, Jack A. Churchhouse, Claire L. Rivas, Manuel A. Neale, Benjamin M. TI Discovery of rare variants for complex phenotypes SO HUMAN GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; TRANSMISSION DISEQUILIBRIUM TEST; FAST-LMM-SELECT; MISSING HERITABILITY; GENETIC ASSOCIATION; DIABETES-MELLITUS; GENERAL FRAMEWORK; SEQUENCE VARIANTS; SPATIAL STRUCTURE AB With the rise of sequencing technologies, it is now feasible to assess the role rare variants play in the genetic contribution to complex trait variation. While some of the earlier targeted sequencing studies successfully identified rare variants of large effect, unbiased gene discovery using exome sequencing has experienced limited success for complex traits. Nevertheless, rare variant association studies have demonstrated that rare variants do contribute to phenotypic variability, but sample sizes will likely have to be even larger than those of common variant association studies to be powered for the detection of genes and loci. Large-scale sequencing efforts of tens of thousands of individuals, such as the UK10K Project and aggregation efforts such as the Exome Aggregation Consortium, have made great strides in advancing our knowledge of the landscape of rare variation, but there remain many considerations when studying rare variation in the context of complex traits. We discuss these considerations in this review, presenting a broad range of topics at a high level as an introduction to rare variant analysis in complex traits including the issues of power, study design, sample ascertainment, de novo variation, and statistical testing approaches. Ultimately, as sequencing costs continue to decline, larger sequencing studies will yield clearer insights into the biological consequence of rare mutations and may reveal which genes play a role in the etiology of complex traits. C1 [Kosmicki, Jack A.; Churchhouse, Claire L.; Rivas, Manuel A.; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kosmicki, Jack A.; Churchhouse, Claire L.; Rivas, Manuel A.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kosmicki, Jack A.; Churchhouse, Claire L.; Rivas, Manuel A.; Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, 7 Cambridge Ctr, Cambridge, MA 02142 USA. [Kosmicki, Jack A.; Churchhouse, Claire L.; Neale, Benjamin M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Kosmicki, Jack A.] Harvard Univ, Bioinformat & Integrat Genom, Cambridge, MA 02138 USA. RP Neale, BM (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.; Neale, BM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Neale, BM (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, 7 Cambridge Ctr, Cambridge, MA 02142 USA.; Neale, BM (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. EM bneale@broadinstitute.org NR 98 TC 2 Z9 2 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD JUN PY 2016 VL 135 IS 6 SI SI BP 625 EP 634 DI 10.1007/s00439-016-1679-1 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA DN4EW UT WOS:000377017000005 PM 27221085 ER PT J AU Orrell, C Bienczak, A Cohen, K Bangsberg, D Wood, R Maartens, G Denti, P AF Orrell, Catherine Bienczak, Andrzej Cohen, Karen Bangsberg, David Wood, Robin Maartens, Gary Denti, Paolo TI Effect of mid-dose efavirenz concentrations and CYP2B6 genotype on viral suppression in patients on first-line antiretroviral therapy SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE Virological failure; Therapeutic drug monitoring; Pharmacokinetic; Pharmacogenetic; Efavirenz; CYP2B6 ID GENOME-WIDE ASSOCIATION; TRIALS GROUP PROTOCOLS; HIV-INFECTED PATIENTS; SOUTH-AFRICA; PLASMA; PHARMACOKINETICS; PHARMACOGENETICS; ADULTS AB The therapeutic range for efavirenz plasma concentrations is unclear and some studies found no correlation with viral non-suppression. Efavirenz concentrations are variable, driven in part by polymorphisms in CYP2B6. We hypothesised that efavirenz mid-dosing concentrations, together with CYP2B6 metaboliser genotype, could predict viral non-suppression. Participants starting first-line efavirenz-based antiretroviral therapy were monitored for 48 weeks. HIV-RNA and efavirenz mid-dose interval concentrations were determined at Weeks 16 and 48. CYP2B6 metaboliser genotype status was determined by 516G -> T and 983T -> C polymorphisms. Cox proportional hazards modelling was used to predict viral non-suppression and to determine the most predictive efavirenz mid-dosing concentration threshold. In total, 180 participants were included. Median efavirenz concentrations were 2.3 mg/L (IQR 1.6-4.6 mg/L) and 2.2 mg/L (IQR 1.5-3.9 mg/L) at Weeks 16 and 48, respectively. Moreover, 49 (27.2%), 84 (46.7%) and 39 (21.7%) participants had extensive, intermediate or slow CYP2B6 metaboliser genotype, respectively. Log(2) efavirenz concentrations [adjusted hazard ratio (aHR) = 0.77, 95% CI 0.67-0.89] and baseline CD4 cell count (aHR = 0.994, 95% CI 0.989-0.998), but not CYP2B6 genotype, were predictive of viral non-suppression. For every doubling of efavirenz concentration there was a 23% decrease in the hazard of non-suppression. A threshold of 0.7 mg/L was found to be the efavirenz mid-dosing concentration that was most predictive of non-suppression. Mid-dosing efavirenz concentrations are predictive of viral non-suppression, but the currently recommended lower therapeutic limit (1 mg/L) is higher than our finding. Knowledge of CYP2B6 metaboliser genotype is not required for prediction of virological outcomes. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. C1 [Orrell, Catherine; Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Orrell, Catherine; Wood, Robin] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Bienczak, Andrzej; Cohen, Karen; Maartens, Gary; Denti, Paolo] Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa. [Bangsberg, David] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. RP Orrell, C (reprint author), Univ Cape Town, Fac Hlth Sci, Desmond Tutu HIV Ctr, Werner Beit Bldg North, ZA-7925 Cape Town, South Africa. EM catherine.orrell@hiv-research.org.za RI Maartens, Gary/F-3836-2014; Cohen, Karen/D-4036-2017; OI Maartens, Gary/0000-0003-3080-6606; Orrell, Catherine/0000-0003-1134-7475; Cohen, Karen/0000-0002-1892-4207 FU Discovery Foundation through an Academic Fellowship Award; European & Developing Countries Clinical Trials Partnership (EDCTP) [TA.2011.40200.015] FX This study was partially supported by The Discovery Foundation through an Academic Fellowship Award to CO in 2013 and by The European & Developing Countries Clinical Trials Partnership (EDCTP) through a senior fellowship awarded to CO from 2012 to 2014 [TA.2011.40200.015]. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 EI 1872-7913 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUN PY 2016 VL 47 IS 6 BP 466 EP 472 DI 10.1016/j.ijantimicag.2016.03.017 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA DN7WW UT WOS:000377291900008 PM 27211824 ER PT J AU Braga, A Moraes, V Maesta, I Amim, J de Rezende-Filho, J Elias, K Berkowitz, R AF Braga, Antonio Moraes, Valeria Maesta, Izildinha Amim Junior, Joffre de Rezende-Filho, Jorge Elias, Kevin Berkowitz, Ross TI Changing Trends in the Clinical Presentation and Management of Complete Hydatidiform Mole Among Brazilian Women SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Gestational trophoblastic disease; Hydatidiform mole; Ultrasound; Preeclampsia; Hyperthyroidism; Uterine hemorrhage ID GESTATIONAL TROPHOBLASTIC NEOPLASIA; EARLY-DIAGNOSIS; FOLLOW-UP; PREGNANCY; DISEASE; FEATURES; RISK; NORMALIZATION; EVACUATION; DECADES AB Objective: The aim of the study was to evaluate potential changes in the clinical, diagnostic, and therapeutic parameters of complete hydatidiform mole in the last 25 years in Brazil. Methods: A retrospective cohort study was conducted involving the analysis of 2163 medical records of patients diagnosed with complete hydatidiform mole who received treatment at the Rio de Janeiro Reference Center for Gestational Trophoblastic Disease between January 1988 and December 2012. For the statistical analysis of the natural history of the patients with complete molar pregnancies, time series were evaluated using the Cox-Stuart test and adjusted by linear regression models. Results: A downward linear temporal trend was observed for gestational age of complete hydatidiform mole at diagnosis, which is also reflected in the reduced occurrence of vaginal bleeding, hyperemesis and pre-eclampsia. We also observed an increase in the use of uterine vacuum aspiration to treat molar pregnancy. Although the duration of postmolar follow-up was found to decline, this was not accompanied by any alteration in the time to remission of the disease or its progression to gestational trophoblastic neoplasia. Conclusions: Early diagnosis of complete hydatidiform mole has altered the natural history of molar pregnancy, especially with a reduction in classical clinical symptoms. However, early diagnosis has not resulted in a reduction in the development of gestational trophoblastic neoplasia, a dilemma that still challenges professionals working with gestational trophoblastic disease. C1 [Braga, Antonio; Moraes, Valeria; Amim Junior, Joffre; de Rezende-Filho, Jorge] Univ Fed Fluminense, Antonio Pedro Univ Hosp, Matern Sch,Rio de Janeiro Fed Univ, Rio de Janeiro Trophoblast Dis Ctr,Matern Santa C, Niteroi, RJ, Brazil. [Braga, Antonio; Moraes, Valeria] Univ Fed Fluminense, Profess Masters Program Maternal & Child Hlth, Niteroi, RJ, Brazil. [Braga, Antonio; Amim Junior, Joffre; de Rezende-Filho, Jorge] Univ Fed Rio de Janeiro, Profess Masters Program Perinatal Hlth, Matern Sch, Rio De Janeiro, Brazil. [Maesta, Izildinha] Sao Paulo State Univ, Botucatu Trophoblast Dis Ctr, Botucatu, SP, Brazil. [Elias, Kevin; Berkowitz, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gynecol Oncol,Dept Obstet & Gynecol & Reprod, New England Trophoblast Dis Ctr,Donald P Goldste, 75 Francis St, Boston, MA 02115 USA. RP Braga, A (reprint author), Univ Fed Rio de Janeiro, Maternidade Escola, Gestat Trophoblast Dis Ctr Rio de Janeiro, Rua Laranjeiras 180, Rio De Janeiro, Brazil. EM bragamed@yahoo.com.br FU Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro/Brazil (FAPERJ)-an agency under the Brazilian Ministry of Science and Technology-; Donald P. Goldstein MD Trophoblastic Tumor Registry Endowment; Dyett Family Trophoblastic Disease Research and Registry Endowment FX This study was supported by the Carlos Chagas Filho Foundation for Research Support in the State of Rio de Janeiro/Brazil (FAPERJ)-an agency under the Brazilian Ministry of Science and Technology-, Donald P. Goldstein MD Trophoblastic Tumor Registry Endowment, and the Dyett Family Trophoblastic Disease Research and Registry Endowment. NR 31 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 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JUN PY 2016 VL 26 IS 5 BP 984 EP 990 DI 10.1097/IGC.0000000000000682 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DN5YD UT WOS:000377146700027 PM 26905335 ER PT J AU Kazis, LE Lee, AF Rose, M Liang, MH Li, NC Ren, XHS Sheridan, R Gilroy-Lewis, J Stoddard, F Hinson, M Warden, G Stubbs, K Blakeney, P Meyer, W McCauley, R Herndon, D Palmieri, T Mooney, K Wood, D Pidcock, F Reilly, D Cullen, M Calvert, C Ryan, CM Schneider, JC Soley-Bori, M Tompkins, RG AF Kazis, Lewis E. Lee, Austin F. Rose, Mary Liang, Matthew H. Li, Nien-Chen Ren, Xinhua S. Sheridan, Robert Gilroy-Lewis, Janet Stoddard, Fred Hinson, Michelle Warden, Glenn Stubbs, Kim Blakeney, Patricia Meyer, Walter, III McCauley, Robert Herndon, David Palmieri, Tina Mooney, Kate Wood, David Pidcock, Frank Reilly, Debra Cullen, Marc Calvert, Catherine Ryan, Colleen M. Schneider, Jeffrey C. Soley-Bori, Marina Tompkins, Ronald G. TI Recovery Curves for Pediatric Burn Survivors Advances in Patient-Oriented Outcomes SO JAMA PEDIATRICS LA English DT Article ID ASSOCIATION/SHRINERS-HOSPITALS; HEALTH OUTCOMES; YOUNG-ADULTS; CHILDREN; INJURY; QUESTIONNAIRE; EXCISION; VALIDATION; MORTALITY; PROGRESS AB IMPORTANCE Patient-reported outcomes serving as benchmarks for recovery of pediatric burn survivors are lacking, and new approaches using longitudinal cohorts for monitoring their expected recovery based on statistical models are needed for patient management during the early years following the burn. OBJECTIVE To describe multidimensional patient-reported outcomes among pediatric burn survivors younger than 5 years to establish benchmarks using recovery curve methods. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of pediatric burn survivors younger than 5 years at 12 burn centers. Age-matched nonburned reference groups were studied to define expected results in normal growth and development. The Burn Outcomes Questionnaire for children aged 0 to 5 years (BOQ(0-5)) was administered to parents of children who had burns and were younger than 5 years. Mixed models were used to generate 48-month recovery curves for each of the 10 BOQ(0-5) domains. The study was conducted between January 1999 and December 2008. MAIN OUTCOMES AND MEASURES The 10BOQ(0-5) domains including play, language, fine motor skills, gross motor skills, emotional behavior, family functioning, pain/itching, appearance, satisfaction with care, and worry/concern up to 48 months after burn injury. RESULTS A total of 336 pediatric burn survivors younger than 5 years (mean [SD] age, 2.0 [1.2] years; 58.4% male; 60.2% white, 18.6% black, and 12.0% Hispanic) and 285 age-matched nonburned controls (mean [SD] age, 2.4 [1.3] years; 51.1% male; 67.1% white, 8.9% black, and 15.0% Hispanic) completed the study. Predicted scores improved exponentially over time for 5 of the BOQ(0-5) domains (predicted scores at 1 month vs 24 months: play, 48.6 vs 52.1 [P = .03]; language, 49.2 vs 54.4 [P < .001]; gross motor skills, 48.7 vs 53.0 [P = .002]; pain/itching, 15.8 vs 33.5 [P < .001]; and worry/concern, 31.6 vs 44.9 [P < .001]). Pediatric burn survivors had higher scores in language, emotional behavior, and family functioning domains compared with healthy children in later months. CONCLUSIONS AND RELEVANCE This study demonstrates significant deficits in multiple functional domains across pediatric burn survivors compared with controls. Recovery curves can be used to recognize deviation from the expected course and tailor care to patient needs. C1 [Kazis, Lewis E.; Li, Nien-Chen; Ren, Xinhua S.; Soley-Bori, Marina] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Ctr Assessment Pharmaceut Practices, Talbot Bldg,715 Albany St, Boston, MA 02118 USA. [Lee, Austin F.] Bentley Univ, Dept Math Sci, Waltham, MA USA. [Lee, Austin F.] Univ Int Business & Econ, Sch Insurance & Econ, Beijing, Peoples R China. [Lee, Austin F.; Ryan, Colleen M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rose, Mary; Blakeney, Patricia; Meyer, Walter, III; McCauley, Robert; Herndon, David] Shriners Hosp Children, Galveston, TX 77550 USA. [Liang, Matthew H.] Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Sheridan, Robert; Gilroy-Lewis, Janet; Stoddard, Fred; Hinson, Michelle; Ryan, Colleen M.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Warden, Glenn; Stubbs, Kim] Shriners Hosp Children, Cincinnati, OH USA. [Palmieri, Tina; Mooney, Kate] Shriners Hosp Children, Sacramento, CA USA. [Palmieri, Tina; Reilly, Debra] Nebraska Med Ctr, Omaha, NE USA. [Wood, David] Univ Florida, Coll Med Jacksonville, Dept Pediat, Jacksonville, FL USA. [Pidcock, Frank] Kennedy Krieger Inst, Baltimore, MD USA. [Cullen, Marc] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Calvert, Catherine] North Carolina Jaycee Burn Ctr, Chapel Hill, NC USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Boston, MA USA. [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. RP Kazis, LE (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Talbot Bldg,715 Albany St, Boston, MA 02118 USA. EM lek@bu.edu FU Shriners Hospitals for Children, Tampa, Florida FX This work was supported by grants from Shriners Hospitals for Children, Tampa, Florida. NR 25 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 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JUN PY 2016 VL 170 IS 6 BP 534 EP 542 DI 10.1001/jamapediatrics.2015.4722 PG 9 WC Pediatrics SC Pediatrics GA DN6LC UT WOS:000377185000011 PM 26953515 ER PT J AU Heck, JE Park, AS Contreras, ZA Davidson, TB Hoggatt, KJ Cockburn, M Ritz, B AF Heck, Julia E. Park, Andrew S. Contreras, Zuelma A. Davidson, Tom B. Hoggatt, Katherine J. Cockburn, Myles Ritz, Beate TI Risk of Childhood Cancer by Maternal Birthplace A Test of the Hispanic Paradox SO JAMA PEDIATRICS LA English DT Article ID UNITED-STATES; PREGNANCY OUTCOMES; PRETERM BIRTH; EPIDEMIOLOGY; CALIFORNIA; CHILDREN; MEXICO; US; POPULATIONS; IMMIGRANTS AB IMPORTANCE The Hispanic epidemiologic paradox is the phenomenon that non-US-born Hispanic mothers who immigrate to the United States have better pregnancy outcomes than their US-born counterparts. It is unknown whether this advantage extends to childhood cancer risk. OBJECTIVE To determine whether the risk for childhood cancers among Hispanic children varies by maternal birthplace. DESIGN, SETTING, AND PARTICIPANTS In this population-based case-control study conducted in June 2015, cohort members were identified through California birth records of children born in California from January 1, 1983, to December 31, 2011. Information on cancer diagnoses was obtained from California Cancer Registry records from 1988 to 2012. Cases (n = 13 666) were identified from among children younger than 6 years in the California Cancer Registry and matched to California birth certificates. Control children (n = 15 513 718) included all other children born in California during the same period. Maternal birthplace and ethnic ancestry were identified from the birth certificate. MAIN EXPOSURES Maternal race/ethnicity and birthplace. MAIN OUTCOMES AND MEASURES We used Cox proportional hazards modeling to estimate hazard ratios (HRs) of childhood cancer. RESULTS Included in the study were 4 246 295 children of non-Hispanic white mothers (51.3% male), 2 548 822 children of US-born Hispanic mothers (51.0% male), and 4 397 703 children of non-US-born Hispanic mothers (51.0% male). Compared with children of non-Hispanic white mothers, the children of non-US-born Hispanic mothers had a reduced risk for glioma (HR, 0.50; 95% CI, 0.44-0.58), astrocytoma (HR, 0.43; 95% CI, 0.36-0.51), neuroblastoma (HR, 0.47; 95% CI, 0.40-0.54), and Wilms tumor (HR, 0.70; 95% CI, 0.59-0.82). For these cancer types, the risk estimates for children of US-born Hispanic mothers fell between those of the children of US-born white and non-US-born Hispanic mothers. Children of Mexican-born mothers had a higher risk of yolk sac tumors (HR, 1.46; 95% CI, 0.99-2.17), while children of US-born Hispanic mothers with ancestry from countries other than Mexico had a higher risk for unilateral retinoblastoma (HR, 2.03; 95% CI, 1.33-3.11). CONCLUSIONS AND RELEVANCE For several cancers, we observed differential risk by maternal place of birth. Examining the differences in health behaviors and environment between Hispanic groups may shed light on childhood cancer etiology. C1 [Heck, Julia E.; Park, Andrew S.; Contreras, Zuelma A.; Hoggatt, Katherine J.; Ritz, Beate] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, 650 Charles Young Dr,Box 951772, Los Angeles, CA 90095 USA. [Davidson, Tom B.] Univ Calif Los Angeles, Div Pediat Hematol Oncol, David Geffen Sch Med, 650 Charles Young Dr,Box 951772, Los Angeles, CA 90095 USA. [Hoggatt, Katherine J.] Vet Affairs Greater Los Angeles, Los Angeles, CA USA. [Cockburn, Myles] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Heck, JE (reprint author), Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, 650 Charles Young Dr,Box 951772, Los Angeles, CA 90095 USA. EM jeheck@ucla.edu RI Heck, Julia/B-5230-2009 OI Heck, Julia/0000-0001-8713-8413 FU US National Institutes of Health [R21ES018960, R21ES019986, T32CA009142]; Department of Veterans Affairs Health Services Research and Development/Quality Enhancement Research Initiative Career Development Award [CDA 11-261]; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U58DP003862-01] FX This work was supported by grants R21ES018960 and R21ES019986 from the US National Institutes of Health. Ms Contreras was supported by predoctoral fellowship T32CA009142 from the US National Institutes of Health. Dr Hoggatt was funded through Department of Veterans Affairs Health Services Research and Development/Quality Enhancement Research Initiative Career Development Award CDA 11-261. Dr Cockburn was supported in part by the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute, as well as the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement U58DP003862-01 awarded to the California Department of Public Health. NR 39 TC 3 Z9 3 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JUN PY 2016 VL 170 IS 6 BP 585 EP 592 DI 10.1001/jamapediatrics.2016.0097 PG 8 WC Pediatrics SC Pediatrics GA DN6LC UT WOS:000377185000018 PM 27110958 ER PT J AU Mikailov, A Liang, MG AF Mikailov, Anar Liang, Marilyn G. TI A Widespread Pruritic Rash With Facial Swelling and Black Streaks SO JAMA PEDIATRICS LA English DT Editorial Material ID SPOT POISON-IVY; DERMATITIS C1 [Mikailov, Anar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Med & Dermatol Residency Program, Boston, MA USA. [Liang, Marilyn G.] Boston Childrens Hosp, Dept Dermatol, 300 Longwood Ave, Boston, MA 02115 USA. RP Liang, MG (reprint author), Boston Childrens Hosp, Dept Dermatol, 300 Longwood Ave, Boston, MA 02115 USA. EM marilyn.liang@childrens.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JUN PY 2016 VL 170 IS 6 BP 617 EP 618 PG 2 WC Pediatrics SC Pediatrics GA DN6LC UT WOS:000377185000022 PM 27273572 ER PT J AU Smith, NB Mota, N Tsai, J Monteith, L Harpaz-Rotem, I Southwick, SM Pietrzak, RH AF Smith, Noelle B. Mota, Natalie Tsai, Jack Monteith, Lindsey Harpaz-Rotem, Ilan Southwick, Steven M. Pietrzak, Robert H. TI Nature and determinants of suicidal ideation among US veterans: Results from the national health and resilience in veterans study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Suicidal ideation; Longitudinal time points; Nationally representative veteran sample; Protective and risk factors ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; SOCIAL SUPPORT; PROTECTIVE FACTORS; DANISH SOLDIERS; FOLLOW-UP; RISK; DEPRESSION; ANXIETY; ADULTS AB Background: Suicidal thoughts and behaviors among U.S. military veterans are a major public health concern. To date, however, scarce data are available regarding the nature and correlates of suicidal ideation (SI) among U.S. veterans. This study evaluated the prevalence and correlates of suicidal ideation in a contemporary, nationally representative, 2-year prospective cohort study. Method: Data were analysed from a total of 2157 U.S. veterans who participated in the National Health and Resilience Veterans Study (NHRVS; Wave 1 conducted in 2011; Wave 2 in 2013). Veterans completed measures assessing SI, sociodemographic characteristics, and potential risk and protective correlates. Results: The majority of veterans (86.3%) denied SI at either time point, 5.0% had SI onset (no SI at Wave 1, SI at Wave 2), 4.9% chronic SI (SI at Waves 1 and 2), and 3.8% had remitted SI (SI at Wave 1, no SI Wave 2). Greater Wave 1 psychiatric distress was associated with increased likelihood of chronic SI (relative risk ratio [RRR]=3.72), remitted SI (RRR=3.38), SI onset (RRR=1.48); greater Wave 1 physical health difficulties were additionally associated with chronic SI (RRR=1.64) and SI onset (RRR=1.47); and Wave 1 substance abuse history was associated with chronic SI (RRR 1.57). Greater protective psychosocial characteristics (e.g., resilience, gratitude) at Wave 1 were negatively related to SI onset (RRR=0.57); and greater social connectedness at Wave 1, specifically perceived social support and secure attachment style, was negatively associated with SI onset (RRR=0.75) and remitted SI (RRR=0.44), respectively. Limitations: Suicidal ideation was assessed using a past two-week timeframe, and the limited duration of follow-up precludes conclusions regarding more dynamic changes in SI over time. Conclusions: These results indicate that a significant minority (13.7%) of U.S. veterans has chronic, onset, or remitted SI. Prevention and treatment efforts designed to mitigate psychiatric and physical health difficulties, and bolster social connectedness and protective psychosocial characteristics may help mitigate risk for SI. Published by Elsevier B.V. C1 [Smith, Noelle B.; Mota, Natalie; Harpaz-Rotem, Ilan; Southwick, Steven M.; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr PTSD, West Haven, CT USA. [Smith, Noelle B.; Mota, Natalie; Tsai, Jack; Harpaz-Rotem, Ilan; Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Tsai, Jack] VA Connecticut Healthcare Syst, Res Educ & Clin Ctr, New England Mental Illness, West Haven, CT USA. [Monteith, Lindsey] Rocky Mt MIRECC, Denver VA Med Ctr, Denver, CO USA. [Monteith, Lindsey] Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO USA. [Harpaz-Rotem, Ilan] VA Northeast Program Evaluat Ctr, West Haven, CT USA. RP Smith, NB (reprint author), Yale Univ, Natl Ctr Posttraumat Stress Disorder, Dept Psychiat, VA Connecticut Healthcare Syst,Sch Med, 950 Campbell Ave 116B, West Haven, CT 06516 USA. EM Noelle.smith2@va.gov FU U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment Department of Veterans Affairs FX The National Health and Resilience in Veterans Study was supported by the U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. Preparation of this manuscript was supported in part by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment Department of Veterans Affairs. Dr. Pietrzak is a scientific consultant to Cogstate and Mitsubishi Tanabe Pharma America, Inc. for work that is unrelated to this manuscript. The other authors have no disclosures. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. NR 59 TC 0 Z9 0 U1 8 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN PY 2016 VL 197 BP 66 EP 73 DI 10.1016/j.jad.2016.02.069 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DJ7EN UT WOS:000374374800010 PM 26970267 ER PT J AU Walcott, BP Reinshagen, C Stapleton, CJ Choudhri, O Rayz, V Saloner, D Lawton, MT AF Walcott, Brian P. Reinshagen, Clemens Stapleton, Christopher J. Choudhri, Omar Rayz, Vitaliy Saloner, David Lawton, Michael T. TI Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE Aneurysm; stroke; computational fluid dynamics; modeling; stenting; bypass ID COMPUTATIONAL FLUID-DYNAMICS; PIPELINE EMBOLIZATION DEVICE; ANTERIOR CHOROIDAL ARTERY; INTRACRANIAL ANEURYSMS; ENDOVASCULAR TREATMENT; DIVERSION TREATMENT; HEMODYNAMICS; SIMULATION; EXPERIENCE; PATENCY AB Cerebral aneurysms are weakened blood vessel dilatations that can result in spontaneous, devastating hemorrhage events. Aneurysm treatment aims to reduce hemorrhage events, and strategies for complex aneurysms often require surgical bypass or endovascular stenting for blood flow diversion. Interventions that divert blood flow from their normal circulation patterns have the potential to result in unintentional ischemia. Recent developments in computational modeling and in vivo assessment of hemodynamics for cerebral aneurysm treatment have entered into clinical practice. Herein, we review how these techniques are currently utilized to improve risk stratification and treatment planning. C1 [Walcott, Brian P.; Choudhri, Omar; Lawton, Michael T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Reinshagen, Clemens] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Reinshagen, Clemens; Stapleton, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Stapleton, Christopher J.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Rayz, Vitaliy] Univ Wisconsin, Coll Engn & Appl Sci, Milwaukee, WI 53201 USA. [Rayz, Vitaliy] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. [Saloner, David] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Walcott, BP (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,M779, San Francisco, CA 94143 USA. EM brian.walcott@gmail.com FU National Institutes of Health [U54 NS065705, RO1 HL114118, RO1 HL115267] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received grant funding from the National Institutes of Health to MTL (grant # U54 NS065705), to DS (grant # RO1 HL114118), and to VR (grant # RO1 HL115267). NR 37 TC 0 Z9 0 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2016 VL 36 IS 6 BP 998 EP 1003 DI 10.1177/0271678X16641125 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA DN0UX UT WOS:000376782700002 PM 27009946 ER PT J AU O'Farrell, TJ Schumm, JA Dunlap, LJ Murphy, MM Muchowski, P AF O'Farrell, Timothy J. Schumm, Jeremiah A. Dunlap, Laura J. Murphy, Marie M. Muchowski, Patrice TI A Randomized Clinical Trial of Group Versus Standard Behavioral Couples Therapy Plus Individually Based Treatment for Patients With Alcohol Dependence SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE alcoholism; couples therapy; group therapy; treatment outcomes ID RELAPSE PREVENTION; USE DISORDERS; WOMEN; DISSEMINATION; EFFICACY AB Objective: Multiple studies show that behavioral couples therapy (BCT) is more efficacious than individually based therapy (IBT) for substance use and relationship outcomes among patients with alcohol use disorder. To facilitate dissemination, a multicouple, rolling admission Group BCT (G-BCT) format has been suggested as an alternative to the 1 couple at a time, conjoint Standard BCT (S-BCT) format. This randomized study compared outcomes of G-BCT versus S-BCT over a 1-year follow-up. The authors predicted that G-BCT, as compared to S-BCT, would have equivalent (i.e., noninferior) improvements on substance and relationship outcomes. Method: Participants were patients (N = 101) with alcohol dependence and their heterosexual relationship partners without substance use disorder. Participants were mostly White, in their 40s, and 30% of patients were women. Patients were randomized to either G-BCT plus 12-step-oriented IBT or S-BCT plus IBT. Primary outcomes included Timeline Followback Interview percentage days abstinent and Inventory of Drug Use Consequences measure of substance-related problems. Secondary outcome was Dyadic Adjustment Scale. Outcome data were collected at baseline, posttreatment, and quarterly for 1-year follow-up. Results: Results overall found no support for the predicted statistical equivalency of G-BCT and S-BCT. Rather than the predicted equivalent outcomes, substance and relationship outcomes were significantly worse for G-BCT than S-BCT in the last 6-9 months of the 12-month follow-up period, because G-BCT deteriorated and S-BCT maintained gains during follow-up. Conclusion: This was the first study of the newer rolling admission group format for BCT. It proved to have worse not equivalent outcomes compared to standard conjoint BCT. C1 [O'Farrell, Timothy J.; Murphy, Marie M.] VA Boston Healthcare Syst, Families & Addict Program, Brockton, MA USA. [O'Farrell, Timothy J.; Murphy, Marie M.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Schumm, Jeremiah A.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Schumm, Jeremiah A.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45221 USA. [Dunlap, Laura J.] RTI Int, Res Triangle Pk, NC USA. [Muchowski, Patrice] AdCare Hosp Worcester Inc, Worcester, MA USA. RP O'Farrell, TJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, VAMC 116B1,940 Belmont St, Brockton, MA 02301 USA. EM timothy_ofarrell@hms.harvard.edu FU National Institute on Alcohol Abuse and Alcoholism [R01AA017865]; Department of Veterans Affairs FX This research was supported by Grant R01AA017865 awarded to Timothy J. O'Farrell by the National Institute on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs. We gratefully acknowledge assistance from Fay Larkin, Anne Gribauskas, and Leslie Reid. NR 32 TC 0 Z9 0 U1 6 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2016 VL 84 IS 6 BP 497 EP 510 DI 10.1037/ccp0000089 PG 14 WC Psychology, Clinical SC Psychology GA DN2WN UT WOS:000376923800004 PM 26963601 ER PT J AU Hopkins, LB Medina, JL Baird, SO Rosenfield, D Powers, MB Smits, JAJ AF Hopkins, Lindsey B. Medina, Johnna L. Baird, Scarlett O. Rosenfield, David Powers, Mark B. Smits, Jasper A. J. TI Heated Hatha Yoga to Target Cortisol Reactivity to Stress and Affective Eating in Women at Risk for Obesity-Related Illnesses: A Randomized Controlled Trial SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE yoga; eating; stress; cortisol; obesity ID SALIVARY CORTISOL; PERCEIVED STRESS; BEHAVIOR; FOOD; QUESTIONNAIRE; DISORDERS; RESPONSES; WEIGHT; BODY; TOOL AB Objective: Cortisol reactivity to stress is associated with affective eating, an important behavioral risk factor for obesity and related metabolic diseases. Yoga practice is related to decreases in stress and cortisol levels, thus emerging as a potential targeted complementary intervention for affective eating. This randomized controlled trial examined the efficacy of a heated, hatha yoga intervention for reducing cortisol reactivity to stress and affective eating. Method: Females (N = 52; ages 25-46 years; 75% White) at risk for obesity and related illnesses were randomly assigned to 8 weeks of Bikram Yoga practice or to waitlist control. Cortisol reactivity to a laboratory stress induction were measured at Weeks 0 (pretreatment) and 9 (posttreatment). Self-reported binge eating frequency and coping motives for eating were assessed at Weeks 0, 3, 6, and 9. Results: Among participants with elevated cortisol reactivity at pretreatment ("high reactors"), those randomized to the yoga condition evidenced greater pre- to posttreatment reductions in cortisol reactivity (p = .042, d = .85), but there were not significant condition differences for the "low reactors" (p = .178, d = .53). Yoga participants reported greater decreases in binge eating frequency (p = .040, d = .62) and eating to cope with negative affect (p = .038, d = .54). Conclusions: This study provides preliminary support for the efficacy of heated hatha yoga for treating physiological stress reactivity and affective eating among women at risk for obesity-related illnesses. C1 [Hopkins, Lindsey B.; Medina, Johnna L.; Baird, Scarlett O.; Rosenfield, David; Powers, Mark B.; Smits, Jasper A. J.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Hopkins, Lindsey B.] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA 94121 USA. [Medina, Johnna L.; Baird, Scarlett O.; Powers, Mark B.; Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Mental Hlth Res Inst, Austin, TX 78712 USA. RP Hopkins, LB (reprint author), San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA 94121 USA. EM lbhopkins@gmail.com OI Hopkins, Lindsey/0000-0002-0577-2961 FU National Institute on Drug Addiction [R01 DA027533, K01 DA035930, F31 DA036919]; Pure Action, Inc., Austin, Texas, a 501c3 nonprofit organization FX Research reported in this article was supported in part by Grants R01 DA027533, K01 DA035930, and F31 DA036919 awarded by the National Institute on Drug Addiction. Cortisol assays for this study were funded by a grant from Pure Action, Inc., Austin, Texas, a 501c3 nonprofit organization. Jasper A. J. Smits receives royalties from Oxford University Press for books on exercise as a treatment for mood and anxiety disorders. This article is based on the first author's doctoral dissertation. Trial Registration: ClinicalTrials.gov, NCT01652807, https:/clinicaltrials.govct2showNCT01652807. NR 31 TC 0 Z9 0 U1 7 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2016 VL 84 IS 6 BP 558 EP 564 DI 10.1037/ccp0000091 PG 7 WC Psychology, Clinical SC Psychology GA DN2WN UT WOS:000376923800009 PM 26963599 ER PT J AU Zhao, G Lee, KC Kwon, G Frederick, PD Onega, TL Piepkorn, MW Knezevich, S Barnhill, RL Elder, DE Elmore, JG AF Zhao, Ge Lee, Kachiu C. Kwon, Gina Frederick, Paul D. Onega, Tracy L. Piepkorn, Michael W. Knezevich, Stevan Barnhill, Raymond L. Elder, David E. Elmore, Joann G. TI The self-reported use of immunostains and cytogenetic testing in the diagnosis of melanoma by practicing US pathologists of 10 selected states SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE CGH; dermatopathology; FISH ID MELANOCYTIC NEOPLASMS; TUMORS; FISH AB Background: The diagnosis of melanoma can be challenging, especially in lesions for which the histopathologic criteria bridge two or more taxonomic categories. Newer genomic analytical methods of fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have been introduced as ancillary techniques to differentiate benign and malignant melanocytic proliferations. Methods: We evaluated how pathologists perceive and are incorporating these new cytogenetic testing technologies into their practices. We conducted a study of 207 U.S. pathologists who interpret melanocytic lesions in clinical practice in 10 SEER states. Pathologists were surveyed regarding perceptions and utilization of FISH and/or CGH in their clinical practices. Results: Results showed that 38% of pathologists use FISH and/or CGH in interpreting melanocytic lesions. Pathologists reporting FISH and/or CGH use were significantly younger (p<0.05), were fellowship trained or board certified in dermatopathology (p<0.001) and were affiliated with an academic institute (p<0.001). Pathologists reporting that their colleagues consider them an expert in the assessment of melanocytic lesions were more likely to employ FISH and/or CGH in their practices than non-experts. Conclusions: Early users of cytogenetic testing technologies in cutaneous pathology are more likely to be younger, affiliated with an academic institution and fellowship trained or board certified in dermatopathology. C1 [Zhao, Ge; Kwon, Gina; Piepkorn, Michael W.] Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA. [Lee, Kachiu C.] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Frederick, Paul D.; Elmore, Joann G.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Onega, Tracy L.] Norris Cotton Canc Ctr, Dept Biomed Data Sci, Lebanon, NH USA. [Onega, Tracy L.] Norris Cotton Canc Ctr, Dept Epidemiol, Lebanon, NH USA. [Onega, Tracy L.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Piepkorn, Michael W.] Dermatopathol Northwest, Bellevue, WA USA. [Knezevich, Stevan] Pathol Associates Inc, Clovis, CA USA. [Barnhill, Raymond L.] Univ Paris 05, Fac Med, Dept Pathol, Paris, France. [Barnhill, Raymond L.] Inst Curie, Paris, France. [Elder, David E.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Elmore, JG (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Dept Med, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. EM jelmore@u.washington.edu OI Frederick, Paul/0000-0002-7936-5488 FU National Cancer Institute; National Institutes of Health [R01 CA 151306, K05 CA 104699, 5T32AR056969] FX Research reported in this publication was supported by the National Cancer Institute and National Institutes of Health under award numbers R01 CA 151306, K05 CA 104699 and 5T32AR056969. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUN PY 2016 VL 43 IS 6 BP 492 EP 497 DI 10.1111/cup.12705 PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA DN7QS UT WOS:000377272900002 PM 26968847 ER PT J AU Glass, K Glass, CR Lynch, RJ AF Glass, Kimberly Glass, Chris R. Lynch, R. Jason TI Student Engagement and Affordances for Interaction With Diverse Peers: A Network Analysis SO JOURNAL OF DIVERSITY IN HIGHER EDUCATION LA English DT Article DE networks; student engagement; cross-racial interaction; campus diversity ID CROSS-RACIAL INTERACTION; COLLEGE-STUDENTS; COMPLEX NETWORKS; HIGHER-EDUCATION; INTERRACIAL FRIENDSHIP; INTERNATIONAL STUDENTS; STRUCTURAL DIVERSITY; SOCIAL RELATIONSHIPS; CAMPUS DIVERSITY; IMPACT AB This study utilized a network model in order to explore the relationship between patterns of student engagement and affordances for interaction with diverse peers for 12,852 students at 7 universities. The institutions are similar in type and size, with relatively moderate levels of structural racial diversity, and a range of overall cross-cultural peer engagement. The findings indicate that students in the "core" (many connections) share 1 dominant perception of affordances for interaction with many other students that also have a high number of connections. Similarly, students in the "fringe" (few connections) may not share their perception of the affordances for interaction with many other students, but when they do, it is most likely with other students that have only have a few connections in our network. Moreover, our network exhibited a high-degree of assortativity, meaning that there is little mixing between the "core" and "fringe" groups. Importantly, the institutional network structure varied by an institution's overall level of cross-cultural peer engagement. White students reported more cocurricular engagement but less openness to cross-cultural interaction than their peers from all other racial groups; White students reported significantly greater campus support for diversity and less openness to cross-cultural interaction than their peers from all other racial groups. Implications for intergroup dialogue, collaborative programming, and the use of assortativity for institutional assessment are discussed. C1 [Glass, Kimberly] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Glass, Chris R.; Lynch, R. Jason] Old Dominion Univ, Darden Coll Educ, Dept Educ Fdn & Leadership, Norfolk, VA 23529 USA. [Glass, Kimberly] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Glass, Kimberly] Harvard Univ, Sch Med, Boston, MA USA. RP Glass, CR (reprint author), 5115 Hampton Blvd,166-1 Educ Bldg, Norfolk, VA 23529 USA. EM crglass@odu.edu NR 64 TC 0 Z9 0 U1 9 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1938-8926 EI 1938-8934 J9 J DIVERS HIGH EDUC JI J. Divers. High. Educ. PD JUN PY 2016 VL 9 IS 2 BP 170 EP 187 DI 10.1037/a0039726 PG 18 WC Education & Educational Research; Psychology, Educational; Psychology, Social SC Education & Educational Research; Psychology GA DN2TN UT WOS:000376916000006 ER PT J AU Singh, P Arora, S Singh, A Strand, TA Makharia, GK AF Singh, Prashant Arora, Shubhangi Singh, Alka Strand, Tor A. Makharia, Govind K. TI Prevalence of celiac disease in Asia: A systematic review and meta-analysis SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE anti-endomysial; China; gluten; India; screening; tissue transglutaminase ID TISSUE-TRANSGLUTAMINASE ANTIBODY; HEALTHY BLOOD-DONORS; SCHOOL-CHILDREN; TURKISH CHILDREN; SAUDI-ARABIA; NORTH-INDIA; POPULATION; DIAGNOSIS; EPIDEMIOLOGY; SEROPREVALENCE AB Background and AimCeliac disease (CD) is emerging in Asia. While a few population-based studies from Asia have reported a prevalence of CD from 0.1% to 1.3%, the exact prevalence of CD in Asia is not known. We conducted a systematic review and meta-analysis to estimate the prevalence of CD in Asia. MethodsOn search of literature, we found 1213 articles, of which 18 articles were included. Diagnosis of CD was based on European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. ResultsPooled sero-prevalence of CD in Asia was 1.6% in 47873 individuals based on positive anti-tissue transglutaminase and/or anti-endomysial antibodies. Pooled prevalence of biopsy proven CD in Asia was 0.5% in 43955 individuals. The prevalence of CD among women was higher than in men (0.5% vs 0.4%, P=0.04). The pooled prevalence of CD was 0.3% in Iran, 0.5% in Turkey, 0.6% in India, and 0.7% in Israel. The pooled prevalence of CD was significantly higher in Israel and India as compared with that in Iran. ConclusionsCeliac disease is not uncommon in Asia, and the sero-prevalence and prevalence of CD in Asia are 1.6% and 0.5%, respectively. The prevalence of CD varies with gender and geographic location. There is a need for population-based prevalence studies in many Asian countries to properly estimate the burden of CD in Asia. C1 [Singh, Prashant] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Arora, Shubhangi] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Singh, Alka; Makharia, Govind K.] All India Inst Med Sci, Dept Gastroenterol & Human Nutr, New Delhi 110029, India. [Strand, Tor A.] Innlandet Hosp Trust, Med Serv Div, Lillehammer, Norway. RP Makharia, GK (reprint author), All India Inst Med Sci, Dept Gastroenterol & Human Nutr, New Delhi 110029, India. EM govindmakharia@gmail.com OI Strand, Tor/0000-0002-4038-151X NR 57 TC 3 Z9 3 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUN PY 2016 VL 31 IS 6 BP 1095 EP 1101 DI 10.1111/jgh.13270 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DN6QG UT WOS:000377200100009 PM 26678020 ER PT J AU Raal, FJ Giugliano, RP Sabatine, MS Koren, MJ Blom, D Seidah, NG Honarpour, N Lira, A Xue, A Chiruvolu, P Jackson, S Di, M Peach, M Somaratne, R Wasserman, SM Scott, R Stein, EA AF Raal, Frederick J. Giugliano, Robert P. Sabatine, Marc S. Koren, Michael J. Blom, Dirk Seidah, Nabil G. Honarpour, Narimon Lira, Armando Xue, Allen Chiruvolu, Padmaja Jackson, Simon Di, Mei Peach, Matthew Somaratne, Ransi Wasserman, Scott M. Scott, Rob Stein, Evan A. TI PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipoprotein (a); low density lipoprotein cholesterol; low density lipoprotein receptor; proprotein convertase subtilisin; kexin type 9 ID SUBTILISIN/KEXIN TYPE 9; DENSITY-LIPOPROTEIN-CHOLESTEROL; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; MONOCLONAL-ANTIBODY; AMG 145; DOUBLE-BLIND; RANDOMIZED-TRIAL; CARDIOVASCULAR RISK; NONHUMAN-PRIMATES; EFFICACY AB Lipoprotein (a) [Lp(a)] is independently associated with CVD risk. Evolocumab, a monoclonal antibody (mAb) to proprotein convertase subtilisin/kexin type 9 (PCSK9), decreases Lp(a). The potential mechanisms were assessed. A pooled analysis of Lp(a) and LDL cholesterol (LDL-C) in 3,278 patients from 10 clinical trials (eight phase 2/3; two extensions) was conducted. Within each parent study, biweekly and monthly doses of evolocumab statistically significantly reduced Lp(a) at week 12 versus control (P < 0.001 within each study); pooled median (quartile 1, quartile 3) percent reductions were 24.7% (40.0, 3.6) and 21.7% (39.9, 4.2), respectively. Reductions were maintained through week 52 of the open-label extension, and correlated with LDL-C reductions [with and without correction for Lp(a)-cholesterol] at both time points (P < 0.0001). The effect of LDL and LDL receptor (LDLR) availability on Lp(a) cell-association was measured in HepG2 cells: cell-associated LDL fluorescence was reversed by unlabeled LDL and Lp(a). Lp(a) cell-association was reduced by coincubation with LDL and PCSK9 and reversed by adding PCSK9 mAb. These studies support that reductions in Lp(a) with PCSK9 inhibition are partly due to increased LDLR-mediated uptake. In most situations, Lp(a) appears to compete poorly with LDL for LDLR binding and internalization, but when LDLR expression is increased with evolocumab, particularly in the setting of low circulating LDL, Lp(a) is reduced. C1 [Raal, Frederick J.] Univ Witwatersrand, Fac Hlth Sci, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa. [Giugliano, Robert P.; Sabatine, Marc S.] Brigham & Womens Hosp, Cardiovasc Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Koren, Michael J.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. [Blom, Dirk] Univ Cape Town, Div Lipidol, ZA-7925 Cape Town, South Africa. [Seidah, Nabil G.] Univ Montreal, IRCM, Montreal, PQ, Canada. [Honarpour, Narimon; Lira, Armando; Xue, Allen; Chiruvolu, Padmaja; Somaratne, Ransi; Wasserman, Scott M.; Scott, Rob] Amgen Inc, Thousand Oaks, CA 91320 USA. [Jackson, Simon; Di, Mei; Peach, Matthew] Amgen Inc, San Francisco, CA USA. [Stein, Evan A.] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA. RP Stein, EA (reprint author), Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA. EM ESteinMRL@aol.com FU Amgen; Sanofi; Leducq Foundation; Canadian Research Chair; Daiichi-Sankyo; Merck; AstraZeneca; AstraZeneca/Bristol-Myers Squibb Alliance; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Eisai; Genzyme; GlaxoSmithKline; Sanofi-Aventis; Takeda; Abbott Laboratories; Accumetrics; Critical Diagnostics; Nonsphere; Roche Diagnostics; Regeneron; Roche; Pfizer FX This study was funded by Amgen. The authors report the following potential conflicts of interest: F.J.R.: Grants/research support: Amgen, Sanofi; Speakers Bureau: AstraZeneca, Pfizer, Merck, Amgen; Honoraria: AstraZeneca, Pfizer, Merck, Amgen, Sanofi; Consultant/Advisory Board: AstraZeneca, Pfizer, Merck; N.G.S.: Grants: Leducq Foundation grant, Canadian Research Chair. R.P.G.: Grants/research Support: Amgen, Daiichi-Sankyo, Merck; Honoraria: Daiichi-Sankyo, Merck; Consultant/Advisory Board: Amgen, Daiichi-Sankyo, Janssen, Lexicon, Merck, Sanofi, Beckman-Coulter. M.S.S.: Grant/research support: Amgen, AstraZeneca, AstraZeneca/Bristol-Myers Squibb Alliance, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Daiichi-Sankyo, Eisai, Genzyme, GlaxoSmithKline, Merck, Sanofi-Aventis, Takeda, Abbott Laboratories, Accumetrics, Critical Diagnostics, Nonsphere, Roche Diagnostics; Consultant/Advisory Board: Aegerion, Amgen, Diasorin, GlaxoSmithKline, Merck, Pfizer, Sanofi-Aventis, AstraZeneca, Vertex. M.J.K.: Grants/research support: Amgen, Regeneron, Sanofi, Roche, Pfizer. D.B.: Honoraria: Amgen, Sanofi-Aventis, MSD, PharmaDynamics, AstraZeneca, Aegerion; Consultant/Advisory Board: Amgen, MSD, Sanofi-Aventis, Aegerion, Gemphire. A.L., N.H., A.X., P.C., S.J., M.D., M.P., R. So., S.M.W., and R. Sc.: Employees of Amgen Inc. E.A.S.: Consultant/Advisory Board: Amgen, Adnexus Therapeutics, Genentech, Regeneron, Sanofi, ISIS, Genzyme. NR 44 TC 12 Z9 12 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 2016 VL 57 IS 6 BP 1086 EP 1096 DI 10.1194/jlr.P065334 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DN3PO UT WOS:000376975100015 PM 27102113 ER PT J AU Teodorescu, DL Nagle, D Hickman, M King, DR AF Teodorescu, Debbie Lin Nagle, Dennis Hickman, Madeline King, David R. TI An Ultraportable Device Platform for Aseptic Surgery in Field Settings SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article; Proceedings Paper CT University-of-Minnesota's Design of Medical Devices (DMD) Conference CY APR 11-14, 2016 CL Minneapolis, MN SP Univ Minnesota C1 [Teodorescu, Debbie Lin; Nagle, Dennis; Hickman, Madeline] MIT, D Lab, Cambridge, MA 02139 USA. [Teodorescu, Debbie Lin; King, David R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [King, David R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Teodorescu, DL (reprint author), MIT, D Lab, Cambridge, MA 02139 USA.; Teodorescu, DL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 EI 1932-619X J9 J MED DEVICES JI J. Med. Devices PD JUN PY 2016 VL 10 IS 2 AR 020924 DI 10.1115/1.4033224 PG 2 WC Engineering, Biomedical SC Engineering GA DN2ZG UT WOS:000376931100025 ER PT J AU Dodgshun, AJ SantaCruz, N Hwang, J Ramkissoon, SH Malkin, H Bergthold, G Manley, P Chi, S MacGregor, D Goumnerova, L Sullivan, M Ligon, K Beroukhim, R Herrington, B Kieran, MW Hansford, JR Bandopadhayay, P AF Dodgshun, Andrew J. SantaCruz, Nadine Hwang, Jaeho Ramkissoon, Shakti H. Malkin, Hayley Bergthold, Guillaume Manley, Peter Chi, Susan MacGregor, Duncan Goumnerova, Liliana Sullivan, Michael Ligon, Keith Beroukhim, Rameen Herrington, Betty Kieran, Mark W. Hansford, Jordan R. Bandopadhayay, Pratiti TI Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Pediatric glioma; Oligodendroglioma; Glioneuronal; Leptomeningeal neoplasms; Protooncogene proteins B-raf ID LOW-GRADE GLIOMAS; LEPTOMENINGEAL OLIGODENDROGLIOMA; PILOCYTIC ASTROCYTOMAS; 1P DELETION; RECURRENT; CHILDREN; ENTITY; GENE; DUPLICATION; ACTIVATION AB Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De-identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana-Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease. C1 [Dodgshun, Andrew J.; Sullivan, Michael; Hansford, Jordan R.] Royal Childrens Hosp, Childrens Canc Ctr, 50 Flemington Rd, Melbourne, Vic 3052, Australia. [Dodgshun, Andrew J.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia. [SantaCruz, Nadine; Hwang, Jaeho; Malkin, Hayley; Bergthold, Guillaume; Manley, Peter; Chi, Susan; Goumnerova, Liliana; Kieran, Mark W.; Bandopadhayay, Pratiti] Dana Farber Boston Childrens Canc & Blood Disorde, 450 Longwood Ave, Boston, MA 02115 USA. [SantaCruz, Nadine; Hwang, Jaeho; Malkin, Hayley; Bergthold, Guillaume; Manley, Peter; Chi, Susan; Goumnerova, Liliana; Beroukhim, Rameen; Kieran, Mark W.; Bandopadhayay, Pratiti] Harvard Univ, Sch Med, Boston, MA 02115 USA. [MacGregor, Duncan] Royal Childrens Hosp, Dept Pathol, Melbourne, Vic 3052, Australia. [Sullivan, Michael; Hansford, Jordan R.] Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia. [Ramkissoon, Shakti H.; Ligon, Keith; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith; Beroukhim, Rameen; Bandopadhayay, Pratiti] Broad Inst MIT & Harvard, Cambridge, MA USA. [Herrington, Betty] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. [Beroukhim, Rameen; Bandopadhayay, Pratiti] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Ligon, Keith] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Ligon, Keith] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Goumnerova, Liliana] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Goumnerova, Liliana] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Ligon, Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Dodgshun, AJ (reprint author), Royal Childrens Hosp, Childrens Canc Ctr, 50 Flemington Rd, Melbourne, Vic 3052, Australia.; Dodgshun, AJ (reprint author), Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia.; Bandopadhayay, P (reprint author), Dana Farber Boston Childrens Canc & Blood Disorde, 450 Longwood Ave, Boston, MA 02115 USA.; Bandopadhayay, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Bandopadhayay, P (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.; Bandopadhayay, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM ajdodgshun@gmail.com; Pratiti_Bandopadhayay@dfci.harvard.edu FU A Kids' Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation; Stop and Shop Pediatric Brain Tumor Program; St Baldrick's Foundation; Team Jack Foundation; Andrysiak Fund for LGG; Jared Branfman Sunflowers For Life Fund For Pediatric Brain And Spinal Cancer Research; Sontag Foundation; Nuovo-Soldati Foundation; Philippe Foundation; Pediatric Brain Tumor Foundation; Royal Children's Hospital Foundation; Robert Connor Dawes Foundation; Murray Jackson Clinical Fellowship, Genesis Oncology Trust, New Zealand FX We acknowledge the following funding sources: A Kids' Brain Tumor Cure Foundation Pediatric Low-Grade Astrocytoma Foundation (PB, KLL, RB, MWK, LG), Stop and Shop Pediatric Brain Tumor Program (NSC, PB, MWK), St Baldrick's Foundation (PB), Team Jack Foundation (PB, MWK, RB, LG), Andrysiak Fund for LGG (MWK), Jared Branfman Sunflowers For Life Fund For Pediatric Brain And Spinal Cancer Research (PB, RB), Sontag Foundation (KLL, RB), Nuovo-Soldati Foundation (GB), Philippe Foundation (GB), Pediatric Brain Tumor Foundation (RB, PB), Royal Children's Hospital Foundation (JH), Robert Connor Dawes Foundation (JH), Dr. Dodgshun is the recipient of the Murray Jackson Clinical Fellowship, Genesis Oncology Trust, New Zealand. NR 31 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 2016 VL 128 IS 2 BP 293 EP 302 DI 10.1007/s11060-016-2109-x PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DN2FM UT WOS:000376879500013 PM 26994902 ER PT J AU Meehan, TM Harvey, HB Duszak, R Meyers, PM McGinty, G Nicola, GN Hirsch, JA AF Meehan, Timothy M. Harvey, H. Benjamin Duszak, Richard, Jr. Meyers, Philip M. McGinty, Geraldine Nicola, Gregory N. Hirsch, Joshua A. TI Accountable Care Organizations: what they mean for the country and for neurointerventionalists SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review AB The Affordable Care Act is celebrating its fifth anniversary and remains one of the most significant attempts to reform healthcare in US history. Prior to the federal legislation, Accountable Care Organizations had largely been part of an academic discussion about how to control rising healthcare costs, but have since become a fixture in our national healthcare landscape. A fundamental shift is underway in the relationship between healthcare delivery and payment models. Some elements of Accountable Care Organizations may remain unfamiliar to most healthcare providers, including neurointerventional specialists. In this paper we review the fundamental concepts behind and the current forms of Accountable Care Organizations, and discuss the challenges and opportunities they present for neurointerventionalists. C1 [Meehan, Timothy M.; Harvey, H. Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Harvey L Neiman Hlth Policy Inst, Reston, VA USA. [Duszak, Richard, Jr.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Radiol, Neurol Inst New York, New York, NY 10032 USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Neurol Surg, Neurol Inst New York, New York, NY 10032 USA. [McGinty, Geraldine] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [Nicola, Gregory N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NeuroEndovasc Program, Boston, MA 02114 USA. RP Meehan, TM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. EM tmmeehan@partners.org RI Duszak, Richard/L-1811-2016; OI Duszak, Richard/0000-0003-0425-3008; McGinty, Geraldine/0000-0001-6111-2514 NR 0 TC 3 Z9 3 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD JUN PY 2016 VL 8 IS 6 BP 655 EP 658 DI 10.1136/neurintsurg-2015-011809 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA DN1PJ UT WOS:000376837600022 PM 25987588 ER PT J AU Rosa, M da Rocha, AJ Maia, ACM Saade, N Veiga, JCE Romero, JM AF Rosa, Marcos, Jr. da Rocha, Antonio Jose Martins Maia, Antonio Carlos, Jr. Saade, Nelson Esteves Veiga, Jose Carlos Romero, Javier M. TI Contusion Contrast Extravasation Depicted on Multidetector Computed Tomography Angiography Predicts Growth and Mortality in Traumatic Brain Contusion SO JOURNAL OF NEUROTRAUMA LA English DT Article DE contrast extravasation; multidetector CT angiography; spot sign; traumatic brain contusion; traumatic brain injury ID LONG-TERM DISABILITY; ACUTE HEAD-INJURY; INTRACEREBRAL HEMORRHAGE; HEMATOMA EXPANSION; SPOT SIGN; INTRACRANIAL HEMORRHAGE; CT ANGIOGRAPHY; UNITED-STATES; ACTIVE EXTRAVASATION; RISK-FACTORS AB Traumatic brain injury (TBI) is the main cause of death in trauma victims and causes high rates of disability and neurological sequelae. Approximately 38-65% of traumatic brain contusions (TBC) demonstrate hemorrhagic expansion on serial computed tomography (CT) scans. Thus far, however, no single variable can accurately predict the hemorrhage expansion of a TBC. Our purpose was to evaluate contrast extravasation (CE) as a predictor of expansion, mortality, and poor outcome in TBC in a Brazilian cohort. After Institutional Review Board approval, we used multidetector CT angiography (MDCTA) to study 121 consecutive patients (106 men, 87.6%) with ages varying from 10 to 85 years. Informed consent was obtained from all subjects. The clinical and imaging findings were correlated with the findings on the initial MDCTA using either the Fisher exact test or Student t test and a multivariate logistic regression model. Of the persons who presented CE in TBC, 21.8% died (in-hospital mortality), whereas in the absence of this sign, the mortality rate was 7.6% (p=0.014). In addition, expansion of the hemorrhagic component of the TBC was detected in 61.1% of the CE-positive patients, whereas expansion was only observed in 10% of the CE-negative patients (p<0.001). Poor outcome was observed in 24.2% of the patients in the CE-negative group, but in the presence of CE, 72.7% evolved with poor outcome (p<0.001). The CE was a strong independent predictor of expansion, poor outcome, and increased risk of in-hospital mortality in our series of patients with TBC. C1 [Rosa, Marcos, Jr.; da Rocha, Antonio Jose; Martins Maia, Antonio Carlos, Jr.] Santa Casa Misericordia Sao Paulo, Neuroradiol Sect, Sao Paulo, SP, Brazil. [Rosa, Marcos, Jr.] Univ Fed Espirito Santo, Sect Radiol, Vitoria, ES, Brazil. [Saade, Nelson; Esteves Veiga, Jose Carlos] Santa Casa Misericordia Sao Paulo, Div Neurosurg, Sao Paulo, SP, Brazil. [Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol, Boston, MA USA. RP Rosa, M (reprint author), Santa Casa Misericordia Sao Paulo, Serv Diagnost Imagem, Rua Dr Cesario Motta Jr 112, BR-01221020 Sao Paulo, SP, Brazil. EM marcosrosajr@hotmail.com NR 43 TC 0 Z9 0 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 1 PY 2016 VL 33 IS 11 BP 1015 EP 1022 DI 10.1089/neu.2015.4062 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DN3SU UT WOS:000376984600005 PM 26214242 ER PT J AU Rautiainen, S Rist, PM Glynn, RJ Buring, JE Gaziano, JM Sesso, HD AF Rautiainen, Susanne Rist, Pamela M. Glynn, Robert J. Buring, Julie E. Gaziano, J. Michael Sesso, Howard D. TI Multivitamin Use and the Risk of Cardiovascular Disease in Men SO JOURNAL OF NUTRITION LA English DT Article DE nutrition; multivitamin supplements; cardiovascular diseases; prevention; epidemiology cohort ID CORONARY-HEART-DISEASE; PHYSICIANS HEALTH; WOMENS-HEALTH; INTEROBSERVER AGREEMENT; DIETARY-SUPPLEMENTS; UNITED-STATES; VITAMIN-C; MORTALITY; PREVENTION; COHORT AB Background: Although multivitamins are widely used by US adults, few prospective studies have investigated their association with the long- and short-term risks of cardiovascular disease (CVD). Objective: The aim of this study was to investigate how multivitamin use is associated with the risk of CVD in initially healthy men at baseline. Methods: We studied 18,530 male physicians aged >= 40 y from the Physicians' Health Study I cohort who were free of CVD and cancer at baseline (1982). All men provided a wide range of self-reported lifestyle and clinical factors plus intake of selected foods and dietary supplements. Cox proportional hazards models were used to calculate multivariable-adjusted HRs (95% Cls). Results: During a mean follow-up of 12.2 y (total of 225,287 person-years), there were 1697 incident cases of major CVD (defined as nonfatal myocardial infarction, nonfatal stroke, and CVD death). In multivariable-adjusted analyses, no significant associations were observed among baseline multivitamin users compared with nonusers for the risk of major CVD events (HR: 0.94; 95% CI: 0.84, 1.05), whereas a self-reported duration of 20 y at baseline was associated with lower risk (HR: 0.56; 95% CI: 0.35, 0.90; P-trend = 0.05). Baseline multivitamin use was also significantly inversely associated with the risk of cardiac revascularization (HR: 0.86; 95% CI: 0.75, 0.98). Baseline use of multivitamins was not significantly associated with other CVD endpoints. Conclusion: In this long-term prospective study in initially healthy men, multivitamin use for y was associated with a lower risk of major CVD events. C1 [Rautiainen, Susanne; Rist, Pamela M.; Glynn, Robert J.; Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Rautiainen, Susanne] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Rist, Pamela M.; Buring, Julie E.; Sesso, Howard D.