FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Koelman, DLH Benkeser, DC Xu, Y Neo, SX Tan, K Katsuno, M Sobue, G Natsume, J Carone, M Mateen, FJ AF Koelman, D. L. H. Benkeser, D. C. Xu, Y. Neo, S. X. Tan, K. Katsuno, M. Sobue, G. Natsume, J. Carone, M. Mateen, F. J. TI Acute disseminated encephalomyelitis in China, Singapore, and Japan: characterization and comparison with the USA SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Koelman, D. L. H.; Mateen, F. J.] Harvard Med Sch, Massachusetts Gen Hosp, Cambridge, MA USA. [Koelman, D. L. H.] Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands. [Benkeser, D. C.] Univ Calif Berkeley, Grp Biostat, Berkeley, CA 94720 USA. [Xu, Y.] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Neo, S. X.; Tan, K.] Natl Inst Neurosci, Singapore, Singapore. [Katsuno, M.; Sobue, G.; Natsume, J.] Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan. [Carone, M.] Univ Washington, Seattle, WA 98195 USA. [Mateen, F. J.] Harvard Med Sch, Boston, MA 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P266 BP 90 EP 91 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201006 ER PT J AU Chitnis, T Arnold, DL Banwell, B Bruck, W Ghezzi, A Giovannoni, G Greenberg, B Krupp, L Rostasy, K Tardieu, M Waubant, E Wolinsky, J Bar-Or, A Stites, T Merschhemke, M Gartner, J AF Chitnis, T. Arnold, D. L. Banwell, B. Brueck, W. Ghezzi, A. Giovannoni, G. Greenberg, B. Krupp, L. Rostasy, K. Tardieu, M. Waubant, E. Wolinsky, J. Bar-Or, A. Stites, T. Merschhemke, M. Gaertner, J. TI PARADIGMS baseline characteristics: a randomised, double-blind study of fingolimod in paediatric patients with multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. [Arnold, D. L.] NeuroRx Res, Montreal, PQ, Canada. [Arnold, D. L.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Banwell, B.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA. [Brueck, W.] Univ Med Ctr, Dept Neuropathol, Gottingen, Germany. [Ghezzi, A.] Osped Gallarate, Gallarate, Italy. [Giovannoni, G.] Queen Mary Univ London, Barts & London Sch Med Ctr & Dent, Blizard Inst, London, England. [Greenberg, B.] Univ Texas Southwestern Med Ctr Dallas, Childrens Hlth, Dallas, TX 75390 USA. [Krupp, L.] NYU Langone, Pediat MS Ctr, New York, NY USA. [Rostasy, K.] Univ Witten Herdecke, Childrens Hosp Datteln, Div Paediat Neurol, Recklinghausen, Germany. [Tardieu, M.] Hop Bicetre, AP HP, Paris, France. [Waubant, E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Wolinsky, J.] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Houston, TX 77030 USA. [Bar-Or, A.] McGill Univ, Montreal Neurol Inst & Hosp, Neuroimmunol Unit, Montreal, PQ, Canada. [Stites, T.] Novartis Pharmaceut, E Hanover, NJ USA. [Merschhemke, M.] Novartis Pharma AG, Basel, Switzerland. [Gaertner, J.] Univ Med Ctr, German Ctr Multiple Sclerosis Childhood & Adolesc, Dept Paediat & Adolescent Med, Gottingen, Germany. FU Novartis Pharma AG, Basel, Switzerland FX This study is supported by Novartis Pharma AG, Basel, Switzerland. The following authors have received compensation for serving as consultants or speakers, or they or the institutions they work for have received research support from the companies indicated: 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P290 BP 102 EP 103 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201030 ER PT J AU Diaz-Cruz, C Chua, AS Healy, BC Sattarnezhad, N Glanz, BI Weiner, HL Chitnis, T AF Diaz-Cruz, C. Chua, A. S. Healy, B. C. Sattarnezhad, N. Glanz, B. I. Weiner, H. L. Chitnis, T. TI An EDSS-based definition of secondary progressive multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Diaz-Cruz, C.; Chua, A. S.; Healy, B. C.; Sattarnezhad, N.; Glanz, B. I.; Weiner, H. L.; Chitnis, T.] Harvard Med Sch, Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA USA. [Healy, B. C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. FU Merck Serono; Google Life Sciences; Genzyme; Novartis; Serono; Biogen FX Camilo Diaz-Cruz received research support from Merck Serono and Google Life Sciences.; Alicia S. Chua has received research support from Google Life Sciences.; Brian C. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis and Google Life Sciences.; Neda Sattarnezhad received research support from Merck Serono and Google Life Sciences.; Tanuja Chitnis: Consulting for: Biogen-Idec, Novartis, Roche-Genetech. Advisory boards: Serves on advisory boards for pediatric clinical trials for Novartis and Genzyme-Sanofi. Research support: Serono, Biogen, Novartis, Google Life Sciences 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P298 BP 107 EP 108 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201038 ER PT J AU Bergendal, G Ouellette, R Shams, S Martola, J Mainero, C Kristoffersen-Wiberg, M Fredrikson, S Granberg, T AF Bergendal, G. Ouellette, R. Shams, S. Martola, J. Mainero, C. Kristoffersen-Wiberg, M. Fredrikson, S. Granberg, T. TI Cognitive decline in multiple sclerosis is linear and associated with lesion accumulation and corpus callosal atrophy: results of an 18-year longitudinal study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Bergendal, G.; Shams, S.; Martola, J.; Kristoffersen-Wiberg, M.; Granberg, T.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Bergendal, G.; Fredrikson, S.] Karolinska Univ Hosp, Dept Neurol, Stockohlm, Sweden. [Ouellette, R.; Mainero, C.; Granberg, T.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ouellette, R.] Harvard Med Sch, Dept Radiol, Cambridge, MA USA. [Shams, S.; Martola, J.; Kristoffersen-Wiberg, M.; Granberg, T.] Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden. [Mainero, C.] Harvard Med Sch, Cambridge, MA USA. [Fredrikson, S.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. FU EMD Merck Serono; Biogen; Stockholm County Council (ALF project) FX Professor Fredrikson has received honoraria for lectures or educational activities from Allergan, Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi and Teva. All other authors report no disclosures. Assistant professor Mainero has received research support from EMD Merck Serono and speaker fees from Biogen. This study was supported by grants provided by the Stockholm County Council (ALF project). 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P479 BP 205 EP 206 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201218 ER PT J AU Granberg, T Fan, Q Treaba, CA Ouellette, R Herranz, E Mangeat, G Louapre, C Klawiter, EC Sloane, JA Mainero, C AF Granberg, T. Fan, Q. Treaba, C. A. Ouellette, R. Herranz, E. Mangeat, G. Louapre, C. Klawiter, E. C. Sloane, J. A. Mainero, C. TI Ultra-high field and gradient strength MRI reveal neuroaxonal pathology in cortex and white matter in early MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Granberg, T.; Fan, Q.; Treaba, C. A.; Ouellette, R.; Herranz, E.; Mangeat, G.; Louapre, C.; Mainero, C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Granberg, T.; Fan, Q.; Treaba, C. A.; Ouellette, R.; Herranz, E.; Louapre, C.; Klawiter, E. C.; Mainero, C.] Harvard Med Sch, Cambridge, MA USA. [Granberg, T.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Mangeat, G.] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada. [Klawiter, E. C.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Sloane, J. A.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. FU National Institute of Health [NIH R01NS078322-01-A1]; Karolinska Institutet (ALF grant); EMD Merck Serono; Biogen; Atlas5d; Roche; Genentech; Genentech and Shire FX This study was supported by the National Institute of Health (NIH R01NS078322-01-A1) and Karolinska Institutet (ALF grant).; Dr. Mainero has received research support from EMD Merck Serono and speaker fees from Biogen.; Dr. Klawiter has received research support for Atlas5d, Biogen, EMD Serono and Roche and received consulting fees from EMD Serono, Genentech and Shire. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P526 BP 234 EP 235 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201265 ER PT J AU Lima, G McCroskery, P Dewar, R Castillo, JJ Holman, J Umans, K Fam, S AF Lima, G. McCroskery, P. Dewar, R. Castillo, J. J. Holman, J. Umans, K. Fam, S. TI Characterisation of the lymphadenopathy events observed in the daclizumab HYP clinical trials SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Lima, G.; McCroskery, P.; Umans, K.; Fam, S.] Biogen, Cambridge, MA USA. [Dewar, R.] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA. [Castillo, J. J.] Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA USA. [Holman, J.] AbbVie Inc, N Chicago, IL USA. FU Biogen; AbbVie Biotherapeutics Inc. FX Supported by: Biogen and AbbVie Biotherapeutics Inc. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P632 BP 297 EP 297 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201371 ER PT J AU Bargiela, D Bianchi, MT Westover, MB Chibnik, LB Healy, BC de Jager, PL Xia, Z AF Bargiela, D. Bianchi, M. T. Westover, M. B. Chibnik, L. B. Healy, B. C. de Jager, P. L. Xia, Z. TI Selection of first-line therapy in multiple sclerosis using risk-benefit decision analysis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Bargiela, D.; Chibnik, L. B.; Healy, B. C.; de Jager, P. L.; Xia, Z.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. [Bargiela, D.; Chibnik, L. B.; de Jager, P. L.; Xia, Z.] Broad Inst, Boston, MA USA. [Bargiela, D.; Bianchi, M. T.; Westover, M. B.; Chibnik, L. B.; de Jager, P. L.] Harvard Med Sch, Boston, MA USA. [Bianchi, M. T.; Westover, M. B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Healy, B. C.] Massachusetts Gen Hosp, Dept Stat, Boston, MA 02114 USA. [Xia, Z.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. FU National Institute of Health FX National Institute of Health 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P719 BP 350 EP 351 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201458 ER PT J AU Hugos, C Chen, Z Chen, Y Cameron, M Wick, K Turner, A Haselkorn, J Sloan, A Chiara, T Mc Coy, S Bever, C Kunce, A Bourdette, D AF Hugos, C. Chen, Z. Chen, Y. Cameron, M. Wick, K. Turner, A. Haselkorn, J. Sloan, A. Chiara, T. Mc Coy, S. Bever, C. Kunce, A. Bourdette, D. TI A multicenter randomized controlled trial of two group programs in multiple sclerosis: effects on fatigue and self-efficacy SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Hugos, C.; Cameron, M.; Wick, K.; Bourdette, D.] VA Portland Hlth Care Syst, Portland, OR USA. [Chen, Z.; Chen, Y.; Bourdette, D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Turner, A.; Haselkorn, J.; Sloan, A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chiara, T.; Mc Coy, S.] North Florida South Georgia Vet Hlth Syst, Gainesville, FL USA. [Bever, C.; Kunce, A.] VA Maryland Hlth Care Syst, Baltimore, MD USA. FU VA RRD [F7777-R]; OCTRI NCATS [UL1TR000128] FX VA RR&D F7777-R and OCTRI NCATS-funded CTSA grant (UL1TR000128 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P759 BP 378 EP 378 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267201498 ER PT J AU Ameli, R Prieto, JC Waltz, M Tillema, J Graves, J Weinstock-Guttman, B Belman, A Olsen, C Aaen, G Benson, L Gorman, M Krupp, L Lotze, T Ness, J Waubant, E Rose, J Rodriguez, M Casper, C Rapalino, O Cotton, F Guttmann, C Chitnis, T AF Ameli, R. Prieto, J. C. Waltz, M. Tillema, J. Graves, J. Weinstock-Guttman, B. Belman, A. Olsen, C. Aaen, G. Benson, L. Gorman, M. Krupp, L. Lotze, T. Ness, J. Waubant, E. Rose, J. Rodriguez, M. Casper, C. Rapalino, O. Cotton, F. Guttmann, C. Chitnis, T. CA US Network Pediat MS Ctr TI Differential MRI lesion features in pediatric NMO and pediatric MS SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Ameli, R.; Prieto, J. C.; Guttmann, C.] Brigham & Womens Hosp, Radiol, 75 Francis St, Boston, MA 02115 USA. [Waltz, M.; Olsen, C.; Casper, C.] Univ Utah, Pediat, Salt Lake City, UT USA. [Tillema, J.; Rodriguez, M.] Mayo Clin, Pediat MS Ctr, Rochester, NY USA. [Graves, J.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA. [Weinstock-Guttman, B.] SUNY Buffalo, Pediat MS Ctr, Jacobs Neurol Inst, Buffalo, NY USA. [Belman, A.; Krupp, L.] Stony Brook Childrens Hosp, Lourie Ctr Pediat MS, Stony Brook, NY USA. [Aaen, G.] Loma Linda Univ, Pediat MS Ctr, Childrens Hosp, Loma Linda, CA 92350 USA. [Benson, L.; Gorman, M.] Boston Childrens Hosp, Boston, MA USA. [Lotze, T.] Baylor Coll Med, Blue Bird Circle MS Ctr, Houston, TX 77030 USA. [Ness, J.] Univ Alabama Birmingham, Ctr Pediat Onset Demyelinating Dis, Childrens Hosp Alabama, Birmingham, AL USA. [Waubant, E.] Univ Calif San Francisco, Benioff Childrens Hosp, Pediat, San Francisco, CA 94143 USA. [Rose, J.] Univ Utah, Neurol, Salt Lake City, UT USA. [Rapalino, O.] Massachusetts Gen Hosp, Neuroradiol, Boston, MA 02114 USA. [Cotton, F.] Univ Claude Bernard, Ctr Hosp Lyon Sud, Radiol, Lyon, France. [Cotton, F.] Univ Lyon, CREATIS, CNRS, UMR 5220, Lyon, France. [Cotton, F.] Univ Lyon, CREATIS, INSERM, U1044, Lyon, France. [Chitnis, T.] Massachusetts Gen Hosp Children, Partners Pediat Multiple Sclerosis Ctr, Boston, MA USA. FU Guthy Jackson Charitable Foundation (TC-Eureka grant) FX This work was funded by the Guthy Jackson Charitable Foundation (TC-Eureka grant). 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P825 BP 415 EP 415 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202027 ER PT J AU Diaz-Cruz, C Chua, AS Healy, BC Chitnis, T AF Diaz-Cruz, C. Chua, A. S. Healy, B. C. Chitnis, T. TI Benign multiple sclerosis in the era of disease modifying therapies SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Diaz-Cruz, C.; Chua, A. S.; Healy, B. C.; Chitnis, T.] Harvard Med Sch, Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA USA. [Healy, B. C.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. FU Merck Serono; Google Life Sciences; Genzyme; Novartis; Serono; Biogen FX Camilo Diaz-Cruz received research support from Merck Serono and Google Life Sciences. Alicia S. Chua has received research support from Google Life Sciences. Brian C. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis and Google Life Sciences. Tanuja Chitnis: Consulting for: Biogen-Idec, Novartis, Roche-Genetech. Advisory boards: Serves on advisory boards for pediatric clinical trials for Novartis and Genzyme-Sanofi. Research support: Serono, Biogen, Novartis, Google Life Sciences 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P843 BP 425 EP 426 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202045 ER PT J AU Van Obberghen, E Girard, O Le Troter, A Soulier, E Viout, P Guye, M Varma, G Alsop, DC Ranjeva, JP Pelletier, J Duhamel, G AF Van Obberghen, E. Girard, O. Le Troter, A. Soulier, E. Viout, P. Guye, M. Varma, G. Alsop, D. C. Ranjeva, J. P. Pelletier, J. Duhamel, G. TI Inhomogeneous magnetization transfer (ihMT): application for multiple sclerosis (MS) SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Van Obberghen, E.; Girard, O.; Le Troter, A.; Soulier, E.; Viout, P.; Guye, M.; Ranjeva, J. P.; Pelletier, J.; Duhamel, G.] Aix Marseille Univ, CRMBM, CEMEREM, CNRS, Marseille, France. [Varma, G.; Alsop, D. C.] Harvard Med Sch, Dept Radiol, BIDMC, Boston, MA USA. [Pelletier, J.] Hop La Timone, APHM, Serv Neurol, Pole Neurosci Clin, Marseille, France. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1014 BP 516 EP 517 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202214 ER PT J AU Palotai, M Nazeri, A Cavallari, M Healy, BC Glanz, B Chitnis, T Guttmann, CRG AF Palotai, M. Nazeri, A. Cavallari, M. Healy, B. C. Glanz, B. Chitnis, T. Guttmann, C. R. G. TI Grey matter atrophy in the fronto-striato-thalamo-cortical circuit and in the insula play a role in the pathophysiology of fatigue in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Palotai, M.; Nazeri, A.; Cavallari, M.; Guttmann, C. R. G.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Ctr Neurol Imaging, Boston, MA USA. [Nazeri, A.] Boston Univ, Div Grad Med Sci, Boston, MA 02215 USA. [Healy, B. C.; Glanz, B.; Chitnis, T.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Partners Multiple Sclerosis Ctr, Boston, MA USA. [Healy, B. C.] Harvard Med Sch, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA USA. FU Multiple Sclerosis International Federation; Mallinckrodt Pharmaceuticals; Genzyme; Merck Serono; Novartis; Verily Life Sciences; Serono; Biogen; Google Life Sciences; Sanofi; National Multiple Sclerosis Society; National Multiple Sclerosis Society [RG-1501-03141] FX Dr. Palotai is currently a recipient of the McDonald Fellowship from the Multiple Sclerosis International Federation. Dr. Nazeri reports no conflict of interest. Dr. Cavallari is supported by a Research Fellowship from Mallinckrodt Pharmaceuticals. Dr. Healy was on the Biogen Worldwide Medical Biostatistics Multiple Sclerosis Advisory Board and received grant support from Genzyme, Merck Serono, Novartis, and Verily Life Sciences. Dr. Glanz received research support from Merck Serono and Verily Life Sciences. Dr. Chitnis is a consultant at Biogen, Novartis and Roche-Genetech and serves on advisory boards for pediatric clinical trials for Novartis and Genzyme-Sanofi. Dr. Chitnis received research support from Serono, Biogen, Novartis and Google Life Sciences. Dr. Guttmann has nothing to disclose that could constitute a potential conflict of interest for this work. Dr. Guttmann has received a grant from Sanofi and a grant from the National Multiple Sclerosis Society.; This investigation was supported by a grant from the National Multiple Sclerosis Society (grant identifier RG-1501-03141). 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1062 BP 547 EP 548 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202263 ER PT J AU Treaba, CA Granberg, T Herranz, E Ouellette, R Louapre, C Kinkel, RP Sloane, JA Mainero, C AF Treaba, C. A. Granberg, T. Herranz, E. Ouellette, R. Louapre, C. Kinkel, R. P. Sloane, J. A. Mainero, C. TI Cortical lesions dynamics in multiple sclerosis at 7T MRI: A longitudinal study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Treaba, C. A.; Granberg, T.; Herranz, E.; Ouellette, R.; Louapre, C.; Mainero, C.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Treaba, C. A.; Granberg, T.; Herranz, E.; Ouellette, R.; Louapre, C.; Mainero, C.] Harvard Med Sch, Cambridge, MA USA. [Granberg, T.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Kinkel, R. P.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Sloane, J. A.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. FU National MS Society [NMSS 4281-RG-A1, NMSS RG 4729A2/1]; NIH [R01NS078322-01-A1]; US Army [W81XWH-13-1-0122]; EMD Merck Serono; Biogen FX This work was supported by grants from the National MS Society (NMSS 4281-RG-A1 and NMSS RG 4729A2/1) and by NIH R01NS078322-01-A1, US Army W81XWH-13-1-0122. Dr. Mainero has received research support from EMD Merck Serono and speaker fees from Biogen. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1066 BP 549 EP 550 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202267 ER PT J AU Ouellette, R Granberg, T Herranz, E Treaba, CA Govindarajan, ST Gianni, C Louapre, C Kinkel, RP Mainero, C AF Ouellette, R. Granberg, T. Herranz, E. Treaba, C. A. Govindarajan, S. T. Gianni, C. Louapre, C. Kinkel, R. P. Mainero, C. TI Longitudinal quantitative T2*imaging at 7T reveals progression of microstructural damage in cortical lesions SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Ouellette, R.; Granberg, T.; Herranz, E.; Treaba, C. A.; Govindarajan, S. T.; Gianni, C.; Louapre, C.; Mainero, C.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ouellette, R.; Granberg, T.; Herranz, E.; Treaba, C. A.; Govindarajan, S. T.; Gianni, C.; Louapre, C.; Mainero, C.] Harvard Med Sch, Cambridge, MA USA. [Granberg, T.] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Kinkel, R. P.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. FU National MS Society [NMSS 4281 RGA]; EMD Merck Serono; Biogen FX This study was supported by the National MS Society (NMSS 4281 RGA). Dr. Mainero has received research support from EMD Merck Serono and speaker fees from Biogen. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1068 BP 550 EP 551 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202269 ER PT J AU Herranz, E Louapre, C Govindarajan, S Treaba, CA Gianni, C Ouellette, R Granberg, T Mangeat, G Sloane, J Klawiter, EC Kinkel, RP Mainero, C AF Herranz, E. Louapre, C. Govindarajan, S. Treaba, C. A. Gianni, C. Ouellette, R. Granberg, T. Mangeat, G. Sloane, J. Klawiter, E. C. Kinkel, R. P. Mainero, C. TI Neuroinflammation and cortical demyelination in multiple sclerosis and their contribution to cognition: a C-11-PBR28 MR-PET and quantitative 7T imaging study SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Herranz, E.; Louapre, C.; Treaba, C. A.; Gianni, C.; Granberg, T.; Klawiter, E. C.; Mainero, C.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Govindarajan, S.; Ouellette, R.; Mangeat, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Granberg, T.] Karolinska Inst, Intervent & Technol, Stockholm, Sweden. [Mangeat, G.] Polytech Montreal, Inst Biomed Engn, Montreal, PQ, Canada. [Sloane, J.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Kinkel, R. P.] Univ Calif San Diego, San Diego, CA 92103 USA. FU Clafin Award; National MS Society (NMSS) [RG 4729A2/1]; Department of Defense (DoD) US Army [W81XWH-13-1-0112]; EMD Merck Serono; Biogen; FISM [2012/B/4]; ARSEP foundation; Biogen Idec; Mallinckrodt Pharmaceuticals; Roche; Atlas5d FX This study was supported partly by the Clafin Award; partly by a grant from the National MS Society (NMSS) RG 4729A2/1, and partly by the Department of Defense (DoD) US Army W81XWH-13-1-0112 Award.; Dr Mainero has received research support from EMD Merck Serono and speaker fees from Biogen.; Dr Gianni has received a fellowship from FISM 2012/B/4; Dr Louapre received a fellowship from ARSEP foundation; Dr Klawiter has received consulting fees from Biogen Idec and Mallinckrodt Pharmaceuticals and research funding from Roche and Atlas5d NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1069 BP 551 EP 551 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202270 ER PT J AU Tobyne, SM Ochoa, WB Bireley, JD Smith, V Schmahmann, JD Klawiter, EC AF Tobyne, S. M. Ochoa, W. B. Bireley, J. D. Smith, V. Schmahmann, J. D. Klawiter, E. C. TI Cerebellar lesion mapping reveals divergent profiles of white matter involvement between cognitively impairment and cognitively preservation in relapsing remitting multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Tobyne, S. M.; Ochoa, W. B.; Bireley, J. D.; Smith, V.; Schmahmann, J. D.; Klawiter, E. C.] Harvard Med Sch, Massachusetts Gen Hosp, Neurol, Boston, MA USA. [Ochoa, W. B.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Ochoa, W. B.] Dept Anat & Neurosci, Amsterdam, Netherlands. FU Atlas5d; Biogen; EMD Serono; Roche; Genentech; Shire; Ataxion; Takeda FX ECK has received research grant support from Atlas5d, Biogen, EMD Serono, and Roche. ECK has received consulting fees from EMD Serono, Genentech, and Shire. JDS has received consulting fees from Ataxion and Takeda. SMT, WBO, JDB and VS have nothing to disclose. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1076 BP 555 EP 555 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202277 ER PT J AU Kappos, L Stefano, ND Sormani, MP Giovannoni, G Haring, D Tomic, D Meier, DP Chitnis, T AF Kappos, L. Stefano, N. D. Sormani, M. P. Giovannoni, G. Haring, D. Tomic, D. Meier, D. Piani Chitnis, T. TI NEDA as a predictor of conversion to secondary progressive multiple sclerosis in patients with relapsing-remitting multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Kappos, L.] Univ Basel Hosp, Neurol Clin & Policlin, Dept Med, Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Neurol Clin & Policlin, Dept Clin Res, Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Neurol Clin & Policlin, Dept Biomed, Basel, Switzerland. [Kappos, L.] Univ Basel Hosp, Neurol Clin & Policlin, Dept Biomed Engn, Basel, Switzerland. [Stefano, N. D.] Univ Siena, Siena, Italy. [Sormani, M. P.] Univ Genoa, Dept Hlth Sci, Biostat Unit, Genoa, Italy. [Giovannoni, G.] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England. [Haring, D.; Tomic, D.; Meier, D. Piani] Novartis Pharma AG, Basel, Switzerland. [Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. FU Novartis Pharma AG, Basel, Switzerland FX This study is supported by Novartis Pharma AG, Basel, Switzerland. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1217 BP 638 EP 639 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202416 ER PT J AU Rinker, JR Meador, W Sung, V Nicholas, A Cutter, G AF Rinker, J. R. Meador, W. Sung, V. Nicholas, A. Cutter, G. TI Results of a pilot trial of lithium in progressive multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Rinker, J. R.; Meador, W.; Sung, V.; Nicholas, A.] Univ Alabama Birmingham, Neurol, Birmingham, AL USA. [Rinker, J. R.; Sung, V.; Nicholas, A.] Birmingham VA Med Ctr, Neurol, Birmingham, AL USA. [Cutter, G.] Univ Alabama Birmingham, Biostat, Birmingham, AL USA. FU Department of Veterans Affairs [CDA2-003-10S] FX Funding for the trial was provided through the Department of Veterans Affairs, CDA2-003-10S. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1282 BP 678 EP 679 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267202481 ER PT J AU Saxena, S Kivisakk, P Keyhanian, K Kim, G Chitnis, T AF Saxena, S. Kivisakk, P. Keyhanian, K. Kim, G. Chitnis, T. TI Expression profile of pro-inflammatory cytokines in memory T cells of pediatric demyelinating patients. SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) CY SEP 14-17, 2016 CL London, ENGLAND SP European Comm Treatment & Res Multiple Sclerosis C1 [Saxena, S.; Kivisakk, P.; Keyhanian, K.; Kim, G.; Chitnis, T.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Chitnis, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIH; National MS Society; Guthy-Jackson Charitable Foundation; CMSC; Merck-Serono; Novartis FX T. Chitnis has served as a consultant for Biogen Idec, Teva Neurosciences, Novartis, and Sanofi-Aventis, and has received grant support from NIH, National MS Society, Guthy-Jackson Charitable Foundation, CMSC and Merck-Serono, and Novartis. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 SU 3 MA P1670 BP 880 EP 881 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV9NJ UT WOS:000383267203342 ER PT J AU Chandregowda, A Arbel, Y Donchin, E AF Chandregowda, Adithya Arbel, Yael Donchin, Emanuel TI HAND MOTOR TASK: LATERALIZED READINESS POTENTIALS AND HEMISPHERIC ASYMMETRY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract DE motor praxis; LRPs; hemispheric dominance C1 [Chandregowda, Adithya; Donchin, Emanuel] Univ S Florida, Tampa, FL 33620 USA. [Arbel, Yael] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2016 VL 53 SU 1 SI SI MA 2-61 BP S52 EP S52 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA EK1FX UT WOS:000393672300194 ER PT J AU Hazlett, E Blair, N Fernandez, N Mascitelli, K Banthin, D Goodman, M AF Hazlett, Erin Blair, Nicholas Fernandez, Nicolas Mascitelli, Kathryn Banthin, David Goodman, Marianne TI AFFECTIVE STARTLE DURING UNPLEASANT PICTURES PREDICTS A FUTURE SUICIDE ATTEMPT IN VETERANS SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract DE startle eyeblink; emotion; depression; suicide C1 Icahn Sch Med Mt Sinai, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY USA. FU Department of Defense [W81XWH0910722]; VA Merit Award [I01CX00026]; VISN 2 South Mental Illness, Research, Education, and Clinical Center (MIRECC) at the James J. Peters VA Medical Center FX This research was supported by a Department of Defense grant (W81XWH0910722) to EAH and MG; MPIs), a VA Merit Award (I01CX00026) to EAH, and the VISN 2 South Mental Illness, Research, Education, and Clinical Center (MIRECC) at the James J. Peters VA Medical Center. 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2016 VL 53 SU 1 SI SI MA 1-12 BP S19 EP S19 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA EK1FX UT WOS:000393672300076 ER PT J AU McCleery, A Wynn, JK Polon, N Szewczyk, W Roach, BJ Mathalon, DH Green, MF AF McCleery, Amanda Wynn, Jonathan K. Polon, Nora Szewczyk, Warren Roach, Brian J. Mathalon, Daniel H. Green, Michael F. TI DIMINISHED CORTICAL PLASTICITY IN CHRONIC PHASE SCHIZOPHRENIA: AN ELECTROPHYSIOLOGICAL STUDY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 [McCleery, Amanda; Wynn, Jonathan K.; Polon, Nora; Szewczyk, Warren; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. [McCleery, Amanda; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles, Los Angeles, CA USA. [Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Hlth Care Syst, San Francisco, CA USA. FU VA Greater Los Angeles VISN 22 Mental Illness Research, Education, and Clinical Center (MIRECC) Pala Grant FX VA Greater Los Angeles VISN 22 Mental Illness Research, Education, and Clinical Center (MIRECC) Pala Grant (PI: McCleery). 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2016 VL 53 SU 1 SI SI MA 1-23 BP S22 EP S22 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA EK1FX UT WOS:000393672300086 ER PT J AU Wlotko, E Kuperberg, G AF Wlotko, Edward Kuperberg, Gina TI INDIVIDUAL DIFFERENCES IN LINGUISTIC AND NONLINGUISTIC SKILLS MODULATE NEURAL PROCESSING OF WORDS IN CONTEXT SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract DE language comprehension; prediction C1 [Wlotko, Edward; Kuperberg, Gina] Tufts Univ, Medford, MA 02155 USA. [Kuperberg, Gina] Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIH [R01-HD082527]; institutional career development award through Tufts [K12-GM074869] FX NIH grant R01-HD082527 to G.K. and K12-GM074869 institutional career development award through Tufts to E.W. 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 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2016 VL 53 SU 1 SI SI MA 2-34 BP S45 EP S45 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA EK1FX UT WOS:000393672300168 ER PT J AU Singh, P Lauwers, GY Garber, JJ AF Singh, Prashant Lauwers, Gregory Y. Garber, John J. TI Outcomes of Seropositive Patients With Marsh 1 Histology in Clinical Practice SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE celiac disease; Marsh 1; duodenal lymphocytosis; minimal enteropathy ID POTENTIAL CELIAC-DISEASE; MILD ENTEROPATHY; NATURAL-HISTORY; DIAGNOSIS; SPECTRUM; CRITERIA; CHILDREN; GLUTEN AB Goals: We retrospectively studied all seropositive Marsh 1 patients seen at 2 tertiary care hospitals in the last 15 years to determine their clinical, serological, and histologic outcomes. Background: Patients with positive celiac serologies and Marsh 1 histology represent an understudied subgroup of patients, and it is unclear whether they should be advised to adopt a gluten-free diet (GFD). Study: Subjects were identified based on positive celiac serologies and Marsh 1 histology while on a full-gluten diet. Clinical presentation and baseline laboratory data were noted. Clinical course, repeat serologies, and histology were determined. Results: Of 620 patients with positive celiac serologies and abnormal duodenal histology, we identified 36 (5.8%) with positive tissue transglutaminase and/or antiendomysial antibodies and Marsh 1 lesions who had adequate follow-up. Abdominal pain was the commonest (47.2%) presenting symptom. Twenty-eight patients were advised to adopt GFD, whereas 8 were not. Among patients treated with GFD, 88.9% improved symptomatically and 95% normalized serology. In contrast, among patients who continued to consume gluten, 85.7% remained symptomatic and 80% had persistently positive serologies. Among the 8 patients on normal diet, 5 underwent repeat biopsy, and 4 of them had the same or worse histology, with 3 patients progressing to Marsh 3c. Among the 28 patients on GFD, 5 underwent repeat biopsy and all improved to normal histology. Conclusions: Most patients with positive celiac serology and Marsh 1 lesions benefit from GFD and, if not treated, a majority will continue to be symptomatic and remain at risk of progressing to villous atrophy. C1 [Singh, Prashant; Garber, John J.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Singh, Prashant; Garber, John J.] Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 712, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Jackson 712, Boston, MA 02114 USA. RP Garber, JJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 712, Boston, MA 02114 USA. EM jjgarber@mgh.harvard.edu FU Career Development Award from the Crohn's & Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK094966] FX J.J.G. is supported by a Career Development Award from the Crohn's & Colitis Foundation of America and by the National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK094966). NR 19 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 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2016 VL 50 IS 8 BP 619 EP 623 DI 10.1097/MCG.0000000000000522 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DT4TB UT WOS:000381472800006 ER PT J AU McCullough, MB AF McCullough, Megan B. TI Fat-Talk Nation: The Human Costs of America's War on Fat SO ANTHROPOLOGICAL QUARTERLY LA English DT Book Review ID OBESITY C1 [McCullough, Megan B.] US Dept Vet Affairs, Washington, DC 20420 USA. RP McCullough, MB (reprint author), US Dept Vet Affairs, Washington, DC 20420 USA. NR 23 TC 0 Z9 0 U1 1 U2 1 PU GEORGE WASHINGTON UNIV INST ETHNOGRAPHIC RESEARCH PI WASHINGTON PA GEORGE WASHINGTON UNIV, 2110 G ST, N W, WASHINGTON, DC 20052 USA SN 0003-5491 EI 1534-1518 J9 ANTHROPOL QUART JI Anthropol. Q. PD FAL PY 2016 VL 89 IS 4 BP 1285 EP 1291 PG 7 WC Anthropology SC Anthropology GA EJ3BY UT WOS:000393087500016 ER PT J AU Hill-Burns, EM Ross, OA Wissemann, WT Soto-Ortolaza, AI Zareparsi, S Siuda, J Lynch, T Wszolek, ZK Silburn, PA Mellick, GD Ritz, B Scherzer, CR Zabetian, CP Factor, SA Breheny, PJ Payami, H AF Hill-Burns, Erin M. Ross, Owen A. Wissemann, William T. Soto-Ortolaza, Alexandra I. Zareparsi, Sepideh Siuda, Joanna Lynch, Timothy Wszolek, Zbigniew K. Silburn, Peter A. Mellick, George D. Ritz, Beate Scherzer, Clemens R. Zabetian, Cyrus P. Factor, Stewart A. Breheny, Patrick J. Payami, Haydeh TI Identification of genetic modifiers of age-at-onset for familial Parkinson's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; RECESSIVE JUVENILE PARKINSONISM; SEGREGATION ANALYSIS; TUMOR-SUPPRESSOR; RISK-FACTORS; MUTATIONS; COMMON; VISUALIZATION; EXPRESSION; VARIANTS AB Parkinson's disease (PD) is the most common cause of neurodegenerative movement disorder and the second most common cause of dementia. Genes are thought to have a stronger effect on age-at-onset of PD than on risk, yet there has been a phenomenal success in identifying risk loci but not age-at-onset modifiers. We conducted a genome-wide study for age-at-onset. We analysed familial and non-familial PD separately, per prior evidence for strong genetic effect on age-at-onset in familial PD. GWAS was conducted in 431 unrelated PD individuals with at least one affected relative (familial PD) and 1544 non-familial PD from the NeuroGenetics Research Consortium (NGRC); an additional 737 familial PD and 2363 non-familial PD were used for replication. In familial PD, two signals were detected and replicated robustly: one mapped to LHFPL2 on 5q14.1 (P-NGRC = 3E-8, P-Replication = 2E-5, PNGRC+Replication = 1E-11), the second mapped to TPM1 on 15q22.2 (P-NGRC = 8E-9, P-Replication = 2E-4, PNGRC+Replication-9E-11). The variants that were associated with accelerated onset had low frequencies (<0.02). The LHFPL2 variant was associated with earlier onset by 12.33 [95% CI: 6.2; 18.45] years in NGRC, 8.03 [2.95; 13.11] years in replication, and 9.79 [5.88; 13.70] years in the combined data. The TPM1 variant was associated with earlier onset by 15.30 [8.10; 22.49] years in NGRC, 9.29 [1.79; 16.79] years in replication, and 12.42 [7.23; 17.61] years in the combined data. Neither LHFPL2 nor TPM1 was associated with age-at-onset in non-familial PD. LHFPL2 ( function unknown) is overexpressed in brain tumours. TPM1 encodes a highly conserved protein that regulates muscle contraction, and is a tumour-suppressor gene. C1 [Hill-Burns, Erin M.; Wissemann, William T.; Payami, Haydeh] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. [Ross, Owen A.; Soto-Ortolaza, Alexandra I.] Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Zareparsi, Sepideh] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Siuda, Joanna] Med Univ Silesia, Dept Neurol, Katowice, Poland. [Lynch, Timothy] Univ Coll Dublin, Mater Misericordiae Univ Hosp, Conway Inst Biomol & Biomed Res, Dublin Neurol Inst, Dublin, Ireland. [Wszolek, Zbigniew K.] Mayo Clin Jacksonville, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. [Silburn, Peter A.; Mellick, George D.] Griffith Univ, Eskitis Inst Drug Discovery, Nathan, Qld, Australia. [Ritz, Beate] Univ Calif Los Angeles, Geffen Sch Med, Fielding Sch Publ Hlth & Neurol, Dept Epidemiol, Los Angeles, CA USA. [Scherzer, Clemens R.] Harvard Med Sch, Neurogen Lab, Cambridge, MA USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Breheny, Patrick J.] Univ Iowa, Dept Biostat, Iowa City, IA USA. [Payami, Haydeh] HudsonAlpha Inst Biotechnol, Ctr Genom Med, Huntsville, AL USA. RP Payami, H (reprint author), MCLM 401,1918 Univ Blvd, Birmingham, AL 35233 USA. EM haydehpayami@uabmc.edu FU National Institute of Neurological Disorders And Stroke [R01NS036960]; National Institutes of Health [P30AG08017, HHSN268200782096C, U01NS082157, P50AG005134, R01ES010544, U54ES012078, R01NS078086, P50NS72187]; Department of Veterans Affairs [1I01BX000531]; Office of Research & Development, Clinical Sciences Research & Development Service, Department of Veteran Affairs; Close to the Cure Foundation; American Parkinson's Disease Association; Stowarzyszenie na Rzecz Rozwoju Neurologii Wieku Podeszlego grant; Harvard NeuroDiscovery Center (HNDC); Parkinson's Disease Biomarkers Program (PDBP); U.S. Department of Defense; M.E.M.O. Hoffman Foundation; University of Alabama at Birmingham FX This work was supported by a grant from the National Institute of Neurological Disorders And Stroke [grant number R01NS036960]. Additional support was provided by National Institutes of Health [grant number P30AG08017]; a Merit Review Award from the Department of Veterans Affairs [grant number 1I01BX000531]; Office of Research & Development, Clinical Sciences Research & Development Service, Department of Veteran Affairs; and the Close to the Cure Foundation. Genomewide array genotyping was conducted by the Center for Inherited Disease Research, which is funded by the National Institutes of Health [grant number HHSN268200782096C]. Studies providing samples and data for replication were supported by National Institutes of Health [grant numbers U01NS082157, P50AG005134, R01ES010544, U54ES012078, R01NS078086 and P50NS72187]; a gift from Carl Edward Bolch, Jr. and Susan Bass Bolch; the American Parkinson's Disease Association; the Stowarzyszenie na Rzecz Rozwoju Neurologii Wieku Podeszlego grant; the Harvard NeuroDiscovery Center (HNDC); the Parkinson's Disease Biomarkers Program (PDBP); the U.S. Department of Defense; and the M.E.M.O. Hoffman Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding to pay the Open Access publication charges for this article was provided by the University of Alabama at Birmingham. NR 66 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2016 VL 25 IS 17 BP 3849 EP 3862 DI 10.1093/hmg/ddw206 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EJ4IW UT WOS:000393181300016 PM 27402877 ER PT J AU Finn, AP Eliott, D Kim, LA Husain, D Wu, DM Young, LHY Kim, IK Andreoli, C Skondra, D Vavvas, DG Miller, JB AF Finn, Avni P. Eliott, Dean Kim, Leo A. Husain, Deeba Wu, David M. Young, Lucy H. Y. Kim, Ivana K. Andreoli, Christopher Skondra, Dimitra Vavvas, Demetrios G. Miller, John B. TI Characteristics and Outcomes of Simultaneous Bilateral Rhegmatogenous Retinal Detachments SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID FELLOW EYE AB BACKGROUND AND OBJECTIVE: To better understand the clinical course and outcomes of simultaneous bilateral retinal detachments managed by modern vitreoretinal surgical techniques. PATIENTS AND METHODS: A retrospective review of 21 patients (42 eyes) presenting between April 2000 and June 2015 with simultaneous bilateral rhegmatogenous retinal detachments. RESULTS: Mean visual acuity (VA) improved from 20/100 at presentation to 20/40 at last follow-up (P = .01). The mean final VA for patients undergoing scleral buckle (SB) alone was 20/30 (log MAR 0.17), pars plana vitrectomy (PPV) alone was 20/40 (logMAR 0.33), and combined PPV/SB was 20/80 (logMAR 0.59) (P = .019). Primary reattachment rate in this series was 98%. CONCLUSION: In contrast to prior studies, which investigated the management of simultaneous bilateral retinal detachments primarily by SB alone, multiple treatment modalities were utilized in this study, including vitrectomy alone, and overall success of retinal detachment repair was high regardless of treatment modality chosen. C1 [Finn, Avni P.; Eliott, Dean; Kim, Leo A.; Husain, Deeba; Wu, David M.; Young, Lucy H. Y.; Kim, Ivana K.; Vavvas, Demetrios G.; Miller, John B.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. [Eliott, Dean; Kim, Leo A.; Husain, Deeba; Wu, David M.; Young, Lucy H. Y.; Kim, Ivana K.; Andreoli, Christopher; Vavvas, Demetrios G.; Miller, John B.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA USA. [Andreoli, Christopher] Atrius Hlth, Harvard Vanguard Med Associates, Boston, MA USA. [Skondra, Dimitra] John H Stroger Jr Hosp, Dept Ophthalmol, Chicago, IL USA. RP Miller, JB (reprint author), Harvard Med Sch, Mass Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM john_miller@meei.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD SEP PY 2016 VL 47 IS 9 BP 840 EP 845 DI 10.3928/23258160-20160901-07 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA EJ3HM UT WOS:000393103200007 PM 27631480 ER PT J AU Phasukkijwatana, N Rahimi, M Iafe, N Sarraf, D AF Phasukkijwatana, Nopasak Rahimi, Mansour Iafe, Nicholas Sarraf, David TI Central Retinal Vein Occlusion and Paracentral Acute Middle Maculopathy Diagnosed With En Face Optical Coherence Tomography SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA LA English DT Article ID CAPILLARY ISCHEMIA AB A 21-year-old healthy female presented with acute-onset vision loss in the left eye. Multimodal imaging, including fundus photography and fluorescein angiography, was unremarkable. En face optical coherence tomography (OCT) demonstrated paracentral acute middle maculopathy (PAMM) lesions in a perivenular fern-like pattern leading to the diagnosis of central retinal vein occlusion (CRVO). En face OCT can be an important modality to identify the distribution of abnormalities of the middle retina such as PAMM. The distribution of PAMM lesions in the posterior pole will be a critical element in the determination of the etiologic disorder. C1 [Phasukkijwatana, Nopasak; Rahimi, Mansour; Iafe, Nicholas; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Los Angeles, CA 90095 USA. [Phasukkijwatana, Nopasak] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Ophthalmol, Bangkok, Thailand. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Genentech; Optovue; Regeneron FX Dr. Sarraf receives research support from Genentech, Optovue, and Regeneron; none of these disclosures have any role in the conduct of the study. The remaining authors report no relevant financial disclosures. NR 6 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2325-8160 EI 2325-8179 J9 OSLI RETINA JI Ophthalmic Surg. Lasers Imag. Retin. PD SEP PY 2016 VL 47 IS 9 BP 862 EP 864 DI 10.3928/23258160-20160901-10 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA EJ3HM UT WOS:000393103200010 PM 27631483 ER PT J AU Urish, KL Conditt, M Roche, M Rubash, HE AF Urish, Kenneth L. Conditt, Michael Roche, Martin Rubash, Harry E. TI Robotic Total Knee Arthroplasty: Surgical Assistant for a Customized Normal Kinematic Knee SO ORTHOPEDICS LA English DT Review ID QUALITY-OF-LIFE; JOINT REPLACEMENT SURGERY; TOTAL HIP; ALIGNMENT; TKA; OUTCOMES; PAIN; SATISFACTION; PROSTHESIS; LOCATION AB Although current total knee arthroplasty (TKA) is considered a highly successful surgical procedure, patients undergoing TKA can still experience substantial functional impairment and increased revision rates as compared with those undergoing total hip arthroplasty. Robotic-assisted surgery has been available clinically for almost 15 years and was developed, in part, to address these concerns. Robotic-assisted surgery aims to improve TKA by enhancing the surgeon's ability to optimize soft tissue balancing, reproduce alignment, and restore normal knee kinematics. Current systems include a robotic arm with a variety of different navigation systems with active, semi-active, or passive control. Semi-active systems have become the dominant strategy, providing a haptic window through which the surgeon consistently prepares a TKA based on preoperative planning. A review of previous designs and clinical studies demonstrates that these robotic systems decrease variability and increase precision, primarily with the mechanical axis and restoration of the joint line. Future design objectives include precise planning and consistent intraoperative execution. Preoperative planning, intraoperative sensors, augmenting surgical instrumentation, and biomimetic surfaces will be used to re-create the 4-bar linkage system in the knee. Implants will be placed so that the knee functions with a medial pivot, lateral rollback, screw home mechanism, and patellar femoral tracking. Soft tissue balancing will become more than equalizing the flexion and extension gaps and will match the kinematics to a normal knee. Together, coupled with advanced knee designs, they may be the key to a patient stating, "My knee feels like my natural knee." C1 [Urish, Kenneth L.] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA USA. [Conditt, Michael] Stryker Mako, Ft Lauderdale, FL USA. [Roche, Martin] Holy Cross Hosp, Ft Lauderdale, FL USA. [Rubash, Harry E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. RP Urish, KL (reprint author), Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Magee Bone & Joint Ctr, 300 Halket St, Pittsburgh, PA 15213 USA. EM urishk2@upmc.edu NR 65 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD SEP-OCT PY 2016 VL 39 IS 5 BP E822 EP E827 DI 10.3928/01477447-20160623-13 PG 6 WC Orthopedics SC Orthopedics GA EJ3JD UT WOS:000393107500002 PM 27398788 ER PT J AU Veves, A AF Veves, Aristidis TI Discussion: Biology and Biomarkers for Wound Healing SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID DIABETIC FOOT ULCERS C1 [Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Rongxiang Xu MD Ctr Regenerat Therapeut, Boston, MA USA. [Veves, Aristidis] Harvard Med Sch, Boston, MA USA. 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 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 2016 VL 138 SU S BP 29S EP 30S DI 10.1097/PRS.0000000000002698 PG 2 WC Surgery SC Surgery GA EI6PQ UT WOS:000392618300005 PM 27556771 ER PT J AU Lee, J Capra, G Klobucar, T AF Lee, Jennifer Capra, Gina Klobucar, Thomas TI Forging New Paths to Integrate Rural Veterans' Care Nationwide SO JOURNAL OF RURAL HEALTH LA English DT Editorial Material DE access to care; community care; integrated health care; rural; veteran C1 [Lee, Jennifer] US Dept Vet Affairs, Secretary Hlth Policy & Serv, Washington, DC USA. [Capra, Gina; Klobucar, Thomas] US Dept Vet Affairs, Off Rural Hlth, Washington, DC USA. RP Klobucar, T (reprint author), VA Off Rural Hlth, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Thomas.Klobucar@va.gov FU US Department of Veterans Affairs FX All authors are funded by the US Department of Veterans Affairs. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD FAL PY 2016 VL 32 IS 4 SI SI BP 374 EP 376 DI 10.1111/jrh.12214 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EI4BP UT WOS:000392438200004 PM 27627732 ER PT J AU Wong, ES Rinne, ST Hebert, PL Cook, MA Liu, CF AF Wong, Edwin S. Rinne, Seppo T. Hebert, Paul L. Cook, Meredith A. Liu, Chuan-Fen TI Hospital Distance and Readmissions Among VA-Medicare Dual-Enrolled Veterans SO JOURNAL OF RURAL HEALTH LA English DT Article DE access to care; econometrics; Medicare; utilization of health services; veterans ID OBSTRUCTIVE PULMONARY-DISEASE; AFFAIRS HEALTH-CARE; SERVICES; RISK; SELECTION; DEMAND; ACCESS; DEATH; MODEL AB Purpose: Geographic access to inpatient care at the Veterans Affairs (VA) Health Care System is challenging for many veterans with chronic obstructive pulmonary disease (COPD) given relatively few VA hospitals nationwide. Veterans with lengthy travel distances may obtain non-VA care, particularly those dually enrolled in Medicare. Our primary objective was to assess whether distance from VA patients' residence to the nearest VA and non-VA hospitals was associated with 30-day all-cause readmission and the system where patients were readmitted (VA or Medicare). Methods: Using VA and Medicare administrative data, we identified 21,273 patients hospitalized for COPD between October 2008 and September 2011 and dually enrolled in VA and fee-for-service Medicare. Outcome variables were dichotomous measures denoting readmission for any cause within 30 days following discharge and whether the readmission occurred in a non-VA hospital through Medicare. Distance to the nearest hospital was defined as the number of miles between patients' residence ZIP code and the ZIP code of the nearest VA and non-VA hospital accepting Medicare, respectively. Probit models with sample selection were applied to examine the relationship between hospital distance and outcome measures. Findings: Respective distances to the nearest VA and non-VA hospital were not associated with 30-day all-cause readmission. Greater distance to the nearest VA hospital was associated with a greater conditional probability of choosing non-VA hospitals for readmission. Conclusions: COPD patients with poor geographic access to VA hospitals did not forgo subsequent inpatient care following their index hospitalization, but they were more likely to seek non-VA substitutes. C1 [Wong, Edwin S.; Hebert, Paul L.; Cook, Meredith A.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, 1660 S Columbian Way,HSR&MS S-152, Seattle, WA 98108 USA. [Wong, Edwin S.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rinne, Seppo T.] VA Connecticut Hlth Care Syst, Dept Vet Affairs, West Haven, CT USA. [Rinne, Seppo T.] Yale Univ, Dept Internal Med, Sect Pulm & Crit Care, New Haven, CT USA. RP Wong, ES (reprint author), VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, 1660 S Columbian Way,HSR&MS S-152, Seattle, WA 98108 USA. EM edwin.wong@va.gov FU Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs (VA) [IIR 09-354]; VA HSR&D Career Development Award [CDA 13-024] FX This research was supported by the Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs (VA), IIR 09-354. Dr. Wong is supported by a VA HSR&D Career Development Award (CDA 13-024). The views expressed are those of the authors and do not necessarily reflect the views of the United States Government, the Department of Veterans Affairs, the University of Washington, and Yale University. 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 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD FAL PY 2016 VL 32 IS 4 SI SI BP 377 EP 386 DI 10.1111/jrh.12191 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EI4BP UT WOS:000392438200005 PM 27424850 ER PT J AU Cordasco, KM Mengeling, MA Yano, EM Washington, DL AF Cordasco, Kristina M. Mengeling, Michelle A. Yano, Elizabeth M. Washington, Donna L. TI Health and Health Care Access of Rural Women Veterans: Findings From the National Survey of Women Veterans SO JOURNAL OF RURAL HEALTH LA English DT Article DE access to care; health-related quality of life; utilization of health services; veterans; women ID QUALITY-OF-LIFE; SHORT SCREENING SCALE; MOS SHORT-FORM; URBAN DISPARITIES; PATIENT POPULATION; AMBULATORY-CARE; FEMALE VETERANS; UNITED-STATES; VA; DISEASE AB Purpose: Disparities in health and health care access between rural and urban Americans are well documented. There is evidence that these disparities are mirrored within the US veteran population. However, there are few studies assessing this issue among women veterans (WVs). Methods: Using the 2008-2009 National Survey of Women Veterans, a population-based cross-sectional national telephone survey, we examined rural WVs' health and health care access compared to urban WVs. We measured health using the Medical Outcomes Study Short-Form (SF-12); access using measures of regular source of care (RSOC), health care utilization, and unmet needs; and barriers to getting needed care. Findings: Rural WVs have significantly worse physical health functioning compared to urban WVs (mean physical component score of 43.6 for rural WVs versus 47.2 for urban WVs; P = .007). Rural WVs were more likely to have a VA RSOC (16.4% versus 10.6%; P = .009) and use VA health care (21.7% versus 12.9%; P < .001), and had fewer non-VA health care visits compared with urban WVs (mean 4.2 versus 5.9; P = .021). They had similar overall numbers of health care visits (mean 5.8 versus 7.1; P = .11). Access barriers were affordability for rural WVs and work release time for urbanWVs. Rural WVs additionally reported that transportation was a major factor affecting health care decisions. Conclusions: Our findings demonstrate VA's crucial role in addressing disparities in health and health care access for rural WVs. As VA continues to strive to optimally meet the needs of all WVs, innovative care models need to account for their high health care needs and persistent barriers to care. C1 [Cordasco, Kristina M.; Yano, Elizabeth M.; Washington, Donna L.] VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Cordasco, Kristina M.; Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Cordasco, Kristina M.; Washington, Donna L.] Univ Calif Los Angeles, Dept Med, Geffen Sch Med, Los Angeles, CA 90024 USA. [Mengeling, Michelle A.] VA Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Mengeling, Michelle A.] Vet Rural Hlth Resource Ctr, Iowa City, IA USA. [Mengeling, Michelle A.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Cordasco, KM (reprint author), 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. EM kristina.cordasco@va.gov FU Department of Veterans Affairs (VA) Women's Health Services, Office of Patient Care Services; VA Health Services Research and Development (HSRD) Service [SDR-08-270]; VA HSR&D Senior Research Career Scientist Award [RCS 05-195]; VA Women's Health Research Network (SDR) [10-012] FX This study was funded by the Department of Veterans Affairs (VA) Women's Health Services, Office of Patient Care Services, and the VA Health Services Research and Development (HSR&D) Service (#SDR-08-270). Dr. Yano's time was supported by a VA HSR&D Senior Research Career Scientist Award (#RCS 05-195), with additional support from the VA Women's Health Research Network (SDR #10-012). NR 51 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD FAL PY 2016 VL 32 IS 4 SI SI BP 397 EP 406 DI 10.1111/jrh.12197 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EI4BP UT WOS:000392438200007 PM 27466970 ER PT J AU Fischer, EP McSweeney, JC Wright, P Cheney, A Curran, GM Henderson, K Fortney, JC AF Fischer, Ellen P. McSweeney, Jean C. Wright, Patricia Cheney, Ann Curran, Geoffrey M. Henderson, Kathy Fortney, John C. TI Overcoming Barriers to Sustained Engagement in Mental Health Care: Perspectives of Rural Veterans and Providers SO JOURNAL OF RURAL HEALTH LA English DT Article DE mental health care; peer support; self-reliance; trust; veterans ID POSTTRAUMATIC-STRESS-DISORDER; HELP-SEEKING; SERVICES; TRUST; PSYCHOTHERAPY; MILITARY; BELIEFS; CULTURE; ILLNESS AB Purpose: To better understand the attitudes, beliefs, and values that influence use of mental health care among rural veterans. Methods: In-depth, semistructured interviews were conducted with 25 rural veterans and 11 rural mental health care providers in 4 states. Experienced qualitative interviewers asked participants about the attitudinal factors they thought most influenced rural veterans' decisions to seek and sustain mental health care. Verbatim transcriptions were analyzed using content analysis and constant comparison. Findings: Rural veterans and their mental health care providers reported the same major attitudinal barriers to veterans' mental health treatment-seeking. Pre-eminent among those barriers was the importance rural veterans place on independence and self-reliance. The centrality of self-reliance was attributed variously to rural, military, religious, and/or gender-based belief systems. Stoicism, the stigma associated with mental illness and health care, and a lack of trust in the VA as a caring organization were also frequently mentioned. Perceived need for care and the support of other veterans were critical to overcoming attitudinal barriers to initial treatment-seeking, whereas critical facilitators of ongoing service use included "warm handoffs" from medical to mental health care providers, perceived respect and caring from providers, as well as provider accessibility and continuity. Conclusions: Attitudes and values, like self-reliance, commonly associated with rural culture may play an important role in underutilization of needed mental health services. System support for peer and provider behaviors that generate trust and demonstrate caring may help overcome attitudinal barriers to treatment-seeking and sustained engagement in mental health care among rural veterans. C1 [Fischer, Ellen P.; Curran, Geoffrey M.; Henderson, Kathy] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr,Bldg 58,NLR 152, North Little Rock, AR 72114 USA. [Fischer, Ellen P.; Curran, Geoffrey M.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Little Rock, AR 72205 USA. [McSweeney, Jean C.; Wright, Patricia] Univ Arkansas Med Sci, Coll Nursing, Little Rock, AR 72205 USA. [Cheney, Ann] Univ Calif Riverside, Sch Med, Dept Social Med & Populat Hlth, Riverside, CA 92521 USA. [Curran, Geoffrey M.] Univ Arkansas Med Sci, Coll Pharm, Dept Pharm Practice, Little Rock, AR 72205 USA. [Fortney, John C.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA USA. [Fortney, John C.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. RP Fischer, EP (reprint author), Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr,Bldg 58,NLR 152, North Little Rock, AR 72114 USA. EM FischerEllenP@uams.edu FU US Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development Service award [IIR 11-290]; VA South Central Mental Illness Research, Education, and Clinical Center FX The research reported here was funded by the US Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development Service award IIR 11-290, and by the VA South Central Mental Illness Research, Education, and Clinical Center. The views expressed in this report are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 38 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD FAL PY 2016 VL 32 IS 4 SI SI BP 429 EP 438 DI 10.1111/jrh.12203 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EI4BP UT WOS:000392438200010 PM 27557334 ER PT J AU Biran, N Jacobus, S Vesole, DH Callander, NS Fonseca, R Williams, ME Abonour, R Katz, MS Rajkumar, SV Greipp, PR Siegel, DS AF Biran, N. Jacobus, S. Vesole, D. H. Callander, N. S. Fonseca, R. Williams, M. E. Abonour, R. Katz, M. S. Rajkumar, S. V. Greipp, P. R. Siegel, D. S. TI Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up SO BLOOD CANCER JOURNAL LA English DT Article ID HIGH-DOSE THERAPY; STANDARD CHEMOTHERAPY; MAINTENANCE; COMBINATION; MULTICENTER; RESCUE AB In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan-Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients <65 years of age, median OS in the early versus no early ASCT groups was NR in both, hazard ratio 0.79, 95% confidence interval: (0.50, 0.25). In patients >= 65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density. C1 [Biran, N.; Vesole, D. H.; Siegel, D. S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Jacobus, S.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA. [Callander, N. S.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Fonseca, R.] AZ Georgetown Univ, Lombardi Canc Ctr, Mayo Clin Scottsdale, Washington, DC USA. [Williams, M. E.] Univ Virginia, Ctr Canc, Div Hematol Oncol, Charlottesville, VA 22908 USA. [Abonour, R.] Indiana Univ Sch Med, Dept Hematol Oncol, Indianapolis, IN 46202 USA. [Katz, M. S.] Int Myeloma Fdn, Los Angeles, CA USA. [Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN USA. [Greipp, P. R.] Mayo Clin, Rochester, MN USA. RP Siegel, DS (reprint author), HUMC, John Theurer Canc Ctr, Myeloma Div, 92 Second St,Suite 340, Hackensack, NJ 07601 USA. EM DSiegel@hackensackumc.org FU Celgene FX NB, Celgene speaker's bureau; DHV, Celgene speaker's bureau; MEW, Celgene clinical research funding and consulting fees; RF, Celgene consulting fees; DSS, Celgene consulting fees and speaker's bureau. All other authors declare no conflict of interest. NR 21 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD SEP PY 2016 VL 6 AR e466 DI 10.1038/bcj.2016.68 PG 6 WC Oncology SC Oncology GA EH5HI UT WOS:000391802800002 PM 27588519 ER PT J AU Bolli, N Li, Y Sathiaseelan, V Raine, K Jones, D Ganly, P Cocito, F Bignell, G Chapman, MA Sperling, AS Anderson, KC Avet-Loiseau, H Minvielle, S Campbell, PJ Munshi, NC AF Bolli, N. Li, Y. Sathiaseelan, V. Raine, K. Jones, D. Ganly, P. Cocito, F. Bignell, G. Chapman, M. A. Sperling, A. S. Anderson, K. C. Avet-Loiseau, H. Minvielle, S. Campbell, P. J. Munshi, N. C. TI A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma SO BLOOD CANCER JOURNAL LA English DT Article ID MYELODYSPLASTIC SYNDROMES; WORKING GROUP; HETEROGENEITY; EXPRESSION; THERAPY; GENE; STRATIFICATION; DYNAMICS; LEUKEMIA; T(4/14) AB Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines. We identified 548 likely oncogenic mutations in 182 genes. By integrating published data sets of NGS in MM, we retrieved a list of genes with significant relevance to myeloma and found that the mutational spectrum of primary samples and MM cell lines is partially overlapping. Gains and losses of chromosomes, chromosomal segments and gene loci were identified with accuracy comparable to conventional arrays, allowing identification of lesions with known prognostic significance. Furthermore, we identified IGH translocations with high positive and negative predictive value. Our approach could allow the identification of novel biomarkers with clinical relevance in myeloma. C1 [Bolli, N.; Li, Y.; Sathiaseelan, V.; Raine, K.; Jones, D.; Bignell, G.; Campbell, P. J.] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Bolli, N.] Univ Milan, Fdn IRCCS Ist Nazl Tumori, Dept Oncol & Oncohematol, Milan, Italy. [Ganly, P.] Univ Otago, UOC, Dept Pathol, Christchurch, New Zealand. [Cocito, F.] Fdn IRCCS Policlin San Matteo Pavia, Div Hematol, Pavia, Italy. [Chapman, M. A.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England. [Sperling, A. S.; Anderson, K. C.; Munshi, N. C.] Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Avet-Loiseau, H.] CHU Rangueil, Unite Genom Myelome, Toulouse, France. [Avet-Loiseau, H.] INSERM U1037, Ctr Rech Cancerol Toulouse, Toulouse, France. [Minvielle, S.] Univ Nantes, Ctr Rech Cancerol Nantes Angers, Ctr Natl Rech Sci 6299, Unite Mixte Rech INSERM 892,Hematol Dept, Nantes, France. [Minvielle, S.] Univ Nantes, Inst Rech Therapeut, Nantes, France. RP Bolli, N (reprint author), Univ Milan, Fdn IRCCS Ist Nazl Tumori, Dept Oncol & Oncohematol, Div Hematol, Via G Venezian 1, I-20133 Milan, Italy. EM Niccolo.bolli@unimi.it RI Bolli, Niccolo/D-4057-2011 OI Bolli, Niccolo/0000-0002-1018-5139 FU NIH [PO1-155258, RO1-124929, P50-100007]; Wellcome Trust [077012/Z/05/Z]; MFAG AIRC grant [17658] FX This work was supported by a grant from NIH PO1-155258 (to NCM, PJC, KCA, HA-L and SM), RO1-124929 (to NCM), P50-100007 (to KCA and NCM) and by the Wellcome Trust (Grant Reference 077012/Z/05/Z). NB was funded by a MFAG AIRC grant no. 17658. PJC is personally funded through a Wellcome Trust Senior Clinical Research Fellowship. KCA is an American Cancer Society Clinical Research Professor. NR 41 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD SEP PY 2016 VL 6 AR e467 DI 10.1038/bcj.2016.72 PG 9 WC Oncology SC Oncology GA EH5HI UT WOS:000391802800003 PM 27588520 ER PT J AU Gokbuget, N Kelsh, M Chia, V Advani, A Bassan, R Dombret, H Doubek, M Fielding, AK Giebel, S Haddad, V Hoelzer, D Holland, C Ifrah, N Katz, A Maniar, T Martinelli, G Morgades, M O'Brien, S Ribera, JM Rowe, JM Stein, A Topp, M Wadleigh, M Kantarjian, H AF Goekbuget, N. Kelsh, M. Chia, V. Advani, A. Bassan, R. Dombret, H. Doubek, M. Fielding, A. K. Giebel, S. Haddad, V. Hoelzer, D. Holland, C. Ifrah, N. Katz, A. Maniar, T. Martinelli, G. Morgades, M. O'Brien, S. Ribera, J-M Rowe, J. M. Stein, A. Topp, M. Wadleigh, M. Kantarjian, H. TI Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia SO BLOOD CANCER JOURNAL LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; MARGINAL STRUCTURAL MODELS; PROPENSITY SCORE; SURVIVAL; SALVAGE; RELAPSE; PHASE-2; TRIALS AB We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR = 2.68, 95% CI: 1.67-4.31) and improved OS (HR = 0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data. C1 [Goekbuget, N.; Hoelzer, D.] Goethe Univ, Univ Hosp, Dept Med, Frankfurt, Germany. [Kelsh, M.; Chia, V.; Katz, A.] Ctr Observat Res, Thousand Oaks, CA USA. [Advani, A.] Cleveland Clin, Dept Hematol Oncol, Cleveland, OH 44106 USA. [Bassan, R.] Osped Angelo, Unita Operat Complessa Ematol, Mestre Venezia, Italy. [Dombret, H.] Hop Saint Louis, Blood Dis Dept, Leukemia Unit, Paris, France. [Doubek, M.] Univ Hosp, Dept Internal Med Hematol & Oncol, Brno, Czech Republic. [Fielding, A. K.] UCL Canc Inst, Dept Res Haematol, London, England. [Giebel, S.] Maria Sklodowska Curie Mem Canc Ctr, Dept Bone Marrow Transplantat & Onco Hematol, Gliwice, Poland. [Giebel, S.] Inst Oncol, Dept Bone Marrow Transplantat & Onco Hematol, Gliwice, Poland. [Haddad, V.] Amgen Ltd, Dept Biostat, Uxbridge, Middx, England. [Holland, C.] Amgen Inc, Dept Biostat, Rockville, MD USA. [Ifrah, N.] Ctr Hosp Univ, Blood Dis Serv, Angers, France. [Maniar, T.] Amgen Inc, Dept Clin Dev, Thousand Oaks, CA 91320 USA. [Martinelli, G.] L&A Seragnoli S Orsola Univ Hosp, Inst Hematol & Med Oncol, Bologna, Italy. [Morgades, M.; Ribera, J-M] ICO Hosp Germans Trias & Pujol, Jose Carreras Res Inst, Dept Clin Haematol, Barcelona, Spain. [O'Brien, S.; Kantarjian, H.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Rowe, J. M.] Rambam Med Ctr, Dept Hematol & Bone Marrow Transplantat, Haifa, Israel. [Stein, A.] City Hope Natl Med Ctr, Dept Hematol & Hematopoiet Cell Transplan, Duarte, CA USA. [Topp, M.] Univ Klinikum Wurzburg, Med Klin & Poliklin 2, Wurzburg, Germany. [Goekbuget, N.; Wadleigh, M.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Gokbuget, N (reprint author), UnivHosp Frankfurt, Goethe Univ, Univ Canc Ctr, Dept Med 2,Hematol Oncol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM goekbuget@em.uni-frankfurt.de FU Pfizer; Amgen FX NG and J-MR have received research support and honoraria from Pfizer and Amgen. AA has received research support from Pfizer and Amgen and honoraria from Pfizer. RB and SG have received honoraria from Amgen. AS has served on speakers' bureau and advisory boards for Amgen. VC, AK, MK and JS are employees and shareholders of Amgen; VH and TM were employees of Amgen when the study was conducted. The remaining authors declare no competing interests. NR 29 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD SEP PY 2016 VL 6 AR e473 DI 10.1038/bcj.2016.84 PG 7 WC Oncology SC Oncology GA EH5HI UT WOS:000391802800009 PM 27662202 ER PT J AU Rajbhandari, R Chung, RT AF Rajbhandari, Ruma Chung, Raymond T. TI Treatment of Hepatitis B: A Concise Review SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Review ID TENOFOVIR DISOPROXIL FUMARATE; FULMINANT VIRAL-HEPATITIS; LIVER-RELATED MORTALITY; LONG-TERM SAFETY; VIRUS INFECTION; VERTICAL TRANSMISSION; NAIVE PATIENTS; UNITED-STATES; SPONTANEOUS REACTIVATION; DECOMPENSATED CIRRHOSIS C1 [Rajbhandari, Ruma; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Rajbhandari, Ruma; Chung, Raymond T.] Harvard Med Sch, Boston, MA USA. [Rajbhandari, Ruma; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [T32 DK007191, K24 DK078772] FX Dr Ruma Rajbhandari was supported by a grant from the National Institutes of Health (T32 DK007191). Dr Raymond Chung is supported, in part, by a grant from the National Institutes of Health (K24 DK078772). NR 95 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD SEP PY 2016 VL 7 AR e190 DI 10.1038/ctg.2016.46 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EH5MA UT WOS:000391816000003 PM 27628420 ER PT J AU Echavarria, C Nasr, S Tootell, R AF Echavarria, Cesar Nasr, Shahin Tootell, Roger TI Smooth versus Textured Surfaces: Feature-Based Category Selectivity in Human Visual Cortex SO ENEURO LA English DT Article DE FFA; fMRI; functional connectivity; LO; texture ID FUSIFORM FACE AREA; PARAHIPPOCAMPAL PLACE AREA; LATERAL OCCIPITAL CORTEX; SUPERIOR TEMPORAL SULCUS; FUNCTIONAL-PROPERTIES; HUMAN BRAIN; ORIENTATION SELECTIVITY; RESPONSE PROPERTIES; RECEPTIVE-FIELDS; CORTICAL-NEURONS AB In fMRI studies, human lateral occipital (LO) cortex is thought to respond selectively to images of objects, compared with nonobjects. However, it remains unresolved whether all objects evoke equivalent levels of activity in LO, and, if not, which image features produce stronger activation. Here, we used an unbiased parametric texture model to predict preferred versus nonpreferred stimuli in LO. Observation and psychophysical results showed that predicted preferred stimuli (both objects and nonobjects) had smooth (rather than textured) surfaces. These predictions were confirmed using fMRI, for objects and nonobjects. Similar preferences were also found in the fusiform face area (FFA). Consistent with this: (1) FFA and LO responded more strongly to nonfreckled (smooth) faces, compared with otherwise identical freckled (textured) faces; and (2) strong functional connections were found between LO and FFA. Thus, LO and FFA may be part of an information-processing stream distinguished by feature-based category selectivity (smooth > textured). C1 [Echavarria, Cesar; Nasr, Shahin; Tootell, Roger] Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. [Nasr, Shahin; Tootell, Roger] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. RP Echavarria, C (reprint author), Massachusetts Gen Hosp, Athinioula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM cechavarria@g.harvard.edu FU National Institutes of Health [R01-EY-017081] FX This research was supported by National Institutes of Health Grant R01-EY-017081. NR 87 TC 0 Z9 0 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 2373-2822 J9 ENEURO JI eNeuro PD SEP-OCT PY 2016 VL 3 IS 5 DI 10.1523/ENEURO.0051-16.2016 PG 18 WC Neurosciences SC Neurosciences & Neurology GA EH7CL UT WOS:000391930400002 ER PT J AU Cena, H De Giuseppe, R Biino, G Persico, F Ciliberto, A Giovanelli, A Stanford, FC AF Cena, Hellas De Giuseppe, Rachele Biino, Ginevra Persico, Francesca Ciliberto, Ambra Giovanelli, Alessandro Stanford, Fatima Cody TI Evaluation of eating habits and lifestyle in patients with obesity before and after bariatric surgery: a single Italian center experience SO SPRINGERPLUS LA English DT Article DE Gastric bypass roux-en-Y; Sleeve gastrectomy; Physical activity; Dietary habits; Smoking habits; Bariatric surgery; Weight loss ID Y GASTRIC BYPASS; WEIGHT-LOSS; PHYSICAL-ACTIVITY; METABOLIC SYNDROME; FOOD QUALITY; SMOKING; MAINTENANCE; ADOLESCENTS; PREVALENCE; BEHAVIOR AB Background: The study evaluated and compared the eating habits and lifestyle of patients with moderate to severe obesity who have undergone Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). Methods: Food frequency (FF), food habits (FH), physical activity and life style (PA) as well as smoking habits (SH) were analyzed in 50 RYGB (25 M; aged: 24-64) and 50 SG patients (25 M; aged: 22-63) by means of a validated questionnaire, before (T-0) and 6 months (T-1) post bariatric surgery. A score for each section (FF, FH, PA, SH) was calculated. Results: ANOVA analysis (age/sex adjusted): FF and FH scores improved at T-1 (RYGB and SG: p < 0.001); PA score improved but not significantly; SH score did not change at T1 neither in RYGB nor in SG. Mixed models: FF and PA scores did not correlate with age, gender, weight, BMI, neither in RYGB nor in SG; FH score was negatively correlated both with weight (RYGB: p = 0.002) and BMI (SG: p = 0.003); SH score was positively correlated with age, in SG (p = 0.002); the correlation was stronger in females than in males (p = 0.004). Conclusions: Although dietary habits improved, patients did not change their physical activity level or their smoking habits. Patients should receive adequate lifestyle counseling to ensure the maximal benefit from bariatric surgery. C1 [Cena, Hellas; De Giuseppe, Rachele] Univ Pavia, Dept Publ Hlth Expt & Forens Med, Unit Human Nutr & Dietet, Via Bassi 21, I-27100 Pavia, PV, Italy. [De Giuseppe, Rachele] Univ Milan, Scuola Specializzaz Sci Alimentaz, Via GB Grassi 74, I-20157 Milan, Italy. [Biino, Ginevra] Natl Res Council Italy, Inst Mol Genet, Via Abbiategrasso 207, I-27100 Pavia, Italy. [Persico, Francesca; Ciliberto, Ambra; Giovanelli, Alessandro] Ist Clin S Ambrogio, Dept Gen Surg, Via Faravelli 16, I-20149 Milan, Italy. [Stanford, Fatima Cody] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. RP Cena, H (reprint author), Univ Pavia, Dept Publ Hlth Expt & Forens Med, Unit Human Nutr & Dietet, Via Bassi 21, I-27100 Pavia, PV, Italy. EM hcena@unipv.it OI Stanford, Fatima/0000-0003-4616-533X NR 38 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PD SEP 1 PY 2016 VL 5 AR 1467 DI 10.1186/s40064-016-3133-1 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EH5FE UT WOS:000391797200002 PM 27652042 ER PT J AU Oncu, E Bayram, B Kantarci, A Gulsever, S Alaaddinoglu, EE AF Oncu, Elif Bayram, Burak Kantarci, Alpdogan Gulsever, Serap Alaaddinoglu, Emine-Elif TI Positive effect of platelet rich fibrin on osseointegration SO MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL LA English DT Article DE Dental implants; platelet rich fibrin; osseointegration; bone regeneration; matrix for growth factors ID GROWTH-FACTORS; IMPLANT SURFACES; PLASMA RICH; IN-VITRO; BONE; PRF; OSTEOBLASTS; REGENERATION; RELEASE; RAT AB Background: Leukocyte-platelet rich fibrin (L-PRF) is a second generation platelet concentrate clinically used to accelerate tissue healing and bone regeneration. Achieving reduced implant osseointegration time could provide immediate or early loading of implants. The aim of this study was to evaluate the L-PRF-induced osseointegration and bone-implant contact (BIC) in an experimental animal model. Material and Methods: Twelve 4-month-old New Zealand white rabbits were used. Following general anesthesia, 3-5 mL of blood was obtained from the central artery in rabbit ear and L-PRF was prepared. Two implant cavities (5 mm long and 3 mm in diameter) were created in each tibia with a total of four cavities in each animal. Two of these cavities were selected and covered with PRF (test group). The remaining L-PRF was used to soak the implants placed into the L-PRF covered sockets. Other cavities were left as controls. In total, 48 implants were placed. Animals were sacrificed after two, three, or four weeks. Histological samples were obtained and peri-implant tissues were histomorphometrically evaluated for bone-to-implant contact and new bone formation. Results: Histomorphometric analyses of the defects revealed that the L-PRF was detectable up to the second week. Application of L-PRF increased the rate and amount of new bone formation in the experimental group compared to the control group. Bone-to-implant contact was enhanced when the surface was pre-wetted with L-PRF (p<0.01). Conclusions: The results of this study demonstrated that L-PRF application may increases amount and rate of new bone formation during the early healing period and provides a faster osseointegration around implants. C1 [Oncu, Elif] Necmettin Erbakan Univ, Dept Periodontol, Konya, Turkey. [Bayram, Burak; Gulsever, Serap] Baskent Univ, Dept Oral & Maxillofacial Surg, Ankara, Turkey. [Kantarci, Alpdogan] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA. [Alaaddinoglu, Emine-Elif] Baskent Univ, Dept Periodontol, Ankara, Turkey. RP Oncu, E (reprint author), Necmettin Erbakan Univ, Dis Hekimligi Fak Karatay, Karacigan Mah,Ankara Cad, Konya, Turkey. EM oncu.elif@hotmail.com NR 21 TC 1 Z9 1 U1 1 U2 1 PU MEDICINA ORAL S L PI VALENCIA PA CALLE DANIEL BALACIART N 4 PTA 17, VALENCIA, 46020, SPAIN SN 1698-6946 J9 MED ORAL PATOL ORAL JI Med. Oral Patol. Oral Cir. Bucal PD SEP PY 2016 VL 21 IS 5 BP E601 EP E607 AR 21026 DI 10.4317/medoral.21026 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA EG6ZA UT WOS:000391193600010 PM 27475686 ER PT J AU Chikarmane, SA Birdwell, RL Poole, PS Sippo, DA Giess, CS AF Chikarmane, Sona A. Birdwell, Robyn L. Poole, Patricia S. Sippo, Dorothy A. Giess, Catherine S. TI Characteristics, Malignancy Rate, and Follow-up of BI-RADS Category 3 Lesions Identified at Breast MR Imaging: Implications for MR Image Interpretation and Management SO RADIOLOGY LA English DT Article ID PROBABLY BENIGN LESIONS; BACKGROUND PARENCHYMAL ENHANCEMENT; FREQUENCY; WOMEN; MAMMOGRAPHY; IMPACT; YIELD AB Purpose: To (a) evaluate the frequency of Breast Imaging Reporting and Data System (BI-RADS) category 3 assessment in screening and diagnostic breast magnetic resonance (MR) imaging, (b) review findings considered indicative of BI-RADS category 3, and (c) determine outcomes of BI-RADS category 3 lesions, including upgrades, downgrades, and malignancy rates. Materials and Methods: This retrospective study was approved by the institutional review board and compliant with HIPAA. The authors retrospectively reviewed the breast MR imaging database (2009-2011) to identify breast MR images classified as showing BI-RADS category 3 lesions. There were 9216 BI-RADS assessments in 5778 examinations (3360 women). Of the 9216 assessments, 567 (6%) in 483 women (average age, 47.2 years; median age, 47.0 years) were assigned BI-RADS category 3. In women with more than one BI-RADS category 3 lesion, the first lesion reported in the impression was used for data analysis. Outcomes data were available for 435 of the 483 women (90.1%). These women comprised the study cohort. Medical records from January 1, 2009, to May 31, 2015, were reviewed to obtain demographic characteristics and outcomes. chi(2) statistics and 95% exact confidence intervals (CIs) were constructed. Results: MR imaging was performed for high-risk screening in 240 of the 435 patients (55.2%) and for diagnostic purposes in 195 (44.8%). Findings included mass (n = 125, 28.7%), focus (n = 111, 25.5%), nonmass enhancement (n = 80, 18.3%), moderate or marked background parenchymal enhancement (BPE) (n = 91, 20.9%), posttreatment changes (n = 16, 3.8%), and other findings (n = 12, 2.8%). Outcomes were as follows: 339 of the 435 patients (78%) did not have evidence of malignancy at more than 24 months, 28 (6.4%) underwent mastectomy (all benign), and 68 (15.6%) had lesion upgrades, with 11 cancers (2.5%). All 11 cancers were diagnosed in women with a genetic mutation or a personal history of breast cancer. No cancer was detected in cases of moderate or marked BPE. Conclusion: Six percent of all breast MR imaging assessments were categorized as BI-RADS category 3, with a cancer rate of 2.5% (95% CI: 1.3%, 4.5%). All cancers were in women with a genetic mutation or personal history of breast cancer. Marked BPE does not necessitate a BI-RADS 3 assessment. (C) RSNA, 2016 C1 [Chikarmane, Sona A.; Birdwell, Robyn L.; Giess, Catherine S.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Chikarmane, Sona A.; Birdwell, Robyn L.; Giess, Catherine S.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA USA. [Poole, Patricia S.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. [Sippo, Dorothy A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Chikarmane, SA (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.; Chikarmane, SA (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging, Boston, MA USA. EM schikarmane@partners.org NR 21 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2016 VL 280 IS 3 BP 707 EP 715 DI 10.1148/radiol.2016151548 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EG8MM UT WOS:000391311200007 PM 27089027 ER PT J AU Hariri, BM Cohen, NA AF Hariri, Benjamin M. Cohen, Noam A. TI New insights into upper airway innate immunity SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID TASTE RECEPTOR T2R38; MUCOID PSEUDOMONAS-AERUGINOSA; UPPER RESPIRATORY-INFECTION; NASAL EPITHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; CHRONIC RHINOSINUSITIS; CYSTIC-FIBROSIS; VITAMIN-D; IN-VITRO; HUMAN BETA-DEFENSIN-2 AB Background: Protecting the upper airway from microbial infection is an important function of the immune system. Proper detection of these pathogens is paramount for sinonasal epithelial cells to be able to prepare a defensive response. Toll-like receptors and, more recently, bitter taste receptors and sweet taste receptors have been implicated as sensors able to detect the presence of these pathogens and certain compounds that they secrete. Activation of these receptors also triggers innate immune responses to prevent or counteract infection, including mucociliary clearance and the production and secretion of antimicrobial compounds (e.g., defensins). Objective: To provide an overview of the current knowledge of the role of innate immunity in the upper airway, the mechanisms by which it is carried out, and its clinical relevance. Methods: A literature review of the existing knowledge of the role of innate immunity in the human sinonasal cavity was performed. Results: Clinical and basic science studies have shown that the physical epithelial cell barrier, mucociliary clearance, and antimicrobial compound secretion play pivotal innate immune roles in defending the sinonasal cavity from infection. Clinical findings have also linked dysfunction of these defense mechanisms with diseases, such as chronic rhinosinusitis and cystic fibrosis. Recent discoveries have elucidated the significance of bitter and sweet taste receptors in modulating immune responses in the upper airway. Conclusion: Numerous innate immune mechanisms seem to work in a concerted fashion to keep the sinonasal cavity free of infection. Understanding sinonasal innate immune function and dysfunction in health and disease has important implications for patients with respiratory ailments, such as chronic rhinosinusitis and cystic fibrosis. C1 [Hariri, Benjamin M.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia VA Med Ctr, Surg Serv, Philadelphia, PA USA. [Cohen, Noam A.] Monell Chem Senses Ctr, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg,5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM noam.cohen@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932 FU NIH [R01DC013588, R21DC013886] FX Funding source NIH R01DC013588 and NIH R21DC013886 to N.A.C. NR 85 TC 0 Z9 0 U1 1 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD SEP-OCT PY 2016 VL 30 IS 5 BP 319 EP 323 DI 10.2500/ajra.2016.30.4360 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA EG2EA UT WOS:000390854700009 ER PT J AU Miyake, MM Gregorio, LL Freitag, SK Lefebvre, DR Gray, ST Holbrook, EH Bleier, BS AF Miyake, Marcel M. Gregorio, Luciano L. Freitag, Suzanne K. Lefebvre, Daniel R. Gray, Stacey T. Holbrook, Eric H. Bleier, Benjamin S. TI Impact of endoscopic dacryocystorhinostomy on sinonasal quality of life SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ENDONASAL DACRYOCYSTORHINOSTOMY; EXTERNAL DACRYOCYSTORHINOSTOMY; CHRONIC RHINOSINUSITIS; SURGERY AB Background: Dacryocystorhinostomy (DCR) is the criterion standard of surgical treatment for complete nasolacrimal obstruction and dacryocystitis. There has been an expansion in the indication of the endonasal DCR (eDCR), but the impact of surgical manipulating an otherwise healthy nasal mucosa on postoperative sinonasal quality of life remains unknown. The purpose of this study was to determine whether patients who underwent eDCR experienced any decrement in sinonasal quality of life. Methods: A retrospective chart review of 44 patients who underwent eDCR between June 2012 and May 2015. The primary outcome was the total and nasal-specific domain 1 scores of the disease specific validated Sino-Nasal Outcomes Test 22. Preoperative scores were compared with the postoperative scores on days 0-30, 30-90, and 90-180 visits. A subgroup analysis of patients without nasal symptoms who underwent concomitant nasal surgical procedures was also performed. Results: A statistically significant increase was observed between the preoperative score and the first postoperative score (days 0-30) in both total (7.5 [0-44] to 24 [0-51], median [interquartile range]) and domain 1 (2.5 [0-11] to 9 [0-18]) scores (p = 0.0066 and p = 0.0001, respectively). In contrast, there was no statistically significant difference between the pre- and postoperative scores on days 30-90 or 90-180. Similar results were observed in the subgroup analysis. Conclusion: Analysis of our findings indicated that, in general, eDCR was well tolerated by patients and nasal symptom scores returned to baseline values within 30-90 days of surgery. The concomitant performance of septoplasty in the setting of asymptomatic septal deviation did not confer any long-term improvement in symptoms of nasal obstruction. C1 [Miyake, Marcel M.; Gregorio, Luciano L.; Freitag, Suzanne K.; Lefebvre, Daniel R.; Gray, Stacey T.; Holbrook, Eric H.; Bleier, Benjamin S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Miyake, Marcel M.] Santa Casa Sao Paulo Sch Med Sci, Dept Otorhinolaryngol, Sao Paulo, SP, Brazil. [Miyake, Marcel M.] Coordenacao Aperfeicoamento Pessoal Nivel Super C, Sao Paulo, Brazil. [Gregorio, Luciano L.] Univ Fed Sao Paulo, Dept Otorhinolaryngol & Head & Neck Surg, Sao Paulo, SP, Brazil. RP Miyake, MM (reprint author), Clin Menon, Rua Afonso Bras 525 Cj 21, BR-04511011 Sao Paulo, SP, Brazil. EM marcelmenon@yahoo.com.br NR 19 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD SEP-OCT PY 2016 VL 30 IS 5 BP E189 EP E191 DI 10.2500/ajra.2016.30.4332 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA EG2EA UT WOS:000390854700007 ER PT J AU Villa, A Sonis, S AF Villa, Alessandro Sonis, Stephen TI Toxicities associated with head and neck cancer treatment and oncology-related clinical trials SO CURRENT PROBLEMS IN CANCER LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; RADIATION-INDUCED XEROSTOMIA; PRO-INFLAMMATORY CYTOKINES; REGIMEN-RELATED TOXICITIES; INDUCED ORAL MUCOSITIS; LOCALLY ADVANCED HEAD; LEVEL LASER THERAPY; PHASE-II-TRIAL; DOUBLE-BLIND C1 [Villa, Alessandro; Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC 3-028, Boston, MA 02120 USA. [Villa, Alessandro; Sonis, Stephen] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Villa, Alessandro; Sonis, Stephen] Dana Farber Canc Inst, Div Oral Med & Dent, Boston, MA 02115 USA. [Sonis, Stephen] Biomodels LLC, Watertown, MA USA. RP Villa, A (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC 3-028, Boston, MA 02120 USA. EM avilla@partners.org NR 130 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 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD SEP-DEC PY 2016 VL 40 IS 5-6 BP 244 EP 257 DI 10.1016/j.currproblcancer.2016.06.001 PG 14 WC Oncology SC Oncology GA EG3ZH UT WOS:000390982700007 PM 27520848 ER PT J AU Taylor, AP Lee, H Webb, ML Joffe, H Finkelstein, JS AF Taylor, Alexander P. Lee, Hang Webb, Matthew L. Joffe, Hadine Finkelstein, Joel S. TI Effects of Testosterone and Estradiol Deficiency on Vasomotor Symptoms in Hypogonadal Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; ANDROGEN DEPRIVATION THERAPY; HOT FLASHES; POSTMENOPAUSAL WOMEN; PROSTATE-CANCER; MENOPAUSAL SYMPTOMS; BODY-COMPOSITION; SEXUAL FUNCTION; NEUROKININ B; ELDERLY-MEN AB Context: The hormonal basis of vasomotor symptoms (VMS) in hypogonadal men is incompletely understood. Objective: To determine the contributions of testosterone and estradiol deficiency to VMS in hypogonadal men. Design: Two randomized trials were conducted sequentially between September 2004 and April 2011. Controls were recruited separately. Setting: A single-site academic medical center. Participants: Healthy men ages 20-50, with normal serum testosterone levels. Intervention: Cohort 1 (n = 198, 81% completion) received goserelin acetate every 4 weeks to suppress gonadal steroids and were randomized to placebo or 1.25, 2.5, 5, or 10 g of testosterone gel daily for 16 weeks. Cohort 2 (n = 202, 78% completion) received the same regimen as cohort 1 plus anastrozole to block aromatization of testosterone. Controls (n = 37, 89% completion) received placebos for goserelin acetate and testosterone. Main Outcome Measures: Incidence of visits with VMS. This was a preplanned secondary analysis. Results: VMS were reported at 26% of visits in cohort 1, and 35% of visits in cohort 2 (P = .02), demonstrating an effect of estradiol deficiency. When adjacent estradiol level groups in cohort 1 were compared, the largest difference in VMS incidence was observed between the 5-9.9 and 10-14.9 pg/mL groups (38% vs 16%, P = .001). In cohort 2, the 10-g testosterone group differed significantly from placebo(16% vs 43%, P = .048) after adjustment for small differences in estradiol levels, indicating that high testosterone levels may suppress VMS. Conclusions: Estradiol deficiency is the key mediator of VMS in hypogonadal men. At high levels, testosterone may have a suppressive effect. C1 [Taylor, Alexander P.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Yale Sch Med, Brigham & Womens Hosp, Ctr Biostat, New Haven, CT 06510 USA. [Joffe, Hadine] Yale Sch Med, Brigham & Womens Hosp, Dept Psychiat, New Haven, CT 06510 USA. [Webb, Matthew L.] Yale Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, New Haven, CT 06510 USA. [Taylor, Alexander P.] Univ Washington, Seattle, WA 98195 USA. [Lee, Hang] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Webb, Matthew L.] Univ Penn, Philadelphia, PA 19104 USA. [Joffe, Hadine] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Taylor, AP (reprint author), Univ Washington, Internal Med Residency Program, 1959 NE Pacific St,Box 356421, Seattle, WA 98195 USA.; Taylor, AP (reprint author), Univ Washington, Seattle, WA 98195 USA. EM aptaylor@uw.edu FU National Institutes of Health [R01 AG030545, K24 DK02759, RR-1066, R01MH082922]; AbbVie Pharmaceuticals FX This work was supported by National Institutes of Health Grants R01 AG030545, K24 DK02759, RR-1066, and R01MH082922 and by an investigator-initiated grant from AbbVie Pharmaceuticals. NR 32 TC 0 Z9 0 U1 2 U2 2 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 SEP PY 2016 VL 101 IS 9 BP 3479 EP 3486 DI 10.1210/jc.2016-1612 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG2CB UT WOS:000390849100034 PM 27300575 ER PT J AU Crowell, JA Davis, CR Joung, KE Usher, N McCormick, SP Dearing, E Mantzoros, CS AF Crowell, Judith A. Davis, Cynthia R. Joung, Kyoung Eun Usher, Nicole McCormick, Sean-Patrick Dearing, Eric Mantzoros, Christos S. TI Metabolic pathways link childhood adversity to elevated blood pressure in midlife adults SO OBESITY RESEARCH & CLINICAL PRACTICE LA English DT Article DE Childhood adversity; Leptin; Blood pressure; Hypertension; Obesity ID INSULIN-RESISTANCE; PSYCHOLOGICAL STRESS; HYPERTENSION; OBESITY; LEPTIN; RISK; HEALTH; LIFE; DISEASE; GENDER AB Childhood adversity is a risk factor for adult health outcomes, including obesity and hypertension. This study examines whether childhood adversity predicted mean arterial pressure through mechanisms of central obesity and Leptin, adiponectin, and/or insulin resistance, and including dietary quality. 210 Black/African Americans and White/European Americans, mean age = 45.8; +/- 3.3 years, were studied cross-sectionally. Path analyses were used to specify a chain of predictive variables in which childhood adversity predicted waist hip ratio and dietary quality, circulating levels of hormones, and in turn, mean arterial pressure, adjusting for race, gender, and antihypertensive medications. Direct paths were found between childhood adversity, waist hip ratio, and leptin levels and between leptin and dietary quality to mean arterial pressure. Systolic and diastolic blood pressures were similarly predicted. Early adversity appears to developmentally overload and dysregulate endocrine systems through increased risk for obesity, and through a direct impact on leptin that in turn, impacts blood pressure. (C) 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. C1 [Crowell, Judith A.] SUNY Stony Brook, Sch Med, Dept Psychiat, Stony Brook, NY 11794 USA. [Crowell, Judith A.; Davis, Cynthia R.; Usher, Nicole; McCormick, Sean-Patrick] Harvard Med Sch, Judge Baker Childrens Ctr, Boston, MA USA. [Davis, Cynthia R.; Mantzoros, Christos S.] Boston VA Healthcare Syst, Boston, MA USA. [Joung, Kyoung Eun; Mantzoros, Christos S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Joung, Kyoung Eun] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [McCormick, Sean-Patrick] Suffolk Univ, Boston, MA 02114 USA. [Dearing, Eric] Boston Coll, Boston, MA USA. RP Crowell, JA (reprint author), SUNY Stony Brook, Child & Adolescent Psychiat, Div Child & Adolescent Psychiat, Putnam Hall,Putnam Hall South Campus, Stony Brook, NY 11794 USA. EM Judith.crowell@stonybrookmedicine.edu FU National Institute of Aging [R01 AG032030]; National Institute of Diabetes and Digestive and Kidney Diseases - Harvard Clinical and Translational Science Center, National Center for Research Resources [81913, UL1 RR025758] FX This study was supported by the National Institute of Aging, R01 AG032030 (for Judith A. Crowell), and National Institute of Diabetes and Digestive and Kidney Diseases grant 81913 (for Christos S. Mantzoros), Grant Number UL1 RR025758 - Harvard Clinical and Translational Science Center, from the National Center for Research Resources (for Christos S. Mantzoros). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 55 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1871-403X EI 1878-0318 J9 OBES RES CLIN PRACT JI Obes. Res. Clin. Pract. PD SEP-OCT PY 2016 VL 10 IS 5 BP 580 EP 588 DI 10.1016/j.orcp.2015.10.009 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EF8AL UT WOS:000390550400008 PM 26598448 ER PT J AU Delahanty, LM Riggs, M Klioze, SS Chew, RD England, RD Digenio, A AF Delahanty, L. M. Riggs, M. Klioze, S. S. Chew, R. D. England, R. D. Digenio, A. TI Maximizing retention in long-term clinical trials of a weight loss agent: use of a dietitian support team SO OBESITY SCIENCE & PRACTICE LA English DT Article DE clinical trial; obesity; retention; type 2 diabetes; weight management ID RANDOMIZED CONTROLLED-TRIALS; LIFE-STYLE INTERVENTION; CONTROLLED-RELEASE; OBESE ADULTS; OVERWEIGHT; PHARMACOTHERAPY; PARTICIPANTS; LORCASERIN; STRATEGIES; AMERICA AB Objective High-attrition rates have been observed in long-term clinical trials of weight loss agents. We evaluated the impact of an innovative retention programme on 1-year retention. Methods Three Phase 3 global multicentre clinical trials evaluated the efficacy and safety of a CB1 receptor antagonist in subjects with BMI >= or = 27 kg/m(2). he impact of a multifaceted retention programme including a dietitian screening interview, a comprehensive culturally adapted lifestyle modification programme, and a dietitian support system to maximize lifestyle adherence, was evaluated in 4,410 subjects from four subpopulations (non-US English-speaking, non-English-speaking, US-without dietitian screening and US-with dietitian screening) comprising 208 centres from 15 countries. Results The median proportion retained over the first year among subjects in three protocols was 82%. Non-English-speaking countries showed higher retention rates (89%) compared with the USA (73%) and non-US English-speaking (81%) countries. Within the USA, behavioural screening was associated with 29% reduction in dropout rate; for every five monthly teleconferences attended above 11, there was a 32% decrease in dropout rate. Conclusions This novel retention programme greatly improved upon reported retention rates of studies conducted with other weight loss agents in long-term clinical trials. Its effectiveness should be confirmed in future trials. C1 [Delahanty, L. M.] Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St Suite 340, Boston, MA 02114 USA. [Delahanty, L. M.] Harvard Med Sch, Boston, MA USA. [Riggs, M.] Cato Res, Durham, NC USA. [Klioze, S. S.; Chew, R. D.; England, R. D.] Pfizer Global Res & Dev, Groton, CT USA. [Digenio, A.] Akcea Therapeut, Cambridge, MA USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St Suite 340, Boston, MA 02114 USA. EM ldelahanty@partners.org FU Pfizer FX This work was funded by Pfizer. NR 24 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2055-2238 J9 OBES SCI PRACT JI OBES. SCI. PRACT. PD SEP PY 2016 VL 2 IS 3 BP 256 EP 265 DI 10.1002/osp4.57 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EF8QE UT WOS:000390593200005 PM 27708842 ER PT J AU Brachtel, E Ly, A Arpin, R Dong, J AF Brachtel, E. Ly, A. Arpin, R. Dong, J. TI Breast cytology continues to be relevant in a large academic medical center SO VIRCHOWS ARCHIV LA English DT Meeting Abstract C1 [Brachtel, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD SEP PY 2016 VL 469 SU 1 MA OFP-03-005 BP S8 EP S8 PG 1 WC Pathology SC Pathology GA ED1OJ UT WOS:000388614500033 ER PT J AU Brachter, E Mahadevan, K Deshpande, V AF Brachter, E. Mahadevan, K. Deshpande, V. TI Estrogen receptor negative breast cancers show quasi-mesenchymal phenotype SO VIRCHOWS ARCHIV LA English DT Meeting Abstract C1 [Brachter, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD SEP PY 2016 VL 469 SU 1 MA OFP-08-010 BP S23 EP S23 PG 1 WC Pathology SC Pathology GA ED1OJ UT WOS:000388614500094 ER PT J AU Kheirkhah, A Qazi, Y Arnoldner, MA Suri, K Dana, R AF Kheirkhah, Ahmad Qazi, Yureeda Arnoldner, Michael A. Suri, Kunal Dana, Reza TI In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE in vivo confocal microscopy; graft-versus-host disease; dry eye disease ID STEM-CELL TRANSPLANTATION; SCANNING LASER MICROSCOPY; CORNEAL LANGERHANS CELL; OCULAR SURFACE; INFECTIOUS KERATITIS; RHEUMATOID-ARTHRITIS; CONJUNCTIVA; SYMPTOMS; INFLAMMATION; DENSITY AB PURPOSE. To compare densities of corneal epithelial dendritic cells (DCs), corneal subbasal nerves, and conjunctival epithelial immune cells (EICs) between patients with dry eye disease (DED) with and without graft-versus-host disease (GVHD) using in vivo confocal microscopy (IVCM). METHODS. This study included 54 patients who had moderate to severe DED either associated with (n = 33) or without (n = 21) chronic GVHD. In addition to evaluating clinical parameters of DED, images obtained by laser-scanning IVCM of the central cornea and superior tarsal conjunctiva were analyzed to measure densities of corneal epithelial DCs, corneal subbasal nerves, and conjunctival EICs. RESULTS. Although there were no significant differences between GVHD and non-GVHD groups in symptom scores, the GVHD group had significantly worse corneal fluorescein staining, tear break-up time, and Schirmer's scores than the non-GVHD group. Corneal epithelial DC density, corneal subbasal nerve density, and conjunctival EIC density were 148 +/- 135 cells/mm(2), 16.3 +/- 6.1 mm/mm(2), and 670 +/- 267 cells/mm(2), respectively, in the GVHD group; and 122 +/- 99 cells/mm(2), 18.3 +/- 5.1 mm/mm(2), and 572 +/- 271 cells/mm(2), respectively, in the non-GVHD group. After adjusting for clinical parameters, including the DED severity, none of the IVCM parameters was significantly different between the GVHD versus non-GVHD groups (P = 0.82, P = 0.21, and P = 0.60, respectively). CONCLUSIONS. In GVHD-associated DED, cellular changes in the cornea and conjunctiva observed by IVCM were similar to those seen in patients who have non-GVHD dry eye with the same level of disease severity. Therefore, corneal and conjunctival IVCM findings in GVHD-associated DED are possibly reflective of the local disease (DED) severity rather than the underlying systemic disease process. C1 [Kheirkhah, Ahmad; Qazi, Yureeda; Arnoldner, Michael A.; Suri, Kunal; Dana, Reza] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Reza_Dana@meei.harvard.edu NR 39 TC 1 Z9 1 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2016 VL 57 IS 11 BP 4686 EP 4691 DI 10.1167/iovs.16-20013 PG 6 WC Ophthalmology SC Ophthalmology GA EF2LP UT WOS:000390156400021 PM 27607414 ER PT J AU Arno, G Hull, S Carss, K Dev-Borman, A Chakarova, C Bujakowska, K van den Born, I Robson, AG Holder, GE Michaelides, M Cremers, FPM Pierce, E Raymond, FL Moore, AT Webster, AR AF Arno, Gavin Hull, Sarah Carss, Keren Dev-Borman, Arundhati Chakarova, Christina Bujakowska, Kinga van den Born, Ingeborgh Robson, Anthony G. Holder, Graham E. Michaelides, Michel Cremers, Frans P. M. Pierce, Eric Raymond, F. Lucy Moore, Anthony T. Webster, Andrew R. TI Reevaluation of the Retinal Dystrophy Due to Recessive Alleles of RGR With the Discovery of a Cis-Acting Mutation in CDHR1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RGR; CDHR1; whole genome sequencing; whole exome sequencing ID DOMINANT RETINITIS-PIGMENTOSA; CONE-ROD DYSTROPHY; INTEGRATIVE GENOMICS VIEWER; OUTER SEGMENT; GENE; IDENTIFICATION; DEGENERATION; CADHERIN; FAMILY AB PURPOSE. Mutation of RGR, encoding retinal G-protein coupled receptor was originally reported in association with retinal dystrophy in 1999. A single convincing recessive variant segregated perfectly in one family of five affected and two unaffected siblings. At least one further individual, homozygous for the same variant has since been reported. The aim of this report was to reevaluate the findings in consideration of data from a whole genome sequencing (WGS) study of a large cohort of retinal dystrophy families. METHODS. Whole genome sequencing was performed on 599 unrelated probands with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography, fundus autofluorescence imaging (FAF) and spectral-domain optical coherence tomography (OCT). RESULTS. Overall we confirmed that affected individuals from six unrelated families were homozygous for both the reported RGR p.Ser66Arg variant and a nearby frameshifting deletion in CDHR1 (p.Ile841Serfs119*). All had generalized rod and cone dysfunction with severe macular involvement. An additional proband was heterozygous for the same CDHR1/RGR haplotype but also carried a second null CDHR1 mutation on a different haplotype. A comparison of the clinical presentation of the probands reported here with other CDHR1-related retinopathy patients shows the phenotypes to be similar in presentation, severity, and rod/cone involvement. CONCLUSIONS. These data suggest that the recessive retinal disorder previously reported to be due to homozygous mutation in RGR is, at least in part, due to variants in CDHR1 and that the true consequences of RGR knock-out on human retinal structure and function are yet to be determined. C1 [Arno, Gavin; Hull, Sarah; Dev-Borman, Arundhati; Chakarova, Christina; Robson, Anthony G.; Holder, Graham E.; Michaelides, Michel; Moore, Anthony T.; Webster, Andrew R.] UCL, UCL Inst Ophthalmol, London, England. [Arno, Gavin; Hull, Sarah; Dev-Borman, Arundhati; Robson, Anthony G.; Holder, Graham E.; Michaelides, Michel; Moore, Anthony T.; Webster, Andrew R.] Moorfields Eye Hosp, London, England. [Carss, Keren] Univ Cambridge & NHS Blood & Transplant, Dept Haematol, Cambridge, England. [Carss, Keren; Raymond, F. Lucy] Cambridge Univ Hosp, NIHR BioResource Rare Dis, Cambridge Biomed Campus, Cambridge, England. [Bujakowska, Kinga; Pierce, Eric] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Boston, MA USA. [van den Born, Ingeborgh] Rotterdam Eye Hosp, Rotterdam, Netherlands. [Cremers, Frans P. M.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands. [Cremers, Frans P. M.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Med Ctr, Nijmegen, Netherlands. [Raymond, F. Lucy] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England. [Moore, Anthony T.] UCSF, Sch Med, Koret Vis Ctr, Ophthalmol Dept, San Francisco, CA USA. RP Webster, AR (reprint author), UCL Inst Ophthalmol, Ocular Biol & Therapeut, 11-43 Bath St, London EC1V 9EL, England. EM andrew.webster@ucl.ac.uk OI Pierce, Eric/0000-0002-2354-4102 FU National Institute for Health Research (NIHR, UK); Biomedical Research Centre at Moorfields Eye Hospital; NIHR BioResource-Rare Diseases; RP Fighting Blindness; Fight For Sight; Foundation Fighting Blindness; Moorfields Eye Hospital Special Trustees; Foundation Fighting Blindness Career Development Award; UCL Institute of Ophthalmology; Cambridge BRC FX Supported by the National Institute for Health Research (NIHR, UK) and Biomedical Research Centre at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, the NIHR BioResource-Rare Diseases, Cambridge BRC, RP Fighting Blindness, Fight For Sight, the Foundation Fighting Blindness, Moorfields Eye Hospital Special Trustees, and a Foundation Fighting Blindness Career Development Award (MM). NR 35 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2016 VL 57 IS 11 BP 4806 EP 4813 DI 10.1167/iovs.16-19687 PG 8 WC Ophthalmology SC Ophthalmology GA EF2LP UT WOS:000390156400035 PM 27623334 ER PT J AU Khawaja, AP Bailey, JNC Kang, JH Allingham, RR Hauser, MA Brilliant, M Budenz, DL Christen, WG Fingert, J Gaasterland, D Gaasterland, T Kraft, P Lee, RK Lichter, PR Liu, YT Medeiros, F Moroi, SE Richards, JE Realini, T Ritch, R Schuman, JS Scott, WK Singh, K Sit, AJ Vollrath, D Wollstein, G Zack, DJ Zhang, K Pericak-Vance, M Weinreb, RN Haines, JL Pasquale, LR Wiggs, JL AF Khawaja, Anthony P. Bailey, Jessica N. Cooke Kang, Jae Hee Allingham, R. Rand Hauser, Michael A. Brilliant, Murray Budenz, Donald L. Christen, William G. Fingert, John Gaasterland, Douglas Gaasterland, Terry Kraft, Peter Lee, Richard K. Lichter, Paul R. Liu, Yutao Medeiros, Felipe Moroi, Syoko E. Richards, Julia E. Realini, Tony Ritch, Robert Schuman, Joel S. Scott, William K. Singh, Kuldev Sit, Arthur J. Vollrath, Douglas Wollstein, Gadi Zack, Donald J. Zhang, Kang Pericak-Vance, Margaret Weinreb, Robert N. Haines, Jonathan L. Pasquale, Louis R. Wiggs, Janey L. TI Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using GeneSet Analyses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE glaucoma; genetics; mitochondria ID GENOME-WIDE ASSOCIATION; OXIDATIVE STRESS; DYSFUNCTION; DISEASE; SUSCEPTIBILITY; METABOLISM; INJURY AB PURPOSE. Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. METHODS. We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. RESULTS. We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P-0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). CONCLUSIONS. We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important. C1 [Khawaja, Anthony P.] Moorfields Eye Hosp NHS Fdn Trust, NIHR, Biomed Res Ctr, London, England. [Khawaja, Anthony P.] UCL, Inst Ophthalmol, London, England. [Bailey, Jessica N. Cooke; Haines, Jonathan L.] Case Western Reserve Univ, Sch Med, Inst Computat Biol, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Kang, Jae Hee] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Allingham, R. Rand] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Brilliant, Murray] Marshfield Clin Res Fdn, Marshfield, WI USA. [Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Christen, William G.] Harvard Med Sch, Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. [Fingert, John] Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA. [Fingert, John] Stephen A Wynn Inst Vis Res, Iowa City, IA USA. [Gaasterland, Douglas] Emmes Corp, Rockville, MD USA. [Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, San Diego, CA 92103 USA. [Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Kraft, Peter] Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA. [Lee, Richard K.] Univ Miami, Bascom Palmer Eye Inst, Miller Sch Med, Miami, FL USA. [Lichter, Paul R.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Liu, Yutao] Augusta Univ, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA USA. [Liu, Yutao] Augusta Univ, James & Jean Culver Vis Discovery Inst, Med Coll Georgia, Augusta, GA USA. [Medeiros, Felipe; Zhang, Kang; Weinreb, Robert N.] Univ Calif San Diego, Hamilton Glaucoma Ctr, Shiley Eye Inst, San Diego, CA 92103 USA. [Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Realini, Tony] West Virginia Univ, Dept Ophthalmol, Eye Inst, Morgantown, WV USA. [Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Dept Ophthalmol, Einhorn Clin Res Ctr, New York, NY USA. [Schuman, Joel S.] NYU, Dept Ophthalmol, 550 1St Ave, New York, NY 10016 USA. [Scott, William K.; Pericak-Vance, Margaret] Univ Miami, Miller Sch Med, Inst Human Genom, Miami, FL 33136 USA. [Singh, Kuldev] Stanford Univ, Sch Med, Dept Ophthalmol, Palo Alto, CA 94304 USA. [Sit, Arthur J.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. [Vollrath, Douglas] Stanford Univ, Sch Med, Dept Genet, Palo Alto, CA 94304 USA. [Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15260 USA. [Zack, Donald J.] Johns Hopkins Univ Hosp, Wimer Eye Inst, Baltimore, MD USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Wiggs, JL (reprint author), Harvard Med Sch, Massachusetts Eye & Ear, Dept Ophthalmol, Ophthalmol, Boston, MA 02114 USA. EM janey-wiggs@meei.harvard.edu FU Harvard Glaucoma Center of Excellence and Margolis fund (Boston, MA, USA); Research to Prevent Blindness, Inc. (New York, NY, USA); Glaucoma Research Foundation (San Francisco, CA, USA); Bright Focus Foundation; Glaucoma Foundation (New York, NY, USA); National Eye Institute Grant [R01EY023242]; National Institutes of Health [UL1TR000427, 1U01HG006389, HHSN268200782096C]; National Institutes of Health/National Eye Institute [R01EY022305]; National Human Genome Research Institute (Bethesda, MD, USA) [GLAUGEN: HG004728, HG004424, HG004446]; National Eye Institute [EY015473, HG005259-01]; National Eye Institute (Bethesda, MD, USA) through American Recovery and Reinvestment Act (ARRA) [EY015872, EY019126]; Berkeley Fellowship; Wellcome Trust [094791/Z/10/Z]; Arthur Ashley Foundation FX The MitoCarta KEGG pathway datasets were kindly provided by Sarah E. Calvo (Broad Institute, Harvard, and MIT). LRP and JLW are supported by the Harvard Glaucoma Center of Excellence and Margolis fund (Boston, MA, USA). DLB, LRP, JER, RNW, and JLW are also supported by Research to Prevent Blindness, Inc. (New York, NY, USA). The Arthur Ashley Foundation also supports LRP.The Glaucoma Research Foundation (San Francisco, CA, USA), Bright Focus Foundation (formerly called American Health Assistance Foundation; Clarksburg, MD, USA), the Glaucoma Foundation (New York, NY, USA), and National Eye Institute Grant R01EY023242 support YL. MB is supported by National Institutes of Health Grants UL1TR000427 and 1U01HG006389. National Institutes of Health/National Eye Institute Grant R01EY022305 supports the NEIGHBORHOOD consortium. The following grants from the National Human Genome Research Institute (Bethesda, MD, USA) supported GLAUGEN: HG004728 (LRP), HG004424 (Broad Institute to support genotyping), HG004446 (C. Laurie, University of Washington, to support genotype data cleaning and analysis). The National Eye Institute supported the formation of the Nurses' Health Study and Health Professional Follow-up Study subset of GLAUGEN (EY015473; LRP). Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research and were supported by the National Eye Institute through Grant HG005259-01 (JLW). In addition, the Center for Inherited Disease Research is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract HHSN268200782096C. The National Eye Institute (Bethesda, MD, USA) through American Recovery and Reinvestment Act (ARRA) Grants EY015872 (JLW) and EY019126 (MAH) supported the collection and processing of samples for the NEIGHBOR dataset. APK received support from the Berkeley Fellowship and the Wellcome Trust (094791/Z/10/Z). NR 29 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2016 VL 57 IS 11 BP 5046 EP 5052 DI 10.1167/iovs.16-20017 PG 7 WC Ophthalmology SC Ophthalmology GA EF2LP UT WOS:000390156400065 PM 27661856 ER PT J AU Herschhorn, A Ma, XC Gu, C Ventura, JD Castillo-Menendez, L Melillo, B Terry, DS Smith, AB Blanchard, SC Munro, JB Mothes, W Finzi, A Sodroski, J AF Herschhorn, Alon Ma, Xiaochu Gu, Christopher Ventura, John D. Castillo-Menendez, Luis Melillo, Bruno Terry, Daniel S. Smith, Amos B., III Blanchard, Scott C. Munro, James B. Mothes, Walther Finzi, Andres Sodroski, Joseph TI Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins SO MBIO LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; AIDS PATIENTS; GP41-GP120 INTERFACE; CD4 INDEPENDENCE; ATOMIC-STRUCTURE; BINDING-SITE; V2 DOMAIN; HTLV-III; FUSION AB Primary human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimers [(gp120/gp41)(3)] typically exist in a metastable closed conformation (state 1). Binding the CD4 receptor triggers Env to undergo extensive conformational changes to mediate virus entry. We identified specific gp120 residues that restrain Env in state 1. Alteration of these restraining residues destabilized state 1, allowing Env to populate a functional conformation (state 2) intermediate between state 1 and the full CD4-bound state (state 3). Increased state 2 occupancy was associated with lower energy barriers between the states. State 2 was an obligate intermediate for all transitions between state 1 and state 3. State 2-enriched Envs required lower CD4 concentrations to trigger virus entry and more efficiently infected cells expressing low levels of CD4. These Envs were resistant to several broadly neutralizing antibodies and small-molecule inhibitors. Thus, state 2 is an Env conformation on the virus entry pathway; sampling state 2 increases the adaptability of HIV-1 to different host cell receptor levels and immune environments. Our results provide new insights into the conformational regulation of HIV-1 entry. IMPORTANCE The envelope glycoproteins (Env) of HIV-1 mediate virus entry and are the sole targets of neutralizing antibodies. Understanding the way that Env promotes HIV-1 entry can expedite drug and vaccine development. By destabilizing Env, we found that it assumes an intermediate state that is functional and obligate for transitions to entry-competent conformations. Increased sampling of this state enhances the ability of HIV-1 to infect cells that express low levels of the CD4 receptor and allows the virus to evade neutralizing antibodies and small-molecule inhibitors. These findings provide new mechanistic insights into the function and inhibition of HIV-1 Env and will contribute to ongoing therapeutic and prevention efforts to combat HIV-1. C1 [Herschhorn, Alon; Gu, Christopher; Castillo-Menendez, Luis; Sodroski, Joseph] Dana Farber Canc Inst, Dept Immunol Canc & Virol, Boston, MA 02115 USA. [Herschhorn, Alon; Castillo-Menendez, Luis; Sodroski, Joseph] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Ma, Xiaochu; Ventura, John D.; Mothes, Walther] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA. [Melillo, Bruno; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Terry, Daniel S.; Blanchard, Scott C.] Cornell Univ, Dept Physiol & Biophys, Weill Cornell Med Coll, New York, NY 10021 USA. [Munro, James B.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Munro, James B.] Sackler Sch Grad Biomed Sci, Boston, MA USA. [Finzi, Andres] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada. [Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Sodroski, Joseph] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Herschhorn, A; Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Immunol Canc & Virol, Boston, MA 02115 USA.; Herschhorn, A; Sodroski, J (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Sodroski, J (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM alon_herschhorn@dfci.harvard.edu; joseph_sodroski@dfci.harvard.edu RI Blanchard, Scott/A-5804-2009 FU HHS \ National Institutes of Health (NIH) [AI24755, GM56550, AI100645, GM116654, GM098859, AI116262]; amfAR, The Foundation for AIDS Research (amfAR) [10850-53-RKNT, 109285-58-RKVA]; Canada Research Chairs (Chaires de recherche du Canada) FX This work, including the efforts of Joseph G. Sodroski, was funded by HHS vertical bar National Institutes of Health (NIH) (AI24755). This work, including the efforts of Joseph G. Sodroski, was funded by HHS vertical bar National Institutes of Health (NIH) (GM56550). This work, including the efforts of Joseph G. Sodroski, was funded by HHS vertical bar National Institutes of Health (NIH) (AI100645). This work, including the efforts of Walther Mothes, was funded by HHS vertical bar National Institutes of Health (NIH) (GM116654). This work, including the efforts of Walther Mothes, was funded by HHS vertical bar National Institutes of Health (NIH) (GM56550). This work, including the efforts of Scott Blanchard, was funded by HHS vertical bar National Institutes of Health (NIH) (GM098859). This work, including the efforts of James Munro, was funded by HHS vertical bar National Institutes of Health (NIH) (AI116262). This work, including the efforts of Alon Herschhorn, was funded by amfAR, The Foundation for AIDS Research (amfAR) (10850-53-RKNT and 109285-58-RKVA). This work, including the efforts of Andres Finzi, was funded by Canada Research Chairs (Chaires de recherche du Canada). NR 62 TC 4 Z9 4 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2016 VL 7 IS 5 AR e01598-16 DI 10.1128/mBio.01598-16 PG 12 WC Microbiology SC Microbiology GA EF2CU UT WOS:000390132900026 ER PT J AU Juttukonda, LJ Chazin, WJ Skaar, EP AF Juttukonda, Lillian J. Chazin, Walter J. Skaar, Eric P. TI Acinetobacter baumannii Coordinates Urea Metabolism with Metal Import To Resist Host-Mediated Metal Limitation SO MBIO LA English DT Article ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; ALLOPHANATE HYDROLASE; HUMAN CALPROTECTIN; DEFENSE PROTEIN; MANGANESE; TRANSPORTER; INFECTIONS; AMIDOLYASE AB During infection, bacterial pathogens must adapt to a nutrient metal-limited environment that is imposed by the host. The innate immune protein calprotectin inhibits bacterial growth in vitro by chelating the divalent metal ions zinc (Zn2+, Zn) and manganese (Mn2+, Mn), but pathogenic bacteria are able to cause disease in the presence of this antimicrobial protein in vivo. One such pathogen is Acinetobacter baumannii, a Gram-negative bacterium that causes pneumonia and bloodstream infections that can be complicated by resistance to multiple antibiotics. A. baumannii inhibition by calprotectin is dependent on calprotectin Mn binding, but the mechanisms employed by A. baumannii to overcome Mn limitation have not been identified. This work demonstrates that A. baumannii coordinates transcription of an NRAMP family Mn transporter and a urea carboxylase to resist the antimicrobial activities of calprotectin. This NRAMP family transporter facilitates Mn accumulation and growth of A. baumannii in the presence of calprotectin. A. baumannii is found to utilize urea as a sole nitrogen source, and urea utilization requires the urea carboxylase encoded in an operon with the NRAMP family transporter. Moreover, urea carboxylase activity is essential for calprotectin resistance in A. baumannii. Finally, evidence is provided that this system combats calprotectin in vivo, as deletion of the transporter impairs A. baumannii fitness in a mouse model of pneumonia, and this fitness defect is modulated by the presence of calprotectin. These findings reveal that A. baumannii has evolved mechanisms to subvert host-mediated metal sequestration and they uncover a connection between metal starvation and metabolic stress. IMPORTANCE Acinetobacter baumannii is a bacterium that causes bloodstream, wound, urinary tract, and pneumonia infections, with a high disease burden in intensive care units. Treatment of A. baumannii infection is complicated by resistance to most antibiotics in use today, and resistance to last-resort therapies has become commonplace. New treatments for A. baumannii infection are desperately needed, but our current understanding of the bacterial factors required to cause infection is limited. We previously found that the abundant innate immune protein calprotectin inhibits the growth of A. baumannii by withholding essential metals. Despite this, A. baumannii is still able to infect wild-type mice, which produce calprotectin during infection. Here, we identify factors employed by A. baumannii during infection to overcome calprotectin-mediated metal sequestration. Moreover, we expose a connection between metal starvation and metabolism that may be a "chink in the armor" of A. baumannii and lead to new treatment options. C1 [Juttukonda, Lillian J.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Chazin, Walter J.] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. [Chazin, Walter J.] Vanderbilt Univ, Dept Chem, Nashville, TN USA. [Chazin, Walter J.] Vanderbilt Univ, Struct Biol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA. [Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. RP Skaar, EP (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA.; Skaar, EP (reprint author), Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. EM eric.skaar@vanderbilt.edu FU HHS \ National Institutes of Health (NIH) [AI101171, T32 GM07347]; U.S. Department of Veterans Affairs (VA) [INFB-024-13F]; American Heart Association (AHA) [15PRE25060007] FX This work, including the efforts of Lillian Johnson Juttukonda, was funded by HHS vertical bar National Institutes of Health (NIH) (AI101171 and T32 GM07347). This work, including the efforts of Eric P. Skaar, was funded by U.S. Department of Veterans Affairs (VA) (INFB-024-13F). This work, including the efforts of Lillian Johnson Juttukonda, was funded by American Heart Association (AHA) (15PRE25060007). NR 53 TC 1 Z9 1 U1 4 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2016 VL 7 IS 5 AR e01475-16 DI 10.1128/mBio.01475-16 PG 11 WC Microbiology SC Microbiology GA EF2CU UT WOS:000390132900031 ER PT J AU Manchikanti, L Singh, V Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Hirsch, Joshua A. TI Facility Payments for Interventional Pain Management Procedures: Impact of Proposed Rules SO PAIN PHYSICIAN LA English DT Review DE Hospital outpatient departments; ambulatory surgery centers; physician in-office services; interventional pain management; interventional techniques ID EPIDURAL STEROID INJECTIONS; AFFORDABLE CARE ACT; US HEALTH-CARE; PREVENT NEUROLOGIC COMPLICATIONS; CENTRAL SPINAL STENOSIS; LUMBAR DISC HERNIATION; COST-UTILITY ANALYSIS; LONG-TERM RELIEF; LOW-BACK-PAIN; UNITED-STATES AB In the face of the progressive implementation of the Affordable Care Act (ACA), a significant regulatory regime, and the Merit-Based Incentive Payment System (MIPS), the Centers for Medicare and Medicaid Services (CMS) released its proposed 2017 hospital outpatient department (HOPD) and ambulatory surgery center (ASC) payment rules on July 14, 2016, and the physician payment schedule was released July 15, 2016. U.S. health care costs continue to increase, occupying 17.5% of the gross domestic product (GDP) in 2014 and surpassing $3 trillion in overall health care expenditure. Solo and independent practices face unique challenges and many are being acquired by hospitals or larger groups. This transfer of services to hospital settings is indisputably leading to an increase in the net cost to the system. Comparison of facility payments for interventional techniques in HOPD, ASC, and in-office settings shows wide variation for multiple interventional techniques. Major discrepancies in payment schedules are related to higher payments for hospitals than comparable treatments in in-office settings and ASCs. In-office procedures, which have been converted to ASC procedures, are reimbursed at as high as 1,366% higher than ASCs and 2,156% higher than in-office settings. The Medicare Payment Advisory Commission (MedPAC) has made recommendations on avoiding the discrepancies and site-of-service differentials in in-office settings, hospital outpatient settings, and ASCs. These have not been implemented by CMS. In addition, there have been slow reductions in reimbursements over the recent years, which continue to accumulate, leading to significant reductions in payments In conclusion, equalization of site-of-service differentials will simultaneously improve reimbursement patterns for interventional pain management procedures, increase access and quality of care, and finally, reduce costs for CMS, extending Medicare solvency. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA USA. [Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 98 TC 1 Z9 1 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD SEP PY 2016 VL 19 IS 7 BP E957 EP E984 PG 28 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA EF1YT UT WOS:000390121800003 PM 27676688 ER PT J AU Manchikanti, L Kaye, AD Hirsch, JA AF Manchikanti, Laxmaiah Kaye, Alan D. Hirsch, Joshua A. TI Proposed Medicare Physician Payment Schedule for 2017: Impact on Interventional Pain Management Practices SO PAIN PHYSICIAN LA English DT Review DE Physician payment policy; physician fee schedule; Medicare; Merit-Based Incentive Payment System; interventional pain management; regulatory tsunami; Medicare Access and CHIP Reauthorization Act of 2015 ID EPIDURAL STEROID INJECTIONS; AFFORDABLE CARE ACT; US HEALTH-CARE; PREVENT NEUROLOGIC COMPLICATIONS; LONG-TERM RELIEF; PERCUTANEOUS ADHESIOLYSIS; RADIOFREQUENCY TREATMENT; UNITED-STATES; KNEE OSTEOARTHRITIS; CONTROLLED-TRIAL AB The Centers for Medicare and Medicaid Services (CMS) released the proposed 2017 Medicare physician fee schedule on July 7, 2016, addressing Medicare payments for physicians providing services either in an office or facility setting, which also includes payments for office expenses and quality provisions for physicians. This proposed rule occurs in the context of numerous policy changes, most notably related to the Medicare Access & CHIP Reauthorization Act of 2015 (MACRA) and its Merit-Based Incentive Payment System (MIPS). The proposed rule affects interventional pain management specialists in reimbursement for evaluation and management services, as well as procedures performed in a facility or in-office setting. Changes in the proposed fee schedule impacting interventional pain management practices include adjustments to the meaningful use (MU) program, care management in patient-centered services, identification and review of potentially misvalued services, evaluation of moderate sedation services, Medicare telehealth services, updated geographic practice cost index, data collection on resources used in furnishing global services, reporting of modifier 25 for zero day global services, Medicare Advantage Part C provider and supplier enrollment, appropriate use criteria (AUC) for advanced imaging services, and Medicare shared savings programs. The proposed schedule has provided rates for new epidural codes with or without imaging (fluoroscopy or computed tomography [CT]) and a fee schedule for a new code covering endoscopic spinal decompression. Review of payment rates show major discrepancies in payment schedules with high payments for hospitals, 2,156% higher than in-office procedures. Some procedures which were converted from in-office settings to ambulatory surgery centers (ASCs) are being reimbursed at 1,366% higher than ASCs. The Medicare Payment Advisory Commission (MedPAC) recommendation on avoiding the discrepancies and site-of-service differentials in in-office settings, hospital outpatient settings, and ASCs has not been agreed to by CMS. Thus, even though the changes appear to be minor in physician services and in-office service payment, these changes cumulatively have been reducing payments for interventional procedures. Further, in-office reimbursement is overall significantly lower than ASCs and hospital outpatient departments (HOPDs) specifically for intraarticular injections, peripheral nerve blocks, and peripheral neurolytic injections. The significant advantage also continues for hospitals in their reimbursement for facility fee for evaluation and management services. This health policy review describes various issues related to health care expenses, health care reform, and finally its effects on physician payments for all services and also for the services provided in an office setting. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, Dept Anesthesia, New Orleans, LA USA. [Kaye, Alan D.] LSU Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 96 TC 2 Z9 2 U1 2 U2 2 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD SEP PY 2016 VL 19 IS 7 BP E935 EP E955 PG 21 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA EF1YT UT WOS:000390121800002 PM 27676687 ER PT J AU Manchikanti, L Helm, S Benyamin, RM Hirsch, JA AF Manchikanti, Laxmaiah Helm, Standiford, II Benyamin, Ramsin M. Hirsch, Joshua A. TI Merit-Based Incentive Payment System (MIPS): Harsh Choices For Interventional Pain Management Physicians SO PAIN PHYSICIAN LA English DT Review DE Medicare Access and CHIP Reauthorization Act of 2015; merit-based incentive payment system; quality performance measures; resource use; clinical practice improvement activities; advancing care information performance category ID HEALTH-CARE REFORM; QUALITY REPORTING SYSTEM; UNITED-STATES; STICK POLICY; ORGANIZATIONS; ICD-10-CM; MEDICINE; ACT; METAMORPHOSIS; IMPROVEMENT AB The Merit-based Incentive Payment System (MIPS) was created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to improve the health of all Americans by providing incentives and policies to improve patient health outcomes. MIPS combines 3 existing programs, Meaningful Use (MU), now called Advancing Care Information (ACI), contributing 25% of the composite score; Physician Quality Reporting System (PQRS), changed to Quality, contributing 50% of the composite score; and Value-based Payment (VBP) system to Resource Use or cost, contributing 10% of the composite score. Additionally, Clinical Practice Improvement Activities (CPIA), contributing 15% of the composite score, create multiple strategic goals to design incentives that drive movement toward delivery system reform principles with inclusion of Advanced Alternative Payment Models (APMs). Under the present proposal, the Centers for Medicare and Medicaid Services (CMS) has estimated approximately 30,000 to 90,000 providers from a total of over 761,000 providers will be exempt from MIPS. About 87% of solo practitioners and 70% of practitioners in groups of less than 10 will be subjected to negative payments or penalties ranging from 4% to 9%. In addition, MIPS also will affect a provider's reputation by making performance measures accessible to consumers and third-party physician rating Web sites. The MIPS composite performance scoring method, at least in theory, utilizes weights for each performance category, exceptional performance factors to earn bonuses, and incorporates the special circumstances of small practices. In conclusion, MIPS has the potential to affect practitioners negatively. Interventional Pain Medicine practitioners must understand the various MIPS measures and how they might participate in order to secure a brighter future. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Hills, CA USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Surg, Urbana, IL 61801 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Woods, CA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP FX Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. NR 60 TC 3 Z9 3 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD SEP PY 2016 VL 19 IS 7 BP E917 EP E934 PG 18 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA EF1YT UT WOS:000390121800001 PM 27676686 ER PT J AU Adeeb, N Griessenauer, CJ Moore, J Stapleton, CJ Patel, AB Gupta, R Patel, AS Thomas, AJ Ogilvy, CS AF Adeeb, Nimer Griessenauer, Christoph J. Moore, Justin Stapleton, Christopher J. Patel, Aman B. Gupta, Raghav Patel, Apar S. Thomas, Ajith J. Ogilvy, Christopher S. TI Pipeline Embolization Device for Recurrent Cerebral Aneurysms after Microsurgical Clipping SO WORLD NEUROSURGERY LA English DT Article DE Clipping; Flow diversion; PED; Pipeline; Salvage; Surgical; Treatment ID RUPTURED INTRACRANIAL ANEURYSMS; TERM-FOLLOW-UP; STENT-ASSISTED COILING; POSTERIOR CIRCULATION ANEURYSMS; ENDOVASCULAR TREATMENT; EXPERIENCE; METAANALYSIS; MULTICENTER; SAFETY; TRIAL AB BACKGROUND: Microsurgical clipping is regarded as the most durable treatment for cerebral aneurysms. Aneurysm recurrence after clipping is uncommon and is associated with an increased risk of rupture. Reoperation for recurrent cerebral aneurysms is particularly challenging because of adhesions and scaring, and it carries a higher rate of morbidity and mortality. Pipeline embolization as a treatment option for recurrent aneurysms has rarely been reported. METHODS: A retrospective analysis of patients who underwent Pipeline Embolization Device (PED) placement for recurrent aneurysms after clipping at two major academic institutions in the United States was performed. RESULTS: Seven patients were identified. The median time between initial clipping and diagnosis of recurrence was 13 years (range, 5-20 years). No morbidity or mortality was associated with PED placement. Complete occlusion was achieved in all patients with imaging follow-up. A history of prior clipping did not affect PED placement or outcome. CONCLUSIONS: PED for recurrent aneurysms after clipping may be a feasible alternative to reoperation. In our experience, treatment with PED for these aneurysms is safe and efficacious. C1 [Adeeb, Nimer; Griessenauer, Christoph J.; Moore, Justin; Gupta, Raghav; Patel, Apar S.; Thomas, Ajith J.; Ogilvy, Christopher S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Neurosurg Serv, Boston, MA 02115 USA. [Stapleton, Christopher J.; Patel, Aman B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. RP Ogilvy, CS (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Neurosurg Serv, Boston, MA 02115 USA. EM cogilvy@bidmc.harvard.edu NR 38 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD SEP PY 2016 VL 93 BP 341 EP 345 DI 10.1016/j.wneu.2016.06.065 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA EF5DX UT WOS:000390352000050 PM 27350300 ER PT J AU Lim, D Oliva, E AF Lim, Diana Oliva, Esther TI Borderline Mucinous Tumors of the Ovary: Updates in Diagnosis SO AJSP-REVIEWS AND REPORTS LA English DT Review DE ovary; mucinous tumor; borderline; intraepithelial carcinoma; microinvasion; mural nodules ID MALIGNANT POTENTIAL TUMORS; LARGE RETROSPECTIVE SERIES; MATURE CYSTIC TERATOMAS; OF-THE-LITERATURE; TERM-FOLLOW-UP; EPITHELIAL TUMORS; INTESTINAL-TYPE; CLINICOPATHOLOGICAL ANALYSIS; MURAL NODULES; PSEUDOMYXOMA PERITONEI AB Mucinous borderline tumors (MBTs) account for approximately 10% of all primary ovarian mucinous neoplasms. These tumors are characteristically heterogeneous in their composition and frequently show a variable admixture of benign and borderline morphologies, and even in some instances, areas of intraepithelial carcinoma and/or small invasive foci. This review discusses the salient clinical and pathological features of MBTs including (1) terminology used to describe tumors with noninvasive carcinoma and stromal microinvasion and the current definitions of these terms, (2) association with mural nodules, (3) immunohistochemical and molecular profile, (4) limitations of frozen section diagnosis, (5) morphological mimics, and (6) recent updates in their treatment and prognosis. Some of the controversial aspects regarding the terminology and diagnosis of these neoplasms will also be explored in this review. C1 [Lim, Diana] Natl Univ Hlth Syst, Singapore, Singapore. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lim, D (reprint author), Natl Univ Singapore Hosp, Dept Pathol, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. EM diana_gz_lim@nuhs.edu.sg NR 112 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 1082-9784 EI 1533-4015 J9 AJSP-REV REP JI AJSP-Rev. Rep. PD SEP-OCT PY 2016 VL 21 IS 5 BP 214 EP 221 DI 10.1097/PCR.0000000000000158 PG 8 WC Pathology SC Pathology GA EF0AI UT WOS:000389987300003 ER PT J AU Stats, MA Stone, JR AF Stats, Miriam A. Stone, James R. TI Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Amyloidosis; Amyloid; Pyrophosphate scan; Bone scan; Nuclear medicine; Macrophage; Microcalcification ID TRANSTHYRETIN AMYLOIDOSIS; MYOCARDIAL INFARCTS; ACID SCINTIGRAPHY; HEART-FAILURE; PYROPHOSPHATE; IDENTIFICATION; CALCIFICATION; NOMENCLATURE; DIAGNOSIS; PATHOLOGY AB Background: Recently, there has been much interest in using nuclear medicine studies to noninvasively identify and subtype cardiac amyloidosis. In particular, modified bone scans using Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-99m-DPD) and Tc-99m-pyrophosphate (Tc-99m-PYP) are being used to selectively identify patients with ATTR amyloidosis rather than AL amyloidosis. The morphologic basis underlying the selectivity of these imaging modalities for ATTR amyloidosis has been unclear. Methods: To determine if variations in microcalcifications and/or macrophages within ATTR and AL amyloidosis might be responsible for the selectivity for these imaging modalities, 8 endomyocardial biopsies of ATTR amyloidosis and 7 endomyocardial biopsies of AL amyloidosis were stained with von Kossa calcium stains and with immunohistochemistry for the macrophage marker CD68. Results: Compared with AL amyloidosis, there was a greater density of small microcalcifications in cases of ATTR amyloidosis (mean = 16.8 vs. 6.5 per 200 x field, P = .008). In contrast, there were fewer macrophages in ATTR amyloidosis compared with AL amyloidosis (mean = 2.5 vs. 11.7 per 200 x field, P = .0004). The density of microcalcifications within each group was not related to patient age, echocardiographic features of cardiac function, or serum levels of calcium and creatinine. Conclusions: These data suggest that microcalcifications but not macrophages likely underlie the selectivity of modified bone scans for ATTR amyloidosis and suggest that other pathologic entities containing microcalcifications might also result in positive scans with these imaging modalities. (C) 2016 Elsevier Inc. All rights reserved. C1 [Stats, Miriam A.; Stone, James R.] Harvard Med Sch, Dept Pathol, Massachusetts Gen Hosp, Boston, MA USA. [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Simches Res Bldg Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org NR 33 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 1054-8807 EI 1879-1336 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD SEP-OCT PY 2016 VL 25 IS 5 BP 413 EP 417 DI 10.1016/j.carpath.2016.07.001 PG 5 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA EE3ST UT WOS:000389519400009 PM 27469499 ER PT J AU Choi, SH Shah, K AF Choi, Sung Hugh Shah, Khalid TI Engineered Bifunctional Proteins and Stem Cells: Next Generation of Targeted Cancer Therapeutics SO DISCOVERY MEDICINE LA English DT Article ID MESENCHYMAL STROMAL CELLS; LUNG METASTASIS MODEL; MOUSE XENOGRAFT MODEL; BISPECIFIC ANTIBODY; ANTITUMOR-ACTIVITY; INTERFERON-BETA; FUSION PROTEIN; BRAIN-TUMORS; PANCREATIC-CANCER; POTENT ANTITUMOR AB Redundant survival signaling pathways and their crosstalk within tumor and/or between tumor and their microenvironment are key impediments to developing effective targeted therapies for cancer. Therefore developing therapeutics that target multiple receptor signaling pathways in tumors and utilizing efficient platforms to deliver such therapeutics are critical to the success of future targeted therapies. During the past two decades, a number of bifunctional multi-targeting antibodies, fusion proteins, and oncolytic viruses have been developed and various stem cell types have been engineered to efficiently deliver them to tumors. In this review, we discuss the design and efficacy of therapeutics targeting multiple pathways in tumors and the therapeutic potential of therapeutic stem cells engineered with bifunctional agents. C1 [Choi, Sung Hugh; Shah, Khalid] Massachusetts Gen Hosp, Harvard Med Sch, Stem Cell Therapeut & Imaging Program, Boston, MA 02129 USA. [Choi, Sung Hugh; Shah, Khalid] Massachusetts Gen Hosp, Harvard Med Sch, Mol Neurotherapy & Imaging Lab, Boston, MA 02129 USA. [Choi, Sung Hugh; Shah, Khalid] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02129 USA. [Shah, Khalid] Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Boston, MA 02129 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Shah, K (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Stem Cell Therapeut & Imaging Program, Boston, MA 02129 USA.; Shah, K (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Mol Neurotherapy & Imaging Lab, Boston, MA 02129 USA.; Shah, K (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02129 USA.; Shah, K (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurol, Boston, MA 02129 USA.; Shah, K (reprint author), Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM kshah@mgh.harvard.edu NR 81 TC 0 Z9 0 U1 3 U2 3 PU DISCOVERY MEDICINE PI TIMONIUM PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA SN 1539-6509 EI 1944-7930 J9 DISCOV MED JI Discov. Med. PD SEP PY 2016 VL 22 IS 120 BP 157 EP 166 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EE3YE UT WOS:000389537500007 PM 27755970 ER PT J AU Verjans, JW Osborn, EA Ughi, GJ Press, MAC Hamidi, E Antoniadis, AP Papafaklis, MI Conrad, MF Libby, P Stone, PH Cambria, RP Tearney, GJ Jaffer, FA AF Verjans, Johan W. Osborn, Eric A. Ughi, Giovanni J. Press, Marcella A. Calfon Hamidi, Ehsan Antoniadis, Antonios P. Papafaklis, Michail I. Conrad, Mark F. Libby, Peter Stone, Peter H. Cambria, Richard P. Tearney, Guillermo J. Jaffer, Farouc A. TI Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis Clinical and Intracoronary Evaluation of Indocyanine Green SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; endothelium; indocyanine green; inflammation; intraplaque hemorrhage; intravascular imaging; lipid; molecular imaging; near-infrared fluorescence ID IN-VIVO; HEMORRHAGE; TRANSPORT AB OBJECTIVES This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. BACKGROUND New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. METHODS Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 +/- 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. RESULTS ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. CONCLUSIONS This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716) (C) 2016 by the American College of Cardiology Foundation. C1 [Verjans, Johan W.; Osborn, Eric A.; Press, Marcella A. Calfon; Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Verjans, Johan W.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands. [Osborn, Eric A.; Jaffer, Farouc A.] Harvard Med Sch, Div Cardiol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ughi, Giovanni J.; Hamidi, Ehsan; Tearney, Guillermo J.; Jaffer, Farouc A.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Antoniadis, Antonios P.; Papafaklis, Michail I.; Libby, Peter; Stone, Peter H.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Div, Boston, MA USA. [Conrad, Mark F.; Cambria, Richard P.] Harvard Med Sch, Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA USA. [Tearney, Guillermo J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Tearney, GJ; Jaffer, FA (reprint author), MGH, Cardiovasc Res Ctr, Simches Res Bldg,Room 3206,55 Fruit St, Boston, MA 02114 USA. EM gtearney@mgh.harvard.edu; fjaffer@mgh.harvard.edu OI Ughi, Giovanni J./0000-0003-3354-0698 FU Netherlands Organization for Scientific Research [825.12.013]; Harvard Catalyst National Institutes of Health [KL2 TR001100]; George D. Behrakis Cardiovascular Research Fellowships; General Electric; GlaxoSmithKline; Novartis; National Institutes of Health [R01 HL080472, R01 HL093717]; Canon Inc.; Ardea Biosciences; Kowa; American Heart Association [13GRNT17060040]; Massachusetts General Hospital SPARK award; Executive Committee on Research (ECOR) FX From the aCardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; bDepartment of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; cCardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; dWellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; eCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; fDivision of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and the gDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Dr. Verjans has received Rubicon grant 825.12.013 from the Netherlands Organization for Scientific Research. Dr. Osborn has received Harvard Catalyst National Institutes of Health grant KL2 TR001100. Drs. Antoniadis and Papafaklis have received George D. Behrakis Cardiovascular Research Fellowships. Dr. Libby has received sponsored research grants from General Electric, GlaxoSmithKline, and Novartis; and has received National Institutes of Health grant R01 HL080472. Dr. Stone has received a George D. Behrakis Cardiovascular Research Fellowship. Dr. Tearney has the right to receive licensing royalties from Terumo, Canon, and MIT; has received sponsored research from Canon Inc. and Ardea Biosciences; has received National Institutes of Health grant R01 HL093717 (for development of imaging console and catheter); and has received catheter components from Terumo. Dr. Jaffer has the right to receive licensing royalties from Canon; received sponsored research grants from Kowa, Siemens, and Canon; has received National Institutes of Health grants R01 HL108229 and R01 HL122388-01A1; has received American Heart Association grant 13GRNT17060040; has received Massachusetts General Hospital SPARK award and Executive Committee on Research (ECOR) support; and has consulting agreements with Boston Scientific and Abbott Vascular. Massachusetts General Hospital has a patent licensing arrangement with Terumo and Canon Corporations. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Verjans, Osborn, and Ughi are joint first authors. Drs. Jaffer and Tearney are joint senior authors. 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 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2016 VL 9 IS 9 BP 1087 EP 1095 DI 10.1016/j.jcmg.2016.01.034 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA EE4CQ UT WOS:000389550000011 PM 27544892 ER PT J AU Wu, AC Li, LL Fung, V Kharbanda, EO Larkin, EK Butler, MG Galbraith, A Miroshnik, I Davis, RL Horan, K Lieu, TA AF Wu, Ann Chen Li, Lingling Fung, Vicki Kharbanda, Elyse O. Larkin, Emma K. Butler, Melissa G. Galbraith, Alison Miroshnik, Irina Davis, Robert L. Horan, Kelly Lieu, Tracy A. TI Mismatching Among Guidelines, Providers, and Parents on Controller Medication Use in Children with Asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Asthma; Children; Controller medications; Adherence; Provider ID PRIMARY-CARE PROVIDERS; MILD PERSISTENT ASTHMA; INHALED CORTICOSTEROIDS; CHILDHOOD ASTHMA; ADHERENCE; BARRIERS; NONADHERENCE; STEROIDS; VISITS; POOR AB BACKGROUND: Underuse of controller medicines among children with asthma remains widespread despite national guidelines. OBJECTIVES: To (1) assess provider prescribing patterns for asthma controller medications; (2) assess how frequently parents' reports of their child's asthma controller medicine use were mismatched with their provider's recommendations; and (3) evaluate parent attitudes and demographic characteristics associated with these mismatches. METHODS: In this cross-sectional study, we conducted linked surveys of parents and providers of children with probable persistent asthma in a Medicaid program and 4 commercial health plans in 2011. Probable persistent asthma was defined as a diagnosis of asthma and 1 or more controller medication dispensing. RESULTS: This study included 740 children (mean age, 8.6 years). Providers for 50% of the children reported prescribing controller medications for daily year-round use, 41% for daily use during active asthma months, and 9% for intermittent use for relief. Among parents, 72% knew which class of controller medication the provider prescribed and 49% knew the administration frequency and the medication class. Parents were less likely to report the same controller medication type as the provider, irrespective of dose and frequency, if they were Latino (odds ratio [OR], 0.23; CI, 0.057-0.90), had a household smoker (OR, 2.87; CI, 0.42-19.6), or believed the controller medicine was not helping (OR, 0.15; CI, 0.048-0.45). CONCLUSIONS: Mismatches between parent reports and providers intentions regarding how the child was supposed to use inhaled steroids occurred for half of the children. Efforts should focus on ways to reduce mismatches between parent and provider intentions regarding controller medication use. (C) 2016 American Academy of Allergy, Asthma & Immunology C1 [Wu, Ann Chen; Li, Lingling; Galbraith, Alison; Miroshnik, Irina; Horan, Kelly] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Healthcare Res Pediat, Boston, MA USA. [Wu, Ann Chen; Li, Lingling; Fung, Vicki; Galbraith, Alison; Miroshnik, Irina; Horan, Kelly] Harvard Med Sch, Boston, MA USA. [Wu, Ann Chen; Galbraith, Alison] Childrens Hosp, Dept Pediat, Div Gen Pediat, Boston, MA USA. [Fung, Vicki] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Kharbanda, Elyse O.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Larkin, Emma K.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Butler, Melissa G.] Kaiser Permanente Georgia, Ctr Clin Outcomes & Res Southeast, Atlanta, GA USA. [Butler, Melissa G.] Argus Grp, Hamilton, Bermuda. [Davis, Robert L.] Univ Tennessee, Hlth Sci Ctr, Ctr Biomed Informat, Memphis, TN USA. [Lieu, Tracy A.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. RP Wu, AC (reprint author), Dept Populat Med, 133 Brookline Ave,6th Fl, Boston, MA 02215 USA. EM ann.wu@childrens.harvard.edu FU Agency for Healthcare Research and Quality [1R01HS019669] FX The Population-Based Effectiveness in Asthma and Lung Diseases Network is supported by the Agency for Healthcare Research and Quality (grant no. 1R01HS019669; principal investigator Steve Soumerai). NR 26 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD SEP-OCT PY 2016 VL 4 IS 5 BP 910 EP 916 DI 10.1016/j.jaip.2016.04.004 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA EE4YW UT WOS:000389612800015 PM 27212379 ER PT J AU Wong, LL Lee, NG Amarnani, D Choi, CJ Bielenberg, DR Freitag, SK D'Amore, PA Kim, LA AF Wong, Lindsay L. Lee, Nahyoung Grace Amarnani, Dhanesh Choi, Catherine J. Bielenberg, Diane R. Freitag, Suzanne K. D'Amore, Patricia A. Kim, Leo A. TI Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease An Analysis of Vascular Growth Factors with Clinical Correlation SO OPHTHALMOLOGY LA English DT Article ID LYMPHATIC VESSELS; FACTOR-C; GRAVES OPHTHALMOPATHY; CORNEAL INFLAMMATION; VEGF-D; MACROPHAGES; MARKER; PROX1 AB Purpose: The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat also were evaluated. Design: Retrospective cohort study. Participants: The study included fat specimens from 26 orbits of 15 patients with TED undergoing orbital decompression. Orbital fat specimens from patients without TED as well as cadaveric orbital fat served as controls. Methods: Tissue specimens were processed as formalin-fixed, paraffin-embedded sections or frozen cryosections for immunohistochemistry. Total RNA was extracted and analyzed via quantitative (real-time) reverse-transcription polymerase chain reaction. Clinicopathologic correlation was made by determining the clinical activity score (CAS) of each patient with TED. Main Outcome Measures: Samples were examined for vascular and lymphatic markers including podoplanin, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and cluster of differentiation 31 (CD31) by immunohistochemistry, as well as for mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptors, semaphorin 3F, neuropilin 1, neuropilin 2, podoplanin, and LYVE-1 by quantitative (real-time) reverse-transcription polymerase chain reaction. Results: Clinicopathologic correlation revealed increased staining of CD31-positive blood vessels in patients with acute TED with a CAS more than 4, as well as rare staining of podoplanin-positive lymphatic vessels within acutely inflamed orbital fat tissue. Additionally, quantitative (real-time) reverse-transcription polymerase chain reaction analysis demonstrated increased expression of VEGF receptor (VEGFR) 2 as well as VEGF signaling molecules VEGF-A, VEGF-C, and VEGF-D. Conclusions: In acute TED, compared with chronic TED and control orbital fat, there is increased blood vessel density, suggesting neovascularization and rare lymphatic vessels suggestive of limited lymphangiogenesis. This proangiogenic and prolymphangiogenic microenvironment is likely the result of the increased expression of VEGFR-2, VEGF-A, VEGF-C, and VEGF-D. These findings imply that orbital edema in acute TED may be mediated, in part, by both the formation of new, immature blood vessels and the formation of lymphatic capillaries that are functionally incapable of draining interstitial fluid. (C) 2016 by the American Academy of Ophthalmology. C1 [Wong, Lindsay L.; Amarnani, Dhanesh; D'Amore, Patricia A.; Kim, Leo A.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Lee, Nahyoung Grace; Choi, Catherine J.; Freitag, Suzanne K.; D'Amore, Patricia A.; Kim, Leo A.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Lee, Nahyoung Grace; Choi, Catherine J.; Freitag, Suzanne K.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. [Bielenberg, Diane R.] Harvard Med Sch, Childrens Hosp Boston, Dept Surg, Boston, MA USA. RP Kim, LA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Leo_Kim@meei.harvard.edu FU American Thyroid Association (Falls Church, VA); Massachusetts Lions Eye Research Foundation (Belmont, MA); Vascular Biology Program at Boston Children's Hospital (Boston, MA); National Eye Institute, National Institutes of Health, Bethesda, Maryland [EY005318, P30EY003790, EY16335] FX Supported by the American Thyroid Association (Falls Church, VA) (L.A.K.); the Massachusetts Lions Eye Research Foundation (Belmont, MA) (L.A.K.); the Vascular Biology Program at Boston Children's Hospital (Boston, MA) (D.R.B.); and the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant nos.: EY005318 [P.A.D.], P30EY003790, and EY16335 [L.A.K.]). The sponsor or funding organizations had no role in the design or conduct of this research. NR 31 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 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 2016 VL 123 IS 9 BP 2028 EP 2036 DI 10.1016/j.ophtha.2016.05.052 PG 9 WC Ophthalmology SC Ophthalmology GA EE3QE UT WOS:000389508500035 PM 27423310 ER PT J AU Aiken, ARA Borrero, S Callegari, LS Dehlendorf, C AF Aiken, Abigail R. A. Borrero, Sonya Callegari, Lisa S. Dehlendorf, Christine TI Rethinking the Pregnancy Planning Paradigm: Unintended Conceptions or Unrepresentative Concepts? SO PERSPECTIVES ON SEXUAL AND REPRODUCTIVE HEALTH LA English DT Editorial Material ID UNITED-STATES; CONTRACEPTIVE USE; YOUNG-ADULTS; WOMEN; AMBIVALENT; FERTILITY; HAPPINESS; HEALTH; RISK; WANTEDNESS C1 [Aiken, Abigail R. A.] Univ Texas Austin, LBJ Sch Publ Affairs, Austin, TX 78712 USA. [Aiken, Abigail R. A.] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. [Borrero, Sonya] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. [Borrero, Sonya] VA Pittsburgh Healthcare System, VA Ctr Hlth Equity Res & Promot, VA Adv Fellowship Program Womens Hlth, Pittsburgh, PA USA. [Callegari, Lisa S.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Callegari, Lisa S.] Dept Vet Affairs, Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Aiken, ARA (reprint author), Univ Texas Austin, LBJ Sch Publ Affairs, Austin, TX 78712 USA.; Aiken, ARA (reprint author), Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA. EM araa2@utexas.edu FU NICHD NIH HHS [P2C HD047879, R21 HD076327, R24 HD042849]; NIMHD NIH HHS [P60 MD006902] NR 29 TC 2 Z9 2 U1 7 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-6341 EI 1931-2393 J9 PERSPECT SEX REPRO H JI Perspect. Sex Reprod. Health PD SEP PY 2016 VL 48 IS 3 BP 147 EP 151 DI 10.1363/48e10316 PG 5 WC Demography; Family Studies SC Demography; Family Studies GA ED9IK UT WOS:000389183200005 PM 27513444 ER PT J AU Ayata, C AF Ayata, Cenk TI Spreading Depolarization Waves in Injured Brain SO ACTA PHYSIOLOGICA LA English DT Meeting Abstract C1 [Ayata, Cenk] Harvard Med Sch, Massachusetts Gen Hosp, Neurovasc Res Lab, Boston, MA USA. [Ayata, Cenk] Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1748-1708 EI 1748-1716 J9 ACTA PHYSIOL JI Acta Physiol. PD SEP PY 2016 VL 218 SU 709 SI SI MA 2 BP 1 EP 1 PG 1 WC Physiology SC Physiology GA DW3YF UT WOS:000383578300003 ER PT J AU High, FA Bhayani, P Wilson, JM Bult, CJ Donahoe, PK Longoni, M AF High, Frances A. Bhayani, Pooja Wilson, Jay M. Bult, Carol J. Donahoe, Patricia K. Longoni, Mauro TI De Novo Frameshift Mutation in COUP-TFII (NR2F2) in Human Congenital Diaphragmatic Hernia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE COUP-TFII; NR2F2; 15q26; congenital diaphragmatic hernia; atrial septal defect; de novo; trio; pleuroperitoneal folds ID COMPARATIVE GENOMIC HYBRIDIZATION; PRENATAL TREATMENT; GENE-EXPRESSION; CANDIDATE GENES; NITROFEN MODEL; DIFFERENTIATION; REGIONS AB COUP-TFII (NR2F2) is mapped to the 15q26 deletion hotspot associated with the common and highly morbid congenital diaphragmatic hernia (CDH). Conditional homozygous deletions of COUP-TFII in mice result in diaphragmatic defects analogous to the human Bochdalek-type hernia phenotype. Despite evidence from animal models however, mutations in the coding sequence of COUP-TFII have not been reported in patients, prompting the speculation that additional coding or non-coding sequences in the 15q26 locus are necessary for diaphragmatic hernias to develop. In this report, we describe a case of a patient with a heterozygous de novo COUP-TFII frameshift mutation, presenting with CDH and an atrial septal defect. The p.Pro33AlafsTer77 mutation specifically disrupts protein isoform 1 which contains the DNA binding domain. In addition, we review other COUP-TFII sequence variations and deletions that have been described in cases of CDH. We conclude that COUP-TFII mutations can cause diaphragmatic hernias, and should be included in the differential diagnosis of CDH patients, particularly those with comorbid congenital heart defects. (C) 2016 Wiley Periodicals, Inc. C1 [High, Frances A.; Bhayani, Pooja; Donahoe, Patricia K.; Longoni, Mauro] Massachusetts Gen Hosp, Pediat Surg Res Labs, Room CPZN 6-216,185 Cambridge St, Boston, MA 02114 USA. [High, Frances A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [High, Frances A.; Wilson, Jay M.; Donahoe, Patricia K.; Longoni, Mauro] Harvard Med Sch, Boston, MA USA. [High, Frances A.; Wilson, Jay M.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Bult, Carol J.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Donahoe, Patricia K.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Longoni, M (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Room CPZN 6-216,185 Cambridge St, Boston, MA 02114 USA. EM mlongoni@partners.org FU National Institute of Child Health and Human Development (NICHD) [P01 HD068250] FX Grant sponsor: National Institute of Child Health and Human Development (NICHD); Grant number: P01 HD068250. NR 28 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2016 VL 170 IS 9 BP 2457 EP 2461 DI 10.1002/ajmg.a.37830 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA DW4JJ UT WOS:000383608700036 PM 27363585 ER PT J AU Basu, S Phillips, RS Song, ZR Landon, BE Bitton, A AF Basu, Sanjay Phillips, Russell S. Song, Zirui Landon, Bruce E. Bitton, Asaf TI Effects of New Funding Models for Patient-Centered Medical Homes on Primary Care Practice Finances and Services: Results of a Microsimulation Model SO ANNALS OF FAMILY MEDICINE LA English DT Article DE primary health care, models; theoretical; capitation fee; fee-for-service plans; patient-centered care ID EMERGENCY-DEPARTMENT USE; HEALTH-CARE; HOSPITAL ADMISSIONS; COMMUNITY CARE; QUALITY; COST; PILOT; IMPACT; TRANSFORMATION; SATISFACTION AB PURPOSE We assess the financial implications for primary care practices of participating in patient-centered medical home (PCMH) funding initiatives. METHODS We estimated practices' changes in net revenue under 3 PCMH funding initiatives: increased fee-for-service (FFS) payments, traditional FFS with additional per-member-per-month (PMPM) payments, or traditional FFS with PMPM and pay-for-performance (P4P) payments. Net revenue estimates were based on a validated microsimulation model utilizing national practice surveys. Simulated practices reflecting the national range of practice size, location, and patient population were examined under several potential changes in clinical services: investments in patient tracking, communications, and quality improvement; increased support staff; altered visit templates to accommodate longer visits, telephone visits or electronic visits; and extended service delivery hours. RESULTS Under the status quo of traditional FFS payments, clinics operate near their maximum estimated possible net revenue levels, suggesting they respond strongly to existing financial incentives. Practices gained substantial additional net annual revenue per full-time physician under PMPM or PMPM plus P4P payments ($ 113,300 per year, 95% CI, $ 28,500 to $ 198,200) but not under increased FFS payments (-$ 53,500, 95% CI, -$ 69,700 to -$ 37,200), after accounting for costs of meeting PCMH funding requirements. Expanding services beyond minimum required levels decreased net revenue, because traditional FFS revenues decreased. CONCLUSIONS PCMH funding through PMPM payments could substantially improve practice finances but will not offer sufficient financial incentives to expand services beyond minimum requirements for PCMH funding. C1 [Basu, Sanjay] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Basu, Sanjay; Phillips, Russell S.; Song, Zirui; Landon, Bruce E.; Bitton, Asaf] Harvard Med Sch, Ctr Primary Care, Boston, MA USA. [Phillips, Russell S.; Landon, Bruce E.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Landon, Bruce E.; Bitton, Asaf] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [Bitton, Asaf] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Bitton, Asaf] Brigham & Womens Hosp, Ariadne Labs, 75 Francis St, Boston, MA 02115 USA. [Bitton, Asaf] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. RP Basu, S (reprint author), Stanford Univ, Sch Med, Off Bldg,X322,1265 Welch R,Mail Code 5411, Stanford, CA 94305 USA. EM basus@stanford.edu NR 70 TC 2 Z9 2 U1 6 U2 6 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD SEP-OCT PY 2016 VL 14 IS 5 BP 404 EP 414 DI 10.1370/afm.1960 PG 11 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA DW5WP UT WOS:000383718600005 PM 27621156 ER PT J AU Lu, YH Chaturvedula, A Haberer, JE Fossler, MJ Sale, ME Bangsberg, D Baeten, JM Celum, CL Hendrix, CW AF Lu, Yanhui Chaturvedula, Ayyappa Haberer, Jessica E. Fossler, Michael J. Sale, Mark E. Bangsberg, David Baeten, Jared M. Celum, Connie L. Hendrix, Craig W. TI Population Pharmacokinetics of Tenofovir in HIV-1-Uninfected Members of Serodiscordant Couples and Effect of Dose Reporting Methods SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PREEXPOSURE PROPHYLAXIS; INFECTED PATIENTS; HIV PREVENTION; AFRICAN WOMEN; ANRS 12109; MODELS; NONMEM; ATAZANAVIR; STRATEGIES; ADHERENCE AB Antiretroviral preexposure prophylaxis (PrEP) with once-daily dosing of tenofovir and tenofovir-emtricitabine was shown to be effective for preventing HIV-1 infection in individuals who had HIV-1-seropositive partners ( the Partners PrEP Study). We developed a population pharmacokinetic model for tenofovir and investigated the impacts of different dose reporting methods. Dosing information was collected as patient-reported dosing information ( PRDI) from 404 subjects ( corresponding to 1,280 drug concentration records) from the main trial and electronic monitoring-based adherence data collected from 211 subjects ( corresponding to 327 drug concentration records) in an ancillary adherence study. Model development was conducted with NONMEM ( 7.2), using PRDI with a steady-state assumption or using PRDI replaced with electronic monitoring records where available. A two-compartment model with first-order absorption was the best model in both modeling approaches, with the need for an absorption lag time when electronic monitoring-based dosing records were included in the analysis. Age, body weight, and creatinine clearance were significant covariates on clearance, but only creatinine clearance was retained in the final models per stepwise selection. Sex was not a significant covariate on clearance. Tenofovir population pharmacokinetic parameter estimates and the precisions of the parameters from the two final models were comparable with the point estimates of the parameters, differing from 0% to 35%, and bootstrap confidence intervals widely overlapped. These findings indicate that PRDI was sufficient for population pharmacokinetic model development in this study, with a high level of adherence per multiple measures. C1 [Lu, Yanhui; Hendrix, Craig W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Chaturvedula, Ayyappa; Haberer, Jessica E.] Mercer Univ, Pharmaceut Sci, Atlanta, GA 30341 USA. [Haberer, Jessica E.; Bangsberg, David] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Bangsberg, David] Harvard Med Sch, Boston, MA USA. [Fossler, Michael J.] Trevena Inc, Quantitat Sci, King Of Prussia, PA USA. [Sale, Mark E.] Nuventra, Durham, NC USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Med, Seattle, WA USA. [Baeten, Jared M.; Celum, Connie L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chaturvedula, Ayyappa] Univ North Texas, Hlth Sci Ctr, Pharmacotherapy, Ft Worth, TX 76107 USA. RP Chaturvedula, A (reprint author), Mercer Univ, Pharmaceut Sci, Atlanta, GA 30341 USA.; Chaturvedula, A (reprint author), Univ North Texas, Hlth Sci Ctr, Pharmacotherapy, Ft Worth, TX 76107 USA. EM ayyappa.chaturvedula@unthsc.edu RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU Bill & Melinda Gates Foundation [OOP47674]; Massachusetts General Hospital [OOP52516]; Johns Hopkins University Center for AIDS Research [5P30AI094189-04] FX The Partners PrEP Study was funded through a research grant from the Bill & Melinda Gates Foundation (grant OOP47674), and the current analysis was supported by a subaward (grant OOP52516) from the Massachusetts General Hospital to Mercer University and by the Johns Hopkins University Center for AIDS Research (grant 5P30AI094189-04). NR 29 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2016 VL 60 IS 9 BP 5379 EP 5386 DI 10.1128/AAC.00559-16 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ED7OH UT WOS:000389055400033 PM 27353269 ER PT J AU Huang, YY Choi, HJ Kushida, Y Bhayana, B Wang, YG Hamblin, MR AF Huang, Ying-Ying Choi, Hwanjun Kushida, Yu Bhayana, Brijesh Wang, Yuguang Hamblin, Michael R. TI Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PHOTODYNAMIC INACTIVATION; IN-VITRO; SINGLET OXYGEN; BACTERIA; THERAPY; TIO2; MYELOPEROXIDASE; DISINFECTION; IRRADIATION; IODINATION AB Photocatalysis describes the excitation of titanium dioxide nanoparticles (a wide-band gap semiconductor) by UVA light to produce reactive oxygen species (ROS) that can destroy many organic molecules. This photocatalysis process is used for environmental remediation, while antimicrobial photocatalysis can kill many classes of microorganisms and can be used to sterilize water and surfaces and possibly to treat infections. Here we show that addition of the nontoxic inorganic salt potassium iodide to TiO2 (P25) excited by UVA potentiated the killing of Gram-positive bacteria, Gram-negative bacteria, and fungi by up to 6 logs. The microbial killing depended on the concentration of TiO2, the fluence of UVA light, and the concentration of KI (the best effect was at 100 mM). There was formation of long-lived antimicrobial species (probably hypoiodite and iodine) in the reaction mixture (detected by adding bacteria after light), but short-lived antibacterial reactive species (bacteria present during light) produced more killing. Fluorescent probes for ROS (hydroxyl radical and singlet oxygen) were quenched by iodide. Tri-iodide (which has a peak at 350 nm and a blue product with starch) was produced by TiO2-UVA-KI but was much reduced when methicillin- resistant Staphylococcus aureus (MRSA) cells were also present. The model tyrosine substrate N-acetyl tyrosine ethyl ester was iodinated in a light dose-dependent manner. We conclude that UVA-excited TiO2 in the presence of iodide produces reactive iodine intermediates during illumination that kill microbial cells and long-lived oxidized iodine products that kill after light has ended. C1 [Huang, Ying-Ying; Choi, Hwanjun; Kushida, Yu; Bhayana, Brijesh; Wang, Yuguang; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Bhayana, Brijesh; Wang, Yuguang; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Choi, Hwanjun] Korea Adv Inst Sci & Technol, Seoul, South Korea. [Kushida, Yu] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. [Wang, Yuguang] Peking Univ, Ctr Digital Dent, Sch & Hosp Stomatol, Beijing, Peoples R China. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM Hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID) [R01AI050875, R21AI121700]; National Science Foundation (NSF) [EEC-1358296] FX This work, including the efforts of Michael R. Hamblin, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R01AI050875). This work, including the efforts of Michael R. Hamblin, was funded by HHS vertical bar NIH vertical bar National Institute of Allergy and Infectious Diseases (NIAID) (R21AI121700). This work, including the efforts of Hwanjun Choi and Yu Kushida, was funded by National Science Foundation (NSF) (EEC-1358296). NR 40 TC 1 Z9 1 U1 12 U2 12 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 SEP PY 2016 VL 60 IS 9 BP 5445 EP 5453 DI 10.1128/AAC.00980-16 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ED7OH UT WOS:000389055400041 PM 27381399 ER PT J AU Wiederhold, NP Kovanda, L Najvar, LK Bocanegra, R Olivo, M Kirkpatrick, WR Patterson, TF AF Wiederhold, Nathan P. Kovanda, Laura Najvar, Laura K. Bocanegra, Rosie Olivo, Marcos Kirkpatrick, William R. Patterson, Thomas F. TI Isavuconazole Is Effective for the Treatment of Experimental Cryptococcal Meningitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PHARMACODYNAMIC TARGET DETERMINATION; ANTIFUNGAL TRIAZOLE BAL4815; MURINE MODEL; DOSE PHARMACOKINETICS; ASPERGILLUS-FUMIGATUS; HEALTHY-VOLUNTEERS; GATTII; FLUCONAZOLE; NEOFORMANS; MENINGOENCEPHALITIS AB We evaluated the efficacy of isavuconazole against cryptococcal meningitis. Treatment with either oral isavuconazole (120 mg/kg and 240 mg/kg twice a day [BID]) or fluconazole as the positive control significantly improved survival in mice infected intracranially with either Cryptococcus neoformans USC1597 or H99 and significantly reduced brain fungal burdens for both isolates. Concentrations of isavuconazole in plasma and brain tissue also demonstrated that the greatest improvements in survival and fungal burden were associated with elevated exposures. C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kovanda, Laura] Astellas Pharma Global Dev Inc, Northbrook, IL USA. [Najvar, Laura K.; Bocanegra, Rosie; Olivo, Marcos; Kirkpatrick, William R.; Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM wiederholdn@uthscsa.edu FU Astellas Pharma US (Astellas) FX This work, including the efforts of Nathan P. Wiederhold and Thomas F. Patterson, was funded by Astellas Pharma US (Astellas). NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2016 VL 60 IS 9 BP 5600 EP 5603 DI 10.1128/AAC.00229-16 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ED7OH UT WOS:000389055400061 PM 27324761 ER PT J AU Arsiwala, T van Tits, LJ Miranda, M Nussbaum, K Weber, J Stivala, S Beer, JH Greter, M Becher, B Hottiger, MO Mostoslavsky, R Auwerx, J Luscher, TF Matter, CM AF Arsiwala, T. van Tits, L. J. Miranda, M. Nussbaum, K. Weber, J. Stivala, S. Beer, J. H. Greter, M. Becher, B. Hottiger, M. O. Mostoslavsky, R. Auwerx, J. Luscher, T. F. Matter, C. M. TI BONE MARROW-SPECIFIC SIRT6 DELETION INCREASES ATHEROGENESIS BY INCREASING MACROPHAGE SCAVENGER RECEPTOR 1 SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT Congress of the European-Atherosclerosis-Society (EAS) CY MAY 29-JUN 01, 2016 CL Innsbruck, AUSTRIA SP European Atherosclerosis Soc C1 [Arsiwala, T.; van Tits, L. J.; Miranda, M.; Weber, J.; Stivala, S.; Hottiger, M. O.] Univ Zurich, Ctr Mol Cardiol, Zurich, Switzerland. [Nussbaum, K.; Greter, M.; Becher, B.] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland. [Beer, J. H.] Kantonsspital Baden, Innere Med, Baden, Switzerland. [Mostoslavsky, R.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Auwerx, J.] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, Lausanne, Switzerland. [Luscher, T. F.; Matter, C. M.] Univ Zurich Hosp, Univ Heart Ctr, Zurich, Switzerland. NR 0 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 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2016 VL 252 MA EAS16-0895 BP E247 EP E247 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ED6PR UT WOS:000388978400828 ER PT J AU Franck, G Sausen, G Mawson, T Salinas, M Masson, G Cole, A Beltrami-Moreira, M Chatzizisis, Y Tesmenitsky, Y Swartz, E Sukhova, G Swirski, F Nahrendorf, M Aikawa, E Croce, K Libby, P AF Franck, G. Sausen, G. Mawson, T. Salinas, M. Masson, G. Cole, A. Beltrami-Moreira, M. Chatzizisis, Y. Tesmenitsky, Y. Swartz, E. Sukhova, G. Swirski, F. Nahrendorf, M. Aikawa, E. Croce, K. Libby, P. TI FLOW PERTURBATION MEDIATES NEUTROPHIL RECRUITMENT AND POTENTIATES ENDOTHELIAL INJURY VIA TLR2 IN MICE. A NOVEL IN VIVO APPROACH FOR PROBING THE PATHOPHYSIOLOGY OF SUPERFICIAL EROSION SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT Congress of the European-Atherosclerosis-Society (EAS) CY MAY 29-JUN 01, 2016 CL Innsbruck, AUSTRIA SP European Atherosclerosis Soc C1 [Franck, G.; Sausen, G.; Mawson, T.; Cole, A.; Beltrami-Moreira, M.; Chatzizisis, Y.; Tesmenitsky, Y.; Swartz, E.; Sukhova, G.; Croce, K.; Libby, P.] Brigham & Womens Hosp, Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Salinas, M.; Aikawa, E.] Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, 75 Francis St, Boston, MA 02115 USA. [Masson, G.; Swirski, F.; Nahrendorf, M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 0 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 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2016 VL 252 MA EAS16-1027 BP E240 EP E241 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ED6PR UT WOS:000388978400806 ER PT J AU Lindau, A Haerdtner, C Swirski, FK Libby, P Hein, L Bode, C Zirlik, A Hilgendorf, I AF Lindau, A. Haerdtner, C. Swirski, F. K. Libby, P. Hein, L. Bode, C. Zirlik, A. Hilgendorf, I. TI EARLY ATHEROPROTECTION BY SYK INHIBITION FAILS IN ESTABLISHED DISEASE WHEN LOCAL MACROPHAGE PROLIFERATION DOMINATES LESION PROGRESSION SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT Congress of the European-Atherosclerosis-Society (EAS) CY MAY 29-JUN 01, 2016 CL Innsbruck, AUSTRIA SP European Atherosclerosis Soc C1 [Lindau, A.; Haerdtner, C.; Bode, C.; Zirlik, A.; Hilgendorf, I.] Univ Heart Ctr Freiburg, Cardiol & Angiol 1, Freiburg, Germany. [Swirski, F. K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Libby, P.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Hein, L.] Univ Freiburg, Inst Expt & Clin Pharmacol & Toxicol, Freiburg, Germany. NR 0 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 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2016 VL 252 MA EAS16-0170 BP E262 EP E262 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ED6PR UT WOS:000388978400875 ER PT J AU Nikkola, E Ko, A Cantor, RM Muxel, R Matikainen, N Soderlund, S Motazacker, MM Kuivenhoven, JA Boren, J Kronenberg, F Schneider, W Palotie, A Laakso, M Taskinen, MR Pajukanta, P AF Nikkola, E. Ko, A. Cantor, R. M. Muxel, R. Matikainen, N. Soderlund, S. Motazacker, M. M. Kuivenhoven, J. A. Boren, J. Kronenberg, F. Schneider, W. Palotie, A. Laakso, M. Taskinen, M. R. Pajukanta, P. TI INVESTIGATION OF MULTIPLE DYSLIPIDEMIAS IN A LARGE AUSTRIAN PEDIGREE BY GENETIC RISK SCORES AND EXOME SEQUENCING SO ATHEROSCLEROSIS LA English DT Meeting Abstract CT Congress of the European-Atherosclerosis-Society (EAS) CY MAY 29-JUN 01, 2016 CL Innsbruck, AUSTRIA SP European Atherosclerosis Soc C1 [Nikkola, E.; Ko, A.; Cantor, R. M.; Pajukanta, P.] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA. [Ko, A.; Pajukanta, P.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Muxel, R.] Gen Practice Ctr, Lech Am Arlberg, Austria. [Matikainen, N.; Soderlund, S.; Taskinen, M. R.] Helsinki Univ Hosp, Helsinki, Finland. [Matikainen, N.; Soderlund, S.; Taskinen, M. R.] Univ Helsinki, Heart & Lung Ctr, Res Programs Unit Diabet & Obes, Helsinki, Finland. [Matikainen, N.] Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland. [Motazacker, M. M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Kuivenhoven, J. A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Boren, J.] Univ Gothenburg, Gothenburg, Sweden. [Boren, J.] Sahlgrens Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden. [Kronenberg, F.] Med Univ Innsbruck, Div Genet Epidemiol, Innsbruck, Austria. [Schneider, W.] Med Univ Vienna, Dept Med Biochem, Vienna, Austria. [Palotie, A.] Univ Helsinki, Inst Mol Med, Helsinki, Finland. [Palotie, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palotie, A.] MIT & Harvard Broad Inst, Cambridge, MA USA. [Laakso, M.] Univ Eastern Finland, Kuopio, Finland. [Laakso, M.] Kuopio Univ Hosp, Dept Med, Kuopio, Finland. [Pajukanta, P.] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA USA. NR 0 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 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2016 VL 252 MA EAS16-0815 BP E253 EP E253 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ED6PR UT WOS:000388978400846 ER PT J AU Spetz, J Dudley, N Trupin, L Rogers, M Meier, DE Dumanovsky, T AF Spetz, Joanne Dudley, Nancy Trupin, Laura Rogers, Maggie Meier, Diane E. Dumanovsky, Tamara TI Few Hospital Palliative Care Programs Meet National Staffing Recommendations SO HEALTH AFFAIRS LA English DT Article ID CANCER-PATIENTS; US HOSPITALS; CONSULTATION; COST; EDUCATION; ACCESS; TEAMS; CONFIDENCE; RESILIENCY; CLINICIAN AB The predominant model for palliative care delivery, outside of hospice care, is the hospital-based consultative team. Although a majority of US hospitals offer palliative care services, there has been little research on the staffing of their program teams and whether those teams meet national guidelines, such as the Joint Commission's standard of including at least one physician, an advanced practice or other registered nurse, a social worker, and a chaplain. Data from the 2012-13 annual surveys of the National Palliative Care Registry indicate that only 25 percent of participating programs met that standard based on funded positions, and even when unfunded positions were included, only 39 percent of programs met the standard. Larger palliative care programs were more likely than smaller ones to include a funded physician position, while smaller programs were more reliant upon advanced practice and registered nurses. To meet current and future palliative care needs, expanded and enhanced education, as well as supportive financing mechanisms for consultations, are needed. C1 [Spetz, Joanne] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, Econ, San Francisco, CA 94143 USA. [Spetz, Joanne] Univ Calif San Francisco, Healthforce Ctr, San Francisco, CA 94143 USA. [Dudley, Nancy] UCSF Dept Geriatr, San Francisco, CA USA. [Dudley, Nancy] San Francisco VA Med Ctr, San Francisco, CA USA. [Trupin, Laura] UCSF, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Rogers, Maggie; Meier, Diane E.] Ctr Adv Palliat Care, New York, NY USA. [Meier, Diane E.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Dumanovsky, Tamara] Ctr Adv Palliat Care, Res & Analyt, New York, NY USA. RP Spetz, J (reprint author), Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, Econ, San Francisco, CA 94143 USA.; Spetz, J (reprint author), Univ Calif San Francisco, Healthforce Ctr, San Francisco, CA 94143 USA. EM joanne.spetz@ucsf.edu FU Health Resources and Services Administration (HRSA) of the Department of Health and Human Services (HHS) under Cooperative Agreement for a Regional Center for Health Workforce Studies [U81HP26494]; Center to Advance Palliative Care; National Palliative Care Research Center; Patty and Jay Baker National Palliative Care Center FX This study was supported by the Health Resources and Services Administration (HRSA) of the Department of Health and Human Services (HHS) under the Cooperative Agreement for a Regional Center for Health Workforce Studies (Grant No. U81HP26494). The information in or content and conclusions of this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, HRSA, HHS, or the US government. The National Palliative Care Registry is supported by the Center to Advance Palliative Care, the National Palliative Care Research Center, and the Patty and Jay Baker National Palliative Care Center. R. Sean Morrison provided helpful suggestions in the interpretation of the National Registry data and editorial suggestions. NR 35 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2016 VL 35 IS 9 BP 1690 EP 1697 DI 10.1377/hlthaff.2016.0113 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA EB1LT UT WOS:000387114300021 PM 27605652 ER PT J AU Marshall, A Li, A Drucker, A Dzik, W AF Marshall, Ariela Li, Ang Drucker, Adrienne Dzik, Walter TI Aminocaproic acid use in hospitalized patients with hematological malignancy: a case series SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE aminocaproic acid; antifibrinolytics; hematological malignancy; thrombocytopenia ID ACUTE PROMYELOCYTIC LEUKEMIA; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ACUTE MYELOID-LEUKEMIA; TRANEXAMIC ACID; REDUCE TRANSFUSION; BLOOD-LOSS; SURGERY; HEMORRHAGE; THERAPY AB The antifibrinolytic aminocaproic acid is widely used in surgical settings to prevent blood loss and decrease transfusion requirements, and small observational studies have suggested that aminocaproic acid may be useful in the setting of malignancy-related bleeding. At our institution, aminocaproic acid is sometimes prescribed to patients with hematological malignancy who experience refractory thrombocytopenia with or without bleeding. We performed a 5-year retrospective review of 54 adult patients with 13 types of hematological malignancy who received aminocaproic acid at our institution. Indications for use included 31 (57.4%) for refractory thrombocytopenia with bleeding, 16 (29.6%) for refractory thrombocytopenia without bleeding, and 7 (13%) for bleeding alone. Patients received both oral and intravenous formulations. Administered doses ranged broadly and median duration of use was 6 days. Three patients (5.7%) developed deep venous thrombosis but none of the thrombotic events were clearly related to administration of aminocaproic acid. We conclude that aminocaproic acid may be a relatively safe and cost-effective adjunct treatment in the setting of bleeding related to the diagnosis and treatment of hematological malignancy. Prospective trials as well as formalized protocols for the use of aminocaproic acid may be indicated. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Marshall, Ariela; Li, Ang; Drucker, Adrienne; Dzik, Walter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marshall, Ariela] Dana Farber Canc Inst, 450 Brookline Ave,Smith 353, Boston, MA 02215 USA. RP Marshall, A (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Smith 353, Boston, MA 02215 USA. EM ariela_marshall@dfci.harvard.edu NR 32 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0278-0232 EI 1099-1069 J9 HEMATOL ONCOL JI Hematol. Oncol. PD SEP PY 2016 VL 34 IS 3 BP 147 EP 153 DI 10.1002/hon.2189 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA ED3CS UT WOS:000388727500004 PM 25641349 ER PT J AU Kroenke, CH Neugebauer, R Meyerhardt, J Prado, CM Weltzien, E Kwan, ML Xiao, JJ Caan, BJ AF Kroenke, Candyce H. Neugebauer, Romain Meyerhardt, Jeffrey Prado, Carla M. Weltzien, Erin Kwan, Marilyn L. Xiao, Jingjie Caan, Bette J. TI Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams SO JAMA ONCOLOGY LA English DT Article ID WOMEN UNITED-STATES; OBESITY PARADOX; COLON-CANCER; HEART-FAILURE; WEIGHT CHANGE; ADJUVANT CHEMOTHERAPY; NATIONAL-INSTITUTES; PHYSICAL-ACTIVITY; SELECTION BIAS; RECTAL-CANCER AB IMPORTANCE Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and collider bias have prevented the ability to draw definitive conclusions. OBJECTIVE To evaluate the association of BMI at the time of, and following, colorectal cancer (CRC) diagnosis with mortality in a complete population using causal diagrams. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study with prospectively collected data included a cohort of 3408 men and women, ages 18 to 80 years, from the Kaiser Permanente Northern California population, who were diagnosed with stage I to III CRC between 2006 and 2011 and who also had surgery. EXPOSURES Body mass index at diagnosis and 15 months following diagnosis. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality compared with normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and prediagnosis BMI. RESULTS This study investigated a cohort of 3408 men and women ages 18 to 80 years diagnosed with stage I to III CRC between 2006 and 2011 who also had surgery. At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with patients who were underweight (BMI <18.5; HR, 2.65; 95% CI, 1.63-4.31) and patients who were class II or III obese (BMI >= 35; HR, 1.33; 95% CI, 0.89-1.98) exhibiting elevated mortality risks, compared with patients who were low-normal weight (BMI 18.5 to <23). In contrast, patients who were high-normal weight (BMI 23 to <25; HR, 0.77; 95% CI, 0.56-1.06), low-overweight (BMI 25 to <28; HR, 0.75; 95% CI, 0.55-1.04), and high-overweight (BMI 28 to <30; HR, 0.52; 95% CI, 0.35-0.77) had lower mortality risks, and patients who were class I obese (BMI 30 to <35) showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants with lowest mortality at a BMI of 28. Associations with CRC-specific mortality were similar. Associations of postdiagnosis BMI and mortality were also similar, but patients who were class I obese had significantly lower all-cause and cancer-specific mortality risks. CONCLUSIONS AND RELEVANCE In this study, body mass index at the time of diagnosis and following diagnosis of CRC was associated with mortality risk. Though evidence shows that exercise in patients with cancer should be encouraged, findings suggest that recommendations for weight loss in the immediate postdiagnosis period among patients with CRC who are overweight may be unwarranted. C1 [Kroenke, Candyce H.; Neugebauer, Romain; Weltzien, Erin; Kwan, Marilyn L.; Caan, Bette J.] Kaiser Permanente, Div Res, 2000 Broadway,Fifth Floor, Oakland, CA 94612 USA. [Meyerhardt, Jeffrey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prado, Carla M.; Xiao, Jingjie] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB, Canada. RP Kroenke, CH (reprint author), Kaiser Permanente, Div Res, 2000 Broadway,Fifth Floor, Oakland, CA 94612 USA. EM Candyce.h.kroenke@kp.org FU National Cancer Institute at the National Institutes of Health [5R01CA175011] FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant No. 5R01CA175011). NR 55 TC 4 Z9 4 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1137 EP 1145 DI 10.1001/jamaoncol.2016.0732 PG 9 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200008 PM 27196302 ER PT J AU Keum, N Bao, Y Smith-Warner, SA Orav, J Wu, K Fuchs, CS Giovannucci, EL AF Keum, Nana Bao, Ying Smith-Warner, Stephanie A. Orav, John Wu, Kana Fuchs, Charles S. Giovannucci, Edward L. TI Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk SO JAMA ONCOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; EXPRESSION; DISEASE; MEN; CYCLOOXYGENASE-2; REPRODUCIBILITY; METAANALYSIS; PREVENTION; EXERCISE AB IMPORTANCE Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for >= 63.0 vs <= 8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for >= 63.0 vs <= 8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation. C1 [Keum, Nana; Smith-Warner, Stephanie A.; Wu, Kana; Giovannucci, Edward L.] Harvard TH Chan Sch of Publ Hlth, Dept Nutr, Bldg 2,Third Floor,665 Huntington Ave, Boston, MA 02115 USA. [Bao, Ying; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Bao, Ying; Giovannucci, Edward L.] Harvard Med Sch, Boston, MA USA. [Smith-Warner, Stephanie A.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Orav, John] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Orav, John; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Med Sch, Dept Med, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP Keum, N (reprint author), Harvard TH Chan Sch of Publ Hlth, Dept Nutr, Bldg 2,Third Floor,665 Huntington Ave, Boston, MA 02115 USA. EM nak212@mail.harvard.edu FU National Institutes of Health (NIH) [UM1 CA167552]; NIH [U54 CA155626, P30 DK046200, KL2 TR001100] FX This work was supported by National Institutes of Health (NIH) grant UM1 CA167552. Dr Bao is funded by NIH grants U54 CA155626, P30 DK046200, and KL2 TR001100. NR 34 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1146 EP 1153 DI 10.1001/jamaoncol.2016.0740 PG 8 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200009 PM 27196375 ER PT J AU Song, MY Giovannucci, E AF Song, Mingyang Giovannucci, Edward TI Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States SO JAMA ONCOLOGY LA English DT Article ID CANCER-RISK ROLE; ALCOHOL-CONSUMPTION; PHYSICAL-ACTIVITY; BREAST-CANCER; DISEASE; HEALTH; WOMEN; MEN; QUESTIONNAIRE; OBESITY AB IMPORTANCE Lifestyle factors are important for cancer development. However, a recent study has been interpreted to suggest that random mutations during stem cell divisions are the major contributor to human cancer. OBJECTIVE To estimate the proportion of cases and deaths of carcinoma (all cancers except skin, brain, lymphatic, hematologic, and nonfatal prostate malignancies) among whites in the United States that can be potentially prevented by lifestyle modification. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study analyzes cancer and lifestyle data from the Nurses' Health Study, the Health Professionals Follow-up Study, and US national cancer statistics to evaluate associations between lifestyle and cancer incidence and mortality. EXPOSURES A healthy lifestyle pattern was defined as never or past smoking (pack-years <5), no or moderate alcohol drinking (<= 1 drink/d for women, <= 2 drinks/d for men), BMI of at least 18.5 but lower than 27.5, and weekly aerobic physical activity of at least 75 vigorous-intensity or 150 moderate-intensity minutes. Participants meeting all 4 of these criteria made up the low-risk group; all others, the high-risk group. MAIN OUTCOMES AND MEASURES We calculated the population-attributable risk (PAR) by comparing incidence and mortality of total and major individual carcinomas between the low- and high-risk groups. We further assessed the PAR at the national scale by comparing the low-risk group with the US population. RESULTS A total of 89 571 women and 46 339 men from 2 cohorts were included in the study: 16 531 women and 11 731 men had a healthy lifestyle pattern (low-risk group), and the remaining 73 040 women and 34 608 men made up the high-risk group. Within the 2 cohorts, the PARs for incidence and mortality of total carcinoma were 25% and 48% in women, and 33% and 44% in men, respectively. For individual cancers, the respective PARs in women and men were 82% and 78% for lung, 29% and 20% for colon and rectum, 30% and 29% for pancreas, and 36% and 44% for bladder. Similar estimates were obtained for mortality. The PARs were 4% and 12% for breast cancer incidence and mortality, and 21% for fatal prostate cancer. Substantially higher PARs were obtained when the low-risk group was compared with the US population. For example, the PARs in women and men were 41% and 63% for incidence of total carcinoma, and 60% and 59% for colorectal cancer, respectively. CONCLUSIONS AND RELEVANCE A substantial cancer burden may be prevented through lifestyle modification. Primary prevention should remain a priority for cancer control. C1 [Song, Mingyang] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Song, Mingyang] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang] Harvard Med Sch, Boston, MA USA. [Song, Mingyang; Giovannucci, Edward] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Song, Mingyang; Giovannucci, Edward] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Giovannucci, Edward] Harvard Med Sch, Dept Med, Channing Div Network Med, Boston, MA USA. RP Song, MY (reprint author), Bartlett Hall Extens,55 Fruit St,Room 906, Boston, MA 02114 USA. EM msong2@mgh.harvard.edu FU National Institutes of Health [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552] FX This work was supported by National Institutes of Health grants P01 CA87969 (Giovannucci), UM1 CA186107, P01 CA55075 (Giovannucci) and UM1 CA167552. NR 45 TC 11 Z9 11 U1 5 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1154 EP 1161 DI 10.1001/jamaoncol.2016.0843 PG 8 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200010 PM 27196525 ER PT J AU Song, MY Nishihara, R Cao, Y Chun, E Qian, ZR Mima, K Inamura, K Masugi, Y Nowak, JA Nosho, K Wu, KN Wang, ML Giovannucci, E Garrett, WS Fuchs, CS Ogino, S Chan, AT AF Song, Mingyang Nishihara, Reiko Cao, Yin Chun, Eunyoung Qian, Zhi Rong Mima, Kosuke Inamura, Kentaro Masugi, Yohei Nowak, Jonathan A. Nosho, Katsuhiko Wu, Kana Wang, Molin Giovannucci, Edward Garrett, Wendy S. Fuchs, Charles S. Ogino, Shuji Chan, Andrew T. TI Marine omega-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells SO JAMA ONCOLOGY LA English DT Article ID MICROSATELLITE INSTABILITY; COLON-CANCER; DIETARY-INTAKE; IMMUNE MICROENVIRONMENT; WOMEN; MEN; FISH; OMEGA-3-FATTY-ACIDS; INFLAMMATION; CONSUMPTION AB IMPORTANCE Marine omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine.-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive. OBJECTIVE To test the hypothesis that marine omega-3 PUFA intakemay be associated with lower risk of CRC subsets characterized by immune infiltrate. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort studywas conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). EXPOSURES Intake of marine omega-3 PUFAs. MAIN OUTCOMES AND MEASURES Incidence of CRC characterized by CD3(+), CD8(+), CD45RO (PTPRC)(+), or FOXP3(+) T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. RESULTS Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine omega-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine omega-3 PUFAs intake with CRC risk differed according to FOXP3(+) T-cell infiltration: compared with intake of less than 0.15 g/d of marine omega-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P <.001 for trend) for FOXP3(+) T-cell-high tumors. In contrast, the HR for FOXP3(+) T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P =.77 for trend; P =.01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3(+), CD8(+), or CD45RO(+) cell density (P >=.34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, >= 64% vs 38%) when preincubated with docosahexaenoic acid at 50 mu M, 100 mu M, and 200 mu M concentrations than without docosahexaenoic acid (P <.001 for all comparisons). CONCLUSIONS AND RELEVANCE High marine omega-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3(+) T-cell density, suggesting a potential role of omega-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells. C1 [Song, Mingyang; Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Harvard Med Sch, Clin & Translat Epidemiol Unit, Boston, MA USA. [Song, Mingyang; Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA. [Song, Mingyang; Nishihara, Reiko; Cao, Yin; Wu, Kana; Giovannucci, Edward] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Nishihara, Reiko; Qian, Zhi Rong; Mima, Kosuke; Masugi, Yohei; Garrett, Wendy S.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Harvard Med Sch, Dept Med Oncol, Boston, MA USA. [Nishihara, Reiko; Wang, Molin; Giovannucci, Edward; Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Nishihara, Reiko; Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Chun, Eunyoung; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA. [Chun, Eunyoung; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA. [Inamura, Kentaro] Inst Canc Res, Japanese Fdn Canc Res, Tokyo, Japan. [Nowak, Jonathan A.; Ogino, Shuji] Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA USA. [Nosho, Katsuhiko] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Giovannucci, Edward; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA USA. [Garrett, Wendy S.; Chan, Andrew T.] Broad Inst Massachusetts, Inst Technol & Harvard, Cambridge, England. 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 [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, K07 CA190673, P50 CA127003, R01 CA151993, R35 CA197735, K24 DK098311, R01 CA137178]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber Cancer Institute; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Uehara Memorial Foundation; Japanese Society for the Promotion of Science; Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research FX This work was supported by National Institutes of Health grants P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, K07 CA190673 (Nishihara), P50 CA127003 (Fuchs), R01 CA151993 (Ogino), R35 CA197735 (Ogino), K24 DK098311 (Chan), and R01 CA137178 (Chan); and by grants from The Paula and Russell Agrusa Fund for Colorectal Cancer Research, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. Dr Mima is supported by a fellowship grant from Uehara Memorial Foundation and a grant from Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japanese Society for the Promotion of Science. Dr Masugi is supported by a fellowship grant of the Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research. NR 51 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1197 EP 1206 DI 10.1001/jamaoncol.2016.0605 PG 10 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200017 PM 27148825 ER PT J AU Sacher, AG Gandhi, L AF Sacher, Adrian G. Gandhi, Leena TI Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer A Review SO JAMA ONCOLOGY LA English DT Review ID DEATH-LIGAND 1; PD-L1 EXPRESSION; CTLA-4 BLOCKADE; NIVOLUMAB; MELANOMA; MUTATIONS; DOCETAXEL; ANTIBODY; SAFETY AB IMPORTANCE The development of programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) checkpoint inhibitors has changed the landscape of non-small-cell lung cancer (NSCLC) therapy, with 2 approvals from the US Food and Drug Administration of PD-1 inhibitors for second-line therapy. However, the rational use of these agents has been limited by the lack of a definitive predictive biomarker. OBSERVATIONS Tumor PD-L1 expression is associated with an increased likelihood of NSCLC response to these agents, although responses can still occur at a low rate in PD-L1-negative tumors. The use of PD-L1 as a predictive biomarker for use of PD-1/PD-L1 inhibitors is limited by the multitude of PD-L1 antibodies, assays, scoring systems, and thresholds for positivity currently used. Alternative biomarkers such as tumor neoantigens identified through whole-exome sequencing and clinical parameters (eg, smoking or oncogene driver status) may also have predictive value. Biomarkers that can direct the rational use of PD-1/PD-L1 checkpoint inhibitors are crucial given the risk of life-threatening immune-related complications associated with these therapies and the reality that most patients still do not benefit from their use. CONCLUSIONS AND RELEVANCE The refinement of existing biomarkers and identification of novel predictive biomarkers will be key to ensuring the effective and safe use of these agents. Since most patients still do not benefit from these agents, it is critical to continue to work to define the select patient population who will derive durable benefit from PD-1/PD-L1 inhibition and identify markers that could have predictive value for combination therapies that could expand the population who benefit. C1 [Sacher, Adrian G.] Columbia Univ, Med Ctr, New York Presbyterian, New York, NY USA. [Gandhi, Leena] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Gandhi, Leena] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA USA. RP Gandhi, L (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Leena_Gandhi@dfci.harvard.edu FU International Association for the Study of Lung Cancer; Canadian Institutes of Health Research; Alice and Steve Cutler Fund for Young Investigators FX This research was supported in part by the International Association for the Study of Lung Cancer and the Canadian Institutes of Health Research (Dr Sacher) and the Alice and Steve Cutler Fund for Young Investigators (Dr Gandhi). NR 40 TC 2 Z9 2 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1217 EP 1222 DI 10.1001/jamaoncol.2016.0639 PG 6 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200019 PM 27310809 ER PT J AU Redig, AJ Costa, DB Taibi, M Boucher, D Johnson, BE Janne, PA Jackman, DM AF Redig, Amanda J. Costa, Daniel B. Taibi, Myriam Boucher, David Johnson, Bruce E. Janne, Pasi A. Jackman, David M. TI Prospective Study of Repeated Biopsy Feasibility and Acquired Resistance at Disease Progression in Patients With Advanced EGFR Mutant Lung Cancer Treated With Erlotinib in a Phase 2 Trial SO JAMA ONCOLOGY LA English DT Letter C1 [Redig, Amanda J.; Taibi, Myriam; Boucher, David; Johnson, Bruce E.; Janne, Pasi A.; Jackman, David M.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,LC-4116, Boston, MA 02215 USA. [Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Redig, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,LC-4116, Boston, MA 02215 USA. EM aredig@partners.org NR 6 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1240 EP 1242 DI 10.1001/jamaoncol.2016.1304 PG 4 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200023 PM 27387964 ER PT J AU Song, MY Giovannucci, E AF Song, Mingyang Giovannucci, Edward TI Self-responsibility for Our Good Health Reply SO JAMA ONCOLOGY LA English DT Letter ID COST-EFFECTIVENESS C1 [Song, Mingyang] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Song, Mingyang] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang] Harvard Med Sch, Boston, MA USA. [Song, Mingyang; Giovannucci, Edward] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Song, Mingyang; Giovannucci, Edward] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Giovannucci, Edward] Harvard Med Sch, Channing Div Network Med, Dept Med, Boston, MA USA. RP Song, MY (reprint author), Bartlett Bldg,55 Fruit St,Rm 906, Boston, MA 02114 USA. EM msong2@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD SEP PY 2016 VL 2 IS 9 BP 1242 EP 1243 DI 10.1001/jamaoncol.2016.3074 PG 3 WC Oncology SC Oncology GA DW5RS UT WOS:000383705200025 PM 27540640 ER PT J AU Clary-Muronda, V Pope, C AF Clary-Muronda, Valerie Pope, Charlene TI Integrative Review of Instruments to Measure Team Performance During Neonatal Resuscitation Simulations in the Birthing Room SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE birthing room; interprofessional; measurement; neonatal; resuscitation; simulation; social ecological model ID IN-SITU SIMULATION; PATIENT SAFETY; HEALTH-CARE; BEHAVIOR; SKILLS; COLLABORATION; COMMUNICATION; SATISFACTION; READINESS; EDUCATION AB Objective: To identify instruments appropriate to measure interprofessional team performance in neonatal resuscitation (NR), describe the validity and reliability of extant NR instruments, and determine instruments for use in interprofessional birthing room NR simulations. Data Sources: The Cumulative Index to Nursing and Allied Health Literature, Ovid MEDLINE, Proquest, ScienceDirect, PubMed, and Scopus databases were searched. Study Selection: We used inclusion and exclusion criteria and screened 641 abstracts from January 2000 through December 2014 for relevance to the research question. We reviewed 78 full-text primary research publications in English and excluded 37 publications not specific to pediatrics or neonatology. After in-depth review of the 41 studies that remained, we excluded additional studies if they did not have an interprofessional focus, include psychometric information, or include a measurement instrument. Ten publications met the inclusion criteria. Data Extraction and Synthesis: Studies were reviewed, categorized, and scored to identify instruments to measure interprofessional team performance in simulations of birthing room NR. A social ecological model was used as a guide framework to identify multiple influencing factors at various levels that affect team performance. Ten instruments with documentation of validity and reliability for technical competence and team processes in interprofessional birthing room NR teams were identified. Conclusion: Extant instruments rarely address the multiple factors that may impede interprofessional team performance in birthing room NR. It is necessary for researchers to engage in rigorous psychometric testing of measurement instruments to ensure their validity and reliability for interprofessional NR teams and consider tests or updates (if necessary) of extant instruments rather than the development of new instruments. C1 [Clary-Muronda, Valerie] Thomas Jefferson Univ, Coll Nursing, 130 S 9th St,Ste 762,Edison Bldg, Philadelphia, PA 19107 USA. [Clary-Muronda, Valerie; Pope, Charlene] Med Univ South Carolina, Coll Nursing, Charleston, SC USA. [Pope, Charlene] Ralph H Johnson VA Med Ctr, Res, Charleston, SC USA. RP Clary-Muronda, V (reprint author), Thomas Jefferson Univ, Coll Nursing, 130 S 9th St,Ste 762,Edison Bldg, Philadelphia, PA 19107 USA. EM vclarymuronda@gmail.com NR 50 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 0884-2175 EI 1552-6909 J9 JOGNN-J OBST GYN NEO JI JOGNN PD SEP-OCT PY 2016 VL 45 IS 5 BP 684 EP 698 DI 10.1016/j.jogn.2016.04.007 PG 15 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA ED4TN UT WOS:000388844600015 PM 27470178 ER PT J AU Sridhar, P Fisichella, PM AF Sridhar, Praveen Fisichella, P. Marco TI Bowel Ischemia and Portal Venous Gas: What to Do? SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Article AB The etiology of pneumatosis and portal venous gas in ischemic colitis is debated, but one theorized cause is transmural ischemia and subsequent bacterial translocation. Traditionally though as a surgical emergency, today not all patients with pneumatosis and portal venous gas need an operation. We have reviewed recent published algorithms and applied them to our practice. C1 [Sridhar, Praveen] Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02118 USA. [Fisichella, P. Marco] Harvard Med Sch, Boston VA Healthcare Syst, Boston, MA USA. RP Sridhar, P (reprint author), Harvard Med Sch, Boston VA Healthcare Syst, Brigham & Womens Hosp, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 5 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 1092-6429 EI 1557-9034 J9 J LAPAROENDOSC ADV S JI J. Laparoendosc. Adv. Surg. Tech. PD SEP PY 2016 VL 26 IS 9 BP 713 EP 714 DI 10.1089/lap.2016.0171 PG 2 WC Surgery SC Surgery GA DW3WG UT WOS:000383573200009 PM 27244100 ER PT J AU Addison, D Farhad, H Shah, RV Mayrhofer, T Abbasi, SA John, RM Michaud, GF Jerosch-Herold, M Hoffmann, U Stevenson, WG Kwong, RY Neilan, TG AF Addison, Daniel Farhad, Hoshang Shah, Ravi V. Mayrhofer, Thomas Abbasi, Siddique A. John, Roy M. Michaud, Gregory F. Jerosch-Herold, Michael Hoffmann, Udo Stevenson, William G. Kwong, Raymond Y. Neilan, Tomas G. TI Effect of Late Gadolinium Enhancement on the Recovery of Left Ventricular Systolic Function After Pulmonary Vein Isolation SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; cardiac dysfunction; cardiovascular magnetic resonance imaging; heart failure; late gadolinium enhancement ID CARDIAC MAGNETIC-RESONANCE; CONGESTIVE-HEART-FAILURE; TACHYCARDIA-INDUCED CARDIOMYOPATHY; IDIOPATHIC DILATED CARDIOMYOPATHY; PERSISTENT ATRIAL-FIBRILLATION; TERM-FOLLOW-UP; CATHETER ABLATION; MYOCARDIAL SCAR; PROGNOSTIC-SIGNIFICANCE; DYSFUNCTION AB Background-The factors that predict recovery of left ventricular (LV) systolic dysfunction among patients with atrial fibrillation (AF) are not completely understood. Late gadolinium enhancement (LGE) of the LV has been reported among patients with AF, and we aimed to test whether the presence LGE was associated with subsequent recovery of LV systolic function among patients with AF and LV dysfunction. Methods and Results-From a registry of 720 consecutive patients undergoing a cardiac magnetic resonance study prior to pulmonary vein isolation (PVI), patients with LV systolic dysfunction (ejection fraction [EF] <50%) were identified. The primary outcome was recovery of LVEF defined as an EF >50%; a secondary outcome was a combined outcome of subsequent heart failure (HF), admission, and death. Of 720 patients, 172 (24%) had an LVEF of <50% prior to PVI. The mean LVEF pre-PVI was 41 +/- 6% (median 43%, range 20% to 49%). Forty-three patients (25%) had LGE (25 [58%] ischemic), and the extent of LGE was 7.5 +/- 4% (2% to 19%). During follow-up (mean 42 months), 91 patients (53%) had recovery of LVEF, 68 (40%) had early recurrence of AF, 65 (38%) had late AF, 18 (5%) were admitted for HF, and 23 died (13%). Factors associated with nonrecovery of LVEF were older age, history of myocardial infarction, early AF recurrence, late AF recurrence, and LGE. In a multivariable model, the presence of LGE and any recurrence of AF had the strongest association with persistence of LV dysfunction. Additionally, all patients without recurrence of AF and LGE had normalization of LVEF, and recovery of LVEF was associated with reduced HF admissions and death. Conclusions-In patients with AF and LV dysfunction undergoing PVI, the absence of LGE and AF recurrence are predictors of LVEF recovery and LVEF recovery in AF with associated reduction in subsequent death and heart failure. C1 [Addison, Daniel; Mayrhofer, Thomas; Hoffmann, Udo; Neilan, Tomas G.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Radiol, Boston, MA 02114 USA. [Farhad, Hoshang; Abbasi, Siddique A.; John, Roy M.; Michaud, Gregory F.; Stevenson, William G.; Kwong, Raymond Y.] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA. [Farhad, Hoshang; Abbasi, Siddique A.; John, Roy M.; Michaud, Gregory F.; Stevenson, William G.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Shah, Ravi V.; Neilan, Tomas G.] Harvard Med Sch, Div Cardiol, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Neilan, TG (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Div Cardiol,Dept Med, 165 Cambridge St, Boston, MA 02114 USA. EM tneilan@mgh.harvard.edu FU American Heart Association [12FTF12060588]; National Institutes of Health [RO1HL090634, RO1HL091157]; Swiss Society of Hypertension/AstraZeneca FX Dr Neilan is supported by an American Heart Association Fellow to Faculty Grant (12FTF12060588). Dr Jerosch-Herold and Dr Kwong were supported by research grants from the National Institutes of Health (RO1HL090634, RO1HL091157, respectively). Dr Farhad received the Swiss Society of Hypertension/AstraZeneca 2013 Scholarship. NR 35 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD SEP PY 2016 VL 5 IS 9 AR e003570 DI 10.1161/JAHA.116.003570 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EA6DX UT WOS:000386716900024 ER PT J AU Butt, AA Yan, P Shaikh, OS Chung, RT Sherman, KE AF Butt, Adeel A. Yan, Peng Shaikh, Obaid S. Chung, Raymond T. Sherman, Kenneth E. TI Treatment adherence and virological response rates in hepatitis C virus infected persons treated with sofosbuvir-based regimens: results from ERCHIVES SO LIVER INTERNATIONAL LA English DT Article DE adherence; directly acting antiviral agents; ERCHIVES; HCV; sofosbuvir ID HIV/HCV-COINFECTED PATIENTS; TREATMENT-NAIVE PATIENTS; PEGYLATED INTERFERON; PHASE-2 TRIAL; HCV TREATMENT; BOCEPREVIR; TELAPREVIR; RIBAVIRIN; SURVIVAL; THERAPY AB Background & Aims: Role of non-adherence upon virological success with newer oral regimens is unknown. We sought to determine the impact of treatment adherence upon virological outcomes in hepatitis C virus (HCV) infected persons on sofosbuvir (SOF)-based regimens, using pharmacy prescription data as a measure of adherence. Methods: We analysed HCV infected persons in Electronically Retrieved Cohort of HCV Infected Veterans, who were initiated on SOF-based regimens, excluding those with human immunodeficiency virus, positive hepatitis-B surface antigen, hepatocellular carcinoma and missing HCV RNA. Results: The final dataset included following regimens: SOF+simeprevir (SIM) (n = 1050), SOF+ledipasvir (LDV) (n = 974), SOF+ribavirin (RBV) (n = 663, genotype 2 or 3), and SOF+pegylated interferon (PEG)+RBV (n = 519, genotype 1 or 4). Those treated with a SOF-based regimen were older and more likely to have cirrhosis, diabetes, chronic kidney disease, higher HCV RNA levels, higher body mass index, compared with 1652 controls receiving a boceprevir-based (BOC) regimen. Sustained virological response (SVR12) rates for the SOF+SIM and SOF+LDV groups did not decline significantly even when as low as 50% of the full course was prescribed (except SOF+LDV, 90-99% prescriptions had SVR12 of 84.6%; n = 13). SOF+RBV for genotype 2/3 who received 50-80% of the prescriptions, 23/34 (67.6%) achieved SVR12. For persons with genotype 1/4 infection treated with SOF+PEG+RBV, no declines in SVR12 were seen with lower rates of prescriptions (40/43, or 93% SVR12 rate). Conclusions: Sofosbuvir-based treatment regimens are highly effective in achieving SVR12. This efficacy is not significantly affected when treated persons receive less than a full prescribed course of treatment. C1 [Butt, Adeel A.; Yan, Peng; Shaikh, Obaid S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Hamad Healthcare Qual Inst, Doha, Qatar. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. [Butt, Adeel A.] Weill Cornell Med Coll, Doha, Qatar. [Butt, Adeel A.] Weill Cornell Med Coll, New York, NY USA. [Shaikh, Obaid S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Med Sch, Boston, MA USA. [Sherman, Kenneth E.] Univ Cincinnati, Coll Med, UC Hlth, Cincinnati, OH USA. RP Butt, AA (reprint author), Univ Dr C,Bldg 30,Mailstop 151, Pittsburgh, PA 15240 USA. EM aabutt@pitt.edu FU Gilead Sciences; Gilead; AbbVie; MedImmune; Merck; Vertex FX This study was supported in part by an investigator initiated grant from Gilead Sciences to Veterans Research Foundation of Pittsburgh. (Principal Investigator Dr Butt) Dr Butt has received grant support (to the institution) from Gilead and AbbVie. Dr Shaikh has received grant support (to the institution) from Gilead. Dr Sherman's institution has received grants/contracts from AbbVie, Gilead, MedImmune, Merck, and Vertex. Dr Sherman has served on a DSMB for Janssen, MedPace and SynteractHCR. Mr Yan and Dr Chang have nothing to disclose. NR 26 TC 1 Z9 1 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 SEP PY 2016 VL 36 IS 9 BP 1275 EP 1283 DI 10.1111/liv.13103 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DW3UQ UT WOS:000383569000006 PM 26928927 ER PT J AU Morland, LA Niehaus, J Taft, C Marx, BP Menez, U Mackintosh, MA AF Morland, Leslie A. Niehaus, James Taft, Casey Marx, Brian P. Menez, Ursula Mackintosh, Margaret-Anne TI Using a Mobile Application in the Management of Anger Problems Among Veterans: A Pilot Study SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER AGGRESSION; VIETNAM VETERANS; PROLONGED EXPOSURE; HEALTH-CARE; AFGHANISTAN; PTSD; IRAQ; INTERVENTIONS; DEPRESSION AB Objective: This feasibility pilot study evaluated the usability of a mobile application (app), Remote Exercises for Learning Anger and Excitation Management (RELAX), as an adjunct to an anger management treatment delivered to Veterans. Methods: Four Veterans completed pre-and post-treatment measures of anger, post-traumatic stress disorder, depression, interpersonal functioning, and app use. Results: Descriptive results of clinical outcomes are provided. Qualitative data included Veterans' and therapists' feedback regarding the acceptability of the technology, satisfaction with the RELAX app, homework facilitation, and suggestions for improvement. Large reductions in anger, post-traumatic stress disorder and depression symptoms, and improvements in social functioning were evidenced post-treatment. Veterans reported that the RELAX app was helpful and appreciated its functionality. Conclusions: Our findings support using an app as an adjunct to traditional anger management. C1 [Morland, Leslie A.; Mackintosh, Margaret-Anne] Pacific Isl Healthcare Syst, Dept Vet Affairs, Pacific Isl Div, Natl Ctr PTSD, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA. [Morland, Leslie A.] Univ Hawaii, John Burns Sch Med, 651 Ilalo St, Honolulu, HI 96813 USA. [Niehaus, James] Charles River Analyt Inc, 625 Mt Auburn St 3, Cambridge, MA 02138 USA. [Marx, Brian P.] VA Boston Healthcare Syst, Dept Vet Affairs, Behav Sci Div, Natl Ctr PTSD, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA. [Taft, Casey; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston Med Ctr, 1 Boston Med Ctr Pl, Boston, MA 02118 USA. [Menez, Ursula] Pacif Hlth Res & Educ Inst, 3375 Koapaka St,Suite I-540, Honolulu, HI 96819 USA. RP Morland, LA (reprint author), Pacific Isl Healthcare Syst, Dept Vet Affairs, Pacific Isl Div, Natl Ctr PTSD, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA.; Morland, LA (reprint author), Univ Hawaii, John Burns Sch Med, 651 Ilalo St, Honolulu, HI 96813 USA. FU U.S. Army Medical Research and Material Command [W81XWH-12-C-0067, SBIR 12.2, OSD11-H13, 11271015]; VA National Center for PTSD FX The work is, in part, supported by the U.S. Army Medical Research and Material Command under Contract No. W81XWH-12-C-0067 (Department of Defense SBIR 12.2, Topic No. OSD11-H13, Phase II as a subcontract through Charles River Analytics, ERMS Log No. 11271015, Contract No. W81XWH-12-C-0067). Charles River Analytics has Small Business Innovation Research data rights to the RELAX app system. Support was also provided by the VA National Center for PTSD and with resources and the use of facilities at the Spark M. Matsunaga, VA Pacific Islands Health Care System. NR 42 TC 0 Z9 0 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD SEP PY 2016 VL 181 IS 9 BP 990 EP 995 DI 10.7205/MILMED-D-15-00293 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DW5MV UT WOS:000383690500015 PM 27612342 ER PT J AU Chao, LL Abadjian, LR Esparza, IL Reeb, R AF Chao, Linda L. Abadjian, Linda R. Esparza, Iva L. Reeb, Rosemary TI Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea in Veterans With Gulf War Illness SO MILITARY MEDICINE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; ORGANOPHOSPHATE PESTICIDES; IMMUNE FUNCTION; SHEEP FARMERS; FIBROMYALGIA; DEPRESSION; SYMPTOMS; EXPOSURE; HEALTH; INDEX AB Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p <= 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI. C1 [Chao, Linda L.; Abadjian, Linda R.; Esparza, Iva L.; Reeb, Rosemary] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St 114M, San Francisco, CA 94121 USA. [Chao, Linda L.; Reeb, Rosemary] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave, San Francisco, CA 94143 USA. [Chao, Linda L.] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. RP Chao, LL (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St 114M, San Francisco, CA 94121 USA.; Chao, LL (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave, San Francisco, CA 94143 USA.; Chao, LL (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. FU Department of Veterans Affairs Merit grant [I01BX007080]; San Francisco Veterans Affairs Medical Center FX Support for this work was provided by a Department of Veterans Affairs Merit grant No. I01BX007080 entitled "Longitudinal Assessment of Gulf War Veterans with Suspected Sarin Exposure" as well as resources and the use of facilities at the San Francisco Veterans Affairs Medical Center. The authors would like to thank all the GW veterans who participated in this study. NR 61 TC 0 Z9 0 U1 2 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD SEP PY 2016 VL 181 IS 9 BP 1127 EP 1134 DI 10.7205/MILMED-D-15-00474 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DW5MV UT WOS:000383690500037 PM 27612364 ER PT J AU Ward, L Pasinetti, GM AF Ward, Libby Pasinetti, Giulio Maria TI Recommendations for Development of Botanical Polyphenols as "Natural Drugs'' for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment SO NEUROMOLECULAR MEDICINE LA English DT Review DE Polyphenols; Botanicals; Resilience; Stress-induced depression; Sleep deprivation-induced cognitive impairment; Microbiome ID ALZHEIMERS-DISEASE; DIETARY POLYPHENOLS; MAJOR DEPRESSION; COLONIC METABOLISM; SLEEP-DEPRIVATION; ANXIETY DISORDERS; GUT MICROBIOTA; BRAIN; SEED; HEALTH AB E xtensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compounds into potential preventative and therapeutic agents in studies promoting brain health is hindered by the fact that most orally consumed botanicals are extensively metabolized during absorption and/or by postabsorptive xenobiotic metabolism. Therefore, the primary objective of this review article is to provide recommendations for developing natural compounds as novel therapeutic strategies to promote resilience in susceptible subjects. The development of botanical polyphenols to ultimately attenuate mood disorders and cognitive impairment will rely on understanding (1) the absorption and bioavailability of botanical polyphenols with emphasis on flavan-3-ols, (2) the characterization of tissue-specific accumulation of biologically available polyphenols and their mechanisms of action in the brain, and eventually (3) the characterization of biologically available polyphenol metabolites in mechanisms associated with the promotion of resilience against mood disorders and cognitive impairment in response to stress. We also summarize exciting new lines of investigation about the role of botanicals such as polyphenols in the promotion of cognitive and psychological resilience. This information will provide a strategical framework for the future development of botanicals as therapeutic agents to promote resilience, ultimately preventing and/or therapeutically treating cognitive impairment and psychological dysfunction. C1 [Ward, Libby; Pasinetti, Giulio Maria] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, 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 National Center for Complementary and Integrative Health (NCCIH) [P50 AT008661-01]; Office of Dietary Supplements (ODS); Career Scientist Award in the Research and Development unit FX This publication was supported by Grant Number P50 AT008661-01, titled "Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience," from the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS). 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 NCCIH, ODS, National Institutes of Health, U.S. Department of Veterans Affairs, or the United States Government. NR 61 TC 0 Z9 0 U1 3 U2 4 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 SEP PY 2016 VL 18 IS 3 BP 487 EP 495 DI 10.1007/s12017-016-8418-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA EC1GA UT WOS:000387851700021 PM 27342633 ER PT J AU Mattison, SM Beheim, B Chak, B Buston, P AF Mattison, Siobhan M. Beheim, Bret Chak, Bridget Buston, Peter TI Offspring sex preferences among patrilineal and matrilineal Mosuo in Southwest China revealed by differences in parity progression SO Royal Society Open Science LA English DT Article DE kinship; parity progression; fertility behaviour; microdemography; human behavioural ecology ID TRIVERS-WILLARD HYPOTHESIS; SON PREFERENCE; PARENTAL INVESTMENT; LEVEL ANALYSIS; INDIA; FERTILITY; RATIO; CHILDREN; POLICY; POPULATIONS AB Son preference predominates in China, yet there are patterned exceptions to this rule. In this paper, we test whether lineality (patrilineal versus matrilineal inheritance and descent) is associated with son versus daughter preference among the ethnic Mosuo (Na) of Southwest China. Our results show (i) an increased probability of continued fertility among matrilineal women after having a son compared with a daughter and (ii) an increased probability of continued fertility among patrilineal women after having a daughter compared with a son. These results are consistent with son preference among patrilineal Mosuo andmore muted daughter preference among the matrilineal Mosuo. Furthermore, we show (iii) the lowest probability of continued fertility at parity 2 once women have one daughter and one son across both systems, suggesting that preferences for at least one of each sex exist alongside preferences for the lineal sex. The Mosuo are the only known small-scale society in which two kinship systems distinguish sub-groups with many otherwise shared cultural characteristics. We discuss why this, in conjunction with differences in subsistence, may shed light on the evolutionary underpinnings of offspring sex preferences. C1 [Mattison, Siobhan M.] Univ New Mexico, Dept Anthropol, MSC 01, Albuquerque, NM 87111 USA. [Beheim, Bret] Max Planck Inst Evolutionary Demog, D-04103 Leipzig, Germany. [Chak, Bridget] Massachusetts Gen Hosp, Ctr Human Genet Res, 55 Fruit St, Boston, MA 02114 USA. [Buston, Peter] Boston Univ, Dept Biol, 5 Cummington Mall, Boston, MA 02215 USA. RP Mattison, SM (reprint author), Univ New Mexico, Dept Anthropol, MSC 01, Albuquerque, NM 87111 USA. EM siobhan.mattison@gmail.com OI Mattison, Siobhan/0000-0002-9537-5459 FU National Science Foundation [BCS 0717918]; Undergraduate Research Opportunity (UROP) award from Boston University FX This research was funded by the National Science Foundation (BCS 0717918) grant to S.M.M., and B.C. was funded by an Undergraduate Research Opportunity (UROP) award from Boston University. NR 66 TC 0 Z9 0 U1 2 U2 2 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 2054-5703 J9 ROY SOC OPEN SCI JI R. Soc. Open Sci. PD SEP PY 2016 VL 3 IS 9 AR 160526 DI 10.1098/rsos.160526 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA EE0AW UT WOS:000389236700036 ER PT J AU Feldt-Rasmussen, U Vanderpump, M Okosieme, O Williams, G Lazarus, JH Ross, DS AF Feldt-Rasmussen, Ulla Vanderpump, Mark Okosieme, Onyebuchi Williams, Graham Lazarus, John H. Ross, Douglas S. TI Peter M. Laurberg (June 14, 1945-June 20, 2016) IN MEMORIAM SO THYROID LA English DT Biographical-Item C1 [Feldt-Rasmussen, Ulla] Copenhagen Univ Hosp, Copenhagen, Denmark. [Vanderpump, Mark] Univ Coll London Hosp, London, England. [Okosieme, Onyebuchi] Cwm Taf Univ Hlth Board, Merthyr Tydfil, M Glam, Wales. [Williams, Graham] Imperial Coll, Endocrinol, London, England. [Lazarus, John H.] Univ Wales Hosp, Cardiff, S Glam, Wales. [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Feldt-Rasmussen, U (reprint author), Copenhagen Univ Hosp, Copenhagen, Denmark. EM ufeldt@rh.dk; mark.vanderpump@nhs.net; OkosiemeOE@cardiff.ac.uk; graham.williams@imperial.ac.uk; lazarus@cardiff.ac.uk; DROSS@mgh.harvard.edu NR 1 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 SEP PY 2016 VL 26 IS 9 BP 1149 EP 1153 DI 10.1089/thy.2016.29025.mem PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW3UP UT WOS:000383568900001 ER PT J AU Sternberg, KM Eisner, B Larson, T Hernandez, N Han, J Pais, VM AF Sternberg, Kevan M. Eisner, Brian Larson, Troy Hernandez, Natalia Han, Jullet Pais, Vernon M. TI Ultrasonography Significantly Overestimates Stone Size When Compared to Low-dose, Noncontrast Computed Tomography SO UROLOGY LA English DT Article ID ACUTE FLANK PAIN; UNENHANCED HELICAL CT; URETERAL CALCULI; RENAL STONE; NEPHROLITHIASIS; UROGRAPHY; STANDARD; PASSAGE; DISEASE; US AB OBJECTIVE To evaluate the differences between low-dose noncontrast computed tomography (NCCT) and renal ultrasound (US) in the identification and measurement of urinary calculi. MATERIALS AND METHODS A retrospective review was conducted at 3 institutions of patients evaluated for flank pain with both renal US and NCCT, within 1 day of one another, from 2012 to 2015. Stone presence and size were compared between imaging modalities. Stone size was determined by largest measured diameter. Stones were grouped into size categories (<= 5 mm, 5.1-10 mm, and > 10 mm) based on NCCT and compared with US. Statistical analysis was performed using 2-sided t tests. RESULTS One hundred fifty-five patients received both a renal US and NCCT within 1 day. In 79 patients (51.0%), both US and NCCT identified a stone for size comparison. Fifty-eight patients (37.4%) had a stone visualized on NCCT but not on US, and 2 patients (1.3%) had a stone documented on US but not seen on NCCT. The average NCCT size of the stones missed on US was 4.5 mm. When comparing the average largest stone diameter for US (9.1 mm) vs NCCT (6.9 mm), US overestimated stone size by 2.2 mm (P < .001). US overestimated stone size by 84.6% for stones <= 5 mm, 27.1% for stones 5.1-10 mm, and 3.0% for stones >10 mm. CONCLUSION US significantly overestimated stone size and this was most pronounced for small (<= 5 mm) stones. The potential for systematic overestimation of stone size with standard US techniques should be taken into consideration when evaluating endourologic treatment options. (C) 2016 Elsevier Inc. C1 [Sternberg, Kevan M.] Univ Vermont, Med Ctr, Div Urol, 111 Colchester Ave,Main Campus,East Pavill, Burlington, VT 05401 USA. Harvard Med Sch, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA. Univ Vermont, Med Ctr, Burlington, VT USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Urol Sect, Lebanon, NH 03766 USA. RP Sternberg, KM (reprint author), Univ Vermont, Med Ctr, Div Urol, 111 Colchester Ave,Main Campus,East Pavill, Burlington, VT 05401 USA. EM kevan.sternberg@uvmhealth.org NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD SEP PY 2016 VL 95 BP 67 EP 71 DI 10.1016/j.urology.2016.06.002 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA DW5PK UT WOS:000383698300020 PM 27289025 ER PT J AU Kwan, W Cortes, M Frost, I Esain, V Theodore, LN Liu, SY Budrow, N Goessling, W North, TE AF Kwan, Wanda Cortes, Mauricio Frost, Isaura Esain, Virginie Theodore, Lindsay N. Liu, Sarah Y. Budrow, Nadine Goessling, Wolfram North, Trista E. TI The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling SO CELL STEM CELL LA English DT Article ID PITUITARY-ADRENAL AXIS; STEM-CELL DEVELOPMENT; HEMATOPOIETIC STEM; CUSHINGS-DISEASE; ZEBRAFISH; EXPRESSION; PROGENITOR; ERYTHROPOIESIS; METABOLISM; EMERGENCE AB Hematopoietic stem and progenitor cell (HSPC) specification is regulated by numerous defined factors acting locally within the hemogenic niche; however, it is unclear whether production can adapt to fluctuating systemic needs. Here we show that the CNS controls embryonic HSPC numbers via the hypothalamic-pituitary-adrenal/interrenal (HPA/I) stress response axis. Exposure to serotonin or the reuptake inhibitor fluoxetine increased runx1 expression and Flk1(+)/cMyb(+) HSPCs independent of peripheral innervation. Inhibition of neuronal, but not peripheral, tryptophan hydroxlyase (Tph) persistently reduced HSPC number. Consistent with central HPA/I axis induction and glucocorticoid receptor (GR) activation, GR agonists enhanced, whereas GR loss diminished, HSPC formation. Significantly, developmental hypoxia, as indicated by Hif1 alpha function, induced the HPA/I axis and cortisol production. Furthermore, Hif1a-stimulated HSPC enhancement was attenuated by neuronal tph or GR loss. Our data establish that embryonic HSC production responds to physiologic stress via CNS-derived serotonin synthesis and central feedback regulation to control HSC numbers. C1 [Kwan, Wanda; Cortes, Mauricio; Frost, Isaura; Esain, Virginie; Theodore, Lindsay N.; Liu, Sarah Y.; Budrow, Nadine; North, Trista E.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram; North, Trista E.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP North, TE (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.; North, TE (reprint author), Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM tnorth@bidmc.harvard.edu FU CIHR; NIH [1R01DK098241] FX We thank the BIDMC Flow Cytometry Core and Children's Hospital Genomics Core Facility for assistance. We thank K. Alexa for providing 5-HTR drugs. We thank H. Burgess (NIH), H. Baier (Max Planck Martinsried), F. van Eeden (University of Sheffield), and D. Traver (UCSD) for transgenic lines. We thank R. George (Dana Farber), B. Thisse (University of Virginia), and C. Burns (Harvard Medical School) for in situ probes. We thank T. Tsai, S.G. Megason, B. Paw, R. Karlstrom, I. Drummond, D. Langenau, and D. Robson for advice. This study was supported by a CIHR postdoctoral fellowship (to W.K.) and NIH 1R01DK098241 (to T.E.N.). NR 33 TC 4 Z9 4 U1 3 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD SEP 1 PY 2016 VL 19 IS 3 BP 370 EP 382 DI 10.1016/j.stem.2016.06.004 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA ED6UG UT WOS:000388991400014 PM 27424782 ER PT J AU Soto-Pina, AE Franklin, C Rani, CSS Gottlieb, H Hinojosa-Laborde, C Strong, R AF Soto-Pina, Alexandra E. Franklin, Cynthia Rani, C. S. Sheela Gottlieb, Helmut Hinojosa-Laborde, Carmen Strong, Randy TI A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CATECHOLAMINE BIOSYNTHETIC-ENZYMES; ADRENAL-MEDULLA; GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; BLOOD-PRESSURE; XANTHINE-OXIDASE; UP-REGULATION; RAT; GLUCOCORTICOIDS; STRESS AB Our objective was to study hypertension induced by chronic administration of synthetic glucocorticoid, dexamethasone (DEX), under nonstressful conditions and examine the role of catecholamine biosynthesis. To achieve this, we did the following: 1) used radiotelemetry to record mean arterial pressure (MAP) and heart rate (HR) in freely moving rats, and 2) administered different doses of DEX in drinking water. To evaluate the involvement of tyrosine hydroxylase (TH), the rate-limiting step in catecholamine biosynthesis, we treated rats with the TH inhibitor, alpha-methyl-paratyrosine (alpha-MPT), for 3 days prior to administration of DEX and assessed TH mRNA and protein expression by quantitative realtime polymerase chain reaction and Western blot in the adrenal medulla. We observed a dose-dependent elevation in blood pressure with a DEX dose of 0.3 mg/kg administered for 10 days, significantly increasing MAP by +15.0 +/- 1.1 mm Hg, while concomitantly reducing HR. Although this DEX treatment also significantly decreased body weight, pair-fed animals that showed similar decreases in body weight due to lowered food intake were not hypertensive, suggesting that body weight changes may not account for DEX-induced hypertension. Chronic DEX treatment significantly increased the TH mRNA and protein levels in the adrenal medulla, and alpha-MPT administration not only reduced DEX pressor effects, but also inhibited TH (serine(40)) phosphorylation. Our study thus validates a novel model to study hypertension induced by chronic intake of DEX in freely moving rats not subject to the confounding factors of previous models and establishes its dependence on concomitant activation of peripheral catecholamine biosynthesis. C1 [Soto-Pina, Alexandra E.] Univ Autonoma Estado Mexico, Fac Med, Toluca, Mexico. [Rani, C. S. Sheela; Hinojosa-Laborde, Carmen; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Franklin, Cynthia; Gottlieb, Helmut] Univ Incarnate Word, Feik Sch Pharm, San Antonio, TX USA. [Strong, Randy] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Soto-Pina, AE (reprint author), Paseo Tollocan Esq Jesus Carranza, Toluca 50180, Estado De Mexic, Mexico. EM aesotop@uaemex.mx FU Department of Veteran Affairs; Consejo Nacional de Ciencia y Technologia; American Heart Association FX This work was supported by the Department of Veteran Affairs (to R.S.), Consejo Nacional de Ciencia y Technologia (to A.E.S.-P.), and a predoctoral award from the American Heart Association (to A.E.S.-P.). NR 71 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP 1 PY 2016 VL 358 IS 3 BP 528 EP 536 DI 10.1124/jpet.116.234005 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ED7RA UT WOS:000389065700019 PM 27405316 ER PT J AU Braga, A Maesta, I Soares, RR Elias, KM Domingues, MAC Barbisan, LF Berkowitz, RS AF Braga, Antonio Maesta, Izildinha Soares, Renan Rocha Elias, Kevin M. Custodio Domingues, Maria Aparecida Barbisan, Luis Fernando Berkowitz, Ross S. TI Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE apoptotic index; Brazil; complete hydatidiform mole; gestational trophoblastic neoplasia; receiver operating characteristic; survivin ID COMPLETE HYDATIDIFORM MOLE; FOLLOW-UP; CLINICOPATHOLOGICAL PARAMETERS; BCL-2 EXPRESSION; DISEASE; PREGNANCY; SURVIVIN; DIAGNOSIS; GENE AB BACKGROUND: Although 85% of patients with a complete hydatidiform mole achieve spontaneous remission after a few months, 15% of them will experience gestational trophoblastic neoplasia, which requires chemotherapy. To date, there is no biomarker to predict post-molar gestational trophoblastic neoplasia before the initiation of human chorionic gonadotropin surveillance. OBJECTIVE: The purpose of this study was to assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of gestational trophoblastic neoplasia after the evacuation of a complete hydatidiform mole. STUDY DESIGN: This was a retrospective cohort study of patients with complete hydatidiform mole who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/Sao Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) from 1995-2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the proeapoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic curves were then constructed, and the area under the curve was calculated to test the performance characteristics of the staining to predict the subsequent development of gestational trophoblastic neoplasia. RESULTS: The final study population comprised 780 patients, with 390 patients in each temporal cohort: 590 patients entered spontaneous remission, and 190 patients experienced post-molar gestational trophoblastic neoplasia. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent gestational trophoblastic neoplasia. The caspase-3 apoptotic index was a strong risk factor for subsequent gestational trophoblastic neoplasia development. When the apoptotic index was < 4%, the risk of gestational trophoblastic neoplasia had an odds ratio of 35.55 (95% confidence interval, 14.02-90.14; P < .0001) in the derivation cohort and an odds ratio of 25.71 (95% confidence interval, 10.13-65.29; P <.0001) in the validation cohort. However, in both cohorts, the positive predictive value for gestational trophoblastic neoplasia of an apoptotic index < 4.0% was modest (49% in the derivation cohort and 41% in the validation cohort); the negative predictive value for gestational trophoblastic neoplasia of an apoptotic index >= 4.0% was high (97% in both cohorts). CONCLUSION: The subsequent development of gestational trophoblastic neoplasia after evacuation of complete hydatidiform mole is tied closely to the apoptotic index, which may be a useful biomarker for future prospective studies. C1 [Braga, Antonio] Univ Fed Rio de Janeiro, Matern Sch, Rio de Janeiro Trophoblast Dis Ctr, BR-21941 Rio De Janeiro, Brazil. [Braga, Antonio] Univ Fed Fluminense, Antonio Pedro Univ Hosp, BR-24220000 Niteroi, RJ, Brazil. [Braga, Antonio; Maesta, Izildinha; Soares, Renan Rocha] Sao Paulo State Univ, Botucatu Med Sch, Postgrad Program Gynecol Obstet & Mastol, Sao Paulo, Brazil. [Custodio Domingues, Maria Aparecida] Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Sao Paulo, Brazil. [Barbisan, Luis Fernando] Sao Paulo State Univ, Biosci Inst, Dept Morphol, Sao Paulo, Brazil. [Elias, Kevin M.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Obstet & Gynecol & Reprod Biol,Div Gynecol O, New England Trophoblast Dis Ctr,Donald P Goldstei, 75 Francis St, Boston, MA 02115 USA. RP Elias, KM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Obstet & Gynecol & Reprod Biol,Div Gynecol O, New England Trophoblast Dis Ctr,Donald P Goldstei, 75 Francis St, Boston, MA 02115 USA. EM kelias1@partners.org OI Elias, Kevin/0000-0003-1502-5553 NR 26 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2016 VL 215 IS 3 AR 336.e1-e12 DI 10.1016/j.ajog.2016.04.010 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DU8WA UT WOS:000382495100026 PM 27094961 ER PT J AU Gockley, AA Joseph, NT Melamed, A Sun, SY Goodwin, B Bernstein, M Goldstein, DP Berkowitz, RS Horowitz, NS AF Gockley, Allison A. Joseph, Naima T. Melamed, Alexander Sun, Sue Yazaki Goodwin, Benjamin Bernstein, Marilyn Goldstein, Donald P. Berkowitz, Ross S. Horowitz, Neil S. TI Effect of race/ethnicity on clinical presentation and risk of gestational trophoblastic neoplasia in patients with complete and partial molar pregnancy at a tertiary care referral center SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th World Congress on Gestational Trophoblastic Diseases CY SEP 15-18, 2015 CL Bali, INDONESIA DE ethnicity; gestational trophoblastic neoplasia; molar pregnancy; race ID HYDATIDIFORM MOLE; CANCER INCIDENCE; MATERNAL AGE; DISEASE; EPIDEMIOLOGY; POPULATION; MANAGEMENT; DIAGNOSIS; ORIGIN; CHEMOTHERAPY AB BACKGROUND: The reported incidence of molar pregnancy varies widely among different geographic locations. This variation has been attributed, at least in part, to racial/ethnic differences. While the incidence of molar pregnancies is decreasing, certain ethnic groups such as Hispanics, Asians, and American Indians continue to have an increased risk of developing gestational trophoblastic disease across the globe. OBJECTIVE: We sought to describe the potential effect of ethnicity/race on the presentation and clinical course of complete mole and partial mole. STUDY DESIGN: All patients followed up for complete mole and partial mole at a single institution referral center from 1994 through 2013 were identified. Variables including age, race, gravidity, parity, gestational age, presenting signs/symptoms, serum human chorionic gonadotropin values, and development of gestational trophoblastic neoplasia were extracted from medical records and patient surveys. Patients with complete mole and partial mole were categorized into race/ethnicity groups defined as white, black, Asian, or Hispanic. Due to low numbers of non-white patients with partial mole in each non-white category, patients with partial mole were grouped as white or non-white. Continuous variables were compared using the Kruskal-Wallis test and binary variables were compared using the Fisher exact test. RESULTS: A total of 167 complete mole patients with known race/ethnicity status were included (57.48% white, 14.97% Asian, 14.37% black, 13.17% Hispanic). Hispanics presented at younger age (median 24.5 years) compared to whites (median 32.0 years, P = .04) and Asians median 31.0 years, P = .03). Blacks had higher gravidity than whites (P < .001) and Hispanics (P = .05). There was no significant difference in presenting symptoms, gestational age at diagnosis, and preevacuation serum human chorionic gonadotropin level by race/ethnicity. Hispanics were significantly less likely than whites to develop gestational trophoblastic neoplasia (absolute risk difference, 28.6%; 95% confidence interval, 8.1-39.2%; P = .02). A total of 144 patients with partial mole were analyzed. There were 108 white and 36 non-white patients. Median age was 31 years for white and 29 years for non-white patients (P = .006). Median gravidity was 2 for white and 3 for non-white patients (P < .001), and median parity was 0 for white patients and 1 for non-white patients (P = .003). There were no significant differences with respect to presenting signs and symptoms, gestational age, preevacuation human chorionic gonadotropin level, or risk of progression to gestational trophoblastic neoplasia. CONCLUSION: Hispanic patients with complete molar pregnancy had a significantly lower risk of developing gestational trophoblastic neoplasia than white patients. There were no significant differences among groups in terms of presenting symptoms, gestational age at diagnosis, or preevacuation human chorionic gonadotropin levels for either complete mole or partial mole patients. C1 [Gockley, Allison A.; Joseph, Naima T.; Melamed, Alexander; Goodwin, Benjamin; Bernstein, Marilyn; Goldstein, Donald P.; Berkowitz, Ross S.; Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. [Gockley, Allison A.; Joseph, Naima T.; Melamed, Alexander] Massachusetts Gen Hosp, Vincent Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. [Gockley, Allison A.; Joseph, Naima T.; Melamed, Alexander; Goldstein, Donald P.; Berkowitz, Ross S.; Horowitz, Neil S.] Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. [Goldstein, Donald P.; Berkowitz, Ross S.; Horowitz, Neil S.] Harvard Canc Ctr, Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, Gynecol Oncol Program, Boston, MA USA. [Sun, Sue Yazaki; Bernstein, Marilyn; Goldstein, Donald P.; Berkowitz, Ross S.; Horowitz, Neil S.] Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. [Sun, Sue Yazaki] Univ Fed Sao Paulo, Paulista Sch Med, Sao Paulo Hosp, Dept Obstet, Sao Paulo, Brazil. [Sun, Sue Yazaki] Univ Fed Sao Paulo, Paulista Sch Med, Sao Paulo Hosp, Trophoblast Dis Ctr, Sao Paulo, Brazil. RP Horowitz, NS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA.; Horowitz, NS (reprint author), Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA.; Horowitz, NS (reprint author), Harvard Canc Ctr, Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, Gynecol Oncol Program, Boston, MA USA.; Horowitz, NS (reprint author), Donald P Goldstein MD Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA. EM nhorotwitz@partners.org NR 32 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2016 VL 215 IS 3 AR 334.e1-e6 DI 10.1016/j.ajog.2016.04.019 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DU8WA UT WOS:000382495100025 PM 27130239 ER PT J AU Zuschlag, ZD Lalich, CJ Short, EB Hamner, M Kahn, DA AF Zuschlag, Zachary D. Lalich, Callie J. Short, Edward B. Hamner, Mark Kahn, David A. TI Pyrotherapy for the Treatment of Psychosis in the 21st Century: A Case Report and Literature Review SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Review DE pyrotherapy; pyretotherapy; schizophrenia; schizoaffective disorder; psychosis; fever; Wagner-Jauregg; heat shock response; sulforaphane ID INSULIN COMA; THERAPY; FEVER; SULFORAPHANE; PARALYSIS; MALARIA AB The concept that fevers can improve the condition of patients with certain medical and psychiatric diseases dates back to Hippocrates. Over the centuries, it has been observed that fevers and infectious agents have been beneficial for a broad spectrum of diseases, including neurologic conditions such as epilepsy and psychiatric illnesses including melancholy and psychosis. Interest in the concept of fever as a treatment for disease, termed pyrotherapy or pyretotherapy, peaked in the late 1800s and early 1900s thanks to the Nobel Prize winning work of Julius Wagner-Jauregg for his studies with malaria therapy for general paralysis of the insane, now more commonly referred to as neurosyphilis. The use of inoculations of infectious agents for their fever-inducing effects in the treatment of neurosyphilis quickly spread throughout the world, and, by the 1920s, it was considered by many to be the treatment of choice for neurosyphilis as well as other psychotic disorders. However, with the discovery of penicillin for the treatment of syphilis, which coincided with the advent of convulsion-oriented practices including electroconvulsive therapy and insulin coma for the treatment of psychotic disorders, pyrotherapy soon lost favor among psychiatrists and, since the 1950s, it has largely been overlooked by the scientific community. In this article, the authors provide a brief literature review of the history of pyrotherapy and present a case report of a woman with schizoaffective disorder and severe psychotic symptoms who experienced a remarkable resolution of psychotic symptoms following an episode of bacteremia with high fever. C1 [Zuschlag, Zachary D.; Lalich, Callie J.; Short, Edward B.; Hamner, Mark] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Hamner, Mark] Ralph H Johnson Vet Adm, Charleston, SC USA. [Kahn, David A.] Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. RP Zuschlag, ZD (reprint author), 102 Doughty St, Charleston, SC 29425 USA. EM zuschlagzd@gmail.com NR 51 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 1527-4160 EI 1538-1145 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD SEP PY 2016 VL 22 IS 5 BP 410 EP 415 DI 10.1097/PRA.0000000000000181 PG 6 WC Psychiatry SC Psychiatry GA EC5AY UT WOS:000388146700008 PM 27648506 ER PT J AU Pusztaszeri, M Rossi, ED Auger, M Baloch, Z Bishop, J Bongiovanni, M Chandra, A Cochand-Priollet, B Faddda, G Hirokawa, M Hong, S Kakudo, K Krane, JF Nayar, R Parangi, S Schmitt, F Faquin, WC AF Pusztaszeri, Marc Rossi, Esther Diana Auger, Manon Baloch, Zubair Bishop, Justin Bongiovanni, Massimo Chandra, Ashish Cochand-Priollet, Beatrix Faddda, Guido Hirokawa, Mitsuyoshi Hong, SoonWon Kakudo, Kennichi Krane, Jeffrey F. Nayar, Ritu Parangi, Sareh Schmitt, Fernando Faquin, William C. TI The Bethesda System for Reporting Thyroid Cytopathology: Proposed Modifications and Updates for the Second Edition from an International Panel SO ACTA CYTOLOGICA LA English DT Editorial Material DE Bethesda system; Thyroid lesion; Classification systems; Diagnostic categories; NIFTP ID FINE-NEEDLE-ASPIRATION; NONINVASIVE FOLLICULAR VARIANT; GENE-EXPRESSION CLASSIFIER; UNDETERMINED SIGNIFICANCE; INSTITUTIONAL EXPERIENCE; ASSOCIATION GUIDELINES; CYTOLOGIC DIAGNOSIS; NUCLEAR FEATURES; CARCINOMA; NODULES AB The Bethesda System for Reporting Thyroid Cytology (TBSRTC) was proposed in 2007 at the National Cancer Institute Thyroid Fine Needle Aspiration State of the Art and Science Conference held in Bethesda, Maryland. The aim was to address the inconsistent and sometimes confusing reporting terminologies used for thyroid FNA throughout the world. The TBSRTC consists of 6 diagnostic categories, each associated with an implied risk of malignancy that translates directly into a clinical management algorithm. Since the publication of the TBSRTC cytology Atlas in January 2010, considerable experience has been gained regarding its application in cytology practice, clinical impact, and limitations. In conjunction with the International Academy of Cytology (IAC), an international panel composed of sixteen cytopathologists and an endocrinologist with special interest in thyroid cytology, including several co-authors of the 2010 TBSRTC Atlas, was created to: ( 1) analyze the current worldwide impact of TBSRTC, ( 2) report on the current state of TBSRTC based upon a review of the published literature, and ( 3) provide possible recommendations for a future update of TBSRTC. Herein, we summarize the panel's deliberations and key recommendations that our panel hopes will be useful during the preparation of the second edition of TBSRTC. (C) 2016 S. Karger AG, Basel. C1 [Pusztaszeri, Marc] Univ Hosp Geneva, Dept Pathol, Geneva, Switzerland. [Rossi, Esther Diana; Faddda, Guido] Univ Cattolica Sacro Cuore, Agostino Gemelli Sch Med, Div Anat Pathol & Histol, Rome, Italy. [Auger, Manon] McGill Univ, Dept Pathol, Montreal, PQ, Canada. [Auger, Manon] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Baloch, Zubair] Hosp Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Bishop, Justin] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. [Bongiovanni, Massimo] CHU Vaudois, Inst Pathol, Lausanne, Switzerland. [Chandra, Ashish] Guys & St Thomas NHS Fdn Trust, Dept Cellular Pathol, London, England. [Cochand-Priollet, Beatrix] Cochin Hosp, Dept Pathol, Paris, France. [Hirokawa, Mitsuyoshi] Kuma Hosp, Dept Diagnost Pathol, Kobe, Hyogo, Japan. [Hong, SoonWon] Yonsei Univ, Gang Nam Severance Hosp, Dept Pathol, Seoul, South Korea. [Kakudo, Kennichi] Kinki Univ, Fac Med, Nara Hosp, Dept Pathol, Nara, Japan. [Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Krane, Jeffrey F.; Parangi, Sareh; Faquin, William C.] Harvard Med Sch, Boston, MA USA. [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. [Nayar, Ritu] Northwestern Med, Chicago, IL USA. [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Schmitt, Fernando] Lab Natl Sante, Dept Med, Dudelange, Luxembourg. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Head & Neck Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM WFAQUIN@mgh.harvard.edu RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 52 TC 2 Z9 2 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5547 EI 1938-2650 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 2016 VL 60 IS 5 BP 399 EP 405 DI 10.1159/000451020 PG 7 WC Pathology SC Pathology GA ED1SB UT WOS:000388624100002 PM 27764825 ER PT J AU Abujaber, S Chang, CY Reynolds, TA Mowafi, H Obermeyer, Z AF Abujaber, Samer Chang, Cindy Y. Reynolds, Teri A. Mowafi, Hani Obermeyer, Ziad TI Developing metrics for emergency care research in low- and middle-income countries SO AFRICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MORTALITY; SYSTEMS; MEDICINE; ACCESS; WORLD AB Introduction: There is little research on emergency care delivery in low-and middle-income countries (LMICs). To facilitate future research, we aimed to assess the set of key metrics currently used by researchers in these settings and to propose a set of standard metrics to facilitate future research. Methods: Systematic literature review of 43,109 published reports on general emergency care from 139 LMICs. Studies describing care for subsets of emergency conditions, subsets of populations, and data aggregated across multiple facilities were excluded. All facility-and patient-level statistics reported in these studies were recorded and the most commonly used metrics were identified. Results: We identified 195 studies on emergency care delivery in LMICs. There was little uniformity in either patient-or facility-level metrics reported. Patient demographics were inconsistently reported: only 33% noted average age and 63% the gender breakdown. The upper age boundary used for paediatric data varied widely, from 5 to 20 years of age. Emergency centre capacity was reported using a variety of metrics including annual patient volume (n = 175, 90%); bed count (n = 60, 31%), number of rooms (n = 48, 25%); frequently none of these metrics were reported (n = 16, 8%). Many characteristics essential to describe capabilities and performance of emergency care were not reported, including use and type of triage; level of provider training; admission rate; time to evaluation; and length of EC stay. Conclusion: We found considerable heterogeneity in reporting practices for studies of emergency care in LMICs. Standardised metrics could facilitate future analysis and interpretation of such studies, and expand the ability to generalise and compare findings across emergency care settings. C1 [Abujaber, Samer] Brigham & Womens Hosp, Dept Emergency Med, Neville House,10 Vining St, Boston, MA 02115 USA. [Chang, Cindy Y.] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, 75 Francis St, Boston, MA 02115 USA. [Chang, Cindy Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reynolds, Teri A.] Univ Calif San Francisco, Dept Emergency Med, 505 Parnassus Ave, San Francisco, CA 94143 USA. [Mowafi, Hani] Yale Univ, Dept Emergency Med, 464 Congress Ave,Suite 260, New Haven, CT 06519 USA. [Obermeyer, Ziad] Harvard Med Sch, Dept Emergency Med, 25 Shattuck St, Boston, MA 02115 USA. RP Obermeyer, Z (reprint author), Harvard Med Sch, Dept Emergency Med, 25 Shattuck St, Boston, MA 02115 USA. EM zobermeyer@partners.org NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-419X EI 2211-4203 J9 AFR J EMERG MED JI Afr. J. Emerg. Med. PD SEP PY 2016 VL 6 IS 3 BP 116 EP 124 DI 10.1016/j.afjem.2016.06.003 PG 9 WC Emergency Medicine SC Emergency Medicine GA EC9DB UT WOS:000388443200004 ER PT J AU Rice, MS Eliassen, AH Hankinson, SE Lenart, EB Willett, WC Tamimi, RM AF Rice, Megan S. Eliassen, A. Heather Hankinson, Susan E. Lenart, Elizabeth B. Willett, Walter C. Tamimi, Rulla M. TI Breast Cancer Research in the Nurses' Health Studies: Exposures Across the Life Course SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GENOME-WIDE ASSOCIATION; MODERATE ALCOHOL-CONSUMPTION; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; PROSPECTIVE COHORT; HORMONE-LEVELS; BODY FATNESS; YOUNG-WOMEN; WEIGHT-GAIN AB Objectives. To review the contribution of the Nurses' Heath Study (NHS) and the NHS II in identifying risk and protective factors for breast cancer incidence and survival. Methods. We conducted a narrative review of NHS and NHS II articles on breast cancer incidence and survival published from 1976 to 2016, with a focus on exogenous and endogenous hormones; lifestyle factors, including diet, physical activity, and aspirin use; intermediate markers of risk; and genetic factors. Results. With the investigation of individual risk factors, as well as their incorporation into risk prediction models, the NHS has contributed to the identification of ways in which women may reduce breast cancer risk, including limiting alcohol consumption, reducing the duration of postmenopausal estrogen-plus-progestin use, avoiding weight gain, and increasing vegetable consumption. In addition, the NHS has helped elucidate the roles of several biomarkers and contributed to the identification of risk alleles. Conclusions. The NHS has contributed to our understanding of lifestyle, hormonal, and genetic risk factors for breast cancer, highlighting the importance of exposures across the life course, and has helped identify lifestyle changes that may reduce risk and improve survival after a diagnosis of breast cancer. C1 [Rice, Megan S.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Rice, Megan S.; Eliassen, A. Heather; Tamimi, Rulla M.] Harvard Med Sch, Boston, MA USA. [Eliassen, A. Heather; Tamimi, Rulla M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Lenart, Elizabeth B.; Willett, Walter C.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. RP Rice, MS (reprint author), Massachusetts Gen Hosp, Dept Med, Clin & Translat Epidemiol Unit, 55 Fruit St,Bartlett 9, Boston, MA 02114 USA. EM mrice1@mgh.harvard.edu FU National Cancer Institute, National Institutes of Health [UM1CA186107, P01CA87969, R01CA49449, UM1CA176726, R01CA67262] FX The Nurses' Health Study and Nurses' Health Study II are supported by research grants from the National Cancer Institute, National Institutes of Health (UM1CA186107, P01CA87969, R01CA49449, UM1CA176726, and R01CA67262). NR 45 TC 2 Z9 2 U1 3 U2 3 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 SEP PY 2016 VL 106 IS 9 BP 1592 EP 1598 DI 10.2105/AJPH.2016.303325 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EC4CB UT WOS:000388072300023 PM 27459456 ER PT J AU Birmann, BM Barnard, ME Bertrand, KA Bao, Y Crous-Bou, M Wolpin, BM De Vivo, I Tworoger, SS AF Birmann, Brenda M. Barnard, Mollie E. Bertrand, Kimberly A. Bao, Ying Crous-Bou, Marta Wolpin, Brian M. De Vivo, Immaculata Tworoger, Shelley S. TI Nurses' Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NON-HODGKIN-LYMPHOMA; PLASMA ORGANOCHLORINE LEVELS; PHYSICAL-ACTIVITY; MULTIPLE-MYELOMA; TUBAL-LIGATION; CIGARETTE-SMOKING; POOLED ANALYSIS; RISK; CONSORTIUM; COHORT AB Objectives. To review the contributions of the Nurses' Health Study (NHS) to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. Methods. We reviewed selected NHS publications from 1976 to 2016, including publications from consortia and other pooled studies. Results. NHS studies on less common cancers have identified novel risk factors, such as a reduced risk of endometrial cancer in women of advanced age at last birth, and have clarified or prospectively confirmed previously reported associations, including an inverse association between tubal ligation and ovarian cancer. Through biomarker research, the NHS has furthered understanding of the pathogenesis of rare cancers, such as the role of altered metabolism in pancreatic cancer risk and survival. NHS investigations have also demonstrated the importance of the timing of exposure, such as the finding of a positive association of early life body fatness, but not of usual adult body mass index, with non-Hodgkin lymphoma risk. Conclusions. Evidence from the NHS has informed prevention strategies and contributed to improved survival from less common but often lethal malignancies, including endometrial, ovarian, pancreatic, and hematologic cancers. C1 [Birmann, Brenda M.; Bao, Ying; Crous-Bou, Marta; De Vivo, Immaculata; Tworoger, Shelley S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. [Birmann, Brenda M.; Bao, Ying; Crous-Bou, Marta; Wolpin, Brian M.; De Vivo, Immaculata; Tworoger, Shelley S.] Harvard Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. [Barnard, Mollie E.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bertrand, Kimberly A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA USA. [Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Birmann, BM (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.; Birmann, BM (reprint author), Harvard Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. EM brenda.birmann@channing.harvard.edu FU National Institutes of Health [CA186107, CA87969, CA49449, CA09001, CA098566, CA115687, CA082838, CA149445, CA127435, CA098122, CA163451, CA176726, CA140790, CA155626, DK046200, ES007155, KL2 TR001100]; American Society of Clinical Oncology Career Development Award; Howard Hughes Medical Institute Early Career Physician Scientist Award; Lustgarten Foundation; Department of Defense [CA130288]; Promises for Purple FX The authors and the research summarized in this review were funded in part by the National Institutes of Health (CA186107, CA87969, CA49449, CA09001, CA098566, CA115687, CA082838, CA149445, CA127435, CA098122, CA163451, CA176726, CA140790, CA155626, DK046200, ES007155, and KL2 TR001100 [to Y. B]). Work by B. M. W. was also supported by an American Society of Clinical Oncology Career Development Award, a Howard Hughes Medical Institute Early Career Physician Scientist Award, the Lustgarten Foundation, Department of Defense (award CA130288), and Promises for Purple. NR 44 TC 0 Z9 0 U1 3 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 SEP PY 2016 VL 106 IS 9 BP 1608 EP 1615 DI 10.2105/AJPH.2016.303337 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EC4CB UT WOS:000388072300025 PM 27459458 ER PT J AU Kang, JH Wu, J Cho, EY Ogata, S Jacques, P Taylor, A Chiu, CJ Wiggs, JL Seddon, JM Hankinson, SE Schaumberg, DA Pasquale, LR AF Kang, Jae H. Wu, Juan Cho, Eunyoung Ogata, Soshiro Jacques, Paul Taylor, Allen Chiu, Chung-Jung Wiggs, Janey L. Seddon, Johanna M. Hankinson, Susan E. Schaumberg, Debra A. Pasquale, Louis R. TI Contribution of the Nurses' Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OPEN-ANGLE GLAUCOMA; INTRAOCULAR-PRESSURE; VISUAL IMPAIRMENT; PREVALENCE; RISK; PSEUDOEXFOLIATION; SUSCEPTIBILITY; PATHWAY; DISEASE; LOCI AB Objectives. To review the contribution of the Nurses' Health Study (NHS) to understanding the genetic and lifestyle factors that influence the risk of cataract, age-related macular degeneration, and glaucoma. Methods. We performed a narrative review of the publications of the NHS between 1976 and 2016. Results. The NHS has helped to elucidate the roles of genetics, lifestyle factors (e.g., cigarette smoking associated with cataract extraction and age-related macular degeneration), medical conditions (e.g., diabetes associated with cataract extraction and glaucoma), and dietary factors (e.g., greater carotenoid intake and lower glycemic diet associated with lower risk of age-related macular degeneration) in the etiology of degree and progression of lens opacities, cataract extraction, age-related macular degeneration, primary open-angle glaucoma, and exfoliation glaucoma. Conclusions. The findings from the NHS, combined with those of other studies, have provided compelling evidence to support public health recommendations for helping to prevent age-related eye diseases: abstinence from cigarette smoking, maintenance of healthy weight and diabetes prevention, and a healthy diet rich in fruits and vegetables. C1 [Kang, Jae H.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Kang, Jae H.; Wiggs, Janey L.; Pasquale, Louis R.] Harvard Med Sch, Boston, MA USA. [Wu, Juan] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA. [Ogata, Soshiro] Osaka Univ, Grad Sch Med, Dept Hlth Promot Sci, Suita, Osaka, Japan. [Jacques, Paul; Taylor, Allen; Chiu, Chung-Jung] Tufts Univ, Lab Nutr & Vis Res, Jean Mayer USDA Human Nutr Ctr Aging, Boston, MA 02111 USA. [Wiggs, Janey L.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Seddon, Johanna M.] Tufts Univ, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr, Tufts Med Ctr,Sch Med, Boston, MA 02111 USA. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Schaumberg, Debra A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Kang, JH (reprint author), Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu FU National Institutes of Health; Arthur Ashley Foundation [UM1 CA186107, UM1 CA167552, EY09611, EY015473, R21 EY022766, R01 EY020928, R01 EY022305]; Harvard Medical Distinguished Ophthalmology Scholar award; JSPS KAKENHI [15J03698]; Harvard Glaucoma Center of Excellence FX This work was supported by the National Institutes of Health and the Arthur Ashley Foundation (grants UM1 CA186107; UM1 CA167552; EY09611; EY015473 to L. R. P.; and R21 EY022766, R01 EY020928, and R01 EY022305 to J. L. W); a Harvard Medical Distinguished Ophthalmology Scholar award (to L. R. P.); and JSPS KAKENHI (grant 15J03698 to S. O.). L. R. P. and J. L. W. were also supported by the Harvard Glaucoma Center of Excellence. NR 44 TC 1 Z9 1 U1 1 U2 3 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 SEP PY 2016 VL 106 IS 9 BP 1684 EP 1689 DI 10.2105/AJPH.2016.303317 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EC4CB UT WOS:000388072300036 PM 27459452 ER PT J AU Schouten, R Brennan, DV AF Schouten, Ronald Brennan, Douglas V. TI Targeted violence against law enforcement officers SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID POLITICAL EXPLANATIONS; RISK-ASSESSMENT; UNITED-STATES; POLICE; SCHIZOPHRENIA; PROBABILITY; HOMICIDES; TERRORISM; DISORDER; ASSAULTS AB As highly visible representatives and guardians of society, law enforcement officers ( LEOs) are very public figures. Injury or death in the line of duty, whether due to accidents or intentional acts of violence, is an occupational hazard for LEOs. Targeted assaults on police officers, referred to as ambushes in previous literature, are a particularly perplexing problem with significant implications for society at large. In the summer of 2016, the latest in a series of high-profile acts of violence aimed at police occurred, leading to increased examination of the acts themselves and their causes. This article examines recent trends in assaults on LEOs, focusing on predatory rather than reactive attacks, and applies a threat assessment model to a case of targeted violence against police. We use State of Washington v. Christopher Monfort ( 2015), a prosecution for arson, assault with intent to murder, and murder, as a case example, to examine how the threat assessment model, and the concepts of affective versus predatory violence help in understanding targeted violence against LEOs, assessing its risk, and managing it. Copyright (C) 2016 John Wiley & Sons, Ltd. C1 [Schouten, Ronald] Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. [Schouten, Ronald; Brennan, Douglas V.] Harvard Med Sch, Psychiat, One Bowdoin Sq,10th Floor,15 New Chardon St, Boston, MA 02114 USA. Harvard Med Sch, One Bowdoin Sq,10th Floor,15 New Chardon St, Boston, MA 02114 USA. [Brennan, Douglas V.] Harvard Med Sch, MGH McLean Psychiat Residency Program, Boston, MA USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA.; Schouten, R (reprint author), Harvard Med Sch, Psychiat, One Bowdoin Sq,10th Floor,15 New Chardon St, Boston, MA 02114 USA. EM rschouten@mgh.harvard.edu NR 54 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0735-3936 EI 1099-0798 J9 BEHAV SCI LAW JI Behav. Sci. Law PD SEP-OCT PY 2016 VL 34 IS 5 SI SI BP 608 EP 621 DI 10.1002/bsl.2256 PG 14 WC Psychology, Applied; Law SC Psychology; Government & Law GA EC7CI UT WOS:000388293000003 PM 27859545 ER PT J AU Bauer, MS Miller, CJ Li, MF Bajor, LA Lee, A AF Bauer, Mark S. Miller, Christopher J. Li, Mingfei Bajor, Laura A. Lee, Austin TI A population-based study of the comparative effectiveness of second-generation antipsychotics vs older antimanic agents in bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; carbamazepine; comparative effectiveness; lithium; outcome; oxcarbazepine; second-generation antipsychotics; valproate ID RANDOMIZED CONTROLLED-TRIALS; ATYPICAL ANTIPSYCHOTICS; SCHIZOPHRENIA; LITHIUM; RISK; METAANALYSIS; DEPRESSION; VALPROATE; DRUGS; MANIA AB Objectives: Numerous antimanic treatments have been introduced over the past two decades, particularly second-generation antipsychotics (SGAs). However, it is not clear whether such newer agents provide any advantage over older treatments. Methods: A historical cohort design investigated the nationwide population of outpatients with bipolar disorder treated in the Department of Veterans Affairs who were newly initiated on an antimanic agent between 2003 and 2010 (N = 27 727). The primary outcome was likelihood of all-cause hospitalization during the year after initiation, controlling for numerous demographic, clinical, and treatment characteristics. Potential correlates of effect were explored by investigating time to initiation of a second antimanic agent or antidepressant. Results: After control for covariates, those initiated on lithium or valproate monotherapy, compared to those beginning SGA monotherapy, were significantly less likely to be hospitalized, had a longer time to hospitalization, and had fewer hospitalizations in the subsequent year. Those on combination treatment had a significantly higher likelihood of hospitalization, although they also had a longer time to addition of an additional antimanic agent or antidepressant. Conclusions: The present analysis of a large and unselected nationwide population provides important complementary data to that from controlled trials. Although various mechanisms may be responsible for the results, the data support the utilization of lithium or valproate, rather than SGAs, as the initial antimanic treatment in bipolar disorder. A large-scale, prospective, randomized, pragmatic clinical trial comparing the initiation of SGA monotherapy to that of lithium or valproate monotherapy is a logical next step. C1 [Bauer, Mark S.; Miller, Christopher J.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Bauer, Mark S.; Miller, Christopher J.; Bajor, Laura A.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Li, Mingfei] Bentley Univ, Dept Math Sci, Boston, MA USA. [Bajor, Laura A.] North Tampa Behav Hlth, CORE Mil Mental Hlth Program, Wesley Chapel, FL USA. [Lee, Austin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Lee, Austin] Univ Int Business & Econ, Sch Insurance & Econ, Beijing, Peoples R China. RP Bauer, MS (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Jamaica Plain, MA USA. EM mark.bauer@va.gov NR 44 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2016 VL 18 IS 6 BP 481 EP 489 DI 10.1111/bdi.12425 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EC7HS UT WOS:000388308400002 PM 27650468 ER PT J AU Gonzalez, S Gupta, J Villa, E Mallawaarachchi, I Rodriguez, M Ramirez, M Zavala, J Armas, R Dassori, A Contreras, J Flores, D Jerez, A Ontiveros, A Nicolini, H Escamilla, M AF Gonzalez, Suzanne Gupta, Jayanta Villa, Erika Mallawaarachchi, Indika Rodriguez, Marco Ramirez, Mercedes Zavala, Juan Armas, Regina Dassori, Albana Contreras, Javier Flores, Deborah Jerez, Alvaro Ontiveros, Alfonso Nicolini, Humberto Escamilla, Michael TI Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; Central American; family studies; genetics; lysosomal associated membrane protein 3 (LAMP3); Latinos; Mexican; Mexican-American; nuclear factor kappa B subunit 1 (NFKB1); serologically defined colon cancer antigen 8 (SDCCAG8) ID FAMILY-BASED ASSOCIATION; COMMON VARIANTS; JEWISH POPULATION; CANDIDATE GENES; SCHIZOPHRENIA; HAPLOTYPE; DEPRESSION; DISEASE; LINKAGE; RISK AB Objectives: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. Methods: A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. Results: Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P <=.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. Conclusions: These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD. C1 [Gonzalez, Suzanne; Villa, Erika; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Ctr Excellence Neurosci,Dept Biomed Sci, El Paso, TX 79430 USA. [Gupta, Jayanta] Florida Gulf Coast Univ, Dept Hlth Sci, Coll Hlth Profess & Social Work, Ft Myers, FL USA. [Mallawaarachchi, Indika] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Biostat & Epidemiol Consulting Lab, El Paso, TX USA. [Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Paul L Foster Sch Med, Dept Psychiat, Hlth Sci Ctr, El Paso, TX USA. [Armas, Regina] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. [Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Dassori, Albana] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Contreras, Javier] Univ Costa Rica, Ctr Invest Biol Celular & Mol, San Jose, Costa Rica. [Contreras, Javier] Univ Costa Rica, Escuela Biol, San Jose, Costa Rica. [Flores, Deborah] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Ctr Harbor, Torrance, CA 90509 USA. [Jerez, Alvaro] Ctr Int Trastornos Afect & Conducta Adict, Guatemala City, Guatemala. [Ontiveros, Alfonso] Inst Informac & Invest Salud Mental AC, Monterrey, Nuevo Leon, Mexico. [Nicolini, Humberto] Grp Estudios Med & Familiares Carracci SC, Mexico City, DF, Mexico. RP Gonzalez, S (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Ctr Excellence Neurosci,Dept Biomed Sci, El Paso, TX 79430 USA. EM suzanne.gonzalez@ttuhsc.edu OI Jerez Magana, Alvaro Antonio/0000-0002-1208-3769 NR 62 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2016 VL 18 IS 6 BP 520 EP 527 DI 10.1111/bdi.12438 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EC7HS UT WOS:000388308400006 PM 27759212 ER PT J AU Ospina, LH Russo, M Nitzburg, GC Cuesta-Diaz, A Shanahan, M Perez-Rodriguez, MM Mcgrath, M Levine, H Mulaimovic, S Burdick, KE AF Ospina, Luz H. Russo, Manuela Nitzburg, George C. Cuesta-Diaz, Armando Shanahan, Megan Perez-Rodriguez, Mercedes M. Mcgrath, Meaghan Levine, Hannah Mulaimovic, Sandra Burdick, Katherine E. TI The effects of cigarette smoking behavior and psychosis history on general and social cognition in bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; neurocognition; psychosis; smoking; social cognition ID SERIOUS MENTAL-ILLNESS; RATING-SCALE; TOBACCO SMOKING; WORKING-MEMORY; SCREENING-TEST; AUDIT-C; SCHIZOPHRENIA; NICOTINE; DEPRESSION; DEFICITS AB Objectives: Several studies have documented the prevalence and effects of cigarette smoking on cognition in psychotic disorders; fewer have focused on bipolar disorder (BD). Cognitive and social dysfunction are common in BD, and the severity of these deficits may be related both to illness features (e.g., current symptoms, psychosis history) and health-related behaviors (e.g.,smoking, alcohol use). The current study assessed the influence of cigarette smoking on general and social cognition in a BD cohort, accounting for illness features with a focus on psychosis history. Methods: We assessed smoking status in 105 euthymic patients with BD, who completed a comprehensive battery including social (facial affect recognition, emotional problem-solving, and theory of mind) and general (the MATRICS Consensus Cognitive Battery and executive functioning) cognitive measures. We compared smokers vs nonsmokers on cognitive performance and tested for the effects of psychosis history, premorbid intellectual functioning, substance use, and current affective symptoms. Results: Within the nonpsychotic subgroup with BD (n=45), smokers generally outperformed nonsmokers; by contrast, for subjects with BD with a history of psychosis (n=41), nonsmokers outperformed smokers. This pattern was noted more globally using a general composite cognitive score and on social/affective measures assessing patients' ability to identify emotions of facial stimuli and solve emotional problems. Conclusions: Cigarette smoking differentially affects performance on both general and social cognition in patients with BD as a function of psychosis history. These results suggest that there may be at least partially divergent underlying neurobiological causes for cognitive dysfunction in patients with BD with and without psychosis. C1 [Ospina, Luz H.; Russo, Manuela; Nitzburg, George C.; Cuesta-Diaz, Armando; Shanahan, Megan; Perez-Rodriguez, Mercedes M.; Mcgrath, Meaghan; Levine, Hannah; Mulaimovic, Sandra; Burdick, Katherine E.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ospina, Luz H.; Russo, Manuela; Nitzburg, George C.; Cuesta-Diaz, Armando; Shanahan, Megan; Perez-Rodriguez, Mercedes M.; Mcgrath, Meaghan; Levine, Hannah; Mulaimovic, Sandra; Burdick, Katherine E.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Burdick, Katherine E.] James J Peters VA Med Ctr, Bronx, NY USA. RP Burdick, KE (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.; Burdick, KE (reprint author), Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. EM katherine.burdick@mssm.edu FU NIMH NIH HHS [R01 MH100125] NR 79 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2016 VL 18 IS 6 BP 528 EP 538 DI 10.1111/bdi.12420 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EC7HS UT WOS:000388308400007 PM 27650399 ER PT J AU Abreu, MHNG Lee, KH Luquetti, DV Starr, JR AF Abreu, Mauro Henrique Nogueira Guimaraes Lee, Kyu Ha Luquetti, Daniela Varela Starr, Jacqueline Rose TI Temporal Trend in the Reported Birth Prevalence of Cleft Lip and/or Cleft Palate in Brazil, 2000 to 2013 SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE time series analysis; cleft lip; cleft palate; epidemiology; health information systems ID ORAL CLEFTS; FOLIC-ACID; OROFACIAL CLEFTS; PREGNANCY; DEFECTS AB Background: The birth prevalence of cleft lip with or without cleft palate (CL/P) in Brazil increased between the years from 1975 to 1994 but has not been evaluated for temporal trend since then. Methods: We used data from the Brazilian National Health Information System for the years 2000 through 2013. We calculated the reported CL/P birth prevalence each year per 10,000 live births and estimated the average increase in reported prevalence per year (and 95% confidence interval [CI]) by fitting a negative binomial regression model. We also estimated the temporal trend in each of the five Brazilian regions for this time period. Results: The overall reported birth prevalence was 4.85 (95% CI, 4.78-4.91) per 10,000 live births. The reported birth prevalence of CL/P increased over this time period, from 3.94 (95% CI, 3.73-4.17) per 10,000 in 2000 to 5.46 (95% CI, 5.20-5.74) per 10,000 in 2013. The temporal trend differed for different Brazilian geographic regions, being confined primarily to the Northeast (4.7% per year; 95% CI, 4.0%-5.5%), North (3.3% per year; 95% CI, 1.8%-4.7%), and Central (2.9% per year; 95% CI, 0.9%-4.9%) regions. Conclusion: In recent years, there appears to be an upward trend in the reported prevalence of CL/P in Brazil, confined to the less developed regions of the country. The increase likely reflects improved surveillance; whether it also reflects etiologic differences is unknown. (C) 2016 Wiley Periodicals, Inc. C1 [Abreu, Mauro Henrique Nogueira Guimaraes] Univ Fed Minas Gerais, Dept Community & Prevent Dent, Belo Horizonte, MG, Brazil. [Lee, Kyu Ha; Starr, Jacqueline Rose] Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. [Luquetti, Daniela Varela] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. RP Abreu, MHNG; Starr, JR (reprint author), Forsyth Inst, Dept Appl Oral Sci, 245 First St, Cambridge, MA 02142 USA. EM maurohenriqueabreu@gmail.com; jstarr@forsyth.org NR 16 TC 0 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD SEP PY 2016 VL 106 IS 9 BP 789 EP 792 DI 10.1002/bdra.23528 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA EC7IA UT WOS:000388309200007 PM 27256471 ER PT J AU Dodson, JA Matlock, DD Forman, DE AF Dodson, John A. Matlock, Daniel D. Forman, Daniel E. TI Geriatric Cardiology: An Emerging Discipline SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID AORTIC-VALVE-REPLACEMENT; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE ENTERPRISES; OLDER-ADULTS; HEART-FAILURE; ELDERLY-PATIENTS; COGNITIVE IMPAIRMENT; MAJOR SHAREHOLDERS; DECISION-MAKING; UNITED-STATES AB Given changing demographics, patients with cardiovascular (CV) disease in developed countries are now older and more complex than even a decade ago. This trend is expected to continue into the foreseeable future; accordingly, cardiologists are encountering patients with a greater number of comorbid illnesses as well as "geriatric conditions," such as cognitive impairment and frailty, which complicate management and influence outcomes. Simultaneously, technological advances have widened the therapeutic options available for patients, including those with the most advanced CV disease. In the setting of these changes, geriatric cardiology has recently emerged as a discipline that aims to adapt principles from geriatric medicine to everyday cardiology practice. Accordingly, the tasks of a "geriatric cardiologist" may include both traditional evidence-based CV management plus comprehensive geriatric assessment, medication reduction, team-based coordination of care, and explicit incorporation of patient goals into management. Given that the field is still in its relative infancy, the training pathways and structure of clinical programs in geriatric cardiology are still being delineated. In this review, we highlight the rationale behind geriatric cardiology as a discipline, several current approaches by geriatric cardiology programs, and future directions for the field. C1 [Dodson, John A.] NYU, Sch Med, Leon H Charney Div Cardiol, New York, NY USA. [Dodson, John A.] NYU, Sch Med, Dept Med, New York, NY USA. [Dodson, John A.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Matlock, Daniel D.] Univ Colorado, Sch Med, Dept Med, Div Geriatr, Aurora, CO USA. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Dept Med, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Dodson, JA (reprint author), NYU, Sch Med, 227 E 30th St, New York, NY 10016 USA. EM john.dodson@nyumc.org FU American Heart Association; Peter A. Lefkow, MD Lead Charitable Trust; NIA grant [P30 AG024827]; VA Office of Rehabilitation Research and Development grant [F0834-R]; National Institutes on Aging [K23AG040696] FX J.A.D. is supported in part by a Mentored Clinical and Population Research Award from the American Heart Association and by the Peter A. Lefkow, MD Lead Charitable Trust. D.E.F. is supported in part by NIA grant P30 AG024827 and VA Office of Rehabilitation Research and Development grant F0834-R. D.D.M. is supported by a career development award from the National Institutes on Aging (K23AG040696). NR 75 TC 1 Z9 1 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2016 VL 32 IS 9 BP 1056 EP 1064 DI 10.1016/j.cjca.2016.03.019 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EC7DU UT WOS:000388296800005 PM 27476988 ER PT J AU Forman, DE Alexander, KP AF Forman, Daniel E. Alexander, Karen P. TI Frailty: A Vital Sign for Older Adults With Cardiovascular Disease SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID AORTIC-VALVE-REPLACEMENT; CORONARY-ARTERY-DISEASE; ALL-CAUSE MORTALITY; GAIT SPEED; PHYSICAL PERFORMANCE; ELDERLY-PATIENTS; CARDIAC-SURGERY; HEART-FAILURE; EYEBALL TEST; RISK AB Mechanisms of aging predispose to cardiovascular disease (CVD), as well as to aggregate health challenges. For older adults, CVD is likely to exist in combination with comorbid conditions, disability, polypharmacy, falling risks, and body composition changes. These other dimensions of health result in cumulative weakening with greater clinical complexity that confound basic precepts of CVD presentation, prognosis, and treatments. A convenient operational tool is needed to gauge this age-related vulnerability such that it can be integrated in the evaluation and treatment of CVD. Frailty is a concept that is neither disease-nor age-specific, but is used to characterize the reserve that a person has available to tolerate stresses associated with aging, disease, and even therapy. Frailty arises from specific biological mechanisms in association with cumulative physiological decrements, psychosocial stresses, and physical impairments. Performance-based and survey tools have been developed and tested to measure frailty. Although different frailty tools vary in practicality, measured domains, and precise applications, all are useful in identifying risks that commonly accrue with age. Although comparisons between frailty tools are ongoing and sometimes even controversial, the rationale to integrate routine use of frailty screening as part of routine care is relatively straightforward and easy to envision. Frailty assessment applied as a vital sign (for standard maintenance and evaluation of new symptoms) enhances perspectives of risk, decision-making, and opportunities for tailored CVD management. C1 [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. RP Forman, DE (reprint author), Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Div Cardiol, 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA.; Forman, DE (reprint author), Univ Pittsburgh, Med Ctr, Div Geriatr, 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA. EM formand@pitt.edu FU NIA grant [P30 AG024827]; VA Office of Rehabilitation Research and Development grant [F0834-R] FX Dr Forman is supported in part by NIA grant P30 AG024827 and VA Office of Rehabilitation Research and Development grant F0834-R. NR 73 TC 2 Z9 2 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2016 VL 32 IS 9 BP 1082 EP 1087 DI 10.1016/j.cjca.2016.05.015 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EC7DU UT WOS:000388296800008 PM 27476987 ER PT J AU Schopfer, DW Forman, DE AF Schopfer, David W. Forman, Daniel E. TI Cardiac Rehabilitation in Older Adults SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Review ID AMERICAN-HEART-ASSOCIATION; RANDOMIZED CONTROLLED-TRIALS; ARTERY-DISEASE PATIENTS; FRAIL ELDERLY-PATIENTS; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; MYOCARDIAL-INFARCTION; PULMONARY-REHABILITATION; CARDIOVASCULAR EVENTS; SCIENTIFIC STATEMENT AB The biology of aging and the pathophysiology of cardiovascular disease (CVD) overlap, with the effect that CVD is endemic in the growing population of older adults. Moreover, CVD in older adults is usually complicated by age-related complexities, including multimorbidity, polypharmacy, frailty, and other intricacies that add to the risks of ambiguous symptoms, deconditioning, iatrogenesis, falls, disability, and other challenges. Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with cardiovascular conditions. Although CR was originally designed primarily as an exercise training program for younger adults after a myocardial infarction or coronary artery bypass surgery, it has evolved as a comprehensive lifestyle program (promoting physical activity as well as education, diet, risk reduction, and adherence) for a broader range of CVD (coronary heart disease, heart failure, and valvular heart disease). It provides a valuable opportunity to address and moderate many of the challenges pertinent for the large and growing population of older adults with CVD. Cardiac rehabilitation promotes physical function (cardiorespiratory fitness as well as strength and balance) that helps overcome disease and deconditioning as well as related vulnerabilities such as disability, frailty, and falls. Similarly, CR facilitates education, monitoring, and guidance to reduce iatrogenesis and promote adherence. Furthermore, CR fosters cognition, socialization, and independence in older patients. Yet despite all its conceptual benefits, CR is significantly underused in older populations. This review discusses benefits and the paradoxical underuse of CR, as well as evolving models of care that may achieve greater application and efficacy. C1 [Schopfer, David W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Schopfer, David W.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geriatr Res & Clin Ctr, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Forman, DE (reprint author), Div Geriatr, Sect Geriatr Cardiol, 3471 Fifth Ave, Pittsburgh, PA 15213 USA.; Forman, DE (reprint author), Div Cardiol, 3471 Fifth Ave, Pittsburgh, PA 15213 USA. EM formand@pitt.edu FU National Center for Advancing Translational Sciences of the NIH [KL2TR000143]; NIA grant [P30 AG024827]; VA Office of Rehabilitation Research and Development grant [F0834-R] FX D.W.S. is supported by the National Center for Advancing Translational Sciences of the NIH under Award Number KL2TR000143. D.E.F. is supported in part by NIA grant P30 AG024827 and VA Office of Rehabilitation Research and Development grant F0834-R. NR 77 TC 1 Z9 1 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X EI 1916-7075 J9 CAN J CARDIOL JI Can. J. Cardiol. PD SEP PY 2016 VL 32 IS 9 BP 1088 EP 1096 DI 10.1016/j.cjca.2016.03.003 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EC7DU UT WOS:000388296800009 PM 27297002 ER PT J AU Rudolph, JW Palaganas, J Fey, MK Morse, CJ Onello, R Dreifuerst, KT Simon, R AF Rudolph, Jenny W. Palaganas, Janice Fey, Mary K. Morse, Catherine J. Onello, Rachel Dreifuerst, Kristina Thomas Simon, Robert TI A DASH to the Top: Educator Debriefing Standards as a Path to Practice Readiness for Nursing Students SO CLINICAL SIMULATION IN NURSING LA English DT Editorial Material ID HEALTH-CARE; DELIBERATE PRACTICE; SIMULATION; PERFORMANCE; FEEDBACK C1 [Rudolph, Jenny W.] Harvard Med Sch, Ctr Med Simulat, Inst Med Simulat, Boston, MA USA. [Rudolph, Jenny W.; Palaganas, Janice] Harvard Med Sch, Anesthesia, Boston, MA USA. [Rudolph, Jenny W.; Palaganas, Janice; Fey, Mary K.; Morse, Catherine J.; Simon, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Palaganas, Janice] Harvard Med Sch, Ctr Med Simulat, Educ Innovat & Dev, Boston, MA USA. [Fey, Mary K.] Harvard Med Sch, Ctr Med Simulat, Boston, MA 02115 USA. [Fey, Mary K.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Morse, Catherine J.; Simon, Robert] Ctr Med Simulat, Educ Leadership Program, Boston, MA USA. [Morse, Catherine J.; Simon, Robert] Ctr Med Simulat, Int Program, Boston, MA USA. [Morse, Catherine J.; Simon, Robert] Harvard Med Sch, Boston, MA USA. [Onello, Rachel] Univ Maryland, Sch Nursing, Org Syst & Adult Hlth, Baltimore, MD 21201 USA. [Dreifuerst, Kristina Thomas] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. RP Fey, MK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Fey, MK (reprint author), Harvard Med Sch, Ctr Med Simulat, Boston, MA 02115 USA.; Fey, MK (reprint author), Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. EM MFEY@mgh.harvard.edu NR 26 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 1876-1399 EI 1876-1402 J9 CLIN SIMUL NURS JI Clin. Simul. Nurs. PD SEP PY 2016 VL 12 IS 9 BP 412 EP 417 DI 10.1016/j.ecns.2016.05.003 PG 6 WC Nursing SC Nursing GA EC9RV UT WOS:000388482800008 ER PT J AU Hooper, DC Jacoby, GA AF Hooper, David C. Jacoby, George A. TI Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID MULTIDRUG EFFLUX PUMP; MULTIPLE ANTIBIOTIC-RESISTANCE; MEDIATED QUINOLONE RESISTANCE; MEXA-MEXB-OPRM; PENTAPEPTIDE REPEAT PROTEINS; GRAM-NEGATIVE BACTERIA; DNA GYRASE INHIBITOR; 16S RIBOSOMAL-RNA; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI AB Quinolone antimicrobials are widely used in clinical medicine and are the only current class of agents that directly inhibit bacterial DNA synthesis. Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity. Resistance has emerged with clinical use of these agents and is common in some bacterial pathogens. Mechanisms of resistance include mutational alterations in drug target affinity and efflux pump expression and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes are commonly in a localized domain of the GyrA and ParC subunits of gyrase and topoisomerase IV, respectively, and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include other antimicrobials as well as quinolones. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is because of Qnr proteins that protect the target enzymes from quinolone action, a mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. C1 [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM dhooper@partners.org FU U.S. Public Health Service, National Institutes of Health [R01 AI057576, R37 AI023988, P01 AI083214] FX This work is supported by Grants R01 AI057576 (to D.C.H and G.A.J.), R37 AI023988 (to D.C.H.), and P01 AI083214 (to D.C.H.) from the U.S. Public Health Service, National Institutes of Health. NR 192 TC 0 Z9 0 U1 8 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD SEP PY 2016 VL 6 IS 9 AR a025320 DI 10.1101/cshperspect.a025320 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA EC7KQ UT WOS:000388317500006 ER PT J AU Jiang, WP Zhou, IY Wen, LY Zhou, X Sun, PZ AF Jiang, Weiping Zhou, Iris Yuwen Wen, Lingyi Zhou, Xin Sun, Phillip Zhe TI A theoretical analysis of chemical exchange saturation transfer echo planar imaging (CEST-EPI) steady state solution and the CEST sensitivity efficiency-based optimization approach SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE chemical exchange saturation transfer (CEST); contrast-to-noise ratio (CNR); quantitative CEST (qCEST); signal-to-noise ratio (SNR); specific absorption rate (SAR) ID PH-WEIGHTED MRI; PROTON FRACTION RATIO; MAGNETIC-RESONANCE; IN-VIVO; RF IRRADIATION; ISCHEMIC PENUMBRA; RATIOMETRIC APPROACH; CEREBRAL-ISCHEMIA; BRAIN-TUMOR; TISSUE PH AB Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironmental properties, augmenting routine relaxation-based MRI. Recent developments of quantitative CEST (qCEST) analysis such as omega plots and RF-power based ratiometric calculation have extended our ability to elucidate the underlying CEST system beyond the simplistic apparent CEST measurement. CEST MRI strongly varies with experimental factors, including the RF irradiation level and duration as well as repetition time and flip angle. In addition, the CEST MRI effect is typically small, and experimental optimization strategies have to be carefully evaluated in order to enhance the CEST imaging sensitivity. Although routine CEST MRI has been optimized largely based on maximizing the magnitude of the CEST effect, the CEST signal-to-noise (SNR) efficiency provides a more suitable optimization index, particularly when the scan time is constrained. Herein, we derive an analytical solution of the CEST effect that takes into account key experimental parameters including repetition time, imaging flip angle and RF irradiation level, and solve its SNR efficiency. The solution expedites CEST imaging sensitivity calculation, substantially faster than the Bloch-McConnell equation-based numerical simulation approach. In addition, the analytical solution-based SNR formula enables the exhaustive optimization of CEST MRI, which simultaneously predicts multiple optimal parameters such as repetition time, flip angle and RF saturation level based on the chemical shift and exchange rate. The sensitivity efficiency-based optimization approach could simplify and guide imaging of CEST agents, including glycogen, glucose, creatine, gamma-aminobutyric acid and glutamate. Copyright (C) 2016 John Wiley & Sons, Ltd. C1 [Jiang, Weiping; Zhou, Xin] Chinese Acad Sci, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan, Peoples R China. [Jiang, Weiping; Zhou, Iris Yuwen; Wen, Lingyi; Sun, Phillip Zhe] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Jiang, Weiping; Zhou, Iris Yuwen; Wen, Lingyi; Sun, Phillip Zhe] Harvard Med Sch, Charlestown, MA USA. [Sun, Phillip Zhe] Univ Illinois, Dept Radiol, Chicago, IL USA. RP Zhou, X (reprint author), Chinese Acad Sci, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan, Peoples R China.; Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.; Sun, PZ (reprint author), Harvard Med Sch, Charlestown, MA USA. EM xinzhou@wipm.ac.cn; pzhesun@mgh.harvard.edu RI Zhou, Iris Yuwen/A-2089-2017 OI Zhou, Iris Yuwen/0000-0002-4351-7398 FU National Natural Science Foundation of China [NSFC81227902]; National Institutes of Health [1R01NS083654, 1U01HD087211] FX This study was supported in part by grants from the National Natural Science Foundation of China, NSFC81227902 (Zhou), and the National Institutes of Health, 1R01NS083654 (Sun) and 1U01HD087211 (Grant/Adalsteinsson/Wald). NR 65 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 EI 1555-4317 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD SEP-OCT PY 2016 VL 11 IS 5 BP 415 EP 423 DI 10.1002/cmmi.1699 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EC9ZK UT WOS:000388502600009 PM 27312932 ER PT J AU Adler, JT Chang, DC Chan, AT Faiz, O Maguire, LH AF Adler, Joel T. Chang, David C. Chan, Andrew T. Faiz, Omar Maguire, Lillias H. TI Seasonal Variation in Diverticulitis: Evidence From Both Hemispheres SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Diverticulitis; Seasonal variation ID UNITED-STATES; DISEASE; RISK AB BACKGROUND: Diverticulitis is a common and morbid disease with incompletely understood risk factors and pathophysiology. Geographic and, recently, seasonal trends in diverticulitis have been described in the United States. OBJECTIVE: The purpose of this study was to investigate and compare seasonal trends in urgent hospital admission for diverticulitis in geographically distinct populations in the northern and southern hemispheres. DESIGN: Inpatient, urgent admissions for diverticulitis were identified within the Dr Foster Intelligence Global Comparators Dataset, a global benchmarking collaborative. SETTINGS: Admissions to participating hospitals in the United Kingdom, Australia, and the United States were identified between 2008 and 2013. PATIENTS: A total of 18,672 urgent admissions for diverticulitis were identified among 5.5-million admissions. MAIN OUTCOME MEASURES: Four separate hypothesis testing methods were used to identify seasonal trends in diverticulitis admissions among international patient populations. RESULTS: Seasonal trends were present in all 3 countries. A summer peak was observed in both hemispheres using multiple statistical testing methods. Logistic regression analyses identified summer months as significantly associated with diverticulitis admission in all 3 countries. LIMITATIONS: This study is limited by restriction to inpatient admissions, reliance on administrative data, and participation of select hospitals within the database. CONCLUSIONS: These data suggest a shared seasonal risk factor among geographically distinct populations for diverticulitis. C1 [Adler, Joel T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [Adler, Joel T.; Chang, David C.; Maguire, Lillias H.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Faiz, Omar] North West London NHS Trust, St Marks Hosp, London, England. [Faiz, Omar] Imperial Coll London, London, England. RP Maguire, LH (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM lhmaguire@partners.org OI Adler, Joel/0000-0001-8190-3444 FU Arthur Tracy Cabot Fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital FX Dr Adler is funded by the Arthur Tracy Cabot Fellowship from the Center for Surgery and Public Health at Brigham and Women's Hospital. NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD SEP PY 2016 VL 59 IS 9 BP 870 EP 877 DI 10.1097/DCR.0000000000000657 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA EC8EP UT WOS:000388373600009 PM 27505116 ER PT J AU Sibaud, V Leboeuf, NR Roche, H Belum, VR Gladieff, L Deslandres, M Montastruc, M Eche, A Vigarios, E Dalenc, F Lacouture, ME AF Sibaud, Vincent Leboeuf, Nicole R. Roche, Henri Belum, Viswanath R. Gladieff, Laurence Deslandres, Marion Montastruc, Marion Eche, Audrey Vigarios, Emmanuelle Dalenc, Florence Lacouture, Mario E. TI Dermatological adverse events with taxane chemotherapy SO EUROPEAN JOURNAL OF DERMATOLOGY LA English DT Review DE hair; nab-paclitaxel; nail; skin; taxanes; toxicity; docetaxel; paclitaxel ID CUTANEOUS LUPUS-ERYTHEMATOSUS; BREAST-CANCER PATIENTS; ALBUMIN-BOUND PACLITAXEL; HAND-FOOT SYNDROME; OF-THE-LITERATURE; INDUCED ACRAL ERYTHEMA; DOCETAXEL-INDUCED ONYCHOLYSIS; RADIATION-RECALL DERMATITIS; RANDOMIZED CONTROLLED-TRIAL; STEVENS-JOHNSON-SYNDROME AB Taxanes (docetaxel and paclitaxel) are among the most commonly prescribed anticancer drugs approved for the treatment of metastatic or locally advanced breast, non-small cell lung, prostate, gastric, head and neck, and ovarian cancers, as well as in the adjuvant setting for operable node-positive breast cancers. Although the true incidence of dermatological adverse events (AEs) in patients receiving taxanes is not known, and has never been prospectively analysed, they clearly represent one of the major AEs associated with these agents. With an increase in the occurrence of cutaneous AEs during treatment with novel targeted and immunological therapies when used in combination with taxanes, a thorough understanding of reactions attributable to this class is imperative. Moreover, identification and management of dermatological AEs is critical for maintaining the quality of life in cancer patients and for minimizing dose modifications of their antineoplastic regimen. This analysis represents a systematic review of the dermatological conditions reported with the use of these drugs, complemented by experience at comprehensive cancer centres. The conditions reported herein include skin, hair, and nail toxicities. Lastly, we describe the dermatological data available for the new, recently FDA-and EMA-approved, solvent-free nab-paclitaxel. C1 [Sibaud, Vincent] Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Oncodermatol, Toulouse, France. [Sibaud, Vincent] Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Clin Res, Toulouse, France. [Leboeuf, Nicole R.] Harvard Med Sch, Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Boston, MA USA. [Roche, Henri; Gladieff, Laurence; Deslandres, Marion; Montastruc, Marion; Eche, Audrey; Dalenc, Florence] Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Oncol, Toulouse, France. [Belum, Viswanath R.; Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, Dermatol Serv, 1275 York Ave, New York, NY 10021 USA. [Vigarios, Emmanuelle] Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Oral Med, Toulouse, France. RP Sibaud, V (reprint author), Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Oncodermatol, Toulouse, France.; Sibaud, V (reprint author), Toulouse Oncopole, Inst Univ Canc, Inst Claudius Regaud, Dept Clin Res, Toulouse, France. EM sibaud.vincent@iuct-oncopole.fr RI Roche, Henri/O-9211-2014 OI Roche, Henri/0000-0001-7463-205X NR 161 TC 1 Z9 1 U1 5 U2 5 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1167-1122 EI 1952-4013 J9 EUR J DERMATOL JI Eur. J. Dermatol. PD SEP-OCT PY 2016 VL 26 IS 5 BP 427 EP 443 DI 10.1684/ejd.2016.2833 PG 17 WC Dermatology SC Dermatology GA EC4XF UT WOS:000388137000001 PM 27550571 ER PT J AU Mak, KS van Bommel, ACM Stowell, C Abrahm, JL Baker, M Baldotto, CS Baldwin, DR Borthwick, D Carbone, DP Chen, AB Fox, J Haswell, T Koczywas, M Kozower, BD Mehran, RJ Schramel, FM Senan, S Stirling, RG van Meerbeeck, JP Wouters, MWJM Peake, MD AF Mak, Kimberley S. van Bommel, Annelotte C. M. Stowell, Caleb Abrahm, Janet L. Baker, Matthew Baldotto, Clarissa S. Baldwin, David R. Borthwick, Diana Carbone, David P. Chen, Aileen B. Fox, Jesme Haswell, Tom Koczywas, Marianna Kozower, Benjamin D. Mehran, Reza J. Schramel, Franz M. Senan, Suresh Stirling, Robert G. van Meerbeeck, Jan P. Wouters, Michel W. J. M. Peake, Michael D. CA Lung Canc Working Grp ICHOM TI Defining a standard set of patient-centred outcomes for lung cancer SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID QUALITY-OF-LIFE; REPORTED OUTCOMES; PALLIATIVE CARE; CLINICAL-TRIALS; EORTC QLQ-C30; SELF-REPORT; SURVIVAL; QUESTIONNAIRE; CHEMOTHERAPY; COMORBIDITY AB In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes. The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation ("the set") on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment. The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons. We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally. C1 [Mak, Kimberley S.; van Bommel, Annelotte C. M.; Stowell, Caleb] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Mak, Kimberley S.] Harvard Radiat Oncol Program, Boston, MA USA. [Mak, Kimberley S.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [van Bommel, Annelotte C. M.] Dutch Inst Clin Auditing, Leiden, Netherlands. [Abrahm, Janet L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Baldotto, Clarissa S.] Clin Oncol Integradas, Dept Med Oncol, Rio De Janeiro, Brazil. [Baldwin, David R.] Univ Nottingham Hosp, Dept Resp Med, Nottingham, England. [Borthwick, Diana] Edinburgh Canc Res Ctr, Dept Thorac Oncol, Edinburgh, Midlothian, Scotland. [Baldwin, David R.] Ohio State Univ, Ctr Comprehens Canc, Dept Med Oncol, Columbus, OH 43210 USA. [Chen, Aileen B.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Fox, Jesme] Roy Castle Lung Canc Fdn, Liverpool, Merseyside, England. [Koczywas, Marianna] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Kozower, Benjamin D.] Univ Virginia Hlth Syst, Dept Thorac Surg, Charlottesville, VA USA. [Mehran, Reza J.] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX USA. [Schramel, Franz M.] St Antonius Hosp, Dept Pulmonol, Nieuwegein, Netherlands. [Senan, Suresh] Vrije Univ Amsterdam, Med Ctr, Dept Radiat Oncol, Amsterdam, Netherlands. [Stirling, Robert G.] Monash Univ, Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia. [van Meerbeeck, Jan P.] Univ Antwerp Hosp, Dept Thorac Oncol, Edegem, Belgium. [Wouters, Michel W. J. M.] Netherlands Canc Inst, Dept Surg Oncol, Amsterdam, Netherlands. [Wouters, Michel W. J. M.] Dutch Inst Clin Auditing, Sci Bur, Leiden, Netherlands. [Peake, Michael D.] Univ Hosp Leicester, Dept Resp Med, Leicester LE3 9QP, Leics, England. [Peake, Michael D.] Publ Hlth England, NCRAS, London, England. RP Peake, MD (reprint author), Univ Hosp Leicester, Dept Resp Med, Leicester LE3 9QP, Leics, England. EM mick.peake@uhl-tr.nhs.uk OI Senan, Suresh/0000-0003-3995-2204 FU Alliance of Dedicated Cancer Centers FX The Lung Cancer Standard Set is made possible through the generous support of the Alliance of Dedicated Cancer Centers. Funding information for this article has been deposited with the Open Funder Registry. NR 40 TC 0 Z9 0 U1 1 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2016 VL 48 IS 3 BP 852 EP 860 DI 10.1183/13993003.02049-2015 PG 9 WC Respiratory System SC Respiratory System GA EC7GL UT WOS:000388304800033 PM 27390281 ER PT J AU Lipworth, B Wedzicha, J Devereux, G Vestbo, J Dransfield, MT AF Lipworth, Brian Wedzicha, Jadwiga Devereux, Graham Vestbo, Jorgen Dransfield, Mark T. TI Beta-blockers in COPD: time for reappraisal SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; REGRESSION-ANALYSIS; EXERCISE CAPACITY; PERSISTENT ASTHMA; CLINICAL-OUTCOMES; EJECTION FRACTION AB The combined effects on the heart of smoking and hypoxaemia may contribute to an increased cardiovascular burden in chronic obstructive pulmonary disease (COPD). The use of beta-blockers in COPD has been proposed because of their known cardioprotective effects as well as reducing heart rate and improving systolic function. Despite the proven cardiac benefits of beta-blockers post-myocardial infarction and in heart failure they remain underused due to concerns regarding potential bronchoconstriction, even with cardioselective drugs. Initiating treatment with beta-blockers requires dose titration and monitoring over a period of weeks, and beta-blockers may be less well tolerated in older patients with COPD who have other comorbidities. Medium-term prospective placebo-controlled safety studies in COPD are warranted to reassure prescribers regarding the pulmonary and cardiac tolerability of beta-blockers as well as evaluating their potential interaction with concomitant inhaled long-acting bronchodilator therapy. Several retrospective observational studies have shown impressive reductions in mortality and exacerbations conferred by beta-blockers in COPD. However, this requires confirmation from long-term prospective placebo-controlled randomised controlled trials. The real challenge is to establish whether beta-blockers confer benefits on mortality and exacerbations in all patients with COPD, including those with silent cardiovascular disease where the situation is less clear. C1 [Lipworth, Brian] Univ Dundee, Ninewells Hosp & Med Sch, Scottish Ctr Resp Res, Dundee DD1 9SY, Scotland. [Wedzicha, Jadwiga] Imperial Coll London, Natl Heart & Lung Inst, Airways Dis Sect, London, England. [Devereux, Graham] Univ Aberdeen, Appl Hlth Sci, Aberdeen, Scotland. [Vestbo, Jorgen] Univ Manchester, Univ Hosp South Manchester NHS Fdn Trust, Ctr Resp Med & Allergy, Manchester, Lancs, England. [Dransfield, Mark T.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Lung Hlth Ctr, Birmingham, AL USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Lipworth, B (reprint author), Univ Dundee, Ninewells Hosp & Med Sch, Scottish Ctr Resp Res, Dundee DD1 9SY, Scotland. EM b.j.lipworth@dundee.ac.uk FU Medical Research Council [G1001372, G0800570, G1001365] NR 79 TC 4 Z9 4 U1 4 U2 4 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2016 VL 48 IS 3 BP 880 EP 888 DI 10.1183/13993003.01847-2015 PG 9 WC Respiratory System SC Respiratory System GA EC7GL UT WOS:000388304800036 PM 27390282 ER PT J AU Fisher, JA Puett, RC Hart, JE Camargo, CA Varraso, R Yanosky, JD Laden, F AF Fisher, Jared A. Puett, Robin C. Hart, Jaime E. Camargo, Carlos A., Jr. Varraso, Raphaelle Yanosky, Jeff D. Laden, Francine TI Particulate matter exposures and adult-onset asthma and COPD in the Nurses' Health Study SO EUROPEAN RESPIRATORY JOURNAL LA English DT Letter ID AMBIENT AIR-POLLUTION; OBSTRUCTIVE PULMONARY-DISEASE; COHORT; WOMEN C1 [Fisher, Jared A.; Puett, Robin C.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Fisher, Jared A.; Puett, Robin C.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Hart, Jaime E.; Camargo, Carlos A., Jr.; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Hart, Jaime E.; Camargo, Carlos A., Jr.; Laden, Francine] Harvard Med Sch, Boston, MA USA. [Hart, Jaime E.; Laden, Francine] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.; Laden, Francine] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Varraso, Raphaelle] VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, INSERM U1168, Villejuif, France. [Varraso, Raphaelle] Univ Versailles St Quentin En Yvelines, UMR S 1168, Versailles, France. [Yanosky, Jeff D.] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA. RP Fisher, JA (reprint author), Univ Maryland, Sch Publ Hlth, 255 Valley Dr,Room 1222, College Pk, MD 20742 USA. EM jafisher@umd.edu OI Varraso, raphaelle/0000-0002-3338-7825 NR 15 TC 0 Z9 0 U1 3 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD SEP PY 2016 VL 48 IS 3 BP 921 EP 924 DI 10.1183/13993003.00845-2015 PG 4 WC Respiratory System SC Respiratory System GA EC7GL UT WOS:000388304800040 PM 27288040 ER PT J AU Jain, SH Goodman, EB Powers, BW Katz, JT AF Jain, Sachin H. Goodman, Elaine B. Powers, Brian W. Katz, Joel T. TI The residency-MBA program: A novel approach to training physician leaders SO HEALTHCARE-THE JOURNAL OF DELIVERY SCIENCE AND INNOVATION LA English DT Article DE Management training; Residency; Post-graduate medical education ID MANAGEMENT C1 [Jain, Sachin H.] CareMore Hlth Syst, Cerritos, CA USA. [Jain, Sachin H.; Powers, Brian W.; Katz, Joel T.] Harvard Sch Business, Boston, MA USA. [Jain, Sachin H.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Goodman, Elaine B.; Powers, Brian W.] Harvard Med Sch, Boston, MA USA. [Goodman, Elaine B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katz, Joel T.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Katz, JT (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jkatz@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-0764 EI 2213-0772 J9 HEALTHCARE JI HealthCare PD SEP PY 2016 VL 4 IS 3 BP 142 EP 144 DI 10.1016/j.hjdsi.2015.10.009 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EC4NE UT WOS:000388107800006 PM 27637817 ER PT J AU Liao, JM Emanuel, EJ Navathe, AS AF Liao, Joshua M. Emanuel, Ezekiel J. Navathe, Amol S. TI Six health care trends that will reshape the patient-provider dynamic SO HEALTHCARE-THE JOURNAL OF DELIVERY SCIENCE AND INNOVATION LA English DT Article ID PHYSICIAN; MEDICINE AB Six trends - movement towards value-based payment, rapid adoption of digital health technology, care delivery in non-traditional settings, development of individualized clinical guidelines, increased transparency, and growing cultural awareness about the harms of medical overuse are driving the US health care system towards a future defined by quality- and patient-centric care. Health care organizations are responding to these changes by implementing provider and workforce changes, pursuing stronger payer provider integration, and accelerating the use of digital technology and data. While these efforts can also improve the clinical relationship and create positive system redesign among health care organizations, they require alignment between organizational and physician incentives that can inadvertently harm the dynamic between patients and providers. Organizations can utilize several strategies to preserve the patient-physician relationship and advance the positive benefits of new organizational strategies while guarding against unintended consequences. (C) 2016 Elsevier Inc. All rights reserved. C1 [Liao, Joshua M.; Emanuel, Ezekiel J.; Navathe, Amol S.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel J.; Navathe, Amol S.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Navathe, Amol S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Liao, JM (reprint author), Div Gen Internal Med, 1205 Blockley,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 17 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-0764 EI 2213-0772 J9 HEALTHCARE JI HealthCare PD SEP PY 2016 VL 4 IS 3 BP 148 EP 150 DI 10.1016/j.hjdsi.2016.06.008 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EC4NE UT WOS:000388107800008 PM 27396533 ER PT J AU Neuman, MD Passarella, MR Werner, RM AF Neuman, Mark D. Passarella, Molly R. Werner, Rachel M. TI The relationship between historical risk-adjusted 30-day mortality and subsequent hip fracture outcomes: Retrospective cohort study SO HEALTHCARE-THE JOURNAL OF DELIVERY SCIENCE AND INNOVATION LA English DT Article DE Hip fracture; Quality measurement; Aging/geriatrics; Surgical outcomes ID MINIMUM DATA SET; NURSING-HOME RESIDENTS; QUALITY-OF-CARE; FUNCTIONAL STATUS; PSYCHOMETRIC CHARACTERISTICS; SURGICAL MORTALITY; OLDER-ADULTS; SURGERY; MDS; COMORBIDITIES AB Background: While 30-day risk-adjusted mortality is a performance measure for hip fracture care, it has not been shown to predict long-term outcomes. We assessed whether hospital rankings based on historical 30-day mortality predicted subsequent hip fracture outcomes. Methods: Using national Medicare data, we calculated annual hospital performance rankings based on standardized 30-day hip fracture mortality ratios. We used logistic regression to measure the association of patients' survival at 180 days with their hospital's ranking for the year prior to admission. Subgroup analyses assessed whether associations between hospital performance and 180-day outcomes were similar for community-dwelling patients as well as those living in nursing homes prior to fracture. Results: Out of 378,077 patients hospitalized with hip fractures between January 1, 2007 and June 30, 2009, 81,653 (21.6%) died by 180 days. Worse historical hospital performance was associated with a greater adjusted odds of 30 day mortality (odds ratio (OR), fourth vs. first quartile: 1.24, 95% confidence interval (CI): 1.18,1.29, P< 0.001) and 180 day mortality (OR, fourth vs. first quartile: 1.15, 95% CI 1.11,1.18, P< 0.001). Past hospital performance was associated with death or new nursing home placement among community dwellers (OR, fourth vs. first quartile: 1.09, 95% CI 1.05, 1.13, P < 0.001), but was not associated with death or new dependence in locomotion among nursing home residents (OR 1.05, 95% CI 0.97, 1.15, P=0.229). Conclusions: Better historical hospital hip fracture mortality predicts modest decreases in mortality at 180 days for subsequent patients, but is inconsistently associated with changes in functional outcomes. Level of evidence: Level 3 (Non-randomized controlled cohort study). (C) 2015 Elsevier Inc. All rights reserved. C1 [Neuman, Mark D.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, 423 Guardian Dr,1119A Blockley Hall, Philadelphia, PA 19104 USA. [Neuman, Mark D.; Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Neuman, Mark D.] Univ Penn, Perelman Sch Med, Dept Internal Med, Div Geriatr Med, Philadelphia, PA 19104 USA. [Passarella, Molly R.] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Univ Penn, Perelman Sch Med, Dept Internal Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Neuman, MD (reprint author), Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, 423 Guardian Dr,1119A Blockley Hall, Philadelphia, PA 19104 USA. EM neumanm@mail.med.upenn.edu FU NIA NIH HHS [K08 AG043548, K24 AG047908] NR 51 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-0764 EI 2213-0772 J9 HEALTHCARE JI HealthCare PD SEP PY 2016 VL 4 IS 3 BP 192 EP 199 DI 10.1016/j.hjdsi.2015.10.008 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EC4NE UT WOS:000388107800016 PM 27637826 ER PT J AU Rolfson, O Donahue, GS Hallsten, M Garellick, G Karrholm, J Nemes, S AF Rolfson, Ola Donahue, Gabrielle S. Hallsten, Mattias Garellick, Goran Karrholm, Johan Nemes, Szilard TI Patient-reported outcomes in cemented and uncemented total hip replacements SO HIP INTERNATIONAL LA English DT Article DE Cemented; Fixation; Hip arthroplasty; Hip replacement; Patient-reported outcomes; Uncemented ID RANDOMIZED-TRIAL; ARTHROPLASTY; REGISTER AB Introduction: Data from national registries have favored the use of cemented fixation in total hip replacement (THR) while other reports show no significant differences in implant survival between cemented and uncemented fixation using modern implants. It is important to investigate whether the method of fixation itself may affect patient-reported outcomes. Hence, this study sought to analyse if patient-reported outcomes measures (PROMs) differ depending on the type of fixation. Methods: Data was used from the follow-up programme of the Swedish Hip Arthroplasty Register which comprises the EQ-5D, a visual analogue scale (VAS) on hip pain, as well as a VAS addressing satisfaction with the outcome of the hip replacement. 3,118 patients with uncemented THR due to primary osteoarthritis performed from 2002 to 2011 with complete 1-year follow-up were included in the study. A control group of patients with cemented THR (n = 3,118) were selected by matching on age, gender, Charnley class, and preoperative health-related quality of life. Results: After adjusting for age, gender, Charnley class, and baseline PROMs, multivariate linear regression analyses showed that uncemented fixation is associated with a larger improvement in EQ-5D index (B = 0.03, 95% CI 0.019, 0.041), EQ VAS (B = 2.58, 95% CI 1.65, 3.51), greater pain relief (B = -2.68, 95% CI -3.54, -1.82) and superior patient satisfaction (B = -2.56, 95% CI -3.52, -1.60) (all p<0.001). Discussions: This study demonstrates that uncemented fixation is associated with better patient-reported outcomes. Factors unrelated to implant fixation, such as performance or selection bias, may also contribute to the difference. C1 [Rolfson, Ola; Hallsten, Mattias; Garellick, Goran; Karrholm, Johan; Nemes, Szilard] Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Rolfson, Ola; Hallsten, Mattias; Garellick, Goran; Karrholm, Johan; Nemes, Szilard] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. [Rolfson, Ola; Donahue, Gabrielle S.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Rolfson, O (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed,Sahlgrenska Univ Hosp,Molndal Hosp, S-43180 Molndal, Sweden. EM ola.rolfson@vgregion.se FU Doktor Felix Neuberghs Foundation; Goran Bauer Grant; Swedish Society of Medicine FX Grants from Doktor Felix Neuberghs Foundation, the Goran Bauer Grant, and the Swedish Society of Medicine were received by OR. NR 17 TC 0 Z9 0 U1 0 U2 0 PU WICHTIG PUBLISHING PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-7000 EI 1724-6067 J9 HIP INT JI Hip Int. PD SEP-OCT PY 2016 VL 26 IS 5 BP 451 EP 457 DI 10.5301/hipint.5000371 PG 7 WC Orthopedics SC Orthopedics GA EC9ZU UT WOS:000388503600009 ER PT J AU Le, L Shaw, MY Yang, Y Mao, MY Yang, YM Hu, T AF Le, Lei Shaw, Meiying Yang, Yan Mao, Mengying Yang, Yingming Hu, Tao TI Exopolysaccharide dispelled by calcium hydroxide with volatile vehicles related to bactericidal effect for root canal medication SO JOURNAL OF APPLIED ORAL SCIENCE LA English DT Article DE Calcium hydroxide; Medications; Disinfection; Enterococcus faecalis; Exopolysaccharide ID IN-VITRO EVALUATION; ENTEROCOCCUS-FAECALIS; 2-PERCENT CHLORHEXIDINE; SODIUM-HYPOCHLORITE; MEDICAMENTS; BIOFILMS; DENTIN; VIVO; MICROORGANISMS; DISINFECTION AB Objective: Enterococcus faecalis is the dominant microbial species responsible for persistent apical periodontitis with ability to deeply penetrate into the dentin. Exopolysaccharides (EPS) contribute to the pathogenicity and antibiotic resistance of E. faecalis. Our aim was to investigate the antimicrobial activity of calcium hydroxide (CH), camphorated parachlorophenol (CMCP), and chlorhexidine (CHX) against E. faecalis in dentinal tubules. Material and Methods: Decoronated single-canal human teeth and semicylindrical dentin blocks were incubated with E. faecalis for 3 weeks. Samples were randomly assigned to six medication groups for 1 week (n=10 per group): CH + 40% glycerin-water solution (1:1, wt/vol); CMCP; 2% CHX; CH + CMCP (1:1, wt/vol); CH + CMCP (2:3, wt/vol); and saline. Bacterial samples were collected and assayed for colony-forming units. After dentin blocks were split longitudinally, confocal laser scanning microscopy was used to assess the proportion of viable bacteria and EPS production in dentin. Results: CMCP exhibited the best antimicrobial activity, while CH was the least sensitive against E. faecalis (p<0.05). CHX showed similar antimicrobial properties to CH + CMCP (1:1, wt/vol) (p>0.05). CH combined with CMCP inhibited EPS synthesis by E. faecalis, which sensitized biofilms to antibacterial substances. Moreover, increasing concentrations of CMCP decreased EPS matrix formation, which effectively sensitized biofilms to disinfection agents. Conclusion: The EPS matrix dispelled by CH paste with CMCP may be related to its bactericidal effect; the visualization and analysis of EPS formation and microbial colonization in dentin may be a useful approach to verify medicaments for antimicrobial therapy. C1 [Le, Lei; Yang, Yan; Mao, Mengying; Hu, Tao] Sichuan Univ, West China Hosp Stomatol, Dept Operat Dent & Endodont, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China. [Yang, Yingming; Hu, Tao] Sichuan Univ, West China Hosp Stomatol, Dept Prevent Dent, Chengdu, Sichuan, Peoples R China. [Shaw, Meiying] Sichuan Univ, Coll Life Sci, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China. [Le, Lei] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. RP Yang, YM (reprint author), Sichuan Univ, West China Hosp Stomatol, Dept Prevent Dent, Chengdu, Sichuan, Peoples R China.; Hu, T (reprint author), West China Hosp Stomatol, Dept Prevent Dent, Dept Operat Dent & Endodont, 14,3rd Sect Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China. EM hutao@scu.edu.cn FU National Natural Science Foundation of China [81400507, 81670980] FX The authors deny any conflicts of interest. This study was supported by the National Natural Science Foundation of China (Grants 81400507, 81670980) NR 29 TC 0 Z9 0 U1 8 U2 8 PU UNIV SAO PAULO FAC ODONTOLOGIA BAURU PI BAURU-SP PA AL DR OCTAVIO PINHEIRO BRISOLLA, 9-75, BAURU-SP, 17012-901, BRAZIL SN 1678-7757 EI 1678-7765 J9 J APPL ORAL SCI JI J. Appl. Oral Sci. PD SEP-OCT PY 2016 VL 24 IS 5 BP 487 EP 495 DI 10.1590/1678-77520160014 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA EC0HJ UT WOS:000387779600010 PM 27812619 ER PT J AU Hu, G Zhang, Q Ivkovic, V Strangman, GE AF Hu, Gang Zhang, Quan Ivkovic, Vladimir Strangman, Gary E. TI Ambulatory diffuse optical tomography and multimodality physiological monitoring system for muscle and exercise applications SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE wearable; laser; tissue oxygenation; muscle; diffuse optical imaging ID NEAR-INFRARED SPECTROSCOPY; SKELETAL-MUSCLE; OXYGEN-SATURATION; TISSUE OXYGENATION; BRAIN ACTIVATION; CYCLING EXERCISE; SEIZURE ONSET; DEOXYGENATION; SPACEFLIGHT; NIRS AB Ambulatory diffuse optical tomography (aDOT) is based on near-infrared spectroscopy (NIRS) and enables three-dimensional imaging of regional hemodynamics and oxygen consumption during a person's normal activities. Although NIRS has been previously used for muscle assessment, it has been notably limited in terms of the number of channels measured, the extent to which subjects can be ambulatory, and/or the ability to simultaneously acquire synchronized auxiliary data such as electromyography (EMG) or electrocardiography (ECG). We describe the development of a prototype aDOT system, called NINscan-M, capable of ambulatory tomographic imaging as well as simultaneous auxiliary multimodal physiological monitoring. Powered by four AA size batteries and weighing 577 g, the NINscan-M prototype can synchronously record 64-channel NIRS imaging data, eight channels of EMG, ECG, or other analog signals, plus force, acceleration, rotation, and temperature for 24+ h at up to 250 Hz. We describe the system's design, characterization, and performance characteristics. We also describe examples of isometric, cycle ergometer, and free-running ambulatory exercise to demonstrate tomographic imaging at 25 Hz. NINscan-M represents a multiuse tool for muscle physiology studies as well as clinical muscle assessment. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Hu, Gang; Zhang, Quan; Ivkovic, Vladimir; Strangman, Gary E.] Massachusetts Gen Hosp, Neural Syst Grp, Harvard Med Sch, Bldg 149,13th St, Charlestown, MA 02129 USA. [Zhang, Quan; Strangman, Gary E.] Baylor Coll Med, Ctr Space Med, 6500 Main St, Houston, TX 77030 USA. RP Strangman, GE (reprint author), Massachusetts Gen Hosp, Neural Syst Grp, Harvard Med Sch, Bldg 149,13th St, Charlestown, MA 02129 USA.; Strangman, GE (reprint author), Baylor Coll Med, Ctr Space Med, 6500 Main St, Houston, TX 77030 USA. EM strang@nmr.mgh.harvard.edu FU National Space Biomedical Research Institute through NASA [NCC 9-58] FX This work was supported by the National Space Biomedical Research Institute through NASA NCC 9-58. NR 85 TC 0 Z9 0 U1 2 U2 2 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP PY 2016 VL 21 IS 9 AR 091314 DI 10.1117/1.JBO.21.9.091314 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA EC5YH UT WOS:000388212700021 PM 27467190 ER PT J AU Ray, SK Samntaray, S Banik, NL AF Ray, Swapan K. Samntaray, Supriti Banik, Naren L. TI Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury SO NEURAL REGENERATION RESEARCH LA English DT Editorial Material ID VSC4.1 MOTONEURONS; DOSE ESTROGEN; NEUROPROTECTION C1 [Ray, Swapan K.] Univ South Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. [Samntaray, Supriti] Med Univ South Carolina, Dept Neurosci, Charleston, SC USA. [Banik, Naren L.] Med Univ South Carolina, Dept Neurol & Neurosurg, Charleston, SC USA. [Banik, Naren L.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Ray, SK (reprint author), Univ South Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA. EM swapan.ray@uscmed.sc.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1673-5374 EI 1876-7958 J9 NEURAL REGEN RES JI Neural Regen. Res. PD SEP PY 2016 VL 11 IS 9 BP 1418 EP 1419 DI 10.4103/1673-5374.191212 PG 2 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA EC0DP UT WOS:000387768400020 PM 27857741 ER PT J AU Kyle, TK Stanford, FC AF Kyle, Theodore K. Stanford, Fatima Cody TI Low Utilization of Obesity Medications: What are the Implications for Clinical Care? SO OBESITY LA English DT Editorial Material C1 [Kyle, Theodore K.] ConscienHealth, Pittsburgh, PA 15241 USA. [Stanford, Fatima Cody] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Stanford, Fatima Cody] Massachusetts Gen Hosp, Div Endocrinol, Dept Pediat, Boston, MA 02114 USA. [Stanford, Fatima Cody] Harvard Med Sch, Boston, MA USA. RP Kyle, TK (reprint author), ConscienHealth, Pittsburgh, PA 15241 USA. EM ted.kyle@conscienhealth.org OI Stanford, Fatima/0000-0003-4616-533X NR 4 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 SEP PY 2016 VL 24 IS 9 BP 1832 EP 1832 DI 10.1002/oby.21566 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EC6VW UT WOS:000388275800002 PM 27569116 ER PT J AU Honea, RA Szabo-Reed, AN Lepping, RJ Perea, R Breslin, F Martin, LE Brooks, WM Donnelly, JE Savage, CR AF Honea, Robyn A. Szabo-Reed, Amanda N. Lepping, Rebecca J. Perea, Rodrigo Breslin, Florence Martin, Laura E. Brooks, William M. Donnelly, Joseph E. Savage, Cary R. TI Voxel-Based Morphometry Reveals Brain Gray Matter Volume Changes in Successful Dieters SO OBESITY LA English DT Article ID WEIGHT-LOSS MAINTENANCE; ANOREXIA-NERVOSA; HUMAN OBESITY; FOOD; IMAGE; ABNORMALITIES; BEHAVIOR AB Objective: To compare regional brain volume predictors of percent weight loss (WL) in dieters with obesity (DwO) and in the same participants categorized as "successful" (>= 7% WL) or "unsuccessful" dieters (<7% WL). Methods: DwO (n = 72) and participants with healthy weight (n = 22) completed a structural MRI at baseline and 3 months. All DwO participants were enrolled in a 12-week program consisting of a reduced calorie diet, increased physical activity, and behavioral modification. SPM8-based voxel-based morphometry processing streams were used for measurements of regional gray (GMV) and white matter volume and longitudinal changes in volume. Correlations between WL and baseline brain volume and change in brain volume, as well as differences between groups, were then tested. Results: % WL was positively correlated with baseline GMV in right parahippocampal and orbitofrontal gyri in DwO. Successful dieters showed greater GMV loss in the left precentral gyrus and the insula compared with unsuccessful dieters. A negative correlation was found between % WL and GMV change from baseline in the left prefrontal regions. Conclusions: Findings illustrate that WL is related to volumetric changes in brain areas previously linked to interoception and food motivation. C1 [Honea, Robyn A.; Brooks, William M.] Univ Kansas, Sch Med, Dept Neurol, Kansas City, KS USA. [Szabo-Reed, Amanda N.; Donnelly, Joseph E.] Univ Kansas, Med Ctr, Cardiovasc Res Inst, Kansas City, KS 66103 USA. [Lepping, Rebecca J.] Univ Kansas, Dept Psychiat, Sch Med, Kansas City, KS USA. [Perea, Rodrigo] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Breslin, Florence; Savage, Cary R.] Univ Kansas, Med Ctr, Ctr Hlth Behav Neurosci, Kansas City, KS 66103 USA. [Martin, Laura E.; Brooks, William M.] Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. [Martin, Laura E.] Univ Kansas, Med Ctr, Dept Prevent Med & Publ Hlth, Kansas City, KS 66103 USA. [Brooks, William M.] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66103 USA. RP Savage, CR (reprint author), Univ Kansas, Med Ctr, Ctr Hlth Behav Neurosci, Kansas City, KS 66103 USA. EM cary.savage@bannerhealth.com FU National Institutes of Health [UL1 TR000001, R01-DK080090, K01-AG035042, P30-AG010129, F32-DK103493] FX National Institutes of Health (UL1 TR000001; R01-DK080090, to CRS; K01-AG035042 and P30-AG010129, to RAH; and F32-DK103493, to ANS-R). NR 39 TC 1 Z9 1 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 SEP PY 2016 VL 24 IS 9 BP 1842 EP 1848 DI 10.1002/oby.21551 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EC6VW UT WOS:000388275800005 PM 27430417 ER PT J AU Pownall, HJ Schwartz, AV Bray, GA Berkowitz, RI Lewis, CE Boyko, EJ Jakicic, JM Chen, HY Heshka, S Gregg, EW Johnson, KC AF Pownall, Henry J. Schwartz, Anne V. Bray, George A. Berkowitz, Robert I. Lewis, Cora E. Boyko, Edward J. Jakicic, John M. Chen, Haiying Heshka, Stanley Gregg, Edward W. Johnson, Karen C. CA Look AHEAD Res Grp TI Changes in Regional Body Composition over 8 Years in a Randomized Lifestyle Trial: The Look AHEAD Study SO OBESITY LA English DT Article ID MUSCLE STRENGTH; OLDER-ADULTS; OBESITY; INTERVENTION; WOMEN; MASS; MEN AB Objective: To test the hypothesis that an 8-year intensive lifestyle intervention (ILI) suppresses aging-dependent changes in regional lean mass (LM) and fat mass (FM) among people with overweight/obesity and type 2 diabetes. Methods: Regional body composition was measured by dual-energy X-ray absorptiometry within a subset of 1,019 volunteers (45-75 years old) in the Look AHEAD study randomized to ILI or diabetes support and education (DSE). The ILI goal was to achieve and maintain >= 7% weight loss through increased physical activity and reduced caloric intake. Results: Over 8 years, the DSE group exhibited a linear loss of LM and FM. During year 1, the ILI group lost LM and FM. Between years 1 and 8, the ILI group regained most FM in all regions; regional LM converged with that of the DSE group; the percent of LM loss was greater for the leg than for the trunk. Among both groups, regional LM and FM change was proportional to the size of the region, trunk>leg>arm. Conclusions: Aging-dependent LM losses, particularly in the leg region, were not suppressed by ILI. The long-term consequences of rapid LM and FM loss and subsequent regain mostly as fat are unknown. C1 [Pownall, Henry J.] Houston Methodist Res Inst, Dept Cardiol, Houston, TX 77030 USA. [Pownall, Henry J.] Baylor Coll Med, Houston, TX 77030 USA. [Schwartz, Anne V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bray, George A.] LSU, Dept Clin Obes & Metab, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Berkowitz, Robert I.] Univ Penn, Sch Med, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Dept Internal Med, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Seattle, WA 98195 USA. [Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA. [Chen, Haiying] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA. [Heshka, Stanley] St Lukes Roosevelt Hosp, Inst Human Nutr, New York, NY 10025 USA. [Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Johnson, Karen C.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Pownall, HJ (reprint author), Houston Methodist Res Inst, Dept Cardiol, Houston, TX 77030 USA.; Pownall, HJ (reprint author), Baylor Coll Med, Houston, TX 77030 USA. EM hjpownall@houstonmethodist.org FU NIH; NIDDK [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; NHLBI; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; Centers for Disease Control and Prevention; NIDDK; Johns Hopkins Bayview General Clinical Research Center (GCRC) [M01RR02719]; Massachusetts General Hospital Mallinckrodt GCRC; Massachusetts Institute of Technology GCRC [M01RR01066]; University of Colorado Health Sciences GCRC [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis GCRC [M01RR0021140]; University of Pittsburgh GCRC [M01RR000056]; Clinical Translational Research Center [UL1 RR 024153]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter GCRC [M01RR01346] FX NIH cooperative agreements with NIDDK: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992 and by NHLBI; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women's Health; and Centers for Disease Control and Prevention. Other support was from the Intramural Research Program of NIDDK. Other support was from Johns Hopkins Bayview General Clinical Research Center (GCRC; M01RR02719); Massachusetts General Hospital Mallinckrodt GCRC and Massachusetts Institute of Technology GCRC (M01RR01066); University of Colorado Health Sciences GCRC (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); University of Tennessee at Memphis GCRC (M01RR0021140); University of Pittsburgh GCRC (M01RR000056), the Clinical Translational Research Center (UL1 RR 024153), and NIH grant (DK 046204); VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and Frederic C. Bartter GCRC (M01RR01346). Contributions to Look AHEAD were from FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST (R) (Nestle HealthCare Nutrition) Inc.; Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast Brand (Unilever North America). NR 29 TC 0 Z9 0 U1 2 U2 2 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 SEP PY 2016 VL 24 IS 9 BP 1899 EP 1905 DI 10.1002/oby.21577 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EC6VW UT WOS:000388275800013 PM 27465756 ER PT J AU MacIntosh, PW Jakobiec, FA Stagner, A Rashid, A Sutula, FC Yoon, MK Fay, AM AF MacIntosh, Peter W. Jakobiec, Frederick A. Stagner, Anna Rashid, Alia Sutula, Francis C. Yoon, Michael K. Fay, Aaron M. TI Failed Cartilaginous Grafts in the Eyelid: A Retrospective Clinicopathological Analysis of 5 Cases SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HARD PALATE MUCOSA; CONCHAL CARTILAGE; EAR PERICHONDRIUM; RECONSTRUCTION; RETRACTION; FLAP; MANAGEMENT; SUPPORT AB Purpose: To analyze the clinical and histopathologic features of 5 failed autologous cartilaginous grafts to the lower eyelids and to analyze the reasons for these failures. Methods: In this retrospective case series, the data collected included patient ages, reasons for and duration of cartilaginous graft implants, sources of cartilaginous grafts, and clinical and histopathologic findings at time of graft removal using hematoxylin and eosin, elastic, Alcian blue, and Masson trichrome staining for analysis of tissue alterations. Results: Five cartilaginous, posterior lamellar lower eyelid grafts were complicated by eyelid thickening or retraction, graft extrusion, and entropion. Histopathologic findings included segmentation of the original single implant, stripped of its perichondrium, due to "kerfing," sometimes with overlapping of the segments and scar formation between the segments. In place of the perichondrium that had been removed during the preparation the graft implants, a fibrous pseudoperichondrial capsule had formed. Pyknotic nuclei in varying degrees were typically found in the center of the grafts, despite a high degree of preservation of the extracellular matrix (collagenous, elastic, and proteoglycan components). No evidence of inflammation, cartilaginous vascularization, or necrosis was identified in any graft. Conclusion: Despite minimal reactive processes, kerfing (partial thickness cuts made in the graft to increase its pliancy) may be partially responsible for graft migration, deformation, and surgical failure. The consequences were graft fragmentation and overlapping of the multiple fragments. Graft migration can be exacerbated if a posterior lamellar graft is used to correct an anterior lamellar deficiency. Interference with the overall architectural integrity of the graft and its extracellular matrix appears to play no role in failure, despite removal of the perichondrium. Mild to moderate degrees of chondrocytic dropout in the absence of necrosis and inflammation are probably attributable to the thick and coarsely textured collagen of the fibrous pseudoperichondrial capsule that may impede diffusion of nutrients into the center of the graft. C1 [MacIntosh, Peter W.; Sutula, Francis C.; Yoon, Michael K.; Fay, Aaron M.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. [MacIntosh, Peter W.; Jakobiec, Frederick A.; Stagner, Anna; Rashid, Alia; Sutula, Francis C.; Yoon, Michael K.; Fay, Aaron M.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Jakobiec, Frederick A.; Stagner, Anna; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 25 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2016 VL 32 IS 5 BP 347 EP 353 DI 10.1097/IOP.0000000000000540 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA EC5QJ UT WOS:000388190700018 PM 26352748 ER PT J AU Chen, X Bleier, BS Lefebvre, DR Lee, NG AF Chen, Xi Bleier, Benjamin S. Lefebvre, Daniel R. Lee, Nahyoung Grace TI Pseudomonas Aeruginosa: A Masquerader in Sino-Orbital Infections SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INVASIVE FUNGAL SINUSITIS; IMMUNODEFICIENCY-VIRUS-INFECTION; OF-THE-LITERATURE; ECTHYMA GANGRENOSUM; OPTIC-NERVE; MUCORMYCOSIS; DIFFUSION AB Purpose: To report 2 immunocompromised patients with sino-orbital necrotizing pseudomonas infections and review the literature. Methods: This is a noncomparative, retrospective case series, and review. The clinical data of 2 patients with histopathologic and microbiologic diagnoses of pseudomonas sinus infections causing orbital cellulitis were obtained from medical records. A retrospective literature review was performed on all reported cases of periorbital pseudomonas infections. Results: One patient with acquired immune deficiency syndrome was noted to have orbital cellulitis with clear visualization of eschar in the middle turbinate on nasal endoscopy. A second patient also had orbital cellulitis with ophthalmoplegia and presence of eschar in the sinus. Both patients had some degree of erosion through the lamina papyracea found on orbital imaging and both had intact vision without optic neuropathy. Pseudomonas infection was confirmed in both cases with permanent histopathology and cultures from conservative sinus debridement. Conclusions: Pseudomonas sino-orbital infections must be considered in the differential diagnosis in cases of eschar and orbital wall erosion especially when vision is preserved in immunocompromised individuals. This finding obviates the need for radical debridement including orbital exenteration, which can be indicated in cases of invasive fungal disease. C1 [Chen, Xi; Lefebvre, Daniel R.; Lee, Nahyoung Grace] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Bleier, Benjamin S.] Harvard Med Sch, Dept Otolaryngol, Boston, MA USA. [Lefebvre, Daniel R.; Lee, Nahyoung Grace] Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Serv, Boston, MA 02114 USA. RP Lee, NG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM grace_lee@meei.harvard.edu NR 17 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 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2016 VL 32 IS 5 BP 374 EP 377 DI 10.1097/IOP.0000000000000558 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA EC5QJ UT WOS:000388190700023 PM 26398244 ER PT J AU Wolf, EJ Schnurr, PP AF Wolf, Erika J. Schnurr, Paula P. TI Posttraumatic Stress Disorder-Related Cardiovascular Disease and Accelerated Cellular Aging SO PSYCHIATRIC ANNALS LA English DT Article ID CORONARY-HEART-DISEASE; DNA METHYLATION AGE; METABOLIC SYNDROME; PHYSICAL-ACTIVITY; METAANALYSIS; RISK; ASSOCIATIONS; COMPONENTS; PROFILES; PEOPLE AB We reviewed the literature from 2010 to 2016 on the relationship between posttraumatic stress disorder (PTSD) and cardiometabolic health conditions, including metabolic syndrome, coronary artery disease, stroke, and myocardial infarction, among others. Collectively, PTSD was associated with increased risk of cardiometabolic health problems, with preclinical and clinical studies offering evidence of behavioral (eg, poor sleep, cigarette use, poor diet, and insufficient exercise) and biological (eg, autonomic reactivity, inflammation) mediators of these associations. We discuss the possibility that these behavioral and biological mechanisms lead to accelerated cellular aging, as regulated in the epigenome, which contributes to premature cardiometabolic health decline. This has implications for the assessment, prevention, and treatment of cardiometabolic conditions among those with PTSD. It also highlights the need to better understand the mechanisms linking PTSD to accelerated aging and to develop interventions to attenuate or reverse this phenomenon. C1 [Wolf, Erika J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Schnurr, Paula P.] Natl Ctr PTSD, Boston, MA USA. [Schnurr, Paula P.] Dartmouth Coll, Geisel Sch Med, Psychiat, Dartmouth, NS, Canada. RP Wolf, EJ (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM erika.wolf@va.gov FU United States Department of Veterans Affairs, Clinical Sciences Research and Development Program FX This work was supported by a Career Development Award to E.J.W. from the United States Department of Veterans Affairs, Clinical Sciences Research and Development Program. NR 37 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 EI 1938-2456 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD SEP PY 2016 VL 46 IS 9 BP 527 EP 532 DI 10.3928/00485713-20160729-01 PG 6 WC Psychiatry SC Psychiatry GA EC9EY UT WOS:000388448400007 PM 27990033 ER PT J AU Baumel, A Correll, CU Hauser, M Brunette, M Rotondi, A Ben-Zeev, D Gottlieb, JD Mueser, KT Achtyes, ED Schooler, NR Robinson, DG Gingerich, S Marcy, P Meyer-Kalos, P Kane, JM AF Baumel, Amit Correll, Christoph U. Hauser, Marta Brunette, Mary Rotondi, Armando Ben-Zeev, Dror Gottlieb, Jennifer D. Mueser, Kim T. Achtyes, Eric D. Schooler, Nina R. Robinson, Delbert G. Gingerich, Susan Marcy, Patricia Meyer-Kalos, Piper Kane, John M. TI Health Technology Intervention After Hospitalization for Schizophrenia: Service Utilization and User Satisfaction SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHOSIS; MODEL AB Objective: The authors examined patients' acceptance of the Health Technology Program (HTP), an integrative approach to relapse prevention after hospitalization of adults with schizophrenia or related disorders. The program combines use of digital tools with support from a mental health technology coach (MHTC). Methods: Patients with schizophrenia spectrum disorders received six months of treatment that began within 60 days of a psychiatric hospitalization and included the development of a personalized relapse prevention plan, three digital tools, and contacts with MHTCs. Results: A total of 200 patients (mean +/- SDage=34.6 +/- 10.6 years) had 28.2 +/- 2.0 contacts with the MHTC that lasted 38.3 +/- 14.2 minutes. The most discussed topic was case management (52%), and digital tools were discussed in 45% of meetings. Altogether, 87% of patients used at least one of the digital tools, with 96% of patients rating the HTP as satisfying to at least some extent. Conclusions: These data suggest very high acceptance of the HTP, a program that integrates available human support with digital tools. C1 [Baumel, Amit; Correll, Christoph U.; Hauser, Marta; Schooler, Nina R.; Robinson, Delbert G.; Marcy, Patricia; Kane, John M.] Northwell Hlth, Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA. [Baumel, Amit; Correll, Christoph U.; Robinson, Delbert G.; Kane, John M.] Hofstra Northwell Sch Med, Hempstead, NY USA. [Hauser, Marta; Marcy, Patricia] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Schooler, Nina R.] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA. [Brunette, Mary; Ben-Zeev, Dror] Dartmouth Coll, Geisel Sch Med, Dartmouth Psychiat Res Ctr, Ctr Technol & Behav Hlth, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Rotondi, Armando] Clin & Translat Sci Inst, Dept Crit Care Med, Pittsburgh, PA USA. [Rotondi, Armando] US Dept Vet Affairs, Mental Illness Res Educ & Clin Ctr, Med Ctr, Pittsburgh, PA USA. [Gottlieb, Jennifer D.; Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Achtyes, Eric D.] Cherry Hlth, E Lansing, MI USA. [Achtyes, Eric D.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Meyer-Kalos, Piper] Minnesota Ctr Chem & Mental Hlth, Dept Social Work, St Paul, MN USA. RP Baumel, A (reprint author), Northwell Hlth, Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA. OI Achtyes, Eric/0000-0001-8939-1535 FU Centers for Medicare and Medicaid Services, Department of Health and Human Services [1C1CMS331052-01-00]; AssurEx; Avanir; CMMS; Janssen; Network180; Novartis; Otsuka; Pfizer; Pine Rest Foundation; Priority Health; Vanguard Research Group; Bristol-Myers Squibb; Lundbeck; Takeda; Genentech; Neurocrine FX The project described was made possible by grant 1C1CMS331052-01-00 from the Centers for Medicare and Medicaid Services, Department of Health and Human Services. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the U.S. Department of Health and Human Services or any of its agencies.; Dr. Correll has been a consultant or advisor to or has received honoraria from AbbVie, Acadia, Actavis, Alkermes, Eli Lilly, Forum, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen, Johnson and Johnson, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Reviva, Roche, Sunovion, Supernus, Takeda, and Teva. He has received grant support from Bristol-Myers Squibb, Lundbeck, Otsuka, and Takeda. Dr. Hauser has been a consultant to Otsuka. Dr. Brunette holds a research contract with Alkermes. Dr. Ben-Zeev has an intervention content licensing agreement with Pear Therapeutics. Dr. Achtyes has received research support from AssurEx, Avanir, CMMS, Janssen, Network180, Novartis, Otsuka, Pfizer, Pine Rest Foundation, Priority Health, and Vanguard Research Group, and he has been an advisor to Roche. Dr. Schooler has served on advisory boards or as a consultant for Abbott, Alkermes, Amgen, Eli Lilly, Forum (formerly EnVivo), Janssen Psychiatry, Roche, and Sunovion. She has received grant or research support from Genentech, Neurocrine, and Otsuka. She served on a Data Monitoring Board for Shire and on the faculty of the Lundbeck International Neuroscience Foundation. Dr. Robinson has been a consultant to Asubio, Costello, Innovative Science Solutions, and Shire, and he has received grants from Bristol-Myers Squibb, Janssen, and Otsuka. Ms. Marcy is a shareholder in Pfizer. Dr. Kane has been a consultant for Alkermes, Eli Lilly, EnVivo Pharmaceuticals (Forum), Forest, Genentech, Intracellular Therapeutics, Janssen Pharmaceutica, Johnson and Johnson, Lundbeck, Otsuka, Reviva, Roche, Sunovion, and Teva. He has received lecture honoraria from Genentech, Janssen, Lundbeck, and Otsuka. He is a shareholder in MedAvante Inc., LB Pharmaceuticals, and Vanguard Research Group. Dr. Baumel, Dr. Rotondi, Dr. Gottlieb, Dr. Mueser, Ms. Gingerich, and Dr. Meyer-Kalos report no financial relationships with commercial interests. NR 13 TC 0 Z9 0 U1 2 U2 2 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 SEP 1 PY 2016 VL 67 IS 9 BP 1035 EP 1038 DI 10.1176/appi.ps.201500317 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA EC6SS UT WOS:000388267600018 PM 27247171 ER PT J AU Reid, MW May, FP Martinez, B Cohen, S Wang, H Williams, DL Spiegel, BMR AF Reid, Mark W. May, Folasade P. Martinez, Bibiana Cohen, Samuel Wang, Hank Williams, Demetrius L., Jr. Spiegel, Brennan M. R. TI Preventing Endoscopy Clinic No-Shows: Prospective Validation of a Predictive Overbooking Model SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NON-ATTENDANCE; SCREENING COLONOSCOPY; OUTPATIENT ENDOSCOPY; PATIENT ABSENTEEISM; GENERAL-PRACTICE; PRIMARY-CARE; HEALTH-CARE; APPOINTMENTS; ACCESS; NONATTENDANCE AB OBJECTIVES: Patient absenteeism for scheduled visits and procedures ("no-show") occurs frequently in healthcare systems worldwide, resulting in treatment delays and financial loss. To address this problem, we validated a predictive overbooking system that identifies patients at high risk for missing scheduled gastrointestinal endoscopy procedures ("no-shows" and cancellations), and offers their appointments to other patients on short notice. METHODS: We prospectively tested a predictive overbooking system at a Veterans Administration outpatient endoscopy clinic over a 34-week period, alternating between traditional booking and predictive overbooking methods. For the latter, we assigned a no-show risk score to each scheduled patient, utilizing a previously developed logistic regression model built with electronic health record data. To compare booking methods, we measured service utilization-defined as the percentage of daily total clinic capacity occupied by patients-and length of clinic workday. RESULTS: Compared to typical booking, predictive overbooking resulted in nearly all appointment slots being filled-2.5 slots available during control weeks vs. 0.35 slots during intervention weeks, t(161)=4.10, P=0.0001. Service utilization increased from 86% during control weeks to 100% during intervention weeks, allowing 111 additional patients to undergo procedures. Physician and staff overages were more common during intervention weeks, but less than anticipated (workday length of 7.84h (control) vs. 8.31h (intervention), t(161)=2.28, P=0.02). CONCLUSIONS: Predictive overbooking may be used to maximize endoscopy scheduling. Future research should focus on adapting the model for use in primary care and specialty clinics. C1 [Reid, Mark W.; May, Folasade P.; Cohen, Samuel; Williams, Demetrius L., Jr.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Reid, Mark W.; Martinez, Bibiana; Williams, Demetrius L., Jr.] CS CORE, Los Angeles, CA USA. [May, Folasade P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Wang, Hank] Kaiser Permanente Northern Calif, Oakland, CA USA. Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. Pacific Theatre Bldg,116 North Robertson Blvd, Los Angeles, CA 90048 USA. RP Spiegel, BMR (reprint author), Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. EM brennan.spiegel@cshs.org FU VA Health Services Research and Development (HSRD) Merit Award [IIR 12-055] FX This study was funded by a VA Health Services Research and Development (HSR&D) Merit Award (IIR 12-055). The study funder approved the study design, but did not contribute to this manuscript. NR 43 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 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2016 VL 111 IS 9 BP 1267 EP 1273 DI 10.1038/ajg.2016.269 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EB1YX UT WOS:000387154000014 PM 27377518 ER PT J AU Ahn, J Lim, JK Lee, HM Lok, AS Nguyen, M Pan, CQ Mannalithara, A Te, H Reddy, KR Trinh, H Chu, D Tran, T Lau, D Leduc, TS Min, A Le, LT Bae, H Tran, SV Do, S Hann, HWL Wong, C Han, S Pillai, A Park, JS Tong, M Scaglione, S Woog, J Kim, WR AF Ahn, Joseph Lim, Joseph K. Lee, Hannah M. Lok, Anna S. Mindie Nguyen Pan, Calvin Q. Mannalithara, Ajitha Te, Helen Reddy, K. Rajender Huy Trinh Chu, Danny Tram Tran Lau, Daryl Leduc, Truong-Sinh Min, Albert Loc Trong Le Bae, Ho Sang Van Tran Do, Son Hann, Hie-Won L. Wong, Clifford Han, Steven Pillai, Anjana Park, James S. Tong, Myron Scaglione, Steve Woog, Jocelyn Kim, W. Ray TI Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID DISEASE PROGRESSION; ANTIVIRAL THERAPY; PREDICTIVE SCORE; NATURAL-HISTORY; VIRUS INFECTION; LIVER-DISEASE; RISK; CAUCASIANS; TENOFOVIR AB OBJECTIVES: Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS: The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS: Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905). CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment. C1 [Ahn, Joseph] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, 3181 SW Sam Jackson Pk Rd,L-461, Portland, OR 97239 USA. [Lim, Joseph K.] Yale Univ, Dept Digest Dis, New Haven, CT USA. [Lee, Hannah M.] Virginia Commonwealth Univ, Div Gastroenterol Hepatol, Richmond, VA USA. [Lok, Anna S.] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA. [Mindie Nguyen; Mannalithara, Ajitha; Kim, W. Ray] Stanford Univ, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Pan, Calvin Q.] NYU Langone, Dept Med, New York, NY USA. [Te, Helen] Univ Chicago, Ctr Digest Dis, Chicago, IL 60637 USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA. [Huy Trinh] San Jose GI, San Jose, CA USA. [Chu, Danny] NYU, Sch Med, New York, NY USA. [Tram Tran] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Lau, Daryl] BIDMC, Dept Gastroenterol & Hepatol, Boston, MA USA. [Leduc, Truong-Sinh] Leduc Med Grp, Fountain Valley, CA USA. [Min, Albert] Mt Sinai Beth Israel, Div Gastroenterol, New York, NY USA. [Loc Trong Le] Woodholme Gastroenterol Associates, Pikeville, MD USA. [Bae, Ho] Asian Pacific Liver Ctr, Los Angeles, CA USA. [Sang Van Tran] Falls Church Family Practice, Falls Church, VA USA. [Do, Son] Digest Hlth Associates Texas, Plano, TX USA. [Hann, Hie-Won L.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Han, Steven] Univ Calif Los Angeles, Los Angeles, CA USA. [Pillai, Anjana; Tong, Myron] Emory Univ, Atlanta, GA 30322 USA. [Park, James S.] NYU Langone, New York, NY USA. [Scaglione, Steve] Loyola Univ, Maywood, IL 60153 USA. [Woog, Jocelyn] Asian Hlth Fdn, Philadelphia, PA USA. RP Ahn, J (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, 3181 SW Sam Jackson Pk Rd,L-461, Portland, OR 97239 USA. EM ahnj@ohsu.edu OI Park, James/0000-0001-6248-4117 FU Bristol Myers Squibb FX This work was supported by an investigator-initiated research grant to the Asian Health Foundation by Bristol Myers Squibb. NR 24 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 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2016 VL 111 IS 9 BP 1297 EP 1304 DI 10.1038/ajg.2016.257 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EB1YX UT WOS:000387154000019 PM 27325221 ER PT J AU Yang, J Zhao, YF Zhang, P Li, YH Yang, Y Yang, Y Zhu, JJ Song, X Jiang, GN Fan, J AF Yang, Jie Zhao, Yanfeng Zhang, Peng Li, Yuehua Yang, Yong Yang, Yang Zhu, Junjie Song, Xiao Jiang, Gening Fan, Jie TI Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS SO CELL DEATH & DISEASE LA English DT Article ID NLRP3 INFLAMMASOME; INTRACELLULAR LPS; MACROPHAGE DEATH; ENDOTOXIC-SHOCK; INNATE IMMUNITY; GASDERMIN D; CASPASE 1; ACTIVATION; INJURY; MECHANISMS AB Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI. C1 [Yang, Jie; Zhao, Yanfeng; Zhang, Peng; Yang, Yong; Yang, Yang; Zhu, Junjie; Song, Xiao; Jiang, Gening; Fan, Jie] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Thorac Surg, 507 Zhengmin Rd, Shanghai 200433, Peoples R China. [Yang, Jie; Li, Yuehua; Yang, Yong; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. [Li, Yuehua; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA. [Fan, Jie] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA. RP Jiang, GN; Fan, J (reprint author), Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Thorac Surg, 507 Zhengmin Rd, Shanghai 200433, Peoples R China.; Fan, J (reprint author), Univ Pittsburgh, Sch Med, Dept Surg, VAPHS, Bldg 1,1W142,151U,Univ Dr, Pittsburgh, PA 15213 USA. EM jgnwp@aliyun.com; jif7@pitt.edu FU National Institutes of Health [HL-079669, HL-123882, HL076179]; VA Merit Award [1I01BX002729]; National Natural Science Foundation of China [81470262, 81400056]; Shanghai Rising-Star Program [14QA1403200]; Shanghai Medical New Excellent Youth [XYQ2013115] FX This work was supported by the National Institutes of Health Grant HL-079669 (JF), National Institutes of Health Grant HL-123882 (JF), National Institutes of Health Grant HL076179 (JF), VA Merit Award 1I01BX002729 (JF), National Natural Science Foundation of China 81470262 (JF), National Natural Science Foundation of China 81400056 (YZ), Shanghai Rising-Star Program 14QA1403200 (PZ), and Shanghai Medical New Excellent Youth XYQ2013115 (PZ). NR 55 TC 1 Z9 1 U1 5 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD SEP PY 2016 VL 7 AR e2363 DI 10.1038/cddis.2016.274 PG 16 WC Cell Biology SC Cell Biology GA EC2QF UT WOS:000387968100014 PM 27607578 ER PT J AU Garrido-Castro, AC Metzger, O AF Garrido-Castro, A. C. Metzger-Filho, O. TI Novel Strategies in Hormone Receptor-Positive Advanced Breast Cancer: Overcoming Endocrine Resistance SO CURRENT BREAST CANCER REPORTS LA English DT Article DE Breast cancer; Hormone receptor; Endocrine resistance; CDK4/6; PI3K ID KINASE 4/6 INHIBITOR; CYCLIN-DEPENDENT KINASES; GROWTH-FACTOR RECEPTOR; ADVANCED SOLID TUMORS; RANDOMIZED PHASE-II; ESTROGEN-RECEPTOR; DOUBLE-BLIND; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITOR; THERAPY RESISTANCE AB Resistance to standard endocrine therapies in hormone receptor-positive advanced breast cancer represents a significant clinical challenge. Different intracellular signaling pathways mediate independent activation of the estrogen receptor (ER), promoting tumor cell proliferation despite anti-hormonal treatment. Recently, the inhibition of cell cycle regulators, CDK4 and CDK6, has demonstrated to significantly enhance the effectiveness of endocrine therapy by overcoming or delaying resistance to estrogen blockade. Strategies such as inhibition of the PI3K/mTOR pathway or epigenetic modulation of ER-related gene expression are closely following the trail of CDK inhibitors. Here, we seek to review the most recent efforts to improve outcomes in these patients, in an attempt to extend endocrine treatment and defer the need for cytotoxic regimens. We also discuss future directions to be considered in the treatment of ER-positive disease, as mechanisms of resistance to these new agents arise. C1 [Garrido-Castro, A. C.; Metzger-Filho, O.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. RP Metzger, O (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Otto_Metzger@dfci.harvard.edu NR 83 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-4588 EI 1943-4596 J9 CURR BREAST CANCER R JI Curr. Breast Cancer Rep PD SEP PY 2016 VL 8 IS 4 BP 193 EP 205 DI 10.1007/s12609-016-0228-1 PG 13 WC Oncology SC Oncology GA EB5KE UT WOS:000387412300002 ER PT J AU Wilder, E Fernandez, MP Krejci-Manwaring, J AF Wilder, Elizabeth Fernandez, Martin P. Krejci-Manwaring, Jennifer TI Mucous Membrane Pemphigoid Involving the Trachea and Bronchi: An Extremely Rare and Life-Threatening Presentation SO CUTIS LA English DT Letter ID MEDICAL-TREATMENT; INVOLVEMENT C1 [Wilder, Elizabeth] Baylor Univ, Med Ctr, Dallas, TX USA. [Fernandez, Martin P.] Scott & White Mem Hosp & Clin, Sect Dermatopathol, Temple, TX 76508 USA. [Krejci-Manwaring, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, Div Dermatol & Cutaneous Surg, San Antonio, TX 78229 USA. [Krejci-Manwaring, Jennifer] Audie Murphy Vet Hosp, San Antonio, TX USA. RP Krejci-Manwaring, J (reprint author), 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM KrejciManwar@uthscsa.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 EI 2326-6929 J9 CUTIS JI Cutis PD SEP PY 2016 VL 98 IS 3 BP E24 EP E27 PG 4 WC Dermatology SC Dermatology GA EC3IV UT WOS:000388020700008 PM 27814419 ER PT J AU Chapman, MA Meza, R Lieber, RL AF Chapman, Mark A. Meza, Rachel Lieber, Richard L. TI Skeletal muscle fibroblasts in health and disease SO DIFFERENTIATION LA English DT Review ID DUCHENNE MUSCULAR-DYSTROPHY; CONNECTIVE-TISSUE FIBROBLASTS; COLLAGEN GENE-EXPRESSION; NORMAL MYOGENIC CELLS; EXTRACELLULAR-MATRIX; ROTATOR CUFF; REGENERATIVE CAPACITY; MECHANICAL-PROPERTIES; FORCE TRANSMISSION; MODULATED CELLS AB As the primary producer of extracellular matrix (ECM) proteins in skeletal muscle, fibroblasts play an important role providing structural support to muscle. Skeletal muscle ECM is vital for force transduction from muscle cells to tendons and bones to create movement It is these ECM connections that allow the movement created in muscle to be transmitted to our skeleton. This review discusses how fibroblasts participate in maintaining this healthy ECM within skeletal muscle. Additionally, from a basic science perspective, we discuss current methods to identify and study skeletal muscle fibroblasts, as this is critical to bettering our understanding of these important cells. Finally, skeletal muscle fibrosis is discussed, which is a devastating clinical condition characterized by an overproduction of ECM within skeletal muscle. We discuss the role that fibroblasts and other cells play in muscle fibrosis as well as the implications of this work. Published by Elsevier B.V. on behalf of International Society of Differentiation C1 [Chapman, Mark A.; Lieber, Richard L.] Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr, La Jolla, CA 92093 USA. [Meza, Rachel] Univ Calif San Diego, Dept Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA. [Lieber, Richard L.] Univ Calif San Diego, Dept Orthopaed Surg, 9500 Gilman Dr, La Jolla, CA 92093 USA. [Lieber, Richard L.] US Dept Vet Affairs, 9500 Gilman Dr, La Jolla, CA 92093 USA. [Lieber, Richard L.] Rehabil Inst Chicago, 345 East Super St, Chicago, IL 60611 USA. RP Lieber, RL (reprint author), Northwestern Univ, Rehabil Inst Chicago, Sch Med, 345 East Super Dr, Chicago, IL 60611 USA. EM rlieber@ric.org FU NIAMS NIH HHS [P30 AR061303] NR 83 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 EI 1432-0436 J9 DIFFERENTIATION JI Differentiation PD SEP PY 2016 VL 92 IS 3 SI SI BP 108 EP 115 DI 10.1016/j.diff.2016.05.007 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA EC3WI UT WOS:000388057400006 PM 27282924 ER PT J AU Oberg, K Krenning, E Sundin, A Bodei, L Kidd, M Tesselaar, M Ambrosini, V Baum, RP Kulke, M Pavel, M Cwikla, J Drozdov, I Falconi, M Fazio, N Frilling, A Jensen, R Koopmans, K Korse, T Kwekkeboom, D Maecke, H Paganelli, G Salazar, R Severi, S Strosberg, J Prasad, V Scarpa, A Grossman, A Walenkamp, A Cives, M Virgolini, I Kjaer, A Modlin, IM AF Oberg, Kjell Krenning, Eric Sundin, Anders Bodei, Lisa Kidd, Mark Tesselaar, Margot Ambrosini, Valentina Baum, Richard P. Kulke, Matthew Pavel, Marianne Cwikla, Jaroslaw Drozdov, Ignat Falconi, Massimo Fazio, Nicola Frilling, Andrea Jensen, Robert Koopmans, Klaus Korse, Tiny Kwekkeboom, Dik Maecke, Helmut Paganelli, Giovanni Salazar, Ramon Severi, Stefano Strosberg, Jonathan Prasad, Vikas Scarpa, Aldo Grossman, Ashley Walenkamp, Annemeik Cives, Mauro Virgolini, Irene Kjaer, Andreas Modlin, Irvin M. TI A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management SO ENDOCRINE CONNECTIONS LA English DT Article DE biomarker; carcinoid; CTC; CT scan; Delphic consensus; imaging; mRNA; MRI; multianalyte; NETest; neuroendocrine tumor; PET; RECIST; somatostatin ID MEDIATED RADIONUCLIDE THERAPY; POSITRON-EMISSION-TOMOGRAPHY; ENDOCRINE NEOPLASIA TYPE-1; CHROMOGRANIN-A; PROGNOSTIC-FACTORS; GA-68-DOTA-TYR(3)-OCTREOTIDE PET; TRANSCRIPT ANALYSIS; GUIDELINES UPDATE; CLINICAL UTILITY; BREAST-CANCER AB The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (> 75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy. C1 [Oberg, Kjell; Sundin, Anders] Uppsala Univ, Uppsala, Sweden. [Krenning, Eric; Kwekkeboom, Dik] Erasmus MC, Rotterdam, Netherlands. [Bodei, Lisa] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Kidd, Mark; Drozdov, Ignat] Wren Labs, Branford, CT USA. [Tesselaar, Margot; Korse, Tiny] Netherlands Canc Inst, Amsterdam, Netherlands. [Ambrosini, Valentina] Univ Bologna, Bologna, Italy. [Baum, Richard P.] Zent Klin Bad Berka, Bad Berka, Germany. [Kulke, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pavel, Marianne; Prasad, Vikas] Charite Hosp, Berlin, Germany. [Cwikla, Jaroslaw] Univ Warmia & Mazury, Olsztyn, Poland. [Falconi, Massimo] Osped San Raffaele, Milan, Italy. [Fazio, Nicola] IEO European Inst Oncol, Milan, Italy. [Frilling, Andrea] Imperial Coll London, London, England. [Jensen, Robert] NIH, Bldg 10, Bethesda, MD 20892 USA. [Koopmans, Klaus] Martini Ziekenhuis, Groningen, Netherlands. [Maecke, Helmut] Univ Hosp Freiburg, Freiburg, Germany. [Paganelli, Giovanni; Severi, Stefano] Inst Sci Romagnolo Studio & Cura Tumori, Meldola, Italy. [Salazar, Ramon] Inst Catala Oncol, Barcelona, Spain. [Strosberg, Jonathan; Cives, Mauro] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Scarpa, Aldo] Univ Verona, Verona, Italy. [Grossman, Ashley] Univ Oxford, Oxford, England. [Walenkamp, Annemeik] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Virgolini, Irene] Med Univ Innsbruck, Innsbruck, Austria. [Kjaer, Andreas] Univ Copenhagen, Copenhagen, Denmark. [Modlin, Irvin M.] Yale Univ, New Haven, CT USA. RP Modlin, IM (reprint author), Yale Univ, New Haven, CT USA. EM imodlin@optonline.net OI Kjaer, Andreas/0000-0002-2706-5547; fazio, nicola/0000-0001-6869-0704 FU Clifton Life Sciences FX Financial support was provided by Clifton Life Sciences. NR 87 TC 2 Z9 2 U1 5 U2 5 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 2049-3614 J9 ENDOCR CONNECT JI Endocr. Connect. PD SEP 1 PY 2016 VL 5 IS 5 BP 174 EP 187 DI 10.1530/EC-16-0043 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EB6FL UT WOS:000387476900009 PM 27582247 ER PT J AU Niquet, J Baldwin, R Norman, K Suchomelova, L Lumley, L Wasterlain, CG AF Niquet, Jerome Baldwin, Roger Norman, Keith Suchomelova, Lucie Lumley, Lucille Wasterlain, Claude G. TI Midazolam-ketamine dual therapy stops cholinergic status epilepticus and reduces Morris water maze deficits SO EPILEPSIA LA English DT Article DE Refractory status epilepticus; Cholinergic seizures; Neuronal injury; Hippocampal sclerosis; Spatial memory; Epileptogenesis ID REFRACTORY STATUS EPILEPTICUS; CONVULSIVE STATUS EPILEPTICUS; SOMAN-INDUCED SEIZURES; GABA(A) RECEPTORS; HIPPOCAMPAL-NEURONS; PILOCARPINE MODEL; GUINEA-PIGS; EPILEPSY; RATS; ACCUMULATION AB Objective: Pharmacoresistance remains an unsolved therapeutic challenge in status epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE triggers a rapid internalization of synaptic c-aminobutyric acid A (GABA(A)) receptors and externalization of N-methyl-D-aspartate (NMDA) receptors that may explain the loss of potency of standard antiepileptic drugs (AEDs). We hypothesized that a drug combination aimed at correcting the consequences of receptor trafficking would reduce SE severity and its long-term consequences. Methods: A severe model of SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABA(A) receptor agonist midazolam, the NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min after SE onset in combination or as monotherapy. Measures of SE severity were the primary outcome. Secondary outcomes were acute neuronal injury, spontaneous recurrent seizures (SRS), and Morris water maze (MWM) deficits. Results: Midazolam-ketamine dual therapy was more efficient than double-dose midazolam or ketamine monotherapy or than valproate-midazolam or valproate-ketamine dual therapy in reducing several parameters of SE severity, suggesting a synergistic mechanism. In addition, midazolam-ketamine dual therapy reduced SE-induced acute neuronal injury, epileptogenesis, and MWM deficits. Significance: This study showed that a treatment aimed at correcting maladaptive GABA(A) receptor and NMDA receptor trafficking can stop SE and reduce its long-term consequences. Early midazolam-ketamine dual therapy may be superior to monotherapy in the treatment of benzodiazepine-refractory SE. C1 [Niquet, Jerome; Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Niquet, Jerome; Baldwin, Roger; Norman, Keith; Suchomelova, Lucie; Wasterlain, Claude G.] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA USA. [Lumley, Lucille] USAMRICD, Aberdeen Proving Ground, MD USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd,Bldg 114,Room 139, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU U.S. Department of Veterans Affairs (Biomedical Laboratory Research and Development Service) [I01 BX000273-07]; National Institute of Neurological Diseases and Stroke (NINDS) [UO1 NS074926] FX This work was supported in part by Merit Review Award #I01 BX000273-07 from the U.S. Department of Veterans Affairs (Biomedical Laboratory Research and Development Service) and National Institute of Neurological Diseases and Stroke (NINDS; grant UO1 NS074926; CW). NR 35 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD SEP PY 2016 VL 57 IS 9 BP 1406 EP 1415 DI 10.1111/epi.13480 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA EB8QJ UT WOS:000387655600014 PM 27500978 ER PT J AU Park, KJ Menendez, ME Mears, SC Barnes, CL AF Park, Kwan Jun Menendez, Mariano E. Mears, Simon C. Barnes, C. Lowry TI Patients With Multiple Myeloma Have More Complications After Surgical Treatment of Hip Fracture SO GERIATRIC ORTHOPAEDIC SURGERY & REHABILITATION LA English DT Article DE multiple myeloma; mortality; complications; hip fractures; outcome; perioperative ID LONG-TERM SURVIVAL; METASTATIC-DISEASE; UNITED-STATES; BONE-DISEASE; ARTHROPLASTY; CANCER; OUTCOMES; SURGERY; HOSPITALIZATION; REPLACEMENT AB Objectives: Bone lesions from multiple myeloma may lead to pathological fracture of the proximal femur, requiring either fixation or arthroplasty. Little is known about the impact of multiple myeloma on hip fracture care. We investigated whether the patients with multiple myeloma undergoing surgical treatment of hip fractures would be at increased risk for adverse outcomes versus patients who sustain a hip fracture without multiple myeloma. Methods: Using discharge records from the Nationwide Inpatient Sample (2002-2011), we identified 2 440 513 patients older than 50 years of age with surgically treated hip fractures. Of which, 4011 (0.2%) were found to have multiple myeloma. We compared perioperative outcomes between the patients with multiple myeloma and the nonmultiple myeloma patients using multivariable logistic regression modeling. Results: Patients with multiple myeloma were more likely to have several postoperative complications, such as in-hospital pneumonia (odds ratio [ OR]: 1.31, 95% confidence interval [CI]: 1.14-1.51), sepsis (OR: 1.72, 95% CI: 1.32-2.25), surgical site infection (OR: 1.66, 95% CI: 1.38-2.00), and acute renal failure (OR: 1.28, 95% CI: 1.14-1.43). We found that myeloma was not associated with increased inpatient mortality, myocardial infarction, respiratory failure, thromboembolic events, or pulmonary embolism. Conclusion: Patients with multiple myeloma are at increased risk for immediate postoperative complications following surgical treatment of hip fractures including in-hospital pneumonia, surgical site infection, and acute renal failure but not hospital mortality, when compared to hip fracture patients without multiple myeloma. Perioperative management of hip fractures in patients with myeloma may be optimized by increased awareness of these risks in this subset of patients. C1 [Park, Kwan Jun; Mears, Simon C.; Barnes, C. Lowry] Univ Arkansas Med Sci, Dept Orthopaed Surg, Slot 531,4301 West Markham St, Little Rock, AR 72205 USA. [Menendez, Mariano E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA USA. RP Barnes, CL (reprint author), Univ Arkansas Med Sci, Dept Orthopaed Surg, Slot 531,4301 West Markham St, Little Rock, AR 72205 USA. EM clbarnes@uams.edu NR 35 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2151-4585 EI 2151-4593 J9 GERIATR ORTHOP SURG JI Geriatr. Orthop. Surg. Rehabil. PD SEP PY 2016 VL 7 IS 3 BP 158 EP 162 DI 10.1177/2151458516658330 PG 5 WC Orthopedics SC Orthopedics GA EC0IJ UT WOS:000387783100008 PM 27551575 ER PT J AU Deshpande, V Zane, NA Kraft, S Stone, JH Faquin, WC AF Deshpande, Vikram Zane, Nicolas A. Kraft, Stefan Stone, John H. Faquin, William C. TI Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall SO HEAD & NECK PATHOLOGY LA English DT Article DE IgG4 related disease; Mastoiditis; IgG4 ID IGG4-RELATED SYSTEMIC-DISEASE; PANCREATITIS; NOMENCLATURE; PATHOLOGY; FEATURES; CRITERIA; NECK; HEAD AB IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed [50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of[40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection. C1 [Deshpande, Vikram; Zane, Nicolas A.; Kraft, Stefan; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 27 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 SEP PY 2016 VL 10 IS 3 BP 314 EP 320 DI 10.1007/s12105-016-0710-0 PG 7 WC Pathology SC Pathology GA EC3IL UT WOS:000388019600006 PM 27091207 ER PT J AU Polsunas, PJ Sowa, G Fritz, JM Gentili, A Morone, NE Raja, SN Rodriguez, E Schmader, K Scholten, JD Weiner, DK AF Polsunas, Patrick J. Sowa, Gwendolyn Fritz, Julie M. Gentili, Angela Morone, Natalia E. Raja, Srinivasa Naga Rodriguez, Eric Schmader, Kenneth Scholten, Joel D. Weiner, Debra K. TI Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment: Part X: Sacroiliac Joint Syndrome SO PAIN MEDICINE LA English DT Article DE Chronic Low Back Pain; Sacroiliac Joint Pain; Older Adults ID INJECTION ARTHROGRAPHY TECHNIQUE; PROVOCATION TESTS; SELF-MANAGEMENT; REFERRAL MAPS; LUMBAR DISC; DIAGNOSIS; PREVALENCE; VALIDITY; DISEASE AB Objective. To present an algorithm of sequential treatment options for managing sacroiliac joint ( SIJ) pain in the setting of chronic low back pain ( CLBP) in the older adult. This is the tenth part in a series, and includes an illustrative clinical case. Methods. The stepped care drug table and evaluation and treatment algorithm were created following a thorough literature review of approaches and subsequent analysis through a modified Delphi process. The principal investigator developed the initial draft, which was refined for content by an interdisciplinary panel of five experts. The refined materials were then assessed for the feasibility of implementation and validity of recommendations for older adults in a primary care setting by a panel of nine primary care providers. While not exclusive to Veteran's Health Administration (VHA) facilities, an emphasis was made to include resources and medications available to providers in the VHA. Results. The algorithm and drug table developed to systematically identify and address SIJ pain in the older adult is presented here. The process should begin with recognizing the presenting symptoms of CLBP stemming from the SI region, and supporting physical exam testing using the compression test and thigh thrust maneuver. Identification of the SIJ as a pain generator is followed by assessment and treatment of contributory factors. SIJ pain treatment should begin with education and self-management including exercise, and may escalate to include interventional procedures and/or referral to a pain rehabilitation program. Conclusions. Pain originating from the SIJ is often under-recognized, but a structured and consistent approach can help identify older patients who would benefit from treatment of this contributor to CLBP. Key Words. Chronic Low Back Pain; Sacroiliac Joint Pain; Older Adults. C1 [Polsunas, Patrick J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Sowa, Gwendolyn] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Sowa, Gwendolyn] Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Fritz, Julie M.] Univ Utah, Coll Hlth, Dept Phys Therapy, Salt Lake City, UT USA. [Gentili, Angela] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Gentili, Angela] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Morone, Natalia E.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Morone, Natalia E.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Morone, Natalia E.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Sowa, Gwendolyn; Raja, Srinivasa Naga] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD USA. [Raja, Srinivasa Naga] Johns Hopkins Univ, Sch Med, Crit Care Med, Baltimore, MD USA. [Raja, Srinivasa Naga] Johns Hopkins Univ, Sch Med, Div Pain Med, Baltimore, MD USA. [Rodriguez, Eric] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Schmader, Kenneth] GRECC, Durham VA Med Ctr, Durham, NC USA. [Schmader, Kenneth] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Scholten, Joel D.] Washington DC VA Med Ctr, Washington, DC USA. [Scholten, Joel D.] Vet Hlth Adm, Rehabil Serv, Washington, DC USA. [Scholten, Joel D.] Vet Hlth Adm, Prosthet Serv, Washington, DC USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] Dept Med, Div Geriatr Med, Pittsburgh, PA USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Bldg 30,00GR, Pittsburgh, PA 15240 USA. EM debra.weiner@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States government. NR 32 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD SEP PY 2016 VL 17 IS 9 BP 1638 EP 1647 DI 10.1093/pm/pnw151 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EC3IZ UT WOS:000388021100007 PM 27605679 ER PT J AU Hanna, GM Fishman, I Edwards, DA Shen, SQ Kram, C Liu, XL Shotwell, M Gilligan, C AF Hanna, George M. Fishman, Irina Edwards, David A. Shen, Shiqian Kram, Cheryl Liu, Xulei Shotwell, Matthew Gilligan, Christopher TI Development and Patient Satisfaction of a New Telemedicine Service for Pain Management at Massachusetts General Hospital to the Island of Martha's Vineyard SO PAIN MEDICINE LA English DT Article DE Telemedicine; Telehealth; Pain Medicine; Pain Management ID PROJECT ECHO; TELEHEALTH; CARE; INTERVENTION; MODEL AB Objective. Patients in remote areas lack access to specialist care and pain management services. In order to provide pain management care to patients remote from our center, we created a telemedicine pain clinic ( telepain) at Massachusetts General Hospital ( MGH) in Boston, MA to extend services to the Island of Martha's Vineyard. Design. Over 13 months, 238 telepain video clinic evaluations were conducted. A pain physician visited the island 1-2 days per month and performed 121 interventions. Given the novelty of telemedicine clinics, we surveyed patients to gauge satisfaction and identify perceived weaknesses in our approach that could be addressed. Forty-nine consecutive patients answered a 14-question, 5-point balanced Likert-scale survey with 1 (no, definitely not) being most negative and 5 (yes, definitely) being most positive. Setting. Patients on Martha's Vineyard referred for pain management consultation services via telemedicine. Patients. Forty-nine consecutive patients evaluated via telemedicine. Interventions. Likert-scale survey administered. Measures. Questions measured patient impressions of video-based visits with their doctor, convenience of the visit, concerns about privacy, and whether they would recommend such a visit, among other items. Results. Mean respondent scores for each question were > 4.3 indicating a favorable impression of the telepain clinic experience. Lowest mean scores were found when respondents were asked to compare the care they received by telepain versus an in-person visit, or whether they were able to develop a friendly relationship with the doctor. Conclusions. The results suggest an overall positive reception of telepain by patients, yet highlight the challenge of building a patient-physician relationship remotely. C1 [Hanna, George M.; Shen, Shiqian] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Ctr Pain Med, 55 Fruit St, Boston, MA 02114 USA. [Fishman, Irina; Gilligan, Christopher] Beth Israel Deaconess Med Ctr, Dept Anesthesiol, Boston, MA 02215 USA. [Edwards, David A.; Liu, Xulei; Shotwell, Matthew] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Kram, Cheryl] Marthas Vineyard Hosp, Pain Management Ctr, Oak Bluffs, MA USA. RP Hanna, GM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Ctr Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM ghanna2@mgh.harvard.edu FU NIGMS NIH HHS [T32 GM007592] NR 21 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD SEP PY 2016 VL 17 IS 9 BP 1658 EP 1663 DI 10.1093/pm/pnw069 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EC3IZ UT WOS:000388021100009 PM 27121891 ER PT J AU Vadva, Z Laufer, MR Weldon, CB Frazier, AL Vargas, SO AF Vadva, Zareen Laufer, Marc R. Weldon, Christopher B. Frazier, A. Lindsay Vargas, Sara O. TI Diagnostic Impact of Peritoneal Fluid Cytology in the Setting of Pediatric Uterine Adnexal Biopsy or Resection SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE cytopathology; peritoneal fluid; ascites; adnexa uteri; adnexal diseases; pediatrics; ovarian neoplasms ID OVARIAN-TUMORS; CHILDREN; ADOLESCENTS; WASHINGS; BENIGN; SURGERY; MASSES AB Peritoneal fluid sampling has been recommended during surgery to resect an ovarian or fallopian tube mass, particularly for its staging relevance in ovarian carcinoma. Guidelines specifically for children are not well established, partly because of incomplete knowledge of the test characteristics in this age group. We sought to determine whether peritoneal fluid cytology sampling aids in diagnosis or staging of pediatric uterine adnexal masses. Children who underwent adnexal mass biopsy or excision from 1993 to 2014 were identified via archival review. Accompanying peritoneal fluid (washings or ascites) was assessed to determine whether it provided information beyond that in the accompanying surgical pathology specimen. Of 656 patients who underwent adnexal mass resection, 350 had concurrent cytologic sampling of peritoneal fluid. Median age at surgery was 14 years. Adnexal mass histologic examination showed tumors with malignant potential in 54 (8%) patients. Malignancy was identified in 3 cytology specimens (2 dysgerminomas and 1 mixed germ cell tumor). By today's guidelines, the malignant cytology specimens would have upstaged 1 of the 3 patients, and her therapy may not have changed. Cytology findings did not refine the histologic diagnosis in any benign or malignant case. Our findings demonstrated a low rate of malignancy (<1%) in peritoneal washing/ascites samples accompanying resection of a pediatric adnexal mass. Influencing staging or treatment by cytology sampling was rare in our cohort. Our findings provided benchmark data in an area dominated by adult studies. Furthermore, they may guide recommendations for cytologic fluid collection and processing tailored for pediatric populations. C1 [Vadva, Zareen; Vargas, Sara O.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Laufer, Marc R.] Boston Childrens Hosp, Div Gynecol, Boston, MA USA. [Weldon, Christopher B.] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Weldon, Christopher B.; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA. [Frazier, A. Lindsay] Boston Childrens Hosp, Div Pediat Oncol, Boston, MA USA. RP Vargas, SO (reprint author), Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. EM sara.vargas@childrens.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD SEP-OCT PY 2016 VL 19 IS 5 BP 401 EP 408 DI 10.2350/15-10-1716-OA.1 PG 8 WC Pathology; Pediatrics SC Pathology; Pediatrics GA EC3ED UT WOS:000388007200006 PM 26579785 ER PT J AU Cheng, FX Murray, JL Zhao, JF Sheng, JS Zhao, ZM Rubin, DH AF Cheng, Feixiong Murray, James L. Zhao, Junfei Sheng, Jinsong Zhao, Zhongming Rubin, Donald H. TI Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXPRESSION SIGNATURES; MUTATIONAL LANDSCAPE; REOVIRUS INFECTION; ONCOLYTIC REOVIRUS; BINDING PROTEIN; BREAST-CANCER; TUMOR TYPES; EBOLA; REPLICATION AB Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics. C1 [Cheng, Feixiong] Sichuan Univ, West China Med Sch, West China Hosp, State Key Lab Biotherapy,Collaborat Innovat Ctr B, Chengdu 610041, Sichuan, Peoples R China. [Cheng, Feixiong; Zhao, Zhongming] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA. [Murray, James L.] Zirus Inc, Buford, GA USA. [Zhao, Junfei; Zhao, Zhongming] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Ctr Precis Hlth, Houston, TX 77030 USA. [Sheng, Jinsong; Rubin, Donald H.] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. [Zhao, Zhongming] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Zhao, Zhongming] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. [Rubin, Donald H.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Rubin, Donald H.] Vet Tennessee Valley Healthcare Syst, Res Med, Nashville, TN USA. [Cheng, Feixiong] Harvard Med Sch, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Cheng, Feixiong] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Murray, James L.] GeneTAG Technol Inc, Atlanta, GA USA. RP Cheng, FX (reprint author), Sichuan Univ, West China Med Sch, West China Hosp, State Key Lab Biotherapy,Collaborat Innovat Ctr B, Chengdu 610041, Sichuan, Peoples R China.; Cheng, FX (reprint author), Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.; Cheng, FX (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.; Cheng, FX (reprint author), Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. EM fxcheng1985@gmail.com; zhongming.zhao@uth.tmc.edu; don.h.rubin@vanderbilt.edu FU National Natural Science Foundation of China [81573020]; National Institutes of Health (NIH) [R01LM011177] FX This work was supported by the National Natural Science Foundation of China (81573020). This work was also partially supported by National Institutes of Health (NIH) grants (R01LM011177) to ZZ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 92 TC 5 Z9 5 U1 1 U2 1 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 SEP PY 2016 VL 12 IS 9 AR e1005074 DI 10.1371/journal.pcbi.1005074 PG 27 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA EB8RN UT WOS:000387658600013 PM 27632082 ER PT J AU Platig, J Castaldi, PJ DeMeo, D Quackenbush, J AF Platig, John Castaldi, Peter J. DeMeo, Dawn Quackenbush, John TI Bipartite Community Structure of eQTLs SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; GENOME-WIDE ASSOCIATION; METABOLIC NETWORKS; IDENTIFICATION; INTEGRATION; POPULATION AB Genome Wide Association Studies (GWAS) and expression quantitative trait locus (eQTL) analyses have identified genetic associations with a wide range of human phenotypes. However, many of these variants have weak effects and understanding their combined effect remains a challenge. One hypothesis is that multiple SNPs interact in complex networks to influence functional processes that ultimately lead to complex phenotypes, including disease states. Here we present CONDOR, a method that represents both cis- and trans-acting SNPs and the genes with which they are associated as a bipartite graph and then uses the modular structure of that graph to place SNPs into a functional context. In applying CONDOR to eQTLs in chronic obstructive pulmonary disease (COPD), we found the global network "hub" SNPs were devoid of disease associations through GWAS. However, the network was organized into 52 communities of SNPs and genes, many of which were enriched for genes in specific functional classes. We identified local hubs within each community ("core SNPs") and these were enriched for GWAS SNPs for COPD and many other diseases. These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions. These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits. C1 [Platig, John; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Platig, John; Quackenbush, John] Harvard Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Castaldi, Peter J.; DeMeo, Dawn; Quackenbush, John] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Castaldi, Peter J.