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Glynn, Robert J.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. RP Rautiainen, S (reprint author), Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.; Rautiainen, S (reprint author), Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. EM susanne.rautiainen@ki.se FU NIH [CA 097193, CA 34944, CA 40360, HL 26490, HL 34595]; Cofas 2 Marie Curie Fellowship (Sweden) FX Supported by the NIH (CA 097193, CA 34944, CA 40360, HL 26490, and HL 34595) and a Cofas 2 Marie Curie Fellowship (Sweden). NR 28 TC 0 Z9 0 U1 3 U2 5 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JUN PY 2016 VL 146 IS 6 BP 1235 EP 1240 DI 10.3945/jn.115.227884 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DN4RI UT WOS:000377054500012 PM 27121531 ER PT J AU Inverso, G Resnick, CM Gonzalez, ML Chuang, SK AF Inverso, Gino Resnick, Cory M. Gonzalez, Martin L. Chuang, Sung-Kiang TI Anesthesia Complications of Diazepam Use for Adolescents Receiving Extraction of Third Molars SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INTRAVENOUS DIAZEPAM; SEDATION; MIDAZOLAM; DENTISTRY AB Purpose: To evaluate the safety of midazolam and diazepam for adolescents during third molar extraction and whether any differences in perioperative complications exist when using the 2 benzodiazepines alone or in combination. Materials and Methods: A prospective study was performed in adolescents (< 21 yr old) who underwent at least 1 third molar extraction by an oral and maxillofacial surgeon in the ambulatory setting from January 2001 through December 2010 using the Oral and Maxillofacial Surgery Outcomes System. The primary predictor variable was type of benzodiazepine used, divided into the total number of patients who received diazepam with or without midazolam. The outcome of interest was adverse complications resulting from anesthesia. Multivariable logistic regression was applied to measure the association between benzodiazepine type and adverse complications. Results: Patients in the diazepam group (n = 4,213) and in the combination group (n = 426) had a complication rate of 1.4%, whereas those in the midazolam group (n = 13,451) had a complication rate of 1.0% (P =.027). Multiple logistic regression analysis showed a 50% increased odds of adverse complications in patients receiving diazepam (adjusted odds ratio = 1.50; 95% confidence interval, 1.05 to 2.16; P =.027). Conclusions: Adolescent patients who received intravenous diazepam during third molar procedures had an increased odds of anesthesia-related complications compared with those given midazolam. (C) 2016 American Association of Oral and Maxillofacial Surgeons C1 [Inverso, Gino] Hosp Univ Penn, Dept Oral & Maxillofacial Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [Resnick, Cory M.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Gonzalez, Martin L.] Amer Assoc Oral & Maxillofacial Surg, Rosemont, IL USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Inverso, G (reprint author), Univ Penn, Dept Oral & Maxillofacial Surg, Perelman Ctr Adv Med, 4 South Pavil,3400 Civ Ctr, Philadelphia, PA 19104 USA. EM gino.inverso@uphs.upenn.edu NR 16 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2016 VL 74 IS 6 BP 1140 EP 1144 DI 10.1016/j.joms.2016.01.055 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DN4GD UT WOS:000377020800015 PM 26968802 ER PT J AU Inverso, G Mahal, BA Aizer, AA Donoff, RB Chuang, SK AF Inverso, Gino Mahal, Brandon A. Aizer, Ayal A. Donoff, R. Bruce Chuang, Sung-Kiang TI Health Insurance Affects Head and Neck Cancer Treatment Patterns and Outcomes SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OROPHARYNGEAL CANCER; COSTS; MUCOSITIS; DIAGNOSIS; ALCOHOL; SMOKING; TOBACCO; LARYNX; ADULTS; IMPACT AB Purpose: The purpose of this study is to examine the effect of insurance coverage on stage of presentation, treatment, and survival of head and neck cancer (HNC). Materials and Methods: A retrospective study was conducted using the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with HNC. The primary variable of interest was insurance analyzed as a dichotomous variable: Patients were considered uninsured if they were classified as "uninsured'' by SEER, whereas patients were considered insured if they were defined by SEER as "any Medicaid,'' "insured,'' or "insured/no specifics.'' The outcomes of interest were cancer stage at presentation (M0 vs M1), receipt of definitive treatment, and HNC-specific mortality (HNCSM). Multivariable logistic regression modeled the association between insurance status and stage at presentation, as well as between insurance status and receipt of definitive treatment, whereas HNCSM was modeled using Fine and Gray competing risks. Sensitivity logistic regression analysis was used to determine whether observed interactions remained significant by insurance type (privately insured, Medicaid, and uninsured). Results: Patients without medical insurance were more likely to present with metastatic cancer (adjusted odds ratio, 1.60; P <.001), were more likely to not receive definitive treatment (adjusted odds ratio, 1.64; P <.001), and had a higher risk of HNCSM (adjusted hazard ratio, 1.20; P =.002). Sensitivity analyses showed that when results were stratified by insurance type, significant interactions remained for uninsured patients and patients with Medicaid. Conclusions: Uninsured patients and patients with Medicaid are more likely to present with metastatic disease, are more likely to not be treated definitively, and are at a higher risk of HNCSM. The treatment gap between Medicaid and private insurance observed in this study should serve as an immediate policy target for health care reform. (C) 2016 American Association of Oral and Maxillofacial Surgeons C1 [Inverso, Gino] Hosp Univ Penn, Dept Oral & Maxillofacial Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [Mahal, Brandon A.] Harvard Radiat Oncol Program, Boston, MA USA. [Aizer, Ayal A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Donoff, R. Bruce; Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. [Donoff, R. Bruce] Massachusetts Gen Hosp, Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Inverso, G (reprint author), Univ Penn, Perelman Ctr Adv Med, Dept Oral & Maxillofacial Surg, 4 South Pavil,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM gino.inverso@uphs.upenn.edu NR 21 TC 1 Z9 1 U1 2 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2016 VL 74 IS 6 BP 1241 EP 1247 DI 10.1016/j.joms.2015.12.023 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DN4GD UT WOS:000377020800033 PM 26851312 ER PT J AU Selvi, F Faquin, WC Michaelson, MD August, M AF Selvi, Firat Faquin, William C. Michaelson, Marc Dror August, Meredith TI Three Synchronous Atypical Metastases of Clear Cell Renal Carcinoma to the Maxillary Gingiva, Scalp and the Distal Phalanx of the Fifth Digit: A Case Report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Oral cavity metastasis of malignant tumors is extremely rare and accounts for only 1% of all malignant oral tumors. Renal cell carcinoma (RCC) can metastasize to any part of the body, with a 15% risk of metastasis to the head and neck region when the disease is disseminated and a 1% risk when it is not. RCC also is the third most common infraclavicular neoplasm that metastasizes to the oral cavity, after lung carcinoma in men and breast carcinoma in women. In the maxillofacial region, the nasal cavity and paranasal sinuses are the most commonly affected sites, followed by the oral cavity. This report describes the case of a 51-year-old man with a history of clear RCC presenting with 3 synchronous atypical metastases of this tumor to the maxillary gingiva, scalp, and distal phalanx of the fifth digit. Clinical findings, diagnosis, pathology, and treatment of these lesions are discussed. Metastasis of RCC should always be included in the differential diagnosis when a new oral and maxillofacial lesion appears in a patient with a history of RCC because the metastatic lesions can often present in a broad spectrum of forms. The rapid growth of these lesions should alert clinicians to avoid any delays in biopsy examination and subsequent treatment, which is usually palliative, because prognosis is usually poor. C1 [Selvi, Firat; August, Meredith] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Selvi, Firat; August, Meredith] Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. [Selvi, Firat] Istanbul Univ, Fac Dent, Dept Oral Surg, Istanbul, Turkey. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Pathol, Boston, MA 02114 USA. [Faquin, William C.; Michaelson, Marc Dror] Harvard Univ, Sch Med, Boston, MA USA. [Michaelson, Marc Dror] Massachusetts Gen Hosp, Hematol Oncol Dept Med, Genitourinary Canc Ctr, Boston, MA 02114 USA. RP Selvi, F (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM fselvi@mgh.harvard.edu NR 19 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 JUN PY 2016 VL 74 IS 6 DI 10.1016/j.joms.2016.01.054 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DN4GD UT WOS:000377020800041 ER PT J AU Poorvu, PD Barton, SE Duncan, CN London, WB Laufer, MR Lehmann, LE Marcus, KJ AF Poorvu, Philip D. Barton, Sara E. Duncan, Christine N. London, Wendy B. Laufer, Marc R. Lehmann, Leslie E. Marcus, Karen J. TI Use and Effectiveness of Gonadotropin-Releasing Hormone Agonists for Prophylactic Menstrual Suppression in Postmenarchal Women Who Undergo Hematopoietic Cell Transplantation SO JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY LA English DT Article DE Gonadotropin-releasing hormone; Menorrhagia; Hematopoietic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; PREMENOPAUSAL WOMEN; PREVENTION; ACETATE; MENORRHAGIA; AMENORRHEA; LEUPROLIDE AB Study Objective: To describe the rates of use and effectiveness of gonadotropin-releasing hormone (GnRH) agonists and other forms of hormonal menstrual suppression in prevention of vaginal bleeding among young women who underwent hematopoietic stem cell transplantation (HCT). Design: Retrospective descriptive study. Setting: University-based pediatric HCT practice. Participants: Fifty-five postmenarchal women who underwent HCT between 2004 and 2011. Interventions: Administration of GnRH agonists or other forms of hormonal menstrual suppression. Main Outcome Measures: Rates of use of GnRH agonists and other forms of hormonal menstrual suppression, and rates and descriptions of vaginal bleeding. Results: Forty-six of the 55 patients had experienced regular or irregular vaginal bleeding before HCT and were considered to be at risk for thrombocytopenia-associated menorrhagia. Forty of the 46 (87%) received hormonal menstrual suppression. Thirty-three patients were treated with a GnRH agonist, 4 with combined hormonal contraceptive pills, 1 with a combined hormonal contraceptive patch, 1 with depot medroxyprogesterone, and 1 with oral norethindrone. Twenty-nine of the 33 patients (88%) who received a GnRH agonist had complete amenorrhea during HCT and 4 of 33 (12%) experienced some degree of vaginal bleeding. Conclusion: GnRH agonists appear effective in prevention of vaginal bleeding complications in most postmenarchal women who underwent HCT. Some patients who might benefit do not receive a GnRH agonist and multiple barriers exist in identification and treatment of them. C1 [Poorvu, Philip D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Barton, Sara E.] Heartland Ctr Reprod Med, Omaha, NE USA. [Duncan, Christine N.; Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [London, Wendy B.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Laufer, Marc R.] Boston Childrens Hosp, Div Gynecol, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA USA. [Marcus, Karen J.] Boston Childrens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA USA. [Marcus, Karen J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Poorvu, PD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ppoorvu@partners.org NR 11 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 1083-3188 EI 1873-4332 J9 J PEDIATR ADOL GYNEC JI J. Pediatr Adolesc. Gynecol. PD JUN PY 2016 VL 29 IS 3 BP 265 EP 268 DI 10.1016/j.jpag.2015.10.013 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA DN5ZH UT WOS:000377149900011 PM 26506031 ER PT J AU Conroy, KN Engelhart, TG Martins, Y Huntington, NL Snyder, AF Coletti, KD Cox, JE AF Conroy, K. N. Engelhart, T. G. Martins, Y. Huntington, N. L. Snyder, A. F. Coletti, K. D. Cox, J. E. TI The Enigma of Rapid Repeat Pregnancy: A Qualitative Study of Teen Mothers SO JOURNAL OF PEDIATRIC AND ADOLESCENT GYNECOLOGY LA English DT Article DE Pregnancy in adolescence; Sexual behavior; Unplanned pregnancy; Rapid repeat pregnancy ID ACTING REVERSIBLE CONTRACEPTION; ADOLESCENT MOTHERS; MOTIVATIONAL INTERVENTION; PROGRAM; CHILDBEARING; INTENTIONS; CHILDREN; HEALTH; IMPACT; BIRTHS AB Study Objective: Rapid repeat pregnancy accounts for 18% of teen pregnancies and leads to adverse health, economic, and developmental outcomes for teen mothers and their children. Few interventions have been successful in reducing rapid repeat pregnancy. In this qualitative study we examined adolescent mothers' perceptions of their decision-making and behaviors that helped prevent or promote a rapid repeat pregnancy. Design, Setting, Participants, Interventions, and Main Outcome Measures: Semistructured interviews were conducted with 31 adolescent mothers, aged 16-21 years; 15 of these subjects experienced a repeat pregnancy within a year of their first child's birth and 16 had not. Two researchers used a grounded, inductive technique to identify emergent themes; interviews were subsequently coded accordingly. Counts were tabulated of the number of times themes were endorsed among those with or without a repeat pregnancy. Results: Four overarching themes emerged from the interviews: intentionality regarding pregnancy planning, patients' degree of independence in making contraceptive choices, sense of control over life experience, and barriers to follow-through on contraceptive planning. Teens who had not experienced a rapid repeat pregnancy more often endorsed themes of intentionality in preventing or promoting a pregnancy, independence in decision-making, and feelings of control over their experience. Ambivalence and lack of decision-making about seeking another pregnancy were frequently endorsed by mothers who had experienced a second pregnancy. Conclusion: Decision-making regarding seeking or preventing a rapid repeat pregnancy is complex for teen mothers; techniques to help support decision-making or to delay pregnancy until decision-repeat making is complete might be important in reducing rapid pregnancy. C1 [Conroy, K. N.; Engelhart, T. G.; Huntington, N. L.; Cox, J. E.] Boston Childrens Hosp, Div Gen Pediat, 300 Longwood Ave, Boston, MA 02115 USA. [Martins, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Snyder, A. F.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL USA. [Coletti, K. D.] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21205 USA. RP Engelhart, TG (reprint author), Boston Childrens Hosp, Div Gen Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM talia.engelhart@childrens.harvard.edu FU Office of Adolescent Pregnancy Programs [APHPA0020033-08-01] FX This research was supported in part by the Office of Adolescent Pregnancy Programs, Grant # APHPA0020033-08-01. NR 38 TC 0 Z9 0 U1 5 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-3188 EI 1873-4332 J9 J PEDIATR ADOL GYNEC JI J. Pediatr Adolesc. Gynecol. PD JUN PY 2016 VL 29 IS 3 BP 312 EP 317 DI 10.1016/j.jpag.2015.12.003 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA DN5ZH UT WOS:000377149900019 PM 26703479 ER PT J AU Kim, IW Park, JM Roh, YJ Kim, JH Choi, MG Hasan, T AF Kim, In-Wook Park, Jae Myung Roh, Yoon Jin Kim, Ju Hee Choi, Myung-Gyu Hasan, Tayyaba TI Direct measurement of singlet oxygen by using a photomultiplier tube-based detection system SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Photosensitizer; Photodynamic therapy; Singlet oxygen; Validation ID PHOTODYNAMIC THERAPY DOSIMETRY; QUANTUM YIELDS; PHOTOSENSITIZER; LUMINESCENCE; PDT; PORPHYRIN AB The effective dosimetry for photodynamic therapy (PDT) can be specified by direct measurement of singlet oxygen (O-1(2)) production. The purpose of this study was to investigate the feasibility of a newly developed photomultiplier tube (PMT)-based singlet oxygen detection (SOD) system. The lowest and highest O-1(2) concentrations detectable by the PMT-SOD system were 15 nM and 10 mu M, respectively. Dose-dependent quenching, by NaN3, of the fluorogenic reaction was observed, which was negatively correlated with the O-1(2) level measured by the PMT-SOD system. The lifetime of O-1(2), as measured by the PMT-SOD system, was found to be lengthened when H2O was replaced with deuterium oxide. O-1(2) photon counts were significantly and dose-dependently correlated with intracellular fluorescence intensity after photosensitizer treatments. In vitro cell viability test and in vivo xenografted-tumor mass shrinkage showed a positive association between PDT-induced cytotoxicity and O-1(2) production concomitantly measured by the PMT-SOD system. It was concluded that the PMT-SOD system is capable of measuring O-1(2) production directly and accurately, demonstrating that this system can be useful in the determination of dosimetry for PDT. (C) 2016 Elsevier B.V. All rights reserved. C1 [Kim, In-Wook; Park, Jae Myung; Roh, Yoon Jin; Kim, Ju Hee; Choi, Myung-Gyu] Catholic Univ Korea, Div Gastroenterol, Dept Internal Med, Coll Med, Seoul 137701, South Korea. [Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Park, JM (reprint author), Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Div Gastroenterol,Dept Internal Med, 222 Banpo Daero, Seoul 137701, South Korea. EM parkjerry@catholic.ac.kr FU program of Global Research and Development Center through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2011-0031644] FX This research was supported by program of Global Research and Development Center through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2011-0031644). NR 27 TC 1 Z9 1 U1 8 U2 21 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 JUN PY 2016 VL 159 BP 14 EP 23 DI 10.1016/j.jphotobiol.2016.03.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DM9RC UT WOS:000376702400003 PM 26995671 ER PT J AU Freire, F Ferraresi, C Jorge, AOC Hamblin, MR AF Freire, Fernanda Ferraresi, Cleber Jorge, Antonio Olavo C. Hamblin, Michael R. TI Photodynamic therapy of oral Candida infection in a mouse model SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Bioluminescence imaging; Luciferase; Photodynamic therapy; Oral candidiasis; Candida albicans; Biofilm ID ANTIMICROBIAL CHEMOTHERAPY PACT; BUCCAL EPITHELIAL-CELLS; ALBICANS INFECTIONS; ANTIFUNGAL THERAPY; ANIMAL-MODELS; MURINE MODEL; IN-VITRO; INACTIVATION; BIOFILMS; EPIDEMIOLOGY AB Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (IQ), and red laser (660 nm) at four different light doses (10 J, 20 J, 40 J and 60 J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40 J (231 log; p < 0.001); and NMB without KI with 60 J (1.77 log; p < 0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5 days of treatment the disease was practically eradicated, especially using MB plus KI with 40 J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis. (C) 2016 Elsevier B.V. All rights reserved. C1 [Freire, Fernanda; Ferraresi, Cleber; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Freire, Fernanda; Jorge, Antonio Olavo C.] Univ Estadual Paulista UNESP, Inst Sci & Technol, Dept Biosci & Oral Diag, Sao Paulo, Brazil. [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 Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Ferraresi, Cleber/B-2458-2014; OI Freire, Fernanda/0000-0002-1240-3988; Hamblin, Michael/0000-0001-6431-4605 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2014/25772-9]; CNPq; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [202313/2014-0]; Lemann Foundation; US NIH [R01AI050875] FX This work was supported by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil (Scholarship 2014/25772-9). CF was supported by CNPq, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Scholarship 202313/2014-0) and Lemann Foundation; MR Hamblin was supported by US NIH grant R01AI050875. NR 37 TC 2 Z9 3 U1 6 U2 13 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 JUN PY 2016 VL 159 BP 161 EP 168 DI 10.1016/j.jphotobiol.2016.03.049 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DM9RC UT WOS:000376702400024 PM 27074245 ER PT J AU Brink, JA AF Brink, James A. TI Radiation Dose Management: Are We Doing Enough to Ensure Adoption of Best Practices? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Brink, James A.] Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA. RP Brink, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM jabrink@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2016 VL 13 IS 6 BP 601 EP 602 DI 10.1016/j.jacr.2016.04.018 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4QY UT WOS:000377053500001 PM 27262054 ER PT J AU Prabhakar, AM Harvey, HB Misono, AS Erwin, AE Jones, N Heffernan, J Rosenthal, DI Brink, JA Saini, S AF Prabhakar, Anand M. Harvey, H. Benjamin Misono, Alexander S. Erwin, Ann E. Jones, Nan Heffernan, James Rosenthal, Daniel I. Brink, James A. Saini, Sanjay TI Imaging Decision Support Does Not Drive Out-of-Network Leakage of Referred Imaging SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Leakage; decision support; referral management ID ORDER ENTRY AB Purpose: Leakage (out-of-network referral) is undesirable because it limits ability to control costs of services. Clinical decision support (CDS) systems seek to ensure appropriate imaging of patients but theoretically could drive leakage if ordering providers attempt to circumvent CDS recommendations and obtain studies from other imaging providers. This study assessed the incidence of leakage of imaging studies that had low appropriateness scores. Methods: We queried our outpatient CDS system over a three-year period (2011-2013) for studies that received a low CDS appropriateness score and were canceled by the ordering physician. For patients meeting these criteria and participating in risk-shared contracts, we cross-referenced their imaging utilization reports in the risk-contract insurance payment database to determine if they received outpatient imaging within 60 days of the index order, contrary to the decision support recommendation. Results: The risk-shared insurance database contained an average of 63,378 patients who had 18,008 MRIs and 18,014 CTs. A total of 11,234 (31.2%) studies were leaked: 3,513 (9.8%) to affiliated institutions; 7,721 (21.4%) to unaffiliated imaging facilities. Overall, 111 imaging studies received a low appropriateness score in the risk-shared patient population and were performed within 60 days despite the low score. Of these studies, 106 of 111 (95.5%) were ultimately performed within our hospital system (104 at the home institution; 2 at affiliated institutions); only 5 of 111 (4.5%) were performed outside of our hospital system. Conclusions: Decision support systems for ordering providers do not seem to drive imaging referrals out of hospital systems to other institutions. Hospital systems can implement decision support without fear of this occurring. C1 [Prabhakar, Anand M.] Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging, Boston, MA USA. [Prabhakar, Anand M.; Harvey, H. Benjamin; Misono, Alexander S.; Rosenthal, Daniel I.; Brink, James A.; Saini, Sanjay] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Erwin, Ann E.; Jones, Nan; Heffernan, James] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Sch Med, Dept Radiol, Div Cardiovasc Imaging,Massachusetts Gen Hosp, 55 Fruit Sr,Gray 2, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu OI Jones, Nan/0000-0001-5117-1713 NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2016 VL 13 IS 6 BP 606 EP 610 DI 10.1016/j.jacr.2016.01.004 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4QY UT WOS:000377053500005 PM 26908201 ER PT J AU Ai, J Oglevee, C Pianykh, O AF Ai, Jing Oglevee, Catherine Pianykh, Oleg TI Determining Waiting Room Occupancy at an Outpatient Clinic Using Simulated Observations and Probability-Duration Curves SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE RIS; linear regression; waiting room ID EMERGENCY-DEPARTMENT; PATIENT SATISFACTION; CARE; MEDICINE; TIME AB Adequate allocation of physical resources in hospitals has become increasingly important with the rise of health care costs. Seat utilization in outpatient clinic waiting rooms is one resource that is particularly important to monitor, to not only ensure patient satisfaction but also accommodate patient flow. Currently, very few studies are available on seat occupancy and patient flow in standard waiting rooms, and studies often neglect important factors, such as hourly patterns of patient influx and occupancy duration. These factors were taken into consideration in our study of visitor occupancy and patient flow in an imaging-facility waiting room. This paper discusses the simulated observation approach that we have developed, which coupled in-person observations with RIS data analysis. Using RIS data to guide our initial in-person observations, we built a model for simulated observations, based on the merged RIS and observation data. To determine the appropriate number of seats needed to accommodate patients and their companions, simulated observation results were analyzed using a probability-duration curve. This curve considers maximum room occupancies as temporal events, with certain probabilities and durations. We demonstrated how simulated observations and probability-duration curves can provide hospital managers with an efficient and pragmatic way to determine waiting room occupancy. C1 [Ai, Jing; Oglevee, Catherine; Pianykh, Oleg] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St, Boston, MA 02114 USA. RP Ai, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St, Boston, MA 02114 USA. EM Jinga63@gmail.com NR 15 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2016 VL 13 IS 6 BP 620 EP 627 DI 10.1016/j.jacr.2016.01.008 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4QY UT WOS:000377053500007 PM 27118098 ER PT J AU Harvey, HB Alkasab, TK Prabhakar, AM Halpern, EF Rosenthal, DI Pandharipande, PV Gazelle, GS AF Harvey, H. Benjamin Alkasab, Tarik K. Prabhakar, Anand M. Halpern, Elkan F. Rosenthal, Daniel I. Pandharipande, Pari V. Gazelle, G. Scott TI Radiologist Peer Review by Group Consensus SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Review DE Radiology; peer review; RADPEER; quality; safety; error; quality assurance; quality improvement; regulation; consensus; COGR ID RATES AB Purpose: The objective of this study was to evaluate the feasibility of the consensus-oriented group review (COGR) method of radiologist peer review within a large subspecialty imaging department. Methods: This study was institutional review board approved and HIPAA compliant. Radiologist interpretations of CT, MRI, and ultrasound examinations at a large academic radiology department were subject to peer review using the COGR method from October 2011 through September 2013. Discordance rates and sources of discordance were evaluated on the basis of modality and division, with ' group differences compared using a chi(2) test. Potential associations between peer review outcomes and the time after the initiation of peer review or the number of radiologists participating in peer review were tested by linear regression analysis and the t test, respectively. Results: A total of 11,222 studies reported by 83 radiologists were peer reviewed using COGR during the two-year study period. The average radiologist participated in 112 peer review conferences and had 3.3% of his or her available CT, MRI and ultrasound studies peer reviewed. The rate of discordance was 2.7% (95% confidence interval [CI], 2.4%-3.0%), with significant differences in discordance rates on the basis of division and modality. Discordance rates were highest for MR (3.4%; 95% CI, 2.8%-4.1%), followed by ultrasound (2.7%; 95% CI, 2.0%-3.4%) and CT (2.4%; 95% CI, 2.0%-2.8%). Missed findings were the most common overall cause for discordance (43.8%; 95% CI, 38.2%-49.4%), followed by interpretive errors (23.5%; 95% CI, 18.8%-28.3%), dictation errors (19.0%; 95% CI, 14.6%-23.4%), and recommendation (10.8%; 95% CI, 7.3%-14.3%). Discordant cases, compared with concordant cases, were associated with a significantly greater number of radiologists participating in the peer review process (5.9 vs 4.7 participating radiologists, P < .001) and were significantly more likely to lead to an addendum (62.9% vs 2.7%, P < .0001). Conclusions: COGR permits departments to collect highly contextualized peer review data to better elucidate sources of error in diagnostic imaging reports, while reviewing a sufficient case volume to comply with external standards for ongoing performance review. C1 [Harvey, H. Benjamin; Alkasab, Tarik K.; Prabhakar, Anand M.; Rosenthal, Daniel I.; Pandharipande, Pari V.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. [Harvey, H. Benjamin; Alkasab, Tarik K.; Prabhakar, Anand M.; Halpern, Elkan F.; Rosenthal, Daniel I.; Pandharipande, Pari V.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Harvey, H. Benjamin; Halpern, Elkan F.; Pandharipande, Pari V.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. EM hbharvey@partners.org FU Medical Imaging and Technology Alliance FX Outside the submitted work, Dr Gazelle has received personal fees from GE Healthcare. Dr Pandharipande has received research funding from the Medical Imaging and Technology Alliance, for unrelated research. NR 21 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2016 VL 13 IS 6 BP 656 EP 662 DI 10.1016/j.jacr.2015.11.013 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4QY UT WOS:000377053500013 PM 26908200 ER PT J AU Wyatt, A Shriki, JE Bhargava, P AF Wyatt, Alvin, II Shriki, Jabi E. Bhargava, Puneet TI Dealing With No Shows: A Quality Improvement Initiative at a Tertiary Care Veterans Affairs Medical Center SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; RATES C1 [Wyatt, Alvin, II; Bhargava, Puneet] Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Room BB308,Box 357115, Seattle, WA 98195 USA. [Shriki, Jabi E.] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Shriki, Jabi E.] Univ Washington, Sch Med, Seattle, WA USA. RP Bhargava, P (reprint author), Univ Washington, Med Ctr, Dept Radiol, 1959 NE Pacific St,Room BB308,Box 357115, Seattle, WA 98195 USA. EM bhargp@uw.edu NR 13 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUN PY 2016 VL 13 IS 6 BP 702 EP 704 DI 10.1016/j.jacr.2015.08.013 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DN4QY UT WOS:000377053500020 PM 26475374 ER PT J AU Ali, MT Yucel, E Bouras, S Wang, L Fei, HW Halpern, EF Scherrer-Crosbie, M AF Ali, Mohammed T. Yucel, Evin Bouras, Souhila Wang, Lin Fei, Hong-wen Halpern, Elkan F. Scherrer-Crosbie, Marielle TI Myocardial Strain Is Associated with Adverse Clinical Cardiac Events in Patients Treated with Anthracyclines SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Chemotherapy; Echocardiography; Heart failure; Left ventricular function; Strain; Anthracycline ID CONGESTIVE-HEART-FAILURE; VENTRICULAR EJECTION FRACTION; ACUTE PROMYELOCYTIC LEUKEMIA; BREAST-CANCER; TASK-FORCE; INDUCED CARDIOTOXICITY; DEFORMATION INDEXES; AMERICAN-COLLEGE; TRASTUZUMAB; DOXORUBICIN AB Background: Anthracycline-induced symptomatic heart failure is often irreversible, underlining the usefulness of pretreatment risk assessment. Global longitudinal strain (GLS) before or after chemotherapy is associated with a later decrease in left ventricular ejection fraction (LVEF); however, whether prechemotherapy GLS is associated with symptomatic heart failure and cardiac death in patients treated with anthracyclines is unknown. Methods: Patients with hematologic cancers treated with anthracyclines who underwent prechemotherapy echocardiography between November 2006 and June 2011 were retrospectively recruited. Basic demographic data, end-diastolic and end-systolic left ventricular volumes, LVEF, and GLS were measured. Clinical cardiac events (CEs) were defined as cardiac death or symptomatic heart failure. The association of prechemotherapy parameters with CEs was analyzed using proportional hazard analysis. Results: Over a median follow-up period of 1,593 days (range, 13-2,891 days) after the start of chemotherapy, 28 of 450 patients (6%) experienced CEs. Prechemotherapy LVEF and GLS were lower in patients with CEs compared with those without CEs (58 6 10% vs 62 6 7% [P = .005] and - 15.0 +/- 2.8% vs - 19.7 +/- 2.7% [P < .0001], respectively). Diabetes (hazard ratio [HR], 7.06; P < .0001), hypertension (HR, 2.22; P = .04), LVEF (HR, 0.93; P = .005), and GLS (HR, 1.47; P < .0001) were associated with CEs. After controlling for clinical variables, prechemotherapy GLS remained independently associated with CEs (P < .0001). GLS less than the absolute value of - 17.5% was found in 105 patients (23%) and was associated with a sixfold increase in CEs (P < .0001). Conclusions: Prechemotherapy GLS is an effective tool to stratify patients at high risk for CEs after anthracycline therapy and may help tailor treatments to decrease anthracycline-induced cardiotoxicity. C1 [Ali, Mohammed T.; Yucel, Evin; Bouras, Souhila; Wang, Lin; Fei, Hong-wen; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM marielle@crosbie.com NR 33 TC 1 Z9 1 U1 4 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2016 VL 29 IS 6 BP 522 EP + DI 10.1016/j.echo.2016.02.018 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN2MR UT WOS:000376898200006 PM 27068546 ER PT J AU Gupta, DK Giugliano, RP Ruff, CT Claggett, B Murphy, S Antman, E Mercuri, MF Braunwald, E Solomon, SD AF Gupta, Deepak K. Giugliano, Robert P. Ruff, Christian T. Claggett, Brian Murphy, Sabina Antman, Elliott Mercuri, Michele F. Braunwald, Eugene Solomon, Scott D. CA Effective Anticoagulation Factor TI The Prognostic Significance of Cardiac Structure and Function in Atrial Fibrillation: The ENGAGE AF-TIMI 48 Echocardiographic Substudy SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Atrial fibrillation; ENGAGE AF-TIMI 48; Echocardiography; Thromboembolism; Stroke; Death ID VENTRICULAR DIASTOLIC FUNCTION; HEART-FAILURE; OLDER-ADULTS; STROKE; DEATH; WARFARIN; RISK; MORTALITY; COMMUNITY; RECOMMENDATIONS AB Background: Atrial fibrillation (AF) is associated with increased risk for thromboembolism and death; however, the relationships between cardiac structure and function and adverse outcomes among individuals with AF are incompletely understood. Methods: The Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 study tested the once-daily oral factor Xa inhibitor edoxaban in comparison with warfarin for the prevention of stroke (ischemic or hemorrhagic) or systemic embolism in 21,105 subjects with nonvalvular AF and increased risk for thromboembolic events (CHADS(2) score >= 2). In a prospective substudy of 971 subjects who underwent transthoracic echocardiography at baseline, Cox proportional hazards models were used to evaluate associations between cardiac structure and function and the risks for death and thromboembolism (ischemic stroke, transient ischemic attack, or systemic embolism). Results: Over a median follow-up period of 2.5 years, 89 deaths (9.2%) and 48 incident thromboembolic events (4.9%) occurred in 971 subjects. In models adjusted for CHADS2 score, aspirin use, and randomized treatment, larger left ventricular (LV) end-diastolic volume index (hazard ratio per 1 SD [12.9 mL/m(2)], 1.49; 95% CI, 1.16-1.91) and higher LV filling pressures measured by E/e' ratio (hazard ratio per 1 SD [4.6], 1.32; 95% CI, 1.08-1.61) were independently associated with increased risks for death. E/e' ratio > 13 significantly improved the prediction of death beyond clinical factors alone. No features of cardiac structure and function were independently associated with thromboembolism in this population. Findings were similar when adjusted for CHA(2)DS(2)-VASc score in place of CHADS(2) score. Conclusions: In a contemporary population of patients with AF at increased risk for thromboembolic events, larger LV size and higher filling pressures were significantly associated with increased risk for death, but neither left atrial nor LV measures were associated with thromboembolic risk. LV size and filling pressures may help identify patients with AF at increased risk for death. C1 [Gupta, Deepak K.] Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Heart & Vasc Inst, Nashville, TN 37203 USA. [Gupta, Deepak K.] Vanderbilt Univ, Med Ctr, Vanderbilt Translat & Clin Cardiovasc Res Ctr, Nashville, TN 37203 USA. [Giugliano, Robert P.; Ruff, Christian T.; Murphy, Sabina; Antman, Elliott; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA. [Claggett, Brian; Solomon, Scott D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Mercuri, Michele F.] Daiichi Sankyo Pharma Dev, Edison, NJ USA. RP Gupta, DK (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Vanderbilt Translat & Clin Cardiovasc Res Ctr, 2525 West End Ave,Suite 300, Nashville, TN 37203 USA. EM d.gupta@vanderbilt.edu FU Daiichi Sankyo Pharma Development (Edison, NJ); National Heart, Lung, and Blood Institute [T32 HL094301-02, K12 HL109019]; Daiichi Sankyo; Merck; Johnson Johnson; Sanofi; AstraZeneca; Brigham and Women's Hospital FX The ENGAGE AF-TIMI 48 study was funded by Daiichi Sankyo Pharma Development (Edison, NJ). Support was provided by the National Heart, Lung, and Blood Institute training grants (T32 HL094301-02 and K12 HL109019). Dr. Giugliano is the principal investigator for the ENGAGE AF-TIMI 48 study, has served as a consultant for and received honoraria from Bristol-Myers Squibb, Janssen, Daiichi Sankyo, Merck, Pfizer, and Sanofi, and has received grants (through the Brigham and Women's Hospital) from Daiichi Sankyo, Merck, Johnson & Johnson, Sanofi, and AstraZeneca. Drs. Antman, Braunwald, and Solomon have received research support from Daiichi Sankyo. Drs. Ruff and Solomon have consulted for Daiichi Sankyo. Dr. Mercuri is an employee of Daiichi Sankyo. Dr. Ruff has received honoraria for consulting from Alere, Beckman Coulter, and Boerhinger-Ingelheim. NR 29 TC 0 Z9 0 U1 2 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2016 VL 29 IS 6 BP 537 EP 544 DI 10.1016/j.echo.2016.03.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DN2MR UT WOS:000376898200008 PM 27106009 ER PT J AU Saito, A Ferhadian, D Sowd, GA Serrao, E Shi, J Halambage, UD Teng, S Soto, J Siddiqui, MA Engelman, AN Aiken, C Yamashita, M AF Saito, Akatsuki Ferhadian, Damien Sowd, Gregory A. Serrao, Erik Shi, Jiong Halambage, Upul D. Teng, Samantha Soto, Juan Siddiqui, Mohammad Adnan Engelman, Alan N. Aiken, Christopher Yamashita, Masahiro TI Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMPLEMENTARY ASSAYS REVEAL; NUCLEAR ENTRY; TYPE-1 INFECTION; REVERSE TRANSCRIPTION; NONDIVIDING CELLS; STRUCTURAL BASIS; DNA INTEGRATION; CYCLOPHILIN-A; PROTEIN AB The viral capsid of HIV-1 interacts with a number of host factors to orchestrate uncoating and regulate downstream events, such as reverse transcription, nuclear entry, and integration site targeting. PF-3450074 (PF74), an HIV-1 capsid-targeting low-molecular-weight antiviral compound, directly binds to the capsid (CA) protein at a site also utilized by host cell proteins CPSF6 and NUP153. Here, we found that the dose-response curve of PF74 is triphasic, consisting of a plateau and two inhibitory phases of different slope values, consistent with a bimodal mechanism of drug action. High PF74 concentrations yielded a steep curve with the highest slope value among different classes of known antiretrovirals, suggesting a dose-dependent, cooperative mechanism of action. CA interactions with both CPSF6 and cyclophilin A (CypA) were essential for the unique dose-response curve. A shift of the steep curve at lower drug concentrations upon blocking the CA-CypA interaction suggests a protective role for CypA against high concentrations of PF74. These findings, highlighting the unique characteristics of PF74, provide a model in which its multimodal mechanism of action of both noncooperative and cooperative inhibition by PF74 is regulated by interactions of cellular proteins with incoming viral capsids. IMPORTANCE PF74, a novel capsid-targeting antiviral against HIV-1, shares its binding site in the viral capsid protein (CA) with the host factors CPSF6 and NUP153. This work reveals that the dose-response curve of PF74 consists of two distinct inhibitory phases that are differentially regulated by CA-interacting host proteins. PF74's potency depended on these CA-binding factors at low doses. In contrast, the antiviral activity of high PF74 concentrations was attenuated by cyclophilin A. These observations provide novel insights into both the mechanism of action of PF74 and the roles of host factors during the early steps of HIV-1 infection. C1 [Saito, Akatsuki; Ferhadian, Damien; Teng, Samantha; Soto, Juan; Siddiqui, Mohammad Adnan; Yamashita, Masahiro] Aaron Diamond AIDS Res Ctr, New York, NY USA. [Sowd, Gregory A.; Serrao, Erik; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Shi, Jiong; Halambage, Upul D.; Aiken, Christopher] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Saito, Akatsuki] Osaka Univ, Microbial Dis Res Inst, Osaka, Japan. [Ferhadian, Damien] Univ Strasbourg, CNRS, IBMC, Architecture & React ARN, Strasbourg, France. RP Yamashita, M (reprint author), Aaron Diamond AIDS Res Ctr, New York, NY USA. EM myamashi@adarc.org FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [R01AI100720, R01AI114339, R01AI052014]; HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [GM082251] FX This work, including the efforts of Masahiro Yamashita, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R01AI100720). This work, including the efforts of Christopher Aiken, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R01AI114339). This work, including the efforts of Alan Engelman, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R01AI052014). This work, including the efforts of Christopher Aiken and Masahiro Yamashita, was funded by HHS vertical bar NIH vertical bar National Institute of General Medical Sciences (NIGMS) (GM082251). NR 70 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2016 VL 90 IS 12 BP 5808 EP 5823 DI 10.1128/JVI.03116-15 PG 16 WC Virology SC Virology GA DN7AL UT WOS:000377227600026 PM 27076642 ER PT J AU D'Amico, AV AF D'Amico, Anthony V. TI Can short-term hormone therapy for rising PSA prolong survival? SO LANCET ONCOLOGY LA English DT Editorial Material ID METASTATIC PROSTATE-CANCER; RADICAL PROSTATECTOMY; CHEMOTHERAPY C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.; D'Amico, AV (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM adamico@partners.org NR 7 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUN PY 2016 VL 17 IS 6 BP 687 EP 688 DI 10.1016/S1470-2045(16)00115-7 PG 2 WC Oncology SC Oncology GA DN4VX UT WOS:000377066400030 PM 27160478 ER PT J AU Suker, M Beumer, BR Sadot, E Marthey, L Faris, JE Mellon, EA El-Rayes, BF Wang-Gillam, A Lacy, J Hosein, PJ Moorcraft, SY Conroy, T Hohla, F Allen, P Taieb, J Hong, TS Shridhar, R Chau, I van Eijck, CH Koerkamp, BG AF Suker, Mustafa Beumer, Berend R. Sadot, Eran Marthey, Lysiane Faris, Jason E. Mellon, Eric A. El-Rayes, Bassel F. Wang-Gillam, Andrea Lacy, Jill Hosein, Peter J. Moorcraft, Sing Yu Conroy, Thierry Hohla, Florian Allen, Peter Taieb, Julien Hong, Theodore S. Shridhar, Ravi Chau, Ian van Eijck, Casper H. Koerkamp, Bas Groot TI FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis SO LANCET ONCOLOGY LA English DT Review ID ADENOCARCINOMA; GEMCITABINE; THERAPY; EFFICACY; TRIAL; FLUOROURACIL; CHEMOTHERAPY; RADIOTHERAPY; MULTICENTER; RESECTION AB Background 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. Methods We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. Findings We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10.0 months (95% CI 4.0-16.0) to 32.7 months (23.1-42.3) across studies with a pooled patient-level median overall survival of 24.2 months (95% CI 21.7-26.8). Median progression-free survival ranged from 3.0 months (95% CI not calculable) to 20.4 months (6.5-34.3) across studies with a patient-level median progression-free survival of 15.0 months (95% 13.8-16.2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60.4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63.5% (95% CI 43.3-81.6, I-2 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25.9% (95% CI 20.2-31.9, I-2 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78.4% (95% CI 60.2-92.2, I-2 64%). Interpretation Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24.2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. C1 [Suker, Mustafa; Beumer, Berend R.; van Eijck, Casper H.; Koerkamp, Bas Groot] Erasmus Univ, Med Ctr, Dept Surg, NL-3015 CE Rotterdam, Netherlands. [Sadot, Eran; Allen, Peter] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. [Marthey, Lysiane] Univ Paris 11, Antoine Beclere Hosp, Assistance Publ Hop Paris, Dept Hepatogastroenterol, Clamart, France. [Faris, Jason E.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Hemato Oncol, Boston, MA 02114 USA. [Mellon, Eric A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL 33612 USA. [El-Rayes, Bassel F.] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Wang-Gillam, Andrea] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Lacy, Jill] Yale Univ, Sch Med, Dept Med, Yale Canc Ctr, New Haven, CT 06510 USA. [Hosein, Peter J.] Univ Kentucky, Dept Med, Markey Canc Ctr, Div Med Oncol, Lexington, KY 40506 USA. [Moorcraft, Sing Yu] Royal Marsden Natl Hlth Serv Fdn Trust, Dept Med, London, England. [Moorcraft, Sing Yu] Royal Marsden Natl Hlth Serv Fdn Trust, Dept Med, Surrey, England. [Conroy, Thierry] Inst Cancerol Lorraine, Dept Med Oncol, Vandoeuvre Les nancy, France. [Conroy, Thierry] Lorraine Univ, Vandoeuvre Les nancy, France. [Hohla, Florian] Paracelsus Med Univ Salzburg, Dept Hematol Med Oncol Hemostasis Rheumatol & Inf, Salzburg, Austria. [Taieb, Julien] Paris Descartes Univ, Canc Res Personalized Med CARPEM, Georges Pompidou European Hosp, AP HP,Dept Gastroenterol & Digest Oncol, Paris, France. [Shridhar, Ravi] Florida Hosp, Inst Canc, Dept Radiat Oncol, Orlando, FL USA. RP Koerkamp, BG (reprint author), Erasmus Univ, Med Ctr, Dept Surg, NL-3015 CE Rotterdam, Netherlands. EM b.grootkoerkamp@erasmusmc.nl NR 41 TC 7 Z9 9 U1 7 U2 12 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 JUN PY 2016 VL 17 IS 6 BP 801 EP 810 DI 10.1016/S1470-2045(16)00172-8 PG 10 WC Oncology SC Oncology GA DN4VX UT WOS:000377066400064 PM 27160474 ER PT J AU Krop, IE Mayer, IA Ganju, V Dickler, M Johnston, S Morales, SN Yardley, DA Melichar, B Forero-Torres, A Lee, SC de Boer, R Petrakova, K Vallentin, S Perez, EA Piccart, M Ellis, M Winer, E Gendreau, S Derynck, M Lackner, M Levy, G Qiu, JH He, J Schmid, P AF Krop, Ian E. Mayer, Ingrid A. Ganju, Vinod Dickler, Maura Johnston, Stephen Morales, Serafi N. Yardley, Denise A. Melichar, Bohuslav Forero-Torres, Andres Lee, Soo Chin de Boer, Richard Petrakova, Katarina Vallentin, Susanne Perez, Edith A. Piccart, Martine Ellis, Matthew Winer, Eric Gendreau, Steven Derynck, Mika Lackner, Mark Levy, Gallia Qiu, Jiaheng He, Jing Schmid, Peter TI Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID TAMOXIFEN RESISTANCE; PIK3CA MUTATIONS; EVEROLIMUS; MECHANISMS; GDC-0941; KINASE; WOMEN AB Background Inhibition of phosphatidylinositol 3-kinase (PI3K) is a promising approach to overcome resistance to endocrine therapy in breast cancer. Pictilisib is an oral inhibitor of multiple PI3K isoforms. The aim of this study is to establish if addition of pictilisib to fulvestrant can improve progression-free survival in oestrogen receptor-positive, endocrine-resistant breast cancer. Methods In this two-part, randomised, double-blind, placebo-controlled, phase 2 study, we recruited postmenopausal women aged 18 years or older with oestrogen receptor-positive, HER2-negative breast cancer resistant to treatment with an aromatase inhibitor in the adjuvant or metastatic setting, from 123 medical centres across 21 countries. Part 1 included patients with or without PIK3CA mutations, whereas part 2 included only patients with PIK3CA mutations. Patients were randomly allocated (1: 1 in part 1 and 2: 1 in part 2) via a computer-generated hierarchical randomisation algorithm to daily oral pictilisib (340 mg in part 1 and 260 mg in part 2) or placebo starting on day 15 of cycle 1, plus intramuscular fulvestrant 500 mg on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles in both groups. In part 1, we stratified patients by presence or absence of PIK3CA mutation, primary or secondary aromatase inhibitor resistance, and measurable or non-measurable disease. In part 2, we stratified patients by previous aromatase inhibitor treatment for advanced or metastatic disease or relapse during or within 6 months of an aromatase inhibitor treatment in the adjuvant setting and measurable or non-measurable disease. All patients and those administering treatment and assessing outcomes were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population for both parts 1 and 2 and also separately in patients with PIK3CA-mutated tumours in part 1. Tumour assessment (physical examination and imaging scans) was investigator-assessed and done at screening and after 8 weeks, 16 weeks, 24 weeks, and 32 weeks of treatment from day 1 of cycle 1 and every 12 weeks thereafter. We assessed safety in as-treated patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT01437566. Findings In part 1, between Sept 27, 2011, and Jan 11, 2013, we randomly allocated 168 patients to the pictilisib (89 [53%]) or placebo (79 [47%]) group. In part 2, between March 18, 2013, and Jan 2, 2014, we randomly allocated 61 patients to the pictilisib (41 [67%]) or placebo (20 [33%]) group. In part 1, we found no difference in median progression-free survival between the pictilisib (6.6 months [95% CI 3.9-9.8]) and placebo (5.1 months [3.6-7.3]) group (hazard ratio [HR] 0.74 [95% CI 0.52-1.06]; p=0.096). We also found no difference when patients were analysed according to presence (pictilisib 6.5 months [95% CI 3.7-9.8] vs placebo 5.1 months [2.6-10.4]; HR 0.73 [95% CI 0.42-1.28]; p=0.268) or absence (5.8 months [3.6-11.1] vs 3.6 months [2.8-7.3]; HR 0.72 [0.42-1.23]; p= 0.23) of PIK3CA mutation. In part 2, we also found no diff erence in progression-free survival between groups (5.4 months [95% CI 3.8-8.3] vs 10.0 months [3.6-13.0]; HR 1.07 [95% CI 0.53-2.18]; p=0.84). In part 1, grade 3 or worse adverse events occurred in 54 (61%) of 89 patients in the pictilisib group and 22 (28%) of 79 in the placebo group. 19 serious adverse events related to pictilisib treatment were reported in 14 (16%) of 89 patients. Only one (1%) of 79 patients reported treatment-related serious adverse events in the placebo group. In part 2, grade 3 or worse adverse events occurred in 15 (36%) of 42 patients in the pictilisib group and seven (37%) of 19 patients in the placebo group. Four serious adverse events related to pictilisib treatment were reported in two (5%) of 42 patients. One treatment-related serious adverse event occurred in one (5%) of 19 patients in the placebo group. Interpretation Although addition of pictilisib to fulvestrant did not significantly improve progression-free survival, dosing of pictilisib was limited by toxicity, potentially limiting its efficacy. For future assessment of PI3K inhibition as an approach to overcome resistance to hormonal therapy, inhibitors with greater selectivity than that of pictilisib might be needed to improve tolerability and potentially increase efficacy. No further investigation of pictilisib in this setting is ongoing. C1 [Krop, Ian E.; Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mayer, Ingrid A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ganju, Vinod] Peninsula Oncol Ctr, Melbourne, Vic, Australia. [Dickler, Maura] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Johnston, Stephen] Royal Marsden Hosp, London SW3 6JJ, England. [Morales, Serafi N.] Hosp Arnau Vilanova, Lleida, Spain. [Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Yardley, Denise A.] Tennessee Oncol, Nashville, TN USA. [Melichar, Bohuslav] Palacky Univ, Sch Med, CR-77147 Olomouc, Czech Republic. [Melichar, Bohuslav] Palacky Univ, Teaching Hosp, CR-77147 Olomouc, Czech Republic. [Forero-Torres, Andres] Univ Alabama Birmingham, Birmingham, AL USA. [Lee, Soo Chin] Natl Univ Singapore Hosp, Singapore, Singapore. [de Boer, Richard] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Petrakova, Katarina] Masaryk Mem Canc Inst, Brno, Czech Republic. [Vallentin, Susanne] Herlev Univ Hosp, Copenhagen, Denmark. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Piccart, Martine] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium. [Ellis, Matthew] Washington Univ, Sch Med, St Louis, MO USA. [Gendreau, Steven; Derynck, Mika; Lackner, Mark; Levy, Gallia; Qiu, Jiaheng; He, Jing] Genentech Inc, San Francisco, CA 94080 USA. [Schmid, Peter] Queen Mary Univ London, Barts Canc Inst, London, England. RP Krop, IE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ian_krop@dfci.harvard.edu RI Lackner, Mark/G-4597-2012 OI Lackner, Mark/0000-0002-6375-2037 FU Amgen; Novartis; Roche/Genentech; Eli Lilly; AstraZeneca; GlaxoSmithKline; Pfizer FX IEK reports grant support from Genentech during the conduct of the study and personal fees from Amgen. IAM reports research support from Novartis. MDi reports grants from Genentech/Roche during the conduct of the study and personal fees from Genentech/Roche and Novartis, grants from Eli Lilly, and grants and personal fees from Pfizer and AstraZeneca, outside the submitted work. SJ reports personal fees from Roche/Genentech, Eli Lilly, AstraZeneca, Novartis, and GlaxoSmithKline, and research funding from Pfizer. DAY reports personal fees from Genentech/Roche outside the submitted work. BM reports personal fees and travel support from Roche, Novartis, and Merck, and personal fees from AstraZeneca, Pfizer, Bristol-Myers Squibb, Astellas, Merck Sharp & Dohme, Janssen, Bayer, and Amgen, outside the submitted work. SCL reports personal fees and travel support from Roche and AstraZeneca, personal fees from Novartis, and research support from Elsai and GlaxoSmithKline, outside the submitted work. RdB reports personal fees from Roche Australia outside the submitted work. EAP reports personal fees from Genentech outside the submitted work and became an employee of Genentech after the submitted work was completed. MP reports personal fees from Genentech outside the submitted work. ME reports personal fees and non-financial support from Bioclassifier outside the submitted work, has a patent pending for PAM50, and has interest in Prosigna through patents and ownership of commercialisation rights. EW reports grants from Genentech and Novartis outside the submitted work. SG, MDe, ML, GL, JQ, and JH are employees of Genentech/Roche. MDe has a pending patent (pictilisib treatment in breast cancer; 62/001,764). All other authors declare no competing interests. NR 30 TC 11 Z9 11 U1 4 U2 8 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 JUN PY 2016 VL 17 IS 6 BP 811 EP 821 DI 10.1016/S1470-2045(16)00106-6 PG 11 WC Oncology SC Oncology GA DN4VX UT WOS:000377066400065 PM 27155741 ER PT J AU Schmiegelow, K Attarbaschi, A Barzilai, S Escherich, G Frandsen, TL Halsey, C Hough, R Jeha, S Kato, M Liang, DC Mikkelsen, TS Moricke, A Niinimaki, R Piette, C Putti, MC Raetz, E Silverman, LB Skinner, R Tuckuviene, R van der Sluis, I Zapotocka, E AF Schmiegelow, Kjeld Attarbaschi, Andishe Barzilai, Shlomit Escherich, Gabriele Frandsen, Thomas Leth Halsey, Christina Hough, Rachael Jeha, Sima Kato, Motohiro Liang, Der-Cherng Mikkelsen, Torben Stamm Moericke, Anja Niinimaeki, Riitta Piette, Caroline Putti, Maria Caterina Raetz, Elizabeth Silverman, Lewis B. Skinner, Roderick Tuckuviene, Ruta van der Sluis, Inge Zapotocka, Ester CA Ponte Legno Toxicity Working Grp TI Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus SO LANCET ONCOLOGY LA English DT Review ID POPULATION-BASED COHORT; CLINICAL-TRIALS; PERIPHERAL NEUROPATHY; CANCER; CHILDREN; CLASSIFICATION; METHOTREXATE; RISK; OSTEONECROSIS; ASPARAGINASE AB Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects ( hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. C1 [Schmiegelow, Kjeld; Frandsen, Thomas Leth] Rigshosp, Dept Pediat & Adolescent Med, DK-2100 Copenhagen, Denmark. [Schmiegelow, Kjeld] Univ Copenhagen, Inst Clin Med, Fac Med, Copenhagen, Denmark. [Schmiegelow, Kjeld] NYU, Dept Pediat Oncol, Langone Med Ctr, New York, NY USA. [Attarbaschi, Andishe] St Anna Childrens Hosp, Dept Pediat Hematol & Oncol, A-1090 Vienna, Austria. [Attarbaschi, Andishe] Med Univ Vienna, Dept Pediat & Adolescent Med, Vienna, Austria. [Barzilai, Shlomit] Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, Petah Tiqwa, Israel. [Escherich, Gabriele] Univ Med Ctr Eppendorf, Clin Pediat Hematol & Oncol, Hamburg, Germany. [Halsey, Christina] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Hough, Rachael] Univ Coll Londons NHS Fdn Trust, London, England. [Jeha, Sima] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Kato, Motohiro] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Tokyo, Japan. [Liang, Der-Cherng] Mackay Mem Hosp, Div Pediat Hematol Oncol, Taipei, Taiwan. [Mikkelsen, Torben Stamm] Aarhus Univ Hosp, Dept Pediat, Aarhus N, Denmark. [Moericke, Anja] Univ Kiel, Kiel, Germany. [Moericke, Anja] Univ Med Ctr Schleswig Holstein, Dept Pediat, Kiel, Germany. [Niinimaeki, Riitta] Oulu Univ Hosp, Dept Pediat, Oulu, Finland. [Piette, Caroline] CHR Citadelle, EORTC Childrens Leukemia Grp, Liege, Belgium. [Piette, Caroline] CHR Citadelle, Univ Dept Pediat Oncol, Liege, Belgium. [Putti, Maria Caterina] Clin Pediat Hematol Oncol, Dept Womens & Childrens Hlth, Padua, Italy. [Raetz, Elizabeth] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Raetz, Elizabeth] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA. [Skinner, Roderick] Great North Childrens Hosp, Dept Paediat & Adolescent Haematol Oncol, Newcastle Upon Tyne, Tyne & Wear, England. [Skinner, Roderick] Great North Childrens Hosp, Childrens Haemopoiet Stem Cell Transplant Unit, Newcastle Upon Tyne, Tyne & Wear, England. [Tuckuviene, Ruta] Aalborg Univ Hosp, Dept Pediat, Aalborg, Denmark. [van der Sluis, Inge] Dutch Childhood Oncol Grp, The Hague, Netherlands. [van der Sluis, Inge] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Hematol Oncol, Rotterdam, Netherlands. [Zapotocka, Ester] Univ Hosp Motol, Dept Pediat Hematol Oncol, Prague, Czech Republic. RP Schmiegelow, K (reprint author), Rigshosp, Dept Pediat & Adolescent Med, DK-2100 Copenhagen, Denmark. EM kschmiegelow@rh.dk NR 31 TC 4 Z9 4 U1 4 U2 5 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 JUN PY 2016 VL 17 IS 6 BP E231 EP E239 PG 9 WC Oncology SC Oncology GA DN4VX UT WOS:000377066400023 PM 27299279 ER PT J AU Han, MLK Martinez, CH Au, DH Bourbeau, J Boyd, CM Branson, R Criner, GJ Kalhan, R Kallstrom, TJ King, A Krishnan, JA Lareau, SC Lee, TA Lindell, K Mannino, DM Martinez, FJ Meldrum, C Press, VG Thomashow, B Tycon, L Sullivan, JL Walsh, J Wilson, KC Wright, J Yawn, B Zueger, PM Bhatt, SP Dransfield, MT AF Han, MeiLan K. Martinez, Carlos H. Au, David H. Bourbeau, Jean Boyd, Cynthia M. Branson, Richard Criner, Gerard J. Kalhan, Ravi Kallstrom, Thomas J. King, Angela Krishnan, Jerry A. Lareau, Suzanne C. Lee, Todd A. Lindell, Kathleen Mannino, David M. Martinez, Fernando J. Meldrum, Catherine Press, Valerie G. Thomashow, Byron Tycon, Laura Sullivan, Jamie Lamson Walsh, John Wilson, Kevin C. Wright, Jean Yawn, Barbara Zueger, Patrick M. Bhatt, Surya P. Dransfield, Mark T. TI Meeting the challenge of COPD care delivery in the USA: a multiprovider perspective SO LANCET RESPIRATORY MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS ANALYSIS; VOLUME-REDUCTION SURGERY; QUALITY-OF-CARE; LONG-ACTING BRONCHODILATORS; ACUTE MYOCARDIAL-INFARCTION; AMERICAN THORACIC SOCIETY; POSITIVE-PRESSURE VENTILATION; SELF-MANAGEMENT INTERVENTION AB The burden of chronic obstructive pulmonary disease (COPD) in the USA continues to grow. Although progress has been made in the the development of diagnostics, therapeutics, and care guidelines, whether patients' quality of life is improved will ultimately depend on the actual implementation of care and an individual patient's access to that care. In this Commission, we summarise expert opinion from key stakeholders-patients, caregivers, and medical professionals, as well as representatives from health systems, insurance companies, and industry-to understand barriers to care delivery and propose potential solutions. Health care in the USA is delivered through a patchwork of provider networks, with a wide variation in access to care depending on a patient's insurance, geographical location, and socioeconomic status. Furthermore, Medicare's complicated coverage and reimbursement structure pose unique challenges for patients with chronic respiratory disease who might need access to several types of services. Throughout this Commission, recurring themes indude poor guideline implementation among health-care providers and poor patient access to key treatments such as affordable maintenance drugs and pulmonary rehabilitation. Although much attention has recently been focused on the reduction of hospital readmissions for COPD exacerbations, health systems in the USA struggle to meet these goals, and methods to reduce readmissions have not been proven. There are no easy solutions, but engaging patients and innovative thinkers in the development of solutions is crucial. Financial incentives might be important in raising engagement of providers and health systems. Lowering co-pays for maintenance drugs could result in improved adherence and, ultimately, decreased overall health-care spending. Given the substantial geographical diversity, health systems will need to find their own solutions to improve care coordination and integration, until better data for interventions that are universally effective become available. C1 [Han, MeiLan K.; Martinez, Carlos H.; Meldrum, Catherine] Univ Michigan Hlth Syst, Div Pulm & Crit Care, Ann Arbor, MI 48109 USA. [Au, David H.] US Dept Vet Affairs, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Au, David H.] US Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Bourbeau, Jean] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Branson, Richard] Univ Cincinnati, Dept Surg, 231 Bethesda Ave, Cincinnati, OH 45267 USA. [Criner, Gerard J.] Temple Univ, Dept Thorac Med & Surg, Lewis Katz Sch Med, Philadelphia, PA 19122 USA. [Kalhan, Ravi] Northwestern Univ, Feinberg Sch Med, Asthma & COPD Program, Chicago, IL 60611 USA. [Kallstrom, Thomas J.] Amer Assoc Resp Care, Dallas, TX USA. [King, Angela] Mobile Med Homecare, Leo, IN USA. [Krishnan, Jerry A.] Univ Illinois, Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Syst Outcomes & Policy, Chicago, IL USA. [Zueger, Patrick M.] Univ Illinois, Coll Pharm, Dept Pharm Syst Outcomes & Policy, Chicago, IL USA. [Lareau, Suzanne C.] Univ Colorado Denver, Anschutz Med Campus, Aurora, CO USA. [Tycon, Laura] Univ Pittsburgh, Med Ctr, Palliat & Support Inst, Pittsburgh, PA USA. [Lindell, Kathleen] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Mannino, David M.] Univ Kentucky, Dept Prevent Med & Environm Hlth, Lexington, KY USA. [Martinez, Fernando J.] Weill Cornell Sch Med, Dept Internal Med, New York, NY USA. [Press, Valerie G.] Univ Chicago Med, Sect Hosp Med, Chicago, IL USA. [Thomashow, Byron] Columbia Univ, Med Ctr, Div Pulm Crit Care & Sleep Med, New York, NY USA. [Sullivan, Jamie Lamson] COPD Fdn, Washington, DC USA. [Walsh, John] COPD Fdn, Miami, FL USA. [Wilson, Kevin C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wilson, Kevin C.] Amer Thorac Soc, New York, NY USA. [Wright, Jean] Carolinas HealthCare Syst, Charlotte, NC USA. [Yawn, Barbara] Univ Minnesota, Sch Med, Family & Community Hlth, Minneapolis, MN 55455 USA. [Bhatt, Surya P.; Dransfield, Mark T.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Bhatt, Surya P.; Dransfield, Mark T.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Han, MLK (reprint author), Univ Michigan Hlth Syst, Div Pulm & Crit Care, Ann Arbor, MI 48109 USA. EM mrking@umich.edu OI Mannino, David/0000-0003-3646-7828; Zueger, Patrick/0000-0002-3412-9895 FU Society of Hospital Medicine; 6 American Board of Internal Medicine; Novartis Pharmaceuticals; Patient-Centered Outcomes Research Institute; US National Institutes of Health; Maryland Cigarette Restitution Fund; UpToDate; Boehringer Ingelheim; GlaxoSmithKline; Astra Zeneca; Society of Hospital Medicine COPD Expert Panel; US National Heart, Lung, and Blood Institute; American Lung Association; American Thoracic Society; Seattle VA; Regeneron; Novartis; Forest Laboratories; Smith Medical; PneumRx; Spiration; McGill University; Research Institute of the McGill University Health Centre; Canadian Respiratory Research Network; Canadian Institute of Health Research; Aerocrine; Almirall; AstraZeneca; Boston Scientific; Ikaria; Aeris; Pearl; Pulmonx; Otsuka; American Heart Association; US Department of Defense; Celerion; Pfizer; Merck; Amgen FX DHA reports personal fees from the Society of Hospital Medicine, the 6 American Board of Internal Medicine, and Novartis Pharmaceuticals outside of the submitted work. CMB reports grants from the Patient-Centered Outcomes Research Institute, the US National Institutes of Health, and the Maryland Cigarette Restitution Fund; and personal fees from UpToDate. BT reports personal fees from Boehringer Ingelheim, GlaxoSmithKline, and Astra Zeneca outside of the submitted work; he is the Chairman of Board of COPD Foundation, a non-profit organisation. KCW is employed by the American Thoracic Society. SCL reports being on the advisory board of Boehringer Ingelheim outside of the submitted work VGP reports personal fees from the Society of Hospital Medicine COPD Expert Panel during the conduct of the study; and grants from the US National Heart, Lung, and Blood Institute, the American Lung Association, the American Thoracic Society, and the Patient-Centered Outcomes Research Institute, and personal fees from Seattle VA Consulting outside of the submitted work MKH reports personal fees from GlaxoSmithKline, Regeneron, Boehringer Ingelheim, and Novartis outside of the submitted work SPB reports grants from the US National Institutes of Health during the conduct of the study. RK reports personal fees from Forest Laboratories; grants and personal fees from Boehringer Ingelheim; personal fees from Merck and Smith Medical; and grants from GlaxoSmithKline, PneumRx (BTG), and Spiration outside of the submitted work JB has received funding for a COPD Research Chair from McGill University and GlaxoSmithKline; grants from the Research Institute of the McGill University Health Centre, the Canadian Respiratory Research Network, and the Canadian Institute of Health Research; and a consortium of the pharmaceutical industry (Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis). MTD reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Boston Scientific; personal fees from Ikaria; and grants from AstraZeneca, Aeris, Pearl, PneumRx, Pulmonx, Otsuka, Forest Laboratories, the American Heart Association, the US National Institutes of Health, the US Department of Defense, Novartis, and Celerion outside of the submitted work DMM has received honoraria and consulting fees from and served on speaker bureaus for GlaxoSmithKline, Novartis, Pfizer, Boehringer Ingelheim, AstraZeneca, Forest Laboratories, Merck, and Amgen; he has received royalties from UpToDate, is on the Board of Directors of the COPD Foundation, and has served as an expert witness in litigation involving tobacco use. BY is an advisory board member of Boehringer Ingelheim, Novartis, and GlaxoSmithKline; and has received grants from Boehringer Ingelheim and the US National Heart, Lung, and Blood Institute outside of the submitted work TJK is on the Board of Directors for the Allergy and Asthma Network All other authors declare no competing interests. NR 438 TC 4 Z9 4 U1 13 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD JUN PY 2016 VL 4 IS 6 BP 473 EP 526 DI 10.1016/S2213-2600(16)00094-1 PG 54 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN4TC UT WOS:000377059100023 PM 27185520 ER PT J AU Nandivada, P Fell, GL Pan, AH Nose, V Ling, PR Bistrian, BR Puder, M AF Nandivada, Prathima Fell, Gillian L. Pan, Amy H. Nose, Vania Ling, Pei-Ra Bistrian, Bruce R. Puder, Mark TI Eucaloric Ketogenic Diet Reduces Hypoglycemia and Inflammation in Mice with Endotoxemia SO LIPIDS LA English DT Article DE Ketogenic diet; Hypoglycemia; Endotoxin; Inflammation ID HEPATIC INSULIN-RESISTANCE; FATTY LIVER-DISEASE; BETA-HYDROXYBUTYRATE; OXIDATIVE STRESS; KETONE-BODIES; GLUCOSE; METABOLISM; NUTRITION; HYPERGLYCEMIA; RESPONSES AB Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-alpha in the postabsorptive period, with a fivefold higher expression of hepatic NF kappa B compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice. C1 [Nandivada, Prathima; Fell, Gillian L.; Pan, Amy H.; Puder, Mark] Harvard Univ, Vasc Biol Program, Boston Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. [Nandivada, Prathima; Fell, Gillian L.; Pan, Amy H.; Puder, Mark] Harvard Univ, Dept Surg, Boston Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. [Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ling, Pei-Ra; Bistrian, Bruce R.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Puder, M (reprint author), Harvard Univ, Vasc Biol Program, Boston Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA.; Puder, M (reprint author), Harvard Univ, Dept Surg, Boston Childrens Hosp, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Mark.puder@childrens.harvard.edu FU Boston Children's Hospital Surgical Foundation, Boston, MA; Corkin and Maher Family Fund, Boston, MA; National Institutes of Health [F32DK104525-01]; Joshua Ryan Rappaport Fellowship FX Research reported in this publication was supported by The Boston Children's Hospital Surgical Foundation, Boston, MA; The Corkin and Maher Family Fund, Boston, MA; National Institutes of Health grant F32DK104525-01 (GLF); and the Joshua Ryan Rappaport Fellowship (PN). The funders did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 28 TC 3 Z9 3 U1 3 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD JUN PY 2016 VL 51 IS 6 BP 703 EP 714 DI 10.1007/s11745-016-4156-7 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA DN3CO UT WOS:000376940200005 PM 27117864 ER PT J AU Yu, HJ Cowan, CA AF Yu, Haojie Cowan, Chad A. TI Minireview: Genome Editing of Human Pluripotent Stem Cells for Modeling Metabolic Disease SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID ZINC-FINGER NUCLEASES; TYPE-2 DIABETES SUSCEPTIBILITY; DUCHENNE MUSCULAR-DYSTROPHY; SCALE ASSOCIATION ANALYSIS; FUNCTIONAL HEPATIC CELLS; TARGETED GENE CORRECTION; CORONARY-ARTERY-DISEASE; RNA-GUIDED ENDONUCLEASE; SKELETAL-MUSCLE CELLS; HEPATOCYTE-LIKE CELLS AB The pathophysiology of metabolic diseases such as coronary artery disease, diabetes, and obesity is complex and multifactorial. Developing new strategies to prevent or treat these diseases requires in vitro models with which researchers can extensively study the molecular mechanisms that lead to disease. Human pluripotent stem cells and their differentiated derivatives have the potential to provide an unlimited source of disease-relevant cell types and, when combined with recent advances in genome editing, make the goal of generating functional metabolic disease models, for the first time, consistently attainable. However, this approach still has certain limitations including lack of robust differentiation methods and potential off-target effects. This review describes the current progress in human pluripotent stem cell-based metabolic disease research using genome-editing technology. C1 [Yu, Haojie; Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Sherman Fairchild 153,7 Divin Ave, Cambridge, MA 02138 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Sherman Fairchild 153,7 Divin Ave, Cambridge, MA 02138 USA. EM chad_cowan@harvard.edu FU National Institutes of Health [R21HL120781, R01DK097768, U01HL107440] FX This work was supported by National Institutes of Health Grants R21HL120781, R01DK097768, and U01HL107440. NR 136 TC 0 Z9 0 U1 3 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2016 VL 30 IS 6 BP 575 EP 586 DI 10.1210/me.2015-1290 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DN6TZ UT WOS:000377210500002 PM 27075706 ER PT J AU Beglopoulos, V Tulloch, J Roe, AD Daumas, S Ferrington, L Watson, R Fan, Z Hyman, BT Kelly, PAT Bard, F Morris, RGM AF Beglopoulos, V. Tulloch, J. Roe, A. D. Daumas, S. Ferrington, L. Watson, R. Fan, Z. Hyman, B. T. Kelly, P. A. T. Bard, F. Morris, R. G. M. TI Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice SO NATURE COMMUNICATIONS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TRANSGENIC MICE; A-BETA; MOUSE MODEL; NETWORK ACTIVITY; PDAPP MOUSE; WATER MAZE; IMMUNIZATION; IMPAIRMENT AB Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-beta-amyloid antibody. Our data suggest a biomarker strategy for the early detection of beta-amyloid-related abnormalities. C1 [Beglopoulos, V.; Tulloch, J.; Ferrington, L.; Watson, R.; Kelly, P. A. T.; Morris, R. G. M.] Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh Neurosci, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. [Roe, A. D.; Fan, Z.; Hyman, B. T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mass Gen Inst Neurodegenerat, 114 16th St, Charlestown, MA 02129 USA. [Daumas, S.] Univ Paris 06, Univ Sorbonne, Neurosci Paris Seine, Inst Biol Paris Seine,UM CR18,INSERM U1130,CNRS U, F-75005 Paris, France. [Ferrington, L.] Queen Margaret Univ, Sch Hlth Sci, Dept Dietet Nutr & Biol Sci, Musselburgh EH21 6UU, Scotland. [Bard, F.] Janssen Pharmaceut Co Johnson & Johnson, Janssen Prevent Ctr, 3210 Merryfield Row, San Diego, CA 92121 USA. [Morris, R. G. M.] CSIC UMH, Inst Neurociencias, Alacant 03550, Spain. RP Morris, RGM (reprint author), Univ Edinburgh, Ctr Cognit & Neural Syst, Edinburgh Neurosci, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.; Morris, RGM (reprint author), CSIC UMH, Inst Neurociencias, Alacant 03550, Spain. EM r.g.m.morris@ed.ac.uk OI MORRIS, Richard G M/0000-0001-8661-1520; Daumas, Stephanie/0000-0001-7048-7617 FU EU; Janssen Alzheimer Immunotherapy; Medical Research Council (UK); European Research Council [EC268800]; [NIH-R01-AG04150] FX This study was supported by EU Framework 7 grant MEMOLOAD, Janssen Alzheimer Immunotherapy, the Medical Research Council (UK) and the European Research Council (EC268800). F.B. acknowledges a potential conflict of interest. Contribution by B.T.H. was supported NIH-R01-AG04150. We thank Antonios Asiminas, Lisa Genzel, Ann Paterson, Hannah Rowe and Patrick Spooner for technical assistance. NR 64 TC 0 Z9 0 U1 3 U2 17 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 JUN PY 2016 VL 7 AR 11761 DI 10.1038/ncomms11761 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN3NU UT WOS:000376969900001 PM 27249364 ER PT J AU Lamas, B Richard, ML Leducq, V Pham, HP Michel, ML Da Costa, G Bridonneau, C Jegou, S Hoffmann, TW Natividad, JM Brot, L Taleb, S Couturier-Maillard, A Nion-Larmurier, I Merabtene, F Seksik, P Bourrier, A Cosnes, J Ryffel, B Beaugerie, L Launay, JM Langella, P Xavier, RJ Sokol, H AF Lamas, Bruno Richard, Mathias L. Leducq, Valentin Pham, Hang-Phuong Michel, Marie-Laure Da Costa, Gregory Bridonneau, Chantal Jegou, Sarah Hoffmann, Thomas W. Natividad, Jane M. Brot, Loic Taleb, Soraya Couturier-Maillard, Aurelie Nion-Larmurier, Isabelle Merabtene, Fatiha Seksik, Philippe Bourrier, Anne Cosnes, Jacques Ryffel, Bernhard Beaugerie, Laurent Launay, Jean-Marie Langella, Philippe Xavier, Ramnik J. Sokol, Harry TI CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands SO NATURE MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ADAPTER PROTEIN CARD9; BACTERIAL-INFECTION; IL-22; CELLS; RESPONSES; INTERLEUKIN-22; ACTIVATION; IDENTIFICATION; PREVALENCE AB Complex interactions between the host and the gut microbiota govern intestinal homeostasis but remain poorly understood. Here we reveal a relationship between gut microbiota and caspase recruitment domain family member 9 (CARD9), a susceptibility gene for inflammatory bowel disease (IBD) that functions in the immune response against microorganisms. CARD9 promotes recovery from colitis by promoting interleukin (IL)-22 production, and Card9(-/-) mice are more susceptible to colitis. The microbiota is altered in Card9(-/-) mice, and transfer of the microbiota from Card9(-/-) to wild-type, germ-free recipients increases their susceptibility to colitis. The microbiota from Card9(-/-) mice fails to metabolize tryptophan into metabolites that act as aryl hydrocarbon receptor (AHR) ligands. Intestinal inflammation is attenuated after inoculation of mice with three Lactobacillus strains capable of metabolizing tryptophan or by treatment with an AHR agonist. Reduced production of AHR ligands is also observed in the microbiota from individuals with IBD, particularly in those with CARD9 risk alleles associated with IBD. Our findings reveal that host genes affect the composition and function of the gut microbiota, altering the production of microbial metabolites and intestinal inflammation. C1 [Lamas, Bruno; Leducq, Valentin; Jegou, Sarah; Brot, Loic; Sokol, Harry] Univ Paris 06, Sorbonne Univ, Paris, France. [Lamas, Bruno; Leducq, Valentin; Jegou, Sarah; Brot, Loic; Sokol, Harry] INSERM, Avenir Team Gut Microbiota & Immun, Equipe Rech Labelisee ERL 1157, Paris, France. [Lamas, Bruno; Leducq, Valentin; Jegou, Sarah; Brot, Loic; Sokol, Harry] CNRS, Unite Mixte Rech UMR 7203, Paris, France. [Lamas, Bruno; Leducq, Valentin; Jegou, Sarah; Brot, Loic; Sokol, Harry] Ctr Hosp Univ CHU St Antoine, Lab BioMol LBM, 27 Rue Chaligny, Paris, France. [Lamas, Bruno; Richard, Mathias L.; Michel, Marie-Laure; Da Costa, Gregory; Bridonneau, Chantal; Hoffmann, Thomas W.; Natividad, Jane M.; Langella, Philippe; Sokol, Harry] Univ Paris Saclay, Micalis Inst, INRA, AgroParisTech, Jouy En Josas, France. [Lamas, Bruno; Richard, Mathias L.; Leducq, Valentin; Michel, Marie-Laure; Da Costa, Gregory; Bridonneau, Chantal; Jegou, Sarah; Hoffmann, Thomas W.; Natividad, Jane M.; Brot, Loic; Langella, Philippe; Sokol, Harry] Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France. [Pham, Hang-Phuong] Hop La Pitie Salpetriere, ILTOO Pharma Incubateur & Pepiniere Entreprises P, Paris, France. [Taleb, Soraya] INSERM, Paris Cardiovasc Res Ctr, U970, Paris, France. [Taleb, Soraya] Univ Paris 05, Paris, France. [Couturier-Maillard, Aurelie; Ryffel, Bernhard] Univ Orleans, CNRS, Lab Expt & Mol Immunol & Neurogenet, UMR 7355, Orleans, France. [Nion-Larmurier, Isabelle; Seksik, Philippe; Bourrier, Anne; Cosnes, Jacques; Beaugerie, Laurent; Sokol, Harry] UPMC, St Antoine Hosp, AP HP, Dept Gastroenterol, Paris, France. [Merabtene, Fatiha] INSERM, Ctr Rech St Antoine, Plateforme Morphol Petit Anim, UMR S938, Paris, France. [Ryffel, Bernhard] Univ Cape Town, Inst Infect Dis & Mol Med IDM, ZA-7925 Cape Town, South Africa. [Launay, Jean-Marie] Hop Lariboisiere, INSERM, Dept Biochem, UMR S942, F-75475 Paris, France. [Launay, Jean-Marie] Hop Lariboisiere, Ctr Biol Resources BB 0033 00064, F-75475 Paris, France. [Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Xavier, Ramnik J.] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Sokol, H (reprint author), Univ Paris 06, Sorbonne Univ, Paris, France.; Sokol, H (reprint author), INSERM, Avenir Team Gut Microbiota & Immun, Equipe Rech Labelisee ERL 1157, Paris, France.; Sokol, H (reprint author), CNRS, Unite Mixte Rech UMR 7203, Paris, France.; Sokol, H (reprint author), Ctr Hosp Univ CHU St Antoine, Lab BioMol LBM, 27 Rue Chaligny, Paris, France.; Sokol, H (reprint author), Univ Paris Saclay, Micalis Inst, INRA, AgroParisTech, Jouy En Josas, France.; Sokol, H (reprint author), Inflammat Immunopathol Biotherapy Dept DHU i2B, Paris, France.; Sokol, H (reprint author), UPMC, St Antoine Hosp, AP HP, Dept Gastroenterol, Paris, France. EM harry.sokol@aphp.fr OI PHAM, Hang-Phuong/0000-0002-7896-7401; sokol, harry/0000-0002-2914-1822 FU Equipe ATIP-Avenir; INSERM-ITMO SP; ECCO grant FX We thank the members of the ANAXEM germ-free platform, the members of the animal facilities of INRA, and T. Ledent of the animal facilities of Saint-Antoine Hospital for their assistance in mouse care; M. Moroldo and J. Lecardonnel from the CRB GADIE core facility for technical assistance in performing the microarray analyses; S. Dumont for technical help in histology and immunochemistry; and C. Aubry, N.M. Breyner, F. Chain, S. Le Guin, C. Cherbuy, N. Lapaque, and D. Skurnik for fruitful discussions and technical help. We also thank E. Drouet and the Clinical Research Assistant team of Unite de Recherche Clinique de l'Est Parisien for their help in obtaining samples from patients with IBD. Ido1-/- and Il22-/- mice were provided by S. Taleb (INSERM Unit 970) and B. Ryffel (CNRS, UMR7355), respectively. The H1L1.1c2 cell line was provided by M.S. Denison (University of California, Davis). Funding was provided by Equipe ATIP-Avenir 2012 (H.S.), INSERM-ITMO SP 2013 (H.S.) and ECCO grant 2012 (H.S.). NR 52 TC 26 Z9 26 U1 11 U2 24 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 JUN PY 2016 VL 22 IS 6 BP 598 EP + DI 10.1038/nm.4102 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DO0NQ UT WOS:000377476000012 PM 27158904 ER PT J AU Carlson, JM Du, VY Pfeifer, N Bansal, A Tan, VYF Power, K Brumme, CJ Kreimer, A DeZiel, CE Fusi, N Schaefer, M Brockman, MA Gilmour, J Price, MA Kilembe, W Haubrich, R John, M Mallal, S Shapiro, R Frater, J Harrigan, PR Ndung'u, T Allen, S Heckerman, D Sidney, J Allen, TM Goulder, PJR Brumme, ZL Hunter, E Goepfert, PA AF Carlson, Jonathan M. Du, Victor Y. Pfeifer, Nico Bansal, Anju Tan, Vincent Y. F. Power, Karen Brumme, Chanson J. Kreimer, Anat DeZiel, Charles E. Fusi, Nicolo Schaefer, Malinda Brockman, Mark A. Gilmour, Jill Price, Matt A. Kilembe, William Haubrich, Richard John, Mina Mallal, Simon Shapiro, Roger Frater, John Harrigan, P. Richard Ndung'u, Thumbi Allen, Susan Heckerman, David Sidney, John Allen, Todd M. Goulder, Philip J. R. Brumme, Zabrina L. Hunter, Eric Goepfert, Paul A. TI Impact of pre-adapted HIV transmission SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL REPLICATION CAPACITY; IMMUNE ESCAPE PATHWAYS; CLASS-I; MAXIMUM-LIKELIHOOD; DISEASE PROGRESSION; LYMPHOCYTE RESPONSE; DISCORDANT COUPLES; ELITE CONTROLLERS AB Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs. C1 [Carlson, Jonathan M.; Pfeifer, Nico; Tan, Vincent Y. F.; Kreimer, Anat; DeZiel, Charles E.; Fusi, Nicolo; Heckerman, David] Microsoft Res, Redmond, WA USA. [Du, Victor Y.; Bansal, Anju; Goepfert, Paul A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Power, Karen; Ndung'u, Thumbi; Allen, Todd M.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. [Brumme, Chanson J.; Brockman, Mark A.; Harrigan, P. Richard; Brumme, Zabrina L.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Schaefer, Malinda; Hunter, Eric] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Gilmour, Jill; Price, Matt A.] Int AIDS Vaccine Initiat, New York, NY USA. [Gilmour, Jill] Univ London Imperial Coll Sci Technol & Med, London, England. [Price, Matt A.] Univ San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA. [Kilembe, William; Allen, Todd M.; Hunter, Eric] Rwanda Zambia HIV Res Grp, Zambia Emory HIV Res Project, Lusaka, Zambia. [Haubrich, Richard] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [John, Mina; Mallal, Simon] Murdoch Univ, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia. [John, Mina] Royal Perth Hosp, Dept Clin Immunol, GPO Box X2213, Perth, WA 6001, Australia. [Mallal, Simon] Vanderbilt Univ, Sch Med, Ctr Translat Immunol & Infect Dis, Nashville, TN 37212 USA. [Shapiro, Roger] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Frater, John] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [Frater, John] Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England. [Frater, John] Univ Oxford, Oxford Martin Sch, Inst Emerging Infect, Oxford, England. [Harrigan, P. Richard] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV K RITH, Nelson R Mandela Sch Med, Durban, South Africa. [Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany. [Allen, Susan; Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Allen, Susan] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. [Sidney, John] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA. [Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford, England. [Pfeifer, Nico] Max Planck Inst Informat, Dept Computat Biol & Appl Algorithm, Saarbrucken, Germany. [Tan, Vincent Y. F.] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117548, Singapore. [Tan, Vincent Y. F.] Natl Univ Singapore, Dept Math, 10 Kent Ridge Crescent, Singapore 117548, Singapore. [Kreimer, Anat] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. RP Carlson, JM (reprint author), Microsoft Res, Redmond, WA USA.; Goepfert, PA (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.; Hunter, E (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA.; Hunter, E (reprint author), Rwanda Zambia HIV Res Grp, Zambia Emory HIV Res Project, Lusaka, Zambia.; Hunter, E (reprint author), Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. EM carlson@microsoft.com; ehunte4@emory.edu; paulg@uab.edu RI Allen, Todd/F-5473-2011; Pfeifer, Nico/G-1559-2016; OI Carlson, Jonathan/0000-0001-6618-3653; Pfeifer, Nico/0000-0002-4647-8566; Brockman, Mark/0000-0001-6432-1426 FU Merck; NIH National Institute of Allergy and Infectious Diseases (NIAID); NIAID [R01 AI112566, R56 AI098551, R01 AI64060, R37 AI51231, P01 AI074415, U01 AI 66454, RO1 AI46995, R01 AI071906]; Canadian Institutes of Health Research [MOP-93536, HOP-115700]; Wellcome Trust [WT104748MA]; NIH [U01 AI 068636]; National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); International AIDS Vaccine Initiative; Virology Core at the Emory Center for AIDS Research [P30 AI050409]; Flow Cytometry Core at the University of Alabama at Birmingham Center for AIDS Research [P30 AI027767]; Tennessee Center for AIDS Research [P30 AI110527]; Yerkes National Primate Research Center through NIH Office of the Director [P51OD11132]; Action Cycling Fellowship; South African Department of Science and Technology; National Research Foundation through South Africa Research Chairs Initiative; Howard Hughes Medical Institute; Victor Daitz Foundation; CIHR/GSK; Michael Smith Foundation for Health Research FX We thank M. Carrington for comments on the manuscript, S. Riddler (University of Pittsburgh, Pittsburgh, Pennsylvania, USA) for access to HLA and sequence data from the ACTG trials, D. Claiborne (Emory University, Atlanta, Georgia, USA) for providing MJ4 proviruses with nonadapted and adapted epitopes, R.A. Kaslow and J. Tang (University of Alabama, Birmingham, Alabama, USA) for access to Zambian HLA data, and D. Goedhals and C. van Vuuren (University of Free State, Bloemfontein, South Africa) for curating additional clinical data from the Bloemfontein cohort. We thank Merck, the NIH National Institute of Allergy and Infectious Diseases (NIAID) and the NIAID-funded HIV Vaccine Trials Network for providing the clinical data set, viral sequences, HLA types and CTL response data from the Step Study (HVTN 502). We also thank the Step and ACTG 5142 and 5128 staff and trial participants, as well as the staff and volunteers of the HOMER, WAHCS, ZEHRP, Durban, Gaborone, Kimberley and Bloemfontain cohorts, for their contributions. This study was funded by NIAID (grants R01 AI112566 (P.A.G.), R56 AI098551 (P.A.G.), R01 AI64060 (E.H.), R37 AI51231 (E.H.), P01 AI074415 (T.M.A.), U01 AI 66454 (R.S.), RO1 AI46995 (P.J.R.G.) and R01 AI071906 (R. A. Kaslow and J. Tang)), the Canadian Institutes of Health Research (grants MOP-93536 and HOP-115700 (both to M.A.B. and Z.L.B.)) and the Wellcome Trust (grant WT104748MA (P.J.R.G.)). HLA typing and viral sequencing of the ACTG cohorts were supported by the NIH (grant U01 AI 068636 to R.H.), the National Institute of Mental Health (NIMH) and the National Institute of Dental and Craniofacial Research (NIDCR). Support for the ZEHRP cohort was also provided by the International AIDS Vaccine Initiative (S. A.) and made possible in part by the support of the American people through the US Agency for International Development (USAID). A full list of IAVI donors is available at http://www.iavi.org. This work was also supported in part by the Virology Core at the Emory Center for AIDS Research (grant P30 AI050409 (E.H.)), the Flow Cytometry Core at the University of Alabama at Birmingham Center for AIDS Research (grant P30 AI027767 (P.A.G.)), the Tennessee Center for AIDS Research (P30 AI110527 (S. M.)) and the Yerkes National Primate Research Center base (grant P51OD11132 (E.H.)) through the NIH Office of the Director. M. S. was supported in part by an Action Cycling Fellowship. T.N. was supported by the International AIDS Vaccine Initiative, the South African Department of Science and Technology and the National Research Foundation through the South Africa Research Chairs Initiative, by an International Early Career Scientist award from the Howard Hughes Medical Institute, and by the Victor Daitz Foundation. P.R.H. is supported by a CIHR/GSK Professorship in Clinical Virology. Z.L.B. is supported by a Scholar Award from the Michael Smith Foundation for Health Research. NR 109 TC 6 Z9 6 U1 7 U2 12 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 JUN PY 2016 VL 22 IS 6 BP 606 EP + DI 10.1038/nm.4100 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DO0NQ UT WOS:000377476000013 PM 27183217 ER PT J AU Souroullas, GP Jeck, WR Parker, JS Simon, JM Liu, JY Paulk, J Xiong, J Clark, KS Fedoriw, Y Qi, J Burd, CE Bradner, JE Sharpless, NE AF Souroullas, George P. Jeck, William R. Parker, Joel S. Simon, Jeremy M. Liu, Jie-Yu Paulk, Joshiawa Xiong, Jessie Clark, Kelly S. Fedoriw, Yuri Qi, Jun Burd, Christin E. Bradner, James E. Sharpless, Norman E. TI An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation SO NATURE MEDICINE LA English DT Article ID B-CELL LYMPHOMA; EMBRYONIC STEM-CELLS; POLYCOMB-GROUP GENES; SOMATIC MUTATIONS; METHYLTRANSFERASE EZH2; INTEGRATIVE ANALYSIS; CANCER GENOMICS; PROTEIN EZH2; MOUSE MODEL; EXPRESSION AB B cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase (EZH2), but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic Ezh2 gain-of-function mutation (EZH2(Y646F) in human; Ezh2(Y641F) in mouse) is conditionally expressed. Expression of Ezh2(Y641F) in mouse B cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Overexpression of the anti-apoptotic protein Bcl2, but not the oncoprotein Myc, or loss of the tumor suppressor protein p53 (encoded by Trp53 in mice) further accelerated lymphoma progression. Expression of the mutant Braf but not the mutant Nras oncoprotein further accelerated melanoma progression. Although expression of Ezh2(Y641F) globally increased the abundance of trimethylated Lys27 of histone H3 (H3K27me3), it also caused a widespread redistribution of this repressive mark, including a loss of H3K27me3 that was associated with increased transcription at many loci. These results suggest that Ezh2(Y641F) induces lymphoma and melanoma through a vast reorganization of chromatin structure, inducing both repression and activation of polycomb-regulated loci. C1 [Souroullas, George P.; Jeck, William R.; Simon, Jeremy M.; Liu, Jie-Yu; Sharpless, Norman E.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Souroullas, George P.; Jeck, William R.; Simon, Jeremy M.; Liu, Jie-Yu; Xiong, Jessie; Clark, Kelly S.; Fedoriw, Yuri; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Paulk, Joshiawa; Qi, Jun; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Fedoriw, Yuri] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Burd, Christin E.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. [Burd, Christin E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sharpless, Norman E.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA.; Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.; Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. EM nes@med.unc.edu FU US National Cancer Institute [R01-CA163896, CA185353, T32-CA009156]; US National Institute of Aging [R01-AG024379]; US National Heart, Lung and Blood Institute [F32-HL117581] FX We thank the UNC Lineberger Animal Histopathology Core, Flow Cytometry Core, Animal Models Core and Microscopy Services Laboratory for technical assistance, and the Mouse Phase 1 Unit (D. Darr and J. Roques) for providing animals and expertise. This work was supported by the US National Cancer Institute grants R01-CA163896 (N.E.S.), CA185353 (N.E.S.) and T32-CA009156 (G.P.S.), the US National Institute of Aging grant R01-AG024379 (N.E.S.) and the US National Heart, Lung and Blood Institute grant F32-HL117581 (G.P.S.). NR 56 TC 10 Z9 10 U1 4 U2 11 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 JUN PY 2016 VL 22 IS 6 BP 632 EP + DI 10.1038/nm.4092 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DO0NQ UT WOS:000377476000020 PM 27135738 ER PT J AU Cejas, P Li, L O'Neill, NK Duarte, M Rao, P Bowden, M Zhou, CSW Mendiola, M Burgos, E Feliu, J Moreno-Rubio, J Guadalajara, H Moreno, V Garcia-Olmo, D Bellmunt, J Mullane, S Hirsch, M Sweeney, CJ Richardson, A Liu, XS Brown, M Shivdasani, RA Long, HW AF Cejas, Paloma Li, Lewyn O'Neill, Nicholas K. Duarte, Melissa Rao, Prakash Bowden, Michaela Zhou, Chensheng W. Mendiola, Marta Burgos, Emilio Feliu, Jaime Moreno-Rubio, Juan Guadalajara, Hector Moreno, Victor Garcia-Olmo, Damin Bellmunt, Joaquim Mullane, Stephanie Hirsch, Michelle Sweeney, Christopher J. Richardson, Andrea Liu, X. Shirley Brown, Myles Shivdasani, Ramesh A. Long, Henry W. TI Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles SO NATURE MEDICINE LA English DT Article ID EMBRYONIC STEM-CELLS; CIS-REGULATORY REGIONS; TRANSCRIPTION FACTORS; EXPRESSION ANALYSIS; ANTIGEN RETRIEVAL; GENE-EXPRESSION; SELF-RENEWAL; GENOME; CANCER; IMMUNOHISTOCHEMISTRY AB Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatinstate maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation. C1 [Cejas, Paloma; Li, Lewyn; Duarte, Melissa; Rao, Prakash; Liu, X. Shirley; Brown, Myles; Shivdasani, Ramesh A.; Long, Henry W.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Cejas, Paloma; Li, Lewyn; O'Neill, Nicholas K.; Duarte, Melissa; Rao, Prakash; Bellmunt, Joaquim; Mullane, Stephanie; Sweeney, Christopher J.; Brown, Myles; Shivdasani, Ramesh A.; Long, Henry W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cejas, Paloma; Mendiola, Marta; Feliu, Jaime] Hosp La Paz, Inst Hlth Res IdiPAZ, Dept Med Oncol, Madrid, Spain. [Bowden, Michaela; Zhou, Chensheng W.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Mendiola, Marta; Burgos, Emilio] Hosp La Paz, Dept Pathol, Inst Hlth Res IdiPAZ, Madrid, Spain. [Moreno-Rubio, Juan] Infanta Sofia Univ Hosp, Precis Oncol Lab, Madrid, Spain. [Guadalajara, Hector; Garcia-Olmo, Damin] Fdn Jimenez Diaz, Dept Surg, E-28040 Madrid, Spain. [Moreno, Victor] Fdn Jimenez Diaz, Clin Res Unit, E-28040 Madrid, Spain. [Hirsch, Michelle; Richardson, Andrea] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Hirsch, Michelle; Richardson, Andrea] Harvard Univ, Sch Med, Boston, MA USA. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RP Shivdasani, RA; Long, HW (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA.; Shivdasani, RA; Long, HW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu; henry_long@dfci.harvard.edu FU DFCI-Novartis Drug Discovery Program; US NIH [P50CA127003]; Susan F. Smith Center for Women's Cancers; Susan G. Komen foundation; Breast Cancer Research foundation; Medical Oncology Translational Grant Program from Dana-Farber Cancer Institute; Instituto de Salud Carlos III the Spanish Economy and Competitiveness Ministry [PI13-01818]; ConSEPOC-Comunidad de Madrid [S2010/BMD-2542]; Asociacion Espanola Contra el Cancer (Programa de Formacion Avanzada en Oncologia); Fundacion Caja Madrid FX This work was supported by the DFCI-Novartis Drug Discovery Program (R.A.S.), the US NIH grant P50CA127003 (R.A.S.), the Susan F. Smith Center for Women's Cancers (M. Brown), grants from the Susan G. Komen and the Breast Cancer Research foundations (M. Brown), the Medical Oncology Translational Grant Program from the Dana-Farber Cancer Institute (C.J.S.), a grant from Instituto de Salud Carlos III the Spanish Economy and Competitiveness Ministry (grant PI13-01818; P.C.), the ConSEPOC-Comunidad de Madrid (grant S2010/BMD-2542; P.C.), and fellowships from the Asociacion Espanola Contra el Cancer (Programa de Formacion Avanzada en Oncologia 2010; P.C.) and the Fundacion Caja Madrid (P.C.). We thank E. Diaz and M. de Miguel for technical assistance. NR 37 TC 3 Z9 3 U1 2 U2 6 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 JUN PY 2016 VL 22 IS 6 BP 685 EP + DI 10.1038/nm.4085 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DO0NQ UT WOS:000377476000027 PM 27111282 ER PT J AU Gondi, V Yock, TI Mehta, MP AF Gondi, Vinai Yock, Torunn I. Mehta, Minesh P. TI Proton therapy for paediatric CNS tumours - improving treatment-related outcomes SO NATURE REVIEWS NEUROLOGY LA English DT Review ID LONG-TERM SURVIVORS; CONFORMAL RADIATION-THERAPY; CHILDHOOD-CANCER SURVIVOR; NERVOUS-SYSTEM TUMORS; PHASE-II TRIAL; ATYPICAL TERATOID/RHABDOID TUMORS; WHITE-MATTER LOSS; QUALITY-OF-LIFE; BRAIN-TUMORS; PHOTON RADIATION AB Radiotherapy is an integral and highly effective aspect of the management of many paediatric CNS tumours, including embryonal tumours, astrocytic tumours and ependymal tumours. Nevertheless, continued improvements in long-term survivorship of such tumours means that radiotherapy-related toxicities that affect quality of life and overall functional status for survivors are increasingly problematic, and strategies that mitigate these adverse effects are needed. One such strategy is proton therapy, which has distinct advantages over conventional photon therapy and enables greater precision in the delivery of tumoricidal radiation doses with reduced irradiation of healthy tissues. These dose distribution advantages can translate into clinical benefits by reducing the risk of long-term adverse effects of radiotherapy, such as secondary malignancy, cognitive toxicity, endocrinopathy, hearing loss and vasculopathic effects. As the availability of proton therapy increases with the development of new proton centres, this treatment modality is increasingly being used in the management of paediatric CNS tumours. In this Review, we provide an introduction to the types of paediatric CNS tumours for which proton therapy can be considered, and discuss the available evidence that proton therapy limits toxicities and improves quality of life for patients. We will also consider uncertainties surrounding the use of proton therapy, evidence for its cost-effectiveness, and its future role in the management of paediatric CNS tumours. C1 [Gondi, Vinai] Northwestern Med Chicago Proton Ctr, 4455 Weaver Pkwy, Warrenville, IL 60555 USA. [Yock, Torunn I.] Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Mehta, Minesh P.] Univ Maryland, Sch Med, 655 West Baltimore St, Baltimore, MD 21201 USA. RP Mehta, MP (reprint author), Univ Maryland, Sch Med, 655 West Baltimore St, Baltimore, MD 21201 USA. EM mmehta@umm.edu OI mehta, minesh/0000-0002-4812-5713 FU Cellectar; NIH; Novocure FX V.G. has received speaking honoraria from prIME Oncology and US Oncology. None of these activities are related to this paper. M.P.M. has served as a consultant for BMS, Cavion, Celldex, Elekta, Novartis, Novocure and Roche; has previously held stock options in Pharmacyclics where he served on the Board of Directors; and has received research funding from Cellectar, NIH and Novocure. None of these activities are related to this paper. T.I.Y. declares no competing interests. NR 104 TC 1 Z9 1 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUN PY 2016 VL 12 IS 6 BP 334 EP 345 DI 10.1038/nrneurol.2016.70 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA DN1LR UT WOS:000376827800008 PM 27197578 ER PT J AU Struck, AF Westover, MB Hall, LT Deck, GM Cole, AJ Rosenthal, ES AF Struck, Aaron F. Westover, M. Brandon Hall, Lance T. Deck, Gina M. Cole, Andrew J. Rosenthal, Eric S. TI Metabolic Correlates of the Ictal-Interictal Continuum: FDG-PET During Continuous EEG SO NEUROCRITICAL CARE LA English DT Article DE FDG-PET; EEG; Status epilepticus; Ictal-interictal continuum ID POSITRON-EMISSION-TOMOGRAPHY; PERIODIC EPILEPTIFORM DISCHARGES; NONCONVULSIVE SEIZURES; GLUCOSE-METABOLISM; LOCALIZATION; HEMORRHAGE; PATTERNS; ADULTS; LOBE AB Ictal-interictal continuum (IIC) continuous EEG (cEEG) patterns including periodic discharges and rhythmic delta activity are associated with poor outcome and in the appropriate clinical context, IIC patterns may represent "electroclinical" status epilepticus (SE). To clarify the significance of IIC patterns and their relationship to "electrographic" SE, we investigated FDG-PET imaging as a complementary metabolic biomarker of SE among patients with IIC patterns. A single-center prospective clinical database was ascertained for patients undergoing FDG-PET during cEEG. Following MRI-PET co-registration, the maximum standardized uptake value in cortical and subcortical regions was compared to contralateral homologous and cerebellar regions. Consensus cEEG review and clinical rating of etiology and treatment response were performed retrospectively with blinding. Electrographic SE was classified as discrete seizures without interictal recovery or > 3-Hz rhythmic IIC patterns. Electroclinical SE was classified as IIC patterns with electrographic and clinical response to anticonvulsants; clonic activity; or persistent post-ictal encephalopathy. Eighteen hospitalized subjects underwent FDG-PET during contemporaneous IIC patterns attributed to structural lesions (44 %), neuroinflammatory/neuroinfectious disease (39 %), or epilepsy (11 %). FDG-PET hypermetabolism was common (61 %) and predicted electrographic or electroclinical SE (sensitivity 79 % [95 % CI 53-93 %] and specificity 100 % [95 % CI 51-100 %]; p = 0.01). Excluding electrographic SE, hypermetabolism also predicted electroclinical SE (sensitivity 80 % [95 % CI 44-94 %] and specificity 100 % [95 % CI 51-100 %]; p = 0.01). In hospitalized patients with IIC EEG patterns, FDG-PET hypermetabolism is common and is a candidate metabolic biomarker of electrographic SE or electroclinical SE. C1 [Struck, Aaron F.; Westover, M. Brandon; Deck, Gina M.; Cole, Andrew J.; Rosenthal, Eric S.] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang 735, Boston, MA 02114 USA. [Hall, Lance T.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. RP Struck, AF (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang 735, Boston, MA 02114 USA. EM astruck@mgh.harvard.edu FU NIH-NINDS [K23 NS090900]; Rappaport Foundation; Andrew David Heitman Neuroendovascular Research Fund; Merck/GE Healthcare [R01 CA158800-01, R21 CA198392-01]; SAGE Therapeutics; Andrew David Heitman Neuroendovascular Research Foundation; NIBIB [5U54EB007954-04]; NINDS [5U10NS080369-02]; U.S. Army Medical Research and Materiel Command [W81XWH-08-2-0154] FX Aaron F Struck, MD: Dr. Struck reports no disclosures. M. Brandon Westover, MD PhD: Dr. Westover receives funding from NIH-NINDS (K23 NS090900), the Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund. Lance Hall, MD: receives research funding from, R01 CA158800-01 (NIH/NCI), R21 CA198392-01 (NIH/NCI), Merck/GE Healthcare. Gina M Deck, MD: Dr. Deck reports no disclosures. Andrew J Cole, MD: Dr. Cole reports no disclosures. Eric S. Rosenthal, MD: Dr. Rosenthal receives research support from an institutional contract with SAGE Therapeutics, and Grant funding from the Andrew David Heitman Neuroendovascular Research Foundation, NIBIB (5U54EB007954-04), NINDS (5U10NS080369-02), and the U.S. Army Medical Research and Materiel Command (W81XWH-08-2-0154). NR 27 TC 4 Z9 4 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2016 VL 24 IS 3 BP 324 EP 331 DI 10.1007/s12028-016-0245-y PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DN2ZP UT WOS:000376932100002 PM 27169855 ER PT J AU Edlow, BL Copen, WA Izzy, S van der Kouwe, A Glenn, MB Greenberg, SM Greer, DM Wu, O AF Edlow, Brian L. Copen, William A. Izzy, Saef van der Kouwe, Andre Glenn, Mel B. Greenberg, Steven M. Greer, David M. Wu, Ona TI Longitudinal Diffusion Tensor Imaging Detects Recovery of Fractional Anisotropy Within Traumatic Axonal Injury Lesions SO NEUROCRITICAL CARE LA English DT Article DE Traumatic brain injury; Diffusion tensor imaging; Traumatic axonal injury; Fractional anisotropy; Apparent diffusion coefficient ID WHITE-MATTER INJURY; BRAIN-INJURY; HEAD-INJURY; CORPUS-CALLOSUM; ACUTE MILD; DAMAGE; COMA; MRI; FEATURES; DISCONNECTION AB Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome. Patients who underwent both an acute DTI scan (a parts per thousand currency signday 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation. Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores. In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance. C1 [Edlow, Brian L.; Izzy, Saef; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. [Edlow, Brian L.; van der Kouwe, Andre; Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Copen, William A.; van der Kouwe, Andre; Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Glenn, Mel B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp,Dept Phys Med & Rehabil, Boston, MA USA. [Greer, David M.] Yale Univ, Sch Med, Yale New Haven Hosp, Dept Neurol, New Haven, CT USA. RP Edlow, BL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.; Edlow, BL (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM bedlow@mgh.harvard.edu FU National Institutes of Health [R25NS065743, K23NS094538, R01NS059775, P41EB015896]; American Academy of Neurology/American Brain Foundation; National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living, U.S. Department Health and Human Services to Spaulding Rehabilitation Hospital [H133A120085] FX This study was supported by the National Institutes of Health (R25NS065743, K23NS094538, R01NS059775, and P41EB015896), the American Academy of Neurology/American Brain Foundation, and the National Institute on Disability, Independent Living, and Rehabilitation Research, Administration for Community Living, U.S. Department Health and Human Services to Spaulding Rehabilitation Hospital (H133A120085). However, the contents of this manuscript do not necessarily represent the policy of the Department of Health and Human Services and endorsement by the Federal Government should not be assumed. NR 57 TC 0 Z9 0 U1 5 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2016 VL 24 IS 3 BP 342 EP 352 DI 10.1007/s12028-015-0216-8 PG 11 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DN2ZP UT WOS:000376932100004 PM 26690938 ER PT J AU Asuzu, D Nystrom, K Sreekrishnan, A Schindler, J Wira, C Greer, D Halliday, J Kimberly, WT Sheth, KN AF Asuzu, David Nystroem, Karin Sreekrishnan, Anirudh Schindler, Joseph Wira, Charles Greer, David Halliday, Janet Kimberly, W. Taylor Sheth, Kevin N. TI TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis SO NEUROCRITICAL CARE LA English DT Article DE IV thrombolysis; Severe outcomes; Predictive scores; Intracerebral hemorrhage ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; BLOOD-BRAIN-BARRIER; HEMORRHAGIC TRANSFORMATION; INTRACEREBRAL HEMORRHAGE; MATRIX-METALLOPROTEINASE; INTRAVENOUS THROMBOLYSIS; COMPUTED-TOMOGRAPHY; PERMEABILITY; INFARCTION AB Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema. We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC). Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63-0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61-0.73). Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis. C1 [Asuzu, David; Sreekrishnan, Anirudh; Schindler, Joseph; Wira, Charles; Greer, David; Sheth, Kevin N.] Yale Univ, Sch Med, New Haven, CT USA. [Nystroem, Karin; Schindler, Joseph; Wira, Charles; Greer, David; Halliday, Janet; Sheth, Kevin N.] Yale New Haven Med Ctr, Yale Dept Emergency Med, Div Vasc Neurol, Div Neurocrit Care & Emergency Neurol, LCI 10,15 York St, New Haven, CT 06504 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Neurosci Intens Care Unit, Dept Neurol, Boston, MA 02114 USA. RP Sheth, KN (reprint author), Yale Univ, Sch Med, New Haven, CT USA.; Sheth, KN (reprint author), Yale New Haven Med Ctr, Yale Dept Emergency Med, Div Vasc Neurol, Div Neurocrit Care & Emergency Neurol, LCI 10,15 York St, New Haven, CT 06504 USA. EM kevin.sheth@yale.edu FU Yale Department of Neurology; Yale Lowe Endowment fund FX The NINDS dataset was purchased using internal funds from the Yale Department of Neurology. A laptop computer for statistical analyses was purchased using funds from the Yale Lowe Endowment fund. NR 42 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2016 VL 24 IS 3 BP 381 EP 388 DI 10.1007/s12028-015-0198-6 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DN2ZP UT WOS:000376932100008 PM 26341364 ER PT J AU Muir, ER Cardenas, DP Duong, TQ AF Muir, Eric R. Cardenas, Damon P. Duong, Timothy Q. TI MRI of brain tissue oxygen tension under hyperbaric conditions SO NEUROIMAGE LA English DT Article DE Hyperbaric oxygen; MRI; T-1; Tissue oxygenation ID CEREBRAL-BLOOD-FLOW; LONGITUDINAL RELAXATION-TIME; MAGNETIC-FIELD STRENGTHS; PARTIAL-PRESSURE; BOLD FMRI; MITOCHONDRIAL-FUNCTION; RAT-BRAIN; ARTERIAL; HYPOXIA; HYPEROXIA AB The brain depends on a continuous supply of oxygen to maintain its structural and functional integrity. This study measured T-1 from MRI under normobaric air, normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous contrast agent. Brain tissue T-1 decreased corresponding to increased pO2 with increasing inhaled oxygen concentrations, and tissue oxygenation was estimated from the T-1 changes between different inhaled oxygen levels. Tissue pO2 difference maps between different oxygen conditions showed heterogeneous pO2 changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial pO2 but was slightly higher than venous pO2. Additionally, for comparison with published extracellular tissue pO2 data obtained using oxygen electrodes and other invasive techniques, a model was used to estimate extracellular and intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple assumptions, and so the effects of the assumptions and parameters used in modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent on assumptions about the extra- and intracellular compartments but were relatively less sensitive to variations in the relaxivity constant of oxygen and contribution from oxygen in the cerebral blood compartment. This approach may prove useful in evaluating tissue oxygenation in disease states such as stroke. (C) 2016 Elsevier Inc. All rights reserved. C1 [Muir, Eric R.; Cardenas, Damon P.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Cardenas, Damon P.] Univ Texas Hlth Sci Ctr San Antonio, Grad Sch Biomed Sci, 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 NIGMS NIH HHS [R25 GM060655] NR 45 TC 1 Z9 1 U1 1 U2 5 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 JUN PY 2016 VL 133 BP 498 EP 503 DI 10.1016/j.neuroimage.2016.03.040 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DN4PB UT WOS:000377048600045 PM 27033683 ER PT J AU Tahmasian, M Rosenzweig, I Eickhoff, SB Sepehry, AA Laird, AR Fox, PT Morrell, MJ Khazaie, H Eickhoff, CR AF Tahmasian, Masoud Rosenzweig, Ivana Eickhoff, Simon B. Sepehry, Amir A. Laird, Angela R. Fox, Peter T. Morrell, Mary J. Khazaie, Habibolah Eickhoff, Claudia R. TI Structural and functional neural adaptations in obstructive sleep apnea: An activation likelihood estimation meta-analysis SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Voxel-based morphometry (VBM); Functional magnetic resonance imaging (fMRI); Insula; Amygdala; Hippocampus; Obstructive sleep apnea ID POSITIVE AIRWAY PRESSURE; HUMAN PARIETAL OPERCULUM; HUMAN BRAIN NETWORKS; WORKING-MEMORY TASK; CEREBRAL-BLOOD-FLOW; INTERMITTENT HYPOXIA; RESTING-STATE; BASOLATERAL AMYGDALA; INSULAR CORTEX; NEUROCOGNITIVE FUNCTION AB Obstructive sleep apnea (OSA) is a common multisystem chronic disorder. Functional and structural neuroimaging has been widely applied in patients with OSA, but these studies have often yielded diverse results. The present quantitative meta-analysis aims to identify consistent patterns of abnormal activation and grey matter loss in OSA across studies. We used PubMed to retrieve task/resting-state functional magnetic resonance imaging and voxel-based morphometry studies. Stereotactic data were extracted from fifteen studies, and subsequently tested for convergence using activation likelihood estimation. We found convergent evidence for structural atrophy and functional disturbances in the right basolateral amygdala/hippocampus and the right central insula. Functional characterization of these regions using the BrainMap database suggested associated dysfunction of emotional, sensory, and limbic processes. Assessment of task-based co-activation patterns furthermore indicated that the two regions obtained from the meta-analysis are part of a joint network comprising the anterior insula, posterior-medial frontal cortex and thalamus. Taken together, our findings highlight the role of right amygdala, hippocampus and insula in the abnormal emotional and sensory processing in OSA. (C) 2016 The Authors. Published by Elsevier Ltd. C1 [Tahmasian, Masoud; Khazaie, Habibolah] Kermanshah Univ Med Sci KUMS, Sleep Disorders Res Ctr, POB 6719851151, Kermanshah, Iran. [Tahmasian, Masoud] Shahid Beheshti Univ, Natl Brain Mapping Ctr, Gen & Med Campus, Tehran, Iran. [Rosenzweig, Ivana; Morrell, Mary J.] Kings Coll London, Dept Neuroimaging, Sleep & Brain Plast Ctr, IOPPN, London WC2R 2LS, England. [Rosenzweig, Ivana; Morrell, Mary J.] Univ London Imperial Coll Sci Technol & Med, London, England. [Eickhoff, Simon B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany. [Eickhoff, Simon B.; Eickhoff, Claudia R.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany. [Sepehry, Amir A.] Univ British Columbia, Fac Med, Div Neurol, Vancouver, BC, Canada. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Morrell, Mary J.] Univ London Imperial Coll Sci Technol & Med, Acad Unit Sleep & Breathing, Natl Heart & Lung Inst, London, England. [Morrell, Mary J.] Royal Brompton & Harefield NHS Fdn Trust, NIHR Resp Dis Biomed Res Unit, London, England. [Eickhoff, Claudia R.] Rhein Westfal TH Aachen, Dept Psychiat Psychotherapy & Psychosomat, Aachen, Germany. RP Khazaie, H (reprint author), Kermanshah Univ Med Sci KUMS, Sleep Disorders Res Ctr, POB 6719851151, Kermanshah, Iran. EM Sepehryaa@alumni.ubc.ca; hakhazaie@gmail.com OI Sepehry, Amir/0000-0002-6055-4457 FU Kermanshah University of Medical Sciences; Wellcome Trust [103952/Z/14/Z] FX Author M.T is supported by the Kermanshah University of Medical Sciences; Author I. R. is supported by the Wellcome Trust [103952/Z/14/Z]. NR 144 TC 3 Z9 3 U1 2 U2 5 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 JUN PY 2016 VL 65 BP 142 EP 156 DI 10.1016/j.neubiorev.2016.03.026 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DN0WJ UT WOS:000376787400007 PM 27039344 ER PT J AU Jarlenski, M Borrero, S La Charite, T Zite, NB AF Jarlenski, Marian Borrero, Sonya La Charite, Trey Zite, Nikki B. TI Episode-Based Payment for Perinatal Care in Medicaid Implications for Practice and Policy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID REFORM; START AB Medicaid is an important source of health insurance coverage for low-income pregnant women and covers nearly half of all deliveries in the United States. In the face of budgetary pressures, several state Medicaid programs have implemented or are considering implementing episode-based payments for perinatal care. Under the episode-based payment model, Medicaid programs make a single payment for all pregnancy-related medical services provided to women with low- and medium-risk pregnancies from 40 weeks before delivery through 60 days postpartum. The health care provider who delivers a live birth is assigned responsibility for all care and must meet certain quality metrics and stay within delineated cost-per-episode parameters. Implementation of cost- and quality-dependent episode-based payments for perinatal care is notable because there is no published evidence about the effects of such initiatives on pregnancy or birth outcomes. In this article, we highlight challenges and potential adverse consequences related to defining the perinatal episode and assigning a responsible health care provider. We also describe concerns that perinatal care quality metrics may not address the most pressing health care issues that are likely to improve health outcomes and reduce costs. In their current incarnations, Medicaid programs' episode-based payments for perinatal care may not improve perinatal care delivery and subsequent health outcomes. Rigorous evaluation of the new episode-based payment initiatives is critically needed to inform policymakers about the intended and unintended consequences of implementing episode-based payments for perinatal care. C1 [Jarlenski, Marian] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,A647, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Womens Hlth Res & Innovat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Tennessee, Grad Sch Med, Dept Internal Med, Div Hosp Med, Knoxville, TN USA. Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA. RP Jarlenski, M (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,A647, Pittsburgh, PA 15261 USA. EM marian.jarlenski@pitt.edu OI Jarlenski, Marian/0000-0001-6907-5447 NR 13 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2016 VL 127 IS 6 BP 1080 EP 1084 DI 10.1097/AOG.0000000000001423 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DN3CH UT WOS:000376939500016 PM 27159762 ER PT J AU Leung, KJ Quesnel, AM Juliano, AF Curtin, HD AF Leung, Katherine J. Quesnel, Alicia M. Juliano, Amy F. Curtin, Hugh D. TI Correlation of CT, MR, and Histopathology in Incomplete Partition-II Cochlear Anomaly SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Computed tomography; Histopathology; Incomplete partition-II; Magnetic resonance imaging; Scala communis ID HUMAN EMBRYO AB Objective: To correlate the computed tomography (CT) and magnetic resonance imaging (MR) findings in a patient with incomplete partition-type II (IP-II) anomaly with histopathology in a similar human temporal bone specimen. To discover the histologic correlate of a common finding on MR of an "apparent'' interscalar septum (IS). Patients: A patient with sensorineural hearing loss and imaging findings characteristic of IP-II, and a patient with histopathologic IP-II anomaly. Intervention: High-resolution CT, MR, and review of postmortem temporal bone histopathology. Main Outcome Measure: Correlation of temporal bone histopathology with CT and MR findings. Results: Consistent findings of IP-II anomaly on CT, absence of the IS between the more distal turns and flattening of the interscalar ridge between the distal basal turn and the middle turn, were present. The signal void surrounding the cochlea on MR also demonstrated flattening of the interscalar ridge. However, a thin band-like area of low T2 signal was seen, which could be mistaken for an IS. Correlation with temporal bone histopathology revealed that the modiolus was foreshortened, and the spiral ganglion neuron dendritic processes continued toward the upper middle turn through the osseous spiral lamina, likely accounting for the MR finding. Conclusion: Correlation of CT, MR, and histopathology in IP-II shows an "apparent'' segmentation representing a continuum of neurosensory elements in approximately the same location of the expected location of a normal IS. Care should be taken when interpreting MR imaging in isolation. Understanding the bony outline of the cochlea on imaging may prove to be complementary. C1 [Leung, Katherine J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Quesnel, Alicia M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Juliano, Amy F.; Curtin, Hugh D.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02115 USA. RP Curtin, HD (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Hugh_Curtin@meei.harvard.edu OI Leung, Katherine/0000-0003-3705-1082 NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2016 VL 37 IS 5 BP 434 EP 437 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DN6OI UT WOS:000377194300007 PM 27093025 ER PT J AU Merker, VL Bergner, AL Vranceanu, AM Muzikansky, A Slattery, W Plotkin, SR AF Merker, Vanessa L. Bergner, Amanda L. Vranceanu, Ana-Maria Muzikansky, Alona Slattery, William, III Plotkin, Scott R. TI Health-related Quality of Life of Individuals With Neurofibromatosis Type 2: Results From the NF2 Natural History Study SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Acoustic neuroma; Facial paralysis; Hearing loss; Neurofibromatosis 2; Quality of life ID VESTIBULAR SCHWANNOMA GROWTH; HEARING CHANGES; CONSORTIUM; QOL AB Objective: To explore health-related quality of life (HRQoL) reported by individuals with neurofibromatosis type 2 (NF2) and to assess for correlations between HRQoL and objective measures of disease manifestations. Study Design: Prospective observational study. Setting: Seven international NF2 centers. Subjects: Eighty-one individuals with NF2, 73 adults (>18 years) and 8 children/adolescents (10-17 years). Outcome Measures: Quality of life was measured by Short Form-36 (SF-36) norm-based scores. Objective clinical measures were hearing (categorized by word-recognition scores), facial function (categorized by the House-Brackmann scale) and the volume of subjects' larger vestibular schwannoma (VS). Results: At baseline, adults showed significant deficits in all but two subscales of the SF-36 compared with age-and gender-adjusted United States population norms. In linear regression models including age, gender, inheritance status, hearing, facial weakness and VS volume, demographic and functional measures showed no relationship to any SF-36 subscale. Larger baseline VS volume was significantly related to reduced physical role performance, reduced mental health, and increased pain (p<0.05). In bivariate analysis, previous VS surgery was not significantly associated with baseline HRQoL; receipt of VS surgery or tumor growth during the observation period was not significantly associated with changes in HRQoL. Conclusion: NF2 patients report reduced HRQoL in physical, social, and mental domains, but this was not significantly related to objective measures of hearing or facial functioning. Larger baseline VS volume negatively impacted patient-reported HRQoL whereas VS surgery or tumor growth did not. Future studies should explore the relationship between tumor volume and HRQoL and psychosocial factors that may moderate this relationship. C1 [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bergner, Amanda L.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Slattery, William, III] House Clin, Dept Neurotol, Los Angeles, CA USA. RP Merker, VL (reprint author), 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM vmerker@mgh.harvard.edu OI Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense [DAMD 17-98-1-8612] FX The NF2 Natural History Consortium was supported by the Department of Defense award number DAMD 17-98-1-8612, for which W.S. served as overall PI and S.P. served as a site PI. NR 22 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 1531-7129 EI 1537-4505 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2016 VL 37 IS 5 BP 574 EP 579 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DN6OI UT WOS:000377194300028 PM 27050651 ER PT J AU Zarifi, M Tzika, AA AF Zarifi, Maria Tzika, A. Aria TI Proton MRS imaging in pediatric brain tumors SO PEDIATRIC RADIOLOGY LA English DT Article DE Brain; Children; Magnetic resonance spectroscopy; Tumor ID MAGNETIC-RESONANCE-SPECTROSCOPY; RECURRENT MALIGNANT GLIOMAS; GAMMA-KNIFE RADIOSURGERY; P-31 NMR-SPECTROSCOPY; IN-VIVO; PATTERN-RECOGNITION; VOLUME MRI; PHOSPHOLIPID-METABOLISM; GLIOBLASTOMA-MULTIFORME; DIFFERENTIAL-DIAGNOSIS AB Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors. C1 [Zarifi, Maria] Aghia Sophia Childrens Hosp, Dept Radiol, Athens, Greece. [Tzika, A. Aria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Tzika, A. Aria] Shriners Burn Hosp, 51 Blossom St,Room 261, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA.; Tzika, AA (reprint author), Shriners Burn Hosp, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu NR 94 TC 0 Z9 0 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD JUN PY 2016 VL 46 IS 7 BP 952 EP 962 DI 10.1007/s00247-016-3547-5 PG 11 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA DN4FX UT WOS:000377020100002 PM 27233788 ER PT J AU Lopez, J Lopez, S Means, J Mohan, R Soni, A Milton, J Tufaro, AP May, JW Dorafshar, A AF Lopez, Joseph Lopez, Sandra Means, Jessica Mohan, Raja Soni, Ashwin Milton, Jacqueline Tufaro, Anthony P. May, James W., Jr. Dorafshar, Amir TI Reply: Financial Conflicts of Interest: An Association between Funding and Findings in Plastic Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID BIOMEDICAL-RESEARCH; PUBLICATION BIAS C1 [Lopez, Joseph; Lopez, Sandra; Mohan, Raja; Tufaro, Anthony P.; Dorafshar, Amir] Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. [Means, Jessica] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. [Soni, Ashwin] Univ Washington, Med Ctr, Div Plast Surg, Seattle, WA 98195 USA. [Milton, Jacqueline] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [May, James W., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Lopez, J (reprint author), Univ Maryland, Johns Hopkins Hosp, Dept Plast Surg, Med Ctr, 1780 E Fayette St,Bloomberg 7th Floor,Room 7314, Baltimore, MD USA. EM jlopez37@jhmi.edu NR 6 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 JUN PY 2016 VL 137 IS 6 BP 1067E EP 1068E DI 10.1097/PRS.0000000000002219 PG 3 WC Surgery SC Surgery GA DN5HV UT WOS:000377098100039 PM 26895581 ER PT J AU Clarke-Pearson, EM Lin, AM Hertl, C Austen, WG Colwell, AS AF Clarke-Pearson, Emily M. Lin, Alex M. Hertl, Catherine Austen, William G. Colwell, Amy S. TI Revisions in Implant-Based Breast Reconstruction: How Does Direct-to-Implant Measure Up? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-of-Plastic-Surgeons CY APR 11-14, 2015 CL Scottsdale, AZ SP Amer Assoc Plast Surg ID NIPPLE-SPARING MASTECTOMY; IMMEDIATE SINGLE-STAGE; RADIATION-THERAPY; SURGICAL OUTCOMES; COMPLICATIONS; SATISFACTION; PREDICTORS; TRENDS AB Background: Immediate direct-to-implant breast reconstruction is increasingly performed for breast cancer treatment or prevention. The advantage over traditional tissue expander/implant reconstruction includes the potential for fewer surgical procedures. Methods: Retrospective, single-institution, three-surgeon review identified patients undergoing implant-based reconstruction from 2006 to 2011. Results: Six hundred eighty-two reconstructions were performed in 432 women with an average follow-up of 5 years. Four hundred sixty-five were direct-to-implant reconstructions with acellular dermal matrix while 217 were tissue expander/implant reconstructions without acellular dermal matrix. The overall revision rate in direct-to-implant reconstruction was 20.9 percent. There was no difference in total revision rates between direct-to-implant and tissue expander reconstruction (20.9 percent versus 20.3 percent; p = 0.861). Subgroup analysis showed no difference in revision for malposition (3.4 percent versus 5.5 percent; p = 0.200), size change (6.7 percent versus 5.5 percent; p = 0.569), fat grafting (8.6 percent versus 9.7 percent; p = 0.647), or capsular contracture (4.5 percent versus 3.2 percent; p = 0.429). Multivariable logistic regression analysis showed complications were associated with higher rates of revision for malposition or size in both groups (OR, 2.8; 95 percent CI, 1.56 to 5.13; p = 0.001). Smoking, preoperative irradiation, skin necrosis, and one surgeon were associated with higher rates of fat grafting, whereas increasing body mass index was associated with lower rates. Postoperative radiotherapy and hematoma were predictive of revision for capsular contracture. Conclusions: The 5-year revision rate in this series of direct-to-implant reconstruction was approximately 21 percent and similar to the revision rate in tissue expander/implant reconstruction. Surgical complications, radiotherapy, and the surgeon influenced the rate of revision similarly in both groups. C1 [Clarke-Pearson, Emily M.; Lin, Alex M.; Hertl, Catherine; Austen, William G.; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Colwell, AS (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM acolwell@mgh.harvard.edu NR 22 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 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2016 VL 137 IS 6 BP 1690 EP 1699 DI 10.1097/PRS.0000000000002173 PG 10 WC Surgery SC Surgery GA DN5HV UT WOS:000377098100047 PM 27219225 ER PT J AU Wang, Y Liu, G Hong, DD Chen, FH Ji, XM Cao, GD AF Wang, Yuan Liu, Gang Hong, Dandan Chen, Fenghua Ji, Xunming Cao, Guodong TI White matter injury in ischemic stroke SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID SMALL-VESSEL DISEASE; CHRONIC CEREBRAL HYPOPERFUSION; INDUCED MOVEMENT THERAPY; DAMAGE FOLLOWING STROKE; TENSOR IMAGING DETECTS; DIFFUSION TENSOR; MAGNETIC-RESONANCE; COGNITIVE IMPAIRMENT; NEUROTROPHIC FACTOR; NMDA RECEPTORS AB Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions. Published by Elsevier Ltd. C1 [Wang, Yuan; Liu, Gang] Capital Univ Med, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China. [Hong, Dandan] Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA. [Chen, Fenghua; Cao, Guodong] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Ji, Xunming] Capital Univ Med, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China. [Cao, Guodong] VA Pittsburgh Healthcare Syst, Geriatr Res Educ Ctr, Pittsburgh, PA 15240 USA. [Cao, Guodong] VA Pittsburgh Healthcare Syst, Ctr Clin, Pittsburgh, PA 15240 USA. RP Ji, XM (reprint author), Capital Univ Med, Xuanwu Hosp, Dept Neurosurg, Beijing 100053, Peoples R China.; Cao, GD (reprint author), Univ Pittsburgh, Dept Neurol, BST S505,3500 Terrace St, Pittsburgh, PA 15260 USA. EM robertjixm@hotmail.com; caog@upmc.edu FU National Institutes of Health/NINDS [NS079345]; VA Merit Review grant [BX002346]; Chinese 12th Five science and technology support program [2013BAI07B01] FX This project was supported by National Institutes of Health/NINDS grant NS079345 (to G. C.) and VA Merit Review grant BX002346 (to G. C.), and Chinese 12th Five science and technology support program 2013BAI07B01 (to X. J). NR 191 TC 1 Z9 1 U1 6 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUN PY 2016 VL 141 BP 45 EP 60 DI 10.1016/j.pneurobio.2016.04.00 PG 16 WC Neurosciences SC Neurosciences & Neurology GA DN1FM UT WOS:000376811700003 PM 27090751 ER PT J AU Jalal, B Hinton, DE AF Jalal, Baland Hinton, Devon E. TI Lifetime presence and rates of sleep paralysis in Denmark of ethnic Danes and non-ethnic Danes SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 [Jalal, Baland] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England. [Jalal, Baland] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Jalal, B (reprint author), Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge, England.; Jalal, B (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM bj272@medschl.cam.ac.uk NR 1 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-1316 EI 1440-1819 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PD JUN PY 2016 VL 70 IS 6 BP 253 EP 253 DI 10.1111/pcn.12385 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DN6UX UT WOS:000377213100003 PM 26940006 ER PT J AU Klompas, M Berra, L AF Klompas, Michael Berra, Lorenzo TI Should Ventilator-Associated Events become a Quality Indicator for ICUs? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 54th Respiratory Care Journal Conference on Respiratory Care Controversies III CY JUN 05-06, 2015 CL St Petersburg, FL DE ventilator-associated events; ventilator-associated pneumonia; quality improvement; surveillance and prevention ID CRITICALLY-ILL PATIENTS; COATED ENDOTRACHEAL-TUBES; INTENSIVE-CARE UNITS; ACUTE KIDNEY INJURY; MECHANICAL VENTILATION; ATTRIBUTABLE MORTALITY; PNEUMONIA SURVEILLANCE; HOSPITAL MORTALITY; RISK-FACTORS; PREVENTION AB The United States Centers for Disease Control and Prevention replaced their longstanding ventilator-associated pneumonia (VAP) definitions with ventilator-associated event (VAE) definitions in 2013. Controversy abounds as to whether VAE definitions are potentially suitable to serve as quality indicators for ICUs. On the pro side, VAE definitions overcome many of the weaknesses of traditional VAP surveillance. VAE definitions are objective, reproducible, electronically computable, and strongly predict poor outcomes for patients. There is an increasing amount of data on clinical correlates, risk factors, and approaches to prevent VAEs. Potential strategies to prevent VAEs are highly aligned with accepted best practices in critical care. VAE surveillance therefore has the potential to catalyze better care and to help hospitals track outcomes in ventilated patients more rigorously and more efficiently. On the con side, the complete VAE definition set with subtiers is complicated, neither sensitive nor specific for VAP, non-physiological compared with other ICU metrics, susceptible to gaming, and may bring about changes in clinician behavior that could paradoxically end up harming patients. (C) 2016 Daedalus Enterprises C1 [Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, 401 Pk Dr,Suite 401, Boston, MA 02215 USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, 401 Pk Dr,Suite 401, Boston, MA 02115 USA. [Klompas, Michael] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Klompas, M (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 401 Pk Dr,Suite 401, Boston, MA 02215 USA.; Klompas, M (reprint author), Harvard Pilgrim Hlth Care Inst, 401 Pk Dr,Suite 401, Boston, MA 02115 USA. EM mklompas@partners.org NR 57 TC 1 Z9 1 U1 0 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 JUN PY 2016 VL 61 IS 6 SI SI BP 723 EP 733 DI 10.4187/respcare.04548 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN7CU UT WOS:000377233700002 PM 27235309 ER PT J AU Zhang, CS Berra, L Klompas, M AF Zhang, Changsheng Berra, Lorenzo Klompas, Michael TI Should Aerosolized Antibiotics Be Used to Treat Ventilator-Associated Pneumonia? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 54th Respiratory Care Journal Conference on Respiratory Care Controversies III CY JUN 05-06, 2015 CL St Petersburg, FL DE ventilator-associated pneumonia; aerosol; antibiotics; delivery device; mechanical ventilation ID INTENSIVE-CARE-UNIT; GRAM-NEGATIVE PNEUMONIA; AIR-SPACE ENLARGEMENT; MECHANICAL VENTILATION; CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; NEBULIZED CEFTAZIDIME; INTRAVENOUS COLISTIN; ADJUNCTIVE THERAPY; RESPIRATORY-TRACT AB In patients with ventilator-associated pneumonia, systemic use of antibiotics is the cornerstone of medical management. Supplemental use of aerosolized antibiotics with intravenous antibiotics in both experimental and clinical studies has been shown to have the following pharmacologic benefits: (1) aerosolized antibiotics reach the infected lung parenchyma without crossing the pulmonary alveolar capillary barrier; (2) aerosolized antibiotics increase anti-bacterial efficacy through increased local antibiotic concentration; and (3) aerosolized antibiotics decrease systemic toxicity. These benefits may be particularly beneficial to treat pneumonia caused by multidrug-resistant pathogens. Clinical data on the benefits of aerosolized antibiotics are more limited. Studies to date have not clearly shown improvements in time to extubation, mortality, or other patient-centered outcomes. At present, amikacin, colistin, and ceftazidime are the most frequently used and studied aerosolized antibiotics. This review summarizes the characteristics of aerosolized antibiotics, reviews the advantages and disadvantages of using aerosolized antibiotics, and calls for future investigations based on animal study data. (C) 2016 Daedalus Enterprises C1 [Zhang, Changsheng; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, White 434B,55 Fruit St, Boston, MA 02114 USA. [Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Klompas, Michael] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, White 434B,55 Fruit St, Boston, MA 02114 USA. EM lberra@partners.org NR 71 TC 0 Z9 0 U1 2 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 JUN PY 2016 VL 61 IS 6 SI SI BP 737 EP 746 DI 10.4187/respcare.04748 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN7CU UT WOS:000377233700004 PM 27235310 ER PT J AU Mireles-Cabodevila, E Kacmarek, RM AF Mireles-Cabodevila, Eduardo Kacmarek, Robert M. TI Should Airway Pressure Release Ventilation Be the Primary Mode in ARDS? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 54th Respiratory Care Journal Conference on Respiratory Care Controversies III CY JUN 05-06, 2015 CL St Petersburg, FL DE Airway pressure release ventilation; biphasic positive-pressure breathing; lung injury; work of breathing; auto PEEP ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; HIGH-FREQUENCY OSCILLATION; MECHANICAL BREATH PROFILE; INVERSE RATIO VENTILATION; END-EXPIRATORY PRESSURE; PHYSIOLOGICAL DETERMINANTS; PERFUSION DISTRIBUTIONS; CLINICAL IMPORTANCE; CONTROLLED-TRIAL AB Airway pressure release ventilation (APRV) was originally described as a mode to treat lung injured patients with the goal to maintain a level of airway pressure that would not depress the cardiac function, deliver mechanical breaths without excessive airway pressure, and to allow unrestricted spontaneous ventilation. Indeed, based on its design, APRV has technological features that serve the goals of safety and comfort. Animal studies suggest that APRV leads to alveolar stability and recruitment which result in less lung injury. These features are sought in patients at risk for lung injury or with ARDS. APRV allows unrestricted spontaneous ventilation, which is welcome in the era of less sedation and increased patient mobility (the effects in terms of lung injury remain to be explored). However, we must highlight that the performance of APRV is dependent on the operator-selected settings and the ventilator's performance. The clinician must select the appropriate settings in order to make effective the imputed benefits. This is a challenge when the ventilator's performance is not uniform, and the outcomes depend on high precision settings (very short expiratory time), where small variations can lead to undesired outcomes (de-recruitment or large tidal volumes leading to lung injury). Finally, we do not have evidence that APRV (as originally described) improves relevant clinical outcomes of patients with ARDS. For APRV to become the primary mode of ventilation for ARDS, it will require development of sound protocols and technological enhancements to ensure its performance and safety. For now, APRV does have a greater potential for adversely affecting patient outcome than improving it; unless definitive data are forthcoming demonstrating outcome benefits from the use of APRV in ARDS, there is no reason to,consider this approach to ventilatory support. (C) 2016 Daedalus Enterprises C1 [Mireles-Cabodevila, Eduardo] Cleveland Clin, Resp Inst, 9500 Euclid Ave,A90, Cleveland, OH 44195 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Mireles-Cabodevila, E (reprint author), Cleveland Clin, Resp Inst, 9500 Euclid Ave,A90, Cleveland, OH 44195 USA.; Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care, 55 Fruit St, Boston, MA 01460 USA. EM mirelee@ccf.org; rkacmarek@partners.org NR 58 TC 2 Z9 2 U1 2 U2 5 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 JUN PY 2016 VL 61 IS 6 SI SI BP 761 EP 772 DI 10.4187/respcare.04653 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN7CU UT WOS:000377233700008 PM 27235312 ER PT J AU Kacmarek, RM Branson, RD AF Kacmarek, Robert M. Branson, Richard D. TI Should Intermittent Mandatory Ventilation Be Abolished? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT 54th Respiratory Care Journal Conference on Respiratory Care Controversies III CY JUN 05-06, 2015 CL St Petersburg, FL DE Mechanical ventilation; intermittent mandatory ventilation; synchronized intermittent mandatory ventilation; asynchrony and work of breathing ID PRESSURE SUPPORT VENTILATION; RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; DISCONTINUE MECHANICAL VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; SPONTANEOUS BREATHING TRIAL; POSITIVE AIRWAY PRESSURE; CANINE LUNG INJURY; PERFUSION DISTRIBUTIONS; ADAPTIVE SUPPORT AB Intermittent mandatory ventilation (IMV) was introduced nearly 50 years ago. Despite the initial fanfare and early adoption by many, the role of IMV continues to be questioned. The use of small tidal volumes complicates the application of IMV, and issues with work of breathing, weaning and lack of clear advantages have many calling for a moratorium on its use. Spontaneous breathing, however, has a number of salutatory effects on gas exchange, the distribution of ventilation, and hemodynamics. These issues will be explored in light of a growing body of evidence. (C) 2016 Daedalus Enterprises C1 [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Branson, Richard D.] Univ Cincinnati, Dept Surg, 231 Bethesda Ave, Cincinnati, OH 45267 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care, Warren 1225, Boston, MA 01460 USA.; Branson, RD (reprint author), Univ Cincinnati, 231 Albert Sabin Way,ML 0558, Cincinnati, OH 45267 USA. EM rkacmarek@partners.org; Richard.branson@uc.edu NR 91 TC 2 Z9 2 U1 0 U2 1 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 JUN PY 2016 VL 61 IS 6 SI SI BP 854 EP 864 DI 10.4187/respcare.04887 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DN7CU UT WOS:000377233700022 PM 27235318 ER PT J AU Jung, Y Klein, OJ Wang, HQ Evans, CL AF Jung, Yookyung Klein, Oliver J. Wang, Hequn Evans, Conor L. TI Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT SO SCIENTIFIC REPORTS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; HUMAN OVARIAN-CANCER; IN-VITRO; SPHEROIDS; PDT AB Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation. C1 [Jung, Yookyung; Klein, Oliver J.; Wang, Hequn; Evans, Conor L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, CNY149-3,13th St, Charlestown, MA USA. RP Evans, CL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, CNY149-3,13th St, Charlestown, MA USA. EM evans.conor@mgh.harvard.edu FU National Institutes of Health (NIH) Innovative Molecular Analysis Technologies (IMAT) program [R21 CA155535]; NIH Director's New Innovator Award [DP2 OD007096]; Canadian Institute of Health Research FX The authors would like to acknowledge the members of Evans group for their assistance in editing this manuscript, in particular Sam Osseiran, Nick Nowell, and Lauren Austin. This research was support by the National Institutes of Health (NIH) Innovative Molecular Analysis Technologies (IMAT) program, grant number R21 CA155535, and the NIH Director's New Innovator Award, grant number DP2 OD007096. Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. Hequn Wang would like to acknowledge the funding support from Canadian Institute of Health Research. NR 27 TC 1 Z9 1 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUN 1 PY 2016 VL 6 AR 27017 DI 10.1038/srep27017 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN6CP UT WOS:000377159500001 PM 27248849 ER PT J AU Wang, SJ Huttmann, G Scholzen, T Zhang, ZX Vogel, A Hasan, T Rahmanzadeh, R AF Wang, Sijia Huettmann, Gereon Scholzen, Thomas Zhang, Zhenxi Vogel, Alfred Hasan, Tayyaba Rahmanzadeh, Ramtin TI A light-controlled switch after dual targeting of proliferating tumor cells via the membrane receptor EGFR and the nuclear protein Ki-67 SO SCIENTIFIC REPORTS LA English DT Article ID DRUG-DELIVERY SYSTEMS; OVARIAN-CANCER; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; LIPOSOME; THERAPY; IMMUNOLIPOSOMES; IMMUNOTHERAPY AB Using nanotechnology for optical manipulation of molecular processes in cells with high spatial and temporal precision promises new therapeutic options. Especially tumor therapy may profit as it requires a combination of both selectivity and an effective cell killing mechanism. Here we show a dual targeting approach for selective and efficient light-controlled killing of cells which are positive for epidermal growth factor receptor (EGFR) and Ki-67. Liposomes with the covalently linked EGFR antibody Erbitux enabled selective uptake of FITC-labeled Ki-67 antibody TuBB-9 in EGFR-positive cells pre-loaded with the photoactive dye BPD. After irradiation at 690 nm, BPD disrupted the endosomal membranes and delivered the antibodies to the nucleoli of the cells. The second irradiation at 490 nm activated the FITC-labeled TuBB-9, which caused inactivation of the Ki-67 protein and subsequent cell death via apoptosis. Efficient cell killing was possible at nanomolar concentrations of TuBB-9 due to the effective transport by immune liposomes and the high efficacy of the Ki-67 light-inactivation. Delivery of the liposomal constructs and cell destruction correlated well with the EGFR expression pattern of different cell lines (HeLa, OVCAR-5, MCF-7, and human fibroblasts), demonstrating an excellent selectivity. C1 [Wang, Sijia; Zhang, Zhenxi] Xi An Jiao Tong Univ, Inst Biomed Analyt Technol & Instrumentat, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China. [Wang, Sijia; Huettmann, Gereon; Vogel, Alfred; Rahmanzadeh, Ramtin] Med Univ Lubeck, Inst Biomed Opt, Peter Monnik Weg 4, D-23562 Lubeck, Germany. [Scholzen, Thomas] Res Ctr Borstel, Dept Immunol & Cell Biol, Pk Allee 22, D-23845 Borstel, Germany. [Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. RP Rahmanzadeh, R (reprint author), Med Univ Lubeck, Inst Biomed Opt, Peter Monnik Weg 4, D-23562 Lubeck, Germany. EM rahmanzadeh@bmo.uni-luebeck.de RI Rahmanzadeh, Ramtin/L-7941-2016; Vogel, Alfred/D-9852-2011; Huttmann, Gereon/A-9072-2012; OI Scholzen, Thomas/0000-0002-5556-9144 FU German Research Foundation (DFG) [Ra1771/3-1]; National Natural Science Foundation of China (NSFC) [61120106013]; National Cancer Institute of the National Institutes of Health [R01CA160998] FX Research reported in this publication was supported by the German Research Foundation (DFG, no. Ra1771/3-1), The National Natural Science Foundation of China (NSFC, no. 61120106013) and by the National Cancer Institute of the National Institutes of Health under award number R01CA160998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 32 TC 1 Z9 1 U1 11 U2 21 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 JUN 1 PY 2016 VL 6 AR 27032 DI 10.1038/srep27032 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DN6CU UT WOS:000377160000001 PM 27246531 ER PT J AU Tsai, J Link, B Rosenheck, RA Pietrzak, RH AF Tsai, Jack Link, Bruce Rosenheck, Robert A. Pietrzak, Robert H. TI Homelessness among a nationally representative sample of US veterans: prevalence, service utilization, and correlates SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Homelessness; Veterans; Epidemiology; Health services ID RISK-FACTORS; UNITED-STATES; UNINSURED VETERANS; 5-YEAR PREVALENCE; MENTAL-ILLNESS; HEALTH; MANAGEMENT; LIFETIME; NEEDS; CARE AB To examine the prevalence of lifetime homelessness among veterans and use of Veterans Affairs (VA) homeless services, as well as their association with sociodemographic and clinical characteristics. A nationally representative sample of 1533 US veterans was surveyed July-August 2015. Among all veterans, 8.5 % reported any lifetime homelessness in their adult life, but only 17.2 % of those reported using VA homeless services. Prevalence of homelessness and VA homeless service use did not significantly differ by gender. Being low income, aged 35-44, and having poor mental and physical health were each independently associated with lifetime homelessness. Veterans who were White or lived in rural areas were significantly less likely to have used VA homeless services. Homelessness remains a substantial problem across different generations of veterans. The low reported uptake of VA homeless services suggests there are barriers to care in this population, especially for veterans who live in rural areas. Governmental resources dedicated to veteran homelessness should be supported, and obtaining accurate prevalence estimates are important to tracking progress over time. C1 [Tsai, Jack; Rosenheck, Robert A.] New England Mental Illness Res Educ & Clin Ctr, US Dept Vet Affairs, 950 Campbell Ave,151D, West Haven, CT 06516 USA. [Tsai, Jack; Rosenheck, Robert A.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Link, Bruce] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Link, Bruce] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pietrzak, Robert H.] Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, West Haven, CT 06516 USA. RP Tsai, J (reprint author), New England Mental Illness Res Educ & Clin Ctr, US Dept Vet Affairs, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu NR 47 TC 0 Z9 0 U1 4 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUN PY 2016 VL 51 IS 6 BP 907 EP 916 DI 10.1007/s00127-016-1210-y PG 10 WC Psychiatry SC Psychiatry GA DN7IQ UT WOS:000377249200014 PM 27075492 ER PT J AU Atlas, SJ AF Atlas, Steven J. TI Point of View SO SPINE LA English DT Article ID LOW-BACK-PAIN; RANDOMIZED-CONTROLLED-TRIALS; LUMBAR FUSION; DEGENERATIVE DISEASE; GUIDELINE UPDATE; SPINAL-FUSION; PERFORMANCE; STENOSIS; SURGERY C1 [Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUN PY 2016 VL 41 IS 11 BP 956 EP 957 DI 10.1097/BRS.0000000000001388 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DN2RA UT WOS:000376909500017 PM 26679878 ER PT J AU Khaleel, MA Bono, CM White, AP Wood, KB Harris, MB Wagner, K Zurakowski, D McGuire, KJ AF Khaleel, Mohammed A. Bono, Christopher M. White, Andrew P. Wood, Kirkham B. Harris, Mitchel B. Wagner, Katiri Zurakowski, David McGuire, Kevin J. TI Defining Avoidable and Unavoidable Complications in Spine Surgery: A Survey-based Study of Spine Fellowship Directors SO SPINE LA English DT Article DE Centers for Medicare and Medicaid; expert consensus; hospital-acquired conditions; never events; orthopedic spine surgeons; patient outcomes and quality improvement; provider reimbursement; spine surgery complications; surgical site infections; survey of spine fellowship directors; unavoidable complication ID INFECTION AB Study Design.A cross-sectional survey of orthopedic spine surgery fellowship directors in the United States.Objective.The aim of this study was to investigate whether consensus exists with respect to spine-related adverse events and certain hospital-acquired conditions (HACs) or never events.Summary of Background Data.As part of a broad effort to improve health care outcomes, providers are no longer reimbursed for HACs, which are deemed avoidable. Although some HACs are unquestionably preventable with proper quality control measures, research suggests that even scrupulous adherence to evidence-based guidelines cannot eliminate others.Methods.Surveys were distributed via email and post. Participants rated 27 HACs and selected spine-specific events on an ordinal scale. Interobserver reliability was assessed among all 46 spine directors (respondents) using the intraclass correlation coefficient (ICC), based on a two-way random effects model, assuming that the participants were a representative population sample of spine surgeons. Multivariable linear regression analyses were performed on each of the 27 complications to identify potential demographic factors that could be associated with variation among respondents in their ratings of avoidable to unavoidable.Results.Forty-six fellowship directors responded, of whom 98% were orthopedic spine surgeons. The majority (80.4%) of respondents had greater than 10 years' experience as a spine surgeon, and 66.7% had an annual surgical volume >201 cases. The multivariable linear regression analyses found that demographic factors were not predictive of the directors' ratings. The complications thought to be completely avoidable (median scores 1) included Incompatible blood, Retained foreign object, and Wrong level surgery. The HAC considered least avoidable was Site infection with risk factors (median score 8). Among 17 spine-specific complications, L4-L5 disc re-herniation within 3 months (median score 9) was considered least avoidable.Conclusion.This survey suggests that orthopedic spine surgeons consider most never events neither avoidable nor unavoidable. There is strong consensus only about the HACs resulting from obvious medical error.Level of Evidence: 4 C1 [Khaleel, Mohammed A.] Univ Texas SW Med Ctr Dallas, Dept Orthopaed Surg, Dallas, TX 75390 USA. [Bono, Christopher M.; Harris, Mitchel B.] Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. [White, Andrew P.; Wagner, Katiri; McGuire, Kevin J.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA. [Wood, Kirkham B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Zurakowski, David] Boston Childrens Hosp, Dept Anaesthesia, Boston, MA USA. RP McGuire, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA. EM KJMcGuir@bidmc.harvard.edu NR 7 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 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUN PY 2016 VL 41 IS 11 BP 958 EP 962 DI 10.1097/BRS.0000000000001384 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DN2RA UT WOS:000376909500018 PM 26656050 ER PT J AU Morotti, A Phuah, CL Anderson, CD Jessel, MJ Schwab, K Ayres, AM Pezzini, A Padovani, A Gurol, ME Viswanathan, A Greenberg, SM Goldstein, JN Rosand, J AF Morotti, Andrea Phuah, Chia-Ling Anderson, Christopher D. Jessel, Michael J. Schwab, Kristin Ayres, Alison M. Pezzini, Alessandro Padovani, Alessandro Gurol, M. Edip Viswanathan, Anand Greenberg, Steven M. Goldstein, Joshua N. Rosand, Jonathan TI Leukocyte Count and Intracerebral Hemorrhage Expansion SO STROKE LA English DT Article DE hematoma expansion; inflammation; intracerebral hemorrhage; leukocytes; monocytes; neutrophils ID PREDICTS HEMATOMA EXPANSION; TISSUE FACTOR; NEUROPROTECTIVE STRATEGIES; MONOCYTE COUNT; CASE-FATALITY; COAGULATION; INFLAMMATION; MECHANISMS; NEUTROPHILS; DETERIORATION AB Background and Purpose-Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding after acute ICH. Methods-Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up computed tomographic scan available and automated complete white blood cell count performed within 48 hours from onset. Baseline and follow-up hematoma volumes were calculated with semiautomated software, and hematoma expansion was defined as volume increase >30% or 6 mL. The association between white blood cell count and ICH expansion was investigated with multivariate logistic regression. Results-A total of 1302 subjects met eligibility criteria (median age, 75 years; 55.8% men), of whom 207 (15.9%) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (odds ratio for 1000 cells increase, 0.91; 95% confidence interval, 0.86-0.96; P=0.001). The risk of hematoma expansion was inversely associated with neutrophil count (odds ratio, 0.90; 95% confidence interval, 0.85-0.96; P=0.001) and directly associated with monocyte count (odds ratio, 2.71; 95% confidence interval, 1.08-6.83; P=0.034). There was no association between lymphocyte count and ICH expansion (odds ratio, 0.96; 95% confidence interval, 0.79-1.17; P=0.718). Conclusions-Higher admission white blood cell count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade after acute ICH. C1 [Morotti, Andrea; Pezzini, Alessandro; Padovani, Alessandro] Univ Brescia, Dept Clin & Expt Sci, Neurol Unit, Brescia, Italy. [Morotti, Andrea; Phuah, Chia-Ling; Anderson, Christopher D.; Jessel, Michael J.; Goldstein, Joshua N.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Morotti, Andrea; Phuah, Chia-Ling; Anderson, Christopher D.; Jessel, Michael J.; Schwab, Kristin; Ayres, Alison M.; Gurol, M. Edip; Viswanathan, Anand; Greenberg, Steven M.; Goldstein, Joshua N.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Morotti, A (reprint author), Massachusetts Gen Hosp, Hemorrhag Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM amorotti@mgh.harvard.edu RI Gurol, Edip/J-2279-2014; OI Gurol, Edip/0000-0002-2169-4457; Anderson, Christopher/0000-0002-0053-2002 FU National Institute of Neurological Disorders and Stroke [5R01NS073344, K23AG02872605, K23 NS086873, R01NS059727] FX This study was supported by the following awards from the National Institute of Neurological Disorders and Stroke: 5R01NS073344, K23AG02872605, K23 NS086873, and R01NS059727. NR 42 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 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2016 VL 47 IS 6 BP 1473 EP 1478 DI 10.1161/STROKEAHA.116.013176 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DN4MI UT WOS:000377040800019 PM 27103016 ER PT J AU Razavinasab, M Moazzami, K Shabani, M AF Razavinasab, Moazamehosadat Moazzami, Kasra Shabani, Mohammad TI Maternal mobile phone exposure alters intrinsic electrophysiological properties of CAI pyramidal neurons in rat offspring SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Mobile phone exposure; pregnancy; neural excitability; offspring; pyramidal neurons; rat ID MHZ ELECTROMAGNETIC-FIELD; WHOLE-BODY EXPOSURE; INDUCED NEUROTOXICITY; PURKINJE NEURONS; K+ CURRENT; IN-VIVO; MEMORY; CELLS; PERFORMANCE; ACTIVATION AB Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology. Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. C1 [Razavinasab, Moazamehosadat; Shabani, Mohammad] Kerman Univ Med Sci, Inst Neuropharmacol, Kerman Neurosci Res Ctr, Kerman 76198, Iran. [Moazzami, Kasra] Harvard Univ, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Shabani, M (reprint author), Kerman Univ Med Sci, Inst Neuropharmacol, Kerman Neurosci Res Ctr, Kerman 76198, Iran. EM shabani@kmu.ac.ir FU Kerman University of Medical Science FX The present article is the product of a research project that was approved by the Kerman University of Medical Science as a grant for the MsC thesis. The author would like to appreciate the heads of Kimia Mobin Company (Mobin Aghpour) for device design. NR 33 TC 0 Z9 0 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 EI 1477-0393 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2016 VL 32 IS 6 BP 968 EP 979 DI 10.1177/0748233714525497 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA DM9IS UT WOS:000376679500002 PM 24604340 ER PT J AU Jimenez, DE Burrows, K Aschbrenner, K Barre, LK Pratt, SI Alegria, M Bartels, SJ AF Jimenez, Daniel E. Burrows, Kimberly Aschbrenner, Kelly Barre, Laura K. Pratt, Sarah I. Alegria, Margarita Bartels, Stephen J. TI Health behavior change benefits: Perspectives of Latinos with serious mental illness SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE health behavior change; Latino; serious mental illness ID PHYSICAL-ACTIVITY; UNITED-STATES; AMERICAN WOMEN; CULTURAL BELIEFS; DEPRESSION; CARE; INTERVENTION; ATTITUDES; ADULTS; DISPARITIES AB The objective of this study was to explore the perceived benefits of engaging in health behavior change from the viewpoint of overweight and obese Latinos with severe mental illness (SMI) enrolled in the U.S. Qualitative, semistructured interviews were conducted with 20 obese Latinos with SMI who were enrolled in a randomized trial evaluating the effectiveness of a motivational health promotion intervention adapted for persons with SMI. Overweight and obese Latino participants believed that engaging in health behavior change would have both physical and mental health benefits, including chronic disease management, changes in weight and body composition, and increased self-esteem. Interventions that explicitly link physical activity and healthy eating to improvements in mental health and well-being may motivate Latinos with SMI to adopt health behavior change. C1 [Jimenez, Daniel E.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Psychiat, Coral Gables, FL 33124 USA. [Burrows, Kimberly] New Hampshire Hosp, Inpatient Stabilizat Unit, Concord, NH 03301 USA. [Aschbrenner, Kelly; Pratt, Sarah I.] Geisel Sch Med Dartmouth, Dept Psychiat, Psychiat, Hanover, NH 03755 USA. [Barre, Laura K.] Cornell Univ, Coll Human Ecol, Div Nutr Sci, Ithaca, NY 14853 USA. [Alegria, Margarita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bartels, Stephen J.] Geisel Sch Med Dartmouth, Psychiat, Hanover, NH 03755 USA. [Bartels, Stephen J.] Geisel Sch Med Dartmouth, Community & Family Med, Dartmouth Med Sch, Hanover, NH 03755 USA. RP Jimenez, DE (reprint author), 1695 NW 9th Ave,Suite 3208, Miami, FL 33136 USA. EM dej18@miami.edu FU National Institute of Mental Health [R01 MH078052-S1, K23 MH098025] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by grants R01 MH078052-S1 and K23 MH098025 from the National Institute of Mental Health. NR 48 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 1363-4615 EI 1461-7471 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD JUN PY 2016 VL 53 IS 3 BP 313 EP 329 DI 10.1177/1363461516632388 PG 17 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA DN6TH UT WOS:000377208600003 PM 26873582 ER PT J AU Adler, JT Yeh, H Markmann, JF Axelrod, DA AF Adler, Joel T. Yeh, Heidi Markmann, James F. Axelrod, David A. TI Is Donor Service Area Market Competition Associated With Organ Procurement Organization Performance? SO TRANSPLANTATION LA English DT Article ID LIVER-TRANSPLANTATION; US VETERANS; RISK INDEX; ACCESS; CARE; CONSOLIDATION; SURVIVAL; DONATION; PATTERNS; WAITLIST AB Background. Organ procurement organizations (OPOs) are currently evaluated on donation rates and number of organs per donor. However, there is significant variability in market characteristics which affect transplant programs' donor organ acceptance practices and OPOs' ability to successfully place higher risk organs. The impact of transplant market characteristics on OPO performance metrics has not been evaluated. Methods. The OPO performance measures were correlated annually with the Herfindahl Hirschman Index, a standard measure of market competition for centers within the OPO donor service areas from 2003 to 2011. Results. More competitive donor service areas were associated with increased number of donors (P = 0.01) and eligible deaths (P < 0.001). Market competition was associated with increased use of high Donor Risk Index for kidney (P = 0.03) and liver (P = 0.01) allografts. The OPOs with increased competition in liver transplant also were noted to have a higher donor conversion rate (P < 0.001), more donors per million population (P < 0.001), and a higher utilization rate for liver allografts (P= 0.007). Conclusions. These data suggest that proposals to increase district size to increase competition among transplant programs could result in improved organ utilization over time by incentivizing the use of marginal donor organs and increasing access to transplantation. C1 [Adler, Joel T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [Adler, Joel T.; Yeh, Heidi; Markmann, James F.; Axelrod, David A.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Yeh, Heidi; Markmann, James F.] Harvard Univ, Sch Med, Boston, MA USA. [Axelrod, David A.] Dartmouth Hitchcock Med Ctr, Sect Transplant Surg, Lebanon, NH 03766 USA. RP Axelrod, DA (reprint author), One Med Ctr Dr, Lebanon, NH 03756 USA. EM david.a.axelrod@hitchcock.org OI Adler, Joel/0000-0001-8190-3444 NR 28 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUN PY 2016 VL 100 IS 6 BP 1349 EP 1355 DI 10.1097/TP.0000000000000979 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DN5QZ UT WOS:000377126600031 PM 26516674 ER PT J AU Gaudet, S Miller-Jensen, K AF Gaudet, Suzanne Miller-Jensen, Kathryn TI Redefining Signaling Pathways with an Expanding Single-Cell Toolbox SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID NF-KAPPA-B; INDIVIDUAL LIVING CELLS; EPIDERMAL-GROWTH-FACTOR; ERK ACTIVATION; IN-VIVO; INFORMATION-TRANSMISSION; P53 TETRAMERIZATION; KINASE-ACTIVITIES; TEMPORAL CONTROL; FRET BIOSENSORS AB Genetically identical cells respond heterogeneously to uniform environmental stimuli. Consequently, investigating the signaling networks that control these cell responses using 'average' bulk cell measurements can obscure underlying mechanisms and misses information emerging from cell-to-cell variability. Here we review recent technological advances including live-cell fluorescence imaging-based approaches and microfluidic devices that enable measurements of signaling networks, dynamics, and responses in single cells. We discuss how these single-cell tools have uncovered novel mechanistic insights for canonical signaling pathways that control cell proliferation (ERK), DNA-damage responses (p53), and innate immune and stress responses (NF-kappa B). Future improvements in throughput and multiplexing, analytical pipelines, and in vivo applicability will all significantly expand the biological information gained from single-cell measurements of signaling pathways. C1 [Gaudet, Suzanne] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Gaudet, Suzanne] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Miller-Jensen, Kathryn] Yale Univ, Dept Biomed Engn, New Haven, CT 06520 USA. [Miller-Jensen, Kathryn] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. RP Gaudet, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Gaudet, S (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.; Gaudet, S (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.; Miller-Jensen, K (reprint author), Yale Univ, Dept Biomed Engn, New Haven, CT 06520 USA.; Miller-Jensen, K (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. EM suzanne_gaudet@hms.harvard.edu; kathryn.miller-jensen@yale.edu FU National Institutes of Health [R01-GM104247]; National Science Foundation [CBET-1264246, CBET-1454301]; Barr investigator award FX This work was supported by grants from the National Institutes of Health (R01-GM104247 to S.G.) and the National Science Foundation (CBET-1264246 and CBET-1454301 to K.M-J.) and a Barr investigator award (to S.G.). NR 71 TC 0 Z9 0 U1 6 U2 14 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JUN PY 2016 VL 34 IS 6 BP 458 EP 469 DI 10.1016/j.tibtech.2016.02.009 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DN1NW UT WOS:000376833700005 PM 26968612 ER PT J AU Shishehbor, MH Aronow, HD Bartholomew, JR Beckman, JA Froehlich, JB Lookstein, R Misra, S Roberts, AC Rosenfield, K Jaff, MR AF Shishehbor, Mehdi H. Aronow, Herbert D. Bartholomew, John R. Beckman, Joshua A. Froehlich, James B. Lookstein, Robert Misra, Sanjay Roberts, Anne C. Rosenfield, Kenneth Jaff, Michael R. TI Vascular specialist response to Medicare Evidence Development Coverage Advisory Committee (MEDCAC) panel on peripheral artery disease of the lower extremities SO VASCULAR MEDICINE LA English DT Article ID CRITICAL LIMB ISCHEMIA; INTERMITTENT CLAUDICATION; NUTRITION EXAMINATION; COST-EFFECTIVENESS; NATIONAL-HEALTH; REVASCULARIZATION; MANAGEMENT; EXERCISE; AMPUTATION; METAANALYSIS C1 [Shishehbor, Mehdi H.; Bartholomew, John R.] Cleveland Clin, Cleveland, OH 44195 USA. [Aronow, Herbert D.] Brown Univ, Providence, RI 02912 USA. [Beckman, Joshua A.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lookstein, Robert] Mt Sinai, New York, NY USA. [Misra, Sanjay] Mayo Clin, Rochester, MN USA. [Roberts, Anne C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Rosenfield, Kenneth; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shishehbor, MH (reprint author), Cleveland Clin, Inst Heart & Vasc, 9500 Euclid Ave,J3-5, Cleveland, OH 44195 USA. EM shishem@ccf.org OI Beckman, Joshua/0000-0001-8332-8439 NR 32 TC 1 Z9 1 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD JUN PY 2016 VL 21 IS 3 BP 281 EP 286 DI 10.1177/1358863X16636955 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN5IW UT WOS:000377101000012 PM 27063017 ER PT J AU Lather, H Gornik, H Olin, JW Gu, XK Heidt, S Sharma, A Gray, B Jaff, M Froehlich, J AF Lather, Henry Gornik, Heather Olin, Jeffrey W. Gu, Xiaokui Heidt, Steven Sharma, Aditya Gray, Bruce Jaff, Michael Froehlich, James TI Prevalence of Intracranial Aneurysms in Women with Fibromuscular Dysplasia: A Report from the United States Registry for Fibromuscular Dysplasia SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Lather, Henry] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Gornik, Heather] Cleveland Clin Fdn, Cleveland, OH USA. [Olin, Jeffrey W.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Gu, Xiaokui; Heidt, Steven; Froehlich, James] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Sharma, Aditya] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Gray, Bruce] Vasc Hlth Alliance, Greenville, SC USA. [Jaff, Michael] Massachusetts Gen Hosp, Fireman Vasc Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD JUN PY 2016 VL 21 IS 3 MA YIA 4 BP 291 EP 291 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN5IW UT WOS:000377101000017 ER PT J AU Joseph, L Sonny, A AF Joseph, Lee Sonny, Abraham TI National Trends in Outcomes After Elective Pulmonary Endarterectomy SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Joseph, Lee] Univ Iowa, Iowa City, IA USA. [Sonny, Abraham] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD JUN PY 2016 VL 21 IS 3 MA 5 BP 293 EP 293 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN5IW UT WOS:000377101000023 ER PT J AU Weinberg, I AF Weinberg, Ido TI An Automated Reminder System to Improve Inferior Vena Cava Filter Retrieval SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 [Weinberg, Ido] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD JUN PY 2016 VL 21 IS 3 MA 6 BP 294 EP 294 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DN5IW UT WOS:000377101000024 ER PT J AU Suzuki, J Ellison, TV Connery, HS Surber, C Renner, JA AF Suzuki, Joji Ellison, Tatyana V. Connery, Hilary S. Surber, Charles Renner, John A. TI Training in Buprenorphine and Office-Based Opioid Treatment: A Survey of Psychiatry Residency Training Programs SO ACADEMIC PSYCHIATRY LA English DT Article DE Psychiatry residents; Opioid dependence; Office-based opioid treatment; Buprenorphine ID UNITED-STATES; USE DISORDERS; ADDICTION AB Objective Psychiatrists are well suited to provide office-based opioid treatment (OBOT), but the extent to which psychiatry residents are exposed to buprenorphine training and OBOT during residency remains unknown. Methods Psychiatry residency programs in the USA were recruited to complete a survey. Results Forty-one programs were included in the analysis for a response rate of 23.7 %. In total, 75.6 % of the programs currently offered buprenorphine waiver training and 78.1 % provided opportunities to treat opioid dependence with buprenorphine under supervision. Programs generally not only reported favorable beliefs about OBOT and buprenorphine waiver training but also reported numerous barriers. Conclusions The majority of psychiatry residency training programs responding to this survey offer buprenorphine waiver training and opportunities to treat opioid-dependent patients, but numerous barriers continue to be cited. More research is needed to understand the role residency training plays in impacting future practice of psychiatrists. C1 [Suzuki, Joji] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Connery, Hilary S.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. [Ellison, Tatyana V.] Kaiser Permanente So Calif, Ontario, CA USA. [Surber, Charles] Univ Michigan, Ann Arbor, MI 48109 USA. [Renner, John A.] VA Boston HealthCare Syst, Boston, MA USA. RP Suzuki, J (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jsuzuki2@partners.org FU Harvard Medical School Eleanor and Miles Shore Fellowship Program for Scholars in Medicine; National Institute of Drug Abuse [U10DA15831] FX This study was funded in part by Harvard Medical School Eleanor and Miles Shore Fellowship Program for Scholars in Medicine (JS) and grants U10DA15831 from the National Institute of Drug Abuse (HC). NR 12 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1042-9670 EI 1545-7230 J9 ACAD PSYCHIATR JI Acad. Psych. PD JUN PY 2016 VL 40 IS 3 BP 498 EP 502 DI 10.1007/s40596-015-0313-1 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA DM3LV UT WOS:000376248800022 PM 26017618 ER PT J AU Mbugua, KK Holmes, MJ Cotton, MF Ratai, EM Little, F Hess, AT Dobbels, E Van der Kouwe, AJW Laughton, B Meintjes, EM AF Mbugua, Kenneth K. Holmes, Martha J. Cotton, Mark F. Ratai, Eva-Maria Little, Francesca Hess, Aaron T. Dobbels, Els Van der Kouwe, Andre J. W. Laughton, Barbara Meintjes, Ernesta M. TI HIV-associated CD4(+)/CD8(+) depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy SO AIDS LA English DT Article DE antiretroviral therapy; basal ganglia; choline; cluster of differentiation 4/8 (CD4(+)/CD8(+)); creatine; glutamate; HIV; magnetic resonance spectroscopy; metabolites; N-acetyl-aspartate ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN-IMMUNODEFICIENCY-VIRUS; BRAIN-METABOLITES; INFECTED CHILDREN; DEMENTIA; NEURODEVELOPMENT; ENCEPHALOPATHY; ABNORMALITIES; ADOLESCENTS; ACTIVATION AB Objective: Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy. Design: Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development. Methods: Basal ganglia metabolite concentrations were assessed in thirty-eight 5-yearold HIV-infected children previously participating in a randomized trial comparing early limited ART to deferred continuous ART, as well as 15 uninfected controls (12 HIV exposed). Metabolite levels were compared between 26 infected children who initiated ART at/before 12 weeks and 12 who initiated afterward, and were correlated with clinical HIV and treatment-related measures. Results: HIV-infected children initiating ART after 12 weeks had lower creatine, choline and glutamate (P<0.05) than those initiating ART at/before 12 weeks. The CD4(+)/CD8(+) ratio at baseline correlated with N-acetyl-aspartate (r = 0.56, P = 0.003) and choline (r = 0.36, P = 0.03) at 5 years, irrespective of treatment regimen and ART interruption. In comparison with uninfected controls, 80% of whomwere HIV-exposed in utero, children on early treatment had higher N-acetyl-aspartate (P = 0.006) and choline (P = 0.03). Conclusions: Despite early ART (<12 weeks), low baseline CD4(+)/CD8(+) predicts brain metabolite levels in later childhood. Also, HIV exposure and antiretroviral exposure for preventing vertical HIV transmission may hinder metabolite health, but needs further investigation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Mbugua, Kenneth K.; Holmes, Martha J.; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7935 Cape Town, South Africa. [Cotton, Mark F.; Dobbels, Els; Laughton, Barbara] Tygerberg Childrens Hosp, Dept Paediat & Child Hlth, Childrens Infect Dis Clin Res Unit, Cape Town, South Africa. [Cotton, Mark F.; Dobbels, Els; Laughton, Barbara] Univ Stellenbosch, Fac Med & Hlth Sci, Cape Town, South Africa. [Ratai, Eva-Maria; Van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ratai, Eva-Maria; Van der Kouwe, Andre J. W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Little, Francesca] Univ Cape Town, Fac Sci, Dept Stat Sci, ZA-7935 Cape Town, South Africa. [Hess, Aaron T.] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res OCMR, Oxford, England. RP Mbugua, KK (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Human Biol, Observ, ZA-7935 Cape Town, South Africa. EM kenneth.mbugua@gmail.com RI Laughton, Barbara/Q-3496-2016 OI Laughton, Barbara/0000-0001-7260-7723 FU NRF/DST South African Research Chairs Initiative; US National Institute of Allergy and Infectious Diseases (NIAID) through the CIPRA network [U19 AI53217]; NIH [R01HD071664, R21MH 096559]; NRF [CPR20110614000019421]; South African Medical Research Council (SAMRC); Department of Health of the Western Cape; Department of Health of the Gauteng; Department of Health of the South Africa; ViiV Healthcare/GlaxoSmithKline plc FX Support was provided by the NRF/DST South African Research Chairs Initiative; US National Institute of Allergy and Infectious Diseases (NIAID) through the CIPRA network, Grant U19 AI53217; NIH grants R01HD071664 and R21MH 096559; NRF grant CPR20110614000019421, and the South African Medical Research Council (SAMRC). The Departments of Health of the Western Cape and Gauteng, South Africa and ViiV Healthcare/GlaxoSmithKline plc provided additional support for the CHER study. NR 36 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2016 VL 30 IS 9 BP 1353 EP 1362 DI 10.1097/QAD.0000000000001082 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DM6JH UT WOS:000376457300005 PM 26959509 ER PT J AU Palar, K Laraia, B Tsai, AC Johnson, MO Weiser, SD AF Palar, Kartika Laraia, Barbara Tsai, Alexander C. Johnson, Mallory O. Weiser, Sheri D. TI Food insecurity is associated with HIV, sexually transmitted infections and drug use among men in the United States SO AIDS LA English DT Article DE drug use; food insecurity; herpes; HIV; men; sexually transmitted infections ID RISK BEHAVIORS; SOCIAL SUPPORT; MODIFYING ROLE; RURAL UGANDA; LOW-INCOME; BLACK-MEN; HIV/AIDS; SEX; INDIVIDUALS; WOMEN AB Objective: To examine the population-level association between food insecurity, HIV risk factors, and HIV serostatus among men, the group representing the majority of HIV diagnoses in the United States. Design: Cross-sectional secondary data analysis using the National Health and Nutrition Examination Survey 1999-2012, a nationally representative survey of the civilian noninstitutionalized US population. Methods: Logistic regression with design weights and complex survey commands was used to estimate nationally representative associations between food insecurity and HIV serostatus (primary outcome), herpes simplex virus 2, self-reported sexually transmitted infections (STIs), and past-year illicit drug use among men, adjusting for potential confounders. Food security was measured using the 18-item House hold Food Security Survey. Results: We analyzed data for 9150 men representing 61 million individuals in the United States. Unadjusted HIV prevalence was 1.5% among food insecure men, compared with 0.4% among food secure men (P<0.001). In adjusted models, food insecure men had over two times higher odds of HIVseropositivity compared with food securemen [ adjusted odds ratio (AOR) = 2.10; 95% confidence interval (CI) 1.01-4.37; P<0.05]. Food insecurity was associated with higher odds of herpes simplex virus 2 seropositivity (AOR = 1.28; 95% CI 1.04-1.57; P<0.05), self-reported STIs (AOR = 1.54; 95% CI 1.08-2.20; P<0.05), and illicit drug use (AOR = 1.57; 95% CI 1.14-2.15; P<0.01). Results were robust to sensitivity analyses restricted to lower incomes. Conclusion: Food insecurity is associated with prevalent HIV, STIs, and illicit drug use among men in the United States. Further research is needed to establish whether and through what mechanisms improved food security may help prevent new HIV infections. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Palar, Kartika; Weiser, Sheri D.] Univ Calif San Francisco, Dept Med, Div HIV Infect Dis ID & Global Med, San Francisco, CA 94143 USA. [Laraia, Barbara] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA. [Johnson, Mallory O.; Weiser, Sheri D.] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. RP Palar, K (reprint author), Univ Calif San Francisco, Dept Med, Div HIV Infect Dis ID & Global Med, San Francisco, CA 94143 USA. EM kartika.palar@ucsf.edu FU NIH/NIDDK [K01DK107335]; AHRQ [T32HS00046]; NIH/NIMH [K23MH096620, R01MH095683]; NIH/NIDA [K24DA03703] FX The authors acknowledge the following sources of salary support: NIH/NIDDK K01DK107335 and AHRQ T32HS00046 (K.P.), NIH/NIMH K23MH096620 (A.C.T.), NIH/NIMH R01MH095683 (S.D.W.), NIH/NIDA K24DA03703 (M.J.). NR 51 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2016 VL 30 IS 9 BP 1457 EP 1465 DI 10.1097/QAD.0000000000001095 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DM6JH UT WOS:000376457300016 PM 26990632 ER PT J AU Panchal, H Paholpak, P Lee, G Carr, A Barsuglia, JP Mather, M Jimenez, E Mendez, MF AF Panchal, Hemali Paholpak, Pongsatorn Lee, Grace Carr, Andrew Barsuglia, Joseph P. Mather, Michelle Jimenez, Elvira Mendez, Mario F. TI Neuropsychological and Neuroanatomical Correlates of the Social Norms Questionnaire in Frontotemporal Dementia Versus Alzheimer's Disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE social norms; behavioral variant frontotemporal dementia; anterior temporal lobe Alzheimer's disease; tensor-based morphometry ID ANTERIOR TEMPORAL-LOBES; BEHAVIORAL VARIANT; BRAIN; COGNITION; LESIONS AB Traditional neuropsychological batteries may not distinguish early behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) without the inclusion of a social behavioral measure. We compared 33 participants, 15 bvFTD, and 18 matched patients with early-onset AD (eAD), on the Social Norms Questionnaire (SNQ), neuropsychological tests and 3-dimensional T1-weighted magnetic resonance imaging (MRI). The analyses included correlations of SNQ results (total score, overendorsement or overadhere errors, and violations or break errors) with neuropsychological results and tensor-based morphometry regions of interest. Patients with BvFTD had significantly lower SNQ total scores and higher overadhere errors than patients with eAD. On neuropsychological measures, the SNQ total scores correlated significantly with semantic knowledge and the overadhere subscores with executive dysfunction. On MRI analysis, the break subscores significantly correlated with lower volume of lateral anterior temporal lobes (aTL). The results also suggest that endorsement of social norm violations corresponds to the role of the right aTL in social semantic knowledge. C1 [Panchal, Hemali; Paholpak, Pongsatorn; Carr, Andrew; Barsuglia, Joseph P.; Mather, Michelle; Jimenez, Elvira; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Panchal, Hemali; Paholpak, Pongsatorn; Mather, Michelle; Jimenez, Elvira; Mendez, Mario F.] Dept Neurol, Los Angeles, CA USA. [Paholpak, Pongsatorn] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Paholpak, Pongsatorn] Khon Kaen Univ, Dept Psychiat, Khon Khaen, Thailand. [Lee, Grace] Sch Behav Hlth, Dept Psychol, Loma Linda, CA USA. [Jimenez, Elvira; Mendez, Mario F.] Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Panchal, H (reprint author), West Los Angeles VA Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Neurol, 11301 Wilshire Blvd,Mail Code 116AF, Los Angeles, CA 90073 USA. EM hpanchal@g.ucla.edu FU National Institute on Aging (NIA) [5R01AG034499]; VA GRECC Advanced Fellowship in Geriatrics FX This work was supported by grant 5R01AG034499 (Mendez) from the National Institute on Aging (NIA). J.P. Barsuglia was funded by the VA GRECC Advanced Fellowship in Geriatrics. NR 42 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 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD JUN PY 2016 VL 31 IS 4 BP 326 EP 332 DI 10.1177/1533317515617722 PG 7 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA DM4GO UT WOS:000376305200004 PM 26646114 ER PT J AU Vassy, JL Bates, DW Murray, MF AF Vassy, Jason L. Bates, David W. Murray, Michael F. TI Appropriateness: A Key to Enabling the Use of Genomics in Clinical Practice? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Vassy, Jason L.; Bates, David W.] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, 150 South Huntington Ave,152-G, Boston, MA 02115 USA. [Vassy, Jason L.; Bates, David W.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Boston, MA USA. [Murray, Michael F.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA. RP Vassy, JL (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, 150 South Huntington Ave,152-G, Boston, MA 02115 USA. EM jvassy@partners.org FU CSRD VA [IK2 CX001262] NR 9 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 JUN PY 2016 VL 129 IS 6 BP 551 EP 553 DI 10.1016/j.amjmed.2016.02.010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DM6YO UT WOS:000376499100020 PM 26965302 ER PT J AU Lopes, RD Rao, M Simon, DN Thomas, L Ansell, J Fonarow, GC Gersh, BJ Go, AS Hylek, EM Kowey, P Piccini, JP Singer, DE Chang, P Peterson, ED Mahaffey, KW AF Lopes, Renato D. Rao, Meena Simon, DaJuanicia N. Thomas, Laine Ansell, Jack Fonarow, Gregg C. Gersh, Bernard J. Go, Alan S. Hylek, Elaine M. Kowey, Peter Piccini, Jonathan P. Singer, Daniel E. Chang, Paul Peterson, Eric D. Mahaffey, Kenneth W. TI Triple vs Dual Antithrombotic Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Anticoagulants; Antiplatelets; Atrial fibrillation; Combined therapy; Coronary artery disease ID RANDOMIZED CONTROLLED-TRIAL; ORAL ANTICOAGULATION; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; CONCOMITANT ASPIRIN; INFORMED TREATMENT; STROKE PREVENTION; OUTCOMES REGISTRY; PREDICTING STROKE; WARFARIN USE AB BACKGROUND: The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease. METHODS: Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (n = 10,135), we analyzed outcomes in patients with coronary artery disease (n = 1827) according to treatment with triple antithrombotic therapy (defined as concurrent therapy with an oral anticoagulant, a thienopyridine, and aspirin) or dual antithrombotic therapy (comprising either an oral anticoagulant and one antiplatelet agent [OAC plus AA] or 2 antiplatelet drugs and no anticoagulant [DAP]). RESULTS: The use of triple antithrombotic therapy, OAC plus AA, and DAP at baseline was 8.5% (n = 155), 80.4% (n = 1468), and 11.2% (n = 204), respectively. Among patients treated with OAC plus AA, aspirin was the most common antiplatelet agent used (90%), followed by clopidogrel (10%) and prasugrel (0.1%). The use of triple antithrombotic therapy was not affected by patient risk of either stroke or bleeding. Patients treated with triple antithrombotic therapy at baseline were hospitalized for all causes (including cardiovascular) more often than patients on OAC plus AA (adjusted hazard ratio 1.75; 95% confidence interval, 1.35-2.26; P <. 0001) or DAP (hazard ratio 1.82; 95% confidence interval, 1.25-2.65; P = .0018). Rates of major bleeding or a combined cardiovascular outcome were not significantly different by treatment group. CONCLUSIONS: Choice of antithrombotic therapy in patients with atrial fibrillation and coronary artery disease was not affected by patient stroke or bleeding risks. Triple antithrombotic therapy-treated patients were more likely to be hospitalized for all causes than those on OAC plus AA or on DAP. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Lopes, Renato D.; Rao, Meena; Simon, DaJuanicia N.; Thomas, Laine; Piccini, Jonathan P.; Peterson, Eric D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Ansell, Jack] Hofstra North Shore LIJ Sch Med, New York, NY USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Gersh, Bernard J.] Mayo Clin, Coll Med, Rochester, MN USA. [Go, Alan S.] Kaiser Permanente, Oakland, CA USA. [Hylek, Elaine M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Kowey, Peter] Lankenau Inst Med Res, Wynnewood, PA USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, Paul] Janssen Pharmaceut, Raritan, NJ USA. [Mahaffey, Kenneth W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Lopes, RD (reprint author), Duke Clin Res Inst, Box 3850,2400 Pratt St,Room 0311, Durham, NC 27705 USA. EM renato.lopes@duke.edu FU Janssen Scientific Affairs, Raritan, NJ FX The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is sponsored by Janssen Scientific Affairs, Raritan, NJ. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. NR 29 TC 1 Z9 1 U1 2 U2 6 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 JUN PY 2016 VL 129 IS 6 BP 592 EP U197 DI 10.1016/j.amjmed.2015.12.026 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DM6YO UT WOS:000376499100030 PM 26797080 ER PT J AU Peloquin, JM Seraj, SM King, LY Campbell, EJ Ananthakrishnan, AN Richter, JM AF Peloquin, Joanna M. Seraj, Siamak M. King, Lindsay Y. Campbell, Emily J. Ananthakrishnan, Ashwin N. Richter, James M. TI Diagnostic and Therapeutic Yield of Endoscopy in Patients with Elevated INR and Gastrointestinal Bleeding SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Anticoagulation; Gastrointestinal bleeding; Supratherapeutic INR; Warfarin ID WARFARIN; ANTICOAGULATION; HEMORRHAGE; EVENTS; RISKS AB BACKGROUND: Gastrointestinal bleeding is a well-known risk of systemic anticoagulation. However, bleeding in the setting of supratherapeutic anticoagulation may have a milder natural history than unprovoked bleeding. It is a common clinical gestalt that endoscopy is common, but bleeding source identification or intervention is uncommon, yet few data exist to inform this clinical impression. Consequently, we sought to examine our institutional experience with gastrointestinal bleeding in the setting of supratherapeutic international normalized ratio (INR) with the aim of identifying predictors of endoscopically identifiable lesions, interventions, and outcomes. METHODS: A retrospective review was conducted at a tertiary referral academic medical center to identify patients presenting with gastrointestinal bleeding in the setting of warfarin and a supratherapeutic INR (> 3.5) who underwent an endoscopic procedure. Relevant clinical covariates, endoscopic findings, need for intervention, and outcomes were collected by review of the medical record. Logistic regression adjusting for potential confounders identified predictors of endoscopically significant lesions as well as intervention and outcomes. RESULTS: A total of 134 patients with INR 3.5 or greater (mean 5.5, range 3.5-17.1) presented with symptoms of gastrointestinal bleeding, most commonly as melena or symptomatic anemia. Antiplatelet agents were used by 54% of patients, and 60% of patients were on concomitant acid suppression on admission. Procedures included esophagogastroduodenoscopy (upper endoscopy; EGD) (n = 128), colonoscopy (n = 73), and video capsule endoscopy (n = 32). Active bleeding at first EGD or colonoscopy was found in only 19 patients (18%), with endoscopic intervention in only 26 patients (25%). At a critical threshold of INR 7.5 at presentation, the likelihood of finding an endoscopically significant lesion fell to < 20%. On multivariate logistic regression, concomitant antiplatelet therapy (odds ratio [OR] 2.59; 95% confidence interval [CI], 1.13-5.94), timing of EGD within 12 hours of presentation (OR 3.71; 95% CI, 1.05-13.08), and INR level (OR 0.79; 95% CI, 0.64-0.98) were the only significant independent predictors of identifying a source of bleeding. A risk score incorporating these covariates performed modestly in identifying risk of significant finding on EGD (area under the curve 0.68). We found no association between identification of a significant lesion at EGD and future readmission for gastrointestinal bleeding. CONCLUSION: This study demonstrates that the relationship between INR elevation and identification of a bleeding source or endoscopic intervention at EGD are indeed antiparallel. Concomitant antiplatelet therapy increases the likelihood of bleeding source identification and intervention, as does EGD within 12 hours of presentation. However, regardless of source identification or endoscopic intervention, important clinical outcomes were unchanged, suggesting that decisions about endoscopy should be made on a case-by-case basis, particularly in patients with INR > 7.5. Future prospective studies on appropriate indications and timing of endoscopy in such patients are warranted. (C) 2016 Elsevier Inc. All rights reserved. C1 [Peloquin, Joanna M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21205 USA. [Seraj, Siamak M.; Campbell, Emily J.; Ananthakrishnan, Ashwin N.; Richter, James M.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [King, Lindsay Y.] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM jrichter@mgh.harvard.edu NR 16 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUN PY 2016 VL 129 IS 6 BP 628 EP 634 DI 10.1016/j.amjmed.2015.11.030 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DM6YO UT WOS:000376499100035 PM 26714209 ER PT J AU Hutchinson, N Baird, GL Garg, M AF Hutchinson, Nora Baird, Grayson L. Garg, Megha TI Examining the Reading Level of Internet Medical Information for Common Internal Medicine Diagnoses SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Health literacy; Internal medicine; Online education; Patient health information; Readability AB BACKGROUND: The National Institutes of Health (NIH) recommend that health materials be written at a grade 6-7 reading level, which has generally not been achieved in online reading materials. Up to the present time, there have not been any assessments focused on the reading level of online educational materials across the most popular consumer Web sites for common internal medicine diagnoses. In this study, we examined the readability of open-access online health information for 9 common internal medicine diagnoses. METHODS: Nine of the most frequently encountered inpatient and ambulatory internal medicine diagnoses were selected for analysis. In November and December 2014, these diagnoses were used as search terms in Google, and the top 5 Web sites across all diagnoses and a diagnosis-specific site were analyzed across 5 validated reading indices. RESULTS: On average, the lowest reading grade-level content was provided by the NIH (10.7), followed by WebMD (10.9), Mayo Clinic (11.3), and diagnosis-specific Web sites (11.5). Conversely, Wikipedia provided content that required the highest grade-level readability (14.6). The diagnoses with the lowest reading grade levels were chronic obstructive pulmonary disease (10.8), followed by diabetes (10.9), congestive heart failure (11.7), osteoporosis (11.7) and hypertension (11.7). Depression had the highest grade-level readability (13.8). DISCUSSION: Despite recommendations for patient health information to be written at a grade 6-7 reading level, our examination of online educational materials pertaining to 9 common internal medicine diagnoses revealed reading levels significantly above the NIH recommendation. This was seen across both diagnosis-specific and general Web sites. There is a need to improve the readability of online educational materials made available to patients. These improvements have the potential to greatly enhance patient awareness, engagement, and physician-patient communication. Published by Elsevier Inc. C1 [Hutchinson, Nora] Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02912 USA. [Baird, Grayson L.] Rhode Isl Hosp, Lifespan Biostat Core, Providence, RI USA. [Garg, Megha] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Garg, M (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Rm 1A-71, San Francisco, CA 94121 USA. EM megha.garg@ucsf.edu NR 4 TC 1 Z9 1 U1 3 U2 8 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 JUN PY 2016 VL 129 IS 6 BP 637 EP 639 DI 10.1016/j.amjmed.2016.01.008 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DM6YO UT WOS:000376499100041 PM 26829438 ER PT J AU Simon, HB AF Simon, Harvey B. TI Pheidippides Redux Revisited Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID LOW-DOSE ASPIRIN; RANDOMIZED CONTROLLED-TRIAL; PRIMARY PREVENTION; DISEASE; EVENTS; HEALTH C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Harvard Univ, Sch Med, Med, Boston, MA USA.; Simon, HB (reprint author), MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA.; Simon, HB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUN PY 2016 VL 129 IS 6 BP E35 EP E35 DI 10.1016/j.amjmed.2015.12.034 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DM6YO UT WOS:000376499100014 PM 27215995 ER PT J AU Zhang, YJ Chee, A Shi, P Adams, SL Markova, DZ Anderson, DG Smith, HE Deng, YP Plastaras, CT An, HS AF Zhang, Yejia Chee, Ana Shi, Peng Adams, Sherrill L. Markova, Dessislava Z. Anderson, David Greg Smith, Harvey E. Deng, Youping Plastaras, Christopher T. An, Howard S. TI Intervertebral Disc Cells Produce Interleukins Found in Patients with Back Pain SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Intervertebral Disc; Discogenic Back Pain; Chemokine; Cytokine; Interleukin ID MATRIX METALLOPROTEINASES; ASYMPTOMATIC SUBJECTS; PROSTAGLANDIN E(2); NITRIC-OXIDE; EXPRESSION; IL-8; DEGENERATION; DISCOGRAPHY; IL-1-BETA; CYTOKINES AB Objective: To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain. Design: In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients. Results: Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1 beta. IL-8 and IL-7 gene expression was analyzed using real-time polymerase chain reaction. IL-8 protein was quantified by enzyme-linked immunosorbent assay. After IL-1 beta stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, whereas protein released by the NP and AF cells increased 2,389- and 1,784-fold, respectively. IL-7 gene expression increased 3.3-fold in NP cells (P < 0.05). Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81-fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were 6.87 and 4.63 times greater than the corresponding values in controls, respectively (P < 0.05). Conclusion: Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells and may play a key role in back pain. C1 [Zhang, Yejia; Plastaras, Christopher T.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Zhang, Yejia; Smith, Harvey E.] Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USA. [Zhang, Yejia; Smith, Harvey E.] Philadelphia Vet Affairs Med Ctr, TMRC, Philadelphia, PA USA. [Chee, Ana; Shi, Peng; An, Howard S.] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA. [Adams, Sherrill L.] Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. [Deng, Youping] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Markova, Dessislava Z.; Anderson, David Greg] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. RP Zhang, YJ (reprint author), Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA.; Zhang, YJ (reprint author), Philadelphia Vet Affairs Med Ctr, TMRC, Philadelphia, PA USA. FU NICHD [K08 HD049598]; North American Spine Society (NASS); Scott F. Nadler, DO Research Grant Award by the Physiatric Association of Spine, Sports and Occupational Rehabilitation (PASSOR) FX Yejia Zhang was supported by NICHD (K08 HD049598). This work was supported in part by a grant from the North American Spine Society (NASS) and Scott F. Nadler, DO Research Grant Award by the Physiatric Association of Spine, Sports and Occupational Rehabilitation (PASSOR). This work has been presented as a poster presentation at the 2014 Philadelphia Spine Research Society Meeting. NR 29 TC 1 Z9 1 U1 10 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUN PY 2016 VL 95 IS 6 BP 407 EP 415 DI 10.1097/PHM.0000000000000399 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DM7ST UT WOS:000376561000010 PM 26495812 ER PT J AU Baidal, JAW Locks, LM Cheng, ER Blake-Lamb, TL Perkins, ME Taveras, EM AF Baidal, Jennifer A. Woo Locks, Lindsey M. Cheng, Erika R. Blake-Lamb, Tiffany L. Perkins, Meghan E. Taveras, Elsie M. TI Risk Factors for Childhood Obesity in the First 1,000 Days A Systematic Review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID BODY-MASS INDEX; GESTATIONAL WEIGHT-GAIN; PROSPECTIVE BIRTH COHORT; PRESCHOOL-AGED CHILDREN; NUTRITION SURVEILLANCE SYSTEM; MATERNAL SMOKING-CESSATION; AMERICAN-INDIAN CHILDREN; HONG-KONG CHILDREN; GENERATION R; DIABETES-MELLITUS AB Context: Mounting evidence suggests that the origins of childhood obesity and related disparities can be found as early as the "first 1,000 days"-the period from conception to age 2 years. The main goal of this study is to systematically review existing evidence for modifiable childhood obesity risk factors present from conception to age 2 years. Evidence acquisition: PubMed, Embase, and Web of Science were searched for studies published between January 1, 1980, and December 12, 2014, of childhood obesity risk factors present during the first 1,000 days. Prospective, original human subject, English-language research with exposure occurrence during the first 1,000 days and with the outcome of childhood overweight or obesity (BMI >= 85th percentile for age and sex) collected between age 6 months and 18 years were analyzed between December 13, 2014, and March 15, 2015. Evidence synthesis: Of 5,952 identified citations, 282 studies met inclusion criteria. Several risk factors during the first 1,000 days were consistently associated with later childhood obesity. These included higher maternal pre-pregnancy BMI, prenatal tobacco exposure, maternal excess gestational weight gain, high infant birth weight, and accelerated infant weight gain. Fewer studies also supported gestational diabetes, child care attendance, low strength of maternal-infant relationship, low SES, curtailed infant sleep, inappropriate bottle use, introduction of solid food intake before age 4 months, and infant antibiotic exposure as risk factors for childhood obesity. Conclusions: Modifiable risk factors in the first 1,000 days can inform future research and policy priorities and intervention efforts to prevent childhood obesity. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Baidal, Jennifer A. Woo; Cheng, Erika R.; Perkins, Meghan E.; Taveras, Elsie M.] Massachusetts Gen Hosp, Div Gen Acad Pediat, Dept Pediat, Boston, MA 02114 USA. [Baidal, Jennifer A. Woo] Columbia Univ, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, Med Ctr, New York, NY 10027 USA. [Locks, Lindsey M.; Taveras, Elsie M.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Blake-Lamb, Tiffany L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Blake-Lamb, Tiffany L.] Partners Healthcare, Kraft Ctr Community Hlth Leadership, Boston, MA USA. RP Taveras, EM (reprint author), Massachusetts Gen Hosp Children, Div Gen Acad Pediat, Dept Pediat, 125 Nashua St,8th Floor, Boston, MA 02114 USA. EM elsie.taveras@mgh.harvard.edu OI Locks, Lindsey/0000-0002-0019-9545 FU Robert Wood Johnson Foundation's Health Eating Research Program FX The Robert Wood Johnson Foundation's Health Eating Research Program funded this research. NR 301 TC 17 Z9 17 U1 7 U2 25 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 JUN PY 2016 VL 50 IS 6 BP 761 EP 779 DI 10.1016/j.amepre.2015.11.012 PG 19 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DM7CD UT WOS:000376509900015 ER PT J AU Blake-Lamb, TL Locks, LM Perkins, ME Baidal, JAW Cheng, ER Taveras, EM AF Blake-Lamb, Tiffany L. Locks, Lindsey M. Perkins, Meghan E. Baidal, Jennifer A. Woo Cheng, Erika R. Taveras, Elsie M. TI Interventions for Childhood Obesity in the First 1,000 Days A Systematic Review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; INFANT NUTRITIONAL INTERVENTION; FOLLOW-UP; FEEDING PRACTICES; OIL SUPPLEMENTATION; CHILDREN YOUNGER; CHRONIC DISEASE; BLOOD-PRESSURE; PUBLIC-HEALTH; MATERNAL FISH AB Context: The "first 1,000 days"-conception through age 24 months-are critical for the development and prevention of childhood obesity. This study systematically reviews existing and ongoing interventions during this period, identifies gaps in current research, and discusses conceptual frameworks and opportunities for future interventions. Evidence acquisition: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched to identify completed and ongoing interventions implemented during pregnancy through age 24 months that aimed to prevent overweight/obesity between ages 6 months and 18 years. English-language, controlled interventions published between January 1, 1980 and December 12, 2014, were analyzed between December 13, 2014 and March 15, 2015. Evidence synthesis: Of 34 completed studies from 26 unique identified interventions, nine were effective. Effective interventions focused on individual-or family-level behavior changes through home visits, individual counseling or group sessions in clinical settings, a combination of home and group visits in a community setting, and using hydrolyzed protein formula. Protein-enriched formula increased childhood obesity risk. Forty-seven ongoing interventions were identified. Across completed and ongoing interventions, the majority target individual-or family-level changes, many are conducted in clinical settings, and few target early-life systems and policies that may impact childhood obesity. Conclusions: Obesity interventions may have the greatest preventive effect if begun early in life. Yet, few effective interventions in the first 1,000 days exist, and many target individual-level behaviors of parents and infants. Interventions that operate at systems levels and are grounded in salient conceptual frameworks hold promise for improving future models of early-life obesity prevention. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Blake-Lamb, Tiffany L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Blake-Lamb, Tiffany L.] Partners Healthcare, Kraft Ctr Community Hlth Leadership, Boston, MA USA. [Locks, Lindsey M.; Taveras, Elsie M.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Perkins, Meghan E.; Baidal, Jennifer A. Woo; Cheng, Erika R.; Taveras, Elsie M.] Massachusetts Gen Hosp Children, Div Gen Acad Pediat, Dept Pediat, 125 Nashua St,8th Floor, Boston, MA 02114 USA. [Baidal, Jennifer A. Woo] Columbia Univ, Dept Pediat, Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, New York, NY 10027 USA. RP Taveras, EM (reprint author), Massachusetts Gen Hosp Children, Div Gen Acad Pediat, Dept Pediat, 125 Nashua St,8th Floor, Boston, MA 02114 USA. EM elsie.taveras@mgh.harvard.edu OI Locks, Lindsey/0000-0002-0019-9545 FU Robert Wood Johnson Foundation FX The Robert Wood Johnson Foundation's Health Eating Research Program funded this research. NR 64 TC 6 Z9 6 U1 7 U2 18 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 JUN PY 2016 VL 50 IS 6 BP 780 EP 789 DI 10.1016/j.amepre.2015.11.010 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DM7CD UT WOS:000376509900016 PM 26916260 ER PT J AU Gaffney, A Woolhandler, S Angell, M Himmelstein, DU AF Gaffney, Adam Woolhandler, Steffie Angell, Marcia Himmelstein, David U. TI Moving Forward From the Affordable Care Act to a Single-Payer System SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Gaffney, Adam] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Gaffney, Adam] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Woolhandler, Steffie; Himmelstein, David U.] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA. [Woolhandler, Steffie; Angell, Marcia; Himmelstein, David U.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Himmelstein, DU (reprint author), 255 West 90th St, New York, NY 10024 USA. EM dhimmels@hunter.cuny.edu FU NHLBI NIH HHS [T32 HL116275] NR 10 TC 4 Z9 4 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2016 VL 106 IS 6 BP 987 EP 988 DI 10.2105/AJPH.2015.303157 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DM7DZ UT WOS:000376517100030 PM 27148891 ER PT J AU Hu, LQ Flood, P Li, YP Tao, WK Zhao, PS Xia, Y Pian-Smith, MC Stellaccio, FS Ouanes, JPP Hu, FL Wong, CA AF Hu, Ling-Qun Flood, Pamela Li, Yunping Tao, Weike Zhao, Peishan Xia, Yun Pian-Smith, May C. Stellaccio, Francis S. Ouanes, Jean-Pierre P. Hu, Fengling Wong, Cynthia A. TI No Pain Labor & Delivery: A Global Health Initiative's Impact on Clinical Outcomes in China SO ANESTHESIA AND ANALGESIA LA English DT Article ID PLANNED CESAREAN DELIVERY; EPIDURAL ANALGESIA; MATERNAL REQUEST; SECTION RATES; MORTALITY; MORBIDITY; TERM AB The availability of labor analgesia is highly variable in the People's Republic of China. There are widespread misconceptions, by both parturients and health care providers, that labor epidural analgesia is harmful to mother and baby. Meanwhile, China has one of the highest cesarean delivery rates in the world, exceeding 50%. The goal of the nongovernmental No Pain Labor & Delivery (NPLD) is to facilitate sustainable increases in vaginal delivery rates by increasing access to safe neuraxial labor analgesia, thereby decreasing the cesarean delivery rate. NPLD was launched in 2008 with the stated goal of improving labor outcome in China by increasing the absolute labor epidural analgesia rate by 10%. NPLD established 10 training centers over a 10-year period. We hypothesized that increased availability of labor analgesia would result in reduced requests for cesarean delivery and better labor outcomes for mother and baby. Multidisciplinary teams of Western clinicians and support staff traveled to China for 8 to 10 days once a year. The approach involved establishing 24/7 obstetric anesthesia coverage in Chinese hospitals through education and modeling multidisciplinary approaches, including problem-based learning discussions, bedside teaching, daily debriefings, simulation training drills, and weekend conferences. As of November 2015, NPLD has engaged with 31 hospitals. At 24 of these sites, 24/7 obstetric anesthesia coverage has been established and labor epidural analgesia rates have exceeded 50%. Lower rates of cesarean delivery, episiotomy, postpartum blood transfusion, and better neonatal outcomes were documented in 3 impact studies comprising approximately 55,000 deliveries. Changes in practice guidelines, medical policy, and billing codes have been implemented in conjunction with the modernization of perinatal practice that has occurred concurrently in China since the first NPLD trip in 2008. C1 [Hu, Ling-Qun] Northwestern Univ, Feinberg Sch Med, Dept Anesthesiol, 251 E Huron St F4-701, Chicago, IL 60611 USA. [Flood, Pamela] Stanford Univ, Med Ctr, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA 94305 USA. [Li, Yunping] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Tao, Weike] Univ Texas SW Med Ctr Dallas, Dept Anesthesiol & Pain Management, Dallas, TX 75390 USA. [Zhao, Peishan] Tufts Med Ctr, Dept Anesthesiol, Boston, MA USA. [Xia, Yun] Ohio State Univ, Dept Anesthesiol, Wexner Med Ctr, Columbus, OH 43210 USA. [Pian-Smith, May C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Stellaccio, Francis S.] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA. [Ouanes, Jean-Pierre P.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Hu, Fengling] Amherst Coll, Amherst, MA 01002 USA. [Wong, Cynthia A.] Univ Iowa, Dept Anesthesia, Iowa City, IA 52242 USA. RP Hu, LQ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Anesthesiol, 251 E Huron St F4-701, Chicago, IL 60611 USA. EM l-hu2@northwestern.edu NR 40 TC 1 Z9 4 U1 4 U2 7 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 JUN PY 2016 VL 122 IS 6 BP 1931 EP 1938 DI 10.1213/ANE.0000000000001328 PG 8 WC Anesthesiology SC Anesthesiology GA DM6LF UT WOS:000376463000032 PM 27195636 ER PT J AU Baker, K Sun, HP Harman, A Poon, T Rathmell, JP AF Baker, Keith Sun, Huaping Harman, Ann Poon, Trudy Rathmell, James P. TI Clinical Performance Scores Are Independently Associated with the American Board of Anesthesiology Certification Examination Scores SO ANESTHESIA AND ANALGESIA LA English DT Article ID SUCCESS AB BACKGROUND: It is unknown whether clinical performance during residency is related to the American Board of Anesthesiology (ABA) oral examination scores. We hypothesized that resident clinical performance would be independently associated with oral examination performance because the oral examination is designed to test for clinical judgment. METHOD: We determined clinical performance scores (Z(rel)) during the final year of residency for all 124 Massachusetts General Hospital (MGH) anesthesia residents who graduated from 2009 to 2013. One hundred eleven graduates subsequently took the ABA written and oral examinations. We standardized each graduate's written examination score (Z(Part) (1)) and oral examination score (Z(Part) (2)) to the national average. Multiple linear regression analysis was used to determine the partial effects of MGH clinical performance scores and ABA written examination scores on ABA oral examination scores. RESULTS: MGH clinical performance scores (Z(rel)) correlated with both ABA written examination scores (Z(Part) (1)) (r = 0.27; P = 0.0047) and with ABA oral examination scores (Z(Part) (2)) (r = 0.33; P = 0.0005). ABA written examination scores (Z(Part) (1)) correlated with oral examination scores (Z(Part) (2)) (r = 0.46; P = 0.0001). Clinical performance scores (Z(rel)) and ABA written examination scores (Z(Part) (1)) independently accounted for 4.5% (95% confidence interval [CI], 0.5%-12.4%; P = 0.012) and 20.8% (95% CI, 8.0%-37.2%; P < 0.0001), respectively, of the variance in ABA oral examination scores (Z(Part) (2)). CONCLUSIONS: Clinical performance scores and ABA written examination scores independently accounted for variance in ABA oral examination scores. Clinical performance scores are independently associated with the ABA oral examination scores. C1 [Baker, Keith; Poon, Trudy] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. [Baker, Keith] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sun, Huaping; Harman, Ann] Amer Board Anesthesiol Inc, Raleigh, NC USA. [Rathmell, James P.] Brigham & Womens Hosp, Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. RP Baker, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM khbaker@partners.org NR 17 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2016 VL 122 IS 6 BP 1992 EP 1999 DI 10.1213/ANE.0000000000001288 PG 8 WC Anesthesiology SC Anesthesiology GA DM6LF UT WOS:000376463000039 PM 27195641 ER PT J AU Mateen, FJ Clark, SJ Borzello, M Kabore, J Seidi, O AF Mateen, Farrah J. Clark, Sarah J. Borzello, Mia Kabore, Jean Seidi, Osheik TI Neurology Training in Sub-Saharan Africa: A Survey of People in Training from 19 Countries SO ANNALS OF NEUROLOGY LA English DT Article ID EDUCATION; PERSPECTIVE; SERVICES; ISSUES; EUROPE AB Objective: To provide a comprehensive understanding of neurology training from the sub-Saharan African perspective. Methods: A 40-question survey was distributed to attendees of the 7th annual sub-Saharan African neurology teaching course in Khartoum, Sudan (2015). Themes included the student body, faculty, curriculum, assessment and examinations, technology, and work hours and compensation. Results: Of 19 responding countries, 10 had no formal neurology training programs; Burkina Faso, Cameroon, Republic of the Congo, and Mozambique had an adult neurology program; Ethiopia, Madagascar, Nigeria, Senegal, and South Africa had adult and pediatric neurology programs (training duration range = 3-6 years). There was a median of 2.5 full-time neurologists on the teaching faculty at the respondents' training institutions (neurologists on-faculty: in-country ratio = 0.48), with the lowest ratios in Sudan and Nigeria. Neurology was perceived to be a competitive specialty for entrance in 57% of countries, with 78% of respondents reporting a requisite entrance examination. Ninety-five percent had access to a personal smartphone, 62% used the Internet more than occasionally, and 60% had access to online neurology journals. The average number of weekly work hours was 51 (range = 40-75), and average monthly salary among those earning income was 1,191 USD (range = 285-3,560). Twenty percent of respondents reported paying for training. The most common barriers to neurology postgraduate education were few training programs and lack of training in neurodiagnostic tests. Among 17 reporting countries, there is an estimated average of 0.6 neurologists per million people. Interpretation: Neurology training programs in sub-Saharan Africa are relatively limited in number and have several unmet needs including a small cadre of faculty and an opportunity to standardize curricula and financing of programs. C1 [Mateen, Farrah J.; Clark, Sarah J.; Borzello, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. [Kabore, Jean] Univ Ouagadougou, Ouagadougou, Burkina Faso. [Seidi, Osheik] Univ Khartoum, Khartoum, Sudan. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, 165 Cambridge St,627, Boston, MA 02114 USA. EM fmateen@mgh.harvard.edu NR 24 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2016 VL 79 IS 6 BP 871 EP 881 DI 10.1002/ana.24649 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DN0ST UT WOS:000376775400002 PM 27015883 ER PT J AU Singhal, AB Topcuoglu, MA Fok, JW Kursun, O Nogueira, RG Frosch, MP Caviness, VS AF Singhal, Aneesh B. Topcuoglu, Mehmet A. Fok, Joshua W. Kursun, Oguzhan Nogueira, Raul G. Frosch, Matthew P. Caviness, Verne S., Jr. TI Reversible Cerebral Vasoconstriction Syndromes and Primary Angiitis of the Central Nervous System: Clinical, Imaging, and Angiographic Comparison SO ANNALS OF NEUROLOGY LA English DT Article ID POSTERIOR LEUKOENCEPHALOPATHY; THUNDERCLAP HEADACHE; POSTPARTUM ANGIOPATHY; HYPERINTENSE VESSELS; VASCULITIS; CNS; HEMORRHAGE; DIAGNOSIS; STROKES; COHORT AB Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. However, prompt and accurate diagnosis remains challenging. Here we compared the features of 159 RCVS to 47 PACNS patients and developed criteria for prompt bedside diagnosis. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. In patients without TCH and positive angiography, neuroimaging can discriminate RCVS (no lesion) from PACNS (deep/brainstem infarcts). C1 [Singhal, Aneesh B.; Topcuoglu, Mehmet A.; Frosch, Matthew P.; Caviness, Verne S., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singhal, Aneesh B.; Topcuoglu, Mehmet A.; Frosch, Matthew P.; Caviness, Verne S., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Topcuoglu, Mehmet A.] Hacettepe Univ Hosp, Dept Neurol, Ankara, Turkey. [Fok, Joshua W.] Yan Chai Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Kursun, Oguzhan] Ankara Numune Training & Res Hosp, Neurol Clin, Ankara, Turkey. [Nogueira, Raul G.] Grady Mem Hosp, Atlanta, GA USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Atlanta, GA USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM asinghal@partners.org NR 37 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2016 VL 79 IS 6 BP 882 EP 894 DI 10.1002/ana.24652 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DN0ST UT WOS:000376775400003 PM 27043703 ER PT J AU Lee, S Viqar, F Zimmerman, ME Narkhede, A Tosto, G Benzinger, TLS Marcus, DS Fagan, AM Goate, A Fox, NC Cairns, NJ Holtzman, DM Buckles, V Ghetti, B McDade, E Martins, RN Saykin, AJ Masters, CL Ringman, JM Ryan, NS Forster, S Laske, C Schofield, PR Sperling, RA Salloway, S Correia, S Jack, C Weiner, M Bateman, RJ Morris, JC Mayeux, R Brickman, AM AF Lee, Seonjoo Viqar, Fawad Zimmerman, Molly E. Narkhede, Atul Tosto, Giuseppe Benzinger, Tammie L. S. Marcus, Daniel S. Fagan, Anne M. Goate, Alison Fox, Nick C. Cairns, Nigel J. Holtzman, David M. Buckles, Virginia Ghetti, Bernardino McDade, Eric Martins, Ralph N. Saykin, Andrew J. Masters, Colin L. Ringman, John M. Ryan, Natalie S. Forster, Stefan Laske, Christoph Schofield, Peter R. Sperling, Reisa A. Salloway, Stephen Correia, Stephen Jack, Clifford, Jr. Weiner, Michael Bateman, Randall J. Morris, John C. Mayeux, Richard Brickman, Adam M. CA Dominantly Inherited Alzheimer TI White Matter Hyperintensities Are a Core Feature of Alzheimer's Disease: Evidence from the Dominantly Inherited Alzheimer Network SO ANNALS OF NEUROLOGY LA English DT Article ID COGNITIVE IMPAIRMENT; AMYLOID ANGIOPATHY; OLDER PERSONS; DEMENTIA; REGRESSION; AGE; NEURODEGENERATION; NEUROPATHOLOGY; PATHOGENESIS; METAANALYSIS AB Objective: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. Methods: The study comprised participants (n = 299; age = 39.03 +/- 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. Results: Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. Interpretation: Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. C1 [Lee, Seonjoo] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Lee, Seonjoo] New York State Psychiat Inst & Hosp, Div Biostat, New York, NY 10032 USA. [Viqar, Fawad; Narkhede, Atul; Tosto, Giuseppe; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Viqar, Fawad; Zimmerman, Molly E.] Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. [Zimmerman, Molly E.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. [Tosto, Giuseppe; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [Tosto, Giuseppe; Mayeux, Richard; Brickman, Adam M.] Columbia Univ, New York Presbyterian Hosp, New York, NY 10032 USA. [Benzinger, Tammie L. S.; Marcus, Daniel S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Fagan, Anne M.; Holtzman, David M.; Buckles, Virginia; McDade, Eric; Bateman, Randall J.; Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Goate, Alison] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Fox, Nick C.; Ryan, Natalie S.] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England. [Cairns, Nigel J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ghetti, Bernardino] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. [Martins, Ralph N.] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Sch Exercise Biomed & Hlth Sci, Perth, WA, Australia. [Saykin, Andrew J.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Saykin, Andrew J.] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN 46202 USA. [Masters, Colin L.] Univ Melbourne, Florey Inst, Parkville, Vic 3052, Australia. [Ringman, John M.] Univ So Calif, Keck Sch Med, Memory & Aging Ctr, Los Angeles, CA 90033 USA. [Forster, Stefan] Tech Univ Munich, German Ctr Neurodegenerat Dis DZNE Munchen & Tubi, D-80290 Munich, Germany. [Forster, Stefan] Tech Univ Munich, Dept Nucl Med, D-80290 Munich, Germany. [Laske, Christoph] Univ Tubingen, German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany. [Laske, Christoph] Univ Tubingen, Sect Dementia Res, Dept Cellular Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany. [Laske, Christoph] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany. [Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW, Australia. [Schofield, Peter R.] Univ New S Wales, Sydney, NSW, Australia. [Sperling, Reisa A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Salloway, Stephen] Brown Univ, Butler Hosp, Providence, RI 02912 USA. [Salloway, Stephen] Brown Univ, Dept Neurol, Alpert Med Sch, Providence, RI 02912 USA. [Correia, Stephen] Brown Univ, Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Jack, Clifford, Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Weiner, Michael] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Ctr Imaging Neurodegenerat Dis, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Weiner, Michael] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Weiner, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Mayeux, Richard; Brickman, Adam M.] Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. RP Brickman, AM (reprint author), Columbia Univ, Coll Phys & Surg, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, 630 West 168th St,P&S Box 16, New York, NY 10032 USA. EM amb2139@columbia.edu RI Fox, Nick/B-1319-2009 OI Fox, Nick/0000-0002-6660-657X FU NIH/NIA [U19 AG032438, AG051348]; NIHR Queen Square Dementia BRU; German Center for Neurodegenerative Diseases (DZNE); Brain Exit Foundation Fellowship FX This work was supported by NIH/NIA U19 AG032438 and NIHR Queen Square Dementia BRU. S.L. is supported by NIH/NIA AG051348 and the German Center for Neurodegenerative Diseases (DZNE). N.S.R. is supported by a Brain Exit Foundation Fellowship. NR 51 TC 7 Z9 7 U1 7 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2016 VL 79 IS 6 BP 929 EP 939 DI 10.1002/ana.24647 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DN0ST UT WOS:000376775400007 PM 27016429 ER PT J AU Baker, JF Conaghan, PG Emery, P Baker, DG Ostergaard, M AF Baker, Joshua F. Conaghan, Philip G. Emery, Paul Baker, Daniel G. Ostergaard, Mikkel TI Validity of early MRI structural damage end points and potential impact on clinical trial design in rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DISEASE-ACTIVITY; RADIOGRAPHIC PROGRESSION; PHASE-III; DOUBLE-BLIND; FOLLOW-UP; METHOTREXATE; THERAPY; GOLIMUMAB; REMISSION; ANTIBODY AB Objective To evaluate the construct validity of the rheumatoid arthritis MRI score (RAMRIS) erosion evaluation as structural damage end point and to assess the potential impact of incorporation in clinical trials. Methods In a randomised trial of early methotrexatenaive RA (GO-BEFORE), RAMRIS scores were determined from MRIs and van der Heijde-Sharp (vdHS) scores from radiographs, at baseline, week 12, week 24 and week 52. Progression in damage scores was defined as change > 0.5. Associations of X-ray and MRI outcomes with clinical features were evaluated for convergent validity. Iterative Wilcoxon rank sum tests and tests of proportion estimated the sample size required to detect differences between combination therapy (methotrexate + golimumab) and methotrexate-monotherapy arms in (A) change in damage score and (B) proportion of patients progressing. Results Patients with early MRI progression had higher DAS28, C reactive protein (CRP) and vdHS at baseline, and higher 2-year HAQ. Associations were similar to those with 1-year vdHS progression. Differences in change in structural damage between treatment arms achieved significance with fewer subjects when 12-week or 24-week MRI erosion score was the outcome (150 patients; 100 among an enriched sample with baseline-synovitis > 5) compared with the 52-week vdHS (275 patients). Differences in the proportion progressing could be detected in 234 total subjects with 12-week MRI in an enriched sample whereas 1-year X-ray required between 468 and 1160 subjects. Conclusions Early MRI erosion progression is a valid measure of structural damage that could substantially decrease sample size and study duration if used as structural damage end point in RA clinical trials. C1 [Baker, Joshua F.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Baker, Joshua F.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Conaghan, Philip G.; Emery, Paul] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England. [Conaghan, Philip G.; Emery, Paul] NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Baker, Daniel G.] Janssen Res & Dev LLC, Horsham, PA USA. [Ostergaard, Mikkel] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci,Glostrup Hosp, Copenhagen Ctr Arthrit Res,Ctr Rheumatol & Spine, Copenhagen, Denmark. RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU Veterans Affairs Clinical Science Research and Development Career Development Award [IK2 CX000955] FX JFB is supported by a Veterans Affairs Clinical Science Research and Development Career Development Award (IK2 CX000955). NR 20 TC 5 Z9 5 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2016 VL 75 IS 6 BP 1114 EP 1119 DI 10.1136/annrheumdis-2014-206934 PG 6 WC Rheumatology SC Rheumatology GA DM6DP UT WOS:000376440900028 PM 26091907 ER PT J AU Unizony, S Villarreal, M Miloslavsky, EM Lu, N Merkel, PA Spiera, R Seo, P Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Ikle, D Tchao, NK Ding, LN Brunetta, P Choi, HK Monach, PA Fervenza, F Stone, JH Specks, U AF Unizony, Sebastian Villarreal, Miguel Miloslavsky, Eli M. Lu, Na Merkel, Peter A. Spiera, Robert Seo, Philip Langford, Carol A. Hoffman, Gary S. Kallenberg, C. G. M. St Clair, E. William Ikle, David Tchao, Nadia K. Ding, Linna Brunetta, Paul Choi, Hyon K. Monach, Paul A. Fervenza, Fernando Stone, John H. Specks, Ulrich CA RAVE-ITN Res Grp TI Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID WEGENERS-GRANULOMATOSIS; SYSTEMIC VASCULITIDES; RANDOMIZED-TRIAL; RENAL VASCULITIS; RITUXIMAB; CYCLOPHOSPHAMIDE; MAINTENANCE; RELAPSE; DAMAGE; INDEX AB Objective To evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies) predicts treatment response. Methods Treatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper. Results PR3-AAV patients treated with rituximab (RTX) achieved CR at 6 months more frequently than did those randomised to cyclophosphamide (CYC)/azathioprine (AZA) (65% vs 48%; p=0.04). The OR for CR at 6 months among PR3-AAV patients treated with RTX as opposed to CYC/AZA was 2.11 (95% CI 1.04 to 4.30) in analyses adjusted for age, sex and new-onset versus relapsing disease at baseline. PR3-AAV patients with relapsing disease achieved CR more often following RTX treatment at 6 months (OR 3.57; 95% CI 1.43 to 8.93), 12 months (OR 4.32; 95% CI 1.53 to 12.15) and 18 months (OR 3.06; 95% CI 1.05 to 8.97). No association between treatment and CR was observed in the MPO-AAV patient subset or in groups divided according to AAV diagnosis. Conclusions Patients with PR3-AAV respond better to RTX than to CYC/AZA. An ANCA type-based classification may guide immunosuppression in AAV. C1 [Unizony, Sebastian; Miloslavsky, Eli M.; Lu, Na; Choi, Hyon K.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Villarreal, Miguel; Ikle, David] Rho, Chapel Hill, NC USA. [Merkel, Peter A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Spiera, Robert] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, C. G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, Nadia K.] Immune Tolerance Network, San Francisco, CA USA. [Ding, Linna] NIAID, DAIT, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Brunetta, Paul] Genentech Inc, San Francisco, CA USA. [Monach, Paul A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Fervenza, Fernando; Specks, Ulrich] Mayo Clin, Rochester, MN USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU Immune Tolerance Network (NIH) [N01-AI-15416, ITN021AI]; National Institute of Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation; Genentech; Biogen-Idec; Clinical and Translational Science Award (CTSA) [1 UL1 RR024150-01]; NCRR [UL1 RR 025005]; CTSA [UL1RR 025771]; NIH [M01 RR00533, K24 AR02224]; Arthritis Foundation Investigator Award; National Center for Advancing Translational Sciences (NCATS), NIH [UL1TR000439]; [K24 AR049185]; [K23 AR052820] FX This research was performed as a project of the Immune Tolerance Network (NIH Contract N01-AI-15416; Protocol number ITN021AI), an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation; Genentech and Biogen-Idec. At the Mayo Clinic, the trial was supported by Clinical and Translational Science Award (CTSA) Grant Number 1 UL1 RR024150-01 (National Center for Research Resources; NCRR). At Johns Hopkins, the trial was supported by UL1 RR 025005 (NCRR) and by grants K24 AR049185 (JHS) and K23 AR052820 (PS). At Boston University, the trial was supported by CTSA grant number UL1RR 025771, NIH M01 RR00533, K24 AR02224 (PAM), and an Arthritis Foundation Investigator Award (PAM). At Cleveland Clinic, the trial was supported by UL1TR000439, National Center for Advancing Translational Sciences (NCATS), NIH. ANCA ELISA kits were provided by EUROIMMUN AG (Lubeck, Germany). NR 20 TC 9 Z9 9 U1 3 U2 8 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 JUN PY 2016 VL 75 IS 6 BP 1166 EP 1169 DI 10.1136/annrheumdis-2015-208073 PG 4 WC Rheumatology SC Rheumatology GA DM6DP UT WOS:000376440900036 PM 26621483 ER PT J AU Fernandez, FG Furnary, AP Kosinski, AS Onaitis, MW Kim, S Boffa, D Cowper, P Jacobs, JP Wright, CD Putnam, JB AF Fernandez, Felix G. Furnary, Anthony P. Kosinski, Andrzej S. Onaitis, Mark W. Kim, Sunghee Boffa, Daniel Cowper, Patricia Jacobs, Jeffrey P. Wright, Cameron D. Putnam, Joe B., Jr. TI Longitudinal Follow-up of Lung Cancer Resection From the Society of Thoracic Surgeons General Thoracic Surgery Database in Patients 65 Years and Older SO ANNALS OF THORACIC SURGERY LA English DT Article ID MORTALITY; LINKING AB Background. The Society of Thoracic Surgeons (STS) General Thoracic SurgeryDatabase (GTSD) does not capture long-term survival after lung cancer surgery. Our objective was to provide longitudinal follow-up to the STS GTSD through linkage to Centers for Medicare and Medicaid Services (CMS) data for patients 65 years of age or older. Methods. Lung cancer operations reported in the STS GTSD from 2002 through 2012 were linked to CMS data for patients 65 years of age or older using variables common to both databases with a deterministic matching algorithm. Mortality data were abstracted for each linked patient from the CMS data. The Kaplan-Meier method was used to estimate long-term survival for lung cancer surgery patients based on tumor stage. Results. From 2002 through 2012, 60,089 lung cancer resections were identified in the GTSD, and 37,009 (61.7%) were in patients 65 years or older. Of these, 26,055 of 37,099 lung cancer resections (70%) in patients 65 years or older were successfully linked to CMS data. Failure to link was most commonly related to having a health maintenance organization or commercial insurance as the primary payer: 40.5% (5,290 of 13,065) of such patients were not linked from 2009 to 2012 (years payer data available). Median survival after lung cancer resection was 6.7 years for pathologic stage I, 3.5 years for stage II, 2.4 years for stage III, and 2.2 years for stage IV. Conclusions. The CMS data complement the STS GTSD data by enabling examination of long-term survival and resource utilization in patients 65 years or older. Linked data from the STS GTSD and the CMS will allow for longitudinal analyses of comparative effectiveness among different surgical approaches for the treatment of lung cancer. (C) 2016 by The Society of Thoracic Surgeons C1 Emory Univ, Atlanta, GA 30322 USA. Starr Wood Cardiac Grp, Portland, OR USA. Duke Univ, Durham, NC USA. Yale Univ, New Haven, CT USA. Johns Hopkins All Childrens Heart Inst, St Petersburg, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baptist MD Anderson Canc Ctr, Jacksonville, FL USA. RP Fernandez, FG (reprint author), Emory Clin, 1365 Clifton Rd NE,Ste A2214, Atlanta, GA 30322 USA. EM felix.fernandez@emoryhealthcare.org FU Agency for Healthcare Research and Quality [R01 HS022279] FX This project was supported by grant number R01 HS022279 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. NR 13 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 JUN PY 2016 VL 101 IS 6 BP 2067 EP 2076 DI 10.1016/j.athoracsur.2016.03.034 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DM6ZW UT WOS:000376502600013 PM 27157052 ER PT J AU Seder, CW Salati, M Kozower, BD Wright, CD Falcoz, PE Brunelli, A Fernandez, FG AF Seder, Christopher W. Salati, Michele Kozower, Benjamin D. Wright, Cameron D. Falcoz, Pierre-Emmanuel Brunelli, Alessandro Fernandez, Felix G. TI Variation in Pulmonary Resection Practices Between The Society of Thoracic Surgeons and the European Society of Thoracic Surgeons General Thoracic Surgery Databases SO ANNALS OF THORACIC SURGERY LA English DT Article ID CELL LUNG-CANCER; GUIDELINES; RADIOTHERAPY; DEFINITIONS; MANAGEMENT; THERAPY; ESTS AB Background. Clinical guidelines are created to reduce variation in care practices, with the goal of improving patient outcomes. There is currently no international consensus on best practices for pulmonary resection. Our aim was to evaluate variation in treatment patterns and outcomes for pulmonary resection by comparing The Society of Thoracic Surgeons (STS) and the European Society of Thoracic Surgery (ESTS) general thoracic surgery databases (GTSDs). Methods. An international collaboration was established between the STS and ESTS GTSD task forces. Patients who underwent pulmonary resection between 2010 and 2013 were identified from the 2 databases. Data on patient demographics, disease characteristics, treatment strategies, morbidity, and mortality were compared. Results. There were 78,212 lung resections captured in the STS (n = 47,539) and ESTS databases (n = 30,673). Patients from the STS database were more likely to be of the female sex, have no pathologic N2 disease, have had previous cardiothoracic operations, and have received preoperative thoracic irradiation compared with patients from the ESTS database. In addition, patients from the STS database were more likely to have undergone a thoracoscopic operation and have received a sublobar resection. Although there was an increased risk of reintubation, atrial arrhythmias, and return to the operating room in the STS patients, the mean hospital length of stay was shorter than in patients from the ESTS database, regardless of operation performed. Thirty-day mortality was higher in the STS patients for wedge resection (p < 0.001) but lower for lobectomy (p < 0.001) and pneumonectomy (p < 0.001) compared with the ESTS patients. Conclusions. Differences exists in patient population, procedures performed, and outcomes for pulmonary resections between the STS and ESTS databases, suggesting an opportunity for quality improvement initiatives. (C) 2016 by The Society of Thoracic Surgeons C1 Rush Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Chicago, IL 60612 USA. Osped Riuniti Ancona, Unit Thorac Surg, Ancona, Italy. Univ Virginia, Dept Surg, Charlottesville, VA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Nouvel Hosp Civil, Dept Thorac Surg, Strasbourg, France. St James Univ Hosp, Dept Thorac Surg, Leeds LS9 7TF, W Yorkshire, England. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. RP Seder, CW (reprint author), 1725 W Harrison St,Ste 774, Chicago, IL 60612 USA. EM christopher_w_seder@rush.edu RI falcoz, pierre-emmanuel/N-1239-2016; OI Brunelli, Alessandro/0000-0002-6505-1656 NR 20 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 JUN PY 2016 VL 101 IS 6 BP 2077 EP 2084 DI 10.1016/j.athoracsur.2015.12.073 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DM6ZW UT WOS:000376502600014 PM 27021033 ER PT J AU Badhwar, V Rankin, JS He, X Jacobs, JP Gammie, JS Furnary, AP Fazzalari, FL Han, J O'Brien, SM Shahian, DM AF Badhwar, Vinay Rankin, J. Scott He, Xia Jacobs, Jeffrey P. Gammie, James S. Furnary, Anthony P. Fazzalari, Frank L. Han, Jane O'Brien, Sean M. Shahian, David M. TI The Society of Thoracic Surgeons Mitral Repair/Replacement Composite Score: A Report of The Society of Thoracic Surgeons Quality Measurement Task Force SO ANNALS OF THORACIC SURGERY LA English DT Article ID ADULT CARDIAC-SURGERY; VALVE SURGERY; REGURGITATION; REPAIR; CARE; ASSOCIATION; SELECTION; OUTCOMES AB Background. The Society of Thoracic Surgeons (STS) Quality Measurement Task Force is developing a portfolio of composite performance measures for the most commonly performed procedures in adult cardiac surgery. We now describe the fourth in this series, the STS composite measure for mitral valve repair/replacement (MVRR). Methods. We examined all patients undergoing isolated MVRR, with or without concomitant performance of tricuspid valve repair, surgical arrhythmia ablation, or repair of atrial septal defect, between July 1, 2011, and June 30, 2014. In this two-domain model, risk-adjusted mortality and any-or-none major morbidity were combined into a composite score using 3 years of STS data and 95% Bayesian credible intervals to estimate composite scores and star ratings. Results. There were 61,201 MVRR patients studied at 867 participant sites. Mitral valve repair was performed in 57.4% (35,114 of 61,201) and mitral valve replacement in 42.6% (26,087 of 61,201). Mortality was 2.9% (1,773 of 61,201), and occurrence of any major morbidity was 17.0% (10,381 of 61,201). The median composite score was 93.2% (interquartile range, 92.3% to 94.2%). Star rating classifications included 23 of 867 (2.6%) 1-star programs (lower-than-expected performance), 795 of 867 (91.7%) 2-star programs (as-expected or average performance), and 49 of 867 (5.7%) 3-star programs (higher-than-expected performance). Conclusions. STS has developed an MVRR composite performance measure that will be used for participant feedback, quality performance assessment and improvement, and voluntary public reporting. (C) 2016 by The Society of Thoracic Surgeons C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Cardiothorac Surg Associates, Nashville, TN USA. Duke Clin Res Inst, Durham, NC USA. Johns Hopkins Univ, Sch Med, St Petersburg, FL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Starr Wood Cardiac Grp, Portland, OR USA. Univ Michigan, Ann Arbor, MI 48109 USA. Soc Thorac Surg, Chicago, IL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Badhwar, V (reprint author), Univ Pittsburgh, Dept Cardiothorac Surg, 200 Lothrop St,C-721, Pittsburgh, PA 15213 USA. EM badhwarv@upmc.edu NR 16 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2016 VL 101 IS 6 BP 2265 EP 2271 DI 10.1016/j.athoracsur.2015.11.049 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DM6ZW UT WOS:000376502600039 PM 26740032 ER PT J AU Mallee, WH Mellema, JJ Guitton, TG Goslings, JC Ring, D Doornberg, JN AF Mallee, Wouter H. Mellema, Jos J. Guitton, Thierry G. Goslings, J. Carel Ring, David Doornberg, Job N. CA Sci Variation Grp TI 6-week radiographs unsuitable for diagnosis of suspected scaphoid fractures SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE Diagnostics; Fracture; Radiographs; Reference standard; Scaphoid; Occult ID LATENT CLASS ANALYSIS; BONE-SCINTIGRAPHY; INTEROBSERVER RELIABILITY; COMPUTED-TOMOGRAPHY; CT; CLASSIFICATION; ACCURACY; MRI; PERFORMANCE; MANAGEMENT AB Six week follow-up radiographs are a common reference standard for the diagnosis of suspected scaphoid fractures. The main purpose of this study was to evaluate the interobserver reliability and diagnostic performance characteristics of 6-weeks radiographs for the detection of scaphoid fractures. In addition, two online techniques for evaluating radiographs were compared. A total of 81 orthopedic surgeons affiliated with the Science of Variation Group assessed initial and 6-week scaphoid-specific radiographs of a consecutive series of 34 patients with suspected scaphoid fractures. They were randomized in two groups for evaluation, one used a standard website showing JPEG files and one a more sophisticated image viewer (DICOM). The goal was to identify the presence or absence of a (consolidated) scaphoid fracture. Interobserver reliability was calculated using the multirater kappa measure. Diagnostic performance characteristics were calculated according to standard formulas with CT and MRI upon presentation in the emergency department as reference standards. The interobserver agreement of 6-week radiographs for the diagnosis of scaphoid fractures was slight for both JPEG and DICOM (k = 0.15 and k = 0.14, respectively). The sensitivity (range 42-79 %) and negative predictive value (range 79-94 %) were significantly higher using a DICOM viewer compared to JPEG images. There were no differences in specificity (range 53-59 %), accuracy (range 53-58 %), and positive predictive value (range 14-26 %) between the groups. Due to low agreement between observers for the recognition of scaphoid fractures and poor diagnostic performance, 6-week radiographs are not adequate for evaluating suspected scaphoid fractures. The online evaluation of radiographs using a DICOM viewer seem to improve diagnostic performance characteristics compared to static JPEG images and future reliability and diagnostic studies should account for variation due to the method of delivering medical images. Diagnostic level II. C1 [Mallee, Wouter H.; Doornberg, Job N.] Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Guitton, Thierry G.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Goslings, J. Carel] Univ Groningen, Univ Med Ctr Groningen, Dept Plast Surg, NL-9713 AV Groningen, Netherlands. [Ring, David] Univ Amsterdam, Acad Med Ctr, Dept Trauma Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. Dell Med Sch, Dept Surg & Perioperat Care, Austin, TX USA. RP Mallee, WH (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, NL-1105 AZ Amsterdam, Netherlands. EM w.h.mallee@amc.uva.nl NR 31 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0936-8051 EI 1434-3916 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD JUN PY 2016 VL 136 IS 6 BP 771 EP 778 DI 10.1007/s00402-016-2438-4 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DM5UM UT WOS:000376415700006 PM 27026536 ER PT J AU Freeman, MP Sosinsky, AZ Moustafa, D Viguera, AC Cohen, LS AF Freeman, Marlene P. Sosinsky, Alexandra Z. Moustafa, Danna Viguera, Adele C. Cohen, Lee S. TI Supplement use by women during pregnancy: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Supplements; Pregnancy; Antipsychotics; Vitamin; Integrative ID ALTERNATIVE MEDICINE; COMPLEMENTARY; ADULTS; TRENDS AB Women of reproductive age commonly use integrative treatments. However, the reproductive safety for most complementary products lacks systematic study. We aimed to study the use of supplements by women in a prospective pregnancy registry. The Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics was established to evaluate the reproductive safety of atypical antipsychotics. Exposed and control participants were systematically queried about the use of vitamins and supplements. Slightly greater than half (53.2 %) of the participants eligible for analysis (N = 534) were using at least one vitamin or supplement at the time of enrollment, not including prenatal vitamins or folic acid. The most common supplements used were omega-3 fatty acids (38.0 %), vitamin D (11.0 %), calcium (8.2 %), and iron (4.7 %). Probiotics and melatonin were used by 2.6 and 0.9 %, respectively. In this prospective pregnancy registry, we found that over half of the participants were taking supplements or vitamins other than prenatal vitamins and folic acid. These findings underscore the need for active query on the part of health care providers about the use of supplements during pregnancy, and the need to obtain rigorous reproductive safety and efficacy data for supplements used by pregnant women and reproductive aged women. C1 [Freeman, Marlene P.; Sosinsky, Alexandra Z.; Moustafa, Danna; Viguera, Adele C.; Cohen, Lee S.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Perinatal & Reprod Psychiat Program, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. [Viguera, Adele C.] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Perinatal & Reprod Psychiat Program, 185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM mfreeman@partners.org OI Sosinsky, Alexandra/0000-0003-2051-7333 FU AstraZeneca (Wilmington, DE); Bristol-Myers Squibb/Otsuka America Pharmaceutical, Inc. (Plainsboro/Princeton, NJ); Ortho-McNeil-Janssen Pharmaceuticals, Inc. (Raritan, NJ); Pfizer, Inc. (New York, NY); Sunovion Pharmaceuticals, Inc. (Fort Lee, NJ) FX AstraZeneca (Wilmington, DE; 2009-present), Bristol-Myers Squibb/Otsuka America Pharmaceutical, Inc. (Plainsboro/Princeton, NJ; 2008-present), Ortho-McNeil-Janssen Pharmaceuticals, Inc. (Raritan, NJ; 2009-2014), Pfizer, Inc. (New York, NY; 2009-2011), and Sunovion Pharmaceuticals, Inc. (Fort Lee, NJ; 2011-present) had no role in the design and conduct of the study; in the collection, analysis, interpretation of the data; or in the preparation, review, or approval of the manuscript. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD JUN PY 2016 VL 19 IS 3 BP 437 EP 441 DI 10.1007/s00737-015-0586-0 PG 5 WC Psychiatry SC Psychiatry GA DM5UU UT WOS:000376416500001 PM 26472040 ER PT J AU Zhong, QY Gelaye, B Miller, M Fricchione, GL Cai, TX Johnson, PA Henderson, DC Williams, MA AF Zhong, Qiu-Yue Gelaye, Bizu Miller, Matthew Fricchione, Gregory L. Cai, Tianxi Johnson, Paula A. Henderson, David C. Williams, Michelle A. TI Suicidal behavior-related hospitalizations among pregnant women in the USA, 2006-2012 SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Suicidal ideation; Suicide and self-inflicted injury; Pregnant women; National (Nationwide) Inpatient Sample ID EMERGENCY-DEPARTMENT VISITS; SELF-INFLICTED INJURY; LOW-INCOME WOMEN; MATERNAL MORTALITY; UNITED-STATES; PERINATAL-PERIOD; ADOLESCENT GIRLS; SUBSTANCE USE; LEADING CAUSE; POSTPARTUM AB Suicide is one of the leading causes of maternal mortality in many countries, but little is known about the epidemiology of suicide and suicidal behavior among pregnant women in the USA. We sought to examine trends and provide nationally representative estimates for suicidal behavior (including suicidal ideation and suicide and self-inflicted injury) among pregnant women from 2006 to 2012 in the USA. Pregnant women aged 12-55 years were identified through pregnancy- and delivery-related hospitalization records from the National (Nationwide) Inpatient Sample. Suicidal behavior was identified by the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Annual, nationwide estimates and trends were determined using discharge and hospital weights. The prevalence of suicidal ideation more than doubled from 2006 to 2012 (47.5 to 115.0 per 100,000 pregnancy- and delivery-related hospitalizations), whereas the prevalence of suicide and self-inflicted injury remained stable. Nearly 10 % of suicidal behavior occurred in the 12-18-year group, showing the highest prevalence per 100,000 pregnancy- and delivery-related hospitalizations (158.8 in 2006 and 308.7 in 2012) over the study period. For suicidal ideation, blacks had higher prevalence than whites; women in the lowest income quartile had the highest prevalence. Although the prevalence of suicidal behavior was higher among hospitalizations with depression diagnoses, more than 30 % of hospitalizations were for suicidal behavior without depression diagnoses. Our findings highlight the increasing burden and racial differences in suicidal ideation among US pregnant women. Targeted suicide prevention efforts are needed for high-risk pregnant women including teens, blacks, and low-income women. C1 [Zhong, Qiu-Yue; Gelaye, Bizu; Miller, Matthew; Williams, Michelle A.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Miller, Matthew] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Div Psychiat & Med, Pierce Div Global Psychiat, Boston, MA 02114 USA. [Cai, Tianxi] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Johnson, Paula A.] Mary Horrigan Connors Ctr Womens Hlth & Gender Bi, Boston, MA USA. [Johnson, Paula A.] Brigham & Womens Hosp, Div Womens Hlth, 75 Francis St, Boston, MA 02115 USA. [Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zhong, QY (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. EM qyzhong@mail.harvard.edu OI Gelaye, Bizu/0000-0001-7934-548X FU National Institutes of Health (the National Institute on Minority Health and Health Disparities) [T37-MD001449]; National Institutes of Health (National Center for Research Resources (NCRR)); National Institutes of Health (National Center for Advancing Translational Sciences (NCATS)) [8UL1TR 000170-05] FX This research was supported by awards from the National Institutes of Health (the National Institute on Minority Health and Health Disparities T37-MD001449 and the National Center for Research Resources (NCRR), the National Center for Advancing Translational Sciences (NCATS) 8UL1TR 000170-05). The authors would like to thank Dr. Miguel-Angel Luque Fernandez and Dr. Wenyuan Li for their help with programming. The authors would like to thank Kathy Brenner for the help with editing this manuscript. Special thanks are extended to the Research Computing Group at the Faculty of Art and Sciences of Harvard University, for the continuous support with computational resources. NR 65 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD JUN PY 2016 VL 19 IS 3 BP 463 EP 472 DI 10.1007/s00737-015-0597-x PG 10 WC Psychiatry SC Psychiatry GA DM5UU UT WOS:000376416500004 PM 26680447 ER PT J AU Meuret, AE Chmielewski, M Steele, AM Rosenfield, D Petersen, S Smits, JAJ Simon, NM Otto, MW Marques, L Pollack, MH Hofmann, SG AF Meuret, Alicia E. Chmielewski, Michael Steele, Ashton M. Rosenfield, David Petersen, Sibylle Smits, Jasper A. J. Simon, Naomi M. Otto, Michael W. Marques, Luana Pollack, Mark H. Hofmann, Stefan G. TI The desire to belong: Social identification as a predictor of treatment outcome in social anxiety disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Social identification; Stigma; Personality; Cognitive behavioral therapy; Social anxiety disorder; Predictor ID COGNITIVE-BEHAVIORAL THERAPY; MENTAL-ILLNESS STIGMA; SELF-STIGMA; 5-FACTOR MODEL; CLINICAL SETTINGS; MAJOR DEPRESSION; D-CYCLOSERINE; PERSONALITY; PEOPLE; HEALTH AB Objective: Perception of personal identity cannot be separated from the perception of the social context and one's social identity. Full involvement in group psychotherapy may require not only the awareness of personal impairment, but also social identification. The aim of the current study was to examine the association between social identification and symptom improvement in group-based psychotherapy. Method: 169 participants received 12 sessions of group-based cognitive behavioral therapy for social anxiety disorder. Social identification, the extent to which a person identifies with those who suffer from the same psychological problem as themselves and/or with those lacking psychopathology (non-sufferers), and clinical outcome were assessed at baseline, mid-and posttreatment, and 1, 3, and 6-months follow-up. Results: At baseline, patients aspired for closeness with non-sufferers, and viewed themselves as distant from fellow sufferers and non-sufferers. After treatment, participants viewed not only themselves, but also other individuals with social anxiety, as closer to both non-sufferers and fellow sufferers. These ratings were related to clinical outcomes. Conclusions: The increase in closeness to both sufferers and non-sufferers across treatment may reflect a movement towards a more tolerant, less dichotomous and rigid, separation of ill and healthy that occurs with successful social anxiety treatment. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Meuret, Alicia E.; Chmielewski, Michael; Steele, Ashton M.; Rosenfield, David] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. [Petersen, Sibylle] Katholieke Univ Leuven, Dept Psychol, Leuven, Belgium. [Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Smits, Jasper A. J.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA. [Simon, Naomi M.; Marques, Luana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Otto, Michael W.; Hofmann, Stefan G.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Pollack, Mark H.] Rush Med Sch, Dept Psychiat, Chicago, IL USA. RP Meuret, AE (reprint author), So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA. EM ameuret@smu.edu RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Petersen, Sibylle/0000-0002-9597-5075 FU National Institute of Mental Health [R01MH075889, R01MH078308]; National Institutes of Health [NIMH K23 MH096029-01A1]; NIBIB [1U01EB021952-01] FX This report was supported by grants R01MH075889 (to Mark Pollack, M.D.) and R01MH078308 (to Stefan Hofmann, Ph.D.) from the National Institute of Mental Health. Time dedicated to this paper was in part supported by a grant from the National Institutes of Health (NIMH K23 MH096029-01A1, to Luana Marques, Ph.D. and NIBIB 1U01EB021952-01 to Alicia Meuret, Ph.D.). NR 71 TC 0 Z9 0 U1 5 U2 14 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 JUN PY 2016 VL 81 BP 21 EP 34 DI 10.1016/j.brat.2016.03.008 PG 14 WC Psychology, Clinical SC Psychology GA DM9QM UT WOS:000376700800003 PM 27070526 ER PT J AU Stone, RM AF Stone, Richard M. TI Transplantation after Remission in Mixed Phenotype Acute Leukemia: A Good Idea SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material C1 [Stone, Richard M.] Harvard Univ, Sch Med, Adult Leukemia Program, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D-2053, Boston, MA 02215 USA. EM rstone@partners.org 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2016 VL 22 IS 6 BP 971 EP 972 DI 10.1016/j.bbmt.2016.04.001 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DN1GJ UT WOS:000376814000001 PM 27095690 ER PT J AU Ullrich, CK Lehmann, L London, WB Guo, DJ Sridharan, M Koch, R Wolfe, J AF Ullrich, Christina K. Lehmann, Leslie London, Wendy B. Guo, Dongjing Sridharan, Madhumitha Koch, Richard Wolfe, Joanne TI End-of-Life Care Patterns Associated with Pediatric Palliative Care among Children Who Underwent Hematopoietic Stem Cell Transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Stem cell transplant; Pediatric; Palliative care; End of life ID BONE-MARROW-TRANSPLANTATION; PSYCHOLOGICAL DISTRESS; ADVANCED CANCER; ONCOLOGY CARE; PARENTS; PERSPECTIVES; OUTCOMES; CHEMOTHERAPY; MULTICENTER; INTEGRATION AB Stem cell transplantation (SCT) is an intensive therapy offering the possibility of cure for life-threatening conditions but with risk of serious complications and death. Outcomes associated with pediatric palliative care (PPC) for children who undergo SCT are unknown. Therefore, we evaluated whether PPC consultation is associated with differences in end-of-life (EOL) care patterns for children who underwent SCT and did not survive. Medical records of children who underwent SCT at Boston Children's Hospital/Dana-Farber Cancer Institute for any indication from September 2004 to December 2012 and did not survive were reviewed. Child demographic and clinical characteristics and PPC consultation and EOL care patterns were abstracted. Children who received PPC (PPC group) were compared with those who did not (non-PPC group). Children who received PPC consultation (n = 37) did not differ from the non-PPC group (n = 110) with respect to demographic or clinical characteristics, except they were more likely to have undergone unrelated allogeneic SCT (PPC, 68%; non-PPC, 39%; P = .02) or to have died from treatment-related toxicity (PPC, 76%; non-PPC, 54%; P = .03). PPC consultation occurred at a median of .7 months (interquartile range [IQR], .4 to 4.2) before death. PPC consultations most commonly addressed goals of care/decision-making (92%), psychosocial support (84%), pain management (65%), and non pain symptom management (70%). Prognosis discussions (ie, the likelihood of survival) occurred more commonly in the PPC group (PPC, 97%; non-PPC, 83%; P = .04), as did resuscitation status discussions (PPC, 88%; non-PPC, 58%; P = .002). These discussions also occurred earlier in the PPC group, for prognosis a median of 8 days (IQR, 4 to 26) before death compared with 2 days (IQR, 1 to 13) in the non-PPC group and for resuscitation status a median of 7 days (IQR, 3 to 18) compared with 2 days (IQR, 1 to 5) in the non-PPC group (P < .001 for both of the timing of prognosis and resuscitation status discussions). The PPC group was also was more likely to have resuscitation status documented (PPC, 97%; non-PPC, 68%; P = .002). With respect to patterns of care, compared with non-PPC, the PPC group was as likely to die in a medicalized setting (ie, the hospital) (PPC, 84%; non-PPC, 77%; P = .06) or have hospice care (PPC, 22%; non-PPC, 18%; P = .6). However, among children who died in the hospital, those who received PPC were more likely to die outside the intensive care unit (PPC, 80%; non-PPC, 58%; P = .03). In addition, the PPC group was less likely to receive intervention-focused care such as intubation in the 24 hours before death (PPC, 42%; non-PPC, 66%; P = .02) or cardiopulmonary resuscitation (PPC, 3%; non-PPC, 20%; P = .03) at EOL. Children who received PPC for at least a month were more likely to receive hospice care (PPC, 41%; non-PPC, 5%; P = .01). Children who underwent SCT and did not survive were likely to die in a medicalized setting, irrespective of PPC. However, PPC was associated with less intervention-focused care and greater opportunity for EOL communication and advance preparation. In the intense, cure-oriented SCT setting, PPC may facilitate advance care planning in this high-risk population. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Ullrich, Christina K.; Koch, Richard; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Ullrich, Christina K.; Lehmann, Leslie; London, Wendy B.; Guo, Dongjing; Sridharan, Madhumitha] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Ullrich, Christina K.; Koch, Richard] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Ullrich, Christina K.; Lehmann, Leslie; London, Wendy B.; Guo, Dongjing; Sridharan, Madhumitha; Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Ullrich, CK (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM christina_ullrich@dfci.harvard.edu FU National heart, Lung, and Blood Institute [1K23HL107452] FX Financial disclosure: Research support provide by the National heart, Lung, and Blood Institute (grant 1K23HL107452 to C.K.U.). NR 40 TC 0 Z9 0 U1 10 U2 11 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 JUN PY 2016 VL 22 IS 6 BP 1049 EP 1055 DI 10.1016/j.bbmt.2016.02.012 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DN1GJ UT WOS:000376814000013 PM 26903381 ER PT J AU Chaudhury, S Sparapani, R Hu, ZH Nishihori, T Abdel-Azim, H Malone, A Olsson, R Hamadani, M Daly, A Bacher, U Wirk, BM Kamble, RT Gale, RP Wood, WA Hale, G Wiernik, PH Hashmi, SK Marks, D Ustun, C Munker, R Savani, BN Alyea, E Popat, U Sobecks, R Kalaycio, M Maziarz, R Hijiya, N Saber, W AF Chaudhury, Sonali Sparapani, Rodney Hu, Zhen-Huan Nishihori, Taiga Abdel-Azim, Hisham Malone, Adriana Olsson, Richard Hamadani, Mehdi Daly, Andrew Bacher, Ulrike Wirk, Baldeep M. Kamble, Rammurti T. Gale, Robert P. Wood, William A. Hale, Gregory Wiernik, Peter H. Hashmi, Shahrukh K. Marks, David Ustun, Celalettin Munker, Reinhold Savani, Bipin N. Alyea, Edwin Popat, Uday Sobecks, Ronald Kalaycio, Matt Maziarz, Richard Hijiya, Nobuko Saber, Wael TI Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CML; Pediatrics ID CHRONIC MYELOGENOUS LEUKEMIA; TOTAL-BODY IRRADIATION; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; 1ST CHRONIC PHASE; TERM-FOLLOW-UP; PROGNOSTIC-FACTORS; CHRONIC GRAFT; EUROPEAN-LEUKEMIANET; IMATINIB MESYLATE AB Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age < 18 years, n = 177) and young adults (age 18 to 29 years, n = 272) with the goal of identifying prognostic factors. Post-HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in <18-year and 74% and 60% in 18- to 29-year group, respectively, by univariate analysis (P = .1 and = .6). Five-year rates of OS for HLA matched sibling donor (MSD) and bone marrow (BM) stem cell source were 83% and 80%, respectively. In multivariate analysis there was no effect of age (<18 versus 18 to 29) or pre-HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P < .001) and recent HCT (2003 to 2010; P = .04). LFS was superior with MSD (P < .001), BM as graft source (P = .001), and performance scores > 90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Chaudhury, Sonali; Hijiya, Nobuko] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat Hematol Oncol & Stem Cell Transplanta, 225 E Chicago Ave, Chicago, IL 60611 USA. [Sparapani, Rodney; Hu, Zhen-Huan; Hamadani, Mehdi; Saber, Wael] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Abdel-Azim, Hisham] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90033 USA. [Malone, Adriana] Icahn Sch Med Mt Sinai, Bone Marrow & Stem Cell Transplantat, New York, NY 10029 USA. [Olsson, Richard] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, Richard] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Hamadani, Mehdi] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA. [Daly, Andrew] Univ Calgary, Tom Baker Canc Ctr, Cumming Sch Med, Calgary, AB, Canada. [Bacher, Ulrike] Univ Canc Ctr Hamburg, Interdisciplinary Clin Stem Cell Transplantat, Hamburg, Germany. [Wirk, Baldeep M.] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA. [Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Wood, William A.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Hale, Gregory] Univ S Florida, All Childrens Hosp, Dept Hematol Oncol, St Petersburg, FL 33701 USA. [Wiernik, Peter H.] Canc Res Fdn New York, Bronx, NY USA. [Hashmi, Shahrukh K.] Mayo Clin, Dept Blood & Marrow Transplantat, Rochester, MN USA. [Marks, David] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Ustun, Celalettin] Univ Minneapolis, Div Hematol Oncol & Transplantat, Minneapolis, MN USA. [Munker, Reinhold] Louisiana State Univ Hlth Shreveport, Dept Internal Med, Sect Hematol Oncol, Shreveport, LA USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Alyea, Edwin] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Alyea, Edwin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Popat, Uday] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Sobecks, Ronald; Kalaycio, Matt] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA. [Maziarz, Richard] Oregon Hlth & Sci Univ, Knight Canc Inst, Adult Blood & Marrow Stem Cell Transplant Program, Portland, OR 97201 USA. RP Chaudhury, S (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat Hematol Oncol & Stem Cell Transplanta, 225 E Chicago Ave, Chicago, IL 60611 USA. FU NCI NIH HHS [U24 CA076518] NR 56 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2016 VL 22 IS 6 BP 1056 EP 1064 DI 10.1016/j.bbmt.2016.02.015 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DN1GJ UT WOS:000376814000014 PM 26964698 ER PT J AU Liedke, PER Tu, D Shepherd, L Chavarri-Guerra, Y Pritchard, KI Stearns, V Goss, PE AF Liedke, P. E. R. Tu, D. Shepherd, L. Chavarri-Guerra, Y. Pritchard, K. I. Stearns, V. Goss, P. E. TI New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole - Analyses from NCIC CTG MA.17 SO BREAST LA English DT Article DE Breast cancer; Letrozole; Vasomotor symptoms; Musculoskeletal symptoms; Aromatase inhibitors; Extended hormonal therapy ID STAGE BREAST-CANCER; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; ADVERSE EVENTS; TAMOXIFEN; THERAPY; WOMEN; DISCONTINUATION; SURVIVAL; TOXICITY AB Purpose: New onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA. 17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen. Methods: Symptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without. Results: Data post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28-0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24-0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24-0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22-0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint. Conclusions: New onset VM symptoms with extended letrozole may be useful in predicting treatment benefit. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Liedke, P. E. R.] Hosp Clin Porto Alegre, Dept Clin Oncol, Porto Alegre, RS, Brazil. [Liedke, P. E. R.] Hosp Mae de Deus, Mae de Deus Canc Inst, Porto Alegre, RS, Brazil. [Liedke, P. E. R.] Brazilian Breast Canc Study Grp, Porto Alegre, RS, Brazil. [Tu, D.; Shepherd, L.; Pritchard, K. I.; Goss, P. E.] Queens Univ, Canadian Canc Trials Grp, Kingston, ON K7L 3N6, Canada. [Chavarri-Guerra, Y.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol Oncol, Salvador Zubiran, Mexico. [Pritchard, K. I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Stearns, V.] Kimmel Canc Ctr Johns Hopkins, Breast Canc Program, Baltimore, MD USA. [Liedke, P. E. R.; Chavarri-Guerra, Y.; Goss, P. E.] Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Res Program, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,LRH 302, Boston, MA 02114 USA. FU Avon Foundation, NY FX PERL, YCG and PEG received partial support from the Avon Foundation, NY. NR 12 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD JUN PY 2016 VL 27 BP 99 EP 104 DI 10.1016/j.breast.2016.02.010 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DM7CU UT WOS:000376512500014 PM 27058233 ER PT J AU Pagani, O Regan, MM Francis, PA AF Pagani, Olivia Regan, Meredith M. Francis, Prudence A. TI Are SOFT and TEXT results practice changing and how? SO BREAST LA English DT Article DE Premenopausal; Breast cancer; Endocrine therapy; Exemestane; Ovarian suppression; Tamoxifen ID EARLY BREAST-CANCER; ADJUVANT ENDOCRINE THERAPY; OVARIAN-FUNCTION SUPPRESSION; INTERNATIONAL CONSENSUS GUIDELINES; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; YOUNG-WOMEN; AMERICAN SOCIETY; AUSTRIAN BREAST; TAMOXIFEN AB Optimal adjuvant endocrine therapy for premenopausal women with hormone-receptor positive breast cancer has long been debated. In particular, the role of ovarian function suppression in addition to standard tamoxifen divided oncologists worldwide, and more recently, the role of aromatase inhibitors as an alternative to tamoxifen in the setting of ovarian suppression became a key question. In 2014, the long awaited results of the International Breast Cancer Study Group (IBCSG) led randomized, phase 3 trials, Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT), provided additional evidence to inform the discussion. The interpretation of the SOFT and TEXT trial data can facilitate better selection of appropriate endocrine therapy according to individual disease characteristics, recognizing the complexity of the puzzle, which is still not complete. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Pagani, Olivia] Inst Oncol, Bellinzona, Switzerland. [Pagani, Olivia] Breast Unit Southern Switzerland, Bellinzona, Switzerland. [Pagani, Olivia; Regan, Meredith M.; Francis, Prudence A.] Int Breast Canc Study Grp, Bern, Switzerland. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence A.] Univ Newcastle, Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia. RP Pagani, O (reprint author), Inst Oncol, Bellinzona, Switzerland.; Pagani, O (reprint author), Breast Unit Southern Switzerland, Bellinzona, Switzerland. EM olivia.pagani@ibcsg.org FU Pfizer; Ipsen; International Breast Cancer Study Group; National Cancer Institute FX The trials were supported by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute. NR 34 TC 0 Z9 0 U1 3 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD JUN PY 2016 VL 27 BP 122 EP 125 DI 10.1016/j.breast.2016.02.008 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DM7CU UT WOS:000376512500018 PM 27107153 ER PT J AU Sun, FD Skolny, MN Swaroop, MN Rawal, B Catalano, PJ Brunelle, CL Miller, CL Taghian, AG AF Sun, Fangdi Skolny, Melissa N. Swaroop, Meyha N. Rawal, Bhupendra Catalano, Paul J. Brunelle, Cheryl L. Miller, Cynthia L. Taghian, Alphonse G. TI The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Lymphedema; Breast cancer; Quantification; Standardization; Treatment morbidity; Temporal baseline ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; UPPER-LIMB LYMPHEDEMA; QUALITY-OF-LIFE; RISK-FACTORS; NODE DISSECTION; FOLLOW-UP; OPTOELECTRONIC VOLUMETRY; CONSERVING THERAPY; SURGERY; DIAGNOSIS AB Breast cancer-related lymphedema (BCRL) is a feared outcome of breast cancer treatment, yet the push for early screening is hampered by a lack of standardized quantification. We sought to determine the necessity of preoperative baseline in accounting for temporal changes of upper extremity volume. 1028 women with unilateral breast cancer were prospectively screened for lymphedema by perometry. Thresholds were defined: relative volume change (RVC) a parts per thousand yen10 % for clinically significant lymphedema and a parts per thousand yen5 % including subclinical lymphedema. The first postoperative measurement (pseudo-baseline) simulated the case of no baseline. McNemar's test and binomial logistic regression models were used to analyze BCRL misdiagnoses. Preoperatively, 28.3 and 2.9 % of patients had arm asymmetry of a parts per thousand yen5 and 10 %, respectively. Without baseline, 41.6 % of patients were underdiagnosed and 40.1 % overdiagnosed at RVC a parts per thousand yen 5 %, increasing to 50.0 and 54.8 % at RVC a parts per thousand yen 10 %. Increased pseudo-baseline asymmetry, increased weight change between baselines, hormonal therapy, dominant use of contralateral arm, and not receiving axillary lymph node dissection (ALND) were associated with increased risk of underdiagnosis at RVC a parts per thousand yen 5 %; not receiving regional lymph node radiation was significant at RVC a parts per thousand yen 10 %. Increased pseudo-baseline asymmetry, not receiving ALND, and dominant use of ipsilateral arm were associated with overdiagnosis at RVC a parts per thousand yen 5 %; increased pseudo-baseline asymmetry and not receiving ALND were significant at RVC a parts per thousand yen 10 %. The use of a postoperative proxy even early after treatment results in poor sensitivity for identifying BCRL. Providers with access to patients before surgery should consider the consequent need for proper baseline, with specific strategy tailored by institution. C1 [Sun, Fangdi; Skolny, Melissa N.; Swaroop, Meyha N.; Miller, Cynthia L.; Taghian, Alphonse G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. [Rawal, Bhupendra; Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. [Brunelle, Cheryl L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, 100 Blossom St, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund for BCRL FX The study described was supported by Award Number R01CA139118 (AGT) and Award Number P50CA089393 (AGT) from the National Cancer Institute and the Adele McKinnon Research Fund for BCRL. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 63 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2016 VL 157 IS 2 BP 229 EP 240 DI 10.1007/s10549-016-3821-0 PG 12 WC Oncology SC Oncology GA DM7ZU UT WOS:000376580900004 PM 27154787 ER PT J AU Charlton, BM Giovannucci, E Fuchs, CS Chan, AT Lee, JE Cao, Y Missmer, SA Rosner, BA Hankinson, SE Willett, W Wu, K Michels, KB AF Charlton, Brittany M. Giovannucci, Edward Fuchs, Charles S. Chan, Andrew T. Lee, Jung Eun Cao, Yin Missmer, Stacey A. Rosner, Bernard A. Hankinson, Susan E. Willett, Walter Wu, Kana Michels, Karin B. TI A prospective study of oral contraceptive use and colorectal adenomas SO CANCER CAUSES & CONTROL LA English DT Article DE Adenoma; Colorectal neoplasms; Contraceptives; Oral; Intestinal polyps; Reproductive history ID HORMONE REPLACEMENT THERAPY; LARGE-BOWEL-CANCER; BODY-MASS INDEX; REPRODUCTIVE FACTORS; UNITED-STATES; COLON-CANCER; RISK-FACTORS; EXOGENOUS HORMONES; ROYAL-COLLEGE; WOMEN AB The influence of reproductive factors on colorectal cancer, including oral contraceptive (OC) use, has been examined, but less research is available on OC use and adenomas. Participants of the Nurses' Health Study who had a lower bowel endoscopy between 1986 (when endoscopies were first assessed) and 2008 were included in this study. Multivariable logistic regression models for clustered data were used to estimate odds ratios and 95 % confidence intervals [OR (95 % CIs)]. Among 73,058 participants, 51 % (n = 37,382) reported ever using OCs. Ever OC use was associated with a slight increase in non-advanced adenomas [OR 1.11, 95 % CI (1.02, 1.21)] but not with any other endpoints. Duration of OC use was not associated with adenomas, but longer times since last OC use were associated with increased odds of adenomas [e.g., compared to never use, 15+ years since last use: OR 1.17 (1.07, 1.27)]. Shorter times since last OC use were inversely associated [e.g., a parts per thousand currency sign4 years since last use: OR 0.74 (0.65, 0.84)]. We observed a modest borderline increase in risk of colorectal adenomas with any prior OC use. Additionally, more recent OC use may decrease risk, while exposure in the distant past may modestly increase risk of adenomas. C1 [Charlton, Brittany M.; Giovannucci, Edward; Missmer, Stacey A.; Hankinson, Susan E.; Willett, Walter; Michels, Karin B.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Charlton, Brittany M.] Boston Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. [Charlton, Brittany M.] Harvard Univ, Dept Pediat, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. [Giovannucci, Edward; Cao, Yin; Willett, Walter; Wu, Kana] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. [Giovannucci, Edward; Chan, Andrew T.; Missmer, Stacey A.; Rosner, Bernard A.; Hankinson, Susan E.; Willett, Walter; Michels, Karin B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. [Giovannucci, Edward; Chan, Andrew T.; Missmer, Stacey A.; Rosner, Bernard A.; Hankinson, Susan E.; Willett, Walter; Michels, Karin B.] Harvard Univ, Sch Med, 181 Longwood Ave, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Cheongpa Ro 47 Gil 100, Seoul 04310, South Korea. [Missmer, Stacey A.] Brigham & Womens Hosp, Div Reprod Med, 45 St Francis St, Boston, MA 02115 USA. [Missmer, Stacey A.] Harvard Univ, Sch Med, 45 St Francis St, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, 715 North Pleasant St, Amherst, MA 01003 USA. [Michels, Karin B.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. [Michels, Karin B.] Harvard Univ, Sch Med, 221 Longwood Ave, Boston, MA 02115 USA. RP Charlton, BM (reprint author), Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA.; Charlton, BM (reprint author), Boston Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA.; Charlton, BM (reprint author), Harvard Univ, Dept Pediat, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM bcharlton@mail.harvard.edu FU National Institutes of Health [UM1CA186107, P01CA87969]; Training Programs in Cancer Epidemiology from the National Cancer Institute and in Reproductive [T32CA09001]; Perinatal, and Pediatric Epidemiology [T32HD060454]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [F32HD084000]; Entertainment Foundation National Colon Cancer Research Alliance FX The NHS was supported by research Grants UM1CA186107 and P01CA87969 of the National Institutes of Health. BMC was supported by the Training Programs in Cancer Epidemiology (T32CA09001) from the National Cancer Institute and in Reproductive, Perinatal, and Pediatric Epidemiology (T32HD060454) as well as Grant F32HD084000 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. WW was supported by Entertainment Foundation National Colon Cancer Research Alliance. An abstract of this work was presented at the Association for Cancer Research Annual Meeting on 7 April 2014 and the Society for Epidemiologic Research Annual Conference on 26 June 2014. We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. Also, special thanks to Scott Smith for his programming assistance. NR 50 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2016 VL 27 IS 6 BP 749 EP 757 DI 10.1007/s10552-016-0752-3 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DM8MZ UT WOS:000376619500004 PM 27125831 ER PT J AU Lochhead, P Khalili, H Ananthakrishnan, AN Richter, JM Chan, AT AF Lochhead, Paul Khalili, Hamed Ananthakrishnan, Ashwin N. Richter, James M. Chan, Andrew T. TI Association Between Circulating Levels of C-Reactive Protein and Interleukin-6 and Risk of Inflammatory Bowel Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Inflammation; Subclinical; Preclinical; Natural History ID CROHNS-DISEASE; CARDIOVASCULAR-DISEASE; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; PHYSICAL-ACTIVITY; OLMSTED COUNTY; HUMAN SERUM; WOMEN; MARKERS; PREVALENCE AB BACKGROUND & AIMS: There is evidence that immune dysfunction precedes symptoms of inflammatory bowel disease (IBD) by several years. Characterization of preclinical systemic inflammation could contribute to the understanding of the biology of IBD and, ultimately, facilitate development of strategies for early disease detection and intervention. We evaluated associations between circulating levels of interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP) and diagnosis of incident Crohn's disease (CD) or ulcerative colitis (UC). METHODS: We conducted a nested case-control study of participants enrolled in 2 population-based, nationwide, prospective cohort studies (the Nurses' Health Study and the Nurses' Health Study II). We analyzed blood specimens, collected before diagnosis, from 83 persons with CD, 90 persons with UC, and 344 matched individuals without IBD (control subjects). Plasma levels of hsCRP and IL6 were measured. We investigated associations between each inflammatory marker and IBD risk using multivariable logistic regression models to adjust for potential confounding exposures. RESULTS: Compared with the lowest quintile of IL6 level, the highest quintile was associated with an odds ratio (OR) of 4.68 (95% confidence interval, 1.91-11.46) for CD (P-trend < .001) and an OR of 3.43 (95% confidence interval, 1.44-8.15) for UC (P-trend = .004). The highest quintile of hsCRP level, compared with the lowest quintile, was associated with an OR of 2.82 (95% confidence interval, 1.15-6.87) for CD (P-trend = .019) and an OR of 1.79 (95% confidence interval, 0.80-3.99) for UC (P-trend = .015). CONCLUSIONS: Plasma levels of IL6 and hsCRP before diagnosis are associated with risk of incident CD and UC. Subclinical levels of systemic inflammation may be a feature of an early disease state that precedes the development of symptomatic IBD. C1 [Lochhead, Paul; Khalili, Hamed; Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Lochhead, Paul; Khalili, Hamed; Ananthakrishnan, Ashwin N.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Lochhead, Paul; Khalili, Hamed; Ananthakrishnan, Ashwin N.; Richter, James M.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA. EM achan@mgh.harvard.edu FU National Institutes of Health [UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, K24 DK098311, K23 DK091742]; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; Crohn's and Colitis Foundation of America; American Gastroenterological Association FX This study was supported by grants UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, and K24 DK098311 from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr Chan is supported by a senior investigator award from the Crohn's and Colitis Foundation of America. Dr Khalili is supported by a career development award from the American Gastroenterological Association and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). Dr. Ananthakrishnan is supported by the National Institute of Health (K23 DK091742). The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; nor in the preparation, review, and approval of the manuscript. NR 29 TC 4 Z9 4 U1 1 U2 3 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 JUN PY 2016 VL 14 IS 6 BP 818 EP + DI 10.1016/j.cgh.2016.01.016 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DM6IY UT WOS:000376456400013 PM 26844874 ER PT J AU Newton, AW AF Newton, Alice W. TI Child maltreatment: a review of key literature in 2015 SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE abusive head trauma; child maltreatment; child neglect; child physical abuse; child sexual abuse skeletal survey ID ABUSIVE HEAD TRAUMA; YOUNG-CHILDREN AB Purpose of review This review addresses some of the more salient articles in the field of child maltreatment published in 2015, with a goal of helping the general practitioner understand the evolution of research in the field of child abuse pediatrics (a board-certified specialty since 2009). Recent findings Researchers continue to refine the database for child abuse pediatrics. Several articles focus on the inconsistencies in approach to the evaluation of possible physical child abuse between hospitals and practitioners. Multiple researchers aim to develop a protocol that standardizes the response to findings of a sentinel injury, such as a rib fracture, abdominal trauma, or unexplained bruising in a nonambulatory infant. Professionals are also working to improve our understanding about the impact of trauma on children and how best to ameliorate its effects. Summary With solid, evidence-based literature published on various topics in the field of child abuse pediatrics, experts work to refine and unify the clinician's approach to the evaluation of possible physical abuse. C1 [Newton, Alice W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Child Protect Program, Boston, MA 02115 USA. RP Newton, AW (reprint author), Massachusetts Gen Hosp, Dept Pediat, Room 516,175 Cambridge St, Boston, MA 02114 USA. EM anewton@partners.org NR 17 TC 1 Z9 1 U1 8 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD JUN PY 2016 VL 28 IS 3 BP 395 EP 399 DI 10.1097/MOP.0000000000000362 PG 5 WC Pediatrics SC Pediatrics GA DM5KF UT WOS:000376387000020 PM 27093358 ER PT J AU King, GL Park, K Li, Q AF King, George L. Park, Kyoungmin Li, Qian TI Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; ISCHEMIC-HEART-DISEASE; E NULL MICE; RECEPTOR SUBSTRATE-1; VASCULAR COMPLICATIONS; NITRIC-OXIDE; INDUCED PHOSPHORYLATION; MOLECULAR-MECHANISMS AB This review is focused on the factors and potential mechanisms that are causing various cardiovascular pathologies. In diabetes, insulin's actions on the endothelium and other vascular cells have significant influence on systemic metabolisms and the development of cardiovascular pathologies. Our studies showed that insulin receptors on the endothelium are important for insulin transport across the endothelial barrier and mediate insulin's actions in muscle, heart, fat, and the brain. Insulin actions on the vascular cells are mediated by two pathways involving the actions of either IRS/PI3K/Akt or Grb/Shc/MAPK. Insulin's activation of IRS/PI3K/Akt results in mostly antiatherogenic actions, as this pathway induces activation of eNOS, the expressions of HO-1 and VEGF, and the reduction of VCAM-1. In contrast, insulin's activation of the Grb/Shc/MAPK pathway mediates the expressions of ET-1 and PAI-1 and migration and proliferation of contractile cells, which have proatherogenic actions. Elevated levels of glucose, free fatty acids, and inflammatory cytokines due to diabetes and insulin resistance selectively inhibit insulin's antiatherogenic actions via the IRS/PI3K/Akt pathway. This review provides evidence to support the importance of insulin actions in preventing cardiovascular pathology that can be selectively inhibited via the IRS/PI3K/Akt cascade in diabetes. C1 [King, George L.; Park, Kyoungmin; Li, Qian] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat,Dianne Nunnally H, Boston, MA 02115 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat,Dianne Nunnally H, Boston, MA 02115 USA. EM george.king@joslin.harvard.edu FU National Institutes of Health (NIH) [5P30-DK-036836]; NIH [R01-DK-053105]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1DP3-DK-094333-01]; American Diabetes Association FX The authors are grateful for the support of National Institutes of Health (NIH) grant 5P30-DK-036836. G.L.K. is supported by NIH grant R01-DK-053105 and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant 1DP3-DK-094333-01. Q.L. was supported by the American Diabetes Association Mentor-Based Postdoctoral Fellowship Award. NR 69 TC 6 Z9 6 U1 6 U2 12 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 JUN PY 2016 VL 65 IS 6 BP 1462 EP 1471 DI 10.2337/db16-0152 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700002 PM 27222390 ER PT J AU Ferris, HA Kahn, CR AF Ferris, Heather A. Kahn, C. Ronald TI Unraveling the Paradox of Selective Insulin Resistance in the Liver: the Brain-Liver Connection SO DIABETES LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; BODY-WEIGHT; METABOLISM; RECEPTOR C1 [Ferris, Heather A.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [T32 DK007260, K08 DK097293] NR 17 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2016 VL 65 IS 6 BP 1481 EP 1483 DI 10.2337/dbi16-0010 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700004 PM 27222392 ER PT J AU Dirice, E Walpita, D Vetere, A Meier, BC Kahraman, S Hu, J Dancik, V Burns, SM Gilbert, TJ Olson, DE Clemons, PA Kulkarni, RN Wagner, BK AF Dirice, Ercument Walpita, Deepika Vetere, Amedeo Meier, Bennett C. Kahraman, Sevim Hu, Jiang Dancik, Vlado Burns, Sean M. Gilbert, Tamara J. Olson, David E. Clemons, Paul A. Kulkarni, Rohit N. Wagner, Bridget K. TI Inhibition of DYRK1A Stimulates Human beta-Cell Proliferation SO DIABETES LA English DT Article ID INSULIN-RESISTANT STATES; SET ENRICHMENT ANALYSIS; IN-VIVO; KINASE INHIBITORS; ROAD MAP; REPLICATION; EXPANSION; MOLECULE; MICE; MASS AB Restoring functional beta-cell mass is an important therapeutic goal for both type 1 and type 2 diabetes (1). While proliferation of existing beta-cells is the primary means of beta-cell replacement in rodents (2), it is unclear whether a similar principle applies to humans, as human beta-cells are remarkably resistant to stimulation of division (3,4). Here, we show that 5-iodotubercidin (5-IT), an annotated adenosine kinase inhibitor previously reported to increase proliferation in rodent and porcine islets (5), strongly and selectively increases human beta-cell proliferation in vitro and in vivo. Remarkably, 5-IT also increased glucose-dependent insulin secretion after prolonged treatment. Kinome profiling revealed 5-IT to be a potent and selective inhibitor of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) and cell division cycle-like kinase families. Induction of beta-cell proliferation by either 5-IT or harmine, another natural product DYRK1A inhibitor, was suppressed by coincubation with the calcineurin inhibitor FK506, suggesting involvement of DYRK1A and nuclear factor of activated T cells signaling. Gene expression profiling in whole islets treated with 5-IT revealed induction of proliferation- and cell cycle-related genes, suggesting that true proliferation is induced by 5-IT. Furthermore, 5-IT promotes beta-cell proliferation in human islets grafted under the kidney capsule of NOD-scid IL2Rg(null) mice. These results point to inhibition of DYRK1A as a therapeutic strategy to increase human beta-cell proliferation. C1 [Dirice, Ercument; Kahraman, Sevim; Hu, Jiang; Kulkarni, Rohit N.] Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Walpita, Deepika; Vetere, Amedeo; Meier, Bennett C.; Dancik, Vlado; Gilbert, Tamara J.; Clemons, Paul A.; Wagner, Bridget K.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA USA. [Meier, Bennett C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Burns, Sean M.] Harvard Univ, Sch Med, Chem Biol Program, Boston, MA USA. [Burns, Sean M.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Burns, Sean M.] Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. [Olson, David E.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA.; Wagner, BK (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA USA. EM rohit.kulkarni@joslin.harvard.edu; bwagner@broadinstitute.org RI Dirice, Ercument/B-2825-2017 FU JDRF [17-2011-642, JDRF-3-APF-2014-220-A-N, 2-SRA-2015-17]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK67536, R01 DK103215, P30 DK036836] FX This work was supported by a JDRF Strategic Research Agreement (17-2011-642). E.D. is supported by a Senior JDRF Fellowship (JDRF-3-APF-2014-220-A-N), and R.N.K. acknowledges support from the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK67536, R01 DK103215, and P30 DK036836) and JDRF (2-SRA-2015-17). NR 50 TC 6 Z9 6 U1 7 U2 10 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 JUN PY 2016 VL 65 IS 6 BP 1660 EP 1671 DI 10.2337/db15-1127 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700024 PM 26953159 ER PT J AU Molven, A Hollister-Lock, J Hu, J Martinez, R Njolstad, PR Liew, CW Weir, G Kulkarni, RN AF Molven, Anders Hollister-Lock, Jennifer Hu, Jiang Martinez, Rachael Njolstad, Pal R. Liew, Chong Wee Weir, Gordon Kulkarni, Rohit N. TI The Hypoglycemic Phenotype Is Islet Cell-Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase-Deficient Mice SO DIABETES LA English DT Article ID INSULIN-SECRETION; 3-HYDROXYACYL-COA DEHYDROGENASE; HYPERINSULINEMIC HYPOGLYCEMIA; CONGENITAL HYPERINSULINISM; BETA-CELL; MUTATIONS; OXIDATION; RELEASE AB Congenital hyperinsulinism of infancy (CHI) can be caused by inactivating mutations in the gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a ubiquitously expressed enzyme involved in fatty acid oxidation. The hypersecretion of insulin may be explained by a loss of interaction between SCHAD and glutamate dehydrogenase in the pancreatic beta-cells. However, there is also a general accumulation of metabolites specific for the enzymatic defect in affected individuals. It remains to be explored whether hypoglycemia in SCHAD CHI can be uncoupled from the systemic effect on fatty acid oxidation. We therefore transplanted islets from global SCHAD knockout (SCHADKO) mice into mice with streptozotocin-induced diabetes. After transplantation, SCHADKO islet recipients exhibited significantly lower random and fasting blood glucose compared with mice transplanted with normal islets or nondiabetic, nontransplanted controls. Furthermore, intraperitoneal glucose tolerance was improved in animals receiving SCHADKO islets compared with those receiving normal islets. Graft beta-cell proliferation and apoptosis rates were similar in the two transplantation groups. We conclude that hypoglycemia in SCHAD-CHI is islet cell-autonomous. C1 [Molven, Anders; Hollister-Lock, Jennifer; Hu, Jiang; Martinez, Rachael; Liew, Chong Wee; Weir, Gordon; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Islet Cell & Regenerat Biol,Harvard Stem Cell Ins, Boston, MA 02115 USA. [Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway. [Molven, Anders; Njolstad, Pal R.] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. [Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Chicago, IL USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Kulkarni, Rohit N.] Harvard Stem Cell Inst, Boston, MA USA. RP Molven, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Islet Cell & Regenerat Biol,Harvard Stem Cell Ins, Boston, MA 02115 USA.; Molven, A (reprint author), Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway.; Molven, A (reprint author), Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.; Molven, A (reprint author), Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. EM anders.molven@uib.no FU Fulbright fellowship; Novo Nordisk Foundation [NNF150C0016330]; Western Norway Regional Health Authority; KG Jebsen Foundation; Research Council of Norway (Norges Forskningsrad) [FRIMEDBIO 240788]; European Research Council; National Institutes of Health [K99-DK-090210, R01-DK-67536, R01-DK-103215] FX The study was supported by a Fulbright fellowship to A.M. and by grants from the Novo Nordisk Foundation (NNF150C0016330), Western Norway Regional Health Authority, KG Jebsen Foundation, and The Research Council of Norway (Norges Forskningsrad) (FRIMEDBIO 240788). P.R.N. was supported by a European Research Council Advanced Grant. C.W.L. was supported by a grant from the National Institutes of Health (K99-DK-090210). R.N.K. was supported by National Institutes of Health grants R01-DK-67536 and R01-DK-103215. NR 19 TC 0 Z9 0 U1 3 U2 5 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 JUN PY 2016 VL 65 IS 6 BP 1672 EP 1678 DI 10.2337/db15-1475 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700025 PM 26953163 ER PT J AU Cameron-Vendrig, A Reheman, A Siraj, MA Xu, XR Wang, YM Lei, X Afroze, T Shikatani, E El-Mounayri, O Noyan, H Weissleder, R Ni, HY Husain, M AF Cameron-Vendrig, Alison Reheman, Adili Siraj, M. Ahsan Xu, Xiaohong Ruby Wang, Yiming Lei, Xi Afroze, Talat Shikatani, Eric El-Mounayri, Omar Noyan, Hossein Weissleder, Ralph Ni, Heyu Husain, Mansoor TI Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; VON-WILLEBRAND-FACTOR; CARDIOVASCULAR OUTCOMES; ENDOTHELIAL-CELLS; MYOCARDIAL-INFARCTION; GLP-1 RECEPTOR; IN-VITRO; EXENDIN-4 AB Short-term studies in subjects with diabetes receiving glucagon-like peptide 1 (GLP-1)-targeted therapies have suggested a reduced number of cardiovascular events. The mechanisms underlying this unexpectedly rapid effect are not known. We cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human megakaryocyte cell line (MEG-01), and found expression levels of GLP-1Rs in MEG-01 cells to be higher than those in the human lung but lower than in the human pancreas. Incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in MEG-01 cells, and exenatide significantly inhibited thrombin-, ADP-, and collagen-induced platelet aggregation. Incubation with exenatide also inhibited thrombus formation under flow conditions in ex vivo perfusion chambers using human and mouse whole blood. In a mouse cremaster artery laser injury model, a single intravenous injection of exenatide inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r(-/-)) compared with those receiving wild-type bone marrow. Although antithrombotic effects of exenatide were partly lost in mice transplanted with bone marrow from Glp1r(-/-) mice, they were undetectable in mice with a genetic deficiency of endothelial nitric oxide synthase. The inhibition of platelet function and the prevention of thrombus formation by GLP-1R agonists represent potential mechanisms for reduced atherothrombotic events. C1 [Cameron-Vendrig, Alison; Ni, Heyu; Husain, Mansoor] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Cameron-Vendrig, Alison; Xu, Xiaohong Ruby; Afroze, Talat; Shikatani, Eric; El-Mounayri, Omar; Noyan, Hossein; Ni, Heyu; Husain, Mansoor] Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada. [Cameron-Vendrig, Alison; Siraj, M. Ahsan; Afroze, Talat; Shikatani, Eric; El-Mounayri, Omar; Noyan, Hossein; Husain, Mansoor] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada. [Cameron-Vendrig, Alison; Afroze, Talat; El-Mounayri, Omar; Noyan, Hossein; Husain, Mansoor] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Cameron-Vendrig, Alison; Reheman, Adili; Xu, Xiaohong Ruby; Wang, Yiming; Lei, Xi; Ni, Heyu] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, 30 Bond St, Toronto, ON M5B 1W8, Canada. [Xu, Xiaohong Ruby; Wang, Yiming; Shikatani, Eric; Ni, Heyu; Husain, Mansoor] Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02115 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Ni, Heyu; Husain, Mansoor] Univ Toronto, Dept Med, Toronto, ON, Canada. [Ni, Heyu] Canadian Blood Serv, Toronto, ON, Canada. [Husain, Mansoor] Univ Hlth Network, Ted Rogers Ctr Heart Res, Toronto, ON, Canada. RP Husain, M (reprint author), Univ Toronto, Dept Physiol, Toronto, ON, Canada.; Husain, M (reprint author), Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto, ON, Canada.; Husain, M (reprint author), Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada.; Husain, M (reprint author), Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada.; Husain, M (reprint author), Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada.; Husain, M (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada.; Husain, M (reprint author), Univ Hlth Network, Ted Rogers Ctr Heart Res, Toronto, ON, Canada. EM mansoor.husain@uhn.ca OI Ni, Heyu/0000-0002-7621-2945 FU Canadian Institutes of Health Research [MOP 119540]; Merck Canada (IISP) [40363]; Heart and Stroke Foundation of Canada [T6757]; Heart and Stroke Foundation, Ontario Provincial Office FX This work was funded in part by an Operating Grant to H.Ni from the Canadian Institutes of Health Research (MOP 119540), an Investigator-Initiated Research grant to H.Ni and M.H. from Merck Canada (IISP #40363), and a Grant-in-Aid to M.H. from the Heart and Stroke Foundation of Canada (T6757). M.H. was supported by a Career Investigator Award from the Heart and Stroke Foundation, Ontario Provincial Office. NR 49 TC 6 Z9 6 U1 3 U2 6 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 JUN PY 2016 VL 65 IS 6 BP 1714 EP 1723 DI 10.2337/db15-1141 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700029 PM 26936963 ER PT J AU Lane, JM Chang, AM Bjonnes, AC Aeschbach, D Anderson, C Cade, BE Cain, SW Czeisler, CA Gharib, SA Gooley, JJ Gottlieb, DJ Grant, SFA Klerman, EB Lauderdale, DS Lockley, SW Munch, M Patel, S Punjabi, NM Rajaratnam, SMW Rueger, M Hilaire, MAS Santhi, N Scheuermaier, K Van Reen, E Zee, PC Shea, SA Duffy, JF Buxton, OM Redline, S Scheer, FAJL Saxena, R AF Lane, Jacqueline M. Chang, Anne-Marie Bjonnes, Andrew C. Aeschbach, Daniel Anderson, Clare Cade, Brian E. Cain, Sean W. Czeisler, Charles A. Gharib, Sina A. Gooley, Joshua J. Gottlieb, Daniel J. Grant, Struan F. A. Klerman, Elizabeth B. Lauderdale, Diane S. Lockley, Steven W. Munch, Miriam Patel, Sanjay Punjabi, Naresh M. Rajaratnam, Shanthakumar M. W. Rueger, Melanie Hilaire, Melissa A. St. Santhi, Nayantara Scheuermaier, Karin Van Reen, Eliza Zee, Phyllis C. Shea, Steven A. Duffy, Jeanne F. Buxton, Orfeu M. Redline, Susan Scheer, Frank A. J. L. Saxena, Richa TI Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology SO DIABETES LA English DT Article ID FASTING PLASMA-GLUCOSE; INSULIN-SECRETION; ASSOCIATION; DESIGN; METABOLISM; QUALITY; CONSEQUENCES; METAANALYSIS; TOLERANCE; PACEMAKER AB The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele. C1 [Lane, Jacqueline M.; Bjonnes, Andrew C.; Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lane, Jacqueline M.; Bjonnes, Andrew C.; Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Lane, Jacqueline M.; Chang, Anne-Marie; Bjonnes, Andrew C.; Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Lane, Jacqueline M.; Chang, Anne-Marie; Bjonnes, Andrew C.; Aeschbach, Daniel; Anderson, Clare; Cade, Brian E.; Cain, Sean W.; Czeisler, Charles A.; Gooley, Joshua J.; Gottlieb, Daniel J.; Klerman, Elizabeth B.; Lockley, Steven W.; Munch, Miriam; Patel, Sanjay; Rajaratnam, Shanthakumar M. W.; Rueger, Melanie; Hilaire, Melissa A. St.; Santhi, Nayantara; Scheuermaier, Karin; Van Reen, Eliza; Shea, Steven A.; Duffy, Jeanne F.; Buxton, Orfeu M.; Redline, Susan; Scheer, Frank A. J. L.; Saxena, Richa] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. [Chang, Anne-Marie; Aeschbach, Daniel; Anderson, Clare; Cade, Brian E.; Cain, Sean W.; Czeisler, Charles A.; Gooley, Joshua J.; Gottlieb, Daniel J.; Klerman, Elizabeth B.; Lockley, Steven W.; Munch, Miriam; Patel, Sanjay; Rajaratnam, Shanthakumar M. W.; Rueger, Melanie; Hilaire, Melissa A. St.; Santhi, Nayantara; Scheuermaier, Karin; Van Reen, Eliza; Shea, Steven A.; Duffy, Jeanne F.; Buxton, Orfeu M.; Redline, Susan; Scheer, Frank A. J. L.