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Castaldi, Peter J.; DeMeo, Dawn] Harvard Med Sch, Boston, MA USA. [DeMeo, Dawn] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP Platig, J (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.; Platig, J (reprint author), Harvard Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM jplatig@jimmy.harvard.edu OI Castaldi, Peter/0000-0001-9920-4713 FU US National Heart Lung, and Blood Institute of the National Institutes of Health [1P01HL105339, 1R01HL111759]; US National Institute of Allergy and Infections Disease of the National Institutes of Health [1R01AI099204]; US National Heart, Lung, and Blood Institute [K08 HL102265, R01 HL124233]; COPDGene from US National Heart, Lung, and Blood Institute [R01 HL089856, R01 HL089897] FX This work was supported by grants 1P01HL105339 (PJC, DD, JP, JQ) and 1R01HL111759 (DD, JP, JQ) from the US National Heart Lung, and Blood Institute of the National Institutes of Health and grant 1R01AI099204 from the US National Institute of Allergy and Infections Disease of the National Institutes of Health (JP, JQ). PJC was also supported by grants from the US National Heart, Lung, and Blood Institute (K08 HL102265 and R01 HL124233). Primary data used in this analysis was generated by the Lung Genomics Research Consortium (RC2 HL101715 from the US National Heart, Lung, and Blood Institute). Previously published COPD GWAS results were supported by COPDGene (R01 HL089856 and R01 HL089897 from the US National Heart, Lung, and Blood Institute). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD SEP PY 2016 VL 12 IS 9 AR e1005033 DI 10.1371/journal.pcbi.1005033 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA EB8RN UT WOS:000387658600005 PM 27618581 ER PT J AU Dewar, R Jayaram, G Parkash, V Balachandran, I Tambouret, R AF Dewar, Rajan Jayaram, Gita Parkash, Vinita Balachandran, Indra Tambouret, Rosemary TI Massive Open Online Course for Paps: An Electronic Educational Module Building Exercise to Train Cytoscreeners-Making Pap Smears Available in Resource-Limited Settings SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 [Dewar, Rajan] Univ Michigan, Ann Arbor, MI 48109 USA. [Jayaram, Gita] Ramakrishna Diagnost Ctr, Ooty, India. [Parkash, Vinita] Yale Univ, New Haven, CT USA. [Balachandran, Indra] Albany Coll Pharm & Hlth Sci, Albany, NY USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 SEP 1 PY 2016 VL 146 SU 1 MA 195 PG 1 WC Pathology SC Pathology GA EB1TZ UT WOS:000387139400199 ER PT J AU Hoganson, DM Finkelstein, EB Owens, GE Hsiao, JC Eng, KY Kulig, KM Kim, ES Kniazeva, T Pomerantseva, I Neville, CM Turk, JR Fermini, B Borenstein, JT Vacanti, JP AF Hoganson, David M. Finkelstein, Eric B. Owens, Gwen E. Hsiao, James C. Eng, Kurt Y. Kulig, Katherine M. Kim, Ernest S. Kniazeva, Tatiana Pomerantseva, Irina Neville, Craig M. Turk, James R. Fermini, Bernard Borenstein, Jeffrey T. Vacanti, Joseph P. TI A bilayer small diameter in vitro vascular model for evaluation of drug induced vascular injury SO BIOMICROFLUIDICS LA English DT Article ID SMOOTH-MUSCLE; SHEAR-STRESS; INHIBITOR; RAT; BIOMARKERS; COCULTURE; ACTIVATION; MECHANISMS; EXPRESSION; PATHOLOGY AB In pre-clinical safety studies, drug-induced vascular injury (DIVI) is defined as an adverse response to a drug characterized by degenerative and hyperplastic changes of endothelial cells and vascular smooth muscle cells. Inflammation may also be seen, along with extravasation of red blood cells into the smooth muscle layer (i.e., hemorrhage). Drugs that cause DIVI are often discontinued from development after considerable cost has occurred. An in vitro vascular model has been developed using endothelial and smooth muscle cells in co-culture across a porous membrane mimicking the internal elastic lamina. Arterial flow rates of perfusion media within the endothelial chamber of the model induce physiologic endothelial cell alignment. Pilot testing with a drug known to cause DIVI induced extravasation of red blood cells into the smooth muscle layer in all devices with no extravasation seen in control devices. This engineered vascular model offers the potential to evaluate candidate drugs for DIVI early in the discovery process. The physiologic flow within the co-culture model also makes it candidate for a wide variety of vascular biology investigations. Published by AIP Publishing. C1 [Hoganson, David M.] Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. [Hoganson, David M.; Owens, Gwen E.; Kulig, Katherine M.; Pomerantseva, Irina; Neville, Craig M.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Finkelstein, Eric B.] Syracuse Univ, Syracuse Biomat Inst, Syracuse, NY 13244 USA. [Finkelstein, Eric B.] Syracuse Univ, Dept Biomed & Chem Engn, Syracuse, NY 13244 USA. [Hsiao, James C.; Kim, Ernest S.; Kniazeva, Tatiana; Borenstein, Jeffrey T.] Draper Labs, Cambridge, MA 02139 USA. [Eng, Kurt Y.] Pfizer Inc, Cambridge, MA 02139 USA. [Turk, James R.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Fermini, Bernard] Pfizer Inc, Groton, CT 06340 USA. RP Hoganson, DM (reprint author), Boston Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA.; Hoganson, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. FU NIH [F32 DK076349-01] FX This study was supported by a generous research gift from Pfizer, Inc. B.F. is an employee of Pfizer. The authors gratefully acknowledge the critical review provided by Mike Lawton and Bradley Enerson from Pfizer, Inc. The authors also acknowledge the support from the NIH (F32 DK076349-01, DMH). NR 25 TC 0 Z9 0 U1 1 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 1932-1058 J9 BIOMICROFLUIDICS JI Biomicrofluidics PD SEP PY 2016 VL 10 IS 5 AR 054116 DI 10.1063/1.4964814 PG 10 WC Biochemical Research Methods; Biophysics; Nanoscience & Nanotechnology; Physics, Fluids & Plasmas SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Physics GA EB7OI UT WOS:000387577400016 PM 27795748 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Emerging Treatment Options for Carcinoid Syndrome SO CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY LA English DT Editorial Material ID TELOTRISTAT ETIPRATE; NEUROENDOCRINE TUMORS C1 [Kulke, Matthew H.] Harvard Med Sch, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA. [Kulke, Matthew H.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kulke, Matthew H.] Harvard Med Sch, Med, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Harvard Med Sch, Program Neuroendocrine & Carcinoid Tumors, Boston, MA 02115 USA.; Kulke, MH (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA.; Kulke, MH (reprint author), Harvard Med Sch, Med, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU MILLENNIUM MEDICAL PUBLISHING, INC PI NEW YORK PA 611 BROADWAY, STE 310, NEW YORK, NY 10012 USA SN 1543-0790 J9 CLIN ADV HEMATOL ONC JI Clin. Adv. Hematol. Oncol. PD SEP PY 2016 VL 14 IS 9 BP 666 EP 667 PG 2 WC Oncology SC Oncology GA EB4JZ UT WOS:000387339000005 PM 27673284 ER PT J AU Imran, TF Ghazipura, M Liu, S Hossain, T Ashtyani, H Kim, B Gaziano, JM Djousse, L AF Imran, Tasnim F. Ghazipura, Marya Liu, Spencer Hossain, Tanzib Ashtyani, Hormoz Kim, Bernard Gaziano, J. Michael Djousse, Luc TI Effect of continuous positive airway pressure treatment on pulmonary artery pressure in patients with isolated obstructive sleep apnea: a meta-analysis SO HEART FAILURE REVIEWS LA English DT Article DE Obstructive sleep apnea; Pulmonary artery pressure; Pulmonary hypertension; Continuous positive airway pressure ID SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE; LUNG-DISEASE; HYPERTENSION; HEMODYNAMICS; HYPOXIA; VASODILATORS; ENDOTHELIUM; EXPRESSION; HYPOXEMIA AB Pulmonary hypertension (PH) can occur in patients with obstructive sleep apnea (OSA) in the absence of cardiac or lung disease. Data on the development and severity of PH, and the effect of continuous positive airway pressure (CPAP) therapy on pulmonary artery (PA) pressures in these patients have been inconsistent in the literature. We sought to determine whether CPAP therapy affects PA pressures in patients with isolated OSA in this meta-analysis. We searched PubMed, Medline, EMBASE and other databases from January 1980 to August 2015. Studies of patients with OSA, defined as an apnea-hypopnea index[ 10 events/h, and PH, defined as PA pressure [ 25 mmHg were included. Two reviewers independently extracted data and assessed risk of bias. A total of 222 patients from seven studies (341.53 person-years) had reported PA pressures before and after treatment with CPAP therapy. 77 % of participants were men, with a mean age of 52.5 years, a mean apnea-hypopnea index of 58 events/h, and mean PA pressure of 39.3 +/- 6.3 mmHg. CPAP treatment duration ranged from 3 to 70 months. Using fixed effects meta-analysis, CPAP therapy was associated with a decrease in PA pressure of 13.3 mmHg (95 % CI 12.7-14.0) in our study population. This meta-analysis found that CPAP therapy is associated with a significantly lower PA pressure in patients with isolated OSA and PH. C1 [Imran, Tasnim F.; Gaziano, J. Michael; Djousse, Luc] Harvard Med Sch, VA Boston Healthcare Syst, Brigham & Womens Hosp, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. [Ghazipura, Marya] NYU, Langone Med Ctr, Dept Populat Hlth, 650 First Ave, New York, NY 10001 USA. [Liu, Spencer; Hossain, Tanzib; Ashtyani, Hormoz; Kim, Bernard] Rutgers New Jersey Med Sch, Heart Failure & Pulm Hypertens Program, 30 Prospect St, Hackensack, NJ 07103 USA. RP Imran, TF (reprint author), Harvard Med Sch, VA Boston Healthcare Syst, Brigham & Womens Hosp, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM TFImran@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 42 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD SEP PY 2016 VL 21 IS 5 BP 591 EP 598 DI 10.1007/s10741-016-9548-5 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EB2YG UT WOS:000387227900011 PM 27000753 ER PT J AU Sullivan, JL Rivard, PE Shin, MH Rosen, AK AF Sullivan, Jennifer L. Rivard, Peter E. Shin, Marlena H. Rosen, Amy K. TI Applying the High Reliability Health Care Maturity Model to Assess Hospital Performance: A VA Case Study SO JOINT COMMISSION JOURNAL ON QUALITY AND PATIENT SAFETY LA English DT Article ID PATIENT SAFETY; SURGICAL SERVICES; FAILURE MODE; ORGANIZATIONS; COORDINATION; TEAMWORK; OUTCOMES AB Background: The lack of a tool for categorizing and differentiating hospitals according to their high reliability organization (HRO)-related characteristics has hindered progress toward implementing and sustaining evidence-based HRO practices. Hospitals would benefit both from an understanding of the organizational characteristics that support HRO practices and from knowledge about the steps necessary to achieve HRO status to reduce the risk of harm and improve outcomes. The High Reliability Health Care Maturity (HRHCM) model, a model for health care organizations' achievement of high reliability with zero patient harm, incorporates three major domains critical for promoting HROs-Leadership, Safety Culture, and Robust Process Improvement (R). A study was conducted to examine the content validity of the HRHCM model and evaluate whether it can differentiate hospitals' maturity levels for each of the model's components. Methods: Staff perceptions of patient safety at six US Department of Veterans Affairs (VA) hospitals were examined to determine whether all 14 HRHCM components were present and to characterize each hospital's level of organizational maturity. Results: Twelve of the 14 components from the HRHCM model were detected; two additional characteristics emerged that are present in the HRO literature but not represented in the model-teamwork culture and system-focused tools for learning and improvement. Each hospital's level of organizational maturity could be characterized for 9 of the 14 components. Discussion: The findings suggest the HRHCM model has good content validity and that there is differentiation between hospitals on model components. Additional research is needed to understand how these components can be used to build the infrastructure necessary for reaching high-reliability. C1 [Sullivan, Jennifer L.; Rivard, Peter E.] VA Boston Healthcare Syst, CHOIR, Boston, MA 02130 USA. [Sullivan, Jennifer L.] Boston Univ, Sch Publ Health, Boston, MA 02215 USA. [Rivard, Peter E.; Rosen, Amy K.] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Rivard, Peter E.] Suffolk Univ, Sawyer Business Sch, Boston, MA 02114 USA. [Shin, Marlena H.; Rosen, Amy K.] CHOIR, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02215 USA. RP Sullivan, JL (reprint author), VA Boston Healthcare Syst, CHOIR, Boston, MA 02130 USA.; Sullivan, JL (reprint author), Boston Univ, Sch Publ Health, Boston, MA 02215 USA. EM jennifer.sullivan@va.gov NR 41 TC 1 Z9 1 U1 0 U2 0 PU JOINT COMMISSION RESOURCES INC PI OAK BROOK PA 1515 W 22 ST, STE 1300W, OAK BROOK, IL 60523 USA SN 1553-7250 EI 1938-131X J9 JT COMM J QUAL PATIE JI Jt. Comm. J. Qual. Patient Saf. PD SEP PY 2016 VL 42 IS 9 BP 389 EP + PG 23 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EB7GG UT WOS:000387554000002 PM 27535456 ER PT J AU Chen, CT Ackerly, DC Gottlieb, G AF Chen, Christopher T. Ackerly, D. Clay Gottlieb, Gary TI Transforming Healthcare Delivery: Why and How Accountable Care Organizations Must Evolve SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID MANAGEMENT; PAYMENTS AB Accountable care organizations (ACOs) have shown promise in reducing healthcare spending growth, but have proven to be financially unsustainable for many healthcare organizations. Even ACOs with shared savings have experienced overall losses because the shared savings bonuses have not covered the costs of delivering population health. As physicians and former ACO leaders, we believe in the concept of accountable care, but ACOs need to evolve if they are to have a viable future. We propose the novel possibility of allowing ACOs to bill fee-for-service for their population health interventions, a concept we call population health billing. (C) 2016 Society of Hospital Medicine C1 [Chen, Christopher T.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Ackerly, D. Clay] NaviHealth, Brentwood, TN USA. [Gottlieb, Gary] Partners Hlth, Boston, MA USA. [Gottlieb, Gary] Harvard Med Sch, Boston, MA USA. RP Chen, CT (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM chris.chen@post.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2016 VL 11 IS 9 BP 658 EP 661 DI 10.1002/jhm.2589 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA EB0ZC UT WOS:000387074500011 PM 27596543 ER PT J AU Harris, JA Herrel, LA Healy, MA Wancata, LM Perumalswami, CR AF Harris, John A. Herrel, Lindsey A. Healy, Mark A. Wancata, Lauren M. Perumalswami, Chithra R. TI Milestones for the Final Mile: Interspecialty Distinctions in Primary Palliative Care Skills Training SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Primary palliative care; graduate medical education; Accreditation Council for Graduate Medical Education; milestones; content analysis; residency ID OF-LIFE CARE; NATIONAL-SURVEY; MEDICAL-STUDENTS; CURRICULUM; RESIDENTS; EDUCATION; HOSPICE; FELLOWS; ISSUES AB Context. Primary palliative care (PPC) skills are useful in a wide variety of medical and surgical specialties, and the expectations of PPC skill training are unknown across graduate medical education. Objectives. We characterized the variation and quality of PPC skills in residency outcomes-based Accreditation Council for Graduate Medical Education (ACGME) milestones. Methods. We performed a content analysis with structured implicit review of 2015 ACGME milestone documents from 14 medical and surgical specialties chosen for their exposure to clinical situations requiring PPC. For each specialty milestone document, we characterized the variation and quality of PPC skills in residency outcomes-based ACGME milestones. Results. We identified 959 occurrences of 29 palliative search terms within 14 specialty milestone documents. Within these milestone documents, implicit review characterized 104 milestones with direct saliency to PPC skills and 196 milestones with indirect saliency. Initial interrater agreement of the saliency rating among the primary reviewers was 89%. Specialty milestone documents varied widely in their incorporation of PPC skills within milestone documents. PPC milestones were most commonly found in milestone documents for Anesthesiology, Pediatrics, Urology, and Physical Medicine and Rehabilitation. PPC-relevant milestones were most commonly found in the Interpersonal and Communication Skills core competency with 108 (36%) relevant milestones classified under this core competency. Conclusions. Future revisions of specialty-specific ACGME milestone documents should focus on currently underrepresented, but important PPC skills. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Harris, John A.] Univ Michigan, Inst Healthcare Policy & Innovat, Robert Wood Johnson Fdn Clin Scholars Program, Ann Arbor, MI 48109 USA. [Harris, John A.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Herrel, Lindsey A.] Univ Michigan, Dow Div Urol Hlth Serv Res, Dept Urol, Ann Arbor, MI 48109 USA. [Herrel, Lindsey A.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Healy, Mark A.; Wancata, Lauren M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Healy, Mark A.] Univ Michigan, Ctr Healthcare Outcomes & Policy, Ann Arbor, MI 48109 USA. [Perumalswami, Chithra R.] Univ Michigan, Robert Wood Johnson Fdn Clin Scholars Program, US Dept Vet Affairs, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Perumalswami, Chithra R.] Univ Michigan, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. RP Harris, JA (reprint author), 2800 Plymouth Rd,Bldg 14,Room G100, Ann Arbor, MI 48109 USA. EM harrja@med.umich.edu OI Harris, John/0000-0002-7907-8139 FU Robert Wood Johnson Foundation Clinical Scholars Program; U.S. Department of Veterans Affairs [N018080]; NIH T32 grant [CA009672, F025681] FX Dr. Harris is a Robert Wood Johnson Foundation Clinical Scholar at the University of Michigan. Dr. Perumalswami is a Robert Wood Johnson Foundation and Veterans Affairs Clinical Scholar at the University of Michigan. Support for the publication was provided by the Robert Wood Johnson Foundation Clinical Scholars Program and the U.S. Department of Veterans Affairs (N018080). The Robert Wood Johnson Foundation and the Department of Veterans Affairs were not directly involved in study design, data acquisition and interpretation, article preparation or review. Any opinions expressed herein do not necessarily reflect the opinions of the Robert Wood Johnson Foundation or the Department of Veterans Affairs. Drs. Wancata and Healy are supported by NIH T32 grant CA009672. Dr. Herrel is funded by NIH T32 grant F025681. The authors have no pertinent conflicts of interest to disclose. NR 23 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2016 VL 52 IS 3 BP 345 EP + DI 10.1016/j.jpainsymman.2016.03.007 PG 13 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA EA7RV UT WOS:000386830500007 PM 27260828 ER PT J AU Garrido, MM Dowd, B Hebert, PL Maciejewski, ML AF Garrido, Melissa M. Dowd, Bryan Hebert, Paul L. Maciejewski, Matthew L. TI Understanding Treatment Effect Terminology in Pain and Symptom Management Research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Treatment effect; randomized controlled trial; health services research; terminology; observational study; treatment assignment; selection bias ID HEALTH-SERVICES RESEARCH; INSTRUMENTAL VARIABLES; RANDOMIZED-TRIALS; SUBGROUP ANALYSIS; HETEROGENEITY; STATEMENT; MODELS; CANCER; CARE; GUIDELINES AB Within health services and medical research, there is a wide variety of terminology related to treatment effects. Understanding differences in types of treatment effects is especially important in pain and symptom management research where nonexperimental and quasiexperimental observational data analysis is common. We use the example of a palliative care consultation team leader considering implementation of a medication reconciliation program and a care-coordination intervention reported in the literature to illustrate population-level and conditional treatment effects and to highlight the sensitivity of values of treatment effects to sample selection and treatment assignment. Our goal is to facilitate appropriate reporting and interpretation of study results and to help investigators understand what information a decision maker needs when deciding whether to implement a treatment. Greater awareness of the reasons why treatment effects may differ across studies of the same patients in the same treatment settings can help policy makers and clinicians understand to whom a study's results may be generalized. Published by Elsevier Inc. C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, Bronx, NY USA. [Garrido, Melissa M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Dowd, Bryan] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Hebert, Paul L.] VA Puget Sound, Seattle, WA USA. [Hebert, Paul L.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Sch Med, Durham, NC USA. RP Garrido, MM (reprint author), 4A-17,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@va.gov OI Garrido, Melissa/0000-0002-8986-3536 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research, and Development Service [CDA 11-201/CDP 12-255, RCS 10-391] FX Dr. Garrido (CDA 11-201/CDP 12-255) and Dr. Maciejewski (RCS 10-391) receive support from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research, and Development Service. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. The authors declare no conflicts of interest. NR 29 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2016 VL 52 IS 3 BP 446 EP 452 DI 10.1016/j.jpainsymman.2016.01.016 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA EA7RV UT WOS:000386830500019 PM 27220944 ER PT J AU Yoshikawa, TT Ouslander, JG Applegate, WB AF Yoshikawa, Thomas T. Ouslander, Joseph G. Applegate, William B. TI Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID OLDER-ADULTS; CONTROLLED-TRIAL; HIP FRACTURE; FRAILTY; CARE; IMPAIRMENT; EXERCISE; DELIRIUM C1 [Yoshikawa, Thomas T.] Dept Vet Affairs Greater Los Angeles Healthcare S, Los Angeles, CA USA. [Yoshikawa, Thomas T.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ouslander, Joseph G.] Charles E Schmidt Coll Biomed Sci, Dept Integrated Med Sci, Boca Raton, FL USA. [Applegate, William B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med,Dept Med, Winston Salem, NC USA. RP Yoshikawa, TT (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 158, Los Angeles, CA 90073 USA. EM toyoshikawa@cdrewu.edu FU American Geriatrics Society FX All three authors receive a stipend from the American Geriatrics Society in their role as editors of JAGS. The authors have no other conflicts of interest to disclose relevant to this article. NR 20 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2016 VL 64 IS 9 BP 1763 EP 1768 DI 10.1111/jgs.14492 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FC UT WOS:000387017800031 PM 27553684 ER PT J AU Thorpe, CT Fowler, NR Harrigan, K Zhao, XH Kang, YH Hanlon, JT Gellad, WF Schleiden, LJ Thorpe, JM AF Thorpe, Carolyn T. Fowler, Nicole R. Harrigan, Katherine Zhao, Xinhua Kang, Yihuang Hanlon, Joseph T. Gellad, Walid F. Schleiden, Loren J. Thorpe, Joshua M. TI Racial and Ethnic Differences in Initiation and Discontinuation of Antidementia Drugs by Medicare Beneficiaries SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; health disparities; antidementia medications; Medicare; medication discontinuation ID CHOLINESTERASE INHIBITOR THERAPY; CLINICAL-PRACTICE GUIDELINE; SEVERE ALZHEIMERS-DISEASE; PHARMACOLOGICAL-TREATMENT; DEMENTIA; DONEPEZIL; CARE; DISPARITIES; MEMANTINE; PRESCRIPTION AB OBJECTIVES: To examine racial and ethnic differences in initiation and time to discontinuation of antidementia medication in Medicare beneficiaries. DESIGN: Retrospective cohort study. SETTING: Secondary analysis of 2009-10 enrollment, claims, and Part D prescription data for a 10% national sample of U.S. Medicare fee-for-service beneficiaries. PARTICIPANTS: Beneficiaries aged 65 and older with Alzheimer's disease or related dementia (ADRD) before 2009 and no fills for antidementia medications in the first half of 2009 (N = 84,043). MEASUREMENTS: Initiation was defined as having one or more fills for antidementia medication in the second half of 2009 and discontinuation as a gap in coverage of 30 days or more during the year after initiation. The Andersen Behavioral Model was used to guide covariate selection. RESULTS: Overall, 3,481 (4.1%) of previous nonusers initiated antidementia medication in the second half of 2009. Of those initiating one drug class (acetylcholinesterase inhibitors (AChEIs) or memantine), 9% later added the other class, and 2% switched classes. Of initiators, 23% discontinued within 1 month, and 62% discontinued within 1 year. Hispanic beneficiaries were more likely than white beneficiaries to initiate (adjusted odds ratio = 1.25, 95% confidence interval (CI) = 1.10-.41). Black and white beneficiaries did not differ in likelihood of initiation. Hispanic (adjusted hazard ratio (aHR) = 1.56, 95% CI = 1.34-1.82) and black (aHR = 1.25, 95% CI = 1.08-1.44) beneficiaries discontinued at a faster rate than white beneficiaries. CONCLUSION: Initiation of antidementia medications was no different in black and white beneficiaries and more likely in Hispanic beneficiaries; black and Hispanic beneficiaries discontinued at a faster rate. More research into reasons explaining these differences is needed. C1 [Thorpe, Carolyn T.; Harrigan, Katherine; Zhao, Xinhua; Hanlon, Joseph T.; Schleiden, Loren J.; Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 919 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. [Thorpe, Carolyn T.; Zhao, Xinhua; Hanlon, Joseph T.; Gellad, Walid F.; Schleiden, Loren J.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Fowler, Nicole R.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Fowler, Nicole R.] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [Fowler, Nicole R.] Regenstrief Inst Inc, Ctr Hlth Innovat & Implementat, Indianapolis, IN USA. [Zhao, Xinhua; Kang, Yihuang; Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Thorpe, CT (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 919 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ctthorpe@pitt.edu FU RAND-University of Pittsburgh Health Institute; Pittsburgh Claude D. Pepper Older Americans Independence Center [NIA P30 AG024827]; University of Pittsburgh School of Pharmacy FX The RAND-University of Pittsburgh Health Institute, the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AG024827), and the University of Pittsburgh School of Pharmacy provided funding for this study. NR 48 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2016 VL 64 IS 9 BP 1806 EP 1814 DI 10.1111/jgs.14403 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FC UT WOS:000387017800038 PM 27549029 ER PT J AU Alessi, C Martin, JL Fiorentino, L Fung, CH Dzierzewski, JM Tapia, JCR Song, Y Josephson, K Jouldjian, S Mitchell, MN AF Alessi, Cathy Martin, Jennifer L. Fiorentino, Lavinia Fung, Constance H. Dzierzewski, Joseph M. Tapia, Juan C. Rodriguez Song, Yeonsu Josephson, Karen Jouldjian, Stella Mitchell, Michael N. TI Cognitive Behavioral Therapy for Insomnia in Older Veterans Using Nonclinician Sleep Coaches: Randomized Controlled Trial SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE insomnia; sleep; cognitive behavioral therapy; aged; randomized controlled trial ID PRACTICE PARAMETERS; ADULTS; RISK; METAANALYSIS; DISORDERS; UPDATE; DISTURBANCES; SYMPTOMS; EFFICACY; VALIDITY AB OBJECTIVES: To test a new cognitive behavioral therapy for insomnia (CBT-I) program designed for use by nonclinicians. DESIGN: Randomized controlled trial. SETTING: Department of Veterans Affairs healthcare system. PARTICIPANTS: Community-dwelling veterans aged 60 and older who met diagnostic criteria for insomnia of 3 months duration or longer (N = 159). INTERVENTION: Nonclinician "sleep coaches" delivered a five-session manual-based CBT-I program including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy (individually or in small groups), with weekly telephone behavioral sleep medicine supervision. Controls received five sessions of general sleep education. MEASUREMENTS: Primary outcomes, including self-reported (7-day sleep diary) sleep onset latency (SOL-D), wake after sleep onset (WASO-D), total wake time (TWT-D), and sleep efficiency (SE-D); Pittsburgh Sleep Quality Index (PSQI); and objective sleep efficiency (7-day wrist actigraphy, SE-A) were measured at baseline, at the post-treatment assessment, and at 6- and 12-month follow-up. Additional measures included the Insomnia Severity Index (ISI), depressive symptoms (Patient Health Questionnaire-9 (PHQ-9)), and quality of life (Medical Outcomes Study 12-item Short-form Survey version 2 (SF-12v2)). RESULTS: Intervention subjects had greater improvement than controls between the baseline and posttreatment assessments, the baseline and 6-month assessments, and the baseline and 12-month assessments in SOL-D (-23.4, -15.8, and -17.3 minutes, respectively), TWT-D (-68.4, -37.0, and -30.9 minutes, respectively), SE-D (10.5%, 6.7%, and 5.4%, respectively), PSQI (-3.4, -2.4, and -2.1 in total score, respectively), and ISI (-4.5, -3.9, and -2.8 in total score, respectively) (all P < .05). There were no significant differences in SE-A, PHQ-9, or SF-12v2. CONCLUSION: Manual-based CBT-I delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia. C1 [Alessi, Cathy; Martin, Jennifer L.; Fung, Constance H.; Dzierzewski, Joseph M.; Song, Yeonsu; Josephson, Karen; Jouldjian, Stella; Mitchell, Michael N.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Alessi, Cathy; Martin, Jennifer L.; Fung, Constance H.; Dzierzewski, Joseph M.; Tapia, Juan C. Rodriguez; Song, Yeonsu] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Fiorentino, Lavinia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Tapia, Juan C. Rodriguez] Pontificia Univ Catolica Chile, Dept Med, Santiago, Chile. RP Alessi, C (reprint author), 16111 Plummer St 11E, North Hills, CA 91343 USA. EM cathy.alessi@va.gov FU VA Health Services Research and Development [Alessi IIR 08-295]; VA Greater Los Angeles Geriatric Research, Education and Clinical Center FX Funded by VA Health Services Research and Development (Alessi IIR 08-295) and the VA Greater Los Angeles Geriatric Research, Education and Clinical Center. NR 43 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2016 VL 64 IS 9 BP 1830 EP 1838 DI 10.1111/jgs.14304 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FC UT WOS:000387017800041 PM 27550552 ER PT J AU Cenzer, IS Tang, V Boscardin, WJ Smith, AK Ritchie, C Wallhagen, MI Espaldon, R Covinsky, KE AF Cenzer, Irena S. Tang, Victoria Boscardin, W. John Smith, Alexander K. Ritchie, Christine Wallhagen, Margaret I. Espaldon, Roxanne Covinsky, Kenneth E. TI One-Year Mortality After Hip Fracture: Development and Validation of a Prognostic Index SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hip fracture; prediction; mortality ID OLDER-ADULTS; LOGISTIC-REGRESSION; UNITED-STATES; RISK-FACTORS; OUTCOMES; HOSPITALIZATION; MODELS; RACE AB OBJECTIVES: To develop a prediction index for 1-year mortality after hip fracture in older adults that includes predictors from a wide range of domains. DESIGN: Retrospective cohort study. SETTINGS: Health and Retirement Study (HRS). PARTICIPANTS: HRS participants who experienced hip fracture between 1992 and 2010 as identified according to Medicare claims data (N = 857). MEASUREMENTS: Outcome measure was death within 1 year of hip fracture. Predictor measures were participant demographic characteristics, socioeconomic status, social support, health, geriatric symptoms, and function. Variables independently associated with 1-year mortality were identified, and best-subsets regression was used to identify the final model. The selected variables were weighted to create a risk index. The index was internally validated using bootstrapping to estimate model optimism. RESULTS: Mean age at time of hip fracture was 84, and 76% of the participants were women. There were 235 deaths (27%) during the 1-year follow up. Five predictors of mortality were included in the final model: aged 90 and older (2 points), male sex (2 points), congestive heart failure (2 points), difficulty preparing meals (2 points), and not being able to drive (1 point). The point scores of the index were associated with 1-year mortality, with 0 points predicting 10% risk and 7 to 9 points predicting 66% risk. The c-statistic for the final model was 0.73, with an estimated optimism penalty of 0.01, indicating very little evidence of overfitting. CONCLUSION: The prognostic index combines demographic, comorbidity, and function variables and can be used to differentiate between individuals at low and high risk of 1-year mortality after hip fracture. C1 [Cenzer, Irena S.; Tang, Victoria; Boscardin, W. John; Smith, Alexander K.; Ritchie, Christine; Espaldon, Roxanne; Covinsky, Kenneth E.] Univ Calif San Francisco, Sch Nursing, Div Geriatr, San Francisco, CA 94143 USA. [Wallhagen, Margaret I.] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cenzer, Irena S.; Tang, Victoria; Boscardin, W. John; Smith, Alexander K.; Ritchie, Christine; Espaldon, Roxanne; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ritchie, Christine] Jewish Home San Francisco, San Francisco, CA USA. RP Cenzer, IS (reprint author), 4150 Clement St,181G, San Francisco, CA 94121 USA. EM irena.stijacic@ucsf.edu FU National Institutes of Health; National Institute of Nursing Research [R01 NR013347]; National Institute on Aging [K24AG029812, P30AG04428, K23AG040772]; American Federation for Aging Research; John A. Hartford Foundation FX Supported by the National Institutes of Health and National Institute of Nursing Research (R01 NR013347; PI: Covinsky; Co-I: Ritchie). Dr. Covinsky was supported in part by grants from the National Institute on Aging (K24AG029812 and P30AG04428). Dr. Smith was supported in part by a Paul Beeson career development award from the National Institute on Aging (K23AG040772) and the American Federation for Aging Research. Dr. Wallhagen was supported in part by the John A. Hartford Foundation. NR 27 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2016 VL 64 IS 9 BP 1863 EP 1868 DI 10.1111/jgs.14237 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FC UT WOS:000387017800046 PM 27295578 ER PT J AU Ussar, S Fujisaka, S Kahn, CR AF Ussar, Siegfried Fujisaka, Shiho Kahn, C. Ronald TI Interactions between host genetics and gut microbiome in diabetes and metabolic syndrome SO MOLECULAR METABOLISM LA English DT Review DE Obesity; Metabolic syndrome; Microbiome; Microbiota; Microbial diversity; Host genetics; Environment ID DIET-INDUCED OBESITY; BROWN ADIPOSE-TISSUE; INFLAMMATORY-BOWEL-DISEASE; BODY-FAT DISTRIBUTION; INSULIN-RESISTANCE; AKKERMANSIA-MUCINIPHILA; ADULT HUMANS; MICE; MECHANISMS; DIVERSITY AB Background: Diabetes, obesity, and the metabolic syndrome are multifactorial diseases dependent on a complex interaction of host genetics, diet, and other environmental factors. Increasing evidence places gut microbiota as important modulators of the crosstalk between diet and development of obesity and metabolic dysfunction. In addition, host genetics can have important impact on the composition and function of gut microbiota. Indeed, depending on the genetic background of the host, diet and other environmental factors may produce different changes in gut microbiota, have different impacts on host metabolism, and create different interactions between the microbiome and the host. Scope of review: In this review, we highlight how appropriate animal models can help dissect the complex interaction of host genetics with the gut microbiome and how diet can lead to different degrees of weight gain, levels of insulin resistance, and metabolic outcomes, such as diabetes, in different individuals. We also discuss the challenges of identifying specific disease-associated microbiota and the limitations of simple metrics, such as phylogenetic diversity or the ratio of Firmicutes to Bacteroidetes. Major conclusions: Understanding these complex interactions will help in the development of novel treatments for microbiome-related metabolic diseases. This article is part of a special issue on microbiota. (C) 2016 Published by Elsevier GmbH. C1 [Ussar, Siegfried] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Inst Diabet & Obes, JRG Adipocytes & Metab, D-85748 Munich, Germany. [Ussar, Siegfried] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany. [Fujisaka, Shiho] Toyama Univ, Dept Internal Med 1, Toyama 9300194, Japan. [Kahn, C. Ronald] Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, One Joslin Pl, Boston, MA 02215 USA.; Ussar, S (reprint author), Helmholtz Ctr Munich, JRG Adipocytes & Metab, Parkring 13, D-85748 Munich, Germany. EM Siegfried.ussar@helmholtz-muenchen.de; C.Ronald.Kahn@joslin.harvard.edu OI Ussar, Siegfried/0000-0001-7575-0920 FU NIDDK NIH HHS [P30 DK034854, R37 DK031036] NR 77 TC 2 Z9 2 U1 14 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD SEP PY 2016 VL 5 IS 9 BP 795 EP 803 DI 10.1016/j.molmet.2016.07.004 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA8KB UT WOS:000386882600008 PM 27617202 ER PT J AU Goergen, CJ Chen, HH Sakadzic, S Srinivasan, VJ Sosnovik, DE AF Goergen, Craig J. Chen, Howard H. Sakadzic, Sava Srinivasan, Vivek J. Sosnovik, David E. TI Microstructural characterization of myocardial infarction with optical coherence tractography and two- photon microscopy SO PHYSIOLOGICAL REPORTS LA English DT Article DE Fiber architecture; myocardial infarction; Myocardium; optical coherence tomography; tractography; two-photon microscopy ID DIFFUSION TENSOR MRI; MAGNETIC-RESONANCE; IN-VIVO; FIBER ORIENTATION; TOMOGRAPHY; MOUSE; ABSORPTION; MYOFIBERS; ISCHEMIA; CONTRAST AB Myocardial infarction leads to complex changes in the fiber architecture of the heart. Here, we present a novel optical approach to characterize these changes in intact hearts in three dimensions. Optical coherence tomography (OCT) was used to derive a depth-resolved field of orientation on which tractography was performed. Tractography of healthy myocardium revealed a smooth linear transition in fiber inclination or helix angle from the epicardium to endocardium. Conversely, in infarcted hearts, no coherent microstructure could be identified in the infarct with OCT. Additional characterization of the infarct was performed by the measurement of light attenuation and with two-photon microscopy. Myofibers were imaged using autofluorescence and collagen fibers using second harmonic generation. This revealed the presence of two distinct microstructural patterns in areas of the infarct with high light attenuation. In the presence of residual myofibers, the surrounding collagen fibers were aligned in a coherent manner parallel to the myofibers. In the absence of residual myofibers, the collagen fibers were randomly oriented and lacked any microstructural coherence. The presence of residual myofibers thus exerts a profound effect on the microstructural properties of the infarct scar and consequently the risk of aneurysm formation and arrhythmias. Catheter-based approaches to segment and image myocardial microstructure in humans are feasible and could play a valuable role in guiding the development of strategies to improve infarct healing. C1 [Goergen, Craig J.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Goergen, Craig J.; Chen, Howard H.; Sakadzic, Sava; Srinivasan, Vivek J.; Sosnovik, David E.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Chen, Howard H.; Sosnovik, David E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA USA. [Srinivasan, Vivek J.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. RP Sosnovik, DE (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu OI Goergen, Craig/0000-0001-8883-7953 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 2051-817X J9 PHYSIOL REP JI PHYSIOL. REP. PD SEP PY 2016 VL 4 IS 18 AR e12894 DI 10.14814/phy2.12894 PG 10 WC Physiology SC Physiology GA EB5TO UT WOS:000387443500008 ER PT J AU Mak, KS Phillips, JG Barysauskas, CM Lee, LK Mannarino, EG Van Benthuysen, L Raut, CP Mullen, JT Fairweather, M DeLaney, TF Baldini, EH AF Mak, Kimberley S. Phillips, John G. Barysauskas, Constance M. Lee, Leslie K. Mannarino, Edward G. Van Benthuysen, Liam Raut, Chandrajit P. Mullen, John T. Fairweather, Mark DeLaney, Thomas F. Baldini, Elizabeth H. TI Acute gastrointestinal toxicity and bowel bag dose-volume parameters for preoperative radiation therapy for retroperitoneal sarcoma SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID ADVANCED RECTAL-CANCER; CHEMORADIOTHERAPY; CHEMORADIATION; CHEMOTHERAPY; RADIOTHERAPY; DIARRHEA; RTOG AB Purpose: Acute gastrointestinal (GI) toxicity has been studied inGI and gynecological (GYN) cancers, with volume receiving 15 Gy (V15) <830 mL, V25 <650 mL, and V45 <195 mL identified as dose constraints for the peritoneal space (bowel bag [BB]). There are no reported constraints derived from retroperitoneal sarcoma (RPS), and prospective trials for RPS have adopted some of the GI and GYN constraints. This study quantified GI toxicity during preoperative radiation therapy (RT) for RPS, assessed toxicity using published constraints, and evaluated predictors for toxicity. Methods and materials: From 2003 to 2013, 56 patients with RPS underwent preoperative RT at 2 institutions. Toxicity was scored using Radiation Therapy Oncology Group criteria for upper and lower acute GI toxicity. BB was contoured on planning computed tomography scans per Radiation Therapy Oncology Group atlas guidelines with review by a radiologist. Relationships among toxicity, clinical factors, and BB dose were analyzed. Results: Three patients (5%) developed grade >= 3 acute GI toxicity: 2 grade 3 toxicities (anorexia and nausea) and 1 grade 5 toxicity (tumor-bowel fistula). Thirty-six patients (64%) had grade 2 toxicity (nausea, 55%; diarrhea, 23%; pain, 20%). Tumor size was the only significant clinical predictor of grade >= 2 acute GI toxicity. Larger mean BB volumes predicted for grade >= 2 toxicity (P = .001). On receiver operating characteristics analysis, V30 was the best discriminator for toxicity (P = .0001). Median BB V15 was 1375 mL; 75% of patients had V15 >= 830 mL. Median V25 was 1083 mL; 68% had V25 >= 650 mL. Median V45 was 575 mL; 82% had V45 >= 195 mL. V25 >= 650 mL was significantly associated with grade >= 2 toxicity (P = .01). Conclusions: Among patients treated with preoperative RT for RPS, significant acute GI toxicity was very low despite BB dose exceeding established constraints for most cases. Acceptable dose constraints for RPS may be higher than those for GI or GYN cancers. Further assessment of dose-volume constraints for RPS is needed. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Mak, Kimberley S.; Phillips, John G.] Harvard Radiat Oncol Program, Boston, MA USA. [Mak, Kimberley S.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [Phillips, John G.; Mannarino, Edward G.; Baldini, Elizabeth H.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Phillips, John G.; Mannarino, Edward G.; Baldini, Elizabeth H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Barysauskas, Constance M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Leslie K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Van Benthuysen, Liam; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Raut, Chandrajit P.] Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. [Raut, Chandrajit P.; Baldini, Elizabeth H.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Fairweather, Mark] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM ebaldini@partners.org NR 24 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 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD SEP-OCT PY 2016 VL 6 IS 5 BP 360 EP 366 DI 10.1016/j.prro.2015.12.005 PG 7 WC Oncology SC Oncology GA EA8MC UT WOS:000386887900022 PM 27009922 ER PT J AU Cui, J Cai, YH Hu, Y Huang, ZH Luo, YX Kaz, AM Yang, ZH Chen, DK Fan, XJ Grady, WM Wang, JP AF Cui, Ji Cai, Yonghua Hu, Ying Huang, Zenghong Luo, Yanxin Kaz, Andrew M. Yang, Zihuan Chen, Dianke Fan, Xinjuan Grady, William M. Wang, Jianping TI Epigenetic silencing of TPM2 contributes to colorectal cancer progression upon RhoA activation SO TUMOR BIOLOGY LA English DT Article DE Colorectal cancer; DNA methylation; TPM2 ID BETA-TROPOMYOSIN EXPRESSION; IDENTIFICATION; TRANSFORMATION; METHYLATION; SUPPRESSOR; PROTEOMICS; PROTEINS; PATHWAY AB Beta-tropomyosin (beta-tropomyosin, TPM2) has been found to be downregulated in colorectal cancer (CRC) in previous studies. In this study, we aimed to investigate the mechanisms and potential biological consequences of the downregulation of TPM2 in colorectal cancer. TPM2 expression in colorectal cancer was assessed by qRT-PCR and immunostaining. The biological functions of TPM2 were assessed in cell lines either overexpressing or underexpressingTPM2. Aberrant DNA methylation in the promoter region is associated with suppression of TPM2 expression in primary colorectal cancer tissue samples. Treatment with the demethylation agent 5-AZA can induceTPM2 expression in colorectal cancer cell lines. Reconstitution of TPM2 suppresses cell proliferation and migration in colorectal cancer cell lines, whereas the loss of TPM2 expression is associated with increased tumor proliferation and migration in vitro, which was accompanied by RhoA activation. In summary, our findings indicate that TPM2 appears to be commonly silenced by aberrant DNA methylation in colon cancer. TPM2 loss is associated with RhoA activation and tumor proliferation. C1 [Cui, Ji] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, Guangzhou, Guangdong, Peoples R China. [Cai, Yonghua; Huang, Zenghong; Luo, Yanxin; Wang, Jianping] Sun Yat Sen Univ, Dept Colorectal Surg, Affilated Hosp 6, Guangzhou 56055, Guangdong, Peoples R China. [Cai, Yonghua; Huang, Zenghong; Luo, Yanxin; Yang, Zihuan; Chen, Dianke; Wang, Jianping] Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou, Guangdong, Peoples R China. [Hu, Ying] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med 2, Guangzhou, Guangdong, Peoples R China. [Chen, Dianke] Sun Yat Sen Univ, Dept Oncol, Affilated Hosp 6, Guangzhou, Guangdong, Peoples R China. [Fan, Xinjuan] Sun Yat Sen Univ, Dept Pathol, Affilated Hosp 6, Guangzhou, Guangdong, Peoples R China. [Luo, Yanxin; Kaz, Andrew M.; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N D4-100, Seattle, WA 98109 USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. RP Wang, JP (reprint author), Sun Yat Sen Univ, Dept Colorectal Surg, Affilated Hosp 6, Guangzhou 56055, Guangdong, Peoples R China.; Wang, JP (reprint author), Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou, Guangdong, Peoples R China.; Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N D4-100, Seattle, WA 98109 USA.; Grady, WM (reprint author), Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. EM cuiji168@163.com; yonghua.cai@163.com; 974552048@qq.com; huangznh@mail2.sysu.edu.cn; luoyx25@mail.sysu.edu.cn; akaz@fhcrc.org; yzhuan@mail.sysu.edu.cn; chendianke@163.com; juanjuanfan@163.com; wgrady@fhcrc.org; wjp@mail.sysu.edu.cn FU National Basic Research Program of China (973 Program) [2015CB554001]; Program of Introducing Talents of Discipline to Universities of China [B12003]; International Science & Technology Cooperation Program of China [2011DFA32570]; Science and Technology Program of Guangzhou [201506010099, 2014Y2-00160]; National Natural Science Foundation of China [81172040, 81201920, 81472257]; Guangdong Natural Science Funds for Distinguished Young Scholars [2016A030306002]; Fundamental Research Funds for the Central Universities (Sun Yat-sen University) [2015ykzd10, 13ykpy37] FX Support for these studies was provided by a National Basic Research Program of China (973 Program) (No. 2015CB554001, JW), Program of Introducing Talents of Discipline to Universities of China (B12003, JW) and International Science & Technology Cooperation Program of China (2011DFA32570, JW), the Science and Technology Program of Guangzhou (No. 201506010099, YL; No. 2014Y2-00160, JW), National Natural Science Foundation of China (81172040 JW; 81201920 and 81472257, YL), the Guangdong Natural Science Funds for Distinguished Young Scholars (2016A030306002, YL), and the Fundamental Research Funds for the Central Universities (Sun Yat-sen University) (No. 2015ykzd10, YL; No. 13ykpy37, YL). NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1010-4283 EI 1423-0380 J9 TUMOR BIOL JI Tumor Biol. PD SEP PY 2016 VL 37 IS 9 BP 12477 EP 12483 DI 10.1007/s13277-016-5103-1 PG 7 WC Oncology SC Oncology GA EB0ZJ UT WOS:000387075400087 PM 27333992 ER PT J AU Gopal, R Prochazka, A AF Gopal, Ravi Prochazka, Allan TI Measuring Medical Student Well-being: Questions About a Recent Study SO ACADEMIC MEDICINE LA English DT Letter C1 [Gopal, Ravi; Prochazka, Allan] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Gopal, R (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. EM ravi.gopal@va.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2016 VL 91 IS 9 BP 1189 EP 1189 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EA5PX UT WOS:000386674800002 PM 27576029 ER PT J AU McKenna, KM Hashimoto, DA Maguire, MS Bynum, WE AF McKenna, Kathleen M. Hashimoto, Daniel A. Maguire, Michael S. Bynum, William E. TI The Missing Link: Connection Is the Key to Resilience in Medical Education SO ACADEMIC MEDICINE LA English DT Editorial Material ID MATTERS AB Awareness of the risks of burnout, depression, learner mistreatment, and suboptimal learning environments is increasing in academic medicine. A growing wellness and resilience movement has emerged in response to these disturbing trends; however, efforts to address threats to physician resilience have often emphasized strategies to improve life outside of work, with less attention paid to the role of belonging and connection at work. In this Commentary the authors propose that connection to colleagues, patients, and profession is fundamental to medical learners' resilience, highlighting "social resilience" as a key factor in overall well-being. They outline three specific forces that drive disconnection in medical education: the impact of shift work, the impact of the electronic medical record, and the impact of "work-life balance." Finally, the authors propose ways to overcome these forces in order to build meaningful connection and enhanced resilience in a new era of medicine. C1 [McKenna, Kathleen M.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Hashimoto, Daniel A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Maguire, Michael S.] Thomas Jefferson Combined Internal Med Pediat Res, Sidney Kimmel Med Coll, Christiana Care Hlth Syst, Wilmington, DE USA. [Bynum, William E.] Natl Capital Consortium Family Med Residency, Ft Belvoir, VA USA. RP McKenna, KM (reprint author), 2104 NE Couch St, Portland, OR 97232 USA. EM mckennka@ohsu.edu NR 12 TC 2 Z9 2 U1 7 U2 7 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 SEP PY 2016 VL 91 IS 9 BP 1197 EP 1199 DI 10.1097/ACM.0000000000001311 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EA5PX UT WOS:000386674800013 PM 27438155 ER PT J AU Saddawi-Konefka, D Schumacher, DJ Baker, KH Charnin, JE Gollwitzer, PM AF Saddawi-Konefka, Daniel Schumacher, Daniel J. Baker, Keith H. Charnin, Jonathan E. Gollwitzer, Peter M. TI Changing Physician Behavior With Implementation Intentions: Closing the Gap Between Intentions and Actions SO ACADEMIC MEDICINE LA English DT Article ID SELF-REGULATION; GOAL ACHIEVEMENT; EDUCATION; METAANALYSIS; PERFORMANCE; STRATEGIES; INTERVENTION; FANTASIES; PURSUIT; SYSTEMS AB In medical education, even well-intentioned learners struggle to change their practice. This intention-action gap is a well-described phenomenon. Strong commitment to changing behaviors is important, but by itself it is only a modest predictor of goal attainment. Implementation intentions are an extensively studied strategy from cognitive psychology that have been shown to close the intention-action gap and increase goal attainment across myriad domains. Implementation intentions are "if-then" plans that specify an anticipated future situation and a planned response-" If I encounter situation X, then I will respond with action Y." They differ from simple goals, which specify only a desired behavior or outcome-" I intend to perform action Z." Despite this subtle difference, they have shown substantial effectiveness over goals alone in increasing goal attainment. In this article, the authors first describe implementation intentions, review the substantial body of evidence demonstrating their effectiveness, and explain the underlying psychological mechanisms. They then illustrate the connections between implementation intentions and established learning theory. The final section focuses on forming effective implementation intentions in medical education. The authors provide concrete examples across the continuum of learners ( from medical students to attending physicians) and competencies, and make recommendations for when and how to employ implementation intentions. C1 [Saddawi-Konefka, Daniel; Baker, Keith H.; Charnin, Jonathan E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Room 436, Boston, MA 02114 USA. [Schumacher, Daniel J.] Cincinnati Childrens Hosp Med Ctr, Div Emergency Med, Cincinnati, OH 45229 USA. [Gollwitzer, Peter M.] Univ Konstanz, Dept Psychol, Constance, Germany. [Gollwitzer, Peter M.] NYU, Dept Psychol, 6 Washington Pl, New York, NY 10003 USA. RP Saddawi-Konefka, D (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Room 436, Boston, MA 02114 USA. EM dsaddawi-konefka@mgh.harvard.edu NR 54 TC 1 Z9 1 U1 6 U2 6 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 SEP PY 2016 VL 91 IS 9 BP 1211 EP 1216 DI 10.1097/ACM.0000000000001172 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EA5PX UT WOS:000386674800016 PM 27008360 ER PT J AU Mata, DA Ramos, MA Kim, MM Guille, C Sen, S AF Mata, Douglas A. Ramos, Marco A. Kim, Michelle M. Guille, Constance Sen, Srijan TI In Their Own Words: An Analysis of the Experiences of Medical Interns Participating in a Prospective Cohort Study of Depression SO ACADEMIC MEDICINE LA English DT Article ID PRIMARY-CARE; PREVENTION; PHYSICIANS; PREVALENCE; RESILIENCE; RESIDENTS; SYMPTOMS; BURNOUT AB Purpose To compare the subjective experiences of interns with and without symptoms of depression using a mixed-methods approach. Method In 2007-2008, interns from six institutions were screened for depression before and during internship using an online survey that included the Patient Health Questionnaire ( PHQ-9). At the end of internship, participants were asked what made the year difficult, easy, and memorable, and how they had changed. Computerized lexical and qualitative thematic analyses were performed to analyze their free-text responses. Results Sixty-three percent ( 244/388) of invited interns participated in the original cohort study. Of those, 42% ( 103/244) answered the open-ended questions for this analysis. Thirty-five percent ( 36/103) screened positive for clinically significant depression ( i.e., PHQ-9 score >= 10) during their intern year. Respondents with symptoms of depression were more likely to report problems with cynicism, exhaustion, and stress, while those without them were more likely to mention positive patient care and educational experiences. Respondents with symptoms of depression preferentially described experiences that "broke" their confidence, sense of well-being, and belief in the medical profession, while those who did not described profoundly positive, life-changing experiences regarding interactions with patients and supportive colleagues, through which they grew personally and professionally. Conclusions Depression during internship affects not only objective outcomes like medical errors but also how interns value the profession and themselves, with potentially profound consequences for their future career decisions. Residency programs should implement reactive interventions targeting depression and proactive interventions promoting resilience and well-being to address the issues that lead to depression. C1 [Mata, Douglas A.] Brigham & Womens Hosp, Anat & Clin Pathol, 75 Francis St, Boston, MA 02115 USA. [Mata, Douglas A.] Harvard Med Sch, Pathol, Boston, MA USA. [Ramos, Marco A.] Yale Sch Med, New Haven, CT USA. [Kim, Michelle M.] Massachusetts Gen Hosp, Genitourinary Surg, Boston, MA 02114 USA. [Kim, Michelle M.] Harvard Med Sch, Surg, Boston, MA USA. [Guille, Constance] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Sen, Srijan] Univ Michigan, Sch Med, Mol & Behav Neurosci Inst, Ann Arbor, MI USA. [Sen, Srijan] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Mata, DA (reprint author), Harvard Med Sch, Dept Pathol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dmata@bwh.harvard.edu FU National Institute of Mental Health [MH101459, MH095109] FX The project was supported by an R01 grant MH101459 (S.S.) and K23 grant MH095109 (S.S.) from the National Institute of Mental Health. The study funder had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 28 TC 5 Z9 5 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 SEP PY 2016 VL 91 IS 9 BP 1244 EP 1250 DI 10.1097/ACM.0000000000001227 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EA5PX UT WOS:000386674800022 PM 27166863 ER PT J AU Lacouture, ME Keefe, DM Sonis, S Jatoi, A Gernhardt, D Wang, T Doherty, JP Giri, N Nadanaciva, S O'Connell, J Sbar, E Piperdi, B Garon, EB AF Lacouture, M. E. Keefe, D. M. Sonis, S. Jatoi, A. Gernhardt, D. Wang, T. Doherty, J. P. Giri, N. Nadanaciva, S. O'Connell, J. Sbar, E. Piperdi, B. Garon, E. B. TI A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer SO ANNALS OF ONCOLOGY LA English DT Article DE dacomitinib; non-small-cell lung cancer; epidermal growth factor receptor; dermatologic adverse events; gastrointestinal adverse events ID SKIN TREATMENT REGIMEN; QUALITY-OF-LIFE; IMPACT; TRIAL; RELIABILITY; MANAGEMENT; TOXICITIES; VALIDITY; DIARRHEA AB The randomized phase II study ARCHER 1042 explored the impact of prophylactic treatment on select dermatologic and gastrointestinal adverse events (AE) of interest and patient-reported outcomes. Doxycycline reduced the incidence of grade a parts per thousand yen2 select dermatologic AEs of interest by 50% (P = 0.016). Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs.ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade a parts per thousand yen2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade a parts per thousand yen2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade a parts per thousand yen2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade a parts per thousand yen2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade a parts per thousand yen2 diarrhea and did not impact mucositis scores. Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade a parts per thousand yen2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis. C1 [Lacouture, M. E.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Keefe, D. M.] Royal Adelaide Hosp, Dept Med, Adelaide, SA, Australia. [Sonis, S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Sonis, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jatoi, A.] Mayo Clin, Dept Oncol, Rochester, MN USA. [Gernhardt, D.; Wang, T.; Nadanaciva, S.] Pfizer Oncol, Groton, CT USA. [Doherty, J. P.; O'Connell, J.] Pfizer Oncol, New York, NY USA. [Giri, N.] Pfizer Oncol, La Jolla, CA USA. [Sbar, E.] Pfizer Oncol, Collegeville, PA USA. [Piperdi, B.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Garon, E. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Lacouture, ME (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, 16 E 60th St,Suite 407,Rm 4312, New York, NY 10022 USA. EM lacoutum@mskcc.org NR 9 TC 2 Z9 2 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 SEP PY 2016 VL 27 IS 9 BP 1712 EP 1718 DI 10.1093/annonc/mdw227 PG 7 WC Oncology SC Oncology GA DW4FX UT WOS:000383599300010 PM 27287210 ER PT J AU Ben-Ami, E Barysauskas, CM von Mehren, M Heinrich, MC Corless, CL Butrynski, JE Morgan, JA Wagner, AJ Choy, E Yap, JT Van den Abbeele, AD Solomon, SM Fletcher, JA Demetri, GD George, S AF Ben-Ami, E. Barysauskas, C. M. von Mehren, M. Heinrich, M. C. Corless, C. L. Butrynski, J. E. Morgan, J. A. Wagner, A. J. Choy, E. Yap, J. T. Van den Abbeele, A. D. Solomon, S. M. Fletcher, J. A. Demetri, G. D. George, S. TI Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy SO ANNALS OF ONCOLOGY LA English DT Article DE regorafenib; GIST; KIT mutation; SDH-deficient GIST ID IMATINIB MESYLATE; SUNITINIB; MUTATIONS; EFFICACY; SAFETY AB Our study provides the longest follow-up of advanced GIST patients treated with regorafenib in this phase II trial. Particular benefit among exon 11 KIT mutations and SDH-deficient GIST were observed. Liberal use of dose reductions and treatment breaks were required to optimize long-term drug exposure.This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST. The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib. Patients received regorafenib orally, 160 mg once daily, days 1-21 of a 28-day cycle. Clinical benefit rate (CBR), defined as complete or partial response (PR), or stable disease lasting a parts per thousand yen16 weeks per RECIST 1.1, progression-free survival (PFS), overall survival (OS), long-term safety data, and metabolic response by functional imaging were assessed. Thirty-three patients received at least one dose of regorafenib. The median follow-up was 41 months. CBR was documented in 25 of 33 patients [76%; 95% confidence interval (CI) 58% to 89%], including six PRs. The median PFS was 13.2 months (95% CI 9.2-18.3 months) including four patients who remained progression-free at study closure, each achieving clinical benefit for more than 3 years (range 36.8-43.5 months). The median OS was 25 months (95% CI 13.2-39.1 months). Patients whose tumors harbored a KIT exon 11 mutation demonstrated the longest median PFS (13.4 months), whereas patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median 1.6 months PFS (P < 0.0001). Long-term safety profile is consistent with previous reports; hand-foot skin reaction and hypertension were the most common reasons for dose reduction. Notably, regorafenib induced objective responses and durable benefit in SDH-deficient GIST. Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities. NCT01068769. C1 [Ben-Ami, E.; Butrynski, J. E.; Morgan, J. A.; Wagner, A. J.; Solomon, S. M.; Demetri, G. D.; George, S.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Barysauskas, C. M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [von Mehren, M.] Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Heinrich, M. C.] VA Portland Hlth Care Syst, Portland, OR USA. [Heinrich, M. C.; Corless, C. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Choy, E.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Yap, J. T.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Yap, J. T.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Van den Abbeele, A. D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Van den Abbeele, A. D.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Fletcher, J. A.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Med Sch, Boston, MA USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM suzanne_george@dfci.harvard.edu NR 17 TC 3 Z9 3 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 SEP PY 2016 VL 27 IS 9 BP 1794 EP 1799 DI 10.1093/annonc/mdw228 PG 6 WC Oncology SC Oncology GA DW4FX UT WOS:000383599300022 PM 27371698 ER PT J AU Min, L Shen, J Tu, CQ Hornicek, F Duan, ZF AF Min, Li Shen, Jacson Tu, Chongqi Hornicek, Francis Duan, Zhenfeng TI The roles and implications of exosomes in sarcoma SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Exosome; Sarcoma; Biomarker; Targetedcancer therapy ID TUMOR-DERIVED EXOSOMES; BREAST-CANCER CELLS; EXTRACELLULAR VESICLES; OVARIAN-CANCER; LARGE ONCOSOMES; REGULATES SECRETION; APOPTOTIC BODIES; DRUG-DELIVERY; LUNG-CANCER; MOUSE MODEL AB Better diagnostic biomarkers and therapeutic options are still necessary for patients with sarcomas due to the current limitations of diagnosis and treatment. Exosomes are small extracellular membrane vesicles that are released by various cells and are found in most body fluids. Tumor-derived exosomes have been proven to mediate tumorigenesis, intercellular communication, microenvironment modulation, and metastasis in different cancers, including in sarcomas. Recently, exosomes have been considered as potential biomarkers for sarcoma diagnosis and prognosis, and as possible targets for sarcoma therapy. Moreover, due to their specific cell tropism and bioavailability, exosomes can also be engineered as vehicles for drug delivery. In this review, we discuss recent advances in the roles of tumor-derived exosomes in sarcoma and their potential clinical applications. C1 [Min, Li; Shen, Jacson; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Min, Li; Shen, Jacson; Hornicek, Francis; Duan, Zhenfeng] Harvard Med Sch, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA. [Min, Li; Tu, Chongqi] Sichuan Univ, West China Hosp, Dept Orthoped, 37 Guoxue Rd, Chengdu 610041, Sichuan, 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; Jennifer Hunter Yates Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA151452-01] FX This work was supported, in part, by the Gattegno and Wechsler funds, the Kenneth Stanton Fund, and the Jennifer Hunter Yates Foundation. Dr. Duan is supported, in part, by a grant from Sarcoma Foundation of America (SFA) and a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA151452-01. NR 88 TC 0 Z9 0 U1 5 U2 5 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 SEP PY 2016 VL 35 IS 3 BP 377 EP 390 DI 10.1007/s10555-016-9630-4 PG 14 WC Oncology SC Oncology GA EA3NM UT WOS:000386509900002 PM 27342745 ER PT J AU Tambouret, RH AF Tambouret, Rosemary H. TI Use of immunohistochemical staining for p16 in gynecological cytology SO CANCER CYTOPATHOLOGY LA English DT Editorial Material C1 [Tambouret, Rosemary H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tambouret, Rosemary H.] Harvard Med Sch, Pathol, Boston, MA 02115 USA. [Tambouret, Rosemary H.] Massachusetts Gen Hosp, Cytopathol Fellowship, Boston, MA 02114 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Tambouret, RH (reprint author), Harvard Med Sch, Pathol, Boston, MA 02115 USA.; Tambouret, RH (reprint author), Massachusetts Gen Hosp, Cytopathol Fellowship, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD SEP PY 2016 VL 124 IS 9 BP 611 EP 612 DI 10.1002/cncy.21760 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA DW5LE UT WOS:000383685600002 PM 27479463 ER PT J AU Baloch, ZW Seethala, RR Faquin, WC Papotti, MG Basolo, F Fadda, G Randolph, GW Hodak, SP Nikiforov, YE Mandel, SJ AF Baloch, Zubair W. Seethala, Raja R. Faquin, William C. Papotti, Mauro G. Basolo, Fulvio Fadda, Guido Randolph, Gregory W. Hodak, Steven P. Nikiforov, Yuri E. Mandel, Susan J. TI Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A changing paradigm in thyroid surgical pathology and implications for thyroid cytopathology SO CANCER CYTOPATHOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; ULTRASONOGRAPHIC FEATURES; OBSERVER VARIATION; PATTERNED LESIONS; CARCINOMA; VARIANT; DIAGNOSIS; CANCER; BETHESDA; CYTOLOGY AB The change in the diagnosis of noninvasive encapsulated follicular variant papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (ie, not carcinoma) will have significant impact on the risk of malignancy for categories according to The Bethesda System for Reporting Thyroid Cytopathology, and especially for the indeterminate categories. C1 [Baloch, Zubair W.] Hosp Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, 6 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. [Seethala, Raja R.; Nikiforov, Yuri E.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Faquin, William C.] Harvard Med Sch, Boston, MA USA. [Papotti, Mauro G.] Univ Turin, Dept Oncol, Turin, Italy. [Basolo, Fulvio] Univ Pisa, Dept Surg Med & Mol Pathol, Pisa, Italy. [Fadda, Guido] Univ Rome, Dept Pathol, Rome, Italy. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Gen & Thyroid & Parathyroid Endocrine Surg Div, Boston, MA 02114 USA. [Hodak, Steven P.] NYU, Sch Med, Div Endocrinol & Metab, New York, NY USA. [Mandel, Susan J.] Hosp Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, 3400 Spruce St, Philadelphia, PA 19104 USA. RP Baloch, ZW (reprint author), Hosp Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, 6 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM baloch@mail.med.upenn.edu OI BASOLO, FULVIO/0000-0003-1657-5020 NR 27 TC 6 Z9 6 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD SEP PY 2016 VL 124 IS 9 BP 616 EP 620 DI 10.1002/cncy.21744 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA DW5LE UT WOS:000383685600004 PM 27203786 ER PT J AU Naidu, SS Aronow, HD Box, LC Duffy, PL Kolansky, DM Kupfer, JM Latif, F Mulukutla, SR Rao, SV Swaminathan, RV Blankenship, JC AF Naidu, Srihari S. Aronow, Herbert D. Box, Lyndon C. Duffy, Peter L. Kolansky, Daniel M. Kupfer, Joel M. Latif, Faisal Mulukutla, Suresh R. Rao, Sunil V. Swaminathan, Rajesh V. Blankenship, James C. TI SCAI Expert Consensus Statement: 2016 Best Practices in the Cardiac Catheterization Laboratory: (Endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencionista; Affirmation of Value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d'intervention) SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; RADIOGRAPHIC CONTRAST-MEDIA; CARDIOVASCULAR ANGIOGRAPHY; TASK-FORCE; HEART-ASSOCIATION; FEMORAL-ARTERY; INFORMED-CONSENT; MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES; INDUCED NEPHROPATHY C1 [Naidu, Srihari S.] Winthrop Univ Hosp, Div Cardiol, Mineola, NY 11501 USA. [Aronow, Herbert D.] Brown Univ, Warren Alpert Med Sch, Cardiovasc Inst, Providence, RI 02912 USA. [Box, Lyndon C.] West Valley Med Ctr, Caldwell, ID USA. [Duffy, Peter L.] FirstHealth Carolinas, Pinehurst, NC USA. [Kolansky, Daniel M.] Univ Penn, Perelman Sch Med, Cardiovasc Med Div, Philadelphia, PA 19104 USA. [Kupfer, Joel M.] Univ Illinois, Sch Med Peoria, Peoria, IL USA. [Latif, Faisal] Univ Oklahoma, Oklahoma City, OK USA. [Latif, Faisal] VA Med Ctr, Oklahoma City, OK USA. [Mulukutla, Suresh R.] Univ Pittsburgh, Pittsburgh, PA USA. [Mulukutla, Suresh R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Rao, Sunil V.] Duke Univ, Med Ctr, Durham, NC USA. [Swaminathan, Rajesh V.] New York Presbyterian Hosp, Weill Cornell Med Coll, Greenberg Div Cardiol, New York, NY USA. [Blankenship, James C.] Geisinger Med Ctr, Danville, PA 17822 USA. RP Naidu, SS (reprint author), 120 Mineola Blvd,Suite 500, Mineola, NY 11501 USA. EM ssnaidu@winthrop.org NR 74 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP PY 2016 VL 88 IS 3 BP 407 EP 423 DI 10.1002/ccd.26551 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EA7GX UT WOS:000386799900021 PM 27137680 ER PT J AU Lee, DJ Schnitzlein, CW Wolf, JP Vythilingam, M Rasmusson, AM Hoge, CW AF Lee, Daniel J. Schnitzlein, Carla W. Wolf, Jonathan P. Vythilingam, Meena Rasmusson, Ann M. Hoge, Charles W. TI PSYCHOTHERAPY VERSUS PHARMACOTHERAPY FOR POSTTRAUMATIC STRESS DISORDER: SYSTEMIC REVIEW AND META-ANALYSES TO DETERMINE FIRST-LINE TREATMENTS SO DEPRESSION AND ANXIETY LA English DT Article DE PTSD; posttraumatic stress disorder; pharmacotherapy; psychotherapy; VA; DoD; ISTSS; NICE; WHO; Australian; Department of Defense; International Society for the Study of Traumatic Stress; National Institute for Clinical Excellence; World Health Organization ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; EYE-MOVEMENT DESENSITIZATION; COGNITIVE-BEHAVIORAL THERAPY; VENLAFAXINE EXTENDED-RELEASE; DOUBLE-BLIND; CLINICAL-TRIAL; CHRONIC PTSD; PAROXETINE TREATMENT; MILITARY VETERANS AB BackgroundCurrent clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. MethodsSystemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials 8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy pre-/posttreatment. ResultsEffect sizes for trauma-focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. ConclusionsStudy findings support use of TFPs over nontrauma-focused psychotherapy or medication as first-line interventions. Second-line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment-as-usual conditions. Direct head-to-head trials of TFPs versus sertraline or venlafaxine are needed. C1 [Lee, Daniel J.] Off Evidence Based Practice, San Antonio, TX 78234 USA. [Lee, Daniel J.; Schnitzlein, Carla W.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Schnitzlein, Carla W.] Bayne Jones Army Community Hosp, Dept Behav Hlth, Ft Polk, LA USA. [Wolf, Jonathan P.] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, Bethesda, MD USA. [Vythilingam, Meena] Headquarters US Marine Corps, Hlth Serv, Arlington, VA USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Womens Hlth Sci Div,Natl Ctr PTSD, Boston, MA 02118 USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Vet Affairs, Boston, MA 02118 USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hoge, Charles W.] Walter Reed Army Inst Res, Ctr Psychiat & Neurosci, Silver Spring, MD USA. RP Lee, DJ (reprint author), Off Evidence Based Practice, San Antonio, TX 78234 USA. EM Daniel.J.Lee82.mil@mail.mil FU Resilience Therapeutics, Inc. FX Ann Rasmusson is a paid consultant for Resilience Therapeutics, Inc. All other authors have nothing to disclose. NR 78 TC 3 Z9 3 U1 12 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2016 VL 33 IS 9 BP 792 EP 806 DI 10.1002/da.22511 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SR UT WOS:000383707700003 PM 27126398 ER PT J AU Clapp, JD Kemp, JJ Cox, KS Tuerk, PW AF Clapp, Joshua D. Kemp, Joshua J. Cox, Keith S. Tuerk, Peter W. TI PATTERNS OF CHANGE IN RESPONSE TO PROLONGED EXPOSURE: IMPLICATIONS FOR TREATMENT OUTCOME SO DEPRESSION AND ANXIETY LA English DT Article DE Posttraumatic stress disorder; combat disorder; veteran; psychotherapies; treatment outcome; clinical psychology ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; MENTAL-HEALTH PROBLEMS; PSYCHOLOGICAL TREATMENTS; SUDDEN GAINS; PSYCHOMETRIC PROPERTIES; BEHAVIORAL THERAPY; IMAGINAL EXPOSURE; SUICIDAL IDEATION; VIETNAM VETERANS AB BackgroundAssessment of response to Prolonged Exposure (PE) suggests some patients may experience discontinuous change involving sudden symptom reductions and/or temporary exacerbations. The current study looked to (1) isolate profiles of PE response among treatment-seeking veterans and (2) identify factors associated with unique patterns of change. MethodsArchival records were examined for veterans receiving PE through a specialty Veterans Affairs Medical Center (VAMC) clinic (N = 109). Latent profile analysis was used to extract response trajectories defined by change in weekly PTSD Checklist (PCL) scores. Associations with provider status (staff vs. intern), setting (in-person vs. telehealth), initial severity (PTSD; depression), and eventual treatment gains were examined. ResultsThree profiles were observed. Rapid Responders (18.3%) evidenced sharp reductions at Week 2 and again between Weeks 5 and 6. Linear Responders (40.4%) demonstrated gradual reductions throughout the 10-week assessment window. Delayed Responder (41.3%) scores were relatively stable over the evaluation period although final session outcomes indicated reliable change (PCL>10) in 40% of patients. Profiles were similar with respect to provider status, treatment setting, and initial symptom severity. Rapid Responders evidenced lower final session scores relative to Linear (g = 1.13) and Delayed (g = 1.85) groups, with Linear Responders reporting lower end scores than Delayed Responders (g= 1.02). ConclusionsAnticipating patterns of recovery and their association with therapeutic outcome is of immense clinical value. Sudden gains emerged as a strong predictor of enhanced response. Data also suggest potential benefits of extending standard intervention for patients who fail to demonstrate an immediate response to PE. C1 [Clapp, Joshua D.; Kemp, Joshua J.] Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. [Cox, Keith S.] Univ North Carolina Asheville, Dept Psychol, Asheville, NC USA. [Tuerk, Peter W.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Tuerk, Peter W.] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu NR 66 TC 0 Z9 0 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2016 VL 33 IS 9 BP 807 EP 815 DI 10.1002/da.22534 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SR UT WOS:000383707700004 PM 27321062 ER PT J AU Braga, DT Abramovitch, A Fontenelle, LF Ferrao, YA Gomes, JB Vivan, AS Ecker, KK Bortoncello, CF Mittelman, A Miguel, EC Trentini, CM Cordioli, AV AF Braga, Daniela T. Abramovitch, Amitai Fontenelle, Leonardo F. Ferrao, Ygor A. Gomes, Juliana B. Vivan, Analise S. Ecker, Kimberly K. Bortoncello, Cristiane F. Mittelman, Andrew Miguel, Euripides C. Trentini, Clarissa M. Cordioli, Aristides V. TI NEUROPSYCHOLOGICAL PREDICTORS OF TREATMENT RESPONSE TO COGNITIVE BEHAVIORAL GROUP THERAPY IN OBSESSIVE-COMPULSIVE DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE OCD; CBT; group therapy; neuropsychology; executive function; treatment response ID RANDOMIZED CLINICAL-TRIAL; NONVERBAL MEMORY IMPAIRMENT; ORGANIZATIONAL STRATEGIES; EXECUTIVE FUNCTIONS; TASK-PERFORMANCE; INHIBITION; DEFICITS; METAANALYSIS; SYMPTOMS; CONNECTIVITY AB BackgroundThe available research on the relationship between neuropsychological functioning and the therapeutic outcome of obsessive-compulsive disorder (OCD) has yielded inconsistent results. In this study, our aim was twofold. First, we sought to evaluate the effects of cognitive behavioral group therapy (CBGT) on neurocognitive functions in OCD patients. Second, we assessed the viability of neuropsychological test performance as a predictor of treatment response to CBGT. MethodsOne hundred fifty carefully screened OCD patients were randomized to receive either 12-week CBGT (n = 75) or to remain on a waiting list (WL; n = 75) for the corresponding time. Forty-seven participants dropped out of the study, leaving 103 participants that were included in the analysis (CBGT, n = 61; WL, n = 42). Participants had several neuropsychological domains evaluated both at baseline and at end-point. ResultsA significant difference in obsessive-compulsive, anxiety, and depression symptoms was observed between treated patients and controls favoring the CBGT group, but no significant differences were found on neuropsychological measures after 3 months of CBGT. In addition, there were no differences between treatment responders and nonresponders on all neuropsychological outcome measures. Employing a conservative alpha, neuropsychological test performance did not predict CBGT treatment response. ConclusionsAlthough the CBGT group demonstrated significant improvement in OCD symptoms, no significant difference was found on all neuropsychological domains, and test performance did not predict treatment response. C1 [Braga, Daniela T.; Gomes, Juliana B.; Vivan, Analise S.; Bortoncello, Cristiane F.; Trentini, Clarissa M.; Cordioli, Aristides V.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS, Brazil. [Abramovitch, Amitai; Mittelman, Andrew] Texas State Univ, Dept Psychol, San Marcos, TX USA. [Fontenelle, Leonardo F.] Univ Fed Rio de Janeiro, Dept Psychiat & Legal Med, Rio De Janeiro, RJ, Brazil. [Ecker, Kimberly K.] UFCSPA, Porto Alegre, RS, Brazil. [Ferrao, Ygor A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Miguel, Euripides C.] Univ Sao Paulo, Dept Psychiat, Fac Med, Sao Paulo, SP, Brazil. RP Braga, DT (reprint author), Univ Fed Rio Grande do Sul, Dept Psiquiatria, Rua Ramiro Barcelos 2350,Sala 400N, BR-90035903 Porto Alegre, RS, Brazil. EM dtbraga@gmail.com OI Abramovitch, Amitai/0000-0001-9640-0970 FU Fundo de Incentivo a Pesquisa e Eventos (FIPE) FX Contract grant sponsor: Fundo de Incentivo a Pesquisa e Eventos (FIPE). NR 81 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD SEP PY 2016 VL 33 IS 9 BP 848 EP 861 DI 10.1002/da.22509 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DW5SR UT WOS:000383707700008 PM 27100799 ER PT J AU Rentz, DM AF Rentz, Dorene M. TI Validating Use of Technology for Cognitive Test Assessment SO EBIOMEDICINE LA English DT Editorial Material C1 [Rentz, Dorene M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Med Sch, Dept Neurol, 221 Longwood Ave M97, Boston, MA 02115 USA. RP Rentz, DM (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Med Sch, Dept Neurol, 221 Longwood Ave M97, Boston, MA 02115 USA. EM DRENTZ@BICS.BWH.HARVARD.EDU NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD SEP PY 2016 VL 11 BP 23 EP 24 DI 10.1016/j.ebiom.2016.08.002 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EA8II UT WOS:000386878100012 PM 27498366 ER PT J AU Styer, AK AF Styer, Aaron K. TI MicroRNAs in fibroid biology: the lens for pathogenesis and functional significance? SO FERTILITY AND STERILITY LA English DT Editorial Material ID LEIOMYOMAS C1 [Styer, Aaron K.] Harvard Med Sch, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Styer, Aaron K.] Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Styer, AK (reprint author), Harvard Med Sch, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Styer, AK (reprint author), Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. NR 5 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD SEP 1 PY 2016 VL 106 IS 3 BP 556 EP 557 DI 10.1016/j.fertnstert.2016.05.017 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA4GT UT WOS:000386569800014 PM 27318083 ER PT J AU Moole, H Bechtold, ML Cashman, M Volmar, FH Dhillon, S Forcione, D Taneja, D Puli, SR AF Moole, Harsha Bechtold, Matthew L. Cashman, Micheal Volmar, Fritz H. Dhillon, Sonu Forcione, David Taneja, Deepak Puli, Srinivas R. TI Covered versus uncovered self-expandable metal stents for malignant biliary strictures: A meta-analysis and systematic review SO INDIAN JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Bile duct cancer; Palliation; Obstructive jaundice ID COMMON BILE-DUCT; RANDOMIZED-TRIAL; OBSTRUCTIVE-JAUNDICE; CLINICAL-TRIALS; PALLIATION; ENDOPROSTHESIS; PUBLICATION; MULTICENTER; MANAGEMENT; DRAINAGE AB Self-expandable metal stents (SEMS) are used for palliating inoperable malignant biliary strictures. It is unclear if covered metal stents are superior to uncovered metal stents in these patients. We compared clinical outcomes in patients with covered and uncovered stents. Studies using covered and uncovered metallic stents for palliation in patients with malignant biliary stricture were reviewed. Articles were searched in MEDLINE, PubMed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1436 reference articles, of which 132 were selected and reviewed. Thirteen studies (n = 2239) for covered and uncovered metallic stents which met the inclusion criteria were included in this analysis. Odds ratio for stent occlusion rates in covered vs. uncovered stents was 0.79 (95 % CI = 0.65 to 0.96). Survival benefit in patients with covered vs. uncovered stents showed the odds ratio to be 1.29 (95 % CI = 0.95 to 1.74). Pooled odds ratio for migration of covered vs. uncovered stents was 9.9 (95 % CI = 4.5 to 22.3). Covered stents seemed to have significantly lesser occlusion rates, increased odds of migration, and increased odds of pancreatitis compared to uncovered stents. There was no statistically significant difference in the survival benefit, overall adverse event rate, and patency period of covered vs. uncovered metal stents in patients with malignant biliary strictures. C1 [Moole, Harsha] Univ Illinois, Coll Med, Div Gen Internal Med, Peoria, IL 61656 USA. [Bechtold, Matthew L.] Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO USA. [Cashman, Micheal; Volmar, Fritz H.; Dhillon, Sonu; Puli, Srinivas R.] Univ Illinois, Coll Med, Div Gastroenterol & Hepatol, Peoria, IL 61656 USA. [Forcione, David] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Intervent Endoscopy Serv, Boston, MA USA. [Taneja, Deepak] Univ Illinois, Coll Med, Div Pulm Med, Dept Med, Peoria, IL 61656 USA. RP Moole, H (reprint author), Univ Illinois, Coll Med, Div Gen Internal Med, Peoria, IL 61656 USA. EM harsha1778@yahoo.co.in NR 41 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER INDIA PI NEW DELHI PA 7TH FLOOR, VIJAYA BUILDING, 17, BARAKHAMBA ROAD, NEW DELHI, 110 001, INDIA SN 0254-8860 EI 0975-0711 J9 INDIAN J GASTROENTER JI Indian J. Gastroenterol. PD SEP PY 2016 VL 35 IS 5 BP 323 EP 330 DI 10.1007/s12664-016-0682-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA4DC UT WOS:000386557700001 PM 27566620 ER PT J AU Anderson, BJ Wahlquist, AE Hill, EG Marshall, DT Kimchi, ET O'Carroll, KFS Camp, ER AF Anderson, Brandon J. Wahlquist, Amy E. Hill, Elizabeth G. Marshall, David T. Kimchi, Eric T. O'Carroll, Kevin F. Staveley Camp, E. Ramsay TI The impact of metabolic syndrome on outcome and response to neoadjuvant chemoradiation in locally advanced rectal cancer patients SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Article DE Metabolic syndrome; Rectal cancer; Neoadjuvant; Chemoradiation; Hypertension; Diabetes; Obesity ID HYPERTENSION; RISK; CHEMORADIOTHERAPY AB Background and objectives: Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors shown to increase the risk of developing various malignancies, as well as diminish tumor response to conventional therapies. The effects of MetS and its individual components on therapeutic response and treatment-related outcomes were examined in patients with locally advanced rectal cancer (LARC). Methods: Data was retrospectively collected on LARC patients treated with neoadjuvant chemoradiation (nCRT) and surgery. Medical records were reviewed for patient characteristics, staging, treatment plan, and outcomes. Results: One hundred two patients were included in the study. Patients with HTN had a significantly decreased nCRT response and were four times more likely to experience a poor response to treatment compared to patients without HTN. Additionally, HTN was found to significantly increase the rate of surgical complications. Neither DM nor obesity exhibited any significant effect on therapeutic response or complication rates, either individually or in combination with another risk factor. Conclusion: This study demonstrates the importance of considering underlying MetS risk factors, especially HTN, when predicting tumor response in LARC patients undergoing nCRT followed by radical surgery. The results provide support for an increased focus on pre-treatment risk factor control to optimize cancer therapy outcomes. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Anderson, Brandon J.; Kimchi, Eric T.; O'Carroll, Kevin F. Staveley; Camp, E. Ramsay] Med Univ South Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. [Wahlquist, Amy E.; Hill, Elizabeth G.] Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Wahlquist, Amy E.; Hill, Elizabeth G.; Kimchi, Eric T.; O'Carroll, Kevin F. Staveley; Camp, E. Ramsay] Hollings Canc Ctr, Charleston, SC 29425 USA. [Marshall, David T.] Dept Radiat Oncol, Charleston, SC 29425 USA. [Kimchi, Eric T.; O'Carroll, Kevin F. Staveley; Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ South Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. EM campe@musc.edu FU Cancer Center Support Grant [P30 CA138313] FX Cancer Center Support Grant P30 CA138313. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD SEP PY 2016 VL 33 BP 8 EP 12 DI 10.1016/j.ijsu.2016.07.011 PN A PG 5 WC Surgery SC Surgery GA EA8NM UT WOS:000386892400002 PM 27432024 ER PT J AU Yeh, DD AF Yeh, Daniel Dante TI Trauma: Current Practice and Cutting Edge Technology Introduction SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Editorial Material C1 [Yeh, Daniel Dante] Harvard Med Sch, Massachusetts Gen Hosp, Surg, Boston, MA 02115 USA. RP Yeh, DD (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Surg, Boston, MA 02115 USA. EM DYEH2@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD SEP PY 2016 VL 33 SI SI BP 189 EP 189 DI 10.1016/j.ijsu.2016.07.007 PN B PG 1 WC Surgery SC Surgery GA EA8NW UT WOS:000386894000001 ER PT J AU Menendez, ME Schumacher, CS Ring, D Freiberg, AA Rubash, HE Kwon, YM AF Menendez, Mariano E. Schumacher, Charles S. Ring, David Freiberg, Andrew A. Rubash, Harry E. Kwon, Young-Min TI Does "6-Clicks" Day 1 Postoperative Mobility Score Predict Discharge Disposition After Total Hip and Knee Arthroplasties? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; total knee arthroplasty; discharge; mobility; AM-PAC; resource utilization ID TOTAL JOINT ARTHROPLASTY; UNITED-STATES; REPLACEMENT SURGERY; ADMINISTRATIVE DATA; READMISSION RATES; RISK-ASSESSMENT; SHORT FORMS; MORTALITY; PAYMENTS; CARE AB Background: The use of inpatient rehabilitation services after total joint arthroplasty (TJA) is an important driver of episode-of-care costs. We determined the utility of a new standardized instrument collected during the immediate postoperative period, the Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" Mobility score, in predicting discharge disposition after TJA and its accuracy in estimating prolonged hospital stay, readmissions, and emergency department (ED) visits. Methods: Using our institutional database, we retrospectively reviewed 744 patients undergoing primary total hip (40%) or knee (60%) arthroplasty for osteoarthritis during 2014. The AM-PAC Mobility score was prospectively collected by physical therapists within 24 hours of surgery. We constructed 2 multivariable logistic regression models for each study outcome: (1) a base model containing age, sex, Charlson Comorbidity Index, and procedure type and (2) the AM-PAC model including the aforementioned variables and this score. The predictive performance of these models was assessed and compared using the area under the receiver operating characteristic (AUC) curve. Results: The AM-PAC model provided better prediction of discharge disposition (AUC = 0.777) than the base model (AUC = 0.716; 22% relative improvement). Although the AM-PAC model performed 32% and 27% better than the base model in estimating prolonged hospital stay and ED visits, the model's predictive performance was poor (prolonged stay: AUC = 0.639; ED visit: AUC = 0.658). The AM-PAC model also showed poor discrimination of readmissions (AUC = 0.657), and there was no relative improvement in predictive performance compared to that of the base model. Conclusion: The AM-PAC "6-Clicks" Mobility score is a valid, simple tool for predicting discharge disposition after TJA. (C) 2016 Elsevier Inc. All rights reserved. C1 [Menendez, Mariano E.; Schumacher, Charles S.; Ring, David; Freiberg, Andrew A.; Rubash, Harry E.; Kwon, Young-Min] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 38 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 SEP PY 2016 VL 31 IS 9 BP 1916 EP 1920 DI 10.1016/j.arth.2016.02.017 PG 5 WC Orthopedics SC Orthopedics GA DU4VQ UT WOS:000382211200012 PM 26993155 ER PT J AU Kwon, YM Antoci, V Leone, WA Tsai, TY Dimitriou, D Liow, MHL AF Kwon, Young-Min Antoci, Valentin, Jr. Leone, William A. Tsai, Tsung-Yuan Dimitriou, Dimitris Liow, Ming Han Lincoln TI Utility of Serum Inflammatory and Synovial Fluid Counts in the Diagnosis of Infection in Taper Corrosion of Dual Taper Modular Stems SO JOURNAL OF ARTHROPLASTY LA English DT Article DE periprosthetic joint infection; taper corrosion; dual taper modular; synovial counts; ESR; CRP ID TOTAL HIP-ARTHROPLASTY; PERIPROSTHETIC JOINT INFECTION; FAILED METAL; PSEUDOTUMOR; ASSOCIATION; REVISION; JUNCTION; RISK; NECK AB Background: An accurate diagnosis of periprosthetic joint infection PJI) is critical as treatment of the infected total hip arthroplasty differs from aseptic failure. The clinical presentation of PJI may mimic symptoms of taper corrosion. Our aim was to evaluate the utility of serum inflammatory markers and synovial fluid white blood cell WBC)/differential counts in diagnosis of PJI in failed dual taper total hip arthroplasty due to taper corrosion. Methods: We retrospectively reviewed 62 dual taper modular stem patients who underwent revision surgery for symptomatic adverse local tissue reaction due to taper corrosion. All patients had preoperative hip synovial aspirations, serum inflammatory markers, metal ion levels, and intraoperative cultures. Using Musculoskeletal Infection Society PJI criteria, we divided the cohort into infected and noninfected groups. Receiver-operating characteristic curves were constructed to determine the relationship and optimal cutoff values for erythrocyte sedimentation rate ESR), C-reactive protein CRP), and synovial fluid counts. Results: Infection group had significantly higher mean ESR P = .002), CRP P = .01), synovial fluid WBC P < .001), and neutrophil percentage P = .02). Cobalt levels were significantly elevated in noninfection group P = .02). Using receiver-operating characteristic curve analysis, the most ideal tests for diagnosis of PJI were synovial fluid WBC area under the curve = 86%, optimal cutoff 730 WBC/uL) and neutrophil percentage area under the curve = 83%, optimal cutoff 65%). ESR and CRP thresholds of 22 mm/h and 3 mg/L demonstrated 57% sensitivity and 95% specificity and 29% sensitivity and 93% specificity for detection of PJI, respectively. Conclusion: Our study suggests that ESR and CRP are useful in excluding PJI in dual taper modular implants with corrosion, whereas both synovial WBC count and neutrophil percentage are useful markers for diagnosing infection. (C) 2016 Elsevier Inc. All rights reserved. C1 [Kwon, Young-Min; Antoci, Valentin, Jr.; Leone, William A.; Tsai, Tsung-Yuan; Dimitriou, Dimitris; Liow, Ming Han Lincoln] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. OI LIOW, MING HAN LINCOLN/0000-0002-4496-8035; Dimitriou, Dimitris/0000-0002-9558-7080 NR 24 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD SEP PY 2016 VL 31 IS 9 BP 1997 EP 2003 DI 10.1016/j.arth.2016.02.020 PG 7 WC Orthopedics SC Orthopedics GA DU4VQ UT WOS:000382211200026 PM 26994651 ER PT J AU Ferraresi, C Parizotto, NA de Sousa, MVP Kaippert, B Huang, YY Koiso, T Bagnato, VS Hamblin, MR AF Ferraresi, Cleber Parizotto, Nivaldo Antonio Pires de Sousa, Marcelo Victor Kaippert, Beatriz Huang, Ying-Ying Koiso, Tomoharu Bagnato, Vanderlei Salvador Hamblin, Michael R. TI Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation (vol 9, pg 740, 2015) SO JOURNAL OF BIOPHOTONICS LA English DT Correction DE LLLT; LEDT; muscle performance; muscle recovery; ATP AB In the article by C. Ferraresi et al. (DOI: ), published in J. Biophotonics 8, 740-754 (2015), a statement regarding the approval of some data the authors used is incorrect. This erratum is published to rectify this. C1 [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Dept Phys Therapy, Lab Electrothermophototherapy, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos, Postgrad Program Biotechnol, BR-13560 Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Bagnato, Vanderlei Salvador] Univ Sao Paulo, Phys Inst Sao Carlos, Opt Grp, Sao Carlos, SP, Brazil. [Ferraresi, Cleber; Pires de Sousa, Marcelo Victor; Kaippert, Beatriz; Huang, Ying-Ying; Koiso, Tomoharu; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. [Pires de Sousa, Marcelo Victor] Univ Sao Paulo, Inst Phys, Lab Radiat Dosimetry & Med Phys, Sao Carlos, SP, Brazil. [Kaippert, Beatriz] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, RJ, Brazil. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Koiso, Tomoharu] Tohoku Univ, Grad Sch Biomed Engn, Sendai, Miyagi 980, Japan. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM mhamblin@partners.org RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016 FU NIAID NIH HHS [R01 AI050875, R21 AI121700] NR 1 TC 0 Z9 0 U1 3 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD SEP PY 2016 VL 9 IS 9 BP 976 EP 976 DI 10.1002/jbio.201680087 PG 1 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA DW5NF UT WOS:000383691800012 PM 27592534 ER PT J AU Movila, A Ishii, T Albassam, A Wisitrasameewong, W Howait, M Yamaguchi, T Ruiz-Torruella, M Bahammam, L Nishimura, K Van Dyke, T Kawai, T AF Movila, Alexandru Ishii, Takenobu Albassam, Abdullah Wisitrasameewong, Wichaya Howait, Mohammed Yamaguchi, Tsuguno Ruiz-Torruella, Montserrat Bahammam, Laila Nishimura, Kazuaki Van Dyke, Thomas Kawai, Toshihisa TI Macrophage Migration Inhibitory Factor (MIF) Supports Homing of Osteoclast Precursors to Peripheral Osteolytic Lesions SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE MIF; SDF-1; CXCR4; OSTEOCLAST PRECURSORS; PARTICLE-INDUCED OSTEOLYTIC LESIONS ID FACTOR-I SDF-1; PERIPROSTHETIC OSTEOLYSIS; DEFICIENT MICE; KAPPA-B; CELLS; BONE; ARTHRITIS; EXPRESSION; CXCR4; RECRUITMENT AB By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFP+ cells of healthy Csf1r-eGFP-KI mice, Csf1r+/CD11b+ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1r+/RANK+ cells in vitro. Therefore, Csf1r-eGFP+/CD11b+ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1r+/CD11b+ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4+ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4+ OCPs, as well as bone resorption, in the PMMA-injected calvaria, while increasing locally produced SDF-1. Collectively, these data suggest that locally produced MIF in the inflammatory bone lytic site is engaged in the chemoattraction of circulating CXCR4+ OCPs. (c) 2016 American Society for Bone and Mineral Research. C1 [Movila, Alexandru; Ishii, Takenobu; Albassam, Abdullah; Wisitrasameewong, Wichaya; Howait, Mohammed; Yamaguchi, Tsuguno; Ruiz-Torruella, Montserrat; Nishimura, Kazuaki; Van Dyke, Thomas; Kawai, Toshihisa] Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. [Ishii, Takenobu] Tokyo Dent Coll, Dept Orthodont, Tokyo, Japan. [Albassam, Abdullah; Wisitrasameewong, Wichaya; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. [Albassam, Abdullah; Howait, Mohammed; Bahammam, Laila] King Abdulaziz Univ, Fac Dent, Jeddah, Saudi Arabia. [Wisitrasameewong, Wichaya] Chulalongkorn Univ, Dept Periodontol, Fac Dent, Bangkok, Thailand. [Yamaguchi, Tsuguno] LION Corp, Res & Dev Headquarters, Odawara, Kanagawa, Japan. [Nishimura, Kazuaki] Tohoku Univ, Grad Sch Dent, Sendai, Miyagi, Japan. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM tkawai@forsyth.org RI Howait, Mohammed/K-4478-2016 OI Howait, Mohammed/0000-0002-6268-4941 FU NIH from the National Institute of Dental and Craniofacial Research [T32 DE 7327-12, DE-019917, DE-018499] FX This work was supported by NIH grants T32 DE 7327-12, DE-019917 and DE-018499 from the National Institute of Dental and Craniofacial Research. NR 61 TC 1 Z9 1 U1 4 U2 4 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 SEP PY 2016 VL 31 IS 9 BP 1688 EP 1700 DI 10.1002/jbmr.2854 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW5WL UT WOS:000383718100011 PM 27082509 ER PT J AU Filley, CM AF Filley, Christopher M. TI White Matter Dementia: Origin, Development, Progress, and Prospects SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; VASCULAR DEMENTIA; RISK-FACTOR; STRUCTURAL CONNECTIVITY; MEDITERRANEAN DIET; METABOLIC SYNDROME; SERUM-CHOLESTEROL AB The term white matter dementia (WMD) was introduced in 1988 to highlight the role of white matter in the development of dementia. As the concept has been refined with new insights into the structure and function of normal and abnormal white matter, research has expanded to consider normal cognition, network connectivity, novel treatment ideas, and the etiopath-ogenesis of neurodegenerative dementia. Emerging data are also identifying new opportunities for dementia prevention by avoidance of acquired vascular and traumatic white matter insults. The idea of WMD promises to continue as a useful construct informing the study of dementia and the understanding of brain-behavior relationships. C1 [Filley, Christopher M.] Univ Colorado, Sch Med, Behav Neurol Sect, Aurora, CO 80045 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Filley, CM (reprint author), Univ Colorado, Sch Med, Behav Neurol Sect, Aurora, CO 80045 USA.; Filley, CM (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. EM christopher.filley@ucdenver.edu NR 110 TC 0 Z9 0 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2016 VL 28 IS 4 BP 262 EP 272 DI 10.1176/appi.neuropsych.16010003 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EA3NO UT WOS:000386510100002 ER PT J AU Chialant, D Edersheim, J Price, BH AF Chialant, Doriana Edersheim, Judith Price, Bruce H. TI The Dialectic Between Empathy and Violence: An Opportunity for Intervention? SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CALLOUS-UNEMOTIONAL TRAITS; VENTROMEDIAL PREFRONTAL CORTEX; UNSUCCESSFUL CRIMINAL PSYCHOPATHS; ANTISOCIAL PERSONALITY-DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; SOMATIC MARKER HYPOTHESIS; VOXEL-BASED MORPHOMETRY; INFERIOR FRONTAL GYRUS; GRAY-MATTER; CONDUCT DISORDER AB The authors provide a comprehensive review of the neurobiology of empathy and compare this with the neurobiology of psychopathic predatory violence-the most extreme deficit of empathy. This suggests that the specific areas of the prefrontal cortex and limbic system, which have been associated with violent behavior, also appear to subserve the capacity for empathy. Damage to these regions may result in the emergence of aggression, but not of empathy, suggesting a structurally inverse relationship between the two. The authors examine the evidence for a dialectic between empathy and predatory violence and explore the implications for early interventions with empathy training in treatment-resistant psychopathy. C1 [Chialant, Doriana; Edersheim, Judith] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. [Price, Bruce H.] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA. [Chialant, Doriana; Edersheim, Judith; Price, Bruce H.] Massachusetts Gen Hosp, Ctr Law Brain & Behav, Boston, MA 02114 USA. [Edersheim, Judith] Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. [Price, Bruce H.] McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. RP Chialant, D (reprint author), Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA.; Chialant, D (reprint author), Massachusetts Gen Hosp, Ctr Law Brain & Behav, Boston, MA 02114 USA. EM doriana.chialant@gmail.com FU Massachusetts General Hospital Center for Law, Brain, and Behavior; Sidney R. Baer Jr. Foundation FX This work was partially supported by the Massachusetts General Hospital Center for Law, Brain, and Behavior and the Sidney R. Baer Jr. Foundation. NR 187 TC 0 Z9 0 U1 13 U2 13 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2016 VL 28 IS 4 BP 273 EP 285 DI 10.1176/appi.neuropsych.15080207 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EA3NO UT WOS:000386510100003 ER PT J AU Salinas, J Beiser, A Himali, JJ Rosand, J Seshadri, S Dunn, EC AF Salinas, Joel Beiser, Alexa Himali, Jayandra J. Rosand, Jonathan Seshadri, Sudha Dunn, Erin C. TI Factors Associated With New-Onset Depression After Stroke SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTSTROKE DEPRESSION; POSTMENOPAUSAL WOMEN; NATURAL-HISTORY; FOLLOW-UP; PREDICTORS; MORTALITY; SYMPTOMS; METAANALYSIS; BIOMARKERS; FREQUENCY AB To better identify stroke survivors at risk for depression who may benefit from early prevention through targeted strategies in the acute-subacute poststroke period, we examined 118 Framingham Heart Study stroke survivors with longitudinal prestroke depression assessments. Among those who developed poststroke depression, most lacked a history of depressive symptoms 5 years prior to their stroke. Sex (female), advanced age, and prestroke factors (smoking and functional dependence) were associated with new-onset depression poststroke. These findings suggest fully characterizing and accounting for prestroke factors, including psychosocial and behavioral determinants, may inform the predictive modeling needed to determine whether targeted preventive trials early in stroke recovery will improve stroke outcomes. C1 [Salinas, Joel; Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Beiser, Alexa; Himali, Jayandra J.; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Boston, MA USA. [Beiser, Alexa] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Beiser, Alexa; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Dunn, Erin C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Dunn, EC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. EM edunn2@mgh.harvard.edu OI /0000-0003-1391-9481; Salinas, Joel/0000-0002-3735-0018 FU National Heart, Lung, and Blood Institute [N01-HC 25195]; National Institute for Neurologic Disorders and Stroke [NS17950]; National Institute on Aging [AG031287, AG008122, AG033193, HHSN268201500001I]; National Institute of Mental Health [K01MH102403] FX This research was supported by a contract from the National Heart, Lung, and Blood Institute (N01-HC 25195) and by grants from the National Institute for Neurologic Disorders and Stroke (NS17950), the National Institute on Aging (AG031287, AG008122, AG033193, HHSN268201500001I), and the National Institute of Mental Health (K01MH102403). NR 32 TC 0 Z9 0 U1 4 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2016 VL 28 IS 4 BP 286 EP 291 DI 10.1176/appi.neuropsych.15110388 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EA3NO UT WOS:000386510100004 ER PT J AU Doshi, B Ward, JS Oral, E Muratoglu, OK AF Doshi, Brinda Ward, Jerel S. Oral, Ebru Muratoglu, Orhun K. TI Fatigue toughness of irradiated vitamin E/UHMWPE blends SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE fatigue strength; IZOD impact strength; radiation cross-linked UHMWPE; vitamin E ID MOLECULAR-WEIGHT POLYETHYLENE; CROSS-LINKED POLYETHYLENE; HAP-PAUL-AWARD; PROPAGATION RESISTANCE; MECHANICAL-PROPERTIES; GRADE POLYETHYLENE; ALPHA-TOCOPHEROL; FREE-RADICALS; TOTAL KNEES; LOW WEAR AB Radiation cross-linked ultrahigh molecular weight polyethylenes (UHMWPEs) have become the standard-of-care in total joint replacements (TJR) in the last decade because of their superior wear resistance in comparison with previously used conventional gamma sterilized UHMWPE. Some first generation radiation cross-linked UHMWPEs were stabilized against oxidation by post-irradiation melting, which significantly reduced their fatigue crack propagation resistance or fatigue toughness. Second generation cross-linked UHMWPEs incorporated instead an antioxidant such as vitamin E, eliminating the need for melting. In this study, we investigated the fatigue crack propagation resistance and the impact toughness of vitamin E-blended and radiation cross-linked UHMWPEs as a function of vitamin E concentration and radiation dose. Both properties were strongly dependent on the cross-link density and they showed a good correlation with each other (R-2=0.89). (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1514-1520, 2016. C1 [Doshi, Brinda; Ward, Jerel S.; Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1212b, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Med Sch, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1212b, Boston, MA 02114 USA.; Oral, E (reprint author), Harvard Med Sch, Dept Orthopaed Surg, Boston, MA 02115 USA. EM eoral@partners.org FU Harris Orthopaedic Laboratory FX Grant sponsor: Harris Orthopaedic Laboratory. NR 41 TC 0 Z9 0 U1 8 U2 8 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 SEP PY 2016 VL 34 IS 9 BP 1514 EP 1520 DI 10.1002/jor.23168 PG 7 WC Orthopedics SC Orthopedics GA DW5WG UT WOS:000383717600003 PM 26773556 ER PT J AU Gao, Y Liao, YF Shen, JK Feng, Y Choy, E Cote, G Harmon, D Mankin, HJ Hornicek, FJ Duan, ZF AF Gao, Yan Liao, Yunfei Shen, Jacson K. Feng, Yong Choy, Edwin Cote, Gregory Harmon, David Mankin, Henry J. Hornicek, Francis J. Duan, Zhenfeng TI Evaluation of P-glycoprotein (Pgp) expression in human osteosarcoma by high-throughput tissue microarray SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE P-glycoprotein (Pgp); osteosarcoma; tissue microarray (TMA); metastasis; prognosis ID HIGH-GRADE OSTEOSARCOMA; MULTIDRUG-RESISTANCE; MURAMYL TRIPEPTIDE; OSTEOGENIC-SARCOMA; MDR1 GENE; CHEMOTHERAPY; CANCER; TUMOR; METASTASIS; ASSOCIATION AB Survival of osteosarcoma patients is currently limited by the development of metastases and multidrug resistance (MDR). A well-established cause of MDR involves overexpression of P-glycoprotein (Pgp) in tumor cells. However, some discrepancies still exist as to the clinical significance of Pgp in osteosarcoma. We sought to elucidate further whether the Pgp expression correlated with clinical behavior in a series of patients with osteosarcoma via high-throughput tissue microarray (TMA) analysis. Immunohistochemical analysis of Pgp expression in a TMA of 114 specimens with a retrospective review of 70 osteosarcoma patients admitted to the Massachusetts General Hospital (MGH) was performed. High Pgp expression was correlated with metastasis development and poor response to pre-operative chemotherapy in osteosarcoma patients. Eighteen of the fifty-seven patients initially admitted with primary osteosarcoma showed high Pgp expression. Among these 18 patients with high Pgp expression, 13 of 18 (72%) patients eventually developed metastases. There was no significant clinical relevance between Pgp expression and osteosarcoma survival. These results support that high expression of Pgp is important, but cannot be assigned as, an individual predictor in the development of human osteosarcoma. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1606-1612, 2016. C1 [Gao, Yan; Liao, Yunfei; Shen, Jacson K.; Feng, Yong; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. [Gao, Yan; Liao, Yunfei; Shen, Jacson K.; Feng, Yong; Choy, Edwin; Cote, Gregory; Harmon, David; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Med Sch, Boston, MA 02114 USA. [Gao, Yan] Zhengzhou Univ, Affiliated Hosp 3, Dept Clin Lab, Zhengzhou 450052, Henan Province, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu OI Cote, Gregory/0000-0003-0181-886X FU Gattegno and Wechsler Funds; Kenneth Stanton Fund; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA 151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopaedics; China Scholarship Council and Excellent Doctorial Dissertations Grant of Zhengzhou University FX Grant sponsor: Gattegno and Wechsler Funds; Grant sponsor: Kenneth Stanton Fund; Grant sponsor: Sarcoma Foundation of America (SFA); Grant sponsor: National Cancer Institute (NCI)/National Institutes of Health (NIH); Grant number: UO1, CA 151452-01; Grant sponsor: Sarcoma SPORE/NIH; Grant sponsor: Academic Enrichment Fund of MGH Orthopaedics; Grant sponsor: China Scholarship Council and Excellent Doctorial Dissertations Grant of Zhengzhou University. NR 34 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 SEP PY 2016 VL 34 IS 9 BP 1606 EP 1612 DI 10.1002/jor.23173 PG 7 WC Orthopedics SC Orthopedics GA DW5WG UT WOS:000383717600013 PM 26790551 ER PT J AU Kohnen, D Jellicoe, N Sims, N AF Kohnen, David Jellicoe, Nicholas Sims, Nathaniel TI THE U.S. NAVY WON THE BATTLE OF JUTLAND SO NAVAL WAR COLLEGE REVIEW LA English DT Article C1 [Sims, Nathaniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sims, Nathaniel] Harvard Med Sch, Boston, MA 02115 USA. RP Sims, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Sims, N (reprint author), Harvard Med Sch, Boston, MA 02115 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU US NAVAL WAR COLL PI NEWPORT PA 686 CUSHING RD, NEWPORT, RI 02841 USA SN 0028-1484 J9 NAV WAR COLL REV JI Nav. War Coll. Rev. PD FAL PY 2016 VL 69 IS 4 BP 122 EP 145 PG 24 WC International Relations SC International Relations GA EA5TJ UT WOS:000386686100010 ER PT J AU Kilcoyne, A Gervais, DA AF Kilcoyne, Aoife Gervais, Debra A. TI Kidney, Ureter, and Bladder Biopsy SO TECHNIQUES IN VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review DE urologic intervention; kidney biopsy; bladder biopsy; ureteric biopsy ID PERCUTANEOUS RENAL BIOPSY; CELL CARCINOMA; PATHOLOGICAL CORRELATION; UROTHELIAL CARCINOMA; TRANSPLANT BIOPSY; DIAGNOSTIC YIELD; NEEDLE-BIOPSY; MASSES; CT; RISK AB Percutaneous urologic biopsy is a safe and effective technique and can comprise a significant proportion of the daily workload of the interventional radiologist. This article discusses the indications and rationale for the performance of renal, ureter, and bladder biopsy as well as the approach to performing such biopsies, pitfalls, and potential complications. (C) 2016 Elsevier Inc. All rights reserved. C1 [Kilcoyne, Aoife; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. RP Kilcoyne, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM akilcoyne1@mgh.harvard.edu NR 57 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 1089-2516 EI 1557-9808 J9 TECH VASC INTERV RAD JI Tech. Vasc. Interv. Radiol. PD SEP PY 2016 VL 19 IS 3 SI SI BP 237 EP 244 DI 10.1053/j.tvir.2016.06.009 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EA5SO UT WOS:000386683600009 PM 27641458 ER PT J AU Brizzi, K Pelden, S Tshokey, T Nirola, DK Diamond, MB Klein, JP Tshering, L Deki, S Nidup, D Bruno, V Dorny, P Garcia, HH Mateen, FJ AF Brizzi, Kate Pelden, Sonam Tshokey, Tshokey Nirola, Damber K. Diamond, Megan B. Klein, Joshua P. Tshering, Lhab Deki, Sonam Nidup, Dechen Bruno, Veronica Dorny, Pierre Hugo Garcia, Hector Mateen, Farrah J. CA Bhutan Epilepsy Project TI Neurocysticercosis in Bhutan: a cross-sectional study in people with epilepsy SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE Bhutan; Enzyme-linked immunoelectrotransfer blot; Epilepsy; Magnetic resonance imaging; Neurocysticercosis; Seizure ID CYSTICERCOSIS TAENIA-SOLIUM; SEIZURES; PERU; COMMUNITY; DIAGNOSIS; CHILDREN; PROFILE; ELISA; ASSAY AB Background: We sought to provide an assessment of the burden of neurocysticercosis among people with epilepsy (PWE) in Bhutan and evaluate the yield of various tests for Taenia solium. Methods: PWE were enrolled at the National Referral Hospital in Thimphu (2014-2015). Serum was tested for anti-Taenia solium IgG using ELISA (Ab-ELISA), enzyme-linked immunoelectrotransfer blot (EITB), and parasite antigen. Results were compared to brain MRI. Participants were categorized as definite neurocysticercosis (MRI and EITB positive), probable neurocysticercosis (MRI or EITB positive), or without neurocysticercosis. Logistic regression models were constructed to explore clinicodemographic associations. Results: There were 12/205 (6%, 95% CI 2%, 9%) definite and 40/205 (20%, 95% CI 14%, 25%) probable neurocysticercosis cases. 25/205 (12%) with positive EITB did not have neurocysticercosis on MRI, and 15/205 (7%) participants with positive MRI had negative EITB. Participants with neurocysticercosis-suggestive lesions on MRI had an average of 1.2 cysts (parenchymal 26/27; nodular/calcified stage 21/27). In a multivariable analysis, present age (OR 1.05, 95% CI 1.01,1.09, p=0.025) was positively associated with (combined probable or definite) neurocysticercosis while mesial temporal sclerosis on MRI (OR 0.294, 95% CI 0.144, 0.598, p=0.001) was negatively associated. Conclusions: Neurocysticercosis was associated with 6-25% of epilepsy in a Bhutanese cohort. Combining EITB and MRI would aid the diagnosis of neurocysticercosis among PWE since no test identified all cases. C1 [Brizzi, Kate; Diamond, Megan B.; Bruno, Veronica; Mateen, Farrah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pelden, Sonam; Tshokey, Tshokey] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Lab Med, Thimphu, Bhutan. [Nirola, Damber K.; Tshering, Lhab; Deki, Sonam] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Psychiat, Thimphu, Bhutan. [Klein, Joshua P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Klein, Joshua P.; Mateen, Farrah J.] Harvard Med Sch, Boston, MA 02115 USA. [Nidup, Dechen] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Radiol, Thimphu, Bhutan. [Dorny, Pierre] Inst Trop Med, Dept Biomed Sci, Antwerp, Belgium. [Hugo Garcia, Hector] Univ Peruana Cayetan Heredia, Dept Microbiol, Inst Ciencias Neurol, Cysticercosis Unit, Lima, Peru. RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Mateen, FJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM fmateen@partners.org FU Grand Challenges Canada; Government of Canada [338-04]; Partners Center for Expertise in Global Health Travel Grant; Massachusetts General Hospital Center for Global Health Travel Grant FX This work was supported by Grand Challenges Canada, funded by the Government of Canada (338-04); Partners Center for Expertise in Global Health Travel Grant; Massachusetts General Hospital Center for Global Health Travel Grant. NR 29 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0035-9203 EI 1878-3503 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD SEP PY 2016 VL 110 IS 9 BP 517 EP 526 DI 10.1093/trstmh/trw066 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA EA6SI UT WOS:000386758800004 PM 27794094 ER PT J AU Wojciechowski, D Vincenti, F AF Wojciechowski, David Vincenti, Flavio TI Costimulatory Blockade and Use of mTOR Inhibitors: Avoiding Injury Part 2 SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Belatacept; Costimulation blockade; mTOR inhibitors; Renal injury ID DONOR-SPECIFIC ANTIBODY; KIDNEY-TRANSPLANT RECIPIENTS; RENAL-ALLOGRAFT SURVIVAL; EXTENDED-CRITERIA DONORS; CALCINEURIN INHIBITORS; BENEFIT-EXT; PHASE-III; RANDOMIZED-TRIAL; T-CELLS; BELATACEPT AB Kidney transplantation immunosuppression relies on a calcineurin inhibitor backbone. Calcineurin inhibitors have reduced early-acute rejection rates but failed to improve long-term allograft survival. Their nephrotoxicity has shifted the focus of investigation to calcineurin inhibitor free regimens. Costimulation blockade with belatacept, a second generation, higher avidity variant of CTLA4-Ig, has emerged as part of a calcineurin inhibitor free regimen. Belatacept has demonstrated superior glomerular filtration rate compared with calcineurin inhibitors albeit with an increased risk of early and histologically severe rejection. Focus on optimizing the belatacept regimen to reduce the acute rejection rate while maintaining superior renal function is underway. Belatacept has also been utilized as part of a calcineurin inhibitor free conversion strategy in stable renal transplant recipients and has demonstrated superior improvement in glomerular filtration rate with conversion vs calcineurin inhibitor continuation. Additional work is underway to better define the role of belatacept in patients on calcineurin inhibitors with allograft dysfunction not due to rejection. (C) 2016 by the National Kidney Foundation, Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Univ Calif San Francisco, Kidney Transplant Serv, San Francisco, CA 94143 USA. RP Vincenti, F (reprint author), Univ Calif San Francisco, Kidney Transplant Serv, Clin Med & Surg, 505 Parnassus Ave,Room 884M, San Francisco, CA 94143 USA. EM Flavio.Vincenti@ucsfmedctr.org FU Department of Nephrology at UCSF; Department of Nephrology at MGH FX This work was supported by the Department of Nephrology at UCSF and MGH. NR 39 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD SEP PY 2016 VL 23 IS 5 BP 306 EP 311 DI 10.1053/j.ackd.2016.09.004 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA DZ9KV UT WOS:000386194900007 PM 27742385 ER PT J AU Eckerlin, DM Kovalesky, A Jakupcak, M AF Eckerlin, Denise M. Kovalesky, Andrea Jakupcak, Matthew TI Military Sexual Trauma in Male Service Members SO AMERICAN JOURNAL OF NURSING LA English DT Article DE military; military sexual trauma; posttraumatic stress disorder; sexual assault; sexual trauma ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; GENDER-DIFFERENCES; MALE VETERANS; HEALTH; AFGHANISTAN; ASSAULT; IRAQ; MEN; PREVALENCE AB The experience of military sexual trauma (MST), which can result from assault, battery, or harassment of a sexual nature, may jeopardize the mental health of service members as well as that of their family members, colleagues, and community members. Although a greater proportion of female than male service members are subjected to MST, the Department of Defense estimates that the absolute numbers of affected men and women, across all ranks and branches of military service, are nearly equal because roughly 85% of military members are men. Little research has explored the effects of MST on men. This article discusses the unique ways in which men may experience MST, and examines how social stereotypes of masculinity, myths surrounding sexual assault, and military culture and structure often influence a man's interpretation of an attack and his likelihood of reporting the incident or seeking treatment. It describes current treatments for MST-related mental health conditions and addresses implications for nurses and other health care professionals. C1 [Eckerlin, Denise M.] Univ Washington, Med Ctr, RN Resource Team, Seattle, WA 98195 USA. [Eckerlin, Denise M.] Univ Washington, Med Ctr, Resource Team Unit Practice Council, Seattle, WA 98195 USA. [Kovalesky, Andrea] Univ Washington Bothell, Sch Nursing & Hlth Studies, Bothell, WA USA. [Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, Northwest Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Eckerlin, DM (reprint author), Univ Washington, Med Ctr, RN Resource Team, Seattle, WA 98195 USA.; Eckerlin, DM (reprint author), Univ Washington, Med Ctr, Resource Team Unit Practice Council, Seattle, WA 98195 USA. EM deck@u.washington.edu NR 44 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-936X EI 1538-7488 J9 AM J NURS JI Am. J. Nurs. PD SEP PY 2016 VL 116 IS 9 BP 34 EP 43 PG 10 WC Nursing SC Nursing GA DZ8IO UT WOS:000386114300015 PM 27513073 ER PT J AU Shieh, E Lee, R Que, C Srinivasan, V Guo, R Deluna, R Pandit, S Simavli, H Seevaratnam, R Tsikata, E De Boer, J Chen, TC AF Shieh, Eric Lee, Ramon Que, Christian Srinivasan, Vivek Guo, Rong Deluna, Regina Pandit, Sumir Simavli, Huseyin Seevaratnam, Rajini Tsikata, Edem De Boer, Johannes Chen, Teresa C. TI Diagnostic Performance of a Novel Three-Dimensional Neuroretinal Rim Parameter for Glaucoma Using High-Density Volume Scans SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; NERVE-FIBER LAYER; DISC MARGIN ANATOMY; INNER PLEXIFORM LAYER; THICKNESS MEASUREMENTS; HEAD MEASUREMENTS; FALSE POSITIVES; FOURIER-DOMAIN; GANGLION-CELLS; CIRRUS HD AB PURPOSE: To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. DESIGN: Reliability analysis. METHODS: SETTING: Institutional. STUDY POPULATION: Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES: One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. " RESULTS: The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior -temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior -nasal sectors (P =.023.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. CONCLUSIONS: Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region. (C) 2016 Elsevier Inc. All rights reserved. C1 [Shieh, Eric; Lee, Ramon; Que, Christian; Srinivasan, Vivek; Pandit, Sumir; Simavli, Huseyin; Tsikata, Edem; Chen, Teresa C.] Harvard Med Sch, Boston, MA USA. [Que, Christian; Srinivasan, Vivek; Simavli, Huseyin; Tsikata, Edem; Chen, Teresa C.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Guo, Rong] Massachusetts Eye & Ear Infirm, Biostat, Boston, MA 02114 USA. [Deluna, Regina] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Seevaratnam, Rajini] New England Coll Optometry, Boston, MA USA. [De Boer, Johannes] Vrijie Univ, Dept Phys & Astron, LaserLaB Amsterdam, Amsterdam, Netherlands. [De Boer, Johannes] Vrije Univ, Med Ctr, Dept Ophthalmol, Amsterdam, Netherlands. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu OI Simavli, Huseyin/0000-0003-1657-9099 FU AMERICAN GLAUCOMA SOCIETY MID-CAREER AWARD (SAN FRANCISCO, CALIFORNIA); Massachusetts Lions Eye Research Fund (Boston, Massachusetts); Fidelity Charitable Fund (Harvard University, Boston, Massachusetts); Harvard Catalyst Grant (National Institutes of Health, Bethesda, Maryland) [UL RR025758]; Center for Biomedical OCT Research and Translation (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland) [P41 EB015903] FX TERESA CHEN: AMERICAN GLAUCOMA SOCIETY MID-CAREER AWARD (SAN FRANCISCO, CALIFORNIA), Massachusetts Lions Eye Research Fund (Boston, Massachusetts), Fidelity Charitable Fund (Harvard University, Boston, Massachusetts), Harvard Catalyst Grant (National Institutes of Health Award UL RR025758, Bethesda, Maryland), Center for Biomedical OCT Research and Translation (National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health Award P41 EB015903, Bethesda, Maryland). NR 53 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2016 VL 169 BP 168 EP 178 DI 10.1016/j.ajo.2016.06.028 PG 11 WC Ophthalmology SC Ophthalmology GA DW4UA UT WOS:000383637300018 PM 27349414 ER PT J AU Dansingani, KK Tan, ACS Gilani, F Phasukkijwatana, N Novais, E Querques, L Waheed, NK Duker, JS Querques, G Yannuzzi, LA Sarraf, D Freund, KB AF Dansingani, Kunal K. Tan, Anna C. S. Gilani, Fatimah Phasukkijwatana, Nopasak Novais, Eduardo Querques, Lea Waheed, Nadia K. Duker, Jay S. Querques, Giuseppe Yannuzzi, Lawrence A. Sarraf, David Freund, K. Bailey TI Subretinal Hyperreflective Material Imaged With Optical Coherence Tomography Angiography SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; OCT ANGIOGRAPHY; RANIBIZUMAB AB PURPOSE: The range of subretinal hyperreflective material (SHRM) seen in macular disease includes type 2 macular neovascularization, fibrosis, exudation, vitelliform material, and hemorrhage. The prognostic significance of SHRM has been evaluated retrospectively in clinical trials, but discriminating SHRM subtypes traditionally requires multiple imaging modalities. The purpose of this study is to describe optical coherence tomography angiography (OCTA) flow characteristics and artifacts that might help to distinguish SHRM subtypes. DESIGN: Validity analysis. METHODS: Patients with age-related macular degeneration (AMD), myopia, pachychoroid disease, and macular dystrophy, manifesting SHRM on optical coherence tomography (OCT), were recruited. Clinical chart review and multimodal imaging established the SHRM subtype. All patients underwent OCTA. OCT and OCTA images were examined together for (1) intrinsic flow, (2) retinal projection onto the anterior SHRM surface (strong, weak, absent), (3) retinal projection through SHRM onto retinal pigment epithelium (RPE), and (4) masking of choriocapillaris flow. RESULTS: Thirty-three eyes of 25 patients were included (type 2 neovascularization x3; fibrosis x4; exudation x10; hemorrhage x5; vitelliform x17). Mean age per eye was 76 years (standard deviation: 12). Intrinsic flow was strongest in type 2 neovascularization. Subretinal fibrosis showed limited flow in residual large-caliber vessels and branches. Flow was not detected within foci of exudation, hemorrhage, or vitelliform lesions. Retina-SHRM surface projection was strongest onto smooth-surfaced SHRM and weaker onto exudation. Retinal projection was weakest on the surface of vitelliform lesions. Retina-RPE projection was masked by dense hemorrhage and vitelliform material. In compound SHRM, OCTA distinguished between vascular and avascular components. CONCLUSION: Optical coherence tomography angiography can distinguish vascular from avascular SHRM components. OCTA artifacts may distinguish certain avascular SHRM components. (C) 2016 Elsevier Inc. All rights reserved. C1 [Dansingani, Kunal K.; Tan, Anna C. S.; Gilani, Fatimah; Yannuzzi, Lawrence A.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA. [Dansingani, Kunal K.; Tan, Anna C. S.; Gilani, Fatimah; Yannuzzi, Lawrence A.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Dansingani, Kunal K.] Univ Nebraska Med Ctr, Truhlsen Eye Inst, Omaha, NE USA. [Dansingani, Kunal K.] Moorfields Eye Hosp, London, England. [Tan, Anna C. S.] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore. [Phasukkijwatana, Nopasak; Sarraf, David] Univ Calif Los Angeles, Stein Eye Inst, Los Angeles, CA USA. [Phasukkijwatana, Nopasak] Mahidol Univ, Siriraj Hosp, Dept Ophthalmol, Fac Med, Bangkok, Thailand. [Novais, Eduardo; Waheed, Nadia K.; Duker, Jay S.] Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. [Novais, Eduardo] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Querques, Lea; Querques, Giuseppe] Univ Vita Salute San Raffaele, IRCCS Osped San Raffaele, Milan, Italy. [Yannuzzi, Lawrence A.; Freund, K. Bailey] NYU, Dept Ophthalmol, Sch Med, 550 1St Ave, New York, NY 10016 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Freund, KB (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave, New York, NY 10022 USA. EM kbfnyf@aol.com OI Novais, Eduardo/0000-0001-6790-4627; Freund, K. Bailey/0000-0002-7888-9773 FU LUESTHER T. MERTZ RETINAL RESEARCH CENTER; Macula Foundation, Inc, New York, New York FX FUNDING/SUPPORT: FUNDING SUPPORT WAS RECEIVED FROM THE LUESTHER T. MERTZ RETINAL RESEARCH CENTER AND THE Macula Foundation, Inc, New York, New York. The funding bodies supported this research but had no role in the design, conduct, or decision to publish. NR 17 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2016 VL 169 BP 235 EP 248 DI 10.1016/j.ajo.2016.06.031 PG 14 WC Ophthalmology SC Ophthalmology GA DW4UA UT WOS:000383637300025 PM 27349411 ER PT J AU Saeed, HN Kohanim, S Le, HG Chodosh, J Jacobs, DS AF Saeed, Hajirah N. Kohanim, Sahar Le, Hong-Gam Chodosh, James Jacobs, Deborah S. TI Stevens-Johnson Syndrome and Corneal Ectasia: Management and a Case for Association SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TOXIC EPIDERMAL NECROLYSIS; OCULAR SURFACE ECOSYSTEM; PROSTHETIC REPLACEMENT; DRY EYE; INFLAMMATORY MOLECULES; SCLERAL LENSES; KERATOCONUS; DISEASE; TEARS; COMPLICATIONS AB PURPOSE: To report the occurrence of corneal ectasia (ECT) in patients with history of Stevens-Johnson syndrome (SJS), and to make the case for an association between these 2 diagnoses. We also report the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment on visual acuity (VA) in these patients. DESIGN: Retrospective cohort study. METHODS: A manufacturing database of PROSE patients from 2002 to 2014 at Boston Foundation for Sight (BFS), a single-center clinical practice, was reviewed to identify patients with diagnoses of both SJS and ECT. RESULTS: Nine patients were identified with diagnoses of both SJS and ECT. In each case, review of the medical record revealed that diagnosis of SJS preceded that of ECT. The prevalence of ECT in this population exceeded that in the general population (P < .0001). Videokeratography was available for 13 eyes in 7 patients; using Krumeich's classification of keratoconus, 3 eyes were found to be at stage 1, 3 at stage 2, 1 at stage 3, and 6 at stage 4. Sixteen of 18 eyes underwent PROSE treatment. Of these 16 eyes, initial median VA was 20/200 (range, count fingers to 20/20; logMAR 1.0). Median VA after PROSE customization was 20/30 (range, 20/60-20/15; logMAR 0.1761, P < .0025). CONCLUSIONS: ECT occurs at a higher-than-expected rate in patients with a history of SJS. PROSE treatment improves VA in these patients. The basis of the association between SJS and ECT is considered, as well as the role of plausible contributory factors such as corneal microtrauma and matrix metalloproteinases. (C) 2016 The Author(s). Published by Elsevier Inc. C1 [Saeed, Hajirah N.; Kohanim, Sahar; Chodosh, James; Jacobs, Deborah S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Le, Hong-Gam; Jacobs, Deborah S.] Boston Fdn Sight, Needham, MA USA. [Kohanim, Sahar] Vanderbilt Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Nashville, TN USA. [Le, Hong-Gam] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Saeed, Hajirah N.] 243 Charles St, Boston, MA 02114 USA. RP Saeed, HN (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Hajirah_Saeed@meei.harvard.edu FU Research to Prevent Blindness, New York, New York FX FUNDING/SUPPORT: THIS PROJECT WAS SUPPORTED IN PART BY AN UNRESTRICTED GRANT TO THE DEPARTMENT OF Ophthalmology at Harvard Medical School from Research to Prevent Blindness, New York, New York. NR 39 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2016 VL 169 BP 276 EP 281 DI 10.1016/j.ajo.2016.06.039 PG 6 WC Ophthalmology SC Ophthalmology GA DW4UA UT WOS:000383637300029 PM 27386788 ER PT J AU Melzer, AC Feemster, LC Crothers, K Carson, SS Gillespie, SE Henderson, AG Krishnan, JA Lindenauer, PK McBurnie, MA Mularski, RA Naureckas, ET Pickard, AS Au, DH AF Melzer, Anne C. Feemster, Laura C. Crothers, Kristina Carson, Shannon S. Gillespie, Suzanne E. Henderson, Ashley G. Krishnan, Jerry A. Lindenauer, Peter K. McBurnie, Mary Ann Mularski, Richard A. Naureckas, Edward T. Pickard, A. Simon Au, David H. CA COPD Outcomes-Based Network Cl TI Respiratory and Bronchitic Symptoms Predict Intention to Quit Smoking among Current Smokers with, and at Risk for, Chronic Obstructive Pulmonary Disease SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: Smoking cessation is the most important intervention for patients with chronic obstructive pulmonary disease (COPD). What leads smokers with COPD to quit smoking remains unknown. Objectives: We sought to examine the association between respiratory symptoms and other markers of COPD severity with intention to quit smoking among a cohort of patients with probable COPD. Methods: We conducted a cross-sectional study of subjects with COPD or fixed airflow obstruction clinically diagnosed on the basis of pulmonary function testing. The subjects were identified in the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter registry. The primary outcome was the intention to quit smoking within the next 30 days (yes or no), which was examined using model building with multivariable logistic regression, clustered by study site. Measurements and Main Results: We identified 338 current smokers with COPD via the registry. Of these subjects, 57.4% (n = 194) had confirmed airflow obstruction based on pulmonary function testing. Nearly one-third (29.2%; n = 99) intended to quit smoking in the next 30 days. In adjusted analyses, compared with subjects without airflow obstruction based on pulmonary function testing, subjects with Global Initiative for Chronic Obstructive Lung Disease stage I/II COPD were more likely to be motivated to quit (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.37-2.49), with no association found for subjects with Global Initiative for Chronic Obstructive Lung Disease stage III/IV disease. Among the entire cohort, frequent phlegm (OR, 2.10; 95% CI, 1.22-3.64), cough (OR, 1.74; 95% CI, 1.01-2.99), wheeze (OR, 1.73; 95% CI, 1.09-3.18), and higher modified Medical Research Council dyspnea score (OR, 1.26 per point; 95% CI, 1.13-1.41) were associated with increased odds of intending to quit smoking. Low self-reported health was associated with decreased odds of intending to quit (OR, 0.75; 95% CI, 0.62-0.92). Conclusions: Frequent cough, phlegm, wheeze, and shortness of breath were associated with intention to quit smoking in the next 30 days, with a less clear relationship for severity of illness graded by pulmonary function testing and self-rated health. These findings can be used to inform the content of tobacco cessation interventions to provide a more tailored approach for patients with respiratory diseases such as COPD. C1 [Melzer, Anne C.; Feemster, Laura C.; Crothers, Kristina; Au, David H.] Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. [Melzer, Anne C.; Feemster, Laura C.; Au, David H.] VA Puget Sound, Ctr Innovat Vet, Ctr & Value Driven Care, Seattle, WA USA. [Carson, Shannon S.; Henderson, Ashley G.] Univ N Carolina, Chapel Hill, NC USA. [Gillespie, Suzanne E.; McBurnie, Mary Ann; Mularski, Richard A.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Populat Hlth Sci Program, Chicago, IL USA. [Lindenauer, Peter K.] Tufts Univ, Sch Med, Dept Med, Ctr Qual Care Res,Baystate Med Ctr, Springfield, MA 01199 USA. [Naureckas, Edward T.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Pickard, A. Simon] Univ Illinois, Coll Pharm, Dept Pharm Syst Outcomes & Policy, Chicago, IL USA. [Pickard, A. Simon] Univ Illinois, Coll Pharm, Ctr Pharmacoepidemiol & Pharmacoecon, Chicago, IL USA. RP Melzer, AC (reprint author), Minneapolis VA Med Ctr, 1 Vet Way, Minneapolis, MN 55417 USA. EM acmelzer@uw.edu OI Crothers, Kristina/0000-0001-9702-0371 FU Department of Veterans Affairs, Health Services Research and Development Service FX This material is based upon work supported by the Department of Veterans Affairs, Health Services Research and Development Service, which 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. The authors acknowledge the other member sites of the CONCERT Consortium, without which this project could not have been completed. D.H.A. has personally reviewed the data, understands the statistical methods employed for efficacy analysis, and confirms an understanding of this analysis, that the methods are clearly described and that they are a fair way to report the results. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD SEP PY 2016 VL 13 IS 9 BP 1490 EP 1496 DI 10.1513/AnnalsATS.201601-075OC PG 7 WC Respiratory System SC Respiratory System GA DZ8KB UT WOS:000386118200014 PM 27268422 ER PT J AU Courtwright, AM Robinson, EM Feins, K Carr-Loveland, J Donahue, V Roy, N McCannon, J AF Courtwright, Andrew M. Robinson, Ellen M. Feins, Katelyn Carr-Loveland, Jennifer Donahue, Vivian Roy, Nathalie McCannon, Jessica TI Ethics Committee Consultation and Extracorporeal Membrane Oxygenation SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: The clinical ethics literature on extracorporeal membrane oxygenation (ECMO) has been focused primarily on identifying hypothetical ethical dilemmas that may arise with the use of this technology. Little has been written on the actual experience with ECMO-related ethical questions. Objectives: To describe the role of an ethics consultation service during the expansion of a single-center ECMO program in a cardiothoracic surgery intensive care unit (CSICU) and to identify common ethical themes surrounding the use of ECMO. Methods: We conducted a retrospective, descriptive cohort study of all ECMO ethics consultation cases in the CSICU at a large academic hospital between 2013 and 2015. Measurements and Main Results: During the study period, 113 patients were placed on ECMO in the CSICU, 45 (39.5%) of whom were seen by the ethics committee. In 2013, 10 of 46 (21.7%) patients received ethics consults. By 2015, 28 of 30 (93.3%) of patients were seen by ethics consultants. Initial consultation occurred at a median of 2 days (interquartile range, 1-6 d) following initiation of ECMO. The most common ethical issue involved disagreement about the ongoing use of ECMO, which included multiple axes: Disagreement among health care providers, disagreement among surrogates, and disagreement between health care providers and surrogates over stopping or continuing ECMO. Conclusions: In our experience with integrating ethics consultation into the routine care of ECMO patients, most of the ethical questions more closely resembled traditional concerns about the appropriate use of any life-sustaining treatment rather than the novel dilemmas imagined in the current literature. C1 [Courtwright, Andrew M.; Robinson, Ellen M.] Massachusetts Gen Hosp, Inst Patient Care, Patient Care Serv, Boston, MA 02114 USA. [Robinson, Ellen M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Patient Care Serv, Boston, MA 02114 USA. [Feins, Katelyn; Carr-Loveland, Jennifer] Massachusetts Gen Hosp, Cardiothorac Surg Intens Care Unit, Boston, MA 02114 USA. [Donahue, Vivian] Massachusetts Gen Hosp, Cardiac Surg Intens Care Unit, Boston, MA 02114 USA. [Donahue, Vivian] Massachusetts Gen Hosp, Cardiac Intens Care Unit, Boston, MA 02114 USA. [Roy, Nathalie] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [McCannon, Jessica] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. [Courtwright, Andrew M.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP McCannon, J (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM jmccannon@partners.org FU National Institutes of Health [5T32HL007633-30] FX Supported by a grant from the National Institutes of Health (5T32HL007633-30). NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD SEP PY 2016 VL 13 IS 9 BP 1553 EP 1558 DI 10.1513/AnnalsATS.201511-757OC PG 6 WC Respiratory System SC Respiratory System GA DZ8KB UT WOS:000386118200022 PM 27299991 ER PT J AU Balekian, AA Tanner, NT Fisher, JM Silvestri, GA Gould, MK AF Balekian, Alex A. Tanner, Nichole T. Fisher, Joshua M. Silvestri, Gerard A. Gould, Michael K. TI Factors Associated with a Positive Baseline Screening Exam Result in the National Lung Screening Trial SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: Lung cancer screening with low-dose computed tomography (LDCT) has been shown to decrease mortality in eligible high-risk patients. However, this mortality benefit comes with a high rate of false-positive findings, which require further evaluation. Objectives: To identify patient-and center-specific factors associated with having a pulmonary nodule on baseline LDCT, and to develop a prediction rule to help in shared decision making. Methods: We identified individuals who underwent baseline LDCT screening as part of the National Lung Screening Trial. A positive screen was defined as a nodule 4 mm or greater in largest dimension. Using multiple logistic regression, we identified variables independently associated with having a positive screen. Measurements and Main Results: Among the 26,004 patients with complete data who underwent baseline LDCT, 7,123 patients (27%) had a positive screen. In a multivariate analysis, older age (odds ratio [OR] = 1.03 per 1-year increase, 95% confidence interval [CI] = 1.03-1.04), female sex (OR = 1.08, 95% CI = 1.01-1.14), white race (OR = 1.39, 95% CI = 1.25-1.55), heavier smoking history (OR = 1.02 per 5 pack-years smoked over 30, 95% CI = 1.00-1.04), history of chronic obstructive pulmonary disease (OR = 1.08, 95% CI = 1.01-1.17), being married (OR = 1.08, 95% CI = 1.02-1.15), hard rock mining (OR = 1.40, 95% CI = 1.04-1.89), and farm work (OR = 1.13, 95% CI = 1.03-1.23) were independently associated with having a positive screen, whereas having a college degree (OR = 0.94, 95% CI = 0.86-1.00) and abstinence from smoking (OR = 0.98 per year, 95% CI = 0.98-0.99) were associated with not having a positive screen. Patients enrolled at a site in an area highly endemic for histoplasma were 30% more likely to have a positive baseline LDCT screen (OR = 1.30, 95% CI = 1.21-1.40). The area under the receiver operator characteristic curve for the full model was 0.57 (0.56-0.58); including enrollment center as a random effect increased the area under the receiver operator characteristic curve to 0.65. Conclusions: In the National Lung Screening Trial, both patientand center-specific factors were associated with having a positive baseline screen. Although the model does not have sufficient accuracy to provide personalized risk estimates to guide shared decision making on an individual basis, it can nonetheless inform screening centers of the likelihood of further follow-up testing for their populations at large when allocating resources. Data collected from centers as broad-based screening is implemented can be used to improve model accuracy further. C1 [Balekian, Alex A.; Fisher, Joshua M.] Univ Southern Calif, Keck Sch Med, Div Pulm Crit Care & Sleep Med, Los Angeles, CA USA. [Tanner, Nichole T.] Ralph H Johnson Vet Affairs Hosp, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Tanner, Nichole T.; Silvestri, Gerard A.] Med Univ South Carolina, Div Pulm & Crit Care Med, Charleston, SC USA. [Gould, Michael K.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. RP Balekian, AA (reprint author), Univ Southern Calif, Keck Sch Med, 2020 Zonal Ave,IRD 723, Los Angeles, CA 90033 USA. EM alex.balekian@med.usc.edu NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD SEP PY 2016 VL 13 IS 9 BP 1568 EP 1574 DI 10.1513/AnnalsATS.201602-091OC PG 7 WC Respiratory System SC Respiratory System GA DZ8KB UT WOS:000386118200024 PM 27387658 ER PT J AU Courtright, KR Madden, V Gabler, NB Cooney, E Small, DS Troxel, A Casarett, D Ersek, M Cassel, JB Nicholas, LH Escobar, G Hill, SH O'Brien, D Vogel, M Halpern, SD AF Courtright, Katherine R. Madden, Vanessa Gabler, Nicole B. Cooney, Elizabeth Small, Dylan S. Troxel, Andrea Casarett, David Ersek, Mary Cassel, J. Brian Nicholas, Lauren Hersch Escobar, Gabriel Hill, Sarah H. O'Brien, Dan Vogel, Mark Halpern, Scott D. TI Rationale and Design of the Randomized Evaluation of Default Access to Palliative Services (REDAPS) Trial SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB The substantial nationwide investment in inpatient palliative care services stems from their great promise to improve patient-centered outcomes and reduce costs. However, robust experimental evidence of these benefits is lacking. The Randomized Evaluation of Default Access to Palliative Services (REDAPS) study is a pragmatic, stepped-wedge, cluster randomized trial designed to test the efficacy and costs of specialized palliative care consultative services for hospitalized patients with advanced chronic obstructive pulmonary disease, dementia, or end-stage renal disease, as well as the overall effectiveness of ordering such services by default. Additional aims are to identify the types of services that are most beneficial and the types of patients most likely to benefit, including comparisons between ward and intensive care unit patients. We hypothesize that patient-centered outcomes can be improved without increasing costs by simply changing the default option for palliative care consultation from opt-in to opt-out for patients with life-limiting illnesses. Patients aged 65 years or older are enrolled at 11 hospitals using an integrated electronic health record. As a pragmatic trial designed to enroll between 12,000 and 15,000 patients, eligibility is determined using a validated, electronic health record-based algorithm, and all outcomes are captured via the electronic health record and billing systems data. The time at which each hospital transitions from control, opt-in palliative care consultation to intervention, opt-out consultation is randomly assigned. The primary outcome is a composite measure of in-hospital mortality and length of stay. Secondary outcomes include palliative care process measures and clinical and economic outcomes. C1 [Courtright, Katherine R.; Halpern, Scott D.] Univ Penn, Dept Med, Pulm Allergy & Crit Care Med Div, Philadelphia, PA 19104 USA. [Courtright, Katherine R.; Madden, Vanessa; Gabler, Nicole B.; Cooney, Elizabeth; Troxel, Andrea; Halpern, Scott D.] Univ Penn, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Courtright, Katherine R.; Madden, Vanessa; Gabler, Nicole B.; Cooney, Elizabeth; Halpern, Scott D.] Univ Penn, Fostering Improvements End Of Life Decis Sci Prog, Philadelphia, PA 19104 USA. [Madden, Vanessa; Gabler, Nicole B.; Cooney, Elizabeth; Small, Dylan S.; Troxel, Andrea; Halpern, Scott D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Casarett, David; Halpern, Scott D.] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Casarett, David] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ersek, Mary] US Dept Vet Affairs, Philadelphia, PA USA. [Cassel, J. Brian] Virginia Commonwealth Univ, Div Hematol Oncol, Richmond, VA USA. [Nicholas, Lauren Hersch] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. [Escobar, Gabriel] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Hill, Sarah H.; O'Brien, Dan; Vogel, Mark] Ascens Hlth, St Louis, MO USA. [Vogel, Mark] Michigan State Univ, Dept Family Med, E Lansing, MI 48824 USA. RP Halpern, SD (reprint author), Univ Penn, Div Pulm Allergy & Crit Care, Perelman Sch Med, 726 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shalpern@exchange.upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU National Institute of Aging [UH3 AG050311] FX Supported by the National Institute of Aging grant UH3 AG050311 (S.D.H.). NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD SEP PY 2016 VL 13 IS 9 BP 1629 EP 1639 DI 10.1513/AnnalsATS.201604-308OT PG 11 WC Respiratory System SC Respiratory System GA DZ8KB UT WOS:000386118200032 PM 27348271 ER PT J AU Mlinac, ME Feng, MC AF Mlinac, Michelle E. Feng, Michelle C. TI Assessment of Activities of Daily Living, Self-Care, and Independence SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Assessment; Dementia; Disability; Handicaps; Everyday functioning ID NURSING-HOME RESIDENTS; OLDER-ADULTS; DEPRESSIVE SYMPTOMS; INSTRUMENTAL ACTIVITIES; COGNITIVE IMPAIRMENT; FUNCTIONAL DECLINE; EXECUTIVE FUNCTION; ALZHEIMER-DISEASE; NEUROPSYCHOLOGICAL PERFORMANCE; INFORMAL CAREGIVERS AB Activities of daily living (ADL) comprise the basic actions that involve caring for one's self and body, including personal care, mobility, and eating. In this review article, we (1) review useful clinical tools including a discussion on ways to approach ADL assessment across settings, (2) highlight relevant literature evaluating the relationship between cognitive functioning and ADLs, (3) discuss other biopsychosocial factors affecting ADL performance, (4) provide clinical recommendations for enhancing ADL capacity with an emphasis on self-care tasks (eating, grooming, dressing, bathing and toileting), and (5) identify interventions that treatment providers can implement to reduce the burden of ADL care. C1 [Mlinac, Michelle E.] Harvard Med Sch, VA Boston Healthcare Syst, Boston, MA USA. [Feng, Michelle C.] Execut Mental Hlth, Los Angeles, CA USA. RP Mlinac, ME (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM Michelle.mlinac@va.gov NR 100 TC 0 Z9 0 U1 9 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD SEP PY 2016 VL 31 IS 6 BP 506 EP 516 DI 10.1093/arclin/acw049 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA DZ7AU UT WOS:000386016000004 PM 27475282 ER PT J AU Olszewski, AJ Fallah, J Castillo, JJ AF Olszewski, Adam J. Fallah, Jaleh Castillo, Jorge J. TI Human immunodeficiency virus-associated lymphomas in the antiretroviral therapy era: Analysis of the National Cancer Data Base SO CANCER LA English DT Article DE acquired immunodeficiency syndrome (AIDS); epidemiology; human immunodeficiency virus; National Cancer Data Base; non-Hodgkin lymphoma; outcomes research ID NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMA; INFUSIONAL EPOCH CHEMOTHERAPY; HIV-INFECTED INDIVIDUALS; UNITED-STATES; POOLED ANALYSIS; PROGNOSTIC-FACTORS; BURKITT-LYMPHOMA; AIDS; OUTCOMES AB BACKGROUNDAntiviral therapy has altered the prognosis of patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL), but patterns of lymphoma-directed therapy in the community are unknown. METHODSThe authors analyzed the National Cancer Data Base records of 10,769 patients who were diagnosed with HIV-associated lymphoma from 2004 through 2012. Changes in clinical characteristics and chemotherapy delivery over time were evaluated. Factors that were associated with not receiving chemotherapy were studied using multivariable logistic regression, reporting odds ratios (ORs) with 95% confidence intervals (CIs). RESULTSThe proportion of black or Hispanic patients with HIV-associated NHL increased from 41% in 2004 to 55% in 2012 (P<.0001). Chemotherapy was received by 81% of patients with diffuse large B-cell lymphoma, 90% of those with Burkitt lymphoma, 61% of those with primary effusion lymphoma (PEL), and 35% of those with primary central nervous system lymphomas (PCNSL). Between 2004 and 2012, this proportion increased only for patients with PCNSL (P<.00001). Chemotherapy was less likely to be received by patients who were older, black, or without private insurance. It was delivered more frequently in hospitals designated as academic (OR for nonreceipt, 0.68; 95% CI, 0.51-0.92) or in hospitals that had 3 HIV-positive cases per year (OR, 0.71; 95% CI, 0.58-0.86). Survival improved in patients with diffuse large B-cell lymphoma (P=.007), Burkitt lymphoma (P=.0002), and PCNSL (P=.019), but not in those with PEL (P=.94). Receipt of chemotherapy in patients with PEL was not associated with better survival. CONCLUSIONSDisparities in chemotherapy delivery need attention, because a majority of HIV-positive patients with NHL in the United States are now black or Hispanic. Higher volume centers were associated with an increased likelihood of chemotherapy administration. Survival gains in patients with PCNSL parallel an increase in chemotherapy use, supporting its role in therapy. [See Editorial on pages 000-000, this issue.] Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2689-2697. (c) 2016 American Cancer Society. Most patients with newly diagnosed human immunodeficiency virus-associated lymphoma in the United States are black or Hispanic. The risk of not receiving chemotherapy is associated with sociodemographic characteristics and is significantly lower in higher volume or academic/research facilities. See also pages 2621-23. C1 [Olszewski, Adam J.] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Fallah, Jaleh] Mem Hosp Rhode Isl, Dept Med, Pawtucket, RI USA. [Castillo, Jorge J.] Harvard Med Sch, Dept Med, Boston, MA USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Olszewski, AJ (reprint author), Rhode Isl Hosp, Dept Med, 593 Eddy St, Providence, RI 02903 USA. EM adam_olszewski@brown.edu OI Castillo, Jorge/0000-0001-9490-7532; Olszewski, Adam/0000-0002-6472-6658 FU American Society of Hematology Scholar Award FX This work was funded by academic departments. Adam J. Olszewski is supported by an American Society of Hematology Scholar Award. NR 41 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2016 VL 122 IS 17 BP 2689 EP 2697 DI 10.1002/cncr.30112 PG 9 WC Oncology SC Oncology GA DW4MM UT WOS:000383617200012 PM 27337679 ER PT J AU Blum, AS Lavoie, B Eikermann-Haerter, K Tolner, E van den Maagdenberg, A Chen, SP Mawe, G Shapiro, R AF Blum, A. Sprouse Lavoie, B. Eikermann-Haerter, K. Tolner, E. van den Maagdenberg, A. Chen, S. P. Mawe, G. Shapiro, R. TI GASTROINTESTINAL MOTILITY IN FAMILIAL HEMIPLEGIC MIGRAINE MICE SO CEPHALALGIA LA English DT Meeting Abstract CT 5th International Congress of the European-Headache-and-Migraine-Trust (EHMTIC) CY SEP 15-18, 2016 CL Glasgow, SCOTLAND SP European Headache & Migraine Trust C1 [Blum, A. Sprouse; Lavoie, B.; Mawe, G.; Shapiro, R.] Univ Vermont, Dept Neurol Sci, Burlington, VT 05405 USA. [Eikermann-Haerter, K.; Chen, S. P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Tolner, E.; van den Maagdenberg, A.] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Tolner, E.; van den Maagdenberg, A.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. 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 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD SEP PY 2016 VL 36 SU 1 MA EHMTC-0220 BP 149 EP 150 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DZ7BP UT WOS:000386019000280 ER PT J AU Thunshelle, C Yin, R Chen, QQ Hamblin, MR AF Thunshelle, Connor Yin, Rui Chen, Qiquan Hamblin, Michael R. TI Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy SO CURRENT DERMATOLOGY REPORTS LA English DT Article DE 5-Aminolevulinic acid; Protoporphyrin IX; Heme biosynthesis; Skin penetration; Photodynamic therapy; Nanotechnology ID PROTOPORPHYRIN IX ACCUMULATION; NONMELANOMA SKIN-CANCER; CONJUGATED GOLD NANOPARTICLES; BASAL-CELL CARCINOMA; INTENSE-PULSED-LIGHT; IN-VITRO; ALA-PDT; ACTINIC KERATOSIS; TRANSDERMAL DELIVERY; FRACTIONAL LASER AB Kennedy and Pottier discovered that photodynamic therapy (PDT) could be carried out using a procedure consisting of topical application of the porphyrin-precursor, 5-aminolevulinic acid (ALA) to the skin, followed after some time by illumination with various light parameters in the 1980s. Since then, ALA-PDT has expanded enormously and now covers most aspects of dermatological disease. The purpose of this review is to discuss a range of ingenious strategies that investigators have devised for improving the overall outcome (higher efficiency and lower side effects) of ALA-PDT. The big advance of using ALA esters instead of the free acid to improve skin penetration was conceived in the 1990s. A variety of more recent innovative approaches can be divided into three broad groups: (a) those relying on improving delivery or penetration of ALA into the skin; (b) those relying on ways to increase the synthesis of protoporphyrin IX inside the skin; (c) those relying on modification of the illumination parameters. In the first group, we have improved delivery of ALA with penetration-enhancing chemicals, iontophoresis, intracutaneous injection, or fractionated laser. There is also a large group of nanotechnology-related approaches with ALA being delivered using liposomes/ethosomes, ALA dendrimers, niosomes, mesoporous silica nanoparticles, conjugated gold nanoparticles, polymer nanoparticles, fullerene nanoparticles, and carbon nanotubes. In the second group, we can find the use of cellular differentiating agents, the use of iron chelators, and the effect of increasing the temperature. In the third group, we find methods designed to reduce pain as well as improve efficiency including fractionated light, daylight PDT, and wearable light sources for ambulatory PDT. This active area of research is expected to continue to provide a range of intriguing possibilities. C1 [Thunshelle, Connor; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Thunshelle, Connor] Harvard Univ, Cambridge, MA 02138 USA. [Yin, Rui; Chen, Qiquan] Third Mil Med Univ, Southwest Hosp, Chongqing 40038, Peoples R China. [Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM Hamblin@helix.mgh.harvard.edu FU NIAID NIH HHS [R01 AI050875, R21 AI121700] NR 70 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA EI 2162-4933 J9 CURR DERMATOL REP JI Curr. Dermatol. Rep. PD SEP PY 2016 VL 5 IS 3 BP 179 EP 190 DI 10.1007/s13671-016-0154-5 PG 12 WC Dermatology SC Dermatology GA EA1NF UT WOS:000386358300006 PM 28163981 ER PT J AU Magnani, G Giugliano, RP Ruff, CT Murphy, SA Nordio, F Metra, M Moccetti, T Mitrovic, V Shi, MG Mercuri, M Antman, EM Braunwald, E AF Magnani, Giulia Giugliano, Robert P. Ruff, Christian T. Murphy, Sabina A. Nordio, Francesco Metra, Marco Moccetti, Tiziano Mitrovic, Veselin Shi, Minggao Mercuri, Michele Antman, Elliott M. Braunwald, Eugene TI Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF-TIMI 48 SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Atrial fibrillation; Heart failure; Thromboembolic risk prevention; Anticoagulation management; New oral anticoagulants; Edoxaban ID VENTRICULAR SYSTOLIC DYSFUNCTION; STABLE INR CONTROL; ANTICOAGULANT-THERAPY; BLEEDING RISK; STROKE; TRIAL; VALIDATION; PREDICTORS; OUTCOMES; PROGRAM AB AimsIn the ENGAGE AF-TIMI 48 trial, edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding. The higher-dose edoxaban regimen (HDER; 60 mg dose-reduced to 30 mg once daily) has been approved in various countries in Europe, the USA, and Japan. Among patients treated with vitamin K antagonists (VKAs), symptomatic heart failure (HF) is an independent risk factor for lower time-in-therapeutic range, which reduces the efficacy and safety of VKA therapy. We evaluated the efficacy and safety of edoxaban compared with warfarin across the spectrum of HF severity in the ENGAGE AF-TIMI 48 trial. Methods and resultsOf 14 071 patients randomized to well-controlled warfarin or the HDER, 5926 (42%) had no history of HF, 6344 (45%) were in New York Heart Association (NYHA) class I-II, and 1801 (13%) were in NYHA class III-IV. The efficacy of edoxaban compared with warfarin in preventing stroke/SEE was similar in patients without and with HF regardless of the severity of HF; [HDER vs. warfarin: No-HF: hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.69-1.11; NYHA class I-II: HR 0.88, 95% CI 0.69-1.12; NYHA class III-IV: HR 0.83, 95% CI 0.55-1.25; P-interaction = 0.97]. Compared with warfarin, HDER was consistently associated with lower risk of major bleeding (No-HF: HR 0.82, 95% CI 0.68-0.99; NYHA class I-II: HR 0.79, 95% CI 0.65-0.96; NYHA class III-IV: HR 0.79, 95% CI 0.54-1.17; P-interaction = 0.96). ConclusionThe relative efficacy and safety of HDER compared with well-managed warfarin in AF patients with HF were similar to those without HF. C1 [Magnani, Giulia; Giugliano, Robert P.; Ruff, Christian T.; Murphy, Sabina A.; Nordio, Francesco; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. [Magnani, Giulia; Giugliano, Robert P.; Ruff, Christian T.; Murphy, Sabina A.; Nordio, Francesco; Antman, Elliott M.; Braunwald, Eugene] Harvard Med Sch, 350 Longwood Ave, Boston, MA 02115 USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Moccetti, Tiziano] Fdn Cardioctr Ticino, Lugano, Switzerland. [Mitrovic, Veselin] Kerckhoff Klin, Bad Nauheim, Germany. [Shi, Minggao] Daiichi Sankyo, Parsippany, NJ USA. [Mercuri, Michele] Daiichi Sankyo, Edison, NJ USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA.; Braunwald, E (reprint author), Harvard Med Sch, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 29 TC 6 Z9 6 U1 2 U2 2 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 SEP PY 2016 VL 18 IS 9 BP 1153 EP 1161 DI 10.1002/ejhf.595 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW4HW UT WOS:000383604800010 PM 27349698 ER PT J AU Erickson, M Braun, K List, R Utech, A Moore, C White, DL Garcia, JM AF Erickson, Megan Braun, Katie List, Riesa Utech, Anne Moore, Carolyn White, Donna L. Garcia, Jose M. TI Evaluation of US Veterans Nutrition Education for Diabetes Prevention SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE diabetes; prediabetes; nutrition education; veterans ID MANAGEMENT; INTERVENTION; REDUCTION; THERAPY AB Objective: Evaluate the effectiveness of nutrition education interventions for diabetes prevention. Design: Retrospective cohort design. Setting: Tertiary-care US Veterans' Hospital, July 2007 to July 2012, using pre-existing database. Participants: Prediabetic, adult veterans (n = 372), mostly men (94.4%, n = 351). Interventions: Visits with existing nutrition education classes were collected. Main Outcome Measures: Primary outcome: diabetes status; predictors: visits/encounters, age, body mass index, weight change, and hemoglobin A1c. Analysis: Cox proportional hazards method, chi(2) test, and logistic regression. Results: In this sample, prediabetic veterans who received nutrition education were less likely to develop diabetes when compared with prediabetic veterans who did not receive nutrition education (hazard ratio, 0.71; 95% confidence interval, 0.55-0.92; P < .01). This difference remained significant after adjusting for body mass index and weight change. Conclusions and Implications: Nutrition education was significantly associated with preventing the progression from prediabetes to diabetes in US Veterans participating in a nutrition education intervention at the Michael E. DeBakey Veterans Affairs Medical Center. C1 [Erickson, Megan; Braun, Katie; Moore, Carolyn] Texas Womans Univ, Houston, TX USA. [Braun, Katie; Utech, Anne; Garcia, Jose M.] Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,Rm 3B-243, Houston, TX 77030 USA. [List, Riesa] Dept Vet Affairs, Nutr & Food Serv, Houston, TX USA. [List, Riesa] Dept Vet Affairs, Nutr & Food Serv, Hines, IL USA. [White, Donna L.] Michael E DeBakey VA Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX USA. [White, Donna L.] Baylor Coll Med, Houston, TX 77030 USA. [White, Donna L.] Michael E DeBakey VA Med Ctr, Sect Hlth Serv Res IQuESt, Clin Epidemiol & Comparat Effectiveness Program, Houston, TX USA. [White, Donna L.] Texas Med Ctr, Ctr Digest Dis, Houston, TX USA. [White, Donna L.; Garcia, Jose M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [White, Donna L.; Garcia, Jose M.] Michael E DeBakey VA Med Ctr, CTRID, Houston, TX USA. [Garcia, Jose M.] Michael E DeBakey VA Med Ctr, Ctr Translat Res Inflammatory Dis, VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Garcia, Jose M.] Univ Washington, Sch Med, Seattle, WA USA. [Garcia, Jose M.] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. RP Erickson, M (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,Rm 3B-243, Houston, TX 77030 USA. EM Megan.Erickson@sdstate.edu FU Department of Veterans Affairs (MERIT) [I01-BX000507, I01 CX000174]; NIA [T32AG000183, AG040583]; National Institute of Diabetes Digestive and Kidney Diseases [DK095082]; Center for Innovations the in Quality, Effectiveness, and Safety [CIN 13-413]; Michael E. DeBakey VA Medical Center, Houston, TX FX Dr Garcia received research support from the Department of Veterans Affairs (MERIT grants: I01-BX000507 and I01 CX000174 and the NIA T32AG000183 and AG040583). The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding agencies. Dr White's effort was supported in part by the National Institute of Diabetes Digestive and Kidney Diseases (DK095082, PI: White) and the Center for Innovations the in Quality, Effectiveness, and Safety (No. CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, TX. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the National Institutes of Health. The authors would also like to acknowledge the following individuals for their technical and written contributions to the original works in which this project stems: Dr Charles Wright, Karen Moreland, Caroline Nelson, Rose Bush, John Radcliffe, Mary Watson, and Shanil Juma. The Institutional Review Boards at Baylor College of Medicine, The Michael E. DeBakey VA Medical Center, and Texas Woman's University approved both protocols. NR 17 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 1499-4046 EI 1878-2620 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD SEP PY 2016 VL 48 IS 8 BP 538 EP + DI 10.1016/j.jneb.2016.06.007 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA EA1IW UT WOS:000386346700004 PM 27614279 ER PT J AU Trippa, L Parmigiani, G AF Trippa, Lorenzo Parmigiani, Giovanni TI Bayesian Nonparametric Estimation for Dynamic Treatment Regimes With Sequential Transition Times Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Canc Ctr, Harvard TH Chan Sch Publ Hlth, Boston, MA USA. RP Trippa, L (reprint author), Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA. EM ltrippa@jimmy.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2016 VL 111 IS 515 BP 947 EP 948 DI 10.1080/01621459.2016.1200915 PG 2 WC Statistics & Probability SC Mathematics GA EA0ZN UT WOS:000386318200004 ER PT J AU Lee, KH Dominici, F Schrag, D Haneuse, S AF Lee, Kyu Ha Dominici, Francesca Schrag, Deborah Haneuse, Sebastien TI Hierarchical Models for Semicompeting Risks Data With Application to Quality of End-of-Life Care for Pancreatic Cancer SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Bayesian survival analysis; Cluster-correlated data; Illness-death models; Reversible jump Markov chain Monte Carlo; Semicompeting risks; Shared frailty ID SEMI-COMPETING RISKS; SURVIVAL-DATA; FRAILTY MODELS; MEDICARE BENEFICIARIES; MULTISTATE MODELS; READMISSION RATES; BAYESIAN-ANALYSIS; HAZARD FUNCTIONS; UNITED-STATES; REGRESSION AB Readmission following discharge from an initial hospitalization is a key marker of quality of healthcare in the United States. For the most part, readmission has been studied among patients with "acute" health conditions, such as pneumonia and heart failure, with analyses based on a logistic-Normal generalized linear mixed model. Naive application of this model to the study of readmission among patients with "advanced" health conditions such as pancreatic cancer, however, is problematic because it ignores death as a competing risk. A more appropriate analysis is to imbed such a study within the semicompeting risks framework. To our knowledge, however, no comprehensive statistical methods have been developed for cluster-correlated semicompeting risks data. To resolve this gap in the literature we propose a novel hierarchical modeling framework for the analysis of cluster-correlated semicompeting risks data that permits parametric or non parametric specifications for a range of components giving analysts substantial flexibility as they consider their own analyses. Estimation and inference is performed within the Bayesian paradigm since it facilitates the straightforward characterization of (posterior) uncertainty for all model parameters, including hospital specific random effects. Model comparison and choice is performed via the deviance information criterion and the log-pseudo marginal likelihood statistic, both of which are based on a partially marginalized likelihood. An efficient computational scheme, based on the Metropolis-Hastings-Green algorithm, is developed and had been implemented in the R package SemiCompRisks. A comprehensive simulation study shows that the proposed framework performs very well in a range of data scenarios, and outperforms competitor analysis strategies. The proposed framework is motivated by and illustrated with an ongoing study of the risk of readmission among Medicare beneficiaries diagnosed with pancreatic cancer. Using data on n = 5298 patients at J=112 hospitals in the six New England states between 2000-2009, key scientific questions we consider include the role of patient-level risk factors on the risk of readmission and the extent of variation in risk across hospitals not explained by differences in patient case-mix. Supplementary materials for this article are available online. C1 [Lee, Kyu Ha] Forsyth Inst, Epidemiol & Biostat Core, 245 First St, Cambridge, MA 02142 USA. [Lee, Kyu Ha] Harvard Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA USA. [Dominici, Francesca; Haneuse, Sebastien] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lee, KH (reprint author), Forsyth Inst, Epidemiol & Biostat Core, 245 First St, Cambridge, MA 02142 USA. EM klee@forsyth.org FU National Cancer Institute [P01 CA134294-02]; National Institutes of Health [ES012044, K18 HS021991, R01 CA181360-01] FX This work was supported by National Cancer Institute grant (P01 CA134294-02) and National Institutes of Health grants (ES012044, K18 HS021991, R01 CA181360-01). NR 70 TC 0 Z9 0 U1 5 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2016 VL 111 IS 515 BP 1075 EP 1095 DI 10.1080/01621459.2016.1164052 PG 21 WC Statistics & Probability SC Mathematics GA EA0ZN UT WOS:000386318200014 PM 28303074 ER PT J AU Million, M Larauche, M AF Million, M. Larauche, M. TI Stress, sex, and the enteric nervous system SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE development; early life adversity; enteric nervous system; sex differences; stress ID GONADOTROPIN-RELEASING-HORMONE; IRRITABLE-BOWEL-SYNDROME; ESTROGEN-RECEPTOR-ALPHA; GASTROINTESTINAL-TRACT; MYENTERIC NEURONS; GENE-EXPRESSION; SMALL-INTESTINE; EMERGING ROLES; GNRH RECEPTORS; ANIMAL-MODELS AB Made up of millions of enteric neurons and glial cells, the enteric nervous system (ENS) is in a key position to modulate the secretomotor function and visceral pain of the gastrointestinal tract. The early life developmental period, through which most of the ENS development occurs, is highly susceptible to microenvironmental perturbation. Over the past decade, accumulating evidence has shown the impact of stress and early life adversity (ELA) on host gastrointestinal pathophysiology. While most of the focus has been on alterations in brain structure and function, limited experimental work in rodents suggest that the enteric nervous system can also be directly affected, as shown by changes in the number, phenotype, and reactivity of enteric nerves. The work of Medland et al. in the current issue of this journal demonstrates that such alterations also occur in pigs, a larger mammalian species with high translational value to human. This work also highlights a sex-differential susceptibility of the ENS to the effect of ELA, which could contribute to the higher prevalence of GI disorders in women. In this mini-review, we will discuss the development and composition of the ENS and related gastrointestinal sensory motor and secretory functions. We will then focus on the influence of stress on the enteric nervous system, with a particular emphasis on neurodevelopmental changes. Finally, we will discuss the influence of sex on those parameters. C1 [Million, M.; Larauche, M.] UCLA, David Geffen Sch Med, Dept Med, Div Digest Dis,CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Million, M.; Larauche, M.] Oppenheimer Family Ctr Neurobiol Stress & Resilie, Los Angeles, CA USA. [Million, M.; Larauche, M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. RP Larauche, M (reprint author), West Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115 Rm 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu FU NIDDK NIH HHS [K01 DK088937, P30 DK041301, P50 DK064539, R01 DK078676] NR 60 TC 1 Z9 1 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2016 VL 28 IS 9 BP 1283 EP 1289 DI 10.1111/nmo.12937 PG 7 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA DY8HL UT WOS:000385370000001 PM 27561694 ER PT J AU Taylor, AM Phillips, K Patel, KV Turk, DC Dworkin, RH Beaton, D Clauw, DJ Gignac, MAM Markman, JD Williams, DA Bujanover, S Burke, LB Carr, DB Choy, EH Conaghan, PG Cowan, P Farrar, JT Freeman, R Gewandter, J Gilron, I Goli, V Gover, TD Haddox, JD Kerns, RD Kopecky, EA Lee, DA Malamut, R Mease, P Rappaport, BA Simon, LS Singh, JA Smith, SM Strand, V Tugwell, P Vanhove, GF Veasley, C Walco, GA Wasan, AD Witter, J AF Taylor, Ann M. Phillips, Kristine Patel, Kushang V. Turk, Dennis C. Dworkin, Robert H. Beaton, Dorcas Clauw, Daniel J. Gignac, Monique A. M. Markman, John D. Williams, David A. Bujanover, Shay Burke, Laurie B. Carr, Daniel B. Choy, Ernest H. Conaghan, Philip G. Cowan, Penney Farrar, John T. Freeman, Roy Gewandter, Jennifer Gilron, Ian Goli, Veeraindar Gover, Tony D. Haddox, J. David Kerns, Robert D. Kopecky, Ernest A. Lee, David A. Malamut, Richard Mease, Philip Rappaport, Bob A. Simon, Lee S. Singh, Jasvinder A. Smith, Shannon M. Strand, Vibeke Tugwell, Peter Vanhove, Gertrude F. Veasley, Christin Walco, Gary A. Wasan, Ajay D. Witter, James TI Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations SO PAIN LA English DT Review DE OMERACT; IMMPACT; Pain; Physical performance measures; Patient-reported outcomes; Physical functioning; Physical activity; Accelerometer; Work; Employment; HRQOL; Social participation; Caregiver burden; Clinical trials ID PATIENT-REPORTED OUTCOMES; LOW-BACK-PAIN; EARLY RHEUMATOID-ARTHRITIS; QUALITY-OF-LIFE; COMMUNITY INTEGRATION QUESTIONNAIRE; HEALTH-ASSESSMENT QUESTIONNAIRE; WORK LIMITATIONS QUESTIONNAIRE; SICKNESS IMPACT PROFILE; TASK-FORCE REPORT; PSYCHOMETRIC PROPERTIES AB Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development. C1 [Taylor, Ann M.] Cardiff Univ, Sch Med, Ctr Med Educ, Cardiff, S Glam, Wales. [Phillips, Kristine] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Patel, Kushang V.; Turk, Dennis C.; Walco, Gary A.] Univ Washington, Dept Anesthesiol & Pain Med, Box 356540, Seattle, WA 98195 USA. [Dworkin, Robert H.; Gewandter, Jennifer; Smith, Shannon M.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY USA. [Beaton, Dorcas] Univ Toronto, Dept Occupat Sci & Occupat Therapy, Toronto, ON M5S 1A1, Canada. [Beaton, Dorcas; Gignac, Monique A. M.] Univ Toronto, Inst Work & Hlth, Toronto, ON M5S 1A1, Canada. [Clauw, Daniel J.; Williams, David A.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Markman, John D.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Bujanover, Shay] Depomed, Newark, CA USA. [Burke, Laurie B.] LORAGroup LLC, Royal Oak, MD USA. [Burke, Laurie B.] Univ Maryland, Dept Hlth Serv Res, Baltimore, MD 21201 USA. [Carr, Daniel B.] Tufts Univ, Sch Med, Publ Hlth & Community Med, Boston, MA 02111 USA. [Choy, Ernest H.] Cardiff Univ, Div Infect & Immun, Cardiff, S Glam, Wales. [Conaghan, Philip G.] Univ Leeds, NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Conaghan, Philip G.] Univ Leeds, Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Dept Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Freeman, Roy] Harvard Univ, Dept Neurol, Cambridge, MA 02138 USA. [Gilron, Ian] Queens Univ, Dept Anesthesiol, Ottawa, ON, Canada. [Goli, Veeraindar] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Goli, Veeraindar] Pfizer Inc, Durham, NC USA. [Gover, Tony D.] US Army Med Res & Mat Command, Clin & Rehabil Med Res Program, Ft Detrick, MD USA. [Haddox, J. David] Purdue Pharma LP, Stamford, CT USA. [Kerns, Robert D.] Vet Affairs Connecticut Healthcare Syst, Dept Vet Affairs, West Haven, CT USA. [Kerns, Robert D.] Yale Univ, Dept Psychiat & Psychol, New Haven, CT USA. [Kopecky, Ernest A.] Collegium Pharmaceut Inc, Canton, MA USA. [Lee, David A.] Chadds Ford, Pennsylvania, PA USA. [Malamut, Richard] Teva Pharmaceut, N Wales, PA USA. [Mease, Philip] Swedish Med Ctr, Rheumatol Clin Res Div, Seattle, WA USA. [Mease, Philip] Univ Washington, Sch Med, Seattle, WA USA. [Mease, Philip] Stanford Univ, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Rappaport, Bob A.] Analges Concepts LLC, Arlington, VA USA. [Simon, Lee S.] SDG Consulting LLC, Cambridge, MA USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Strand, Vibeke] Stanford Univ, Sch Med, Div Immunol Rheumatol, Palo Alto, CA 94304 USA. [Tugwell, Peter] Univ Ottawa, Fac Med, Ctr Global Hlth, Ottawa, ON, Canada. [Vanhove, Gertrude F.] Jazz Pharmaceut, Palo Alto, CA USA. [Veasley, Christin] Chron Pain Res Alliance, Washington, DC USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA USA. [Witter, James] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Box 356540, Seattle, WA 98195 USA. EM turkdc@uw.edu OI Tugwell, Peter/0000-0001-5062-0556 FU Analgesic; Anesthetic; Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); FDA FX The views expressed in this article are those of the authors. The reader should infer no official endorsement by the US Department of Veterans Affairs, US FDA, or the US National Institutes of Health. Support for the meeting was provided by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the FDA, which has received grants, contracts, and other revenue for its activities from the FDA, multiple pharmaceutical and device companies, and other sources. NR 210 TC 0 Z9 0 U1 13 U2 13 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 SEP PY 2016 VL 157 IS 9 BP 1836 EP 1850 DI 10.1097/j.pain.0000000000000577 PG 15 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DZ7AH UT WOS:000386014700002 PM 27058676 ER PT J AU Kucyi, A Salomons, TV Davis, KD AF Kucyi, Aaron Salomons, Tim V. Davis, Karen D. TI Cognitive behavioral training reverses the effect of pain exposure on brain network activity SO PAIN LA English DT Article DE Pain; CBT; fMRI; Default mode network; Functional connectivity; Cognitive training ID INTRINSIC FUNCTIONAL CONNECTIVITY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC BACK-PAIN; PREFRONTAL CORTEX; PERCEIVED CONTROL; CLINICAL PAIN; RESTING-STATE; THERAPY; FMRI; PERCEPTION AB Repeated sensory exposures shape the brain's function and its responses to environmental stimuli. An important clinical and scientific question is how exposure to pain affects brain network activity and whether that activity is modifiable with training. We sought to determine whether repeated pain exposure would impact brain network activity and whether these effects can be reversed by cognitive behavioral therapy (CBT)-based training. Healthy subjects underwent 8 experimental sessions on separate days on which they received painful thermal stimuli. They were randomly assigned to groups receiving either CBT-based training (regulate group, n = 17) or a non-pain-focused treatment (control group, n = 13). Before and after these sessions, participants underwent functional magnetic resonance imaging (fMRI) during painful stimulation and at rest. The effect of repeated pain over time in the control group was a decrease in the neurotypical pain-evoked default mode network (DMN) deactivation. The regulate group did not show these DMN effects but rather had decreased deactivation of the right ventrolateral prefrontal cortex (R vlPFC) of the executive control network. In the regulate group, reduced pain-evoked DMN deactivation was associated with greater individual reduction in pain intensity and unpleasantness over time. Finally, the regulate group showed enhanced resting functional connectivity between areas of the DMN and executive control network over time, compared with the control group. Our study demonstrates that trainable cognitive states can alter the effect of repeated sensory exposure on the brain. The findings point to the potential utility of cognitive training to prevent changes in brain network connectivity that occur with repeated experience of pain. C1 [Kucyi, Aaron; Salomons, Tim V.; Davis, Karen D.] Univ Hlth Network, Krembil Res Inst, Div Brain Imaging & Behav Syst Neurosci, Toronto, ON, Canada. [Kucyi, Aaron; Davis, Karen D.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Kucyi, Aaron] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Kucyi, Aaron] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Salomons, Tim V.] Univ Reading, Sch Psychol & Clin Language Sci, Reading, Berks, England. [Davis, Karen D.] Univ Hlth Network, Dept Med Imaging, Toronto, ON, Canada. [Davis, Karen D.] Univ Toronto, Dept Surg, Toronto, ON, Canada. RP Davis, KD (reprint author), Univ Hlth Network, Toronto Western Hosp, Krembil Res Inst, Div Brain Imaging & Behav Syst Neurosci, 399 Bathurst St,Room MP12-306, Toronto, ON M5T 2S8, Canada. EM kdavis@uhnres.utoronto.ca FU Canadian Institutes of Health Research; Canada Research Chair program; Clinician-Scientist Award from the University of Toronto Centre for the Study of Pain; Marie Curie Fellowship from the European Commission; Canadian Institutes of Health doctoral scholarship FX This work was supported by the Canadian Institutes of Health Research and the Canada Research Chair program. T. V. Salomons was funded by a Clinician-Scientist Award from the University of Toronto Centre for the Study of Pain and a Marie Curie Fellowship from the European Commission. A. Kucyi was supported by a Canadian Institutes of Health doctoral scholarship. NR 60 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 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD SEP PY 2016 VL 157 IS 9 BP 1895 EP 1904 DI 10.1097/j.pain.0000000000000592 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DZ7AH UT WOS:000386014700006 PM 27101426 ER PT J AU Lubitz, SA Brody, JA Bihlmeyer, NA Roselli, C Weng, LC Christophersen, IE Alonso, A Boerwinkle, E Gibbs, RA Bis, JC Cupples, LA Mohler, PJ Nickerson, DA Muzny, D Perez, MV Psaty, BM Soliman, EZ Sotoodehnia, N Lunetta, KL Benjamin, EJ Heckbert, SR Arking, DE Ellinor, PT Lin, HH AF Lubitz, Steven A. Brody, Jennifer A. Bihlmeyer, Nathan A. Roselli, Carolina Weng, Lu-Chen Christophersen, Ingrid E. Alonso, Alvaro Boerwinkle, Eric Gibbs, Richard A. Bis, Joshua C. Cupples, L. Adrienne Mohler, Peter J. Nickerson, Deborah A. Muzny, Donna Perez, Marco V. Psaty, Bruce M. Soliman, Elsayed Z. Sotoodehnia, Nona Lunetta, Kathryn L. Benjamin, Emelia J. Heckbert, Susan R. Arking, Dan E. Ellinor, Patrick T. Lin, Honghuang CA NHLBI GO Exome Sequencing Project TI Whole Exome Sequencing in Atrial Fibrillation SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CODING VARIANTS; FOLLOW-UP; RISK-FACTORS; RARE; PROTEIN; HEART; INDIVIDUALS; IL17REL; DISEASE AB Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results. We also examined whether genetic variation was enriched in suspected AF genes (N = 37) in AF cases versus controls. The mean age ranged from 59 to 73 years; 8,656 (78%) were of European ancestry. None of the 99,404 common variants evaluated was significantly associated after adjusting for multiple testing. Among the most significantly associated variants was a common (allele frequency = 86%) missense variant in SYNPO2L (rs3812629, p.Pro707Leu, [odds ratio 1.27, 95% confidence interval 1.13-1.43, P = 6.6x10(-5)]) which lies at a known AF susceptibility locus and is in linkage disequilibrium with a top marker from prior analyses at the locus. We did not observe significant associations between rare variants and AF in gene-based tests. Individuals with AF did not display any statistically significant enrichment for common or rare coding variation in previously implicated AF genes. In conclusion, we did not observe associations between coding genetic variants and AF, suggesting that large-effect coding variation is not the predominant mechanism underlying AF. A coding variant in SYNPO2L requires further evaluation to determine whether it is causally related to AF. Efforts to identify biologically meaningful coding variation underlying AF may require large sample sizes or populations enriched for large genetic effects. C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Roselli, Carolina; Weng, Lu-Chen; Christophersen, Ingrid E.; Ellinor, Patrick T.] Broad Insitute Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Brody, Jennifer A.; Bis, Joshua C.; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Bihlmeyer, Nathan A.; Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Weng, Lu-Chen; Christophersen, Ingrid E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Christophersen, Ingrid E.] Vestre Viken Hosp Trust, Dept Med Res, Baerum Hosp, Baerum, Norway. [Alonso, Alvaro] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Boerwinkle, Eric] UTHlth, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric; Gibbs, Richard A.; Muzny, Donna] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, L. Adrienne; Lunetta, Kathryn L.; Benjamin, Emelia J.; Lin, Honghuang] Boston Univ, Framingham, MA 01702 USA. [Cupples, L. Adrienne; Lunetta, Kathryn L.; Benjamin, Emelia J.; Lin, Honghuang] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Mohler, Peter J.] Ohio State Univ, Wexner Med Ctr, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Perez, Marco V.] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Soliman, Elsayed Z.] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.; Lubitz, SA (reprint author), Broad Insitute Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Lin, HH (reprint author), Boston Univ, Framingham, MA 01702 USA.; Lin, HH (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.; Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. EM slubitz@mgh.harvard.edu; hhlin@bu.edu RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Bihlmeyer, Nathan/0000-0002-4415-7419; Body, Jennifer/0000-0001-8509-148X FU NIH [K23HL114724, 1R01HL128914, 2R01HL092577, 3R01HL092577-06S1]; Doris Duke Charitable Foundation Clinical Scientist Development Award [2014105]; Laughlin Family Endowment; NIH through the American Recovery and Reinvestment Act (ARRA) [5RC2HL102419]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; American Heart Association [16EIA26410001]; NHLBI; Boston University [HHSN2682015000011, N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, R01 HL102214, RC2 HL-103010, RC2 HL-102925, RC2 HL-102926]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [R01AG023629]; [HL111089]; [HL116747] FX This work was supported by NIH grants K23HL114724 (SAL) and a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105 (SAL). NS was supported by HL111089, HL116747, and the Laughlin Family Endowment. Funding support for "Building on GWAS for NHLBI-diseases: the U.S. CHARGE Consortium" was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). Data for "Building on GWAS for NHLBI-diseases: the U.S. CHARGE Consortium" was provided by EB on behalf of the Atherosclerosis Risk in Communities (ARIC) Study; LAC, principal investigator for the Framingham Heart Study; and BMP, principal investigator for the Cardiovascular Health Study. Sequencing was carried out at the Baylor Genome Center (U54 HG003273). The ARIC Study was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This work was additionally supported by American Heart Association grant 16EIA26410001 (AA). The Framingham Heart Study was conducted and supported by the NHLBI in collaboration with Boston University (Contract No. HHSN2682015000011; N01-HC-25195), and its contract with Affymetrix, Inc., for genome-wide genotyping services (Contract No. N02-HL-6-4278), for quality control by Framingham Heart Study investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Also funding was provided by NIH grants 1R01HL128914; 2R01HL092577; 3R01HL092577-06S1. CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01 HL102214 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Funding for GO ESP was provided by NHLBI grants RC2 HL-103010 (HeartGO) and exome sequencing was performed through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2016 VL 12 IS 9 AR e1006284 DI 10.1371/journal.pgen.1006284 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA DZ7TF UT WOS:000386069000019 PM 27589061 ER PT J AU Verma, SS Bailey, JNC Lucas, A Bradford, Y Linneman, JG Hauser, MA Pasquale, LR Peissig, PL Brilliant, MH McCarty, CA Haines, JL Wiggs, JL Vrabec, TR Tromp, G Ritchie, MD AF Verma, Shefali Setia Bailey, Jessica N. Cooke Lucas, Anastasia Bradford, Yuki Linneman, James G. Hauser, Michael A. Pasquale, Louis R. Peissig, Peggy L. Brilliant, Murray H. McCarty, Catherine A. Haines, Jonathan L. Wiggs, Janey L. Vrabec, Tamara R. Tromp, Gerard Ritchie, Marylyn D. CA eMERGE Network NEIGHBOR Consortium TI Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium SO PLOS GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; ELECTRONIC MEDICAL-RECORDS; HUMAN TRABECULAR MESHWORK; CENTRAL CORNEAL THICKNESS; COMPLEX TRAITS; MISSING HERITABILITY; COMMON VARIANTS; EXPRESSION; ARCHITECTURE AB Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies. C1 [Verma, Shefali Setia; Lucas, Anastasia; Bradford, Yuki; Ritchie, Marylyn D.] Geisinger Hlth Syst, Dept Biomed & Translat Informat, Danville, PA 17821 USA. [Verma, Shefali Setia] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. [Bailey, Jessica N. Cooke; Haines, Jonathan L.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Inst Computat Biol, Cleveland, OH 44106 USA. [Linneman, James G.; Peissig, Peggy L.; Brilliant, Murray H.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. [Pasquale, Louis R.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [McCarty, Catherine A.] Essentia Rural Hlth, Duluth, MN USA. [Vrabec, Tamara R.] Geisinger Hlth Syst, Dept Ophthalmol, Danville, PA USA. [Tromp, Gerard] Univ Stellenbosch, Div Mol Biol & Human Genet, Dept Biomed Sci, Fac Med & Hlth Sci, Tygerberg, South Africa. [Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Ritchie, MD (reprint author), Geisinger Hlth Syst, Dept Biomed & Translat Informat, Danville, PA 17821 USA.; Ritchie, MD (reprint author), Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. EM mdritchie@geisinger.edu OI Cooke Bailey, Jessica/0000-0002-4001-8702; Tarczy-Hornoch, Peter/0000-0003-1047-179X FU NHGRI [U01HG006828, U01HG006830, U01HG006389, U01HG006382, U01HG006375, U01HG006379, U01HG006380, U01HG006388, U01HG006378, U01HG006385]; NCATS/NIH [UL1TR000427, U01HG004438, U01HG004424]; US National Institutes of Health/National Eye Institute (NIH/NEI) grant [R01EY022305] FX The eMERGE Network was initiated and funded by NHGRI through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative/University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG006389 and NCATS/NIH grant UL1TR000427 (Marshfield); U01HG004438 (CIDR) and U01HG004424 (the Broad Institute). NEIGHBORHOOD data collection and analysis are supported by US National Institutes of Health/National Eye Institute (NIH/NEI) grant R01EY022305 (JLW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 1 Z9 1 U1 4 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2016 VL 12 IS 9 AR e1006186 DI 10.1371/journal.pgen.1006186 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA DZ7TF UT WOS:000386069000003 PM 27623284 ER PT J AU McLaughlin, D Carrion, RE Auther, AM Olvet, DM Addington, J Bearden, CE Cadenhead, KS Cannon, TD Heinssen, RK Mathalon, DH McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Goldberg, TE Harvey, PD Cornblatt, BA AF McLaughlin, Danielle Carrion, Ricardo E. Auther, Andrea M. Olvet, Doreen M. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin S. Cannon, Tyrone D. Heinssen, Robert K. Mathalon, Daniel H. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Goldberg, Terry E. Harvey, Philip D. Cornblatt, Barbara A. TI Functional Capacity Assessed by the Map Task in Individuals at Clinical High-Risk for Psychosis SO SCHIZOPHRENIA BULLETIN LA English DT Article DE prodromal; role functioning; disability; prediction; CHR; NAPLS ID SKILLS ASSESSMENT UPSA; ULTRA-HIGH RISK; INTERRATER RELIABILITY; PREDICTIVE-VALIDITY; PRODROMAL SYNDROMES; SCHIZOPHRENIA; PERFORMANCE; DISABILITY; PEOPLE; SYMPTOMS AB Objectives: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world achievements, rather than on the skills required to carry-out a particular real-world function (ie, capacity). Despite growing evidence that diminished capacity is critical to the etiology of the established disorder, virtually no attention has been directed towards assessing functional capacity in the pre-illness stages. In the present study, we introduce the Map task, a measure to assess functional capacity in adolescent and young-adult high-risk populations. Methods: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. Results: CHR participants showed large impairments across major indices of the Map task, relative to the HCs. Most importantly, poor performance on the Map task significantly predicted conversion to psychosis, even after adjusting for age, IQ, clinical state, and other potential confounders. Conclusions: To the best of our knowledge, the Map task is one of the first laboratory-based measures to assess functional capacity in high-risk populations. Functional capacity deficits prior to the onset of psychosis may reflect a basic mechanism that underlies risk for psychosis. Early intervention targeting this domain may help to offset risk and independently improve long-term outcome. C1 [McLaughlin, Danielle; Carrion, Ricardo E.; Auther, Andrea M.; Olvet, Doreen M.; Goldberg, Terry E.; Cornblatt, Barbara A.] Northwell Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. [Carrion, Ricardo E.; Goldberg, Terry E.; Cornblatt, Barbara A.] Northwell Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Carrion, Ricardo E.; Auther, Andrea M.; Goldberg, Terry E.; Cornblatt, Barbara A.] Hofstra Northwell Sch Med, Dept Psychiat, Hempstead, NY USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Cannon, Tyrone D.] Yale Univ, Sch Med, Dept Psychol, New Haven, CT USA. [Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Heinssen, Robert K.] NIMH, Div Treatment & Prevent Res, Rockville, MD 20857 USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Perkins, Diana O.] Univ North Carolina Chapel Hill, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.; Tsuang, Ming T.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. [Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Harvey, Philip D.