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. [Chang, Anne-Marie; Buxton, Orfeu M.] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. [Aeschbach, Daniel] German Aerosp Ctr, Inst Aerosp Med, Cologne, Germany. [Gharib, Sina A.] Univ Washington, Dept Med, UW Med Sleep Ctr, Computat Med Core,Ctr Lung Biol, Seattle, WA 98195 USA. [Grant, Struan F. A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grant, Struan F. A.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. [Lauderdale, Diane S.] Univ Chicago, Dept Hlth Sci, Chicago, IL 60637 USA. [Lockley, Steven W.] Monash Univ, Sch Psychol Sci, Melbourne, Vic 3004, Australia. [Punjabi, Naresh M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Zee, Phyllis C.] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA. [Buxton, Orfeu M.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA. [Munch, Miriam] Charite, Germany Inst Physiol, Grp Sleep Res & Clin Chronobiol, D-13353 Berlin, Germany. [Gooley, Joshua J.] Duke Natl Univ Singapore, Grad Sch Med, Neurosci & Behav Disorders Programme, Singapore, Singapore. [Rajaratnam, Shanthakumar M. W.] Monash Univ, Sch Psychol Sci, Clayton, Vic 3800, Australia. [Rajaratnam, Shanthakumar M. W.] Monash Univ, Monash Inst Cognit & Clin Neurosci, Clayton, Vic 3800, Australia. [Santhi, Nayantara] Univ Surrey, Surrey Sleep Res Ctr, Div Sleep Med, Surrey, England. [Scheuermaier, Karin] Univ Witwatersrand, Fac Hlth Sci, Sch Physiol, Wits Sleep Lab,Brain Funct Res Grp, Johannesburg, South Africa. [Van Reen, Eliza] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. [Van Reen, Eliza] Brown Univ, Sleep Sci Res Lab, Providence, RI 02912 USA. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Saxena, R (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.; Saxena, R (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.; Saxena, R (reprint author), Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. EM rsaxena@broadinstitute.org OI Cain, Sean/0000-0002-8385-1550 FU National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK089378]; Harvard Catalyst of the Harvard Clinical and Translational Science Center (National Center for Research Resources, NIH) [8UL1TR00017005]; Harvard Catalyst of the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH) [8UL1TR00017005]; NHLBI [T32HL07901, R01HL094806, R01HL118601, K01 HL115458, U01HL53941, U01HL53916, U01HL53934, U01HL53937, U01HL63429, U01HL63463, R01HL077453, R01HL080978, R01HL093279, R01HL094654, R01HL077399, 01EHLE114088, K24EHL105664, R01HL09327, R01HL09465, RC2EHL101340]; National Institute on Aging (NIA) [F32 AG316902]; Harvard University and its affiliated academic health care centers; NIDDK [R01DK099512]; NIA [R01AG06072, P01AG009975, R01AG044416]; Air Force Office of Scientific Research [FA9550]; NIH [R21AT002571, R01NS054277, R01MH45130, M01RR02635, R01EGME10501]; National Space Biomedical Research Institute [HFP01601, HFP02802]; Brain & Behavior Research Foundation; General Clinical Research Center [M01RR02635]; Brigham and Women's Hospital Brigham Research Institute; Brigham and Women's Hospital; [NHLBI R21 HL121728]; [NIDDK F32 DK102323]; [NHLBI R01 HL113338]; [NHLBI R01 HL098433] FX This study was conducted with support from the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK089378 to R.S. and F.A.J.L.S.), support from Harvard Catalyst of the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8UL1TR00017005 to F.A.J.L.S. and R.S.), support from the NHLBI (T32HL07901) and the National Institute on Aging (NIA) (F32 AG316902) to K.S., and financial contributions from Harvard University and its affiliated academic health care centers. J.M.L., S.R., and R.S. were further supported by the following grants: NHLBI R21 HL121728 (R.S.), NIDDK F32 DK102323 (J.M.L.), and NHLBI R01 HL113338 and NHLBI R01 HL098433 (S.R.). F.A.J.L.S. was further supported by the NHLBI (R01HL094806 and R01HL118601) and the NIDDK (R01DK099512). A.-M.C. was also supported by the NHLBI (K01 HL115458). 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 NIH. The CARe study and SHHS are supported by the NHLBI cooperative agreements U01HL53941 (Boston University), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL53937 and U01HL63429 (Johns Hopkins University), and U01HL63463 (Case Western Reserve University). The following funding contributed to phenotype data collection in in-laboratory studies: NIA (R01AG06072, R01AG06072, and P01AG009975), NHLBI (R01HL077453, R01HL080978, R01HL093279, R01HL094654, and R01HL077399), Air Force Office of Scientific Research (FA9550), NIH (R21AT002571, R01NS054277, and R01MH45130), National Space Biomedical Research Institute (HFP01601), Brain & Behavior Research Foundation Young Investigator Award, and General Clinical Research Center (M01RR02635). J.F.D. was supported by the NIA (R01AG044416), the NHLBI (R01HL093279 and R01HL094654), and the Brigham and Women's Hospital Brigham Research Institute Fund to Sustain Research Excellence. Investigators were also funded by financial contributions from Brigham and Women's Hospital and from Harvard University and its affiliated academic health care centers. This study was also funded by the NHLBI (01EHLE114088, K24EHL105664, R01HL09327, R01HL09465, and RC2EHL101340), the National Space Biomedical Research Institute (HFP02802), and the NIH (M01RR02635 and R01EGME10501). NR 45 TC 4 Z9 4 U1 1 U2 2 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 JUN PY 2016 VL 65 IS 6 BP 1741 EP 1751 DI 10.2337/db15-0999 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM7OA UT WOS:000376548700032 PM 26868293 ER PT J AU Cozen, ML Ryan, JC Shen, H Cheung, R Kaplan, DE Pocha, C Brau, N Aytaman, A Schmidt, WN Pedrosa, M Anand, BS Chang, KM Morgan, T Monto, A AF Cozen, Myrna L. Ryan, James C. Shen, Hui Cheung, Ramsey Kaplan, David E. Pocha, Christine Brau, Norbert Aytaman, Ayse Schmidt, Warren N. Pedrosa, Marcos Anand, Bhupinderjit S. Chang, Kyong-Mi Morgan, Timothy Monto, Alexander TI Improved Survival Among all Interferon-alpha-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Hepatitis C; Hepatitis C therapy; Cirrhosis; Hepatocellular carcinoma; Survival ID VIRUS-INFECTION; US VETERANS; CLINICAL-OUTCOMES; ELDERLY-PATIENTS; PLUS RIBAVIRIN; LIVER FIBROSIS; FOLLOW-UP; THERAPY; HCV; METAANALYSIS AB As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated. To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients. Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review. A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility. As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported. C1 [Cozen, Myrna L.; Ryan, James C.; Shen, Hui; Monto, Alexander] San Francisco VA Med Ctr, 4150 Clement St 111B, San Francisco, CA 94121 USA. [Cozen, Myrna L.; Ryan, James C.; Shen, Hui; Monto, Alexander] Univ Calif San Francisco, 4150 Clement St 111B, San Francisco, CA 94121 USA. [Cheung, Ramsey] Palo Alto VA Med Ctr, 3801 Miranda Ave,GI Hepatol 154C, Palo Alto, CA 94304 USA. [Cheung, Ramsey] Stanford Univ, 3801 Miranda Ave,GI Hepatol 154C, Palo Alto, CA 94304 USA. [Kaplan, David E.; Chang, Kyong-Mi] Philadelphia VA Med Ctr, A212 Med Res,Univ & Woodland Ave, Philadelphia, PA 19104 USA. [Kaplan, David E.; Chang, Kyong-Mi] Univ Penn, A212 Med Res,Univ & Woodland Ave, Philadelphia, PA 19104 USA. [Pocha, Christine] Minneapolis VA Med Ctr, 1 Vet Dr,GI, Minneapolis, MN 55417 USA. [Brau, Norbert] Bronx VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. [Aytaman, Ayse] New York Harbor Brooklyn & Manhattan VA Med Ctr, 800 Poly Pl, Brooklyn, NY 11209 USA. [Schmidt, Warren N.] Iowa City VA Med Ctr, 200 Hawkins Dr, Iowa City, IA 52242 USA. [Schmidt, Warren N.] Univ Iowa, 200 Hawkins Dr, Iowa City, IA 52242 USA. [Pedrosa, Marcos] Boston VA Hlth Care Syst & AbbVie Pharmaceut, 85 E Concord St 7700, Boston, MA 02118 USA. [Anand, Bhupinderjit S.] Houston VA Med Ctr, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. [Anand, Bhupinderjit S.] Baylor Univ, Digest Dis Sect, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. [Morgan, Timothy] Long Beach VA Med Ctr, 111G,5901 E 7th St, Long Beach, CA 90822 USA. [Morgan, Timothy] Univ Calif Irvine, 111G,5901 E 7th St, Long Beach, CA 90822 USA. RP Monto, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111B, San Francisco, CA 94121 USA.; Monto, A (reprint author), Univ Calif San Francisco, 4150 Clement St 111B, San Francisco, CA 94121 USA. EM Alexander.Monto@va.gov FU VA Merit [1I01 CX000295-01A1]; UCSF Liver Center NIH [P30 DK026743] FX Grant Support: VA Merit 1I01 CX000295-01A1 (PI: Monto) and the UCSF Liver Center NIH P30 DK026743 (Monto, Ryan). NR 43 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2016 VL 61 IS 6 BP 1744 EP 1756 DI 10.1007/s10620-016-4122-5 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DM8CG UT WOS:000376587600045 PM 27059981 ER PT J AU Sonnenberg, A Bakis, G AF Sonnenberg, Amnon Bakis, Gennadiy TI Probability of Iatrogenesis in Gastroenterology SO DIGESTIVE DISEASES AND SCIENCES LA English DT Letter C1 [Sonnenberg, Amnon; Bakis, Gennadiy] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2016 VL 61 IS 6 BP 1775 EP 1777 DI 10.1007/s10620-015-4030-0 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DM8CG UT WOS:000376587600051 PM 26781257 ER PT J AU Naples, JG Marcum, ZA Perera, S Newman, AB Greenspan, SL Gray, SL Bauer, DC Simonsick, EM Shorr, RI Hanlon, JT AF Naples, Jennifer G. Marcum, Zachary A. Perera, Subashan Newman, Anne B. Greenspan, Susan L. Gray, Shelly L. Bauer, Douglas C. Simonsick, Eleanor M. Shorr, Ronald I. Hanlon, Joseph T. TI Impact of Drug-Drug and Drug-Disease Interactions on Gait Speed in Community-Dwelling Older Adults SO DRUGS & AGING LA English DT Article ID PHYSICAL PERFORMANCE-MEASURES; BODY-COMPOSITION; FUNCTIONAL STATUS; MEDICATION USE; HEALTH ABC; DECLINE; ASSOCIATION; PEOPLE; ELDERS; FALLS AB Background Gait speed decline, an early marker of functional impairment, is a sensitive predictor of adverse health outcomes in older adults. The effect of potentially inappropriate medications, including drug-disease and drug-drug interactions, on gait speed decline is not well known. Objective The aim of this study was to determine if drug interactions impair functional status as measured by gait speed. Methods The sample included 2402 older adults with medication and gait speed data from the Health, Aging and Body Composition study. The independent variable was the frequency of drug-disease and/or drug-drug interactions at baseline and 3 additional years. The main outcome was a clinically meaningful gait speed decline of >= 0.1 m/s the year following drug interaction assessment. Adjusted odds ratios and 95 % confidence intervals (CIs) were calculated using multivariate generalized estimating equations for both the overall sample and a sample stratified by gait speed at time of drug interaction assessment. Results The prevalence of drug-disease and drug-drug interactions ranged from 7.6 to 9.3 and 10.5 to 12.3 %, respectively, with few participants (3.8-5.7 %) having multiple drug interactions. At least 22 % of participants had a gait speed decline of >= 0.1 m/s annually. Drug interactions were not significantly associated with gait speed decline overall or in the stratified sample of fast walkers. There was some evidence, however, that drug interactions increased the risk of gait speed decline among those participants with slower gait speeds, though p values did not reach statistical significance (adjusted odds ratio 1.22; 95 % CIs 0.96-1.56; p = 0.11). Moreover, a marginally significant dose-response relationship was seen with multiple drug interactions and gait speed decline (adjusted odds ratio 1.40; 95 % CIs 0.95-2.04; p = 0.08). Conclusions Drug interactions may increase the likelihood of gait speed decline among older adults with evidence of preexisting debility. Future studies should focus on frail elders with less physiological reserve who may be more susceptible to the harms associated with potentially inappropriate medications. C1 [Naples, Jennifer G.; Perera, Subashan; Newman, Anne B.; Greenspan, Susan L.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Div Geriatr, Dept Med, Kaufmann Med Bldg,Suite 500,3471 Fifth Ave, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Perera, Subashan] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Shorr, Ronald I.] Malcolm Randall Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. RP Naples, JG (reprint author), Univ Pittsburgh, Sch Med, Div Geriatr, Dept Med, Kaufmann Med Bldg,Suite 500,3471 Fifth Ave, Pittsburgh, PA 15213 USA.; Naples, JG (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.; Naples, JG (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. EM jgn13@pitt.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG024827, T32-AG021885, K07-AG033174, R01-AG028050, R01-AG037451]; NINR Grant [R01-NR012459]; Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by NIA contracts (N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106), Grants (P30-AG024827, T32-AG021885, K07-AG033174, R01-AG028050, R01-AG037451), NINR Grant (R01-NR012459), and in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 28 TC 0 Z9 0 U1 5 U2 5 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-229X EI 1179-1969 J9 DRUG AGING JI Drugs Aging PD JUN PY 2016 VL 33 IS 6 BP 411 EP 418 DI 10.1007/s40266-016-0373-2 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA DM5UT UT WOS:000376416400004 PM 27138955 ER PT J AU Amlashi, FG Tritos, NA AF Amlashi, Fatemeh G. Tritos, Nicholas A. TI Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management SO ENDOCRINE LA English DT Review DE Thyrotropinoma; Pituitary adenoma; TSH ID THYROID-STIMULATING HORMONE; FIBROBLAST-GROWTH-FACTOR; OF-THE-LITERATURE; FOLLOW-UP; INAPPROPRIATE SECRETION; SOMATOSTATIN RECEPTOR; ALPHA-SUBUNIT; TSH SECRETION; SINGLE-CENTER; AUTOIMMUNE HYPOTHYROIDISM AB Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas. C1 [Amlashi, Fatemeh G.; Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA. [Amlashi, Fatemeh G.; Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA.; Tritos, NA (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM ntritos@partners.org NR 129 TC 2 Z9 2 U1 8 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD JUN PY 2016 VL 52 IS 3 BP 427 EP 440 DI 10.1007/s12020-016-0863-3 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DM9ER UT WOS:000376668100005 PM 26792794 ER PT J AU McKenzie, ED Nirola, DK Deki, S Tshering, L Patenaude, B Clark, SJ Cash, SS Thibert, R Zepeda, R Leung, ECW Lam, AD Lim, ASP Mantia, J Cohen, J Cole, AJ Mateen, FJ AF McKenzie, Erica D. Nirola, Damber K. Deki, Sonam Tshering, Lhab Patenaude, Bryan Clark, Sarah J. Cash, Sydney S. Thibert, Ronald Zepeda, Rodrigo Leung, Edward C. W. Lam, Alice D. Lim, Andrew S. P. Mantia, Jo Cohen, Joseph Cole, Andrew J. Mateen, Farrah J. TI Medication prescribing and patient-reported outcome measures in people with epilepsy in Bhutan SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Electroencephalography; Antiepileptic drugs; Global health; Resource-limited settings; Epilepsy management gap ID TREATMENT GAP; ANTIEPILEPTIC DRUGS; COUNTRIES; QUALITY; WOMEN AB Objective: The aim of this study was to assess medication prescribing and patient-reported outcomes among people with epilepsy (PWE) in Bhutan and introduce criteria for evaluating unmet epilepsy care needs, particularly in resource-limited settings. Methods: People with epilepsy in Bhutan (National Referral Hospital, 2014-2015) completed a questionnaire, the Quality of Life in Epilepsy Inventory (QOLIE-31), and an electroencephalogram (EEG). Management gap was the proportion of participants meeting any of six prespecified criteria based on best practices and the National Institute for Health and Care Excellence (NICE) guidelines. Results: Among 253 participants (53% female, median: 24 years), 93% (n = 235) were treated with antiepileptic drugs (AEDs). Seventy-two percent (n = 183) had active epilepsy (= 1 seizure in the prior year). At least one criterion was met by 55% (n = 138) of participants, whereas the treatment gap encompassed only 5% (n = 13). The criteria were the following: 1. Among 18 participants taking no AED, 72% (n = 13) had active epilepsy. 2. Among 26 adults on subtherapeutic monotherapy, 46% (n = 12) had active epilepsy. 3. Among 48 participants reporting staring spells, 56% (n = 27) were treated with carbamazepine or phenytoin. 4. Among 101 female participants aged 14-40 years, 23% (n = 23) were treated with sodium valproate. 5. Among 67 participants reporting seizure-related injuries, 87% (n = 58) had active epilepsy. 6. Among 111 participants with a QOLIE-31 score below 50/100, 77% (n = 86) had active epilepsy. Years since first AED treatment (odds ratio: 1.07, 95% CI: 1.03, 1.12) and epileptiform discharges on EEG (odds ratio: 1.95, 95% CI: 1.15, 3.29) were significantly associated with more criteria met. Conclusions: By defining the management gap, subpopulations at greatest need for targeted interventions may be prioritized, including those already taking AEDs. (C) 2016 Elsevier Inc. All rights reserved. C1 [McKenzie, Erica D.; Clark, Sarah J.; Cash, Sydney S.; Thibert, Ronald; Zepeda, Rodrigo; Lam, Alice D.; Cohen, Joseph; Cole, Andrew J.; Mateen, Farrah J.] Massachusetts Gen Hosp, 165 Cambridge St 627, Boston, MA 02114 USA. [Nirola, Damber K.; Deki, Sonam; Tshering, Lhab] Jigme Dorji Wangchuck Natl Referral Hosp, Thimphu, Bhutan. [Patenaude, Bryan] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Leung, Edward C. W.] Hlth Sci Ctr, Winnipeg, MB, Canada. [Lim, Andrew S. P.; Mantia, Jo] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, 165 Cambridge St 627, Boston, MA 02114 USA. EM fmateen@mgh.harvard.edu OI Nirola, Damber/0000-0003-3941-6081 FU Grand Challenges Canada; Thrasher Research Fund FX Tali R. Sorets (Massachusetts General Hospital, Boston, USA), Chencho Dorji (formerly of the Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan), Sonam Wangda (Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan), Kate Brizzi (Massachusetts General Hospital, Boston, USA), Hannah McLane (University of Pennsylvania, Philadelphia, USA), Sarah Wahlster (University of Washington, Seattle, WA, USA), and Karma Ugyen (National Traditional Medicine Hospital, Thimphu, Bhutan) for assistance with data collection and Gretchen Birbeck (University of Rochester, Rochester, USA) for comments on earlier forms of the manuscript. This study was supported by Grand Challenges Canada and the Thrasher Research Fund. NR 23 TC 0 Z9 0 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUN PY 2016 VL 59 BP 122 EP 127 DI 10.1016/j.yebeh.2016.03.035 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DM6IQ UT WOS:000376455600021 PM 27131914 ER PT J AU Bralet, MC Buchsbaum, MS DeCastro, A Hazlett, EA Haznedar, MM Shihabuddin, L Mitelman, SA AF Bralet, Marie-Cecile Buchsbaum, Monte S. DeCastro, Alex Hazlett, Erin A. Haznedar, M. Mehmet Shihabuddin, Lina Mitelman, Serge A. TI FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia (vol 266, pg 379, 2016) SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Correction C1 [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Psychiat, 11388 Sorrento Valley Rd, San Diego, CA 92103 USA. [Buchsbaum, Monte S.] Univ Calif San Diego, Dept Radiol, 11388 Sorrento Valley Rd, San Diego, CA 92103 USA. [Bralet, Marie-Cecile] CHI Clermont Oise, Crisalid Unit FJ5, 2 Rue Finets, F-60607 Clermont, France. [Bralet, Marie-Cecile] Univ Paris 05, Inserm Unit U669, Maison Solenn, F-75014 Paris, France. [Bralet, Marie-Cecile] Univ Paris 11, F-75014 Paris, France. [Bralet, Marie-Cecile] GDR 3557 Rech Psychiat, Paris, France. [DeCastro, Alex] Univ Calif San Diego, Dept Psychiat, 11388 Sorrento Valley Rd, San Diego, CA 92103 USA. [Hazlett, Erin A.; Haznedar, M. Mehmet; Shihabuddin, Lina; Mitelman, Serge A.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Hazlett, Erin A.; Haznedar, M. Mehmet] James J Peters Vet Adm Med Ctr, Bronx, NY USA. [Mitelman, Serge A.] Elmhurst Hosp Ctr, Dept Psychiat, 79 01 Broadway, Elmhurst, NY 11373 USA. RP Buchsbaum, MS (reprint author), Univ Calif San Diego, Dept Psychiat, 11388 Sorrento Valley Rd, San Diego, CA 92103 USA.; Buchsbaum, MS (reprint author), Univ Calif San Diego, Dept Radiol, 11388 Sorrento Valley Rd, San Diego, CA 92103 USA. EM mcbralet@gmail.com; monte.buchsbaum@gmail.com; alexdecastro2@gmail.com; linashihabuddin@comcast.net; serge.mitelman@mssm.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 EI 1433-8491 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUN PY 2016 VL 266 IS 4 BP 379 EP 379 DI 10.1007/s00406-015-0661-6 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DM9GO UT WOS:000376673400012 ER PT J AU Huynh, MA Chen, MH Wu, J Braccioforte, MH Moran, BJ D'Amico, AV AF Mai Anh Huynh Chen, Ming-Hui Wu, Jing Braccioforte, Michelle H. Moran, Brian J. D'Amico, Anthony V. TI Gleason Score 3+5 or 5+3 versus 4+4 Prostate Cancer: The Risk of Death SO EUROPEAN UROLOGY LA English DT Article DE Gleason score; Prostate cancer; Mortality ID CARCINOMA AB The International Society of Urological Pathology recommends that Gleason score (GS) 8 prostate cancer (PC) is one prognostic category, yet heterogeneity in cancer control potentially exists amongst men with GS 3 + 5/5 + 3 versus GS 4 + 4 PC. We compared PC-specific mortality (PCSM) and all-cause mortality (ACM) risk among men with GS 3 + 5/5 + 3 versus GS 4 + 4 PC using competing-risks and Cox regression analyses, adjusting for age, known PC prognostic factors, treatment, and a treatment propensity score. Between 1998 and 2012, 462 men with GS 8 PC were treated using brachytherapy with supplemental external-beam radiation therapy and/or androgen deprivation therapy at the Chicago Prostate Cancer Center. After a median follow-up of 7.6 yr, 118 men died, 26 of PC. PCSM (adjusted hazard ratio [AHR] 2.77, 95% confidence interval [CI] 1.13-6.80; p = 0.026) and ACM (AHR 1.75, 95% CI 1.06-2.87; p = 0.028) were significantly higher for men with GS 3 + 5/5 + 3 PC than for men with GS 4 + 4 PC. Subcategorizing GS 8 into PC with or without grade 5 should be considered as a stratification factor in randomized trials. Patient summary: Long-term success rates for men with Gleason score 8 prostate cancer vary depending on whether the most aggressive type of cancer (grade 5) is present at biopsy. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Mai Anh Huynh] Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. [Chen, Ming-Hui; Wu, Jing] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Chicago Prostate Canc Ctr, Westmont, IL USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. RP Huynh, MA (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM mahuynh@lroc.harvard.edu NR 10 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JUN PY 2016 VL 69 IS 6 BP 976 EP 979 DI 10.1016/j.eururo.2015.08.054 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DN4OP UT WOS:000377047400013 PM 26388503 ER PT J AU Martin, NE Stowell, C AF Martin, Neil E. Stowell, Caleb TI Reply to Daniela Wittmann, Ted A. Skolarus' Letter to the Editor re: Neil E. Martin, Laura Massey, Caleb Stowell, et al. Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer. Eur Urol 2014;67:460-7 SO EUROPEAN UROLOGY LA English DT Letter C1 [Stowell, Caleb] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Martin, Neil E.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Martin, NE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JUN PY 2016 VL 69 IS 6 BP E127 EP E127 DI 10.1016/j.eururo.2016.01.041 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DN4OP UT WOS:000377047400006 PM 26873843 ER PT J AU Sammon, JD Abdollah, FA Trinh, QD AF Sammon, Jesse D. Abdollah, Firas A. Quoc-Dien Trinh TI Reply to Michael Froehner, Rainer Koch, Manfred P. Wirth's Letter to the Editor re: Jesse D. Sammon, Firas Abdollah, Anthony D'Amico, et al. Predicting Life Expectancy in Men Diagnosed with Prostate Cancer. Eur Urol 2015;68:756-65 SO EUROPEAN UROLOGY LA English DT Letter C1 [Sammon, Jesse D.; Abdollah, Firas A.] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. [Sammon, Jesse D.; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Quoc-Dien Trinh] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. RP Sammon, JD (reprint author), Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM jsammon79@gmail.com NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JUN PY 2016 VL 69 IS 6 BP E129 EP E129 DI 10.1016/j.eururo.2015.09.041 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DN4OP UT WOS:000377047400008 PM 26461111 ER PT J AU Zhang, W Szostak, JW Huang, Z AF Zhang, Wen Szostak, Jack W. Huang, Zhen TI Nucleic acid crystallization and X-ray crystallography facilitated by single selenium atom SO FRONTIERS OF CHEMICAL SCIENCE AND ENGINEERING LA English DT Review DE selenium; DNA; RNA; nucleic acid; crystallization ID MULTIWAVELENGTH ANOMALOUS DIFFRACTION; CRYSTAL-STRUCTURE; SYNCHROTRON RADIATION; STRUCTURAL INSIGHTS; ESCHERICHIA-COLI; DNA; OLIGONUCLEOTIDES; RNA; DERIVATIZATION; MAD AB X-ray crystallography is a powerful strategy for 3-D structure determination of macromolecules, such as nucleic acids and protein-nucleic acid complexes. However, the crystallization and phase determination are the major bottle-neck problems in crystallography. Recently we have successfully developed synthesis and strategy of selenium-derivatized nucleic acids (SeNA) for nucleic acid crystallography. SeNA might not only provide the rational strategies to solve the phase determination problem, but also offer a potential strategy to explore crystallization solutions. C1 [Zhang, Wen; Huang, Zhen] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. [Zhang, Wen; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Zhang, Wen; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Zhang, Wen; Huang, Zhen] Sichuan Univ, Coll Life Sci, Chengdu 610041, Peoples R China. RP Huang, Z (reprint author), Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.; Huang, Z (reprint author), Sichuan Univ, Coll Life Sci, Chengdu 610041, Peoples R China. EM huang@gsu.edu NR 48 TC 2 Z9 2 U1 8 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2095-0179 EI 2095-0187 J9 FRONT CHEM SCI ENG JI Front. Chem. Sci. Eng. PD JUN PY 2016 VL 10 IS 2 BP 196 EP 202 DI 10.1007/s11705-016-1565-3 PG 7 WC Engineering, Chemical SC Engineering GA DM8UG UT WOS:000376639400004 ER PT J AU Garcia, MA Solomon, DA Haas-Kogan, DA AF Garcia, Michael A. Solomon, David A. Haas-Kogan, Daphne A. TI Exploiting molecular biology for diagnosis and targeted management of pediatric low-grade gliomas SO FUTURE ONCOLOGY LA English DT Review DE pediatric low-grade glioma; pediatrics; targeted therapy ID TUBEROUS SCLEROSIS COMPLEX; INTRINSIC PONTINE GLIOMA; GIANT-CELL ASTROCYTOMAS; CENTRAL-NERVOUS-SYSTEM; PILOCYTIC ASTROCYTOMAS; ANGIOCENTRIC GLIOMA; SIGNALING PATHWAY; GENE-EXPRESSION; K27M MUTATION; HISTONE H3.3 AB The majority of brain tumors arising in children are low-grade gliomas. Although historically categorized together as pediatric low-grade gliomas (PLGGs), there is significant histologic and genetic diversity within this group. In general, prognosis for PLGGs is excellent, and limitation of sequelae from tumor and treatment is paramount. Advances in high-throughput genetic sequencing and gene expression profiling are fundamentally changing the way PLGGs are classified and managed. Here, we review the histologic subtypes and highlight how recent advances in elucidating the molecular pathogenesis of these tumors have refined diagnosis and prognostication. Additionally, we discuss how characterizing specific genetic alterations has paved the way for the rational use of targeted therapies that are currently in various phase clinical trials. C1 [Garcia, Michael A.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Solomon, David A.] Univ Calif San Francisco, Dept Pathol, Div Neuropathol, San Francisco, CA 94140 USA. [Haas-Kogan, Daphne A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst,Boston Ch, Cambridge, MA 02138 USA. RP Garcia, MA (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. EM michael.garcia@ucsf.edu FU NINDS NIH HHS [R01 NS091620] NR 82 TC 1 Z9 1 U1 2 U2 3 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 JUN PY 2016 VL 12 IS 12 BP 1493 EP 1506 DI 10.2217/fon-2016-0039 PG 14 WC Oncology SC Oncology GA DM3QP UT WOS:000376261500007 PM 27072750 ER PT J AU Khalili, H Granath, F Smedby, KE Ekbom, A Neovius, M Chan, AT Olen, O AF Khalili, Hamed Granath, Fredrik Smedby, Karin E. Ekbom, Anders Neovius, Martin Chan, Andrew T. Olen, Ola TI Association Between Long-term Oral Contraceptive Use and Risk of Crohn's Disease Complications in a Nationwide Study SO GASTROENTEROLOGY LA English DT Article DE Crohn's Disease; Birth Control; Surgery; Swedish National Patient Register ID INFLAMMATORY-BOWEL-DISEASE; CIGARETTE-SMOKING; BARRIER FUNCTION; CLINICAL-COURSE; SEX-DIFFERENCES; REGISTER; RELAPSE AB BACKGROUND & AIMS: Use of exogenous hormones, in the form of oral contraceptives (OCs), has been linked consistently to risk of Crohn's disease (CD). Nonetheless, it is not clear how OCs might contribute to the progression of CD. METHODS: We conducted a prospective study of female patients with CD (age, 16-51 y), identified from the inpatient and outpatient care components of the Swedish National Patient Register from January 2002 through December 2013. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005 and updated until December of 2013. Primary outcomes were defined as first CD-related surgery and first steroid prescription. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratios (MV-adjusted HRs). RESULTS: We identified 482 incident cases of surgery among 4036 patients with CD, with a median follow-up period of 58 months. Compared with nonusers, the MV-adjusted HRs for surgery were 1.14 (95% confidence interval [CI], 0.80-1.63) for past users and 1.30 (95% CI, 0.89-1.92) for current users. The risk of surgery increased with longer duration of use (P-trend = .036) and higher prescribed daily dose (P-trend = .016). Specifically, for women with more than 3 years of OC use, the MV-adjusted HR for surgery was 1.68 (95% CI, 1.06-2.67). The association was confined to the combination type of OC. We estimated that for every 83 patients with CD receiving the combination type of oral contraceptives for at least 1 year, 1 extra surgery is required. The rate of steroid prescriptions did not appear to increase with past or current use of OCs, compared with patients who have not taken OCs (all Pcomparisons > .20). CONCLUSIONS: In a nationwide analysis of patients in Sweden, long-term use of OCs, particularly the combination type, was associated with an increased risk of surgery among women with established CD. Clinicians carefully should evaluate and monitor contraceptive options among women with established CD. C1 [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Granath, Fredrik; Smedby, Karin E.; Ekbom, Anders; Neovius, Martin; Olen, Ola] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Solna, Sweden. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Digest Healthcare Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM hkhalili@mgh.harvard.edu OI Neovius, Martin/0000-0003-2300-3055 FU Crohn's and Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24 DK098311]; American Gastroenterological Association; National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; American College of Gastroenterology FX Supported by a senior investigator grant from the Crohn's and Colitis Foundation of America and by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; K24 DK098311) (A.C.), and by a career development award from the American Gastroenterological Association and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681) (H.K.). This work also was supported by a travel grant from the American College of Gastroenterology. NR 26 TC 6 Z9 6 U1 0 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2016 VL 150 IS 7 BP 1561 EP + DI 10.1053/j.gastro.2016.02.041 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DN0TW UT WOS:000376778800028 PM 26919969 ER PT J AU Serper, M Choi, G Forde, KA Kaplan, DE AF Serper, Marina Choi, Gina Forde, Kimberly A. Kaplan, David E. TI Care Delivery and Outcomes Among US Veterans With Hepatitis B: A National Cohort Study SO HEPATOLOGY LA English DT Article ID C VIRUS-INFECTION; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; ADMINISTRATIVE DATABASE; IDENTIFY PATIENTS; PREVALENCE; SURVEILLANCE; VALIDATION; MANAGEMENT; ADHERENCE AB Previous studies have identified gaps in hepatitis B care. The objectives of this study were to evaluate the delivery of care among a national cohort of US veterans with chronic hepatitis B infection and examine risk factors for adverse clinical outcomes. We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse from 1999 to 2013 to evaluate (1) care delivery and (2) clinical outcomes such as hepatocellular carcinoma, hepatic decompensation, and mortality among US veterans with hepatitis B. Incidence rates with 95% confidence intervals were calculated and Cox regression models were used to evaluate clinical outcomes. We identified 21,419 veterans with a positive hepatitis B surface antigen, and 97% of patients had alanine aminotransferase and 44% had hepatitis B virus DNA testing; hepatitis B e antigen and hepatitis B e antibody were tested <50% of the time. Patients receiving specialty care had a higher prevalence of recommended laboratory testing. Patients with elevated alanine aminotransferase in specialty care were more likely to receive antiviral therapy (50% versus 24% for specialty care versus no specialty care, P < 0.001). Among patients with cirrhosis, 69% received one-time liver imaging. The proportion of follow-up time adherent to annual imaging was 0.39 (standard deviation = 0.42), and the proportion was 0.28 (standard deviation = 0.33) for biannual imaging; both proportions were higher in the specialty care group (all P < 0.05). Antiviral therapy (hazard ratio = 0.85, 95% confidence interval 0.76-0.95, P = 0.005) and liver imaging (hazard ratio = 0.84, 95% confidence interval 0.76-0.91, P < 0.001) were independently associated with decreased mortality in adjusted analyses. Conclusion: We observed a low prevalence of recommended laboratory testing, antiviral therapy initiation, and liver imaging among a national cohort of veterans with hepatitis B infection; antiviral therapy and liver imaging were independently associated with decreased mortality. C1 [Serper, Marina; Kaplan, David E.] Philadelphia VA Med Ctr, Gastroenterol Sect, 3900 Woodland Ave,4th Floor,South Bldg, Philadelphia, PA 19104 USA. [Serper, Marina] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 3900 Woodland Ave,4th Floor,South Bldg, Philadelphia, PA 19104 USA. [Serper, Marina; Choi, Gina; Forde, Kimberly A.; Kaplan, David E.] Hosp Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Forde, Kimberly A.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Serper, M (reprint author), Philadelphia VA Med Ctr, Gastroenterol Sect, 3900 Woodland Ave,4th Floor,South Bldg, Philadelphia, PA 19104 USA.; Serper, M (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, 3900 Woodland Ave,4th Floor,South Bldg, Philadelphia, PA 19104 USA.; Serper, M (reprint author), Hosp Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA.; Serper, M (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave,4th Floor,South Bldg, Philadelphia, PA 19104 USA. EM marina.serper@uphs.upenn.edu OI Kaplan, David E./0000-0002-3839-336X NR 32 TC 3 Z9 3 U1 0 U2 1 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 JUN PY 2016 VL 63 IS 6 BP 1774 EP 1782 DI 10.1002/hep.28340 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DM5BN UT WOS:000376361800008 PM 26561023 ER PT J AU Simon, TG Chung, RT AF Simon, Tracey G. Chung, Raymond T. TI Hypoglycemia in a Diabetic Patient During Hepatitis C Therapy REPLY SO HEPATOLOGY LA English DT Letter ID SUSTAINED VIROLOGICAL RESPONSE; RISK; FIBROSIS; VIRUS C1 [Simon, Tracey G.] Brigham & Womens Hosp, Dept Internal Med, 75 Francis St, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Simon, TG (reprint author), Brigham & Womens Hosp, Dept Internal Med, 75 Francis St, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2016 VL 63 IS 6 BP 2066 EP 2067 DI 10.1002/hep.28136 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DM5BN UT WOS:000376361800045 PM 26316092 ER PT J AU Makris, A Yeung, KR Lim, SM Sunderland, N Heffernan, S Thompson, JF Iliopoulos, J Killingsworth, MC Yong, J Xu, B Ogle, RF Thadhani, R Karumanchi, SA Hennessy, A AF Makris, Angela Yeung, Kristen R. Lim, Shirlene M. Sunderland, Neroli Heffernan, Scott Thompson, John F. Iliopoulos, Jim Killingsworth, Murray C. Yong, Jim Xu, Bei Ogle, Robert F. Thadhani, Ravi Karumanchi, S. Ananth Hennessy, Annemarie TI Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates SO HYPERTENSION LA English DT Article DE animal model; hypertension; placental growth factor; preeclampsia/pregnancy ID CIRCULATING ANGIOGENIC FACTORS; TYROSINE KINASE-1 EXPRESSION; INDUCED HYPERTENSION; UTERINE PERFUSION; PROTEINURIC HYPERTENSION; VASCULAR RELAXATION; NORMAL-PREGNANCY; MOUSE MODEL; RAT MODEL; PLASMA AB An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 mu g/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2 +/- 0.8 mm Hg; from 132.6 +/- 6.6 mm Hg to 124.1 +/- 7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5 +/- 3 mm Hg; from 131.3 +/- 1.5 mm Hg to 138.6 +/- 1.5 mm Hg). Proteinuria reduced in the treated group (-72.7 +/- 55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. C1 [Makris, Angela; Yeung, Kristen R.; Lim, Shirlene M.; Iliopoulos, Jim; Killingsworth, Murray C.; Xu, Bei; Hennessy, Annemarie] Univ Western Sydney, Fac Med, Sydney, NSW, Australia. [Makris, Angela; Yeung, Kristen R.; Lim, Shirlene M.; Iliopoulos, Jim; Killingsworth, Murray C.; Xu, Bei; Hennessy, Annemarie] Ingham Inst, Sydney, NSW, Australia. [Makris, Angela; Killingsworth, Murray C.; Yong, Jim] Univ New S Wales, Fac Med, Sydney, NSW, Australia. [Makris, Angela; Iliopoulos, Jim] Liverpool Hosp, Dept Nephrol, Liverpool, NSW 2170, Australia. [Makris, Angela; Yeung, Kristen R.; Lim, Shirlene M.; Xu, Bei; Hennessy, Annemarie] Heart Res Inst, Vasc Immunol Grp, Sydney, NSW, Australia. [Sunderland, Neroli; Heffernan, Scott] Royal Prince Alfred Hosp, Dept Nephrol, Sydney, NSW, Australia. [Thompson, John F.] Royal Prince Alfred Hosp, Melanoma Unit, Sydney, NSW, Australia. [Ogle, Robert F.] Royal Prince Alfred Hosp, Dept Obstet, Sydney, NSW, Australia. [Thompson, John F.] Univ Sydney, Dept Surg, Sydney, NSW 2006, Australia. [Killingsworth, Murray C.; Yong, Jim] Liverpool Hosp, Dept Anat Pathol, Liverpool, NSW 2170, Australia. [Iliopoulos, Jim] Liverpool Hosp, Dept Vasc Surg, Liverpool, NSW 2170, Australia. [Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA. RP Makris, A (reprint author), Liverpool Hosp, Renal Dept, Clin Bldg,Elizabeth St, Liverpool, NSW 2170, Australia. EM angela.makris@sswahs.nsw.gov.au OI Hennessy, Annemarie/0000-0002-5975-2843 FU NHMRC [APP1025258]; Australian Postgraduate Award; Howard Hughes Medical Institute FX NHMRC Project Grant (APP1025258), Australian Postgraduate Award (K. Yeung), Howard Hughes Medical Institute (S.A. Karumanchi). NR 54 TC 5 Z9 5 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2016 VL 67 IS 6 BP 1263 EP 1272 DI 10.1161/HYPERTENSIONAHA.116.07286 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DM6NK UT WOS:000376469500033 PM 27091894 ER PT J AU Shahul, S Medvedofsky, D Wenger, JB Nizamuddin, J Brown, SM Bajracharya, S Salahuddin, S Thadhani, R Mueller, A Tung, A Lang, RM Arany, Z Talmor, D Karumanchi, SA Rana, S AF Shahul, Sajid Medvedofsky, Diego Wenger, Julia B. Nizamuddin, Junaid Brown, Samuel M. Bajracharya, Surichhya Salahuddin, Saira Thadhani, Ravi Mueller, Ariel Tung, Avery Lang, Roberto M. Arany, Zoltan Talmor, Daniel Karumanchi, S. Ananth Rana, Sarosh TI Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy SO HYPERTENSION LA English DT Article DE biomarkers; echocardiography; hypertension; preeclampsia; pregnancy ID VENTRICULAR EJECTION FRACTION; LONGITUDINAL STRAIN; SOLUBLE ENDOGLIN; PERIPARTUM CARDIOMYOPATHY; GESTATIONAL HYPERTENSION; TYROSINE KINASE-1; HEART-FAILURE; GROWTH-FACTOR; PREECLAMPSIA; WOMEN AB Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS (r=0.44 for sFlt1 and r=0.46 for sEng, both P<0.001), which remained significant after multivariable analysis (r=0.18 and r=0.22, both P=0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis (r=0.20 for sFlt1 and 0.19 for sEng, both P=0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS. C1 [Shahul, Sajid; Nizamuddin, Junaid; Tung, Avery] Univ Chicago, Dept Anesthesia & Crit Care, Box 428, Chicago, IL 60637 USA. [Medvedofsky, Diego; Lang, Roberto M.] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chicago, IL 60637 USA. [Wenger, Julia B.; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA USA. [Brown, Samuel M.] Univ Utah, Dept Med, Intermt Healthcare, Ctr Humanizing Crit Care, Salt Lake City, UT 84112 USA. [Bajracharya, Surichhya; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [Salahuddin, Saira; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol,Dept Med, Boston, MA 02215 USA. [Mueller, Ariel; Talmor, Daniel] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Arany, Zoltan] Univ Penn, Dept Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. RP Shahul, S (reprint author), Univ Chicago, 5841 S,Maryland Ave,MC 4028, Chicago, IL 60637 USA. EM sshahul1@dacc.uchicago.edu RI Brown, Samuel/E-6846-2015 OI Brown, Samuel/0000-0003-1206-6261 FU Foundation for Anesthesia Research; Center for Anesthesia Research Excellence; Howard Hughes Medical Institute FX S. Shahul was supported by the Foundation for Anesthesia Research and the Center for Anesthesia Research Excellence. S.A. Karumanchi was supported by the Howard Hughes Medical Institute. NR 48 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2016 VL 67 IS 6 BP 1273 EP 1280 DI 10.1161/HYPERTENSIONAHA.116.07252 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DM6NK UT WOS:000376469500034 PM 27113052 ER PT J AU Morgan, DJ Safdar, N Milstone, AM Anderson, DJ AF Morgan, Daniel J. Safdar, Nasia Milstone, Aaron M. Anderson, Deverick J. TI Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB Research in Healthcare Epidemiology and Antimicrobial Stewardship (HE&AS) is rapidly expanding with the involvement of researchers from varied countries and backgrounds. Researchers must use scientific methods that will provide the strongest evidence to advance healthcare epidemiology, but there are limited resources for information on specific aspects of HE&AS research or easy ways to access examples of studies using specific methods with HE&AS. In response to this need, the SHEA Research Committee has developed a series of white papers on research methods in HE&AS. The objective of this series is to promote rigorous healthcare epidemiology research by summarizing critical components, practical considerations, and pitfalls of commonly used research methods. C1 [Morgan, Daniel J.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Morgan, Daniel J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel J.] Ctr Dis Dynam Econ & Policy, Washington, DC USA. [Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Infect Dis, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Milstone, Aaron M.] Johns Hopkins Univ, Dept Pediat, Div Infect Dis, Baltimore, MD 21218 USA. [Anderson, Deverick J.] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC USA. RP Anderson, DJ (reprint author), Duke Univ, Med Ctr, Med, DUMC Box 102359, Durham, NC 27710 USA. EM deverick.anderson@duke.edu FU National Insitutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [K23AI095357] FX D.J.A. was supported by a grant from the National Insitutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) (grant no. K23AI095357). NR 3 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 JUN PY 2016 VL 37 IS 6 BP 627 EP 628 DI 10.1017/ice.2016.91 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DM7LO UT WOS:000376541900001 PM 27074955 ER PT J AU Chou, AF Graber, CJ Jones, M Zhang, Y Goetz, MB Madaras-Kelly, K Samore, M Kelly, A Glassman, PA AF Chou, Ann F. Graber, Christopher J. Jones, Makoto Zhang, Yue Goetz, Matthew Bidwell Madaras-Kelly, Karl Samore, Matthew Kelly, Allison Glassman, Peter A. TI Characteristics of Antimicrobial Stewardship Programs at Veterans Affairs Hospitals: Results of a Nationwide Survey SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; INFECTIOUS-DISEASES; ANTIBIOTIC-THERAPY; FRENCH HOSPITALS; CARE; IMPACT; INTERVENTION; ASSOCIATION; MANAGEMENT; GUIDELINE AB BACKGROUND. Antimicrobial stewardship programs (ASPs) are variably implemented. OBJECTIVE. To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage. DESIGN. A web-based survey regarding stewardship activities was administered to each facility's designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined. SETTING. Total of 130 Veterans Affairs facilities with inpatient services. RESULTS. Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P =.03), an ID fellowship program (P =.003), and a clinical pharmacist with formal ID training (P =. 006) as well as frequency of systematic patient-level reviews of antimicrobial use (P =.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P =.01). Stop orders for antimicrobial duration were associated with increased use (P =. 03). CONCLUSIONS. ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices. C1 [Chou, Ann F.] Univ Oklahoma, Coll Publ Hlth, Dept Hlth Adm & Policy, Oklahoma City, OK USA. [Chou, Ann F.] Univ Oklahoma, Coll Med, Dept Family & Prevent Med, 900 NE 10th St, Oklahoma City, OK 73104 USA. [Chou, Ann F.] Vet Affairs VA Greater Los Angeles Healthcare Sys, Los Angeles, CA USA. [Graber, Christopher J.; Goetz, Matthew Bidwell; Glassman, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Graber, Christopher J.; Goetz, Matthew Bidwell] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Jones, Makoto; Samore, Matthew] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. [Jones, Makoto; Samore, Matthew] Univ Utah, Div Epidemiol, Salt Lake City, UT USA. [Jones, Makoto; Samore, Matthew] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Zhang, Yue] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Zhang, Yue] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA. [Madaras-Kelly, Karl] Vet Affairs Med Ctr, Boise, ID USA. [Madaras-Kelly, Karl] Idaho State Univ, Coll Pharm, Meridian, ID USA. [Kelly, Allison] VA Cent Off, Natl Infect Dis Serv, Washington, DC USA. [Glassman, Peter A.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. RP Chou, AF (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Family & Prevent Med, 900 NE 10th St, Oklahoma City, OK 73104 USA. EM ann-chou@ouhsc.edu FU VA Office of Health Services Research and Development [HX-12-018, CRE 12-313] FX VA Office of Health Services Research and Development (HX-12-018, Collaborative Research to Enhance and Advance Transformation and Excellence Initiative, and CRE 12-313, "Cognitive Support Informatics for Antimicrobial Stewardship [PI: P. Glassman]"). NR 37 TC 2 Z9 2 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2016 VL 37 IS 6 BP 647 EP 654 DI 10.1017/ice.2016.26 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DM7LO UT WOS:000376541900004 PM 26905338 ER PT J AU van Leeuwen, WF van der Vliet, QMJ Janssen, SJ Heng, M Ring, D Vranceanu, AM AF van Leeuwen, Wouter F. van der Vliet, Quirine M. J. Janssen, Stein J. Heng, Marilyn Ring, David Vranceanu, Ana-Maria TI Does perceived injustice correlate with pain intensity and disability in orthopaedic trauma patients? SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Perceived injustice; Trauma; Disability; Physical function; Pain intensity; Orthopaedic ID EXPERIENCE QUESTIONNAIRE; PSYCHOLOGICAL-FACTORS; 2-ITEM QUESTIONNAIRE; MUSCULOSKELETAL PAIN; DEPRESSION; OUTCOMES; FIBROMYALGIA; POPULATION; PREVALENCE; VALIDATION AB Introduction: Individuals who experience musculoskeletal trauma may construe the experience as unjust and themselves as victims. Perceived injustice is a cognitive construct comprised by negative appraisals of the severity of loss as a consequence of injury, blame, injury-related loss, and unfairness. It has been associated with worse physical and psychological outcomes in the context of chronic health conditions. The purpose of this study is to explore the association of perceived injustice to pain intensity and physical function in patients with orthopaedic trauma. Methods: A total of 124 orthopaedic trauma patients completed the Injustice Experience Questionnaire (IEQ), the PROMIS Physical Function Computer Adaptive Testing (CAT), the PROMIS Pain Intensity instruments, the short form Patient Health Questionnaire for depression (PHQ-2), the short form Pain Self-Efficacy Questionnaire (PSEQ-2), and the short form Pain Catastrophizing Scale (PCS-4) on a tablet computer. A stepwise linear regression model was used to identify the best combination of predictors explaining variance in PROMIS Physical Function and PROMIS Pain Intensity. Results: The IEQ was associated with PROMIS Physical Function (r = -0.36; P < 0.001) and PROMIS Pain Intensity (r = 0.43; P < 0.001). In multivariable analysis, however, Caucasian race (beta = 5.1, SE: 2.0, P = 0.013, 95% CI: 1.1-9.2), employed work status (beta = 5.1, SE: 1.5, P = 0.001, 95% CI: 2.1-8.2), any cause of injury other than sports, mvc, or fall (b = 7.7, SE: 2.1, P < 0.001, 95% CI: 3.5-12), and higher self-efficacy (PSEQ-2; beta = 0.93, SE: 0.23, P < 0.001, 95% CI: 0.48-1.4) were selected as part of the best model predicting variance in PROMIS Physical Function. Only a higher degree of catastrophic thinking (PCS-4; beta = 1.2, SE: 0.12, P < 0.001, 95% CI: 0.99 to 1.5) was selected as important in predicting higher PROMIS Pain Intensity. Conclusion: Perceived injustice was associated with both physical function and pain intensity in bivariate correlations, but was not deemed as an important predictor when assessed along with other demographic and psychosocial variables in multivariable analysis. This study confirms prior research on the pivotal role of catastrophic thinking and self-efficacy in reports of pain intensity and physical function in patients with acute traumatic musculoskeletal pain. (C) 2016 Elsevier Ltd. All rights reserved. C1 [van Leeuwen, Wouter F.; van der Vliet, Quirine M. J.; Janssen, Stein J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Cambridge, MA 02138 USA. [Heng, Marilyn] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Trauma Serv, Cambridge, MA 02138 USA. [Ring, David] Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, Austin, TX 78712 USA. [Vranceanu, Ana-Maria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Ring, D (reprint author), 1400 Barbara Jordan Blvd Suite 1-114AC MC R1800, Austin, TX 78723 USA. EM wouter.f.vanleeuwen@gmail.com; q.m.j.vandervliet@gmail.com; steinjanssen@gmail.com; mheng@mgh.harvard.edu; david.ring@austin.utexas.edu; avranceanu@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 NR 34 TC 0 Z9 0 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JUN PY 2016 VL 47 IS 6 BP 1212 EP 1216 DI 10.1016/j.injury.2016.02.018 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DM7AQ UT WOS:000376504700009 PM 26994517 ER PT J AU Kachooei, AR Claessen, FMAP Chase, SM Verheij, KKJ van Dijk, CN Ring, D AF Kachooei, Amir Reza Claessen, Femke M. A. P. Chase, Samantha M. Verheij, Kirsten K. J. van Dijk, C. Niek Ring, David TI Factors associated with removal of a radial head prosthesis placed for acute trauma SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Radial head; Prosthesis; Elbow fracture dislocation; Removal; Revision; Survival ID MASON TYPE-III; INTERNAL-FIXATION; FOLLOW-UP; FRACTURES; ARTHROPLASTY; REPLACEMENT; MANAGEMENT; ELBOW; OUTCOMES; LIGAMENT AB Purpose: This study tests the hypothesis that there are no factors associated with removal or revision of a radial head prosthesis. A secondary analysis addressed the time to removal or revision. Methods: We reviewed the database of two large hospitals from 2000 to 2014 and identified 278 patients that had radial head replacement after an acute fracture or fracture dislocation of the elbow: 19 had removal and 3 had revision of the radial head implant within the study period. Explanatory variables including demographics, the type of injury, prosthesis type, surgeon, medical centre, and associated injuries were evaluated. Survival analysis using Kaplan-Meier curves evaluated time to removal/revision. Results: After adjustment for potential confounders using Cox regression multivariable analysis, hospital was the only factor independently associated with removal or revision ( Hazard ratio = 2.4, Confidence interval: 1.03-5.8, P value = 0.043). The highest proportion of removal/revision was during the first year after implantation and decreased by half each year over the second to fourth years. The most common reason for removal of the prosthesis was to facilitate removal of heterotopic ossification ( the majority with proximal radioulnar synostosis) rather than technical error or problems with the prostheses. Conclusion: These findings suggest that the decision to remove a radial head prosthesis may depend more on surgeon or hospital preferences than on objective problems with the prosthesis. Until clarified by additional study, removal of a prosthesis should not be considered an objective outcome in research. In addition, patients offered removal of a radial head prosthesis, might get the opinion of more than one surgeon at more than one hospital before deciding whether or not to proceed. Level of evidence: Level III Prognostic (C) 2016 Elsevier Ltd. All rights reserved. C1 [Kachooei, Amir Reza] Mashhad Univ Med Sci, Orthoped Res Ctr, Mashhad, Iran. [Kachooei, Amir Reza; Claessen, Femke M. A. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv, Boston, MA USA. [Chase, Samantha M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Verheij, Kirsten K. J.] Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [van Dijk, C. Niek] Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Amsterdam, Netherlands. [Ring, David] Univ Texas Austin, Dell Med Sch, 1400 Barbara Jordan Blvd Suite 1-114AC MC R180, Austin, TX 78723 USA. RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, 1400 Barbara Jordan Blvd Suite 1-114AC MC R180, Austin, TX 78723 USA. EM akachooei@mgh.harvard.edu; fclaessen@mgh.harvard.edu; smchase@partners.org; kverheij@mgh.harvard.edu; c.n.vandijk@amc.uva.nl; david.ring@austin.utexas.edu OI Kachooei, Amir Reza/0000-0001-7795-1830; Ring, David/0000-0002-6506-4879 NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD JUN PY 2016 VL 47 IS 6 BP 1253 EP 1257 DI 10.1016/j.injury.2016.02.023 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DM7AQ UT WOS:000376504700016 PM 26975795 ER PT J AU Sciacca, K Reville, B AF Sciacca, Kate Reville, Barbara TI Evaluation of Nurse Practitioners Enrolled in Fellowship and Residency Programs: Methods and Trends SO JNP-JOURNAL FOR NURSE PRACTITIONERS LA English DT Article DE competency and capability assessment; evaluation; fellowship; nurse practitioner; postgraduate education ID COMPETENCE; CAPABILITY; PORTFOLIOS; STANDARDS; EDUCATION; NEED AB The Institute of Medicine's The Future of Nursing report called for expansion of postgraduate training programs for nurse practitioners. Using systematic methods, a literature review was performed, which revealed that publications on postgraduate training program design, guidelines, and methods are limited. There is a crucial need for consensus regarding the definitions, theoretical framework, and appropriate evaluation methods to assess the competency and capability of postgraduate nurse practitioners. The growth of residency and fellowship programs warrants critical investigation and dissemination of methods used by postgraduate training educators in order to support transition to practice and ensure the development of strong practitioners. (C) 2016 Elsevier Inc. All rights reserved. C1 [Sciacca, Kate] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Reville, Barbara] Brigham & Womens Hosp, Dana Farber Canc Inst, Palliat Care Nursing, 75 Francis St, Boston, MA 02115 USA. [Reville, Barbara] Brigham & Womens Hosp, Dana Farber Canc Inst, Palliat Care, 75 Francis St, Boston, MA 02115 USA. RP Sciacca, K (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ksciacca@partners.org NR 30 TC 0 Z9 0 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1555-4155 EI 1878-058X J9 JNP-J NURSE PRACT JI JNP-J. Nurse Pract. PD JUN PY 2016 VL 12 IS 6 BP E275 EP E280 DI 10.1016/j.nurpra.2016.02.011 PG 6 WC Nursing SC Nursing GA DM9FB UT WOS:000376669300008 ER PT J AU Nebergall, AK Troelsen, A Rubash, HE Malchau, H Rolfson, O Greene, ME AF Nebergall, Audrey K. Troelsen, Anders Rubash, Harry E. Malchau, Henrik Rolfson, Ola Greene, Meridith E. TI Five-Year Experience of Vitamin E-Diffused Highly Cross-Linked Polyethylene Wear in Total Hip Arthroplasty Assessed by Radiostereometric Analysis SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; radiostereometric analysis; polyethylene; vitamin E; patient-reported outcome measures ID MOLECULAR-WEIGHT POLYETHYLENE; MECHANICAL-PROPERTIES; ACETABULAR LINERS; UHMWPE; RESISTANCE; OXIDATION; REPLACEMENT; COMPONENTS; PRECISION AB Background: Vitamin E-diffused highly cross-linked polyethylene (VEPE) was developed to reduce oxidation without compromising mechanical strength. The purpose of this study was to evaluate VEPE in vivo using radiostereometric analysis (RSA) and patient-reported outcome measures (PROMs). Methods: Fifty-one hips were enrolled. Each patient received a VEPE liner, a porous titanium shell, and an uncemented stem with a 32-mm cobalt-chrome femoral head. Tantalum beads were inserted into the VEPE to measure femoral head penetration using RSA. RSA radiographs and PROMs were obtained preoperatively immediately after surgery, 6 months, 1, 2, 3, and 5 years after surgery. Results: Forty-seven hips returned at 3 years, and 42 hip at 5 years. The mean +/- standard error of the mean proximal head penetration into the polyethylene was 0.06 +/- 0.01 at 5 years. The amount of head penetration did not change significantly with increasing time in vivo. The mean +/- standard error of the mean Harris Hip Score was 58 +/- 2 preoperatively, which improved significantly to 93 +/- 2 at 5 years (P < .001). Conclusion: The head penetration into VEPE liners was low compared with non-VEPE at 5 years. After settling of the liners in the early period, no significant head penetration occurred from 2- to 5-year follow-up. All PROMs improved significantly from preoperative to postoperative and remained very favorable at 5 years. This study documents the longest-term evaluation of in vivo wear performance of VEPE. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nebergall, Audrey K.; Troelsen, Anders; Rubash, Harry E.; Malchau, Henrik; Rolfson, Ola; Greene, Meridith E.] Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, Boston, MA 02114 USA. [Troelsen, Anders] Univ Copenhagen, Hvidovre Hosp, Dept Orthopaed, DK-2650 Hvidovre, Denmark. [Rolfson, Ola] Univ Gothenburg, Dept Orthopaed, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden. RP Nebergall, AK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA. OI Rolfson, Ola/0000-0001-6534-1242 FU Biomet, Inc (Warsaw, IN); Harris Orthopaedic Laboratory (Boston, MA) FX This study was funded by Biomet, Inc (Warsaw, IN) and the Harris Orthopaedic Laboratory (Boston, MA). NR 35 TC 1 Z9 1 U1 2 U2 4 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 JUN PY 2016 VL 31 IS 6 BP 1251 EP 1255 DI 10.1016/j.arth.2015.12.023 PG 5 WC Orthopedics SC Orthopedics GA DM7BF UT WOS:000376506700024 PM 26777551 ER PT J AU Nebergall, AK Rolfson, O Rubash, HE Malchau, H Troelsen, A Greene, ME AF Nebergall, Audrey K. Rolfson, Ola Rubash, Harry E. Malchau, Henrik Troelsen, Anders Greene, Meridith E. TI Stable Fixation of a Cementless, Proximally Coated, Double Wedged, Double Tapered Femoral Stem in Total Hip Arthroplasty: A 5-Year Radiostereometric Analysis SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; radiostereometric analysis; patient-reported outcome measures; radiolucencies; cementless arthroplasty ID 10-YEAR FOLLOW-UP; LONG-TERM; PROSTHESES; COMPONENT; FAILURE; SURVIVORSHIP; REPLACEMENTS; REGISTER; MINIMUM; DESIGN AB Background: The objective of this 5-year prospective study of 51 hips was to assess migration of a cementless tapered femoral stem using radiostereometric analysis (RSA), plain radiographs (radiolucencies), and patient-reported outcome measures (PROMs). Methods: Forty-seven patients (51 hips) agreed to participate in this prospective RSA study. All patients received a Taperloc stem. Tantalum beads were inserted into the femoral bone surrounding the stem to measure migration using RSA. RSA films, plain radiograph, and PROM follow-up were obtained immediately after surgery, 6 months, 1, 2, 3, and 5 years after surgery. Results: The median (interquartile range) subsidence was 0.03 mm (-0.23 to 0.06) at 5 years, with no significant differences over time. Four outlier stems had >1.5 mm of subsidence by 1 year. No stem showed radiolucencies in more than 3 zones during the 5 years. All PROMs remained favorable at 5 years, suggesting an excellent outcome. There were no stems revised for mechanical loosening; 1 stem was revised for an infection. Conclusion: After initial settling, the cementless tapered femoral stems in our series were stable. The 4 outlier stems with >1.5 mm of subsidence by 1 year remain stable at 5 years. RSA was the most sensitive method of detection for stems at greater risk for potential future failure. This report adds contributions to the positive results associated with this type of fixation. The results at 5 years showed excellent midterm survivorship in this cohort with a cementless tapered femoral component. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nebergall, Audrey K.; Rolfson, Ola; Rubash, Harry E.; Malchau, Henrik; Troelsen, Anders; Greene, Meridith E.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthopaed, 55 Fruit St, Boston, MA 02114 USA. [Rolfson, Ola] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. [Troelsen, Anders] Univ Copenhagen, Hvidovre Hosp, Dept Orthoped, DK-2650 Hvidovre, Denmark. RP Nebergall, AK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthopaed, 55 Fruit St, Boston, MA 02114 USA. OI Rolfson, Ola/0000-0001-6534-1242 FU Biomet Inc (Warsaw, Indiana); Harris Orthopaedic Laboratory FX Biomet Inc (Warsaw, Indiana) and the Harris Orthopaedic Laboratory provided funding for this study. NR 34 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 JUN PY 2016 VL 31 IS 6 BP 1267 EP 1274 DI 10.1016/j.arth.2015.11.036 PG 8 WC Orthopedics SC Orthopedics GA DM7BF UT WOS:000376506700027 PM 26725135 ER PT J AU Lock, R Ingraham, R Maertens, O Miller, AL Weledji, N Legius, E Konicek, BM Yan, SCB Graff, JR Cichowski, K AF Lock, Rebecca Ingraham, Rachel Maertens, Ophelia Miller, Abigail L. Weledji, Nelly Legius, Eric Konicek, Bruce M. Yan, Sau-Chi B. Graff, Jeremy R. Cichowski, Karen TI Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NEUROFIBROMATOSIS TYPE-1; TUMOR-DEVELOPMENT; INHIBITOR; MODELS; GROWTH; MAP; PHOSPHORYLATION; TUMORIGENESIS; TRANSLATION; PROTEINS AB Neurofibromin 1-mutant (NF1-mutant) cancers are driven by excessive Ras signaling; however, there are currently no effective therapies for these or other Ras-dependent tumors. While combined MEK and mTORC1 suppression causes regression of NF1-deficient malignancies in animal models, the potential toxicity of cotargeting these 2 major signaling pathways in humans may necessitate the identification of more refined, cancer-specific signaling nodes. Here, we have provided evidence that MAPK-interacting kinases (MNKs), which converge on the mTORC1 effector eIF4E, are therapeutic targets in NF1-deficient malignancies. Specifically, we evaluated primary human NF1-deficient peripheral nervous system tumors and found that MNKs are activated in the majority of tumors tested. Genetic and chemical suppression of MNKs in NF1-deficient murine tumor models and human cell lines potently cooperated with MEK inhibitors to kill these cancers through effects on eIF4E. We also demonstrated that MNK kinases are important and direct targets of cabozantinib. Accordingly, coadministration of cabozantinib and MEK inhibitors triggered dramatic regression in an aggressive genetically engineered tumor model. The cytotoxicity of this combination required the suppression of MNK-induced eIF4E phosphorylation and was not recapitulated by suppressing other cabozantinib targets. Collectively, these studies demonstrate that combined MNK and MEK suppression represents a promising therapeutic strategy for these incurable Ras-driven tumors and highlight the utility of developing selective MNK inhibitors for these and possibly other malignancies. C1 [Lock, Rebecca; Ingraham, Rachel; Maertens, Ophelia; Miller, Abigail L.; Weledji, Nelly; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. [Lock, Rebecca; Ingraham, Rachel; Maertens, Ophelia; Miller, Abigail L.; Weledji, Nelly; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Legius, Eric] Univ Hosp Leuven, Ctr Human Genet, Leuven, Belgium. [Legius, Eric] Katholieke Univ Leuven, Dept Human Genet, Leuven, Belgium. [Konicek, Bruce M.; Yan, Sau-Chi B.] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Graff, Jeremy R.] Biothera Pharmaceut Inc, Eagan, MN USA. [Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. RP Cichowski, K (reprint author), Brigham & Womens Hosp, 77 Ave Louis Pasteur,NRB 0458C, Boston, MA 02115 USA. EM kcichowski@rics.bwh.harvard.edu FU Department of Defense [W81XWH-13-1-0044]; Children's Tumor Foundation (CTF); National Cancer Institute [R01CA111754]; American Cancer Society-New England Division-Ellison Foundation [PF-15-127-01-CDD]; CTF Young Investigator Award [2012-01-023] FX K. Cichowski, R. Lock, and this work were supported by a grant from the Department of Defense (W81XWH-13-1-0044), the Children's Tumor Foundation (CTF), and the National Cancer Institute (R01CA111754). R. Lock was supported by an American Cancer Society-New England Division-Ellison Foundation postdoctoral fellowship (PF-15-127-01-CDD) and by a CTF Young Investigator Award (2012-01-023). NR 27 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2016 VL 126 IS 6 BP 2181 EP 2190 DI 10.1172/JCI85183 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DN4IF UT WOS:000377027500016 PM 27159396 ER PT J AU Koch, MJ Agarwalla, PK Stapleton, CJ Ogilvy, CS Loeffler, JS AF Koch, Matthew J. Agarwalla, Pankaj K. Stapleton, Christopher J. Ogilvy, Christopher S. Loeffler, Jay S. TI De novo development of a cerebral arteriovenous malformation following radiation therapy: Case report and an update to classical arteriovenous malformation nomenclature SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Arteriovenous malformation; Radiation therapy; Vascular malformation ID OF-THE-LITERATURE; MOYAMOYA-DISEASE; GRADING SYSTEM; CHILD; ADULT; RADIOTHERAPY; IRRADIATION; ANGIOGRAPHY; ANEURYSMS; SURGERY AB Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3 years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19 years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Koch, Matthew J.; Agarwalla, Pankaj K.; Stapleton, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, White 502,55 Fruit St, Boston, MA 02114 USA. [Ogilvy, Christopher S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Div Neurosurg, Boston, MA 02215 USA. [Loeffler, Jay S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Koch, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, White 502,55 Fruit St, Boston, MA 02114 USA. EM mjkoch@MGH.Harvard.edu NR 44 TC 1 Z9 1 U1 0 U2 1 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 JUN PY 2016 VL 28 BP 162 EP 167 DI 10.1016/j.jocn.2015.11.021 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DM9VT UT WOS:000376714500032 PM 26860850 ER PT J AU Mitrasinovic, S Appelboom, G Detappe, A Connolly, ES AF Mitrasinovic, Stefan Appelboom, Geoff Detappe, Alexandre Connolly, E. Sander, Jr. TI Focused ultrasound to transiently disrupt the blood brain barrier SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Editorial Material ID TARGETED DRUG-DELIVERY; MAGNETIC-RESONANCE; GLIOBLASTOMA-MULTIFORME; LIPOSOMAL DOXORUBICIN; BREAST-CANCER; PERMEABILITY; TEMOZOLOMIDE; RADIATION; EFFICACY; PATTERNS C1 [Mitrasinovic, Stefan; Appelboom, Geoff; Connolly, E. Sander, Jr.] Columbia Univ, Med Ctr, Dept Neurosurg, Cerebrovasc Lab, 630 West 168th St, New York, NY 10032 USA. [Detappe, Alexandre] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Connolly, E. Sander, Jr.] Columbia Univ, Med Ctr, Neurointens Care Unit, New York, NY USA. RP Appelboom, G (reprint author), Columbia Univ, Med Ctr, Dept Neurosurg, Cerebrovasc Lab, 630 West 168th St, New York, NY 10032 USA. EM ga@neuro-digital.com OI Mitrasinovic, Stefan/0000-0001-9681-8808; Detappe, Alexandre/0000-0001-9364-1621 NR 56 TC 1 Z9 1 U1 1 U2 7 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 JUN PY 2016 VL 28 BP 187 EP 189 DI 10.1016/j.jocn.2015.12.011 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DM9VT UT WOS:000376714500041 PM 26883350 ER PT J AU Kesselheim, AS Gagne, JJ Franklin, JM Eddings, W Fulchino, LA Avorn, J Campbell, EG AF Kesselheim, Aaron S. Gagne, Joshua J. Franklin, Jessica M. Eddings, Wesley Fulchino, Lisa A. Avorn, Jerry Campbell, Eric G. TI Variations in Patients' Perceptions and Use of Generic Drugs: Results of a National Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE generic drugs; patient survey; FDA ID BRAND-NAME; SUBSTITUTION; METAANALYSIS; ATTITUDES; OUTCOMES; BELIEFS AB Over 84 % of all prescriptions in the US are filled as generic drugs, though in prior surveys, patients reported concerns about their quality. We aimed to survey patients' perceptions and use of generic drugs. Our survey (administered August 2014) assessed patients' skepticism about generic drug safety and effectiveness and how often they requested brand-name drugs. Chi-square tests and two-sample t-tests assessed associations between patient demographics and the outcomes. Our sample frame was the CVS Advisor Panel, a national database of 124,621 CVS customers. We randomly selected 1450 patients with self-reported chronic conditions who filled at least one prescription in the prior 3 months. We assessed how often patients reported asking their physicians to prescribe a brand-name over a generic drug in the last year, and "generic skepticism," defined as not believing generic drugs were as safe, effective, had the same side effects, and contained the same active ingredients as brand-name drugs. Of the 1,442 patients with valid addresses, 933 responded (65 % response rate) and 753 took the full survey. A vast majority (83 %) agreed that physicians should prescribe generic drugs when available, and 54 % said they had not asked their physicians to prescribe a brand-name drug over a generic in the past year. Most respondents considered generic drugs to be as effective (87 %) and safe (88 %) as their brand-name counterparts, and to have the same side effects (80 %) and active ingredients (84 %). Non-Caucasians were more likely than Caucasians to request a brand-name drug over a generic (56 % vs. 43 %, p < 0.01), and were also more skeptical of generic drugs' clinical equivalence (43 % vs. 29 %, p < 0.01). We found a substantial shift towards more patients having positive views of generic drugs, but lingering negative perceptions will have to be overcome to ensure continued cost-savings and improved patient outcomes from generic drugs. C1 [Kesselheim, Aaron S.; Gagne, Joshua J.; Franklin, Jessica M.; Eddings, Wesley; Fulchino, Lisa A.; Avorn, Jerry] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St Suite 3030, Boston, MA USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Kesselheim, Aaron S.; Gagne, Joshua J.; Franklin, Jessica M.; Eddings, Wesley; Fulchino, Lisa A.; Avorn, Jerry; Campbell, Eric G.] Harvard Univ, Sch Med, Boston, MA USA. RP Kesselheim, AS (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St Suite 3030, Boston, MA USA. EM akesselheim@partners.org FU Food and Drug Administration [U01FD004856]; Harvard Program in Therapeutic Science; Laura and John Arnold Foundation FX The authors would like to thank Caron Merrill and Olga Matlin at CVS Health and Jessica Zeidler, Cheryl Montowski, Justin Pilarcik, and Maria Beasley at Research Results for their help in conducting the survey. Funding for this study was made possible, by the Food and Drug Administration through grant U01FD004856. Views expressed in this publication do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government. Dr. Kesselheim is a Greenwall Faculty Scholar in Bioethics and is also funded by the Harvard Program in Therapeutic Science and the Laura and John Arnold Foundation. NR 32 TC 2 Z9 2 U1 7 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2016 VL 31 IS 6 BP 609 EP 614 DI 10.1007/s11606-016-3612-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DM5PY UT WOS:000376403700007 PM 26883524 ER PT J AU Egede, LE Walker, RJ Bishu, K Dismuke, CE AF Egede, Leonard E. Walker, Rebekah J. Bishu, Kinfe Dismuke, Clara E. TI Trends in Costs of Depression in Adults with Diabetes in the United States: Medical Expenditure Panel Survey, 2004-2011 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; COMORBID DEPRESSION; CARE; PEOPLE; INDIVIDUALS; PREVALENCE; AGREEMENT; MODELS AB To investigate differences in healthcare cost trends over 8 years in adults with diabetes and one of four categories of comorbid depression: no depression, unrecognized depression, asymptomatic depression, or symptomatic depression. Data from the 2004-2011 Medical Expenditure Panel Survey (MEPS) was used to create nationally representative estimates. The dependent variable was total healthcare expenditures for the calendar year, including office-based, hospital outpatient, emergency room, inpatient hospital, prescription, dental, and home health care expenditures. The 2004-2011 direct medical costs were adjusted to a common 2014 dollar value. The primary independent variable was four mutually exclusive depression categories created from ICD-9-CM codes and the PHQ-2 depression screening tool. Healthcare expenditures were estimated using a two-part model and were adjusted for age, sex, race, marital status, education, health insurance, metropolitan statistical area status, region, income level, and comorbidities. Based on a national sample of adults with diabetes (unweighted sample of 15,548, weighted sample of 17,465,579), 10.2 % had unrecognized depression, 13.6 % had asymptomatic depression, and 8.9 % had symptomatic depression. In the pooled sample, after adjusting for covariates, the incremental cost of unrecognized depression was $2872 (95 % CI 1660-4084), asymptomatic depression increased by $3347 (95 % CI 2568-4386), and symptomatic depression increased by $5170 (CI 95 % 3610-6731) compared to patients with no depression. Adjusted analyses showed that expenditures were $2000-3000 higher for unrecognized and asymptomatic depression than no depression, and $5000 higher for symptomatic depression. Higher medical expenditures persisted over time, with only symptomatic depression showing a sustained decrease over time. C1 [Egede, Leonard E.; Walker, Rebekah J.; Bishu, Kinfe; Dismuke, Clara E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. [Egede, Leonard E.; Bishu, Kinfe] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.; Walker, Rebekah J.; Dismuke, Clara E.] Ralph H Johnson Vet Affairs Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K24DK093699] FX This study was supported by grant no. K24DK093699 from The National Institute of Diabetes and Digestive and Kidney Diseases (PI: Leonard Egede). NR 38 TC 3 Z9 3 U1 5 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2016 VL 31 IS 6 BP 615 EP 622 DI 10.1007/s11606-016-3650-1 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DM5PY UT WOS:000376403700008 PM 26969312 ER PT J AU Melzer, AC Feemster, LC Collins, MP Au, DH AF Melzer, Anne C. Feemster, Laura C. Collins, Margaret P. Au, David H. TI Predictors of Pharmacotherapy for Tobacco Use Among Veterans Admitted for COPD: The Role of Disparities and Tobacco Control Processes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE COPD; tobacco; smoking; pharmacotherapy; nicotine replacement; disparities; processes of care ID NICOTINE REPLACEMENT THERAPY; OBSTRUCTIVE PULMONARY-DISEASE; SMOKING-CESSATION ADVICE; SERIOUS MENTAL-ILLNESS; RACIAL/ETHNIC DISPARITIES; ETHNIC DISPARITIES; NATIONAL-HEALTH; UNITED-STATES; PREVALENCE; SMOKERS AB Many smokers admitted for chronic obstructive pulmonary disease (COPD) are not given smoking cessation medications at discharge. The reasons behind this are unclear, and may reflect an interplay of patient characteristics, health disparities, and the receipt of inpatient tobacco control processes. We aimed to assess potential disparities in treatment for tobacco use following discharge for COPD, examined in the context of inpatient tobacco control processes. Smokers aged a parts per thousand yen 40 years, admitted for treatment of a COPD exacerbation within the VA Veterans Integrated Service Network 20, identified using ICD-9 discharge codes and admission diagnoses from 2005-2012. The outcome was any tobacco cessation medication dispensed within 48 hours of discharge. We assessed potential predictors administratively up to 1 year prior to admission. We created the final logistic regression model using manual model building, clustered by site. Variables with p < 0.2 in biviariate models were considered for inclusion in the final model. We identified 1511 subjects. 16.9 % were dispensed a medication at discharge. In the adjusted model, several predictors were associated with decreased odds of receiving medications: older age (OR per year older 0.96, 95 % CI 0.95-0.98), black race (OR 0.34, 95 % CI 0.12-0.97), higher comorbidity score (OR 0.89, 95 % CI 0.82-0.96), history of psychosis (OR 0.40, 95 % CI 0.31-0.52), hypertension (OR 0.75, 95 % CI 0.62-0.90), and treatment with steroids in the past year (OR 0.80, 95 % CI 0.70-0.90). Inpatient tobacco control processes were associated with increased odds of receiving medications: documented brief counseling at discharge (OR 3.08, 95 % CI 2.02-4.68) and receipt of smoking cessation medications while inpatient (OR 5.95, 95 % CI 3.19-11.10). Few patients were treated with tobacco cessation medications at discharge. We found evidence for disparities in treatment, but also potentially beneficial effects of inpatient tobacco control measures. Further focus should be on using novel processes of care to improve provision of medications and decrease the observed disparities. C1 [Melzer, Anne C.; Feemster, Laura C.; Au, David H.] Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. [Melzer, Anne C.; Feemster, Laura C.; Collins, Margaret P.; Au, David H.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, 1660 S Columbian Way,Mailstop S-152, Seattle, WA 98108 USA. RP Melzer, AC (reprint author), VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, 1660 S Columbian Way,Mailstop S-152, Seattle, WA 98108 USA. EM acmelzer@uw.edu FU Department of Veterans Affairs, Health Services Research and Development (HSRD); University of Washington Department of Pulmonary and Critical Care [HL007287-36]; NIH NHLBI K23 Mentored Career Development Award [HL111116]; Gilead Sciences; VA Health Services Research and Development (HSRD) FX This material is based upon work supported by the Department of Veterans Affairs, Health Services Research and Development (HSR&D), who provided access to data, office space, and programming and data management. 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. We would like to acknowledge Mr. Robert Plumley, who performed the data extraction and natural language processing necessary to complete this project. Dr. Au is an unpaid research consultant for Analysis Group. Dr. Melzer is supported by an institutional F-32 (HL007287-36) through the University of Washington Department of Pulmonary and Critical Care. Dr. Feemster is supported by an NIH NHLBI K23 Mentored Career Development Award (HL111116). Partial support of this project was provided by Gilead Sciences with research funding to the Seattle Institute for Biomedical and Clinical Research. Additional support was received through the VA Health Services Research and Development (HSR&D). NR 53 TC 1 Z9 1 U1 6 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2016 VL 31 IS 6 BP 623 EP 629 DI 10.1007/s11606-016-3623-4 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DM5PY UT WOS:000376403700009 PM 26902236 ER PT J AU Davis, S Berkson, S Gaines, ME Prajapati, P Schwab, W Pandhi, N Edgman-Levitan, S AF Davis, Sarah Berkson, Stephanie Gaines, Martha E. Prajapati, Pratik Schwab, William Pandhi, Nancy Edgman-Levitan, Susan TI Implementation Science Workshop: Engaging Patients in Team-Based Practice Redesign - Critical Reflections on Program Design SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID CENTERED MEDICAL HOME; PRIMARY-CARE; QUALITY IMPROVEMENT; HEALTH-CARE; ENGAGEMENT; OUTCOMES C1 [Davis, Sarah; Gaines, Martha E.] Univ Wisconsin, Ctr Patient Partnerships, 975 Bascom Mall,Suite 4311, Madison, WI 53706 USA. [Davis, Sarah; Gaines, Martha E.] Univ Wisconsin, Sch Law, Madison, WI 53706 USA. [Berkson, Stephanie; Prajapati, Pratik] Univ Wisconsin Med Fdn, Madison, WI USA. [Schwab, William; Pandhi, Nancy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, Madison, WI 53706 USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Edgman-Levitan, Susan] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA. RP Davis, S (reprint author), Univ Wisconsin, Ctr Patient Partnerships, 975 Bascom Mall,Suite 4311, Madison, WI 53706 USA. EM Sarah.Davis@wisc.edu FU NCATS NIH HHS [UL1 TR000427]; NCI NIH HHS [P30 CA014520]; NIA NIH HHS [K08 AG029527] NR 33 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2016 VL 31 IS 6 BP 688 EP 695 DI 10.1007/s11606-016-3656-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DM5PY UT WOS:000376403700019 PM 26976290 ER PT J AU Peshkin, BN Kelly, S Nusbaum, RH Similuk, M DeMarco, TA Hooker, GW Valdimarsdottir, HB Forman, AD Joines, JR Davis, C McCormick, SR McKinnon, W Graves, KD Isaacs, C Garber, J Wood, M Jandorf, L Schwartz, MD AF Peshkin, Beth N. Kelly, Scott Nusbaum, Rachel H. Similuk, Morgan DeMarco, Tiffani A. Hooker, Gillian W. Valdimarsdottir, Heiddis B. Forman, Andrea D. Joines, Jessica Rispoli Davis, Claire McCormick, Shelley R. McKinnon, Wendy Graves, Kristi D. Isaacs, Claudine Garber, Judy Wood, Marie Jandorf, Lina Schwartz, Marc D. TI Patient Perceptions of Telephone vs. In-Person BRCA1/BRCA2 Genetic Counseling SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE BRCA1/BRCA2; Genetic counseling; Patient satisfaction; Telephone counseling ID NEW-YORK-CITY; RANDOMIZED CONTROLLED-TRIAL; AT-RISK LATINAS; BREAST-CANCER; HEREDITARY BREAST; OVARIAN-CANCER; RACIAL DISPARITIES; AFRICAN DESCENT; COMMUNICATION; HEALTH AB Telephone genetic counseling (TC) for hereditary breast/ovarian cancer risk has been associated with positive outcomes in high risk women. However, little is known about how patients perceive TC. As part of a randomized trial of TC versus usual care (UC; in-person genetic counseling), we compared high risk women's perceptions of: (1) overall satisfaction with genetic counseling; (2) convenience; (3) attentiveness during the session; (4) counselor effectiveness in providing support; and (5) counselor ability to recognize emotional responses during the session. Among the 554 participants (TC, N = 272; UC, N = 282), delivery mode was not associated with self-reported satisfaction. However, TC participants found counseling significantly more convenient than UC participants (OR = 4.78, 95 % CI = 3.32, 6.89) while also perceiving lower levels of support (OR = 0.56, 95 % CI = 0.40-0.80) and emotional recognition (OR = 0.53, 95 % CI = 0.37-0.76). In exploratory analyses, we found that non-Hispanic white participants reported higher counselor support in UC than in TC (69.4 % vs. 52.8 %; OR = 3.06, 95 % CI = 1.39-6.74), while minority women perceived less support in UC vs. TC (58.3 % vs. 38.7 %; OR = 0.80, 95 % CI = 0.39-1.65). We discuss potential research and practice implications of these findings which may further improve the effectiveness and utilization of TC. C1 [Peshkin, Beth N.; Graves, Kristi D.; Isaacs, Claudine; Schwartz, Marc D.] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Peshkin, Beth N.; Graves, Kristi D.; Isaacs, Claudine; Schwartz, Marc D.] Georgetown Univ, Jess & Mildred Fisher Ctr Hereditary Canc & Clin, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. [Kelly, Scott] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA. [Nusbaum, Rachel H.] GeneDx, Gaithersburg, MD USA. [Similuk, Morgan] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [DeMarco, Tiffani A.] Inova Hlth Syst, Inova Translat Med Inst, Canc Genet Counseling Program, Falls Church, VA USA. [Hooker, Gillian W.] NextGxDx Inc, Franklin, TN USA. [Valdimarsdottir, Heiddis B.; Jandorf, Lina] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Valdimarsdottir, Heiddis B.] Reyjavik Univ, Dept Psychol, Reyjavik, Iceland. [Forman, Andrea D.] Fox Chase Canc Ctr, Risk Assessment Program, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Joines, Jessica Rispoli] Univ Maryland, Med Ctr, Dept Med, Marlene & Stewart Greenebaum Canc Ctr,Div Hematol, Baltimore, MD 21201 USA. [Davis, Claire] Sarah Lawrence Coll, Joan H Marks Grad Program Human Genet, Yonkers, NY USA. [McCormick, Shelley R.; Garber, Judy] Harvard Univ, Sch Med, Ctr Canc Genet & Prevent, Dana Farber Canc Inst, Boston, MA 02115 USA. [McKinnon, Wendy; Wood, Marie] Univ Vermont, Ctr Canc, Familial Canc Program, Burlington, VT USA. RP Peshkin, BN (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA.; Peshkin, BN (reprint author), Georgetown Univ, Jess & Mildred Fisher Ctr Hereditary Canc & Clin, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA. EM peshkinb@georgetown.edu RI Kelly, Scott/D-3195-2013 OI Kelly, Scott/0000-0002-0375-1040 FU National Cancer Institute [R01 CA108933, P30 CA051008]; Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research FX The study was supported by Grants R01 CA108933 and P30 CA051008 from the National Cancer Institute and by the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 55 TC 3 Z9 3 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD JUN PY 2016 VL 25 IS 3 BP 472 EP 482 DI 10.1007/s10897-015-9897-6 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA DM4AL UT WOS:000376287800007 PM 26455498 ER PT J AU Jawad, MS Fahim, DK Gerszten, PC Flickinger, JC Sahgal, A Grills, IS Sheehan, J Kersh, R Shin, J Oh, K Mantel, F Guckenberger, M AF Jawad, Maha Saada Fahim, Daniel K. Gerszten, Peter C. Flickinger, John C. Sahgal, Arjun Grills, Inga S. Sheehan, Jason Kersh, Ronald Shin, John Oh, Kevin Mantel, Frederick Guckenberger, Matthias CA Elekta Spine Radiosurg Res TI Vertebral compression fractures after stereotactic body radiation therapy: a large, multi-institutional, multinational evaluation SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE radiosurgery; spinal tumors; stereotactic body radiotherapy; spine SBRT; vertebral fractures; oncology ID SPINAL-CORD COMPRESSION; CLINICAL ARTICLE; METASTASES; RADIOSURGERY; RADIOTHERAPY; INSTABILITY; EXPERIENCE; SURGERY; CANCER; TRIAL AB OBJECTIVE The purpose of this study was to identify factors contributing to an increased risk for vertebral compression fracture (VCF) following stereotactic body radiation therapy (SBRT) for spinal tumors. METHODS A total of 594 tumors were treated with spinal SBRT as primary treatment or re-irradiation at 8 different institutions as part of a multi-institutional research consortium. Patients underwent LINAC-based, image-guided SBRT to a median dose of 20 Gy (range 8-40 Gy) in a median of 1 fraction (range 1-5 fractions). Median patient age was 62 years. Seventy-one percent of tumors were osteolytic, and a preexisting vertebral compression fracture (VCF) was present in 24% of cases. Toxicity was assessed following treatment. Univariate and multivariate analyses were performed using a logistic regression method to determine parameters predictive for post-SBRT VCF. RESULTS At a median follow-up of 10.1 months (range 0.03-57 months), 80% of patients had local tumor control. At the time of last imaging follow-up, at a median of 8.8 months after SBRT, 3% had a new VCF, and 2.7% had a progressive VCF. For development of any (new or progressive) VCF following SBRT, the following factors were predictive for VCF on univariate analysis: short interval from primary diagnosis to SBRT (less than 36.8 days), solitary metastasis, no additional bone metastases, no prior chemotherapy, preexisting VCF, no MRI used for target delineation, tumor volume of 37.3 cm(3) or larger, equivalent 2-Gy-dose (EQD(2)) tumor of 41.8 Gy or more, and EQD(2) spinal cord D-max of 46.1 Gy or more. Preexisting VCF, solitary metastasis, and prescription dose of 38.4 Gy or more were predictive on multivariate analysis. The following factors were predictive of a new VCF on univariate analysis: solitary metastasis, no additional bone metastases, and no MRI used for target delineation. Presence of a solitary metastasis and lack of MRI for target delineation remained significant on multivariate analysis. CONCLUSIONS A VCF following SBRT is more likely to occur following treatment for a solitary spinal metastasis, reflecting a more aggressive treatment approach in patients with adequately controlled systemic disease. Higher prescription dose and a preexisting VCF also put patients at increased risk for post-SBRT VCF. In these patients, pre-SBRT cement augmentation could be considered to decrease the risk of subsequent VCF. C1 [Jawad, Maha Saada; Grills, Inga S.] Oakland Univ, William Beaumont Sch Med, Dept Radiat Oncol, Royal Oak, MI USA. [Fahim, Daniel K.] Oakland Univ, William Beaumont Sch Med, Dept Neurol Surg, Royal Oak, MI USA. [Gerszten, Peter C.; Flickinger, John C.] Univ Pittsburgh, Dept Neurol Surg, Med Ctr, Pittsburgh, PA 15260 USA. [Gerszten, Peter C.; Flickinger, John C.] Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA USA. [Sahgal, Arjun] Sunnybrook Odette Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [Sheehan, Jason] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. [Kersh, Ronald] Riverside Med Ctr, Dept Radiat Oncol, Newport News, VA USA. [Shin, John] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Oh, Kevin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Mantel, Frederick; Guckenberger, Matthias] Univ Hosp Wuerzburg, Dept Radiat Oncol, Wurzburg, Germany. [Guckenberger, Matthias] Univ Zurich, Dept Radiat Oncol, Raemistr 100, CH-8091 Zurich, Switzerland. RP Guckenberger, M (reprint author), Univ Zurich, Dept Radiat Oncol, Raemistr 100, CH-8091 Zurich, Switzerland. EM matthias.guckenberger@usz.ch OI Guckenberger, Matthias/0000-0002-7146-9071 FU Elekta AB; Elekta AB, Stockholm, Sweden FX Dr. Sahgal has received research grants and honoraria for educational seminars from Elekta AB; Dr. Grills owns stock in and is on the board of directors of Greater Michigan Gamma Knife. This research was partially supported through a research grant from Elekta AB, Stockholm, Sweden, with all institutions serving as members of the Elekta Spine SBRT Research Consortium. The data, however, are intellectual property of the individual group members and their sponsoring institutions. NR 27 TC 3 Z9 3 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD JUN PY 2016 VL 24 IS 6 BP 928 EP 936 DI 10.3171/2015.10.SPINE141261 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DM6PY UT WOS:000376476100010 PM 26895526 ER PT J AU Tran, K Staller, K Macklin, E Goldstein, A Belkind-Gerson, J Kuo, B AF Tran, Khoa Staller, Kyle Macklin, Eric Goldstein, Allan Belkind-Gerson, Jaime Kuo, Braden TI Need for Rectal Biopsy for Childhood Constipation Predicts Severity of Illness and Need for Laxatives SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Hirschsprung disease; rectal biopsy; severe constipation ID IRRITABLE-BOWEL-SYNDROME; COLONIC MANOMETRY; CHILDREN; DISORDERS; PREVALENCE; EPIDEMIOLOGY; PERSPECTIVE; DEPRESSION; ENCOPRESIS; MANAGEMENT AB Objectives: This study aimed to examine the long-term clinical outcomes of children with severe constipation, as defined by need for rectal biopsy (RB), and to determine which baseline characteristics were predictors of successful outcome. Methods: Children with severe constipation who underwent RB for evaluation of Hirschsprung disease at a tertiary medical center were eligible. A cohort of children with constipation without a history of RB served as controls (matched 2:1 by sex and age). Retrospective chart review of clinic visits was performed at baseline, 3, 6, 12, 18, and 24 months. Successful clinical outcomes were defined as >= 3 bowel movements weekly for >= 4 weeks, with <= 2 fecal incontinence episodes monthly, irrespective of laxative use. Results: A total of 175 RB children (90 boys, mean age: 6.7 years) were matched to 350 controls. Mean duration of constipation symptoms before intake in the RB group was significantly longer compared with controls (3.7 vs 0.4 years, P < 0.001). By 24 months, the cumulative percentage of children achieving at least 1 period of successful outcome was significantly higher in the control group compared with RB population (73% vs 24%, P < 0.001). Multivariate analysis revealed that younger age (P = 0.001, odds ratio 0.87) and shorter duration of constipation before RB (P = 0.03, odds ratio 0.45) were significant predictors of successful outcome. Conclusions: Only one-quarter of patients with severe constipation achieved successful outcome during 2-year follow-up. Younger age and shorter duration of constipation at time of biopsy were predictors of successful outcomes, emphasizing the importance of early diagnosis and initiation of treatment in this population. C1 [Tran, Khoa] Floating Hosp Children, Tufts Med Ctr, Div Pediat Gastroenterol, Boston, MA USA. [Tran, Khoa] Tufts Med Sch, Boston, MA USA. [Staller, Kyle; Kuo, Braden] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Staller, Kyle; Goldstein, Allan; Kuo, Braden] Harvard Univ, Sch Med, Boston, MA USA. [Macklin, Eric] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. [Goldstein, Allan] Massachusetts Gen Hosp Children, Div Pediat Surg, Boston, MA USA. [Belkind-Gerson, Jaime] Div Pediat GI, Boston, MA USA. [Belkind-Gerson, Jaime] Harvard Univ, Massachusetts Gen Hosp Children, Sch Med, Boston, MA USA. [Staller, Kyle] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. RP Tran, K (reprint author), Floating Hosp Children, Tufts Med Ctr, Pediat Gastroenterol, 800 Washington St,Box 213, Boston, MA 02111 USA. EM ktran1@tuftsmedicalcenter.org OI Staller, Kyle/0000-0003-4925-4290 NR 25 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUN PY 2016 VL 62 IS 6 BP 834 EP 839 DI 10.1097/MPG.0000000000001033 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA DM7SP UT WOS:000376560600018 PM 26551318 ER PT J AU Gros, DF Korte, KJ Horner, MD Brady, KT Back, SE AF Gros, Daniel F. Korte, Kristina J. Horner, Michael David Brady, Kathleen T. Back, Sudie E. TI Co-Occurring Traumatic Brain Injury, PTSD Symptoms, and Alcohol Use in Veterans SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE TBI; Traumatic brain injury; Loss of consciousness; PTSD; Alcohol; Substance use; Comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; ADDICTION SEVERITY INDEX; PROLONGED EXPOSURE; HEAD-INJURIES; IRAQ; CONCUSSION; DIAGNOSIS; VALIDITY; THERAPY AB Traumatic brain injury (TBI) has been identified as a significant health problem among veterans. Recent research demonstrates the potential interaction and magnification of symptoms of posttraumatic stress disorder (PTSD) and substance use disorders (SUD) in veterans with a history of TBI; however, there is very limited research on the co-occurrence of the three conditions. Veterans (N = 115) with comorbid PTSD and SUD completed a baseline assessment for enrollment into a larger treatment study. As part of that assessment, participants completed a TBI screener as well as self-report measures for pain and physical health, affective symptoms, and substance use. Almost half of the sample (48 %) endorsed a history of a previous head trauma with loss of consciousness (LOC). Participants with and without head trauma with LOC were compared across various measures of functioning. Increased severity of physical health complaints and affective symptoms were reported by the TBI group compared to controls. However, the increases in affective symptoms were relatively small. No group differences were observed for alcohol use. Together, the findings suggest that treatment-seeking veterans with a history of head trauma with LOC may present with roughly equivalent symptoms of PTSD and SUD to those without said history. C1 [Gros, Daniel F.; Korte, Kristina J.; Horner, Michael David; Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. [Gros, Daniel F.; Korte, Kristina J.; Horner, Michael David; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA.; Gros, DF (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM grosd@musc.edu FU NIDA [DA021228]; Department of Veteran Affairs CSR & D Career Development Award [CX000845] FX This research was supported by NIDA grant DA021228 (PI: Back) and Department of Veteran Affairs CSR & D Career Development Award CX000845 (PI: Gros). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of NIDA, Department of Veterans Affairs, or the United States government. NR 38 TC 0 Z9 0 U1 5 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2016 VL 38 IS 2 BP 266 EP 273 DI 10.1007/s10862-015-9513-y PG 8 WC Psychology, Clinical SC Psychology GA DM8NY UT WOS:000376622400012 ER PT J AU Liu, W Hu, D Huo, HZ Zhang, WF Adiliaghdam, F Morrison, S Ramirez, JM Gul, SS Hamarneh, SR Hodin, RA AF Liu, Wei Hu, Dong Huo, Haizhong Zhang, Weifeng Adiliaghdam, Fatemeh Morrison, Sarah Ramirez, Juan M. Gul, Sarah S. Hamarneh, Sulaiman R. Hodin, Richard A. TI Intestinal Alkaline Phosphatase Regulates Tight Junction Protein Levels SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID EPITHELIAL BARRIER; METABOLIC SYNDROME; ENTERAL NUTRITION; PERMEABILITY; GUT; EXPRESSION; INCREASE; COLITIS; DISEASE; ZO-1 AB BACKGROUND: Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and wellbeing. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. STUDY DESIGN: The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). RESULTS: Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP overexpression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. CONCLUSIONS: Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function. ((C) 2016 Published by Elsevier Inc. on behalf of the American College of Surgeons.) C1 [Liu, Wei; Hu, Dong; Huo, Haizhong; Zhang, Weifeng; Adiliaghdam, Fatemeh; Morrison, Sarah; Ramirez, Juan M.; Gul, Sarah S.; Hamarneh, Sulaiman R.; Hodin, Richard A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM rhodin@mgh.harvard.edu FU National Institute of Health [NIH/NIDDK T32 DK007754]; Ellison foundation FX This study was supported by National Institute of Health grant NIH/NIDDK T32 DK007754 and a grant from The Ellison foundation (RAH). NR 39 TC 5 Z9 5 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2016 VL 222 IS 6 BP 1009 EP 1017 DI 10.1016/j.jamcollsurg.2015.12.006 PG 9 WC Surgery SC Surgery GA DM7DH UT WOS:000376514300008 PM 27106638 ER PT J AU De Gregorio, L Lubitz, CC Hodin, RA Gaz, RD Parangi, S Phitayakorn, R Stephen, AE AF De Gregorio, Lucia Lubitz, Carrie C. Hodin, Richard A. Gaz, Randall D. Parangi, Sareh Phitayakorn, Roy Stephen, Antonia E. TI The Truth about Double Adenomas: Incidence, Localization, and Intraoperative Parathyroid Hormone SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID 4TH POUCH DISEASE; PRIMARY HYPERPARATHYROIDISM; ASSAY; MONOCLONALITY; HYPERPLASIA; MANAGEMENT; GLANDS; ENTITY; TUMORS AB BACKGROUND: Double adenoma is reported in 3% to 12% of patients with primary hyperparathyroidism. The aim of this study was to determine the true incidence of double adenoma and analyze the use of localization studies and intraoperative parathyroid hormone (IOTPH) assay in these cases. STUDY DESIGN: We conducted a retrospective review of a series of consecutive parathyroid surgical operations from 2010 to 2013. According to the surgical findings, the series was divided into single-gland disease (SGD), double-gland disease (DGD), and multi-gland disease (MGD, more than 2 glands). The sensitivity of ultrasound, technetium 99m-sestamibi, and 4-dimensional CT to correctly lateralize each gland in the DGD group was calculated. Results of the IOPTH assay and how they impacted the extent of surgery were analyzed. RESULTS: Three hundred and forty-seven patients had SGD (69%), 68 patients had DGD (13.5%), and 86 had MGD (17%). In the DGD group, sensitivity of ultrasound, technetium 99m-sestamibi, and 4-dimensional CT to lateralize each adenoma was 42%, 34.5%, and 64%, respectively. Initially, 27 patients (40%) with DGD had been planned for a focal exploration. The conversion to bilateral neck exploration was due to the IOPTH assay in 18 cases (two-thirds of the initially planned focal explorations). At 6-month follow-up, all DGD patients were normocalcemic. CONCLUSIONS: Localization studies in DGD can be misleading by reporting SGD. Four-dimensional CT seems to have the highest sensitivity. In focal explorations, the excision of all hyperfunctioning parathyroid tissue should be verified by IOPTH measurement. ((C) 2016 Published by Elsevier Inc. on behalf of the American College of Surgeons.) C1 [De Gregorio, Lucia; Lubitz, Carrie C.; Hodin, Richard A.; Gaz, Randall D.; Parangi, Sareh; Phitayakorn, Roy; Stephen, Antonia E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Stephen, AE (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM astephen@partners.org OI Phitayakorn, Roy/0000-0002-8327-1484 FU Alfonso Martin Escudero Foundation Research Grant, Madrid, Spain FX This study was supported by the Alfonso Martin Escudero Foundation Research Grant, Madrid, Spain. NR 34 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2016 VL 222 IS 6 BP 1044 EP 1052 DI 10.1016/j.jamcollsurg.2015.12.048 PG 9 WC Surgery SC Surgery GA DM7DH UT WOS:000376514300016 PM 27234627 ER PT J AU Tang, R Coopey, SB Merrill, AL Rai, U Specht, MC Gadd, MA Colwell, AS Austen, WG Brachtel, EF Smith, BL AF Tang, Rong Coopey, Suzanne B. Merrill, Andrea L. Rai, Upahvan Specht, Michelle C. Gadd, Michele A. Colwell, Amy S. Austen, William G., Jr. Brachtel, Elena F. Smith, Barbara L. TI Positive Nipple Margins in Nipple-Sparing Mastectomies: Rates, Management, and Oncologic Safety SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID AREOLA COMPLEX INVOLVEMENT; BREAST-CANCER; IMMEDIATE RECONSTRUCTION; FOLLOW-UP; SUBCUTANEOUS MASTECTOMY; AUTOLOGOUS RECONSTRUCTION; RISK; EXPERIENCE; CONSERVATION; REDUCTION AB BACKGROUND: When a nipple margin of a nipple-sparing mastectomy (NSM) contains malignancy, current practice includes removal of the nipple or nipple areola complex (NAC). We evaluated rates and trends of positive nipple margins, subsequent management, and oncologic outcomes. STUDY DESIGN: A retrospective chart review of all NSM at our institution from 2007 to 2014 was performed. A descriptive analysis was performed of patients with positive nipple/subareolar margins. RESULTS: Among 1,326 NSM, 43 of 642 (6.7%) therapeutic and 3 of 684 (0.4%) prophylactic NSM had positive nipple margins. Nipple or NAC excision was performed for 39 of 46 (85%) positive nipple margins: 20 of 39 (51%) had nipple only and 19 of 39 (49%) had the entire NAC excised. Practice evolved to remove only the nipple and retain the areola for positive nipple margins: in 2007 to 2011, 7 of 17 (41%) underwent nipple-only excision compared with 14 of 22 (64%) in 2012 to 2014. Among 39 excised nipples/NAC, 28 (72%) contained no residual malignancy, while 8 contained ductal carcinoma in situ (DCIS), 2 had invasive lobular carcinoma, and 1 had invasive ductal carcinoma. With experience, rates of positive nipple margins for therapeutic NSM decreased from 11% (17 of 160) in 2007 to 2011 to 5.4% (26 of 482) in 2012 to 2014 (p < 0.05). At 36 month median follow-up, there were no recurrences in the nipple/NAC. CONCLUSIONS: Early results suggest that excision of the nipple with retention of the areola is a safe approach for management of a positive nipple margin after NSM. With experience, low rates of positive nipple margins are possible in therapeutic NSM. Overall risk of nipple/NAC recurrence after NSM remains extremely low. ((C) 2016 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.) C1 [Tang, Rong; Coopey, Suzanne B.; Merrill, Andrea L.; Rai, Upahvan; Specht, Michelle C.; Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Colwell, Amy S.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Brachtel, Elena F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tang, Rong] Cent S Univ, Affiliated Tumor Hosp, Xiangya Med Sch, Div Breast Surg,Hunan Canc Hosp, Changsha, Hunan, Peoples R China. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Ctr Breast Canc, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 32 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2016 VL 222 IS 6 BP 1149 EP 1155 DI 10.1016/j.jamcollsurg.2016.02.016 PG 7 WC Surgery SC Surgery GA DM7DH UT WOS:000376514300031 PM 27118712 ER PT J AU Shindo, M Lee, JA Lubitz, CC McCoy, KL Orloff, LA Tufano, RP Pasieka, JL AF Shindo, Maise Lee, James A. Lubitz, Carrie C. McCoy, Kelly L. Orloff, Lisa A. Tufano, Ralph P. Pasieka, Janice L. TI The Changing Landscape of Primary, Secondary, and Tertiary Hyperparathyroidism: Highlights from the American College of Surgeons Panel, "What's New for the Surgeon Caring for Patients with Hyperparathyroidism" SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CHRONIC KIDNEY-DISEASE; NORMOCALCEMIC PRIMARY HYPERPARATHYROIDISM; NEAR-TOTAL PARATHYROIDECTOMY; RENAL-TRANSPLANT RECIPIENTS; CLINICAL-PRACTICE GUIDELINE; SINGLE-CENTER EXPERIENCE; DISORDER CKD-MBD; QUALITY-OF-LIFE; DIALYSIS PATIENTS; PERSISTENT HYPERPARATHYROIDISM C1 [Shindo, Maise] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lee, James A.] Columbia Univ, Med Ctr, New York, NY USA. [Lubitz, Carrie C.] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. [McCoy, Kelly L.] Univ Pittsburgh, Pittsburgh, PA USA. [Orloff, Lisa A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Tufano, Ralph P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Pasieka, Janice L.] Univ Calgary, Cumming Sch Med, Calgary, AB, Canada. RP Pasieka, JL (reprint author), Foothills Med Ctr, Dept Surg, North Tower,1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM janice.pasieka@ahs.ca NR 69 TC 0 Z9 0 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2016 VL 222 IS 6 BP 1240 EP 1250 DI 10.1016/j.jamcollsurg.2016.02.024 PG 11 WC Surgery SC Surgery GA DM7DH UT WOS:000376514300041 PM 27107975 ER PT J AU Kwolek, CJ LaMuraglia, GM Cambria, RP AF Kwolek, Christopher J. LaMuraglia, Glenn M. Cambria, Richard P. TI Transcarotid Artery Revascularization With High-Rate Flow Reversal Embolic Protection Demonstrates Improved Stroke and Death Rate Following FDA Premarket Clearance SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Kwolek, Christopher J.; LaMuraglia, Glenn M.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA VESS01 BP 4S EP 4S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600003 ER PT J AU Deery, SE Lancaster, RT Gubala, AM Ergul, EA Kwolek, CJ Conrad, MF Cambria, RP Patel, VI AF Deery, Sarah E. Lancaster, Robert T. Gubala, Anna M. Ergul, Emel A. Kwolek, Christopher J. Conrad, Mark F. Cambria, Richard P. Patel, Virendra I. TI Early and Intermediate Outcomes of Open Versus Fenestrated Repair of Complex Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Deery, Sarah E.; Lancaster, Robert T.; Ergul, Emel A.; Kwolek, Christopher J.; Conrad, Mark F.; Cambria, Richard P.; Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gubala, Anna M.] Massachusetts Gen Hosp, Maynard, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA VESS12 BP 12S EP 13S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600014 ER PT J AU Zettervall, SL McCallum, J Soden, PA Shean, KE Deery, SE O'Malley, J Landon, B Schermerhorn, ML AF Zettervall, Sara L. McCallum, John Soden, Peter A. Shean, Katie E. Deery, Sarah E. O'Malley, James Landon, Bruce Schermerhorn, Marc L. TI The Effect of Surgeon and Hospital Volume on Mortality Following Open and Endovascular Repair of Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Zettervall, Sara L.] Beth Israel Deaconess Med Ctr, Cambridge, MA USA. [McCallum, John; Soden, Peter A.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Malley, James] Dartmouth Inst, Lebanon, NH USA. [Landon, Bruce] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA VESS13 BP 13S EP 13S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600015 ER PT J AU Jones, DW Schermerhorn, ML Brooke, BS Conrad, MF Goodney, PP Wyers, MC Stone, DH AF Jones, Douglas W. Schermerhorn, Marc L. Brooke, Benjamin S. Conrad, Mark F. Goodney, Philip P. Wyers, Mark C. Stone, David H. TI Perioperative Clopidogrel Leads to Increased Bleeding, Cardiac, and Respiratory Complications at the Time of Lower Extremity Bypass SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Jones, Douglas W.] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Schermerhorn, Marc L.; Wyers, Mark C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brooke, Benjamin S.] Univ Utah, Salt Lake City, UT USA. [Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodney, Philip P.; Stone, David H.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA VESS23 BP 31S EP 32S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600047 ER PT J AU Zettervall, SL Soden, PA Deery, SE Shean, KE Siracuse, J Alef, M Patel, VI Schermerhorn, ML AF Zettervall, Sara L. Soden, Peter A. Deery, Sarah E. Shean, Katie E. Siracuse, Jeffrey Alef, Matthew Patel, Virendra I. Schermerhorn, Marc L. TI Outcome Differences Between Infrarenal and Suprarenal Fixation for Endografts in the Treatment Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Zettervall, Sara L.] Beth Israel Deaconess Med Ctr, Cambridge, MA USA. [Soden, Peter A.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Deery, Sarah E.; Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Siracuse, Jeffrey] Boston Univ, Sch Med, Boston, MA 02118 USA. [Alef, Matthew] Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP037 BP 68S EP 68S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600107 ER PT J AU Zettervall, SL Soden, PA Deery, SE Shean, K Giles, KA Kalra, M Schermerhorn, ML AF Zettervall, Sara L. Soden, Peter A. Deery, Sarah E. Shean, Katie Giles, Kristina A. Kalra, Manju Schermerhorn, Marc L. TI Effects of Extubation Time on Patient Outcomes Following AAA Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Zettervall, Sara L.] Beth Israel Deaconess Med Ctr, Cambridge, MA USA. [Soden, Peter A.; Shean, Katie; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Giles, Kristina A.] Univ Florida, Gainesville, FL USA. [Kalra, Manju] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP057 BP 75S EP 76S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600117 ER PT J AU Dansey, KD Zettervall, SL Soden, PA Shean, KE Deery, SE Nolan, BW Schermerhorn, ML AF Dansey, Kirsten D. Zettervall, Sara L. Soden, Peter A. Shean, Katie E. Deery, Sarah E. Nolan, Brian W. Schermerhorn, Marc L. TI Sex Differences in Patients Undergoing Carotid Endarterectomy and Stenting SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Dansey, Kirsten D.; Soden, Peter A.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Zettervall, Sara L.] Beth Israel Deaconess Med Ctr, Cambridge, MA USA. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nolan, Brian W.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP091 BP 83S EP 84S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600131 ER PT J AU Soden, PA Zettervall, SL Deery, SE Hughes, K Stoner, M Goodney, PP Vouyouka, A Schermerhorn, ML AF Soden, Peter A. Zettervall, Sara L. Deery, Sarah E. Hughes, Kakra Stoner, Michael Goodney, Philip P. Vouyouka, Ageliki Schermerhorn, Marc L. TI Disparities in Patient Selection/Presentation for Initial Vascular Procedure Between Black and White Patients SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Soden, Peter A.; Zettervall, Sara L.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hughes, Kakra] Howard Univ & Hosp, Washington, DC USA. [Stoner, Michael] Univ Rochester, Rochester, NY USA. [Goodney, Philip P.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Vouyouka, Ageliki] Mt Sinai Hlth Syst, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP151 BP 101S EP 102S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600162 ER PT J AU Brothers, TE Mixson, J AF Brothers, Thomas E. Mixson, Joshua TI Revascularization of Smokers With Claudication Is Associated With Better Patient Quality of Life Despite Higher Failure Risk SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Brothers, Thomas E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29403 USA. [Mixson, Joshua] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP169 BP 107S EP 108S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600171 ER PT J AU Bodewes, TCF Soden, PA Ultee, KHJ Zettervall, SL Shean, KE Deery, SE Moll, F Schermerhorn, ML AF Bodewes, Thomas C. F. Soden, Peter A. Ultee, Klaas H. J. Zettervall, Sara L. Shean, Katie E. Deery, Sarah E. Moll, Frans Schermerhorn, Marc L. TI Risk Factors for 30-Day Unplanned Readmission Following Infrainguinal Endovascular Interventions SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Bodewes, Thomas C. F.; Soden, Peter A.; Zettervall, Sara L.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ultee, Klaas H. J.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moll, Frans] Univ Med Ctr Utrecht, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP179 BP 110S EP 110S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600176 ER PT J AU Liang, P Soden, PA Zettervall, SL Shean, K Deery, SE Guzman, RJ Hamdan, AD Schermerhorn, ML AF Liang, Patric Soden, Peter A. Zettervall, Sara L. Shean, Katie Deery, Sarah E. Guzman, Raul J. Hamdan, Allen D. Schermerhorn, Marc L. TI Treatment Outcomes in Diabetic Patients With Critical Limb Ischemia SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Liang, Patric] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Soden, Peter A.; Zettervall, Sara L.; Shean, Katie; Guzman, Raul J.; Hamdan, Allen D.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP183 BP 112S EP 113S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600178 ER PT J AU Soden, PA Zettervall, SL Shean, KE Deery, SE Kalish, J Healey, CTT Kansal, N Schermerhorn, ML AF Soden, Peter A. Zettervall, Sara L. Shean, Katie E. Deery, Sarah E. Kalish, Jeffrey Healey, Christopher T. T. Kansal, Nikhil Schermerhorn, Marc L. TI Perioperative and 1-Year Outcomes With Adjunctive Femoral Endarterectomy in Lower Extremity Bypass SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Soden, Peter A.; Zettervall, Sara L.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kalish, Jeffrey] Boston Univ, Sch Med, Boston, MA 02118 USA. [Healey, Christopher T. T.] Tufts Univ, Sch Med, Portland, ME USA. [Kansal, Nikhil] St Elizabeths Med Ctr, Brighton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP201 BP 119S EP 120S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600189 ER PT J AU Shean, KE Soden, PA Schermerhorn, ML Zettervall, SL Deery, SE Hamdan, AD Amdur, R LoGerfo, FW AF Shean, Katie E. Soden, Peter A. Schermerhorn, Marc L. Zettervall, Sara L. Deery, Sarah E. Hamdan, Allen D. Amdur, Richard LoGerfo, Frank W. TI Lifelong Limb Salvage: A Patient-Centered Description of Lower Extremity Arterial Reconstruction Outcomes SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Soden, Peter A.; Schermerhorn, Marc L.; Zettervall, Sara L.; Hamdan, Allen D.; LoGerfo, Frank W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amdur, Richard] George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA IP205 BP 121S EP 121S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600191 ER PT J AU Patel, VI Mohebali, J Mehtsun, W Lancaster, RT Nasr, MC Dolan, R Cambria, RP AF Patel, Virendra I. Mohebali, Jahan Mehtsun, Winta Lancaster, Robert T. Nasr, Michael C. Dolan, Robert Cambria, Richard P. TI Open Repair of an Extent I Thoracoabdominal Aortic Aneurysm SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Patel, Virendra I.; Mohebali, Jahan; Mehtsun, Winta; Lancaster, Robert T.; Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nasr, Michael C.; Dolan, Robert] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA VS05 BP 140S EP 140S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600223 ER PT J AU Deery, SE Shean, KE Wang, GJ Black, JH Upchurch, GR Giles, KA Patel, VI Schermerhorn, ML AF Deery, Sarah E. Shean, Katie E. Wang, Grace J. Black, James H., III Upchurch, Gilbert R., Jr. Giles, Kristina A. Patel, Virendra I. Schermerhorn, Marc L. TI Female Sex Independently Predicts Mortality Following Elective Thoracic Endovascular Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Deery, Sarah E.; Patel, Virendra I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shean, Katie E.] Beth Israel Deaconess Med Ctr, Billerica, MA USA. [Wang, Grace J.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Black, James H., III] Johns Hopkins Univ, Baltimore, MD USA. [Upchurch, Gilbert R., Jr.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Giles, Kristina A.] Univ Florida, Gainesville, FL USA. [Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA PC010 BP 155S EP 156S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600246 ER PT J AU Jones, DW Deery, SE Zettervall, SL Soden, PA Shean, KE Meltzer, AJ Schneider, DB Schermerhorn, ML AF Jones, Douglas W. Deery, Sarah E. Zettervall, Sara L. Soden, Peter A. Shean, Katie E. Meltzer, Andrew J. Schneider, Darren B. Schermerhorn, Marc L. TI Differential Outcomes in Small, Medium, and Large Abdominal Aortic Aneurysms Following Elective Endovascular Aneurysm Repair SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-11, 2016 CL National Harbor, MD SP Soc Vasc Surg C1 [Jones, Douglas W.; Shean, Katie E.] Beth Israel Deaconess Med Ctr, Brookline, MA USA. [Deery, Sarah E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zettervall, Sara L.; Soden, Peter A.; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Meltzer, Andrew J.; Schneider, Darren B.] Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2016 VL 63 IS 6 SU S MA PC042 BP 165S EP 166S PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DM3EW UT WOS:000376230600262 ER EF