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Harvey, Philip D.] Bruce W Carter VA Med Ctr, Res Serv, Miami, FL USA. [Cornblatt, Barbara A.] Hofstra Northwell Sch Med, Dept Mol Med, Hempstead, NY USA. RP McLaughlin, D (reprint author), Northwell Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM Dmclaugh@northwell.edu FU National Institute of Mental Health [U01 MH081984, U01 MH081928, P50 MH080272]; Commonwealth of Massachusetts [SCDMH82101008006, R01 MH60720, U01 MH082022, K24 MH76191, U01 MH081902, P50 MH066286, U01 MH082004, U01 MH081988, RO1 MH076989-01, U01 MH081857, MH61523]; Zucker Hillside Hospital NIMH Advanced Center for Intervention and Services Research for the Study of Schizophrenia [MH 074543-01]; Brain and Behavior Research Foundation (NARSAD): Young Investigator Grant [19740]; Let the Sun Shine Run/Walk, Cold Spring, MN FX Supported by grants from the National Institute of Mental Health: U01 MH081984 to J.A.; U01 MH081928; P50 MH080272; Commonwealth of Massachusetts SCDMH82101008006 to L.J.S.; R01 MH60720, U01 MH082022, and K24 MH76191 to K.S.C.; U01 MH081902 to T.D.C.; P50 MH066286 (Prodromal Core) to C.E.B.; grant U01 MH082004 to D.O.P.; U01 MH081988 to E.F.W.; RO1 MH076989-01 to D.H.M.; U01 MH082022 to S.W.W.; U01 MH081857 and MH61523 to B.A.C.; the Zucker Hillside Hospital NIMH Advanced Center for Intervention and Services Research for the Study of Schizophrenia MH 074543-01 to John M. Kane, M.D. REC received funding from the Brain and Behavior Research Foundation (NARSAD): Young Investigator Grant 19740 and the Let the Sun Shine Run/Walk, Cold Spring, MN. No funding agency had any role in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. NR 46 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2016 VL 42 IS 5 BP 1234 EP 1242 DI 10.1093/schbul/sbw039 PG 9 WC Psychiatry SC Psychiatry GA DZ9PK UT WOS:000386209900020 PM 27105902 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Inaccurate information on facet joint injections in the Medicare population SO SPINE JOURNAL LA English DT Letter C1 [Manchikanti, Laxmaiah] Univ Louisville, 530 South Jackson St, Louisville, KY 40202 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Univ Louisville, 530 South Jackson St, Louisville, KY 40202 USA.; Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD SEP PY 2016 VL 16 IS 9 BP 1157 EP 1158 DI 10.1016/j.spinee.2016.04.025 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA EA1RD UT WOS:000386368700050 PM 27659137 ER PT J AU Altrock, PM Brendel, C Renella, R Orkin, SH Williams, DA Michor, F AF Altrock, Philipp M. Brendel, Christian Renella, Raffaele Orkin, Stuart H. Williams, David A. Michor, Franziska TI Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; BETA-GLOBIN GENE; RED-BLOOD-CELLS; FETAL-HEMOGLOBIN; LONG-TERM; MIXED CHIMERISM; STEM-CELLS; LIFE-SPAN; SURVIVAL; ANEMIA AB Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), a heritable disorder caused by a point mutation in the beta-globin gene. The developmental switch from fetal gamma-globin to adult beta-globin is governed in part by the transcription factor (TF) BCL11A. This TF has been proposed as a therapeutic target for reactivation of gamma-globin and concomitant reduction of beta-sickle globin. In this and other approaches, genetic alteration of a portion of the hematopoietic stem cell (HSC) compartment leads to a mixture of sickling and corrected red blood cells (RBCs) in periphery. To reverse the sickling phenotype, a certain proportion of corrected RBCs is necessary; the degree of HSC alteration required to achieve a desired fraction of corrected RBCs remains unknown. To address this issue, we developed a mathematical model describing aging and survival of sickle-susceptible and normal RBCs; the former can have a selective survival advantage leading to their overrepresentation. We identified the level of bone marrow chimerism required for successful stem cell-based gene therapies in SCD. Our findings were further informed using an experimental mouse model, where we transplanted mixtures of Berkeley SCD and normal murine bone marrow cells to establish chimeric grafts in murine hosts. Our integrative theoretical and experimental approach identifies the target frequency of HSC alterations required for effective treatment of sickling syndromes in humans. Our work replaces episodic observations of such target frequencies with a mathematical modeling framework that covers a large and continuous spectrum of chimerism conditions. (C) 2016 Wiley Periodicals, Inc. C1 [Altrock, Philipp M.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Mailstop CLS-11007,450 Brookline Ave, Boston, MA 02115 USA. [Altrock, Philipp M.; Michor, Franziska] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Altrock, Philipp M.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Brendel, Christian; Renella, Raffaele; Orkin, Stuart H.; Williams, David A.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Brendel, Christian; Renella, Raffaele; Orkin, Stuart H.; Williams, David A.] Harvard Med Sch, Boston, MA USA. [Renella, Raffaele; Orkin, Stuart H.; Williams, David A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Cambridge, MA USA. [Orkin, Stuart H.; Williams, David A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Renella, Raffaele] CHU Vaudois, Dept Med Chirurg Pediat, Lausanne, Sui, Switzerland. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Mailstop CLS-11007,450 Brookline Ave, Boston, MA 02115 USA.; Williams, DA (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu FU Deutsche Akademie der Naturforscher Leopoldina [LPDS 2012-12]; NIH [HL117720-03]; Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54CA193461] FX Contract grant sponsor: Deutsche Akademie der Naturforscher Leopoldina; Contract grant number: LPDS 2012-12.; Contract grant sponsor: NIH; Contract grant number: HL117720-03.; Contract grant sponsor: Dana-Farber Cancer Institute Physical Sciences-Oncology Center; Contract grant number: U54CA193461. NR 45 TC 2 Z9 2 U1 5 U2 5 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 SEP PY 2016 VL 91 IS 9 BP 931 EP 937 DI 10.1002/ajh.24449 PG 7 WC Hematology SC Hematology GA DY6LT UT WOS:000385237100162 PM 27299299 ER PT J AU Azar, SS Larson, EA Recht, M Taylor, JA AF Azar, Sharl S. Larson, Emily A. Recht, Michael Taylor, Jason A. TI EVALUATION OF THE CYTOKINE PROFILE OF HUMAN DERIVED FACTOR VIII (FVIII) PRODUCTS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Azar, Sharl S.; Recht, Michael; Taylor, Jason A.] Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. [Azar, Sharl S.; Larson, Emily A.; Taylor, Jason A.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2016 VL 91 IS 9 MA F30 BP E409 EP E410 PG 2 WC Hematology SC Hematology GA DY6LT UT WOS:000385237100108 ER PT J AU Gay, ND Azar, SS Salomon, O Taylor, JA AF Gay, Nathan D. Azar, Sharl S. Salomon, Ophira Taylor, Jason A. TI MANAGEMENT OF A PATIENT WITH FACTOR XI DEFICIENCY WITH INHIBITORS UNDERGOING CARDIAC SURGERY: A CASE REPORT AND REVIEW OF THE LITERATURE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Gay, Nathan D.; Azar, Sharl S.; Taylor, Jason A.] Oregon Hlth & Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Azar, Sharl S.; Taylor, Jason A.] Oregon Hlth & Sci Univ, Hemophilia Ctr, Portland, OR 97201 USA. [Azar, Sharl S.; Taylor, Jason A.] Portland VA Med Ctr, Portland, OR USA. [Salomon, Ophira] Chaim Sheba Med Ctr, Amalia Biron Res Inst Thrombosis & Hemostasis, Tel Hashomer, Israel. [Salomon, Ophira] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2016 VL 91 IS 9 MA F37 BP E413 EP E413 PG 1 WC Hematology SC Hematology GA DY6LT UT WOS:000385237100115 ER PT J AU Porter, AL Staresinic, CE Margolis, AR Ray, CA Schoen, RR Fletcher, CD AF Porter, Andrea L. Staresinic, Carla E. Margolis, Amanda R. Ray, Cheryl A. Schoen, Rebecca R. Fletcher, Christopher D. TI BASELINE CHARACTERISTICS OF PATIENTS ON AN EXTENDED INTERVAL OF INTERNATIONAL NORMALIZED RATIO FOLLOW-UP PROTOCOL IN AN ANTICOAGULATION CLINIC SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Porter, Andrea L.; Staresinic, Carla E.; Margolis, Amanda R.; Ray, Cheryl A.; Schoen, Rebecca R.; Fletcher, Christopher D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Porter, Andrea L.; Margolis, Amanda R.] Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA. [Fletcher, Christopher D.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2016 VL 91 IS 9 MA T2 BP E363 EP E363 PG 1 WC Hematology SC Hematology GA DY6LT UT WOS:000385237100014 ER PT J AU Navathe, AS Sen, AP Rosenthal, MB Pearl, RM Ubel, PA Emanuel, EJ Volpp, KG AF Navathe, Amol S. Sen, Aditi P. Rosenthal, Meredith B. Pearl, Robert M. Ubel, Peter A. Emanuel, Ezekiel J. Volpp, Kevin G. TI New Strategies for Aligning Physicians With Health System Incentives SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material C1 [Navathe, Amol S.; Emanuel, Ezekiel J.; Volpp, Kevin G.] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Navathe, Amol S.; Volpp, Kevin G.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Navathe, Amol S.; Sen, Aditi P.; Emanuel, Ezekiel J.; Volpp, Kevin G.] Leonard Davis Inst Ctr Hlth Incentives & Behav Ec, Philadelphia, PA USA. [Navathe, Amol S.; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Sen, Aditi P.; Emanuel, Ezekiel J.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Rosenthal, Meredith B.] Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Pearl, Robert M.] Permanente Med Grp Inc, Oakland, CA USA. [Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Ubel, Peter A.] Duke Univ, Sanford Sch Publ Policy, Durham, NC USA. RP Navathe, AS (reprint author), Univ Penn, Dept Med Eth & Hlth Policy, Hlth Policy & Med, 1108 Blockley Hall, Philadelphia, PA 19104 USA. EM amol@wharton.upenn.edu FU Commonwealth Fund FX This work has been partially supported by a grant from the Commonwealth Fund. The funding source reviewed the manuscript but did not make any fundamental alterations. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2016 VL 22 IS 9 BP 610 EP 612 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DX9UC UT WOS:000384740300010 PM 27662223 ER PT J AU Saytashev, I Glenn, R Murashova, GA Osseiran, S Spence, D Evans, CL Dantus, M AF Saytashev, Ilyas Glenn, Rachel Murashova, Gabrielle A. Osseiran, Sam Spence, Dana Evans, Conor L. Dantus, Marcos TI Multiphoton excited hemoglobin fluorescence and third harmonic generation for non-invasive microscopy of stored blood SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID CELL STORAGE; RED-CELLS; 3RD-HARMONIC GENERATION; HUMAN ERYTHROCYTES; FIBER LASER; IN-VIVO; TRANSFUSION; EXCITATION; DURATION; DEFORMABILITY AB Red blood cells (RBC) in two-photon excited fluorescence (TPEF) microscopy usually appear as dark disks because of their low fluorescent signal. Here we use 15fs 800nm pulses for TPEF, 45fs 1060nm pulses for three-photon excited fluorescence, and third harmonic generation (THG) imaging. We find sufficient fluorescent signal that we attribute to hemoglobin fluorescence after comparing time and wavelength resolved spectra of other expected RBC endogenous fluorophores: NADH, FAD, biliverdin, and bilirubin. We find that both TPEF and THG microscopy can be used to examine erythrocyte morphology noninvasively without breaching a blood storage bag. (C) 2016 Optical Society of America C1 [Saytashev, Ilyas; Glenn, Rachel; Murashova, Gabrielle A.; Spence, Dana; Dantus, Marcos] Michigan State Univ, Dept Chem, 578 S Shaw Ln, E Lansing, MI 48824 USA. [Osseiran, Sam] Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave E25-519, Cambridge, MA 02139 USA. [Osseiran, Sam; Evans, Conor L.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. [Dantus, Marcos] Michigan State Univ, Dept Phys & Astron, 567 Wilson Rd, E Lansing, MI 48824 USA. RP Dantus, M (reprint author), Michigan State Univ, Dept Chem, 578 S Shaw Ln, E Lansing, MI 48824 USA.; Dantus, M (reprint author), Michigan State Univ, Dept Phys & Astron, 567 Wilson Rd, E Lansing, MI 48824 USA. EM dantus@msu.edu FU NSF [CHE-1464807]; NIH [EB016379]; Frances Keany Rickard Fund Fellowship via MIT FX Partial support for the MD group comes from NSF grant CHE-1464807. Support for the DS group comes from NIH grant EB016379. SO acknowledges the support of the Henry C. (1926) and Frances Keany Rickard Fund Fellowship via MIT. NR 41 TC 0 Z9 0 U1 5 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD SEP 1 PY 2016 VL 7 IS 9 BP 3449 EP 3460 DI 10.1364/BOE.7.003449 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DY8XU UT WOS:000385416500023 PM 27699111 ER PT J AU Langevin, JP Chen, JWY Koek, RJ Sultzer, DL Mandelkern, MA Schwartz, HN Krahl, SE AF Langevin, Jean-Philippe Chen, James W. Y. Koek, Ralph J. Sultzer, David L. Mandelkern, Mark A. Schwartz, Holly N. Krahl, Scott E. TI Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings SO BRAIN SCIENCES LA English DT Article DE amygdala; basolateral nucleus; deep brain stimulation; microelectrode recording; PTSD; targeting technique ID POSTTRAUMATIC-STRESS-DISORDER; CIRCUIT; CORTEX; FEAR AB The amygdala plays a critical role in emotion regulation. It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe our targeting technique, and intra-operative and post-operative electrodiagnostic findings associated with the placement of deep brain stimulation (DBS) electrodes in the amygdala. We used a transfrontal approach to implant DBS electrodes in the basolateral nucleus of the amygdala (BLn) of a patient suffering from severe post-traumatic stress disorder. We used microelectrode recording (MER) and awake intra-operative neurostimulation to assist with the placement. Post-operatively, the patient underwent monthly surveillance electroencephalograms (EEG). MER predicted the trajectory of the electrode through the amygdala. The right BLn showed a higher spike frequency than the left BLn. Intra-operative neurostimulation of the BLn elicited pleasant memories. The monthly EEG showed the presence of more sleep patterns over time with DBS. BLn DBS electrodes can be placed using a transfrontal approach. MER can predict the trajectory of the electrode in the amygdala and it may reflect the BLn neuronal activity underlying post-traumatic stress disorder PTSD. The EEG findings may underscore the reduction in anxiety. C1 [Langevin, Jean-Philippe] VA Greater Los Angeles Healthcare Syst, Neurosurg Serv, Los Angeles, CA 90073 USA. [Chen, James W. Y.] VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. [Koek, Ralph J.; Sultzer, David L.; Schwartz, Holly N.] VA Greater Los Angeles Healthcare Syst, Psychiat & Mental Hlth Serv, Los Angeles, CA 90073 USA. [Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Nucl Med, Serv Radiol, Los Angeles, CA 90073 USA. [Krahl, Scott E.] VA Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. RP Langevin, JP (reprint author), VA Greater Los Angeles Healthcare Syst, Neurosurg Serv, Los Angeles, CA 90073 USA. EM jean-philippe.langevin@va.gov; james.chen1@va.gov; ralph.koek@va.gov; david.sultzer@va.gov; mark.mandelkern@va.gov; holly.schwartz@va.gov; scott.krahl@va.gov NR 20 TC 0 Z9 0 U1 3 U2 3 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2076-3425 EI 2976-3425 J9 BRAIN SCI JI Brain Sci. PD SEP PY 2016 VL 6 IS 3 AR 28 DI 10.3390/brainsci6030028 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DY9XH UT WOS:000385488600009 ER PT J AU Sonny, A Ibrahim, A Schuster, A Jaber, WA Cywinski, JB AF Sonny, Abraham Ibrahim, Ahmed Schuster, Andres Jaber, Wael A. Cywinski, Jacek B. TI Impact and persistence of cirrhotic cardiomyopathy after liver transplantation SO CLINICAL TRANSPLANTATION LA English DT Article DE cirrhotic cardiomyopathy; QTc; diastolic dysfunction; liver transplantation; mortality ID VENTRICULAR DIASTOLIC DYSFUNCTION; CORRECTED QT INTERVAL; HEART-FAILURE; DISEASE; PROLONGATION; ECHOCARDIOGRAPHY; PREVALENCE; RECIPIENTS; SEVERITY; ETIOLOGY AB Cirrhotic cardiomyopathy causes variable degree of systolic and diastolic dysfunction (DD) and conduction abnormalities. The primary aim of our study was to determine whether pre-transplant DD and prolonged corrected QT (QTc) predict a composite of mortality, graft failure, and major cardiovascular events after liver transplantation. We also evaluated the reversibility of cirrhotic cardiomyopathy after transplantation. Adult patients who underwent liver transplantation at our institution from January 2007 to March 2009 were included. Data were obtained from institutional registry, medical record review, and evaluation of echocardiographic images. Among 243 patients, 113 (46.5%) had grade 1 DD, 16 (6.6%) had grade 2 DD, and none had grade 3 DD. The mean pre-transplant QTc was 453 milliseconds. After a mean post-transplant follow-up of 5.2 years, 75 (31%) patients satisfied the primary composite outcome. Cox regression analysis did not show any significant association between DD and the composite outcome (P=.17). However, longer QTc was independently associated with the composite outcome (HR: 1.01, 95% confidence interval: 1.001.02, P=.05). DD (P<.001) and left ventricular mass index (P=.001) worsened after transplantation. In conclusion, QTc prolongation appears to be associated with worse outcomes. Although DD did not impact outcomes, it significantly worsened after transplantation. C1 [Sonny, Abraham] Cleveland Clin, Inst Anesthesiol, Cleveland, OH 44106 USA. [Ibrahim, Ahmed; Schuster, Andres; Jaber, Wael A.] Cleveland Clin, Heart & Vasc Inst, Cleveland, OH 44106 USA. [Cywinski, Jacek B.] Cleveland Clin, Outcomes Res & Transplantat Ctr, Dept Gen Anesthesiol, Cleveland, OH 44106 USA. [Sonny, Abraham] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Schuster, Andres] Clin Alemana Santiago, Dept Cardiol, Santiago, Chile. RP Cywinski, JB (reprint author), Cleveland Clin, Dept Gen Anesthesiol, 9500 Euclid Ave E31, Cleveland, OH 44195 USA. EM cywinsj@ccf.org NR 25 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-0063 EI 1399-0012 J9 CLIN TRANSPLANT JI Clin. Transplant. PD SEP PY 2016 VL 30 IS 9 BP 986 EP 993 DI 10.1111/ctr.12778 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA DZ3OQ UT WOS:000385758400003 PM 27292629 ER PT J AU Kehle-Forbes, SM Drapkin, ML Foa, EB Koffel, E Lynch, KG Polusny, MA Van Horn, DHA Yusko, DA Charlesworth, M Blasco, M Oslin, DW AF Kehle-Forbes, Shannon M. Drapkin, Michelle L. Foa, Edna B. Koffel, Erin Lynch, Kevin G. Polusny, Melissa A. Van Horn, Deborah H. A. Yusko, David A. Charlesworth, Molly Blasco, Molly Oslin, David W. TI Study design, interventions, and baseline characteristics for the Substance use and TRauma Intervention for VEterans (STRIVE) trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Posttraumatic stress disorder; Substance use disorders; Veterans Randomized clinical trial; Prolonged Exposure therapy; Motivational Enhancement Therapy ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; ALCOHOL DEPENDENCE; CLINICAL-TRIAL; PSYCHOLOGICAL TREATMENTS; PSYCHOMETRIC PROPERTIES; IMAGINAL EXPOSURE; MENTAL-HEALTH; PTSD; THERAPY AB While comorbidity between posttraumatic stress disorder (PTSD) and substance use disorders (SUD) is common among veterans, there is debate regarding how to best treat individuals suffering from both conditions. Despite data supporting the effectiveness of integrated treatments that simultaneously address both disorders, due to concerns that an early focus on trauma may increase dropout and reduce the likelihood of achieving SUD-related goals, providers continue to prefer a sequential approach, where the addiction is treated first and PTSD treatment is instituted following sustained abstinence or reduced use. This project is designed to directly examine these provider concerns by evaluating the benefits and harms of an integrated versus a sequential approach to treating comorbid PTSD and SUD. This paper reviews the study's methodology, treatment approaches, and baseline participant characteristics. In this randomized clinical trial, one hundred eighty-three veterans with co-occurring PTSD and SUD have been randomized to one of two psychotherapies that include the same treatment components for SUD and PTSD (Motivational Enhancement Therapy and Prolonged Exposure respectively), but differ by whether the components are delivered sequentially or are integrated such that PTSD and SUD symptoms are addressed concurrently. We hypothesize that veterans assigned to integrated treatment will show greater improvement in PTSD and SUD symptoms than veterans assigned to sequential treatment. If this hypothesis is supported, the findings have the potential to change clinicians' beliefs and challenge long-standing practice patterns that require participation in SUD treatment prior to initiating trauma-focused therapies for PTSD. Published by Elsevier Inc. C1 [Kehle-Forbes, Shannon M.] VA Boston Healthcare Syst, Natl Ctr, PTSD Womens Hlth Sci Div, Boston, MA 02130 USA. [Kehle-Forbes, Shannon M.; Koffel, Erin; Polusny, Melissa A.; Charlesworth, Molly] Minneapolis VA Healthcare Syst, Minneapolis, MN 55417 USA. [Kehle-Forbes, Shannon M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Drapkin, Michelle L.] Rutgers State Univ, New Brunswick, NJ 08901 USA. [Drapkin, Michelle L.; Blasco, Molly; Oslin, David W.] Corporal Michael J Crescenz VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Drapkin, Michelle L.; Blasco, Molly; Oslin, David W.] Ctr Excellence Subst Abuse Treatment & Evaluat, Philadelphia, PA 19104 USA. [Foa, Edna B.; Lynch, Kevin G.; Van Horn, Deborah H. A.; Yusko, David A.; Oslin, David W.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Koffel, Erin; Polusny, Melissa A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA. RP Kehle-Forbes, SM (reprint author), Minneapolis VA Med Ctr, One Vet Dr 152, Minneapolis, MN 55417 USA. EM Shannon.Kehle-Forbes@va.gov FU Merit Review Award from the United States (U.S.) Department of Veterans Affairs [ZDA1-03-W10]; Clinical Science Research Development; Health Services Research & Development Career Development Award [09-020]; Mental Illness Research, Education, and Clinical Center; Center of Excellence for Substance Abuse Treatment and Evaluation at the CMCVAMC FX None of the authors declare conflicts of interest. This material is based upon work supported by Merit Review Award # ZDA1-03-W10 from the United States (U.S.) Department of Veterans Affairs, Clinical Science Research & Development. Dr. Kehle-Forbes was supported by a Health Services Research & Development Career Development Award (09-020). Support was also provided by the Mental Illness Research, Education, and Clinical Center at the Corporal Michael J. Crescenz VA Medical Center (CMCVAMC) and Center of Excellence for Substance Abuse Treatment and Evaluation at the CMCVAMC. ClinicalTrials.gov Identifier: NCT01211106. The funder had no involvement in the study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit this article for publication. NR 59 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2016 VL 50 BP 45 EP 53 DI 10.1016/j.cct.2016.07.017 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DY7PM UT WOS:000385321600007 PM 27444425 ER PT J AU Park, ER Ostroff, JS Perez, GK Hyland, KA Rigotti, NA Borderud, S Regan, S Muzikansky, A Friedman, ER Levy, DE Holland, S Eusebio, J Peterson, L Rabin, J Miller-Sobel, J Gonzalez, I Malloy, L O'Brien, M de Leon-Sanchez, S Whitlock, CW AF Park, Elyse R. Ostroff, Jamie S. Perez, Giselle K. Hyland, Kelly A. Rigotti, Nancy A. Borderud, Sarah Regan, Susan Muzikansky, Alona Friedman, Emily R. Levy, Douglas E. Holland, Susan Eusebio, Justin Peterson, Lisa Rabin, Julia Miller-Sobel, Jacob Gonzalez, Irina Malloy, Laura O'Brien, Maureen de Leon-Sanchez, Suhana Whitlock, C. Will TI Integrating tobacco treatment into cancer care: Study protocol for a randomized controlled comparative effectiveness trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Smoking cessation; Tobacco treatment; Cancer patients; Randomized controlled trial; Motivational interviewing; Pharmacotherapy ID CELL LUNG-CANCER; 2ND PRIMARY CANCERS; SMOKING-CESSATION; 2ND-PRIMARY TUMORS; CIGARETTE-SMOKING; QUIT-SMOKING; NECK CANCER; DIAGNOSIS; NICOTINE; DEPENDENCE AB Background: Despite the well-established risks of persistent smoking, 10-30% of cancer patients continue to smoke after diagnosis. Evidence-based tobacco treatment has yet to be integrated into routine oncology care. This paper describes the protocol, manualized treatment, evaluation plan, and overall study design of comparing the effectiveness and cost of two treatments across two major cancer centers. Methods/design: A two-arm, two-site randomized controlled comparative effectiveness trial is testing the hypothesis that an Intensive Treatment (IT) intervention is more effective than a Standard Treatment (ST) intervention in helping recently diagnosed cancer patients quit smoking. Both interventions include 4 weekly counseling sessions and FDA-approved smoking cessation medication advice. The IT includes an additional 4 biweekly and 3 monthly booster sessions as well as dispensal of the recommended FDA-approved smoking cessation medication at no cost. The trial is enrolling patients with suspected or newly diagnosed cancer who have smoked a cigarette in the past 30 days. Participants are randomly assigned to receive the ST or IT condition. Tobacco cessation outcomes are assessed at 3 and 6 months. The primary study outcome is 7-day point prevalence biochemically-validated tobacco abstinence. Secondary study outcomes include the incremental cost-effectiveness of the IT vs. ST. Discussion: This trial will answer key questions about delivering tobacco treatment interventions to newly diagnosed cancer patients. If found to be efficacious and cost-effective, this treatment will serve as a model to be integrated into oncology care settings nation-wide, as we strive to improve treatment outcomes and quality of life for cancer patients. (C) 2016 Published by Elsevier Inc. C1 [Park, Elyse R.; Perez, Giselle K.; Rigotti, Nancy A.; Regan, Susan; Friedman, Emily R.; Levy, Douglas E.; Rabin, Julia] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Ostroff, Jamie S.; Borderud, Sarah; Holland, Susan; Peterson, Lisa; Miller-Sobel, Jacob; O'Brien, Maureen; de Leon-Sanchez, Suhana; Whitlock, C. Will] Mem Sloan Kettering Canc Ctr, Tobacco Treatment Program, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA. [Hyland, Kelly A.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Park, Elyse R.; Friedman, Emily R.; Eusebio, Justin; Rabin, Julia] Massachusetts Gen Hosp, Canc Outcomes Res Program, Boston, MA 02114 USA. [Park, Elyse R.; Gonzalez, Irina] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Park, Elyse R.; Malloy, Laura] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Park, Elyse R.; Rigotti, Nancy A.] Harvard Med Sch, Dept Med, Boston, MA USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.; Park, ER (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.; Park, ER (reprint author), Massachusetts Gen Hosp, Canc Outcomes Res Program, Boston, MA 02114 USA.; Park, ER (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.; Park, ER (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA.; Park, ER (reprint author), Harvard Med Sch, Dept Med, Boston, MA USA. EM epark@mgh.harvard.edu; ostroffj@mskcc.org; gperez@mgh.harvard.edu; khyland@mail.usf.edu; nrigotti@partners.org; borderus@mskcc.org; sregan@mgh.harvard.edu; amuzikansky@mgh.harvard.edu; erfriedman@mgh.harvard.edu; dlevy3@mgh.harvard.edu; hollands@mskcc.org; jeusebio@mgh.harvard.edu; petersol@mskcc.org; jtrabin@mgh.harvard.edu; millersj@mskcc.org; igonzalez4@mgh.harvard.edu; lmalloy@mgh.harvard.edu; obrienm@mskcc.org; deleonss@mskcc.org; whitlocc@mskcc.org FU National Cancer Institute [5 R01 CA166147-05] FX This work was supported by the National Cancer Institute (5 R01 CA166147-05). The NIH/NCI had no role in the design, data collection or analysis, writing of this article, or decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 92 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2016 VL 50 BP 54 EP 65 DI 10.1016/j.cct.2016.07.016 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DY7PM UT WOS:000385321600008 PM 27444428 ER PT J AU Fox, RJ Coffey, CS Cudkowicz, ME Gleason, T Goodman, A Klawiter, EC Matsuda, K McGovern, M Conwit, R Naismith, R Ashokkumar, A Bermel, R Ecklund, D Koepp, M Long, J Natarajan, S Ramachandran, S Skaramagas, T Thornell, B Yankey, J Agius, M Bashir, K Cohen, B Coyle, P Delgado, S Dewitt, D Flores, A Giesser, B Goldman, M Jubelt, B Lava, N Lynch, S Miravalle, A Moses, H Ontaneda, D Perumal, J Racke, M Repovic, P Riley, C Severson, C Shinnar, S Suski, V Weinstock-Gutman, B Yadav, V Zabeti, A AF Fox, Robert J. Coffey, Christopher S. Cudkowicz, Merit E. Gleason, Trevis Goodman, Andrew Klawiter, Eric C. Matsuda, Kazuko McGovern, Michelle Conwit, Robin Naismith, Robert Ashokkumar, Akshata Bermel, Robert Ecklund, Dixie Koepp, Maxine Long, Jeffrey Natarajan, Sneha Ramachandran, Srividya Skaramagas, Thomai Thornell, Brenda Yankey, Jon Agius, Mark Bashir, Khurram Cohen, Bruce Coyle, Patricia Delgado, Silvia Dewitt, Dana Flores, Angela Giesser, Barbara Goldman, Myla Jubelt, Burk Lava, Neil Lynch, Sharon Miravalle, Augusto Moses, Harold Ontaneda, Daniel Perumal, Jai Racke, Michael Repovic, Pavle Riley, Claire Severson, Christopher Shinnar, Shlomo Suski, Valerie Weinstock-Gutman, Bianca Yadav, Vijayshree Zabeti, Aram TI Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Clinical trial; Ibudilast; Progressive multiple sclerosis; Magnetic resonance imaging ID BRAIN ATROPHY; FUNCTIONAL COMPOSITE; PHOSPHODIESTERASE INHIBITORS; MECHANICAL ALLODYNIA; NEUROPATHIC PAIN; LESION LOAD; RATS; NEUROPROTECTION; IMPAIRMENT; DISABILITY AB Background: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. Methods: SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100 mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. Results: A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. Conclusion: SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of concept PMS trials. (C) 2016 Elsevier Inc. All rights reserved. C1 [Fox, Robert J.; Bermel, Robert; Natarajan, Sneha; Ramachandran, Srividya; Skaramagas, Thomai; Ontaneda, Daniel] Cleveland Clin, Neurol Inst, Cleveland, OH 44106 USA. [Coffey, Christopher S.; Ashokkumar, Akshata; Ecklund, Dixie; Koepp, Maxine; Long, Jeffrey; Yankey, Jon] Univ Iowa, Data Coordinating Ctr, NeuroNEXT, Iowa City, IA USA. [Cudkowicz, Merit E.; McGovern, Michelle; Thornell, Brenda] Harvard Partners, Clin Coordinating Ctr, NeuroNEXT, Boston, MA USA. [Gleason, Trevis] Patient Advocate, Seattle, WA USA. [Goodman, Andrew] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Klawiter, Eric C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matsuda, Kazuko] Medicinova Inc, La Jolla, CA USA. [Conwit, Robin] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Naismith, Robert] Washington Univ, Sch Med, St Louis, MO USA. [Agius, Mark] Univ Calif Davis, Sacramento, CA 95817 USA. [Agius, Mark] Barrows Neurol Inst, Phoenix, AZ USA. [Bashir, Khurram] Univ Alabama Birmingham, Birmingham, AL USA. [Cohen, Bruce] Northwestern Univ, Chicago, IL 60611 USA. [Coyle, Patricia] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Delgado, Silvia] Univ Miami, Sch Med, Miami, FL USA. [Dewitt, Dana] Univ Utah, Salt Lake City, UT USA. [Flores, Angela] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Giesser, Barbara] Univ Calif Los Angeles, Los Angeles, CA USA. [Goldman, Myla] Univ Virginia, Charlottesville, VA USA. [Jubelt, Burk] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Lava, Neil] Emory Univ, Atlanta, GA 30322 USA. [Lynch, Sharon] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Miravalle, Augusto] Univ Colorado Denver, Aurora, CO USA. [Moses, Harold] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Perumal, Jai] Weill Cornell Med Coll, New York, NY USA. [Racke, Michael] Ohio State Univ, Columbus, OH 43210 USA. [Repovic, Pavle] Swedish Med Ctr Seattle, Seattle, WA USA. [Riley, Claire] Columbia Univ, Med Ctr, New York, NY USA. [Severson, Christopher] Brigham & Womens Hosp, Brookline, MA USA. [Shinnar, Shlomo] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Suski, Valerie] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Weinstock-Gutman, Bianca] SUNY Buffalo, Buffalo, NY USA. [Yadav, Vijayshree] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Zabeti, Aram] Univ Cincinnati, Cincinnati, OH USA. RP Fox, RJ (reprint author), Cleveland Clin, Mellen Ctr Multiple Sclerosis, 9500 Euclic Ave,U10, Cleveland, OH 44195 USA. EM foxr@ccf.org RI Goldman, Myla/D-1955-2017 FU NINDS [U01NS082329]; NMSS [RG 4778-A-6]; NINDS (Central Coordinating Center) [U01NS077179]; NINDS (Data Coordinating Center) [U01NS077352] FX This study was funded by the NINDS (U01NS082329) and NMSS (RG 4778-A-6). Ibudilast study drug was provided at no cost by MediciNova Inc. The NeuroNEXT Network is supported by the NINDS (Central Coordinating Center: U01NS077179, Data Coordinating Center: U01NS077352). We thank Dr. Elizabeth McNeil, the former program manager at NINDS, for her steady support through the trial development and start-up process. This study was made possible by the dedication and support of people with MS who volunteered to participate as well as their families and friends who support their involvement in this study. NR 54 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 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2016 VL 50 BP 166 EP 177 DI 10.1016/j.cct.2016.08.009 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DY7PM UT WOS:000385321600021 PM 27521810 ER PT J AU Grunfeld, C Dankner, R AF Grunfeld, Carl Dankner, Rachel TI Diabetes in HIV-infected persons in Cameroon? SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material DE diabetes; HIV-infected patients; protease inhibitors AB In the past, the increased prevalence of diabetes in HIV infection has been attributed to antiretroviral drugs. In this study, Cameroonians with HIV infection were shown in a paper in this issue of the Journal to be more likely to have diabetes if they were not on therapy. Future research should examine if the diabetes is related to the host response to infection or to socioeconomic factors that might both contribute to not being on anti-retroviral therapy and predispose to diabetes. Copyright (C) 2016 John Wiley & Sons, Ltd. C1 [Grunfeld, Carl] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Grunfeld, Carl] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA USA. [Grunfeld, Carl] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Dankner, Rachel] Tel Aviv Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth, IL-69978 Tel Aviv, Israel. [Dankner, Rachel] Feinstein Inst Med Res, Patient Oriented Res, Manhasset, NY USA. RP Grunfeld, C (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM carl.grunfeld@ucsf.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD SEP PY 2016 VL 32 IS 6 BP 512 EP 513 DI 10.1002/dmrr.2796 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ2ZR UT WOS:000385712700005 PM 26936763 ER PT J AU Uren, C Kim, M Martin, AR Bobo, D Gignoux, CR van Helden, PD Moller, M Hoal, EG Henn, BM AF Uren, Caitlin Kim, Minju Martin, Alicia R. Bobo, Dean Gignoux, Christopher R. van Helden, Paul D. Moller, Marlo Hoal, Eileen G. Henn, Brenna M. TI Fine-Scale Human Population Structure in Southern Africa Reflects Ecogeographic Boundaries SO GENETICS LA English DT Article DE ancestry; population structure; KhoeSan; pastoralism ID LACTASE PERSISTENCE ALLELES; GENOMIC DIVERSITY; LOCAL-ANCESTRY; MTDNA; HISTORY; LINEAGES; EUROPE; KHOE; PASTORALISTS; SUBSTRUCTURE AB Recent genetic studies have established that the KhoeSan populations of southern Africa are distinct from all other African populations and have remained largely isolated during human prehistory until approximate to 2000 years ago. Dozens of different KhoeSan groups exist, belonging to three different language families, but very little is known about their population history. We examine new genome-wide polymorphism data and whole mitochondrial genomes for >100 South Africans from the Khomani San and Nama populations of the Northern Cape, analyzed in conjunction with 19 additional southern African populations. Our analyses reveal fine-scale population structure in and around the Kalahari Desert. Surprisingly, this structure does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. Regardless of subsistence strategy, the indigenous Khoe-speaking Nama pastoralists and the N|u-speaking Khomani (formerly hunter-gatherers) share ancestry with other Khoe-speaking forager populations that form a rim around the Kalahari Desert. We reconstruct earlier migration patterns and estimate that the southern Kalahari populations were among the last to experience gene flow from Bantu speakers, approximate to 14 generations ago. We conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited genetic impact from eastern Africa. C1 [Uren, Caitlin; van Helden, Paul D.; Moller, Marlo; Hoal, Eileen G.] Univ Stellenbosch, South African Med Res Council Ctr TB Res, Natl Res Fdn Ctr Excellence Biomed TB Res, Dept Sci & Technol,Div Mol Biol & Human Genet,Fac, ZA-8000 Cape Town, South Africa. [Kim, Minju; Bobo, Dean; Henn, Brenna M.] SUNY Stony Brook, Dept Ecol & Evolut, New York, NY 11794 USA. [Martin, Alicia R.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Martin, Alicia R.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Gignoux, Christopher R.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Henn, BM (reprint author), Dept Ecol & Evolut, Life Sci Bldg,Room 640, Stony Brook, NY 11794 USA.; Hoal, EG (reprint author), SA MRC Ctr TB Res, DST NRF Ctr Excellence Biomed TB Res, Div Mol Biol & Human Genet, Fac Med & Hlth Sci, Tygerberg Campus, ZA-7500 Parow, South Africa. EM egvh@sun.ac.za; brenna.henn@stonybrook.edu OI Moller, Marlo/0000-0002-0805-6741; Martin, Alicia/0000-0003-0241-3522 FU Stanford University Center on the Demographics and Economics of Health and Aging CDEHA seed grant [NIA P30 AG017253-12]; Stanford University Computation, Evolutionary, and Human Genomics trainee research grant; National Research Foundation of South Africa; [32] FX We thank Jeffrey Kidd for assisting with genotyping of samples, David Poznik for providing off-target mtDNA reads from a separate next-generation sequencing experiment, Aaron Behr and Sohini Ramachandran for prepublication use of pong, and Meng Lin for help with analyses. We thank Carlos Bustamante for his encouragement and support of this project and Marcus Feldman for a close reading of our manuscript. We thank Julie Granka, Justin Myrick, and Cedric Werely for assistance with the saliva sample collection and Ben Viljoen for DNA extractions. Guidance from Ryan Raaum with regards to formulating the surface plots is appreciated. We also thank the Working Group of Indigenous Minorities in Southern Africa and the South African San Institute for their encouragement and advice. Finally, we thank Richard Jacobs, Wilhelmina Mondzinger, Hans Padmaker, Willem de Klerk, Hendrik Kaiman, and the communities in which we have sampled; without their support, this study would not have been possible. Funding was provided by a Stanford University Center on the Demographics and Economics of Health and Aging CDEHA seed grant to B.M.H. (National Institutes of Health, National Institute of Aging, NIA P30 AG017253-12) as well as a Stanford University Computation, Evolutionary, and Human Genomics trainee research grant to A.R.M. C.U. was funded by the National Research Foundation of South Africa. C.R.G. was funded by Predoctoral Training Grant 32. NR 64 TC 1 Z9 1 U1 4 U2 4 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 2016 VL 204 IS 1 BP 303 EP + DI 10.1534/genetics.116.187369 PG 36 WC Genetics & Heredity SC Genetics & Heredity GA DW9RD UT WOS:000383998500026 PM 27474727 ER PT J AU Gattoni-Celli, S Young, MRI AF Gattoni-Celli, Sebastiano Young, M. Rita I. TI Restoration of Immune Responsiveness to Glioma by Vaccination of Mice with Established Brain Gliomas with a Semi-Allogeneic Vaccine SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE cytokines; glioblastoma; immune activation; vaccination ID GLIOBLASTOMA; CANCER AB Prior studies had shown the clinical efficacy of a semi-allogeneic glioma vaccine in mice with lethal GL261 gliomas. This was confirmed in the present study. As subcutaneous vaccination resulted in protection against tumor in the brain, the present study assessed the impact of this vaccination of mice bearing established GL261 brain gliomas on their cytokine production upon in vitro exposure to tumor-derived products. Mice with established GL261 brain gliomas were vaccinated subcutaneously with H-2(b) GL261 glioma cells fused with H-2(d) RAG-neo cells or with a mock vaccine of phosphate-buffered saline. The results of these analyses show that the presence of GL261 tumor-conditioned medium resulted in increased production of Th1, inflammatory and inhibitory cytokines by spleen cells from control mice and from vaccinated glioma-bearing mice. In contrast, spleen cells of tumor-bearing, mock-vaccinated mice produced lower levels of cytokines in the presence of tumor-conditioned media. However, these results also show that there was not a heightened level of cytokine production in the presence of tumor-conditioned medium by spleen cells of vaccinated mice over the production by spleen cells of control mice. Overall, these results show that vaccination slows growth of the GL261 tumors to the point where GL261-vaccinated mice do not show the signs of morbidly or splenic dysfunction exhibited by unvaccinated, late stage glioma-bearing mice. C1 [Gattoni-Celli, Sebastiano; Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. [Gattoni-Celli, Sebastiano] Med Univ South Carolina, Dept Radiat Oncol, 173 Ashley Ave, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 173 Ashley Ave, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA.; Young, MRI (reprint author), Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 173 Ashley Ave, Charleston, SC 29425 USA. EM gattonis@musc.edu; rita.young@va.gov FU Department of Veterans Affairs CSR D Merit Awards [I01-CX000851, I01-CX000753] FX This research was funded in part by the Department of Veterans Affairs CSR & D Merit Awards I01-CX000851 (M. Rita I. Young) and I01-CX000753 (Sebastiano Gattoni-Celli). M. Rita I. Young is a Senior Research Career Scientist at the Ralph H. Johnson VA Medical Center (VAMC) and a Professor of Otolaryngology at the Medical University of South Carolina (MUSC) in Charleston, SC, USA. Sebastiano Gattoni-Celli is a Professor of Radiation Oncology at MUSC and a Research Health Scientist at the Ralph H. Johnson VAMC in Charleston, SC, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD SEP PY 2016 VL 17 IS 9 AR 1465 DI 10.3390/ijms17091465 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA DZ0JU UT WOS:000385525500091 ER PT J AU Bhatia, S Storer, BE Iyer, JG Moshiri, A Parvathaneni, U Byrd, D Sober, AJ Sondak, VK Gershenwald, JE Nghiem, P AF Bhatia, Shailender Storer, Barry E. Iyer, Jayasri G. Moshiri, Ata Parvathaneni, Upendra Byrd, David Sober, Arthur J. Sondak, Vernon K. Gershenwald, Jeffrey E. Nghiem, Paul TI Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGE-I; INDEPENDENT PREDICTOR; RADIOTHERAPY; SKIN; POLYOMAVIRUS; RECURRENCE; WIDE AB Background: Merkel cell carcinoma (MCC) has a high risk of recurrence after initial surgical therapy. Adjuvant radiation therapy (RT) and chemotherapy may be used to reduce the risk of locoregional and systemic recurrence, respectively, but there are conflicting data regarding their impact on survival. We performed a retrospective analysis of MCC cases from the National Cancer Data Base (NCDB) to assess whether adjuvant therapy was associated with differences in survival. Methods: Six thousand nine hundred and eight MCC patients with staging, treatment, and survival data were included. Multivariable analyses were conducted for overall survival (OS) with various treatment modalities while adjusting for prognostic variables including age, sex, comorbidities (Charlson/Deyo score), margin status, primary tumor site and size, and lymph node status. All statistical tests were two-sided. Results: For localized MCC (stage I: n = 3369, stage II: n = 1474), surgery plus adjuvant RT was associated with statistically significantly better OS than with surgery alone in multivariable analyses (stage I: hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.80, P < .001; stage II: HR = 0.77, 95% CI = 0.66 to 0.89, P < .001). In patients with regional nodal metastases (stage III: n = 2065), neither adjuvant RT nor chemotherapy was associated with statistically significantly improved or worsened OS. Conclusions: In this study of the largest MCC cohort reported to date, adjuvant RT was associated with improved OS in stages I-II MCC. Neither adjuvant RT nor chemotherapy was associated with improved OS in stage III MCC. These results, with the limitations of retrospective analyses, are consistent with earlier studies suggesting benefit with adjuvant RT but do not support the routine use of adjuvant chemotherapy in MCC. C1 [Bhatia, Shailender; Storer, Barry E.; Iyer, Jayasri G.; Moshiri, Ata; Parvathaneni, Upendra; Byrd, David; Nghiem, Paul] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Sober, Arthur J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sondak, Vernon K.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Bhatia, S (reprint author), 825 Eastlake Ave E, Seattle, WA 98109 USA.; Nghiem, P (reprint author), 850 Republican St,Brotman 242, Seattle, WA 98109 USA. EM sbhatia@uw.edu; pnghiem@uw.edu FU National Center for Advancing Translational Sciences (NCATS) from the National Institutes of Health (NIH) [TL1 TR000422, P30-CA015704-39, K24-CA139052, R01-CA162522]; Michael Piepkorn endowment; Merkel patient gift funds FX This work was supported by: National Center for Advancing Translational Sciences (NCATS) grants TL1 TR000422, P30-CA015704-39, K24-CA139052, and R01-CA162522 from the National Institutes of Health (NIH); Michael Piepkorn endowment; and Merkel patient gift funds. NR 35 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP PY 2016 VL 108 IS 9 AR djw042 DI 10.1093/jnci/djw042 PG 9 WC Oncology SC Oncology GA DZ0KH UT WOS:000385527000004 ER PT J AU Lemanske, RF Kakumanu, S Shanovich, K Antos, N Cloutier, MM Mazyck, D Phipatanakul, W Schantz, S Szefler, S Vandlik, R Williams, P AF Lemanske, Robert F., Jr. Kakumanu, Sujani Shanovich, Kathleen Antos, Nicholas Cloutier, Michelle M. Mazyck, Donna Phipatanakul, Wanda Schantz, Shirley Szefler, Stanley Vandlik, Renee Williams, Paul TI Creation and implementation of SAMPRO (TM): A school-based asthma management program SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; school; school nurse; children; asthma action plan; education; environment; triggers ID ACTION PLANS; CHILDHOOD ASTHMA; HEALTH CENTERS; CARE; CHILDREN; IMPACT; OUTCOMES; BURDEN; NURSES AB Clinicians who care for children with asthma have an obligation to coordinate asthma care with the schools. Aside from routine clinical care of asthmatic children, providers must educate the family and child about the need for an asthma treatment plan in school and support the school nurse meeting the needs of the student requiring school-based asthma care. The following article was developed by multiple stakeholders to address this need. It describes the 4 components of the School-based Asthma Management Program (SAMPRO (TM)). SAMPRO (TM) details elements necessary for the education of children, families, clinicians, and school-based personnel based on a "circle of support'' that would enhance multidirectional communication and promote better care for children with asthma within the school setting. C1 [Lemanske, Robert F., Jr.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat & Med, Madison, WI 53706 USA. [Shanovich, Kathleen] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53706 USA. [Antos, Nicholas] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Cloutier, Michelle M.] Univ Connecticut, Hlth Ctr Farmington, Dept Pediat, Hartford, CT 06112 USA. [Cloutier, Michelle M.] CT Childrens Med Ctr, Asthma Ctr, Hartford, CT USA. [Kakumanu, Sujani] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Kakumanu, Sujani] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Mazyck, Donna; Schantz, Shirley] Natl Assoc Sch Nurses, Silver Spring, MD USA. [Phipatanakul, Wanda] Harvard Med Sch, Boston Childrens Hosp, Div Allergy & Immunol, Boston, MA USA. [Szefler, Stanley] Univ Colorado, Sch Med, Childrens Hosp Colorado, Breathing Inst, Aurora, CO USA. [Szefler, Stanley] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Vandlik, Renee] Amer Acad Allergy Asthma & Immunol, Milwaukee, WI USA. [Williams, Paul] Univ Washington, Sch Med, Allergist NW Asthma & Allergy Ctr, Dept Pediat, Seattle, WA 98195 USA. RP Lemanske, RF (reprint author), 750 Highland Ave 4235 HSLC, Madison, WI 53705 USA. EM rfl@medicine.wisc.edu FU American Academy of Allergy, Asthma Immunology; National Association of School Nurses FX Supported by funds provided by the American Academy of Allergy, Asthma & Immunology and the National Association of School Nurses. NR 35 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 SEP PY 2016 VL 138 IS 3 BP 711 EP 723 DI 10.1016/j.jaci.2016.06.015 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA DY9ZM UT WOS:000385496000006 PM 27596707 ER PT J AU Mattoo, H Mahajan, VS Maehara, T Deshpande, V Della-Torre, E Wallace, ZS Kulikova, M Drijvers, JM Daccache, J Carruthers, MN Castelino, FV Stone, JR Stone, JH Pillai, S AF Mattoo, Hamid Mahajan, Vinay S. Maehara, Takashi Deshpande, Vikram Della-Torre, Emanuel Wallace, Zachary S. Kulikova, Maria Drijvers, Jefte M. Daccache, Joe Carruthers, Mollie N. Castelino, Flavia V. Stone, James R. Stone, John H. Pillai, Shiv TI Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG(4)-related disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Fibrosis; IgG(4)-related disease; IgG4; CD4(+) cytotoxic T cells; T(H)2 cells; rituximab; IL-1 beta ID IGG4-RELATED SYSTEMIC-DISEASE; REGULATORY IMMUNE-REACTIONS; ANTIGEN PRESENTATION; PULMONARY-FIBROSIS; COLLAGEN-SYNTHESIS; PERIPHERAL-BLOOD; MULTIPLE-MYELOMA; FIBROTIC DISEASE; LUNG FIBROBLASTS; IN-VIVO AB Background: IgG(4)-related disease (IgG(4)-RD) is a systemic condition of unknowncause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG(4)-RD lesions. Objective: We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG(4)-RD based on their clonal expansion and ability to infiltrate affected tissue sites. Methods: We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG(4)-RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor beta chain gene was performed on CD4(+) SLAMF7(+) cytotoxic T lymphocytes (CTLs) and CD4(+) GATA3(+) T(H)2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. Results: CD4(+) effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4(+) CTLs but not CD4(+) GATA3(+) memory TH2 cells in patients with IgG4-RD. The dominantTcells infiltrating a range of inflamed IgG(4)-RD tissue sites were clonally expanded CD4(+) CTLs that expressed SLAMF7, granzyme A, IL-1 beta, and TGF-beta 1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4(+) CTLs. Conclusions: IgG(4)-RD is prominently linked to clonally expanded IL-1 beta- and TGF-beta 1-secreting CD4(+) CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4(+) T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. C1 [Mattoo, Hamid; Mahajan, Vinay S.; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S.; Kulikova, Maria; Drijvers, Jefte M.; Daccache, Joe; Carruthers, Mollie N.; Castelino, Flavia V.; Stone, James R.; Stone, John H.; Pillai, Shiv] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Maehara, Takashi] Div Maxillofacial Diagnost & Surg Sci, Sect Oral & Maxillofacial Oncol, Fukuoka, Japan. RP Pillai, S (reprint author), MIT & Harvard, Ragon Inst, Massachusetts Gen Hosp, 400 Tech Sq, Cambridge, MA 02139 USA.; Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org; pillai@helix.mgh.harvard.edu FU National Institutes of Health (NIH) [U19-AI110495, AI 113163]; NIH [S10RR023440] FX Supported by grants U19-AI110495 and AI 113163 from the National Institutes of Health (NIH). The Massachusetts General Hospital flow core is supported by grant S10RR023440 from the NIH. NR 60 TC 10 Z9 10 U1 2 U2 2 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 SEP PY 2016 VL 138 IS 3 BP 825 EP 838 DI 10.1016/j.jaci.2015.12.1330 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA DY9ZM UT WOS:000385496000019 PM 26971690 ER PT J AU Al-Herz, W Chu, JI van der Spek, J Raghupathy, R Massaad, MJ Keles, S Biggs, CM Cockerton, L Chou, J Dbaibo, G Elisofon, SA Hanna-Wakim, R Kim, HB Lehmann, LE McDonald, DR Notarangelo, LD Veys, P Chatila, TA Geha, RS Gaspar, HB Pai, SY AF Al-Herz, Waleed Chu, Julia I. van der Spek, Jet Raghupathy, Raj Massaad, Michel J. Keles, Sevgi Biggs, Catherine M. Cockerton, Lucinda Chou, Janet Dbaibo, Ghassan Elisofon, Scott A. Hanna-Wakim, Rima Kim, Heung Bae Lehmann, Leslie E. McDonald, Douglas R. Notarangelo, Luigi D. Veys, Paul Chatila, Talal A. Geha, Raif S. Gaspar, H. Bobby Pai, Sung-Yun TI Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Primary immunodeficiency; dedicator of cytokinesis 8 deficiency; hematopoietic stem cell transplantation; conditioning mixed chimerism ID HYPER-IGE SYNDROME; DOCK8 DEFICIENCY; MUTATIONS; PHENOTYPE; SURVIVAL AB Background: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited. Objective: We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution. Methods: We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production. Results: Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and T(H)1/T(H)2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination. Conclusion: Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection. C1 [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait. [Raghupathy, Raj] Kuwait Univ, Fac Med, Dept Microbiol, Kuwait, Kuwait. [Al-Herz, Waleed] Al Sabah Hosp, Dept Pediat, Kuwait, Kuwait. [Chu, Julia I.; van der Spek, Jet; Lehmann, Leslie E.; Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Elisofon, Scott A.] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Boston, MA USA. [Kim, Heung Bae] Boston Childrens Hosp, Dept Surg, Boston, MA USA. [Chu, Julia I.; Lehmann, Leslie E.; Pai, Sung-Yun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Massaad, Michel J.; Keles, Sevgi; Biggs, Catherine M.; Chou, Janet; McDonald, Douglas R.; Notarangelo, Luigi D.; Chatila, Talal A.; Geha, Raif S.] Boston Childrens Hosp, Div Immunol, Boston, MA USA. [Cockerton, Lucinda; Veys, Paul; Gaspar, H. Bobby] NHS Fdn Trust, Great Ormond St Hosp Children, London, England. [Dbaibo, Ghassan; Hanna-Wakim, Rima] Amer Univ Beirut, Div Pediat Infect Dis, Beirut, Lebanon. [Gaspar, H. Bobby] UCL Inst Child Hlth, London, England. RP Pai, SY (reprint author), Boston Childrens Hosp, Karp Family Res Labs, Room 08214,One Blackfan Circle, Boston, MA 02115 USA. EM sung-yun.pai@childrens.harvard.edu FU Translational Investigator Service Award; National Institutes of Health [R01 AI100315, R01 AI085090]; National Heart, Lung, and Blood Institute [5T32HL007574-33]; Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences; Ruth L. Kirschstein National Research Service Award; National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital; University College London FX Supported by a Translational Investigator Service Award (to S.-Y.P.) and the National Institutes of Health (R01 AI100315 to R.S.G. and R01 AI085090 to T.A.C). J.I.C. was supported by a training award from National Heart, Lung, and Blood Institute (5T32HL007574-33). J.v.d.S. was supported by a Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences. C.M.B was supported by the Ruth L. Kirschstein National Research Service Award. H.B.G. received support from the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital and University College London. NR 22 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 SEP PY 2016 VL 138 IS 3 BP 852 EP + DI 10.1016/j.jaci.2016.02.022 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA DY9ZM UT WOS:000385496000021 PM 27130861 ER PT J AU Lee, SL Daimon, M Nakao, T Singer, DE Shinozaki, T Kawata, T Kimura, K Hirokawa, M Kato, TS Mizuno, Y Watanabe, M Yatomi, Y Yamazaki, T Komuro, I AF Lee, Seitetsu L. Daimon, Masao Nakao, Tomoko Singer, Daniel E. Shinozaki, Tomohiro Kawata, Takayuki Kimura, Koichi Hirokawa, Megumi Kato, Tomoko S. Mizuno, Yoshiko Watanabe, Masafumi Yatomi, Yutaka Yamazaki, Tsutomu Komuro, Issei TI Factors influencing left atrial volume in a population with preserved ejection fraction: Left ventricular diastolic dysfunction or clinical factors? SO JOURNAL OF CARDIOLOGY LA English DT Article DE Left atrium; Echocardiography; Remodeling; Obesity; Risk factors ID CHRONIC HEART-FAILURE; CARDIOVASCULAR-DISEASE; EUROPEAN-SOCIETY; RISK; FIBRILLATION; OBESITY; ECHOCARDIOGRAPHY; HYPERTENSION; ASSOCIATION; PREVALENCE AB Background: Increased left atrial volume (LAV) predicts a higher incidence of cardiovascular events and is widely recognized as a major surrogate marker of left ventricular (LV) diastolic dysfunction (DD). Although the pathophysiology of LA enlargement is probably multifactorial, few studies have examined comprehensively the clinical factors that lead to LA enlargement in the absence of valvular disease or LV systolic dysfunction. Therefore, we investigated associations between LAV and several clinical and echocardiographic parameters including DD. Methods: We enrolled 557 subjects without significant valve disease or LV systolic dysfunction from the health check-up clinic retrospectively. We performed univariable and multivariable linear regression using In LAV index as the dependent variable and the following independent variables: gender, age, smoking status, drinking habit, hypertension, diabetes, body mass index (BMI), LV ejection fraction, DD, LV mass index, hemoglobin, serum creatinine, serum total cholesterol, serum uric acid, serum sodium, and serum iron. Results: In multivariable analysis, LAV index was independently associated with BMI, lower hemoglobin, and moderate and severe DD compared with normal diastolic function (p < 0.001), but not with mild DD (p = 0.70). Conclusions: LA enlargement was independently associated with moderate and severe DD, but not with mild DD. Furthermore, obesity and lower hemoglobin were associated with LAV independently of DD. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 [Lee, Seitetsu L.; Daimon, Masao; Nakao, Tomoko; Kawata, Takayuki; Kimura, Koichi; Hirokawa, Megumi; Mizuno, Yoshiko; Watanabe, Masafumi; Komuro, Issei] Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan. [Daimon, Masao; Nakao, Tomoko; Kato, Tomoko S.; Yatomi, Yutaka] Univ Tokyo, Dept Clin Lab, Tokyo, Japan. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Med Sch, Boston, MA USA. [Shinozaki, Tomohiro] Univ Tokyo, Dept Biostat, Tokyo, Japan. [Kato, Tomoko S.] Juntendo Univ, Ctr Heart, Sch Med, Tokyo, Japan. [Mizuno, Yoshiko] Univ Tokyo, Dept Clin Epidemiol & Syst, Tokyo, Japan. [Yamazaki, Tsutomu] Univ Tokyo, Clin Res Support Ctr, Tokyo, Japan. RP Daimon, M (reprint author), Tokyo Univ Hosp, Dept Clin Lab, Bunkyo Ku, Hongo 7-3-1, Tokyo 1138655, Japan. EM daimon@muf.biglobe.ne.jp OI Daimon, Masao/0000-0002-7616-3477 FU Japan Society for the Promotion of Science (Masao Daimon) [24500554] FX This work was partially supported by a Grant-in-Aid for Scientific Research C (24500554) from the Japan Society for the Promotion of Science (Masao Daimon). NR 41 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0914-5087 EI 1876-4738 J9 J CARDIOL JI J. Cardiol. PD SEP-OCT PY 2016 VL 68 IS 3-4 BP 275 EP 281 DI 10.1016/j.jjcc.2016.02.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DY7WF UT WOS:000385339300018 PM 26943986 ER PT J AU Nearing, BD Libbus, I Amurthur, B Kenknight, BH Verrier, RL AF Nearing, Bruce D. Libbus, Imad Amurthur, Badri Kenknight, Bruce H. Verrier, Richard L. TI Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE ANTHEM-HF trial; autonomic regulation therapy; heart failure; heart rate; vagus nerve stimulation ID ATRIAL-FIBRILLATION INDUCIBILITY; T-WAVE ALTERNANS; REGULATION THERAPY; VAGAL-STIMULATION; MYOCARDIAL-INFARCTION; PREVENTION AB Acute Heart Rate Dynamics During VNS. Background: Chronic vagus nerve stimulation (VNS) applied to produce biomimetic levels of parasympathetic activation is feasible, well tolerated, safe, improves left ventricular ejection fraction, NYHA class, heart rate variability, and baroreflex function, and reduces T-wave alternans (TWA) in patients with chronic heart failure. However, the acute effects of VNS on beat-to-beat heart rate dynamics have not been systematically characterized in humans. Methods and Results: We evaluated acute effects of VNS on R-R-interval dynamics during the VNS titration period in patients (n = 59) enrolled in ANTHEM-HF trial by quantifying effects during continuous cyclic VNS (14-seconds on-time, 66-seconds off-time) adjusted to the maximum tolerable dose without excessive (<4 bpm) bradycardia during the 10-week titration period. VNS elicited an immediate change in heart rate that was correlated to VNS current amplitude, pulse width, and frequency. Heart rate decreased more in the 28 patients with right-sided stimulation (-2.22 +/- 0.13 bpm) than in the 31 patients with left-sided stimulation (-0.60 +/- 0.08 bpm, P < 0.001). The linear correlation between stimulus intensity and lengthening of the R-R interval was stronger among the 28 patients with right-sided VNS implantation (r = 0.88, P < 0.0001) than among the 31 patients with left-sided VNS implantation (r = 0.49, P < 0.002). In all patients, the heart rate change elicited by VNS was significantly greater than the change during the same timing intervals in 10 randomly selected patients without stimulation (+ 0.08 +/- 0.06 bpm, P < 0.001). Conclusion: Instantaneous heart rate change during therapeutic levels of VNS in patients with heart failure indicates consistent modulation of the autonomic nervous system for both left-and right-sided stimulation. C1 [Nearing, Bruce D.; Verrier, Richard L.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Libbus, Imad; Amurthur, Badri; Kenknight, Bruce H.] LivaNova PLC, Houston, TX USA. RP Verrier, RL (reprint author), Harvard Med Sch, Harvard Thorndike Electrophysiol Inst, Beth Israel Deaconess Med Ctr, Med,Div Cardiovasc Med, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU Liva Nova PLC FX Liva Nova PLC supported this study through a grant to Beth Israel Deaconess Medical Center, RL Verrier, P.I. NR 28 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2016 VL 27 IS 9 BP 1072 EP 1077 DI 10.1111/jce.13017 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ4OT UT WOS:000385838800010 PM 27221316 ER PT J AU Davies, EC Pineda, R AF Davies, Emma C. Pineda, Roberto, II TI Intraocular lens exchange surgery at a tertiary referral center: Indications, complications, and visual outcomes SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID CYSTOID MACULAR EDEMA; 5-YEAR AB PURPOSE: To identify indications for and visual outcomes of intraocular lens (IOL) exchange to understand recent changes in this surgery. SETTING: Academic tertiary referral center. DESIGN: Retrospective case series. METHODS: Cases were identified by searching the institution's electronic medical records from January 2010 to September 2015 for patients treated by 1 staff physician with the American Medical Association's Current Procedural Terminology code for IOL exchange. These cases were reviewed to determine the surgical indication, type of IOL removed, type of IOL implanted, time between surgeries, surgical complications, and visual outcomes. RESULTS: The study comprised medical records of 109 eyes. The mean time between the primary cataract surgery and IOL exchange was 1657 days. Dislocation of an in-the-bag posterior chamber IOL (27.5%), intolerance of a multifocal IOL (18.3%), and uveitis-glaucoma-hyphema syndrome (11.9%) were the most frequent indications for IOL exchange. The final IOL position after exchange was most frequently in the capsular bag (43.1%), anterior chamber (25.7%), or sulcus (22%). The final visual acuity at 1 month was 20/40 or better in 78.9% of cases. Of those not achieving this level of acuity, pathology not related to exchange surgery was identified in 48% of cases. The most frequent complications after IOL exchange surgery were posterior capsule opacification (13.8%), cystoid macular edema (10.1%), and high astigmatism (>1.5 diopters) (8.3%). CONCLUSIONS: The most frequent indication for IOL exchange surgery was dislocated IOLs; the second most frequent indication was patient dissatisfaction after multifocal IOL implantation. The increased ability to place an intracapsular IOL with few intraoperative complications and largely treatable postoperative complications enhances the effectiveness of IOL exchange surgery and patient satisfaction. C1 [Davies, Emma C.; Pineda, Roberto, II] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA USA. RP Pineda, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM rpineda@bics.bwh.harvard.edu NR 11 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 0886-3350 EI 1873-4502 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2016 VL 42 IS 9 BP 1262 EP 1267 DI 10.1016/j.jcrs.2016.06.031 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA DZ2RY UT WOS:000385690100004 PM 27697243 ER PT J AU Dichtel, LE Eajazi, A Miller, KK Torriani, M Bredella, MA AF Dichtel, Laura E. Eajazi, Alireza Miller, Karen K. Torriani, Martin Bredella, Miriam A. TI Short- and Long-Term Reproducibility of Intrahepatic Lipid Quantification by 1H-MR Spectroscopy and CT in Obesity SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE proton MR spectroscopy; computed tomography; intrahepatic lipids; reproducibility; obesity ID FATTY LIVER-DISEASE; MAGNETIC-RESONANCE-SPECTROSCOPY; HEPATIC TRIGLYCERIDE CONTENT; NONALCOHOLIC STEATOHEPATITIS; IN-VIVO; NONINVASIVE ASSESSMENT; BARIATRIC SURGERY; MR SPECTROSCOPY; UNENHANCED CT; DOUBLE-BLIND AB Objective This study aimed to assess short- and long-term reproducibility of intrahepatic lipid (IHL) quantification by proton magnetic resonance spectroscopy (H-1-MRS) and computed tomography (CT). Methods Sixteen obese subjects underwent H-1-MRS using a single-voxel point-resolved single-voxel spectroscopy sequence at 3 T and noncontrast single-slice CT of the liver. Measurements were repeated after 6 weeks and 6 months. Clinical parameters (weight, activity, serum lipids) were collected. Short-term (baseline to 6 weeks) and long-term (baseline to 6 months) reproducibility of IHL was assessed by coefficient of variance (CV), SD, and intraclass correlation coefficient (ICC). Results Short-term reproducibility and long-term reproducibility of H-1-MRS were as follows: CV, 5.9% to 18.8%; SD, 0.7 to 1.9; and ICC, 0.998 to 0.995 (95% confidence interval, 0.942-0.999). Short-term reproducibility and long-term reproducibility of CT were as follows: CV, 4.4% to 14.2%; SD, 2.4 to 8.7; and ICC, 0.766 to 0.982 (95% confidence interval, 0.271-0.994). There was no significant change in clinical parameters (P > 0.3). Conclusions Proton magnetic resonance spectroscopy and CT are reproducible methods for short- and long-term quantification of IHL content. Our results can guide sample size calculations for interventional and longitudinal studies. C1 [Dichtel, Laura E.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eajazi, Alireza; Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@mgh.harvard.edu FU NIH [R01 HL-077674, K23 RR-23090, K24 HL-092902, KL2 TR00110, UL1 RR-025758] FX This study was supported by NIH grants R01 HL-077674, K23 RR-23090, K24 HL-092902, KL2 TR00110 and UL1 RR-025758. NR 41 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2016 VL 40 IS 5 BP 678 EP 682 DI 10.1097/RCT.0000000000000423 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY8IF UT WOS:000385372300002 PM 27116479 ER PT J AU Wortman, JR Tirumani, SH Jagannathan, JP Tirumani, H Shinagare, AB Hornick, JL Ramaiya, NH AF Wortman, Jeremy R. Tirumani, Sree Harsha Jagannathan, Jyothi P. Tirumani, Harika Shinagare, Atul B. Hornick, Jason L. Ramaiya, Nikhil H. TI Primary Extremity Liposarcoma: MRI Features, Histopathology, and Clinical Outcomes SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE liposarcoma; atypical lipomatous tumor; dedifferentiated liposarcoma; myxoid liposarcoma; pleomorphic liposarcoma; MRI ID ROUND-CELL LIPOSARCOMA; MYXOID LIPOSARCOMA; SOFT-TISSUE; PATHOLOGICAL CORRELATION; PATTERNS; TUMOR AB Objective This study aimed to describe magnetic resonance imaging (MRI) features of extremity liposarcoma (LPS) subtypes, correlating with histopathology and clinical outcomes. Methods In this retrospective study, we included 125 patients (80 men, 45 women; mean age, 53 years) with extremity LPS [23 atypical lipomatous tumor (ALT), 9 dedifferentiated (DDLPS), 70 myxoid (MLPS), 23 pleomorphic (PLPS)]. Pretreatment MRI of primary tumors in 56 patients (10 ALT, 4 DDLPS, 28 MLPS, 14 PLPS) was reviewed. Results All subtypes were predominantly T1 isointense relative to skeletal muscle (DDLPS = 3/4, MLPS = 28/28, PLPS = 13/14) and T2 hyperintense (ALT = 10/10, DDLPS = 3/4, MLPS = 28/28, PLPS = 14/14) except for ALT which were T1 hyperintense (8/10). Within MLPS, high grade was associated with unencapsulated margins (P = 0.05) and solid, nodular enhancement (P < 0.0001). Peritumoral edema (P = 0.03) and T2 heterogeneity (P = 0.05) predicted pulmonary (rather than extrapulmonary) metastases in MLPS. Tumor subtype correlated with mortality (P = 0.04). Conclusions The MRI features can help to distinguish between extremity LPS subtypes, and can predict histopathologic grade and metastatic pattern in myxoid LPS. C1 [Wortman, Jeremy R.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Tirumani, Harika; Shinagare, Atul B.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Wortman, JR (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM jwortman@partners.org NR 24 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2016 VL 40 IS 5 BP 791 EP 798 DI 10.1097/RCT.0000000000000431 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY8IF UT WOS:000385372300019 PM 27224232 ER PT J AU Mirabelli, C Pelletier, I Teoule, F Vidalain, PO Brisac, C Tangy, F Delpeyroux, F Blondel, B AF Mirabelli, Carmen Pelletier, Isabelle Teoule, Francois Vidalain, Pierre-Olivier Brisac, Cynthia Tangy, Frederic Delpeyroux, Francis Blondel, Bruno TI The CREB3-Herp signalling module limits the cytosolic calcium concentration increase and apoptosis induced by poliovirus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; PROTEIN HERP; ER STRESS; TRANSCRIPTION FACTORS; CELL-DEATH; PATHWAY; REPLICATION; DEGRADATION; DOMAIN AB Poliovirus (PV)-induced apoptosis seems to play a major role in central nervous system (CNS) tissue injury, a crucial feature of the pathogenesis of poliomyelitis. We have previously shown that calcium (Ca2+) flux from the endoplasmic reticulum (ER) to the cytosol during PV infection is involved in apoptosis induction in human neuroblastoma cells. We show here that PV infection is associated with a transient upregulation of Herp (homocysteine-induced ER protein), a protein known to promote the degradation of ER-resident Ca2+ channels. Herp gene transcription is controlled by the transcription factor CREB3 (cAMP response element-binding protein 3). We found that the CREB3/Herp pathway limited the increase in cytosolic Ca2+ concentration and apoptosis early in PV infection. This may reduce the extent of PV-induced damage to the CNS during poliomyelitis. C1 [Mirabelli, Carmen; Pelletier, Isabelle; Teoule, Francois; Brisac, Cynthia; Delpeyroux, Francis; Blondel, Bruno] Inst Pasteur, Unite Biol Virus Enter, 25 Rue Dr Roux, F-75015 Paris, France. [Mirabelli, Carmen; Pelletier, Isabelle; Teoule, Francois; Brisac, Cynthia; Delpeyroux, Francis; Blondel, Bruno] INSERM, U994, Paris, France. [Teoule, Francois; Brisac, Cynthia] Univ Versailles St Quentin, Versailles, France. [Vidalain, Pierre-Olivier; Tangy, Frederic] Inst Pasteur, Unite Genom Virale & Vaccinat, 25 Rue Dr Roux, F-75015 Paris, France. [Vidalain, Pierre-Olivier; Tangy, Frederic] CNRS, UMR 3569, Paris, France. [Mirabelli, Carmen] KU Leuven Univ Leuven, Dept Microbiol Immunol, Rega Inst Med Res, Lab Virol & Chemotherapy, Leuven, Belgium. [Vidalain, Pierre-Olivier] Ctr Univ St Peres, CICB Paris FR3567, CNRS,UMR 8601, Team Chem & Biol Nucleostides & Immunol Therapy C, Paris, France. [Vidalain, Pierre-Olivier] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Brisac, Cynthia] Harvard Med Sch, Dept Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. RP Blondel, B (reprint author), Inst Pasteur, Unite Biol Virus Enter, 25 Rue Dr Roux, F-75015 Paris, France.; Blondel, B (reprint author), INSERM, U994, Paris, France. EM bblondel@pasteur.fr FU Pasteur Institut (Transverse research programme) [PTR 276]; Agence Nationale de la Recherche [ANR-09MIEN-019]; Fondation pour la Recherche Medicale [DMI20091117313]; Pasteur-Paris University (PPU) International PhD programme; Institut Carnot Pasteur Maladies Infectieuses; Ministere de l'Enseignement Superieur et de la Recherche FX We wish to thank Florence Colbere-Garapin for her invaluable support throughout this work and for fruitful discussions. We thank Santos Susin (Centre de Recherche des Cordeliers, Paris, France) and Victor Yuste (Autonomous University of Barcelona, Spain) for providing IMR5 cells. We also thank the Plate-forme de cytometrie (Pasteur Institut, Paris, France) for assistance with cytometry. This study was supported by grants from the Pasteur Institut (Transverse research programme PTR 276), the Agence Nationale de la Recherche (ANR-09MIEN-019), and the Fondation pour la Recherche Medicale (DMI20091117313). C.M. was supported by a stipend from the Pasteur-Paris University (PPU) International PhD programme and by the Institut Carnot Pasteur Maladies Infectieuses. F.T. and C.B. were supported by grants from the Ministere de l'Enseignement Superieur et de la Recherche. NR 28 TC 0 Z9 0 U1 1 U2 1 PU MICROBIOLOGY SOC PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER ST, LONDON WC1N 2JU, ERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2016 VL 97 BP 2194 EP 2200 DI 10.1099/jgv.0.000544 PN 9 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA DY7EF UT WOS:000385291700016 PM 27405867 ER PT J AU Tonnerre, P Gerard, N Gavlovsky, PJ Mazalrey, S Hourmant, M Cheneau, ML Cesbron-Gautier, A Renaudin, K Bressollette-Bodin, C Charreau, B AF Tonnerre, Pierre Gerard, Nathalie Gavlovsky, Pierre-Jean Mazalrey, Simon Hourmant, Maryvonne Cheneau, Mary-Luce Cesbron-Gautier, Anne Renaudin, Karine Bressollette-Bodin, Celine Charreau, Beatrice TI MICA Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE BK polyomavirus; innate immunity; MICA polymorphism; MICA A5; 1 mutation; kidney transplantation ID NATURAL-KILLER-CELL; ORGAN-TRANSPLANTATION; HIV-1 INFECTION; VIRUS; NKG2D; RECIPIENTS; EXPRESSION; LIGANDS; IMPACT; REPLICATION AB Background. BK polyomavirus (BKPyV) frequently reactivates in kidney transplant recipients during immunosuppressive therapy and triggers BKPyV-associated nephropathy and graft rejection. Determining effective risk factors for BKPyV reactivation is required to achieve efficient prevention. Methods.aEuro integral This study investigated the role of major histocompatibility complex (MHC) class I-related chain A (MICA) in BKPyV reactivation in a cohort of 144 transplant donor/recipient pairs, including recipients with no reactivation (controllers) and those with mild (virurics) or severe (viremics) BKPyV reactivation after graft receipt. Results.aEuro integral We show that, in the kidney, MICA is predominantly expressed in tubule epithelial cells, the natural targets of BKPyV, questioning a role for MICA in the immune control of BKPyV infection. Focusing on MICA genotype, we found a lower incidence of BKPyV reactivation in recipients of a renal graft from a donor carrying the MICA A5.1 mutant, which encodes a truncated nonconventional MICA. We established that a mismatch for MICA A5.1 between transplant donor and recipient is critical for BKPyV reactivation and BKPyV-associated nephropathy. Functionally, we found that a low prevalence of BKPyV reactivation was associated with elevated anti-MICA sensitization and reduced plasma level of soluble MICA in recipients, 2 potential effector mechanisms. Discussions.aEuro integral These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes. C1 [Tonnerre, Pierre; Gerard, Nathalie; Gavlovsky, Pierre-Jean; Charreau, Beatrice] INSERM, UMR1064, LabEx Transplantex, LabEx IGO & IHU CESTI, Nantes, France. [Tonnerre, Pierre; Gerard, Nathalie; Gavlovsky, Pierre-Jean; Hourmant, Maryvonne; Charreau, Beatrice] CHU Nantes, Inst Transplantat & Rech Transplantat Urol, ITUN, Nantes, France. [Tonnerre, Pierre; Gerard, Nathalie; Gavlovsky, Pierre-Jean; Hourmant, Maryvonne; Charreau, Beatrice] Univ Nantes, Fac Med, LUNAM, Nantes, France. [Mazalrey, Simon; Bressollette-Bodin, Celine] Univ Nantes, UFR Pharm, EA4271, Nantes, France. [Cheneau, Mary-Luce; Cesbron-Gautier, Anne] Univ Nantes, CHU Nantes, LabEx Transplantex, Lab HLA,Etab Francais Sang, Nantes, France. [Renaudin, Karine] Univ Nantes, CHU Nantes, Lab Anatomopathol, Nantes, France. [Bressollette-Bodin, Celine] CHU Nantes, Lab Virol, Nantes, France. [Tonnerre, Pierre] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Tonnerre, Pierre] Harvard Med Sch, Boston, MA USA. RP Charreau, B (reprint author), INSERM, UMR1064, 30 Bd J Monnet, F-44093 Nantes 01, France. EM beatrice.charreau@univ-nantes.fr FU IHU-Cesti; LabEx IGO; LabEx Transplantex projects; French government [ANR-10-IBHU-005, ANR-11-LABX-0016-01, ANR-11-LABX-0070]; Nantes Metropole; Pays de la Loire Region; Fondation Centaure; Agence de la Biomedecine FX This work was supported by the IHU-Cesti, LabEx IGO, and LabEx Transplantex projects, which received French government financial support, managed by the National Research Agency, via Investment Into The Future programs ANR-10-IBHU-005, ANR-11-LABX-0016-01, and ANR-11-LABX-0070); Nantes Metropole and the Pays de la Loire Region (support to the IHU-Cesti project); the Fondation Centaure (support to the French Transplantation Research Network); the Agence de la Biomedecine; and the IHU-Cesti (fellowship to P.-J.G.). NR 43 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2016 VL 214 IS 5 BP 807 EP 816 DI 10.1093/infdis/jiw168 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DY7YY UT WOS:000385346400020 PM 27130430 ER PT J AU Piantoni, G Halgren, E Cash, S AF Piantoni, G. Halgren, E. Cash, S. TI Human electrocorticography reveals cortical variability of spindle characteristics SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 23rd Congress of the European-Sleep-Research-Society CY SEP 13-16, 2016 CL Bologna, ITALY SP European Sleep Res Soc C1 [Piantoni, G.; Cash, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Piantoni, G.; Cash, S.] Harvard Med Sch, Boston, MA USA. [Halgren, E.] UCSD, La Jolla, CA 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 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2016 VL 25 SU 1 SI SI MA O279 BP 58 EP 58 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW2AL UT WOS:000383445200120 ER PT J AU Basheer, R AF Basheer, R. TI Neurochemical consequences of sleep deprivation in adult rodent brain SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 23rd Congress of the European-Sleep-Research-Society CY SEP 13-16, 2016 CL Bologna, ITALY SP European Sleep Res Soc C1 [Basheer, R.] Harvard Med Sch, VA Boston Healthcare Syst, Psychiat, West Roxbury, MA 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 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2016 VL 25 SU 1 SI SI MA 322 BP 74 EP 74 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW2AL UT WOS:000383445200155 ER PT J AU McGrath, ER Espie, CA Bostock, S Power, A Murphy, AW Newell, J Kelly, C Duffy, N Gunning, P Gibson, I O'Donnell, MJ AF McGrath, E. R. Espie, C. A. Bostock, S. Power, A. Murphy, A. W. Newell, J. Kelly, C. Duffy, N. Gunning, P. Gibson, I. O'Donnell, M. J. TI Digital cognitive behavioural therapy for insomnia in a medical population: evidence from the sleep to lower elevated blood pressure trial (SLEPT) SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 23rd Congress of the European-Sleep-Research-Society CY SEP 13-16, 2016 CL Bologna, ITALY SP European Sleep Res Soc C1 [McGrath, E. R.; Power, A.; Murphy, A. W.; Newell, J.; Kelly, C.; Duffy, N.; Gunning, P.; O'Donnell, M. J.] Natl Univ Ireland, HRB Clin Res Facil, Galway, Ireland. [McGrath, E. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McGrath, E. R.] Harvard Med Sch, Dept Neurol, Boston, MA USA. [Espie, C. A.] Univ Oxford, Sleep & Circadian Neurosci Inst, Oxford, England. [Espie, C. A.; Bostock, S.] Big Hlth Ltd, London, England. [Bostock, S.] Univ Southampton, Fac Med, Southampton, Hants, England. [Gibson, I.] Natl Univ Ireland, Galway, Ireland. 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 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2016 VL 25 SU 1 SI SI MA P132 BP 136 EP 136 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW2AL UT WOS:000383445200331 ER PT J AU van Rijn, E Reid, AM Edwards, CL Malinowski, JE Ruby, PM Eichenlaub, JB Blagrove, MT AF van Rijn, E. Reid, A. M. Edwards, C. L. Malinowski, J. E. Ruby, P. M. Eichenlaub, J. -B. Blagrove, M. T. TI The dream-lag effect: partial replication for REM sleep dreams that does not extend to daydreams SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 23rd Congress of the European-Sleep-Research-Society CY SEP 13-16, 2016 CL Bologna, ITALY SP European Sleep Res Soc C1 [van Rijn, E.; Reid, A. M.; Edwards, C. L.; Blagrove, M. T.] Swansea Univ, Dept Psychol, Swansea, W Glam, Wales. [Malinowski, J. E.] Univ East London, Sch Psychol, London, England. [Ruby, P. M.] Lyon Neurosci Res Ctr, Lyon, France. [Eichenlaub, J. -B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2016 VL 25 SU 1 SI SI MA P190 BP 151 EP 151 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW2AL UT WOS:000383445200379 ER PT J AU Kim, J Park, JE Nahrendorf, M Kim, DE AF Kim, Jongseong Park, Jung E. Nahrendorf, Matthias Kim, Dong-Eog TI Direct Thrombus Imaging in Stroke SO JOURNAL OF STROKE LA English DT Review DE Acute stroke; Direct thrombus imaging; Positron-emission tomography; X-ray Computed Tomography; Magnetic resonance imaging; Molecular imaging ID ELEVATION MYOCARDIAL-INFARCTION; ACTIVATED PLATELETS ALLOWS; ACUTE ISCHEMIC-STROKE; DEEP-VEIN THROMBOSIS; MRI CONTRAST AGENT; COMPUTED-TOMOGRAPHY; CAROTID-ARTERY; PLASMINOGEN-ACTIVATOR; RESIDUAL THROMBUS; NONINVASIVE DETECTION AB There is an emergent need for imaging methods to better triage patients with acute stroke for tissue plasminogen activator (tPA)-mediated thrombolysis or endovascular clot retrieval by directly visualizing the size and distribution of cerebral thromboemboli. Currently, magnetic resonance (MR) or computed tomography (CT) angiography visualizes the obstruction Of blood flow within the vessel lumen rather than the thrombus itself. The present visualization method, which relies on observation of the dense artery sign (the appearance of cerebral thrombi On a non-enhanced CT), suffers from low sensitivity. When translated into the clinical setting, direct thrombus imaging is likely to enable individualized acute stroke therapy by allowing clinicians to detect the thrombus with high sensitivity, assess the size and nature of the thrombus more precisely, Serially monitor the therapeutic effects of thrombolysis, and detect post-treatment recurrence. This review is intended to provide recent updates on stroke-related direct thrombus imaging using MR imaging, positron emission tomography, or CT. C1 [Kim, Jongseong; Kim, Dong-Eog] Dongguk Univ, Mol Imaging & Neurovasc Res MINER Lab, Ilsan Hosp, Goyang, South Korea. [Kim, Jongseong; Nahrendorf, Matthias; Kim, Dong-Eog] Dongguk Univ, Global Res Lab Thrombus Targeted Theranost, Ilsan Hosp, Goyang, South Korea. [Kim, Jongseong; Nahrendorf, Matthias; Kim, Dong-Eog] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Park, Jung E.; Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Dept Neurol, Goyang, South Korea. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Med Sch, Boston, MA USA. RP Kim, DE (reprint author), Dongguk Univ, Stroke Ctr, Ilsan Hosp, 27 Dorigguk Ro, Goyang 10326, South Korea. EM kdongeog@duih.org OI Kim, Jongseong/0000-0001-9595-2765 FU Global Research Lab (GRL) program of the National Research Foundation [NRF-2015K1A1A2028228]; Korean government FX This work was supported by Global Research Lab (GRL) program (NRF-2015K1A1A2028228 to Drs. Dong-Eog Kim and Matthias Nahrendorf) of the National Research Foundation, funded by the Korean government. NR 65 TC 1 Z9 1 U1 6 U2 6 PU KOREAN STROKE SOC PI SEOUL PA C/O CHIN-SANG CHUNG, DEPT NEUROL, SAMSUNG MED CTR, SUNGKYUNKWAN UNIV, SCH MED, IRWON-RO, GANGNAM-GU, SEOUL, 135-710, SOUTH KOREA SN 2287-6391 EI 2287-6405 J9 J STROKE JI J. Stroke PD SEP PY 2016 VL 18 IS 3 BP 286 EP 296 DI 10.5853/jos.2016.00906 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DY7UT UT WOS:000385335500006 ER PT J AU Cantero, JL Iglesias, JE Van Leemput, K Atienza, M AF Cantero, Jose L. Iglesias, Juan E. Van Leemput, Koen Atienza, Mercedes TI Regional Hippocampal Atrophy and Higher Levels of Plasma Amyloid-Beta Are Associated With Subjective Memory Complaints in Nondemented Elderly Subjects SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Subjective memory complaints; Hippocampus; Plasma amyloid-beta; Alzheimer's disease; Biomarkers ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ADULT NEUROGENESIS; BRAIN ATROPHY; OLDER-ADULTS; IN-VIVO; DECLINE; CSF; PREDICTION; CLEARANCE AB Evidence suggests a link between the presence of subjective memory complaints (SMC) and lower volume of the hippocampus, one of the first regions to show neuropathological lesions in Alzheimer's disease. However, it remains unknown whether this pattern of hippocampal atrophy is regionally specific and whether SMC are also paralleled by changes in peripheral levels of amyloid-beta (A beta). The volume of hippocampal subregions and plasma A beta levels were cross-sectionally compared between elderly individuals with (SMC+; N = 47) and without SMC (SMC-; N = 48). Significant volume differences in hippocampal subregions were further correlated with plasma A beta levels and with objective memory performance. Individuals with SMC exhibited significantly higher A beta(1-42) concentrations and lower volumes of CA1, CA4, dentate gyrus, and molecular layer compared with SMC- participants. Regression analyses further showed significant associations between lower volume of the dentate gyrus and both poorer memory performance and higher plasma A beta(1-42) levels in SMC+ participants. The presence of SMC, lower volumes of specific hippocampal regions, and higher plasma A beta(1-42) levels could be conditions associated with aging vulnerability. If such associations are confirmed in longitudinal studies, the combination may be markers recommending clinical follow-up in nondemented older adults. C1 [Cantero, Jose L.; Atienza, Mercedes] Pablo de Olavide Univ, Lab Funct Neurosci, CIBERNED Network Ctr Biomed Res Neurodegenerat Di, Seville, Spain. [Iglesias, Juan E.; Van Leemput, Koen] Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA USA. [Iglesias, Juan E.] Basque Ctr Cognit Brain & Language, San Sebastian, Spain. [Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, Lyngby, Denmark. RP Cantero, JL (reprint author), Pablo de Olavide Univ, Lab Funct Neurosci, Ctra Utrera Km 1, ES-41013 Seville, Spain. EM jlcanlor@upo.es FU Spanish Ministry of Economy and Competitiveness [SAF2011-25463, PSI2014-55747-R]; Regional Ministry of Innovation, Science and Enterprise; Junta de Andalucia [P12-CTS-2327]; CIBERNED [CB06/05/1111]; Fellows Gipuzkoa Program; National Institutes of Health; National Center for Research Resources [P41-RR14075]; National Institute of Biomedical Imaging and Bioengineering [R01EB013565]; Lundbeck Foundation [R141-2013-13117] FX This work was supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-25463 to J.L.C., PSI2014-55747-R to M.A.), the Regional Ministry of Innovation, Science and Enterprise, Junta de Andalucia (P12-CTS-2327 to J.L.C.), CIBERNED (CB06/05/1111 to J.L.C.), the Fellows Gipuzkoa Program to J.E.I., the National Institutes of Health, National Center for Research Resources (P41-RR14075 to K.V.L.), the National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering (R01EB013565 to K.V.L.), and the Lundbeck Foundation (R141-2013-13117 to K.V.L.). NR 47 TC 2 Z9 2 U1 3 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2016 VL 71 IS 9 BP 1210 EP 1215 DI 10.1093/gerona/glw022 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DY5LA UT WOS:000385139900012 PM 26946100 ER PT J AU Rajbhandari, R Simon, RE Chung, RT Ananthakrishnan, AN AF Rajbhandari, Ruma Simon, Rachel E. Chung, Raymond T. Ananthakrishnan, Ashwin N. TI Racial Disparities in Inhospital Outcomes for Hepatocellular Carcinoma in the United States SO MAYO CLINIC PROCEEDINGS LA English DT Article ID LIVER-TRANSPLANTATION; PORTAL-HYPERTENSION; ADMINISTRATIVE DATA; HEPATITIS-C; CANCER; HEALTH; CIRRHOSIS; RACE; POPULATION; MORTALITY AB Objective: To study racial disparities in therapeutic interventions and hospitalization outcomes for hepatocellular cancer (HCC) in the United States. Patients and Methods: Using the 2011 Nationwide Inpatient Sample (comprising hospitalizations between January 1 and December 31, 2011), we identified patients with HCC-related admissions using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among these, we also identified those that were procedure-related (associated with liver transplantation, hepatic resection, radiofrequency ablation, or transarterial chemoembolization). Multivariate regression was performed to identify the contribution of race to therapeutic interventions and outcomes. Results: A total of 22,933 HCC-related hospitalizations were included, of which 10,285 were procedure related (45%). Blacks had a smaller proportion (35%) of procedure-related HCC hospitalizations than did whites (46%) (odds ratio [OR], 0.65; 95% CI, 0.49-0.86). Specifically, blacks had lower odds of liver transplantation (OR, 0.43; 95% CI, 0.26-0.71), hepatic resection (OR, 0.57; 95% CI, 0.33-0.98), and ablation (OR, 0.46; 95% CI, 0.29-0.74) (P=.002) than did whites. Overall, 10.9% of HCC-related admissions resulted in death in blacks as compared with 6.4% in whites (OR, 1.58; 95% CI, 1.12-2.24). Conclusion: Among patients admitted for HCC-related hospitalizations, blacks were less likely to receive liver transplantation, hepatic resection, and ablation than whites and had higher inhospital mortality. Identifying racial disparities in health care is a necessary first step to appropriately address and eliminate them. (C) 2016 Mayo Foundation for Medical Education and Research C1 [Chung, Raymond T.; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Rajbhandari, Ruma; Simon, Rachel E.; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rajbhandari, Ruma; Simon, Rachel E.; Chung, Raymond T.; Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU National Institutes of Health [T32 DK007191, K24 DK078772, K23 DK097142] FX The work was supported by grant T32 DK007191 (R.R.), grant K24 DK078772 (R.T.C.), and grant K23 DK097142 (A.N.A.) from the National Institutes of Health. NR 31 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2016 VL 91 IS 9 BP 1173 EP 1182 DI 10.1016/j.mayocp.2016.06.009 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DZ6AK UT WOS:000385943700009 PM 27497857 ER PT J AU Steensma, DP Kyle, RA Shampo, MA AF Steensma, David P. Kyle, Robert A. Shampo, Marc A. TI J. Robin Warren: Helicobacter Pylori and Peptic Ulcer SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kyle, Robert A.; Shampo, Marc A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2016 VL 91 IS 9 BP E129 EP E130 DI 10.1016/j.mayocp.2016.01.027 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DZ6AK UT WOS:000385943700002 PM 27594194 ER PT J AU Okai, D Askey-Jones, S Mack, J Martin, A Chaudhuri, KR Samuel, M David, AS Brown, RG AF Okai, David Askey-Jones, Sally Mack, Joel Martin, Anne Chaudhuri, Kallol Ray Samuel, Michael David, Anthony S. Brown, Richard G. TI Parkinson's Impulse-Control Scale for the Severity Rating of Impulse-Control Behaviors in Parkinson's Disease: A Semistructured Clinical Assessment Tool SO MOVEMENT DISORDERS CLINICAL PRACTICE LA English DT Article DE impulse-control disorder; Parkinson's disease; severity; rating; carer ID QUALITY-OF-LIFE; CONTROL DISORDERS; DOPAMINE DYSREGULATION; COMPULSIVE DISORDERS; QUESTIONNAIRE AB BackgroundImpulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome). MethodsThe Parkinson's Impulse-Control Scale (PICS), the first PD-specific, semistructured interview to cover the full range of PD-related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92). ResultsThe scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%-95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa () values for clinician-clinician rating of severity ( = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive-behavioral therapy and medication adjustment (t[22] = 5.47; P < 0.001). ConclusionsThe PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required. C1 [Okai, David; Askey-Jones, Sally; David, Anthony S.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Sect Cognit Neuropsychiat, London, England. [Okai, David] Oxford Univ Hosp NHS Trust, Dept Psychol Med, Oxford, England. [Askey-Jones, Sally] Newcastle Univ, Sch Psychol, Newcastle Upon Tyne, Tyne & Wear, England. [Mack, Joel] Portland VA Med Ctr, Portland, OR USA. [Martin, Anne; Chaudhuri, Kallol Ray; Samuel, Michael] Kings Coll Hosp NHS Trust, Kings Hlth Partners, London, England. [Brown, Richard G.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, PO77, London SE5 8AF, England. RP Brown, RG (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, PO77, London SE5 8AF, England. EM richard.g.brown@kcl.ac.uk RI David, Anthony/C-1315-2011 OI David, Anthony/0000-0003-0967-774X NR 21 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2330-1619 J9 MOV DISORD CLIN PRAC JI MOV. DISORD. CLIN. PRACT. PD SEP-OCT PY 2016 VL 3 IS 5 BP 494 EP 499 DI 10.1002/mdc3.12316 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DY9BD UT WOS:000385426200010 PM 27774496 ER PT J AU Lawrenson, K Kar, S McCue, K Kuchenbaeker, K Michailidou, K Tyrer, J Beesley, J Ramus, SJ Li, QY Delgado, MK Lee, JM Aittomaki, K Andrulis, IL Anton-Culver, H Arndt, V Arun, BK Arver, B Bandera, EV Barile, M Barkardottir, RB Barrowdale, D Beckmann, MW Benitez, J Berchuck, A Bisogna, M Bjorge, L Blomqvist, C Blot, W Bogdanova, N Bojesen, A Bojesen, SE Bolla, MK Bonanni, B Borresen-Dale, AL Brauch, H Brennan, P Brenner, H Bruinsma, F Brunet, J Buhari, SA Burwinkel, B Butzow, R Buys, SS Cai, QY Caldes, T Campbell, I Canniotto, R Chang-Claude, J Chiquette, J Choi, JY Claes, KBM Cook, LS Cox, A Cramer, DW Cross, SS Cybulski, C Czene, K Daly, MB Damiola, F Dansonka-Mieszkowska, A Darabi, H Dennis, J Devilee, P Diez, O Doherty, JA Domchek, SM Dorfling, CM Dork, T Dumont, M Ehrencrona, H Ejlertsen, B Ellis, S Engel, C Lee, E Evans, DG Fasching, PA Feliubadalo, L Figueroa, J Flesch-Janys, D Fletcher, O Flyger, H Foretova, L Fostira, F Foulkes, WD Fridley, BL Friedman, E Frost, D Gambino, G Ganz, PA Garber, J Garcia-Closas, M Gentry-Maharaj, A Ghoussaini, M Giles, GG Glasspool, R Godwin, AK Goldberg, MS Goldgar, DE Gonzalez-Neira, A Goode, EL Goodman, MT Greene, MH Gronwald, J Guenel, P Haiman, CA Hall, P Hallberg, E Hamann, U Hansen, TVO Harrington, PA Hartman, M Hassan, N Healey, S Heitz, F Herzog, J Hogdall, E Hogdall, CK Hogervorst, FBL Hollestelle, A Hopper, JL Hulick, PJ Huzarski, T Imyanitov, EN Isaacs, C Ito, H Jakubowska, A Janavicius, R Jensen, A John, EM Johnson, N Kabisch, M Kang, D Kapuscinski, M Karlan, BY Khan, S Kiemeney, LA Kjaer, SK Knight, JA Konstantopoulou, I Kosma, VM Kristensen, V Kupryjanczyk, J Kwong, A de la Hoya, M Laitman, Y Lambrechts, D Le, N De Leeneer, K Lester, J Levine, DA Li, JM Lindblom, A Long, J Lophatananon, A Loud, JT Lu, KR Lubinski, J Mannermaa, A Manoukian, S Le Marchand, L Margolin, S Marme, F Massuger, LFAG Matsuo, K Mazoyer, S McGuffog, L McLean, C McNeish, I Meindl, A Menon, U Mensenkamp, AR Milne, RL Montagna, M Moysich, KB Muir, K Mulligan, AM Nathanson, KL Ness, RB Neuhausen, SL Nevanlinna, H Nord, S Nussbaum, RL Odunsi, K Offit, K Olah, E Olopade, OI Olson, JE Olswold, C O'Malley, D Orlow, I Orr, N Osorio, A Park, SK Pearce, CL Pejovic, T Peterlongo, P Pfeiler, G Phelan, CM Poole, EM Pylkas, K Radice, P Rantala, J Rashid, MU Rennert, G Rhenius, V Rhiem, K Risch, HA Rodriguez, G Rossing, MA Rudolph, A Salvesen, HB Sangrajrang, S Sawyer, EJ Schildkraut, JM Schmidt, MK Schmutzler, RK Sellers, TA Seynaeve, C Shah, M Shen, CY Shu, XO Sieh, W Singer, CF Sinilnikova, OM Slager, S Song, HL Soucy, P Southey, MC Stenmark-Askmalm, M Stoppa-Lyonnet, D Sutter, C Swerdlow, A Tchatchou, S Teixeira, MR Teo, SH Terry, KL Terry, MB Thomassen, M Tibiletti, MG Tihomirova, L Tognazzo, S Toland, AE Tomlinson, I Torres, D Truong, T Tseng, CC Tung, N Tworoger, SS Vachon, C van den Ouweland, AMW van Doorn, HC van Rensburg, EJ Van't Veer, LJ Vanderstichele, A Vergote, I Vijai, J Wang, Q Wang-Gohrke, S Weitzel, JN Wentzensen, N Whittemore, AS Wildiers, H Winqvist, R Wu, AH Yannoukakos, D Yoon, SY Yu, JC Zheng, W Zheng, Y Khanna, KK Simard, J Monteiro, AN French, JD Couch, FJ Freedman, ML Easton, DF Dunning, AM Pharoah, PD Edwards, SL Chenevix-Trench, G Antoniou, AC Gayther, SA AF Lawrenson, Kate Kar, Siddhartha McCue, Karen Kuchenbaeker, Karoline Michailidou, Kyriaki Tyrer, Jonathan Beesley, Jonathan Ramus, Susan J. Li, Qiyuan Delgado, Melissa K. Lee, Janet M. Aittomaki, Kristiina Andrulis, Irene L. Anton-Culver, Hoda Arndt, Volker Arun, Banu K. Arver, Brita Bandera, Elisa V. Barile, Monica Barkardottir, Rosa B. Barrowdale, Daniel Beckmann, Matthias W. Benitez, Javier Berchuck, Andrew Bisogna, Maria Bjorge, Line Blomqvist, Carl Blot, William Bogdanova, Natalia Bojesen, Anders Bojesen, Stig E. Bolla, Manjeet K. Bonanni, Bernardo Borresen-Dale, Anne-Lise Brauch, Hiltrud Brennan, Paul Brenner, Hermann Bruinsma, Fiona Brunet, Joan Buhari, Shaik Ahmad Burwinkel, Barbara Butzow, Ralf Buys, Saundra S. Cai, Qiuyin Caldes, Trinidad Campbell, Ian Canniotto, Rikki Chang-Claude, Jenny Chiquette, Jocelyne Choi, Ji-Yeob Claes, Kathleen B. M. Cook, Linda S. Cox, Angela Cramer, Daniel W. Cross, Simon S. Cybulski, Cezary Czene, Kamila Daly, Mary B. Damiola, Francesca Dansonka-Mieszkowska, Agnieszka Darabi, Hatef Dennis, Joe Devilee, Peter Diez, Orland Doherty, Jennifer A. Domchek, Susan M. Dorfling, Cecilia M. Doerk, Thilo Dumont, Martine Ehrencrona, Hans Ejlertsen, Bent Ellis, Steve Engel, Christoph Lee, Eunjung Evans, D. Gareth Fasching, Peter A. Feliubadalo, Lidia Figueroa, Jonine Flesch-Janys, Dieter Fletcher, Olivia Flyger, Henrik Foretova, Lenka Fostira, Florentia Foulkes, William D. Fridley, Brooke L. Friedman, Eitan Frost, Debra Gambino, Gaetana Ganz, Patricia A. Garber, Judy Garcia-Closas, Montserrat Gentry-Maharaj, Aleksandra Ghoussaini, Maya Giles, Graham G. Glasspool, Rosalind Godwin, Andrew K. Goldberg, Mark S. Goldgar, David E. Gonzalez-Neira, Anna Goode, Ellen L. Goodman, Marc T. Greene, Mark H. Gronwald, Jacek Guenel, Pascal Haiman, Christopher A. Hall, Per Hallberg, Emily Hamann, Ute Hansen, Thomas V. O. Harrington, Patricia A. Hartman, Mikael Hassan, Norhashimah Healey, Sue Heitz, Florian Herzog, Josef Hogdall, Estrid Hogdall, Claus K. Hogervorst, Frans B. L. Hollestelle, Antoinette Hopper, John L. Hulick, Peter J. Huzarski, Tomasz Imyanitov, Evgeny N. Isaacs, Claudine Ito, Hidemi Jakubowska, Anna Janavicius, Ramunas Jensen, Allan John, Esther M. Johnson, Nichola Kabisch, Maria Kang, Daehee Kapuscinski, Miroslav Karlan, Beth Y. Khan, Sofia Kiemeney, Lambertus A. Kjaer, Susanne Kruger Knight, Julia A. Konstantopoulou, Irene Kosma, Veli-Matti Kristensen, Vessela Kupryjanczyk, Jolanta Kwong, Ava de la Hoya, Miguel Laitman, Yael Lambrechts, Diether Le, Nhu De Leeneer, Kim Lester, Jenny Levine, Douglas A. Li, Jingmei Lindblom, Annika Long, Jirong Lophatananon, Artitaya Loud, Jennifer T. Lu, Karen Lubinski, Jan Mannermaa, Arto Manoukian, Siranoush Le Marchand, Loic Margolin, Sara Marme, Frederik Massuger, Leon F. A. G. Matsuo, Keitaro Mazoyer, Sylvie McGuffog, Lesley McLean, Catriona McNeish, Iain Meindl, Alfons Menon, Usha Mensenkamp, Arjen R. Milne, Roger L. Montagna, Marco Moysich, Kirsten B. Muir, Kenneth Mulligan, Anna Marie Nathanson, Katherine L. Ness, Roberta B. Neuhausen, Susan L. Nevanlinna, Heli Nord, Silje Nussbaum, Robert L. Odunsi, Kunle Offit, Kenneth Olah, Edith Olopade, Olufunmilayo I. Olson, Janet E. Olswold, Curtis O'Malley, David Orlow, Irene Orr, Nick Osorio, Ana Park, Sue Kyung Pearce, Celeste L. Pejovic, Tanja Peterlongo, Paolo Pfeiler, Georg Phelan, Catherine M. Poole, Elizabeth M. Pylkas, Katri Radice, Paolo Rantala, Johanna Rashid, Muhammad Usman Rennert, Gad Rhenius, Valerie Rhiem, Kerstin Risch, Harvey A. Rodriguez, Gus Rossing, Mary Anne Rudolph, Anja Salvesen, Helga B. Sangrajrang, Suleeporn Sawyer, Elinor J. Schildkraut, Joellen M. Schmidt, Marjanka K. Schmutzler, Rita K. Sellers, Thomas A. Seynaeve, Caroline Shah, Mitul Shen, Chen-Yang Shu, Xiao-Ou Sieh, Weiva Singer, Christian F. Sinilnikova, Olga M. Slager, Susan Song, Honglin Soucy, Penny Southey, Melissa C. Stenmark-Askmalm, Marie Stoppa-Lyonnet, Dominique Sutter, Christian Swerdlow, Anthony Tchatchou, Sandrine Teixeira, Manuel R. Teo, Soo H. Terry, Kathryn L. Terry, Mary Beth Thomassen, Mads Tibiletti, Maria Grazia Tihomirova, Laima Tognazzo, Silvia Toland, Amanda Ewart Tomlinson, Ian Torres, Diana Truong, Therese Tseng, Chiu-chen Tung, Nadine Tworoger, Shelley S. Vachon, Celine van den Ouweland, Ans M. W. van Doorn, Helena C. van Rensburg, Elizabeth J. Van't Veer, Laura J. Vanderstichele, Adriaan Vergote, Ignace Vijai, Joseph Wang, Qin Wang-Gohrke, Shan Weitzel, Jeffrey N. Wentzensen, Nicolas Whittemore, Alice S. Wildiers, Hans Winqvist, Robert Wu, Anna H. Yannoukakos, Drakoulis Yoon, Sook-Yee Yu, Jyh-Cherng Zheng, Wei Zheng, Ying Khanna, Kum Kum Simard, Jacques Monteiro, Alvaro N. French, Juliet D. Couch, Fergus J. Freedman, Matthew L. Easton, Douglas F. Dunning, Alison M. Pharoah, Paul D. Edwards, Stacey L. Chenevix-Trench, Georgia Antoniou, Antonis C. Gayther, Simon A. CA GEMO Study Collaborators EMBRACE Hereditary Breast & Ovarian Canc R KConFab Investigators Australian Ovarian Canc Study Grp TI Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; EPITHELIAL-CELLS; COMMON VARIANTS; IDENTIFIES 3; MODIFIERS; REVEALS; GWAS; GENE; INVESTIGATORS AB A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (P<2 x 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 30-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. C1 [Lawrenson, Kate; Ramus, Susan J.; Delgado, Melissa K.; Lee, Janet M.; Lee, Eunjung; Haiman, Christopher A.; Le, Nhu; Pearce, Celeste L.; Tseng, Chiu-chen; Wu, Anna H.; Gayther, Simon A.] Univ Southern Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Kar, Siddhartha; Tyrer, Jonathan; Ghoussaini, Maya; Rhenius, Valerie; Shah, Mitul; Song, Honglin; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England. [McCue, Karen; Beesley, Jonathan; Healey, Sue; Khanna, Kum Kum; French, Juliet D.; Edwards, Stacey L.; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia. [Kuchenbaeker, Karoline; Michailidou, Kyriaki; Barrowdale, Daniel; Bolla, Manjeet K.; Dennis, Joe; Ellis, Steve; Frost, Debra; McGuffog, Lesley; Wang, Qin; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China. [Li, Qiyuan; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02215 USA. [Aittomaki, Kristiina] Univ Helsinki, Helsinki Univ Hosp, Dept Clin Genet, Helsinki 00029, Finland. [Andrulis, Irene L.; Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA. [Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, S-17177 Stockholm, Sweden. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ 08903 USA. [Barile, Monica; Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Barkardottir, Rosa B.] Univ Iceland, Landspitali Univ Hosp, Dept Pathol, Reykjavik 6001692039, Iceland. [Barkardottir, Rosa B.] Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik 6001692039, Iceland. [Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Univ Hosp Erlangen, D-91054 Erlangen, Germany. [Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Canc Genet Program, E-28029 Madrid, Spain. [Benitez, Javier] Ctr Invest Red Enfermedades Raras, Valencia 28029, Spain. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA. [Bjorge, Line; Salvesen, Helga B.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [Bjorge, Line; Salvesen, Helga B.] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, N-5020 Bergen, Norway. [Blomqvist, Carl] Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. [Blot, William; Cai, Qiuyin; Long, Jirong; Shu, Xiao-Ou; Toland, Amanda Ewart; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA. [Blot, William] Int Epidemiol Inst, Rockville, MD 20850 USA. [Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany. [Bojesen, Anders] Vejle Hosp, Dept Clin Genet, DK-7100 Vejle, Denmark. [Bojesen, Stig E.; Osorio, Ana] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark. [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. [Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, DK-2730 Herlev, Denmark. [Borresen-Dale, Anne-Lise; Kristensen, Vessela] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, N-0310 Oslo, Norway. [Borresen-Dale, Anne-Lise; Kristensen, Vessela; Nord, Silje] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany. [Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany. [Brennan, Paul] Int Agcy Res Canc, F-69008 Lyon, France. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, D-69121 Heidelberg, Germany. [Bruinsma, Fiona; Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Brunet, Joan] Catalan Inst Oncol, IDIBGI Inst Invest Biomed Girona, Hereditary Canc Program, Genet Counseling Unit, Girona 08908, Spain. [Buhari, Shaik Ahmad; Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore 119077, Singapore. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, D-69120 Heidelberg, Germany. [Burwinkel, Barbara; Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany. [Butzow, Ralf; Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Butzow, Ralf; Khan, Sofia; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00029, Finland. [Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Med, Salt Lake City, UT 84112 USA. [Caldes, Trinidad; de la Hoya, Miguel; Toland, Amanda Ewart] IdISSC El Inst Invest Sanitaria Hosp Clin San Car, Hosp Clin San Carlos, Mol Oncol Lab, Madrid 28040, Spain. [Campbell, Ian] Peter MacCallum Canc Ctr, Canc Genet Lab, Melbourne, Vic 3002, Australia. [Canniotto, Rikki] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Canc Pathol & Prevent, Buffalo, NY 14263 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69121 Heidelberg, Germany. [Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, D-20246 Hamburg, Germany. [Chiquette, Jocelyne] Univ Quebec, Ctr Hosp, Ctr Rech FRSQ, Ctr Malad Deschenes Fabia,Unite Rech Sante Popula, Quebec City, PQ G1J 1Z4, Canada. [Choi, Ji-Yeob; Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul 08826, South Korea. [Bojesen, Anders; Choi, Ji-Yeob; Kang, Daehee; Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea. [Claes, Kathleen B. M.; De Leeneer, Kim] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield S10 2TN, S Yorkshire, England. [Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, HT Chan Sch Publ Hlth, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA. [Cramer, Daniel W.; Poole, Elizabeth M.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield S10 2TN, S Yorkshire, England. [Cybulski, Cezary; Huzarski, Tomasz; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland. [Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Damiola, Francesca; Mazoyer, Sylvie] Univ Lyon, Ctr Rech Cancerol Lyon, CNRS, INSERM,U1052,UMR5286, F-69373 Lyon, France. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, PL-44101 Warsaw, Poland. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta] Inst Oncol, PL-44101 Warsaw, Poland. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 Leiden, Netherlands. [Diez, Orland] Univ Hosp Vall Hebron, Oncogenet Grp, Vall Hebron Inst Oncol, Barcelona 08035, Spain. [Diez, Orland] Univ Autonoma Barcelona, Barcelona 08035, Spain. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Dept Community & Family Med, Lebanon, NH 03755 USA. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0083 Pretoria, South Africa. [Dumont, Martine; Soucy, Penny; Simard, Jacques] Univ Laval, Quebec Res Ctr, Ctr Hosp Univ, Genom Ctr, Quebec City, PQ G1V 4G2, Canada. [Ehrencrona, Hans] Uppsala Univ, Dept Immunol Genet & Pathol, S-75105 Uppsala, Sweden. [Ehrencrona, Hans; Stenmark-Askmalm, Marie] Univ Lund Hosp, Dept Clin Genet, S-22100 Lund, Sweden. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany. [Evans, D. Gareth] Univ Manchester, Cent Manchester Univ Hosp NHS Fdn Trust, Inst Human Dev, Manchester Acad Hlth Sci Ctr,Genom Med, Manchester M13 9PL, Lancs, England. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Feliubadalo, Lidia] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Mol Diagnost Unit, Hereditary Canc Program, Barcelona 08908, Spain. [Figueroa, Jonine; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Flesch-Janys, Dieter] Univ Med Ctr Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany. [Flesch-Janys, Dieter] Univ Med Ctr Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, D-20246 Hamburg, Germany. [Fletcher, Olivia; Johnson, Nichola; Orr, Nick] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW7 3RP, England. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno 62500, Czech Republic. [Foretova, Lenka] Med Fac MU, Brno 62500, Czech Republic. [Fostira, Florentia; Konstantopoulou, Irene] Aghia Paraskevi Attikis, Natl Ctr Sci Res Demokritos, INRASTES Inst Nucl & Radiol Sci & Technol, Mol Diagnost Lab, Athens 15310, Greece. [Foulkes, William D.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ H2W 1S6, Canada. [Foulkes, William D.] McGill Univ, Dept Oncol, Montreal, PQ H2W 1S6, Canada. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66103 USA. [Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Gambino, Gaetana] Univ & Univ Hosp Pisa, Dept Lab Med, Sect Genet Oncol, I-56126 Pisa, Italy. [Ganz, Patricia A.] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, UCLA Sch Med & Publ Hlth, Los Angeles, CA 90024 USA. [Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02215 USA. [Garcia-Closas, Montserrat; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL EGA Inst Womens Hlth, Womens Canc, London WC1E 6AU, England. [Giles, Graham G.; Hopper, John L.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Glasspool, Rosalind] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow G12 0YN, Lanark, Scotland. [Godwin, Andrew K.] Univ Kansas, Univ Kansas Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal H3A 1A1, PQ, Canada. [Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. [Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT 84132 USA. [Goode, Ellen L.; Hallberg, Emily; Olswold, Curtis; Slager, Susan; Vachon, Celine; Couch, Fergus J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55902 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA. [Greene, Mark H.; Loud, Jennifer T.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Gronwald, Jacek] Pomeranian Med Univ, Dept Genet & Pathol, PL-70204 Szczecin, Poland. [Guenel, Pascal; Truong, Therese] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, F-94805 Villejuif, France. [Guenel, Pascal; Truong, Therese] Univ Paris 11, F-91405 Villejuif, France. [Hamann, Ute; Kabisch, Maria; Rashid, Muhammad Usman; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark. [Harrington, Patricia A.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Dept Oncol, Cambridge CB1 8RN, England. [Hartman, Mikael] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 119077, Singapore. [Hassan, Norhashimah; Teo, Soo H.] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur 50603, Malaysia. [Hassan, Norhashimah; Teo, Soo H.] Canc Res Initiat Fdn, Subang Jaya 47500, Selangor, Malaysia. [Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany. [Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany. [Herzog, Josef; Weitzel, Jeffrey N.] City Hope Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA 91010 USA. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, DK-2730 Copenhagen, Denmark. [Hogdall, Estrid; Kjaer, Susanne Kruger] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, DK-2100 Copenhagen, Denmark. [Hogdall, Claus K.; Jensen, Allan; Kjaer, Susanne Kruger] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, NL-1006 Amsterdam, Netherlands. [Hollestelle, Antoinette; Seynaeve, Caroline] Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, NL-3015 Rotterdam, Netherlands. [Hulick, Peter J.] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL 60201 USA. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg 197758, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Ito, Hidemi] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Aichi 4648681, Japan. [Janavicius, Ramunas] Ctr Innovat Med, State Res Inst, LT-01102 Vilnius, Lithuania. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA. [Kang, Daehee; Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 08826, South Korea. [Kapuscinski, Miroslav] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne, Vic 3010, Australia. [Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Womens Canc Program Samuel Oschin Comprehens Canc, Los Angeles, CA 90048 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6500 Nijmegen, Netherlands. [Bojesen, Anders; Knight, Julia A.] Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5T 3M7, Canada. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio 70210, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, Kuopio 70210, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio 70210, Finland. [Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, N-1478 Oslo, Norway. [Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China. [Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Louvain, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden. [Lophatananon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Manoukian, Siranoush] Ist Nazl Tumori, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA. [Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, SE-17177 Stockholm, Sweden. [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumour Dis, D-69117 Heidelberg, Germany. [Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6500 Nijmegen, Netherlands. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8128582, Japan. [McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic 3004, Australia. [McNeish, Iain] Univ Glasgow, Inst Canc Sci, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, D-81675 Munich, Germany. [Mensenkamp, Arjen R.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 Nijmegen, Netherlands. [Montagna, Marco] IRCCS, Inst Oncol Veneto IOV, Immunol & Mol Oncol Unit, I-35128 Padua, Italy. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England. [Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON M5G 1L7, Canada. [Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L7, Canada. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77030 USA. [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA 91010 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Offit, Kenneth; Vijai, Joseph] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, H-1122 Budapest, Hungary. [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [O'Malley, David] Ohio State Univ, Columbus, OH 43210 USA. [O'Malley, David] James Graham Brown Canc Ctr, Columbus, OH 43210 USA. [Orlow, Irene] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA. [Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid 28019, Spain. [Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid 28029, Spain. [Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 03080, South Korea. [Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. [Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Peterlongo, Paolo] FIRC Italian Fdn Canc Res, Inst Mol Oncol, IFOM, I-20139 Milan 16, Italy. [Pfeiler, Georg; Singer, Christian F.] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, A-1090 Vienna, Austria. [Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33606 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pylkas, Katri; Winqvist, Robert] Ctr NordLab, Northern Finland Lab, Lab Canc Genet & Tumour Biol, FI-90014 Oulu, Finland. [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Dept Clin Chem & Biocenter Oulu, Lab Canc Genet & Tumour Biol, FI-90014 Oulu, Finland. [Radice, Paolo] Ist Nazl Tumori, Fdn IRCCS Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, S-17176 Stockholm, Sweden. [Rashid, Muhammad Usman] Shaukat Khanum Mem Canc Hosp & Res Ctr SKMCH & RC, Dept Basic Sci, Lahore 54000, Pakistan. [Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, IL-34362 Haifa, Israel. [Rennert, Gad] Carmel Hosp, B Rappaport Fac Med, Dept Community Med & Epidemiol, IL-34362 Haifa, Israel. [Rhiem, Kerstin] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany. [Rhiem, Kerstin] Univ Hosp Cologne, Ctr Mol Med Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA. [Rodriguez, Gus] NorthShore Univ HealthSyst, Div Gynecol Oncol, Evanston, IL 60201 USA. [Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok 10400, Thailand. [Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London SE1 9RT, England. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC 27710 USA. [Schmidt, Marjanka K.; Van't Veer, Laura J.] Netherlands Canc Inst, Antoni van Leeuwenhoek Hosp, NL-1066 CX Amsterdam, Netherlands. [Schmutzler, Rita K.] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, D-50676 Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, D-50676 Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med, D-50676 Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, D-50676 Cologne, Germany. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei 115, Taiwan. [Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung 404, Taiwan. [Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Sinilnikova, Olga M.] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequent, F-69008 Lyon, France. [Sinilnikova, Olga M.] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS UMR5286, INSERM U1052, F-69003 Lyon, France. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia. [Stenmark-Askmalm, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, S-58183 Linkoping, Sweden. [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, U830, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Sorbonne Paris Cite, Univ Paris Descartes, F-75270 Paris, France. [Sutter, Christian] Univ Heidelberg Hosp, Dept Human Genet, Inst Human Genet, D-69120 Heidelberg, Germany. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, P-4200072 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4099002 Oporto, Portugal. [Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark. [Tibiletti, Maria Grazia] Univ Insubria, Osped Circolo, UO Anat Patol, I-21100 Varese, Italy. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, LV-1067 Riga, Latvia. [Tognazzo, Silvia] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, I-35128 Padua 64, Italy. [Toland, Amanda Ewart] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England. [Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3015 CE Rotterdam, Netherlands. [van Doorn, Helena C.] Erasmus MC Canc Inst, Dept Gynecol, Family Canc Clin, NL-3015 CE Rotterdam, Netherlands. [Vanderstichele, Adriaan; Vergote, Ignace] Univ Hosp Leuven, Dept Oncol, Div Gynecol Oncol, B-3000 Louvain, Belgium. [Wang-Gohrke, Shan] Univ Hosp Ulm, D-89069 Ulm, Germany. [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wildiers, Hans] Univ Hosp Leuven, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens 15310, Greece. [Yoon, Sook-Yee] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya 47500, Malaysia. [Yoon, Sook-Yee] Univ Malaya, Univ Malaya Med Ctr, Fac Med, Univ Malaya Canc Res Inst, Kuala Lumpur 59100, Malaysia. [Yu, Jyh-Cherng] Natl Def Med Ctr, Triserv Gen Hosp, Dept Surg, Taipei 114, Taiwan. [Zheng, Ying] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China. [Monteiro, Alvaro N.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Canc Epidemiol Program, Tampa, FL 33612 USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Lawrenson, Kate] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Gayther, Simon A.] Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA. RP Antoniou, AC (reprint author), Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. EM aca20@medschl.cam.ac.uk RI manoukian, siranoush/E-7132-2017; montagna, marco/E-2225-2012; Dork, Thilo/J-8620-2012; Nord, Silje/R-5212-2016; Li, Jingmei/I-2904-2012; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; Knight, Julia/A-6843-2012; Osorio, Ana/I-4324-2014 OI Ehrencrona, Hans/0000-0002-5589-3622; Brunet, Joan/0000-0003-1945-3512; Yannoukakos, Drakoulis/0000-0001-7509-3510; Dunning, Alison Margaret/0000-0001-6651-7166; Fox, Stephen/0000-0002-7648-8896; VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans, Gareth/0000-0002-8482-5784; manoukian, siranoush/0000-0002-6034-7562; montagna, marco/0000-0002-4929-2150; Nord, Silje/0000-0002-3271-5356; Li, Jingmei/0000-0001-8587-7511; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; Osorio, Ana/0000-0001-8124-3984 FU National Cancer Institute (USA) [UM1 CA164920, CA 27469]; National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); Victorian Breast Cancer Research Consortium; Dutch Cancer Society [NKI 2007-3839, 2009 4363, RUL 1997-1505, DDHK 2004-3124, DDHK 2009-4318, NKI1998-1854, NKI2004-3088, NKI2007-3756]; Breast Cancer Research Trust, UK; Breakthrough Breast Cancer; NHS; National Cancer Research Network (NCRN); NIHR Comprehensive Biomedical Research Centre; Guy's and St. Thomas' NHS Foundation Trust; King's College London, United Kingdom; Oxford Biomedical Research Centre; Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research Center (DKFZ); Chief Physician Johan Boserup and Lise Boserup Fund; Danish Medical Research Council; Instituto de Salud Carlos III; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI12/00070]; California Breast Cancer Act of 1993; California Breast Cancer Research Fund [97-10500]; National Institutes of Health [R01 CA77398, CA128978]; California Department of Public Health; Lon V Smith Foundation [LVS39420]; Baden Wurttemberg Ministry of Science, Research and Arts; Deutsche Krebshilfe [107 352]; Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114, 01KH0402]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance; Institute of the Ruhr University Bochum (IPA), Bochum; Department of Internal Medicine; Evangelische Kliniken Bonn gGmbH; Johanniter Krankenhaus, Bonn, Germany; Helsinki University Central Hospital Research Fund; Academy of Finland [266528, 250083, 122715]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; Friends of Hannover Medical School; Rudolf Bartling Foundation; special Government Funding (EVO) of Kuopio University Hospital grants; Cancer Fund of North Savo; Finnish Cancer Organizations; University of Eastern Finland; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales, Victoria; Cancer Council of New South Wales, Tasmania; Cancer Council of New South Wales, South Australia; Cancer Foundation of Western Australia; United States Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council Victoria; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; National Health and Medical Research Council of Australia (NHMRC) [400413, 400281, 199600]; California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098]; California Department of Health; National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program [N01CN25403]; 'Stichting tegen Kanker' [232-2008, 196-2010]; FWO; Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419]; Hamburg Cancer Society; Italian Association for Cancer Research (AIRC); Italian citizens [5/1000]; Fondazione IRCCS Istituto Nazionale Tumori; Quebec Breast Cancer Foundation; Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program [CRN-87521]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Malaysian Ministry of Science, Technology and Innovation (MOSTI); Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer Research Initiatives Foundation (CARIF); Biomedical Research Council, Singapore [BMRC08/1/35/19/550]; National medical Research Council, Singapore [NMRC/CG/SERI/2010]; NIH [CA128978, R01CA100374, CA116167, CA176785, R01CA64277, R01CA148667, R37CA70867]; Finnish Cancer Foundation; Academy of Finland (Center of Excellence) [251314]; University of Oulu; University of Oulu Support Foundation; special Governmental EVO funds; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA; Marit and Hans Rausings Initiative Against Breast Cancer; Agency for Science, Technology and Research of Singapore (AstarSTAR); US National Institute of Health (NIH); Susan G. Komen Breast Cancer Foundation; Genetic Associations and Mechanisms in Oncology (GAME-ON) Network [U19 CA148065]; Yorkshire Cancer Research [S295, S299, S305PA]; Sheffield Experimental Cancer Medicine Centre; Cancer Research UK [C490/A10124, C490/A6187, C490/A10119, C536/A13086, C536/A6689, C1287/A10118, C1287/A11990, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565]; UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; NUS start-up Grant; National University Cancer Institute Singapore (NCIS) Centre Grant; NMRC Clinician Scientist Award; Biomedical Research Council [05/1/21/19/425]; DKFZ; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Breast Cancer Research Foundation; David F. and Margaret T. Grohne Family Foundation; Hellenic Cooperative Oncology Group research grant [HR R_BG/04]; Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II; European Union (European Social Fund - ESF); Greek national funds through Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - ARISTEIA; Institute of Cancer Research (ICR), London; American Cancer Society [CRTG-00-196-01-CCE]; California Cancer Research Program [00-01389 V-20170, N01-CN25403, 2II0200]; Canadian Institutes for Health Research [MOP-86727]; Cancer Council Queensland; Cancer Institute of New Jersey; Celma Mastry Ovarian Cancer Foundation; Danish Cancer Society [94-222-52]; ELAN Program of the University of Erlangen-Nuremberg; Eve Appeal; Helse Vest; Imperial Experimental Cancer Research Centre [C1312/A15589]; Norwegian Cancer Society; Norwegian Research Council; Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Ministry of Health Labour and Welfare of Japan; L and S Milken Foundation; Polish Ministry of Science and Higher Education [4 PO5C 028 14, 2 PO5A 068 27]; Cancer Research Initiatives Foundation; Roswell Park Cancer Institute Alliance Foundation; US National Cancer Institute [K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966, R01-CA063678]; US National Cancer Institute (Intramural research funds); US Army Medical Research and Material Command [DAMD17-01-1-0729, DAMD17-98-1-8659, DAMD17-02-1-0666, DAMD17-02-10669, W81XWH-10-1-0280]; National Health and Medical Research Council of Australia [400281, 199600]; German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]; Minnesota Ovarian Cancer Alliance; Mayo Foundation; Fred C. and Katherine B. Andersen Foundation; Lon V. Smith Foundation [LVS-39420]; Oak Foundation; OHSU Foundation; Mermaid I project; Rudolf-Bartling Foundation; UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; Imperial College London; University College Hospital 'Womens Health Theme'; Royal Marsden Hospital; WorkSafeBC; National Cancer Institute [UM1 CA164920, RC4CA153828]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08]; RTICC [06/0020/1060]; Mutua Madrilena Foundation (FMMA); City of Hope Clinical Cancer Genetics Community Network (COH-CCGCRN) [SAF2010-20493]; Hereditary Cancer Research Registry; Office of the Director, National Institutes of Health; Cancer Research - UK [C1287/A10118, C12292/A11174]; NHMRC Program Grant; Greek national funds through Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; NIHR grant; Royal Marsden NHS Foundation Trust; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue Nationale Contre le Cancer; Association 'Le cancer du sein, parlons-en!' Award; Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program; French National Institute of Cancer (INCa); Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant) [P30-CA051008]; Fisher Center for Familial Cancer Research; Swing Fore the Cure; GOA grant (Ghent University) [BOF10/GOA/019]; Ghent University Hospital; ISCIII (Spain) [RD12/0036/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Hospital Research Fund; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hong Kong Hereditary Breast Cancer Family Registry; Dr Ellen Li Charitable Foundation; Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]; Norwegian EEA Financial Mechanism [Hu0115/NA/2008-3/OP-9]; Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290, 2014SGR364]; Icelandic Association 'Walking for Breast Cancer Research'; Landspitali University Hospital Research Fund; Canadian Breast Cancer Research Alliance [019511]; Ministero della Salute; Istituto Oncologico Veneto grant; Liga Portuguesa Contra o Cancro; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201, CA125183, R01 CA142996, 1U01CA161032]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; MH CZ - DRO (MMCI) [00209805]; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Charles University in Prague project [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Research Fund; Intramural Research Program of the US National Cancer Institute, NIH; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Russian Federation for Basic Research [13-04-92613, 14-04-93959, 15-04-01744]; NRG Oncology Statistical and Data Center [CA 37517]; NRG Oncology's Cancer Prevention and Control Committee [CA 101165]; Ohio State University Comprehensive Cancer Center; ITT (Istituto Toscano Tumori); Isreal cancer association; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; CRUK; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Susan G. Komen Foundation; European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Post-Cancer GWAS initiative (GAME-ON initiative) [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; [KULPFV/10/016-SymBioSysII]; [P30 CA68485]; [FISPI08/1120]; [PBZ_KBN_122/P05/2004] FX Funding: BCAC: The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The ACP study is funded by the Breast Cancer Research Trust, UK. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev HospitalThe CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation.; The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP), which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. (MBCSG) is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000'). The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program - grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and the National medical Research Council, Singapore (NMRC/CG/SERI/2010). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities.; The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The pKARMA study was supported by Marit and Hans Rausings Initiative Against Breast CancerThe RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (AstarSTAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065. The SBCS was supported by Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental Cancer Medicine Centre. SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. SKKDKFZS is supported by the DKFZ. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation, the Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, the European Union (European Social Fund - ESF), and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre.; OCAC: Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389 V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L and S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50-CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01-CA071966, R01-CA063678 and Intramural research funds); the US Army Medical Research and Material Command (DAMD17-98-1-8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-10669, W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC.; CIMBA (BCFR-all): This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. (BFBOCC-LT) BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; (BIDMC) BIDMC is supported by the Breast Cancer Research Foundation. (BMBSA) BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. (BRICOH) SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. (CBCS) This work was supported by the NEYE Foundation. (CNIO) This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA) and SAF2010-20493 (COH-CCGCRN) City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. (CONSIT TEAM) Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to Siranoush Manoukian. (CORE) The CIMBA data management and data analysis were supported by Cancer Research - UK grants C12292/A11174 and C1287/A10118. SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research - UK Senior Cancer Research Fellow. (DEMOKRITOS) This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA. Investing in knowledge society through the European Social Fund.(DKFZ) The DKFZ study was supported by the DKFZ. (EMBRACE) EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. (GC-HBOC) The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). (GEMO) The study was supported by the Ligue Nationale Contre le Cancer; the Association 'Le cancer du sein, parlons-en!' Award; the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and the French National Institute of Cancer (INCa).; (GEORGETOWN) CI received support from the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial Cancer Research, and Swing Fore the Cure. (G-FAST) Kim De Leeneer is supported by GOA grant BOF10/GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital. (HCSC) HCSC supported by a grant RD12/0036/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. (HEBCS) The HEBCS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. (HEBON) The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. (HRBCP) HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong (HUNBOCS) Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA Financial Mechanism Hu0115/NA/2008-3/OP-9. (ICO) Contract grant sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290 and 2014SGR364. (IHCC) The IHCC was supported by Grant PBZ_KBN_122/P05/2004(ILUH) The ILUH group was supported by the Icelandic Association 'Walking for Breast Cancer Research' and by the Landspitali University Hospital Research Fund. (INHERIT) This work was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program, the Canadian Breast Cancer Research Alliance-grant # 019511 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. (IOVHBOCS) IOVHBOCS is supported by Ministero della Salute and '5x1,000' Istituto Oncologico Veneto grant. (IPOBCS) This study was in part supported by Liga Portuguesa Contra o Cancro.(KCONFAB) kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; (KOHBRA) KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020350). (MAYO) MAYO is supported by NIH grants CA116167, CA128978 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation.; (MCGILL) Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade (MODSQUAD) MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). (MSKCC) MSKCC is supported by grants from the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin Research Fund. (NAROD) 1R01 CA149429-01. (NCI) The research of Drs MH Greene, JT Loud and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. (NICCC) NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. (NNPIO) This work has been supported by the Russian Federation for Basic Research (grants 13-04-92613, 14-04-93959 and 15-04-01744). (NRG Oncology) This study was supported by National Cancer Institute grants to the NRG Oncology Administrative Office and Tissue Bank (CA 27469), the NRG Oncology Statistical and Data Center (CA 37517), and NRG Oncology's Cancer Prevention and Control Committee (CA 101165). (OSU CCG) OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. (PBCS) This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013. (SEABASS) Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM. C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. (SMC) This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium (SWE-BRCA) SWE-BRCA collaborators are supported by the Swedish Cancer Society. (UCHICAGO) UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor.(UCLA) Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. (UCSF) UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. (UKFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. (UPENN) National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. (UPITT/MWH) Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program; Hackers for Hope Pittsburgh. (VFCTG) Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation.; Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund and grants R01-CA122443 and P50-CA136393. NR 56 TC 2 Z9 2 U1 22 U2 22 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 SEP PY 2016 VL 7 AR 12675 DI 10.1038/ncomms12675 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY7BV UT WOS:000385285100002 PM 27601076 ER PT J AU Lee, H Noh, H Mun, J Gu, C Sever, S Park, S AF Lee, Haeryung Noh, Hyuna Mun, Jiyoung Gu, Changkyu Sever, Sanja Park, Soochul TI Anks1a regulates COPII-mediated anterograde transport of receptor tyrosine kinases critical for tumorigenesis SO NATURE COMMUNICATIONS LA English DT Article ID ALZHEIMERS PRECURSOR PROTEIN; ENDOPLASMIC-RETICULUM; ANKYRIN REPEAT; CANCER; EPHA2; ADAPTER; DOMAINS; COMPLEX; FAMILY; EXPORT AB ErbB2 signalling, which is amplified by EphA2 binding, is an important therapeutic target for breast cancer. Despite the importance of the EphA2/ErbB2 complex in promoting breast tumorigenesis, the mechanism by which these receptor tyrosine kinases (RTKs) are exported from the endoplasmic reticulum (ER) remains poorly understood. Here we report that the PTB adaptor Anks1a is specifically localized to the ER on its own serine phosphorylation. Once there, Anks1a acts as an important regulator of COPII-mediated EphA2 ER export. The Anks1a ankyrin repeat domain binds EphA2 and causes it to accumulate at sites of ER exit. Simultaneously, the Anks1a PTB domain binds Sec23. This induces internalization of EphA2 via COPII vesicles, while Anks1a remains behind on the ER membrane. EphA2 also binds ErbB2 in the ER and seems to load ErbB2 into growing COPII carriers. Together, our study reveals a novel mechanism that regulates the loading of RTKs into COPII vesicles. C1 [Lee, Haeryung; Noh, Hyuna; Park, Soochul] Sookmyung Womens Univ, Dept Biol Sci, Chungpa Ro 47gil 100, Seoul 140742, South Korea. [Mun, Jiyoung] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Songnam 13135, Gyeonggi Do, South Korea. [Gu, Changkyu; Sever, Sanja] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. RP Park, S (reprint author), Sookmyung Womens Univ, Dept Biol Sci, Chungpa Ro 47gil 100, Seoul 140742, South Korea. EM scpark@sookmyung.ac.kr FU National Research Foundation of Korea [2013M3C7A1056565, 2013R1A2A2A01005037, 2015R1A2A1A15052871] FX We are indebted to Yujin Kim for generating the Anksla knockout mice. We also thank Jinoh Kim and Jung Su Park for helpful discussions regarding Trp fluorescence assay. This work was supported by grants 2013M3C7A1056565, 2013R1A2A2A01005037 and 2015R1A2A1A15052871 from the National Research Foundation of Korea. NR 36 TC 1 Z9 1 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 SEP PY 2016 VL 7 AR 12799 DI 10.1038/ncomms12799 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY8FK UT WOS:000385364000004 PM 27619642 ER PT J AU McKean, DM Homsy, J Wakimoto, H Patel, N Gorham, J DePalma, SR Ware, JS Zaidi, S Ma, WJ Patel, N Lifton, RP Chung, WK Kim, R Shen, YF Brueckner, M Goldmuntz, E Sharp, AJ Seidman, CE Gelb, BD Seidman, JG AF McKean, David M. Homsy, Jason Wakimoto, Hiroko Patel, Neil Gorham, Joshua DePalma, Steven R. Ware, James S. Zaidi, Samir Ma, Wenji Patel, Nihir Lifton, Richard P. Chung, Wendy K. Kim, Richard Shen, Yufeng Brueckner, Martina Goldmuntz, Elizabeth Sharp, Andrew J. Seidman, Christine E. Gelb, Bruce D. Seidman, J. G. TI Loss of RNA expression and allele-specific expression associated with congenital heart disease SO NATURE COMMUNICATIONS LA English DT Article ID GENE; MUTATIONS; GENERATION; VARIANTS; GENOME; CELLS; TRANSCRIPTION; FRAMEWORK; MOUSE; MICE AB Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression-this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression. C1 [McKean, David M.; Homsy, Jason; Wakimoto, Hiroko; Gorham, Joshua; DePalma, Steven R.; Ware, James S.; Seidman, Christine E.; Seidman, J. G.] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [McKean, David M.; Homsy, Jason; Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Homsy, Jason] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Patel, Neil; Patel, Nihir; Sharp, Andrew J.; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [DePalma, Steven R.; Seidman, Christine E.] Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA. [Ware, James S.] Royal Brompton & Harefield Natl Hlth Serv Fdn Tru, Natl Inst Hlth Res Cardiovasc Biomed Res Unit, London SW3 6NP, England. [Ware, James S.] Imperial Coll London, London SW3 6NP, England. [Ware, James S.] Imperial Coll London, Natl Heart & Lung Inst, London SW3 6NP, England. [Zaidi, Samir; Lifton, Richard P.; Brueckner, Martina] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Ma, Wenji; Shen, Yufeng] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA. [Lifton, Richard P.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat & Med, Med Ctr, New York, NY 10032 USA. [Kim, Richard] Univ Southern Calif, Keck Sch Med, Sect Cardiothorac Surg, Los Angeles, CA 90089 USA. [Shen, Yufeng] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA. [Goldmuntz, Elizabeth] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Sharp, Andrew J.; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. RP Seidman, JG (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. EM seidman@genetics.med.harvard.edu OI DePalma, Steven/0000-0002-0381-5016; Ware, James/0000-0002-6110-5880 FU National Heart, Lung, and Blood Institute [U01-HL098188, U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162]; Cardiovascular Development Consortium [2UM1-HL098166]; Howard Hughes Medical Institute; John S. LaDue Cardiovascular Fellowship; Alan Lerner Research Award FX We thank Anne Davis, Carolyn Westhoff, Paula Castano, Ana Cepin, Patricia Lanzano, Katrina Celis, Liyong Deng, Kelly Sadamistu and Nhu Tran for assistance with tissue collection. This work was supported by grants from the National Heart, Lung, and Blood Institute to the Pediatric Cardiac Genomics Consortium (U01-HL098188, U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123 and U01-HL098162) and the Cardiovascular Development Consortium (2UM1-HL098166) and the Howard Hughes Medical Institute (R.P.L. and C.E.S.), and the John S. LaDue Cardiovascular Fellowship (J.H.) and an Alan Lerner Research Award (J.H.). The views expressed are those of the authors and do not necessarily reflect those of the National Heart, Lung, and Blood Institute or the National Institutes of Health. NR 39 TC 2 Z9 2 U1 4 U2 4 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 SEP PY 2016 VL 7 AR 12824 DI 10.1038/ncomms12824 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY8LX UT WOS:000385382800004 PM 27670201 ER PT J AU Smid, M Rodriguez-Gonzalez, FG Sieuwerts, AM Salgado, R Prager-Van der Smissen, WJC van der Vlugt-Daane, M van Galen, A Nik-Zainal, S Staaf, J Brinkman, AB de Vijver, MJV Richardson, AL Fatima, A Berentsen, K Butler, A Martin, S Davies, HR Debets, R Meijer-Van Gelder, ME van Deurzen, CHM MacGrogan, G Van den Eynden, GGGM Purdie, C Thompson, AM Caldas, C Span, PN Simpson, PT Lakhani, SR Van Laere, S Desmedt, C Ringner, M Tommasi, S Eyford, J Broeks, A Vincent-Salomon, A Futreal, PA Knappskog, S King, T Thomas, G Viari, A Langerod, A Borresen-Dale, AL Birney, E Stunnenberg, HG Stratton, M Foekens, JA Martens, JWM AF Smid, Marcel Rodriguez-Gonzalez, F. German Sieuwerts, Anieta M. Salgado, Roberto Prager-Van der Smissen, Wendy J. C. van der Vlugt-Daane, Michelle van Galen, Anne Nik-Zainal, Serena Staaf, Johan Brinkman, Arie B. de Vijver, Marc J. van Richardson, Andrea L. Fatima, Aquila Berentsen, Kim Butler, Adam Martin, Sancha Davies, Helen R. Debets, Reno Meijer-Van Gelder, Marion E. van Deurzen, Carolien H. M. MacGrogan, Gaetan Van den Eynden, Gert G. G. M. Purdie, Colin Thompson, Alastair M. Caldas, Carlos Span, Paul N. Simpson, Peter T. Lakhani, Sunil R. Van Laere, Steven Desmedt, Christine Ringner, Markus Tommasi, Stefania Eyford, Jorunn Broeks, Annegien Vincent-Salomon, Anne Futreal, P. Andrew Knappskog, Stian King, Tari Thomas, Gilles Viari, Alain Langerod, Anita Borresen-Dale, Anne-Lise Birney, Ewan Stunnenberg, Hendrik G. Stratton, Mike Foekens, John A. Martens, John W. M. TI Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration SO NATURE COMMUNICATIONS LA English DT Article ID EXPRESSION PATTERNS; SOMATIC MUTATIONS; TP53 MUTATION; E-CADHERIN; C-MYC; TUMORS; CARCINOMAS; LANDSCAPE; GENES; AMPLIFICATION AB A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others. C1 [Smid, Marcel; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Prager-Van der Smissen, Wendy J. C.; van der Vlugt-Daane, Michelle; van Galen, Anne; Debets, Reno; Meijer-Van Gelder, Marion E.; Foekens, John A.; Martens, John W. M.] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CN Rotterdam, Netherlands. [Smid, Marcel; Rodriguez-Gonzalez, F. German; Sieuwerts, Anieta M.; Prager-Van der Smissen, Wendy J. C.; van der Vlugt-Daane, Michelle; van Galen, Anne; Debets, Reno; Meijer-Van Gelder, Marion E.; Foekens, John A.; Martens, John W. M.] Erasmus Univ, Med Ctr, Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands. [Salgado, Roberto; Desmedt, Christine] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Bd Waterloo 121, B-1000 Brussels, Belgium. [Salgado, Roberto; Van den Eynden, Gert G. G. M.] TCRU GZA, Dept Pathol, B-2610 Antwerp, Belgium. [Nik-Zainal, Serena; Butler, Adam; Martin, Sancha; Davies, Helen R.; Stratton, Mike] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Nik-Zainal, Serena] Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England. [Staaf, Johan; Ringner, Markus] Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, SE-22381 Lund, Sweden. [Brinkman, Arie B.; Berentsen, Kim; Stunnenberg, Hendrik G.] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Mol Biol, Fac Sci, NL-6525 GA Nijmegen, Netherlands. [de Vijver, Marc J. van] Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Fatima, Aquila; van Deurzen, Carolien H. M.] Erasmus Univ, Erasmus MC Canc Inst, Dept Pathol, Med Ctr, NL-3015 CN Rotterdam, Netherlands. [MacGrogan, Gaetan] Inst Bergonie, Dept Biopathol, CS 61283, F-33076 Bordeaux, France. [Van den Eynden, Gert G. G. M.] Inst Jules Bordet, Mol Immunol Unit, B-1000 Brussels, Belgium. [Purdie, Colin; Thompson, Alastair M.] Ninewells Hosp & Med Sch, Dept Pathol, Dundee DD1 9SY, Scotland. [Caldas, Carlos] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England. [Span, Paul N.] Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, NL-6525 GA Nijmegen, Netherlands. [Span, Paul N.] Radboud Univ Nijmegen, Dept Lab Med, Med Ctr, NL-6525 GA Nijmegen, Netherlands. [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia. [Simpson, Peter T.; Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia. [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld 4029, Australia. [Van Laere, Steven] Univ Antwerp, Oncol Res Ctr, B-2610 Antwerp, Belgium. [Van Laere, Steven] GZA Hosp Sint Augustinus, B-2610 Antwerp, Belgium. [Tommasi, Stefania] IRCCS, Ist Tumori Giovanni Paolo 2, I-70124 Bari, Italy. [Eyford, Jorunn] Univ Iceland, Canc Res Lab, Fac Med, IS-101 Reykjavik, Iceland. [Broeks, Annegien] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. [Vincent-Salomon, Anne] Inst Curie, Dept Pathol, F-75248 Paris 05, France. [Vincent-Salomon, Anne] Inst Curie, INSERM U934, 26 Rue Ulm, F-75248 Paris 05, France. [Futreal, P. Andrew] UT MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77230 USA. [Knappskog, Stian] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway. [Knappskog, Stian] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. [King, Tari] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. [Thomas, Gilles; Viari, Alain] Synergie Lyon Canc, Ctr Leon Berard, 28 Rue Laennec, Lyon 08, France. [Viari, Alain] INRIA Grenoble Rhone Alpes, Equipe Erable, 655 Av Europe, F-38330 Montbonnot St Martin, France. [Langerod, Anita; Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Canc Genet, Inst Canc Res, N-0310 Oslo, Norway. [Langerod, Anita; Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway. [Birney, Ewan] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Hinxton CB10 1SD, Cambs, England. RP Martens, JWM (reprint author), Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CN Rotterdam, Netherlands.; Martens, JWM (reprint author), Erasmus Univ, Med Ctr, Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands. EM j.martens@erasmusmc.nl RI Span, Paul/G-4710-2012; Ringner, Markus/G-3641-2011; Simpson, Peter/F-1225-2010; OI Span, Paul/0000-0002-1930-6638; Ringner, Markus/0000-0001-5469-8940; Simpson, Peter/0000-0002-4816-8289; Knappskog, Stian/0000-0002-4153-1655; Birney, Ewan/0000-0001-8314-8497; Desmedt, Christine/0000-0002-5223-5579; Martin, Sancha/0000-0001-6213-5259; Tommasi, Stefania/0000-0002-2157-2978 FU ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study; European Community's Seventh Framework Programme [242006]; Wellcome Trust [077012/Z/05/Z]; BASIS; ERC Advanced Grant [ERC-2012-AdG-322737]; Wellcome Trust Intermediate Fellowship [WT100183MA]; Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer [NIH/NCI 5 P50 CA168504-02]; Cancer Genomics Netherlands (CGC.nl) through a grant from Netherlands Organisation of Scientific research (NWO); EU-FP7-DDR response project; Breast Cancer Research Foundation; EMBL; Icelandic Centre for Research (RANNIS) FX This work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (a European research project funded by the European Community's Seventh Framework Programme (FP7/2010-2014) under the grant agreement number 242006); the Triple Negative project funded by the Wellcome Trust (grant reference 077012/Z/05/Z).; Personally funded by grants: FGR-G, SM, KR, SM were funded by BASIS. JAF was funded through an ERC Advanced Grant (ERC-2012-AdG-322737). SN-Z is a Wellcome Beit Fellow and personally funded by a Wellcome Trust Intermediate Fellowship (WT100183MA). ALR is partially supported by the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer (NIH/NCI 5 P50 CA168504-02). AS was supported by Cancer Genomics Netherlands (CGC.nl) through a grant from the Netherlands Organisation of Scientific research (NWO). MS was supported by the EU-FP7-DDR response project. CD was supported by a grant from the Breast Cancer Research Foundation. EB was funded by EMBL. JE was funded by The Icelandic Centre for Research (RANNIS). NR 43 TC 4 Z9 4 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 SEP PY 2016 VL 7 AR 12910 DI 10.1038/ncomms12910 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY7CG UT WOS:000385286300003 PM 27666519 ER PT J AU Dong, TK Ona, K Scandurra, AE Demetriou, SK Oh, DH AF Dong, Tiffany K. Ona, Katherine Scandurra, Amy E. Demetriou, Stephanie K. Oh, Dennis H. TI Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NONMELANOMA SKIN-CANCER; CYCLOBUTANE PYRIMIDINE DIMERS; COMPARATIVE GENOMIC HYBRIDIZATION; XERODERMA-PIGMENTOSUM; HUMAN KERATINOCYTES; DNA-DAMAGE; CHROMOSOMAL-ABERRATIONS; P53; LINES; TUMORS AB Squamous cell carcinomas (SCCs) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation, DNA repair kinetics and DNA repair protein expression. Relative to normal keratinocytes, four SCC cell lines were all variably sensitive to ultraviolet radiation and, except for the SCC25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6-4 photoproducts. Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced mRNA expression from XPC but not DDB2 genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB2 proteins or both were variably reduced in repair-deficient SCC cell lines. p53 levels did not correlate with DNA repair activity or with XPC and DDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair-proficient SCC25 cells depleted of p63 lost XPC expression, early global DNA repair activity and UV resistance. These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCCs. C1 [Dong, Tiffany K.; Ona, Katherine; Scandurra, Amy E.; Demetriou, Stephanie K.; Oh, Dennis H.] San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA. [Dong, Tiffany K.; Demetriou, Stephanie K.; Oh, Dennis H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. RP Oh, DH (reprint author), San Francisco VA Med Ctr, Dermatol Res Unit, San Francisco, CA 94121 USA.; Oh, DH (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM ohd@derm.ucsf.edu FU Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research and Development; NIH [R01 CA105958] FX We thank J. Cleaver for helpful discussions. Work was supported by a Merit Review Award from the Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research and Development (to D.H.O.) and in part by NIH grant R01 CA105958 (to D.H.O.). NR 43 TC 0 Z9 0 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2016 VL 92 IS 5 BP 760 EP 766 DI 10.1111/php.12625 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DW4FG UT WOS:000383597300014 PM 27499003 ER PT J AU Mack, JW Cronin, A Fasciano, K Block, SD Keating, NL AF Mack, Jennifer W. Cronin, Angel Fasciano, Karen Block, Susan D. Keating, Nancy L. TI Cancer treatment decision-making among young adults with lung and colorectal cancer: a comparison with adults in middle age SO PSYCHO-ONCOLOGY LA English DT Article ID CARE OUTCOMES RESEARCH; OF-LIFE CARE; BREAST-CANCER; CLINICAL-TRIALS; ADOLESCENTS; QUALITY; PREFERENCES; ONCOLOGY; HEALTH; PLAY AB Objective: Our aim is to understand experiences with treatment decision-making among young adults with cancer. Methods: We studied patients with lung cancer or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium, a prospective cohort study. We identified 148 young adult patients aged 21-40 years who completed baseline interview questions about cancer treatment decision-making; each was propensity score matched to three middle adult patients aged 41-60 years, for a cohort of 592 patients. Patients were asked about decision-making preferences, family involvement in decision-making, and worries about treatment. An ordinal logistic regression model evaluated factors associated with more treatment worries. Results: Young and middle-aged adults reported similar decision-making preferences (p = 0.80) and roles relative to physicians (p = 0.36). Although family involvement was similar in the age groups (p = 0.21), young adults were more likely to have dependent children in the home (60% younger versus 28% middle-aged adults, p < 0.001). Young adults reported more worries about time away from family (p = 0.002), and, in unadjusted analyses, more cancer treatment-related worries (mean number of responses of 'somewhat' or 'very' worried 2.5 for younger versus 2.2 for middle-aged adults, p = 0.02.) However, in adjusted analyses, worries were associated with the presence of dependent children in the home (odds ratio [OR] 1.55, 95% CI = 1.07-2.24, p = 0.02), rather than age. Conclusions: Young adults involve doctors and family members in decisions at rates similar to middle-aged adults but experience more worries about time away from family. Patients with dependent children are especially likely to experience worries. Treatment decision-making strategies should be based on individual preferences and needs rather than age alone. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Mack, Jennifer W.; Cronin, Angel] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Fasciano, Karen; Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Fasciano, Karen; Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_mack@dfci.harvard.edu FU National Cancer Institute (NCI) [U01CA093344]; Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network) [U01CA093332]; Harvard Medical School/Northern California Cancer Center [U01CA093324]; RAND/UCLA [U01CA093348]; University of Alabama at Birmingham [U01CA093329]; University of Iowa [U01CA093339]; University of North Carolina [U01CA093326]; Department of Veterans' Affairs [CRS02-164]; Young Adult Program at Dana-Farber Cancer Institute; NCI [K24CA181510] FX The authors would like to acknowledge the contributions of Jane C. Weeks, MD MSc, who was involved in the conception of this study, but did not live to see its completion. The work of the CanCORS Consortium was supported by the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01CA093344) and the Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network U01CA093332, Harvard Medical School/Northern California Cancer Center U01CA093324, RAND/UCLA U01CA093348, University of Alabama at Birmingham U01CA093329, University of Iowa U01CA093339, University of North Carolina U01CA093326) and a Department of Veterans' Affairs grant to the Durham VA Medical Center CRS02-164. Drs. Mack and Fasciano were supported by the Young Adult Program at Dana-Farber Cancer Institute. Dr. Keating is supported by K24CA181510 from NCI. NR 28 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2016 VL 25 IS 9 BP 1085 EP 1091 DI 10.1002/pon.3949 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ3CV UT WOS:000385722700011 PM 26335435 ER PT J AU Inhestern, L Bultmann, JC Beierlein, V Moller, B Romer, G Muriel, AC Moore, CW Koch, U Bergelt, C AF Inhestern, Laura Bultmann, Johanna C. Beierlein, Volker Moeller, Birgit Romer, Georg Muriel, Anna C. Moore, Cynthia W. Koch, Uwe Bergelt, Corinna TI Psychometric properties of the Parenting Concerns Questionnaire in cancer survivors with minor and young adult children SO PSYCHO-ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; BREAST-CANCER; PSYCHOLOGICAL DISTRESS; PSYCHOSOCIAL DISTRESS; UNDERAGE CHILDREN; HOSPITAL ANXIETY; DEPRESSION SCALE; EXPERIENCES; FAMILY; ADOLESCENTS AB Objective: Although cancer patients with minor children have become more of a focus of psychooncological research, little is known about specific parenting concerns. Instruments to assess the concerns and worries of parents with cancer are rare. The Parenting Concerns Questionnaire (PCQ) addresses this issue. We analyzed parenting concerns in cancer survivors and evaluated the German version of the PCQ. Methods: A total of 1416 cancer survivors with minor and young adult children (<= 21 years) were recruited in a register-based study. Descriptive analyses as well as reliability and validity analyses were conducted. We performed a confirmatory factorial analysis of the factor structure proposed by the authors of the original version on the PCQ. Results: Seventy-three percent of the cancer survivors were women, average age was 47.5 years (SD 5.9). Mean time since diagnosis was 44 months (SD 23.4). Between 18 and 31% of survivors reported that they were concerned about their children. The PCQ proved to be a reliable and valid instrument showing medium correlations with standardized measures in expected directions and discriminating between survivors with and without use of psychosocial support services. The factor structure was supported by the confirmatory factorial analysis. Conclusions: Assessing parenting concerns gives an additional insight into the situation of parents with cancer. In our sample of cancer survivors, we identified one out of three survivors being concerned regarding the impact of their illness on their children. The PCQ can be considered as a valid and reliable instrument with regard to identifying concerned parents with cancer. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Inhestern, Laura; Bultmann, Johanna C.; Beierlein, Volker; Koch, Uwe; Bergelt, Corinna] Univ Med Ctr Hamburg Eppendorf, Dept Med Psychol, Martinistr 52,W26, D-20246 Hamburg, Germany. [Moeller, Birgit; Romer, Georg] Univ Med Ctr Muenster, Dept Child & Adolescent Psychiat Psychotherapy &, Munster, Germany. [Muriel, Anna C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moore, Cynthia W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Inhestern, L (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Med Psychol, Martinistr 52,W26, D-20246 Hamburg, Germany. EM l.inhestern@uke.de FU German Cancer Aid (Deutsche Krebshilfe) [108303] FX This study is part of the German multisite research project 'Psychosocial Services for Children of Parents with Cancer' supported by the German Cancer Aid (Deutsche Krebshilfe, grant #108303). 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2016 VL 25 IS 9 BP 1092 EP 1098 DI 10.1002/pon.4049 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ3CV UT WOS:000385722700012 PM 26677091 ER PT J AU Manuel, MM Cho, LP Catalano, PJ Damato, AL Miyamoto, DT Tempany, CM Schmidt, EJ Viswanathan, AN AF Manuel, Matthias M. Cho, Linda P. Catalano, Paul J. Damato, Antonio. L. Miyamoto, David T. Tempany, Clare M. Schmidt, Ehud J. Viswanathan, Akila N. TI Outcomes with image-based interstitial brachytherapy for vaginal cancer SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Radiation; Brachytherapy; CT; MRI; Vaginal cancer ID HIGH-DOSE-RATE; CERVICAL-CANCER; GYNECOLOGIC BRACHYTHERAPY; GUIDED BRACHYTHERAPY; VOLUME PARAMETERS; PROSPECTIVE TRIAL; MALIGNANCIES; RECOMMENDATIONS; GUIDELINES; CARCINOMA AB Purpose: To compare clinical outcomes of image-based versus non-image-based interstitial brachytherapy (IBBT) for vaginal cancer. Methods and materials: Of 72 patients with vaginal cancer treated with brachytherapy (BT), 47 had image guidance (CT = 31, MRI = 16) and 25 did not. Kaplan-Meier (KM) estimates were generated for any recurrence, local control (LC), disease-free interval (DFI), and overall survival (OS) and Cox models were used to assess prognostic factors. Results: Median age was 66 and median follow-up time was 24 months. Median cumulative EQD2 dose was 80.8 Gy in the non-IBBT group and 77 Gy in the IBBT group. For non-IBBT versus IBBT, the 2-year KM LC was 71% vs. 93% (p = 0.03); DFI was 54% vs. 86% (p = 0.04); and OS 52% vs. 82% (p = 035). On multivariate analysis, IBBT was associated with better DFI (HR 0.24, 95% CI 0.07-0.73). Having any 2 or more of chemotherapy, high-dose-rate (HDR) BT or IBBT (temporally correlated variables) significantly reduced risk of relapse (HR = 0.33, 95% CI = 0.13-0.83), compared to having none of these factors. Conclusion: Over time, the use of chemotherapy, HDR, and IBBT has increased in vaginal cancer. The combination of these factors resulted in the highest rates of disease control. Image-guided brachytherapy for vaginal cancer patients maximizes disease control. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Manuel, Matthias M.; Cho, Linda P.; Damato, Antonio. L.; Viswanathan, Akila N.] Harvard Med Sch, Dept Radiat Oncol, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Catalano, Paul J.] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Catalano, Paul J.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Miyamoto, David T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Tempany, Clare M.; Schmidt, Ehud J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB 1,L2, Boston, MA 02115 USA. EM akila@post.harvard.edu FU NIH [R21 167800]; Boerner Family Fund; St. Laurent Family Fund; Chua Family Fund; [P41EB 015898] FX Support for this work was provided by NIH R21 167800 and the Boerner, St. Laurent and Chua Family Funds. Dr Tempany and the AMIGO team are supported by P41EB 015898. We would like to thank the AMIGO staff who provided support for Dr. Viswanathan's MR gyn program from 2002 to 2016. NR 23 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2016 VL 120 IS 3 SI SI BP 486 EP 492 DI 10.1016/j.radonc.2016.05.019 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DY7RW UT WOS:000385328000019 PM 27321150 ER PT J AU Okada, Y Hamalainen, M Pratt, K Mascarenas, A Miller, P Han, M Robles, J Cavallini, A Power, B Sieng, K Sun, LM Lew, S Doshi, C Ahtam, B Dinh, C Esch, L Grant, E Nummenmaa, A Paulson, D AF Okada, Yoshio Hamalainen, Matti Pratt, Kevin Mascarenas, Anthony Miller, Paul Han, Menglai Robles, Jose Cavallini, Anders Power, Bill Sieng, Kosal Sun, Limin Lew, Seok Doshi, Chiran Ahtam, Banu Dinh, Christoph Esch, Lorenz Grant, Ellen Nummenmaa, Aapo Paulson, Douglas TI BabyMEG: A whole-head pediatric magnetoencephalography system for human brain development research SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID SPACE SEPARATION METHOD; MAGNETIC-FIELD; EEG DATA; MEG; SKULL; SIGNALS; MAGNETOCARDIOGRAPHY; MAGNETOMETER; DISTORTION; MOVEMENTS AB We developed a 375-channel, whole-head magnetoencephalography (MEG) system ("BabyMEG") for studying the electrophysiological development of human brain during the first years of life. The helmet accommodates heads up to 95% of 36-month old boys in the USA. The unique two-layer sensor array consists of: (1) 270 magnetometers (10 mm diameter, similar to 15 mm coil-to-coil spacing) in the inner layer, (2) thirty-five three-axis magnetometers (20 mm x 20 mm) in the outer layer 4 cm away from the inner layer. Additionally, there are three three-axis reference magnetometers. With the help of a remotely operated position adjustment mechanism, the sensor array can be positioned to provide a uniform short spacing (mean 8.5 mm) between the sensor array and room temperature surface of the dewar. The sensors are connected to superconducting quantum interference devices (SQUIDs) operating at 4.2 K with median sensitivity levels of 7.5 fT/root Hz for the inner and 4 fT/root Hz for the outer layer sensors. SQUID outputs are digitized by a 24-bit acquisition system. A closed-cycle helium recycler provides maintenance-free continuous operation, eliminating the need for helium, with no interruption needed during MEG measurements. BabyMEG with the recycler has been fully operational from March, 2015. Ongoing spontaneous brain activity can be monitored in real time without interference from external magnetic noise sources including the recycler, using a combination of a lightly shielded two-layer magnetically shielded room, an external active shielding, a signal-space projection method, and a synthetic gradiometer approach. Evoked responses in the cortex can be clearly detected without averaging. These new design features and capabilities represent several advances in MEG, increasing the utility of this technique in basic neuroscience as well as in clinical research and patient studies. Published by AIP Publishing. C1 [Okada, Yoshio; Sun, Limin; Lew, Seok; Doshi, Chiran; Ahtam, Banu; Grant, Ellen] Boston Childrens Hosp, Div Newborn Med, Dept Med, Boston, MA 02115 USA. [Hamalainen, Matti; Nummenmaa, Aapo] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Pratt, Kevin; Mascarenas, Anthony; Miller, Paul; Han, Menglai; Robles, Jose; Cavallini, Anders; Power, Bill; Sieng, Kosal; Paulson, Douglas] Tristan Technol Inc, 6191 Cornerstone Court East,Suite 107, San Diego, CA 92121 USA. [Dinh, Christoph; Esch, Lorenz] Tech Univ Ilmenau, Inst Biomed Engn & Informat, Gustav Kirchhoff Str 2, D-98693 Ilmenau, Germany. RP Okada, Y (reprint author), Boston Childrens Hosp, Div Newborn Med, Dept Med, Boston, MA 02115 USA. EM yoshio.okada@childrens.harvard.edu FU NSF Major Research Instrumentation Program [NSF 0958669, NSF 0959294]; NIH [5R01EB009048, P41EB015896]; Boston Children's Hospital; Boston Investment Conference FX We wish to thank the NSF Major Research Instrumentation Program, which supported this Project (Nos. NSF 0958669 and NSF 0959294), the MNE/MNE Scan software development was also supported by NIH Grant Nos. 5R01EB009048 and P41EB015896. We also acknowledge the financial support from Boston Children's Hospital and Boston Investment Conference. We also thank Ms. Kathryn Gill and Ashley Curran of the MEG Program at Boston Children's Hospital with analysis of some of the data. NR 32 TC 1 Z9 1 U1 4 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0034-6748 EI 1089-7623 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD SEP PY 2016 VL 87 IS 9 AR 094301 DI 10.1063/1.4962020 PG 12 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA DZ1XF UT WOS:000385634500044 PM 27782541 ER PT J AU Hirsch, JA Cuesta, GM Jordan, BD Fonzetti, P Levin, L AF Hirsch, Joseph A. Cuesta, George M. Jordan, Barry D. Fonzetti, Pasquale Levin, Leann TI The Auditory Naming Test Improves Diagnosis of Naming Deficits in Dementia SO SAGE OPEN LA English DT Article DE assessment of cognitive disorders; dementia; Alzheimer's disease; naming; anomia; neuropsychology ID MENTAL-STATE-EXAMINATION; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; VASCULAR DEMENTIA; IMPAIRMENT; SCORES; AGE; PERFORMANCE; POPULATION; EDUCATION AB Many patients with presumptive Alzheimer's disease (AD) or other dementias may show minimal impairment on the Boston Naming Test (BNT), a visual confrontation naming measure. We sought to determine whether a semantic naming test, the Auditory Naming Test (ANT), would improve accuracy for identifying naming deficits in patients diagnosed with dementia (N = 458) at an outpatient memory disorders clinic. Factor analysis revealed that both tests measured the same broad construct. Frequency of naming impairment with the ANT was significantly greater than with the BNT for patients with AD, regardless of dementia severity or levels of education (p < .01). Effect size was moderate (phi = 0.45). BNT but not ANT performance declined with age in patients with AD. Sex differences were found for the BNT, but not the ANT, in the AD population. Accuracy rate of naming impairment diagnosis with the ANT in patients with AD was good (72%). Specificity (81%) and positive predictive value (PPV) (89%) with the ANT in AD were excellent, whereas sensitivity (69%) and negative predictive value (NPV) (58%) were modest. Receiver operating characteristic with area under the curve (ROC AUC) was excellent (0.958). A similar pattern was seen in patients with vascular dementia (VaD) or mixed AD/VaD. There was no significant effect in patients with amnestic mild cognitive impairment (aMCI). It is concluded that the ANT substantially improves the ability to diagnose naming impairment in patients with AD, VaD, and mixed AD/VaD dementia, and should be included in a neuropsychological battery administered to elderly patients with suspected dementia. C1 [Hirsch, Joseph A.; Jordan, Barry D.; Fonzetti, Pasquale; Levin, Leann] Burke Rehabil Ctr, Cornell Univ, Weill Med Coll, White Plains, NY USA. [Cuesta, George M.] US Dept Vet Affairs, New York, NY USA. RP Hirsch, JA (reprint author), Burke Rehabil Hosp, Memory Evaluat & Treatment Serv, 785 Mamaroneck Ave, White Plains, NY 10605 USA. EM jhirsch@burke.org NR 41 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2158-2440 J9 SAGE OPEN JI SAGE Open PD SEP PY 2016 VL 6 IS 3 AR 2158244016665693 DI 10.1177/2158244016665693 PG 10 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA DY9ZK UT WOS:000385495800059 ER PT J AU Ritchie, CS Houston, TK Richman, JS Sobko, HJ Berner, ES Taylor, BB Salanitro, AH Locher, JL AF Ritchie, Christine S. Houston, Thomas K. Richman, Joshua S. Sobko, Heather J. Berner, Eta S. Taylor, Benjamin B. Salanitro, Amanda H. Locher, Julie L. TI The E-Coach technology-assisted care transition system: a pragmatic randomized trial SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Article DE Care transitions; Telehealth; Self-management ID INTERACTIVE VOICE RESPONSE; HEART-FAILURE; IDENTIFY PATIENTS; ELDERLY-PATIENTS; HEALTH-CARE; INTERVENTION; QUALITY; HOSPITALIZATION; READMISSION; VALIDATION AB Care transitions from the hospital to home remain a vulnerable time for many patients, especially for those with heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Despite regular use in chronic disease management, it remains unclear how technology can best support patients during their transition from the hospital. We sought to evaluate the impact of a technology-supported care transition support program on hospitalizations, days out of the community and mortality. Using a pragmatic randomized trial, we enrolled patients (511 enrolled, 478 analyzed) hospitalized with CHF/COPD to "E-Coach," an intervention with condition specific customization and in-hospital and post discharge support by a care transition nurse (CTN), interactive voice response post-discharge calls, and CTN follow-up versus usual post-discharge care (UC). The primary outcome was 30-day rehospitalization. Secondary outcomes included (1) rehospitalization and death and (2) days in the hospital and out of the community. E Coach and UC groups were similar at baseline except for gender imbalance (p= 0.02). After adjustment for gender, our primary outcome, 30-day rehospitalization rates did not differ between the E-Coach and UC groups (15.0 vs. 16.3 %, adjusted hazard ratio [95 % confidence interval]: 0.94 [0.60, 1.49]). However, in the COPD subgroup, E Coach was associated with significantly fewer days in the hospital (0.5 vs. 1.6, p= 0.03). E-Coach, an IVRaugmented care transition intervention did not reduce rehospitalization. The positive impact on our secondary outcome (days in hospital) among COPD patients, but not in CHF, may suggest that E-Coach may be more beneficial among patients with COPD. C1 [Ritchie, Christine S.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Houston, Thomas K.] Bedford VAMC, eHlth Qual Enhancement Res Initiat, Bedford, MA 01730 USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, 368 Plantat St, Worcester, MA 01605 USA. [Richman, Joshua S.] Birmingham VA Med Ctr, Birmingham, AL USA. [Sobko, Heather J.] Southern Res Inst, Birmingham, AL 35255 USA. [Berner, Eta S.] UAB, Dept Hlth Serv Adm, Hlth Informat, Sch Hlth Profess, Birmingham, AL USA. [Taylor, Benjamin B.] UAB, Dept Med, Div Gen Internal Med, Birmingham, AL USA. [Salanitro, Amanda H.] Vanderbilt Univ, VA Tennessee & Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA. [Salanitro, Amanda H.] Vanderbilt Univ, Sect Hosp Med, Geriatr Res Educ & Clin Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA. [Locher, Julie L.] UAB, Sch Publ Hlth, Birmingham, AL USA. RP Houston, TK (reprint author), Bedford VAMC, eHlth Qual Enhancement Res Initiat, Bedford, MA 01730 USA.; Houston, TK (reprint author), Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, 368 Plantat St, Worcester, MA 01605 USA. EM Thomas.Houston@umassmed.edu FU Agency for Healthcare Research and Quality of Care of Complex Patients [R18-HS017786-02] FX This study was in part supported by the Agency for Healthcare Research and Quality of Care of Complex Patients grant (R18-HS017786-02). NR 42 TC 0 Z9 0 U1 5 U2 5 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD SEP PY 2016 VL 6 IS 3 BP 428 EP 437 DI 10.1007/s13142-016-0422-8 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DY6TP UT WOS:000385261500011 PM 27339715 ER PT J AU Graves, MC Harris, JR Hannon, PA Hammerback, K Parrish, AT Ahmed, F Zhou, C Allen, CL AF Graves, Meredith C. Harris, Jeffrey R. Hannon, Peggy A. Hammerback, Kristen Parrish, Amanda T. Ahmed, Faruque Zhou, Chuan Allen, Claire L. TI Promoting Influenza Vaccination to Restaurant Employees SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Influenza; Vaccination; Immunization; Workplace; Employee; Promotion; Prevention Research AB Purpose. To evaluate an evidence-based workplace approach to increasing adult influenza vaccination levels applied in the restaurant setting Design. We implemented an intervention and conducted a pre/post analysis to determine effect on vaccination. Setting. Eleven Seattle-area restaurants. Subjects. Restaurants with 25+ employees speaking English or Spanish and over 18 years. Intervention. Restaurants received influenza vaccination promotion materials, assistance arranging on-site vaccination events, and free influenza vaccinations for employees. Measures. Pre/post employee surveys of vaccination status with direct observation and employer interviews to evaluate implementation. Analysis. We conducted descriptive analysis of employee survey data and performed qualitative analysis of implementation data. To assess intervention effect, we used a mixed-effects logistic regression model with a restaurant-specific random effect. Results. Vaccination levels increased from 26% to 46% (adjusted odds ratio 2.33, 95% confidence interval 1.69, 3.22), with 428 employees surveyed pre intervention, 305 surveyed postintervention, and response rates of 73% and 55%, respectively. The intervention was effective across subgroups, but there were restaurant-level differences. Conclusion. An access-based workplace intervention can increase influenza vaccination levels in restaurant employees, but restaurant-level factors may influence success. C1 [Graves, Meredith C.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Harris, Jeffrey R.; Hannon, Peggy A.; Hammerback, Kristen; Parrish, Amanda T.; Zhou, Chuan; Allen, Claire L.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Harris, Jeffrey R.; Hannon, Peggy A.; Hammerback, Kristen; Parrish, Amanda T.; Allen, Claire L.] Hlth Promot Res Ctr, 1107 45th Ave NE,Suite 200, Seattle, WA 98105 USA. [Ahmed, Faruque] Ctr Dis Control & Prevent, Immunizat Serv Div, Atlanta, GA USA. [Zhou, Chuan] Seattle Childrens Res Inst, Seattle, WA USA. RP Harris, JR (reprint author), Hlth Promot Res Ctr, 1107 45th Ave NE,Suite 200, Seattle, WA 98105 USA. EM jh7@uw.edu NR 7 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP PY 2016 VL 30 IS 7 BP 498 EP 500 DI 10.4278/ajhp.131216-ARB-643 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DY0VG UT WOS:000384813700002 PM 26305606 ER PT J AU Stohr, EJ Shave, RE Baggish, AL Weiner, RB AF Stohr, Eric J. Shave, Rob E. Baggish, Aaron L. Weiner, Rory B. TI Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE twist; torsion; exercise; deformation; cardiovascular disease ID AGE-RELATED-CHANGES; PRIMARY MITRAL REGURGITATION; ACUTE MYOCARDIAL-INFARCTION; GLOBAL STRAIN PARAMETERS; MAGNETIC-RESONANCE; EJECTION FRACTION; HYPERTROPHIC CARDIOMYOPATHY; DIASTOLIC FUNCTION; SYSTOLIC TORSION; APICAL ROTATION AB The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease. C1 [Stohr, Eric J.; Shave, Rob E.] Cardiff Metropolitan Univ, Cardiff Sch Sport, Discipline Physiol & Hlth, Cardiff, S Glam, Wales. [Baggish, Aaron L.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Stohr, EJ (reprint author), Cardiff Metropolitan Univ, Cyncoed Campus,Cyncoed Rd, Cardiff CF23 6XD, S Glam, Wales. EM estohr@cardiffmet.ac.uk OI Shave, Rob/0000-0002-0283-037X NR 120 TC 1 Z9 1 U1 4 U2 4 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 SEP PY 2016 VL 311 IS 3 BP H633 EP H644 DI 10.1152/ajpheart.00104.2016 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA DY3DT UT WOS:000384971700013 PM 27402663 ER PT J AU Simons, JCP Pierce, E Diaz-Gil, D Malviya, SA Meyer, MJ Timm, FP Stokholm, JB Rosow, CE Kacmarek, RM Eikermann, M AF Simons, Jeroen C. P. Pierce, Eric Diaz-Gil, Daniel Malviya, Sanjana A. Meyer, Matthew J. Timm, Fanny P. Stokholm, Janne B. Rosow, Carl E. Kacmarek, Robert M. Eikermann, Matthias TI Effects of Depth of Propofol and Sevoflurane Anesthesia on Upper Airway Collapsibility, Respiratory Genioglossus Activation, and Breathing in Healthy Volunteers SO ANESTHESIOLOGY LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; MUSCLE-ACTIVITY; PREDICT IMMOBILITY; PAINFUL STIMULI; NERVE ACTIVITY; HEART-RATE; F-WAVES; PRESSURE; MIDAZOLAM; SEDATION AB Background: Volatile anesthetics and propofol impair upper airway stability and possibly respiratory upper airway dilator muscle activity. The magnitudes of these effects have not been compared at equivalent anesthetic doses. We hypothesized that upper airway closing pressure is less negative and genioglossus activity is lower during deep compared with shallow anesthesia. Methods: In a randomized controlled crossover study of 12 volunteers, anesthesia with propofol or sevoflurane was titrated using a pain stimulus to identify the threshold for suppression of motor response to electrical stimulation. Measurements included bispectral index, genioglossus electromyography, ventilation, hypopharyngeal pressure, upper airway closing pressure, and change in end-expiratory lung volume during mask pressure drops. Results: A total of 393 attempted breaths during occlusion maneuvers were analyzed. Upper airway closing pressure was significantly less negative at deep versus shallow anesthesia (-10.8 +/- 4.5 vs. -11.3 +/- 4.4 cm H2O, respectively [mean +/- SD]) and correlated with the bispectral index (P < 0.001), indicating a more collapsible airway at deep anesthesia. Respiratory genioglossus activity during airway occlusion was significantly lower at deep compared with light anesthesia (26 +/- 21 vs. 35 +/- 24% of maximal genioglossus activation, respectively; P < 0.001) and correlated with bispectral index (P < 0.001). Upper airway closing pressure and genioglossus activity during airway occlusion did not differ between sevoflurane and propofol anesthesia. Conclusions: Propofol and sevoflurane anesthesia increased upper airway collapsibility in a dose-dependent fashion with no difference at equivalent anesthetic concentrations. These effects can in part be explained by a dose-dependent inhibiting effect of anesthetics on respiratory genioglossus activity. C1 [Simons, Jeroen C. P.; Pierce, Eric; Diaz-Gil, Daniel; Malviya, Sanjana A.; Meyer, Matthew J.; Timm, Fanny P.; Stokholm, Janne B.; Rosow, Carl E.; Kacmarek, Robert M.; Eikermann, Matthias] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Simons, Jeroen C. P.] Univ Cologne, Dept Orthopaed & Trauma Surg, Cologne, Germany. [Stokholm, Janne B.] Univ Copenhagen, Herlev Hosp, Dept Anesthesiol, Copenhagen, Denmark. [Kacmarek, Robert M.] Harvard Med Sch, Dept Resp Care, Boston, MA USA. [Eikermann, Matthias] Univ Essen Gesamthsch, Dept Anesthesia & Crit Care, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org FU Covidien; Venner Medical, Danischenhagen, Germany; ResMed foundation, La Jolla, California; Merck, Kenilworth, New Jersey FX Dr. Kacmarek is a consultant for Covidien, Minneapolis, Minnesota, and OrangeMed, Irvine, California, and has received research grants from Covidien and Venner Medical, Danischenhagen, Germany. Dr. Eikermann received investigator-initiated grants from the ResMed foundation, La Jolla, California, and Merck, Kenilworth, New Jersey, and he holds equity stakes at Calabash Bioscience, Inc., College Park, Maryland. The other authors declare no competing interests. NR 40 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2016 VL 125 IS 3 BP 525 EP 534 DI 10.1097/ALN.0000000000001225 PG 10 WC Anesthesiology SC Anesthesiology GA DY3VQ UT WOS:000385024100017 PM 27404221 ER PT J AU Arora, V Rozet, I AF Arora, Vivek Rozet, Irene TI Tarlov Cysts Incidental Finding during Subarachnoid Drain Placement SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Arora, Vivek] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Arora, V (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM varora2@uw.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2016 VL 125 IS 3 BP 598 EP 598 DI 10.1097/ALN.0000000000001118 PG 1 WC Anesthesiology SC Anesthesiology GA DY3VQ UT WOS:000385024100028 PM 27035856 ER PT J AU Gkotzamanidou, M Terpos, E Bamia, C Munshi, NC Dimopoulos, MA Souliotis, VL AF Gkotzamanidou, Maria Terpos, Evangelos Bamia, Christina Munshi, Nikhil C. Dimopoulos, Meletios A. Souliotis, Vassilis L. TI DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7 SO BLOOD LA English DT Article ID STRAND BREAK REPAIR; DEPENDENT PROTEIN-KINASE; INTERSTRAND CROSS-LINKS; MULTIPLE-MYELOMA; HOMOLOGOUS RECOMBINATION; CHROMATIN-STRUCTURE; DAMAGE RESPONSE; EXCISION-REPAIR; CANCER-THERAPY; IN-VITRO AB DNA repair activity of malignant cells seems to influence therapeutic outcome and patients' survival. Herein, we investigated the mechanistic basis for the link between DNA repair efficiency and response to antimyeloma therapy. Nucleotide excision repair (NER), interstrand cross-links repair (ICL/R), double-strand breaks repair (DSB/R), and chromatin structure were evaluated in multiple myeloma (MM) cell lines (melphalan-sensitive RPMI8226; melphalan-resistant LR5) and bone marrow plasma cells (BMPCs) from MM patients who responded (n = 17) or did not respond (n = 9) to subsequent melphalan therapy. The effect of DSB/R inhibition was also evaluated. Responders' BMPCs showed slower rates of NER and DSB/R (P < .0022), similar rates of ICL/R, and more condensed chromatin structure compared with nonresponders. Moreover, apoptosis rates of BMPCs were inversely correlated with individual DNA repair efficiency and were higher in responders' cells compared with those of nonresponders (P = .0011). Similarly, RPMI8226 cells showed slower rates of NER and DSB/R, comparable rates of ICL/R, more condensed chromatin structure, and higher sensitivity than LR5 cells. Interestingly, cotreatment of BMPCs or cell lines with DSB/R inhibitors significantly reduced the rates of DSB/R and increased melphalan sensitivity of the cells, with the nonhomologous end-joining inhibitor SCR7 showing the strongest effect. Together, responders' BMPCs are characterized by lower efficiencies of NER and DSB/R mechanisms, resulting in higher accumulation of the extremely cytotoxic ICLs and DSBs lesions, which in turn triggers the induction of the apoptotic pathway. Moreover, the enhancement of melphalan cytotoxicity by DSB/R inhibition offers a promising strategy toward improvement of existing antimyeloma regimens. C1 [Gkotzamanidou, Maria; Munshi, Nikhil C.] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. [Gkotzamanidou, Maria; Terpos, Evangelos; Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece. [Bamia, Christina] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, Athens, Greece. [Souliotis, Vassilis L.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, 48 Vassileos Constantinou Ave, Athens 11635, Greece. RP Souliotis, VL (reprint author), Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, 48 Vassileos Constantinou Ave, Athens 11635, Greece. EM vls@eie.gr NR 53 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD SEP 1 PY 2016 VL 128 IS 9 BP 1214 EP 1225 DI 10.1182/blood-2016-01-691618 PG 12 WC Hematology SC Hematology GA DX9YU UT WOS:000384754100014 PM 27443291 ER PT J AU Lu, NT Liu, NM Vu, JQ Patel, D Cohn, W Capri, J Ziegler, M Patel, N Tramontano, A Williams, R Whitelegge, J French, SW AF Lu, Nu T. Liu, Natalie M. Vu, James Q. Patel, Darshil Cohn, Whitaker Capri, Joe Ziegler, Mary Patel, Nikita Tramontano, Angela Williams, Roger Whitelegge, Julian French, Samuel W. TI Phospho-Network Analysis Identifies and Quantifies Hepatitis C Virus (HCV)-induced Hepatocellular Carcinoma (HCC) Proteins Regulating Viral-mediated Tumor Growth SO CANCER GENOMICS & PROTEOMICS LA English DT Article DE Hepatocellular carcinoma; hepatitis C virus; mass spectrometry; phosphoproteomics ID POOR-PROGNOSIS; POSTTRANSLATIONAL MODIFICATIONS; QUANTITATIVE PHOSPHOPROTEOMICS; MASS-SPECTROMETRY; EARLY RECURRENCE; CELL-SURVIVAL; LIVER-CANCER; STATHMIN; PHOSPHORYLATION; OVEREXPRESSION AB Background: Patients with chronic hepatitis C virus (HCV) infection are at risk of serious complications of cirrhosis and hepatocellular carcinoma (HCC). Mass spectrometry (MS) is a versatile methodology that produces a global proteomic landscape for analysis of cancer mechanisms. Materials and Methods: Using multiplex peptide stable isotopic labeling and immobilized metal affinity chromatography (IMAC), we enriched and quantified the phosphoproteome of HCC, with and without HCV. While raw data identified protein targets based on expression alone, we also used abundance groups for comprehensive functional analysis. Results: Analysis of functional differences highlighted deregulated phosphoprotein networks. This uncovered additional candidates that could be directly derived from the MS data. Cellular processes and pathways that may differ with HCV infection include: cytoskeletal dynamics, insulin response, gene expression, and PI3K/AKT oncogenesis. Conclusion: This function-focused workflow provides a simple framework to analyze MS data. Phosphoproteome quantitation with inclusive functional analysis can generate hypotheses for liver cancer research to improve early screening and identification of molecular targets for therapy. C1 [Lu, Nu T.; Liu, Natalie M.; Vu, James Q.; Patel, Darshil; Ziegler, Mary; Patel, Nikita; French, Samuel W.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Lu, Nu T.] Univ Calif Los Angeles, Dept Hematol & Oncol, Los Angeles, CA USA. [Cohn, Whitaker; Capri, Joe; Whitelegge, Julian] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Capri, Joe] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Tramontano, Angela] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Williams, Roger] Fdn Liver Res, Inst Hepatol, London, England. RP French, SW (reprint author), Univ Calif Los Angeles, Ctr Hlth Sci, Dept Pathol & Lab Med, 10833 Le Conte Ave,Rm 13-145, Los Angeles, CA 90095 USA. EM sfrench@mednet.ucla.edu FU UCSD/UCLA NIDDK Diabetes Research Center [P30DK063491] FX This research utilized core support from the UCSD/UCLA NIDDK Diabetes Research Center P30DK063491. The Authors would like to thank Dr. Asim Dasgupta and Dr. Santanu Raychaudhuri (Department of Microbiology, Immunology, and Molecular Genetics; University of California Los Angeles) for providing us with the HCV replicon cell line. They thank Johnny Lin from the UCLA Statistical Consulting Center (Institute of Digital Research and Education; University of California Los Angeles) for his assistance with R software. They also thank Roxanna Khosravi and Dr. Jane Cox for editing assistance. Finally, they thank Sarah Bassilian for her help. NR 44 TC 0 Z9 0 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 1109-6535 EI 1790-6245 J9 CANCER GENOM PROTEOM JI Cancer Genomics Proteomics PD SEP-OCT PY 2016 VL 13 IS 5 BP 339 EP 357 PG 19 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA DY3WL UT WOS:000385027300003 PM 27566653 ER PT J AU Zhu, W Carney, KE Pigott, VM Falgoust, LM Clark, PA Kuo, JS Sun, DD AF Zhu, Wen Carney, Karen E. Pigott, Victoria M. Falgoust, Lindsay M. Clark, Paul A. Kuo, John S. Sun, Dandan TI Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1 SO CARCINOGENESIS LA English DT Article ID MT1-MMP EXPRESSION; GLIOBLASTOMA CELLS; MYELOID CELLS; TUMOR-CELLS; NHE1; INVASION; POLARIZATION; MACROPHAGES; METASTASIS; SURVIVAL AB Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na+/H+ exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia-glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1(+) microglia in glioma xenografts and glioblastoma multiforme microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-beta, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via small interfering RNA (siRNA) knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma-microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation. C1 [Zhu, Wen; Carney, Karen E.; Pigott, Victoria M.; Falgoust, Lindsay M.; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Clark, Paul A.; Kuo, John S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Madison, WI 53792 USA. [Clark, Paul A.; Kuo, John S.] Univ Wisconsin, Sch Med & Publ Hlth, Carbone Canc Ctr, Madison, WI 53792 USA. [Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. RP Sun, DD (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.; Sun, DD (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. EM sund@upmc.edu FU National Institutes of Health [R01NS075995, R01NS048216]; HEADRUSH Brain Tumor Research Professorship; Roger Loff Memorial GBM Research Fund; Department of Neurological Surgery [R01CA158800] FX National Institutes of Health (partial support, R01NS075995 and R01NS048216 to D.S. and J.S.K.); HEADRUSH Brain Tumor Research Professorship, Roger Loff Memorial GBM Research Fund, and Department of Neurological Surgery (partial support, R01CA158800 to J.S.K.). NR 56 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2016 VL 37 IS 9 BP 839 EP 851 DI 10.1093/carcin/bgw068 PG 13 WC Oncology SC Oncology GA DY5IV UT WOS:000385133900002 PM 27287871 ER PT J AU Higuma, T Soeda, T Yamada, M Yokota, T Yokoyama, H Nishizaki, F Xing, L Yamamoto, E Bryniarski, K Dai, JN Lee, H Okumura, K Jang, IK AF Higuma, Takumi Soeda, Tsunenari Yamada, Masahiro Yokota, Takashi Yokoyama, Hiroaki Nishizaki, Fumie Xing, Lei Yamamoto, Erika Bryniarski, Krzysztof Dai, Jiannan Lee, Hang Okumura, Ken Jang, Ik-Kyung TI Coronary Plaque Characteristics Associated With Reduced TIMI (Thrombolysis in Myocardial Infarction) Flow Grade in Patients With ST-Segment-Elevation Myocardial Infarction: A Combined Optical Coherence Tomography and Intravascular Ultrasound Study SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE acute coronary syndrome; coronary angiography; optical coherence tomography; percutaneous coronary intervention; vascular remodeling ID PRIMARY ANGIOPLASTY; ARTERY-DISEASE; CALCIFIED NODULE; ACQUISITION; LESIONS; ATHEROSCLEROSIS; VULNERABILITY; REPERFUSION; ANGIOGRAPHY; STANDARDS AB Background Previous studies reported that reduced TIMI (Thrombolysis in Myocardial Infarction) flow grade before procedure was associated with worse clinical outcomes in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. The aim of this study was to identify specific morphological characteristics of the culprit plaque associated with poor TIMI flow grade at baseline in patients with ST-segment-elevation myocardial infarction using both optical coherence tomography and intravascular ultrasound. Methods and Results A total of 111 ST-segment-elevation myocardial infarction patients who underwent percutaneous coronary intervention within 24 hours of symptom onset were included. Both optical coherence tomography and intravascular ultrasound were performed after thrombectomy. Patients were divided into 2 groups according to preprocedural TIMI flow grade (TIMI 0-1 [n=82] and TIMI 2-3 [n=29]). Patients with preprocedural TIMI 0 to 1 had a greater lipid arc (P=0.037), a longer lipid length (P=0.021), and a greater lipid index (P=0.007) determined by optical coherence tomography and a larger external elastic membrane cross-sectional area (P=0.030) and plaque plus media cross-sectional area (P=0.030) determined by intravascular ultrasound, compared with patients with preprocedural TIMI 2 to 3. Conclusions ST-segment-elevation myocardial infarction patients with reduced TIMI flow grade at baseline have greater lipid burden, larger vessel sizes, and larger plaque areas. C1 [Higuma, Takumi; Yamada, Masahiro; Yokota, Takashi; Yokoyama, Hiroaki; Nishizaki, Fumie; Okumura, Ken] Hirosaki Univ, Grad Sch Med, Dept Cardiol, Hirosaki, Aomori, Japan. [Higuma, Takumi; Soeda, Tsunenari; Xing, Lei; Yamamoto, Erika; Bryniarski, Krzysztof; Dai, Jiannan; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul, South Korea. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@mgh.harvard.edu FU St Jude Medical FX Dr Jang has received fellowship grant and consulting fees from St Jude Medical. The other authors report no conflicts. NR 31 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 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD SEP PY 2016 VL 9 IS 9 AR e003913 DI 10.1161/CIRCINTERVENTIONS.116.003913 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5YR UT WOS:000384459100010 ER PT J AU Secemsky, EA Wimmer, NJ Yeh, RW AF Secemsky, Eric A. Wimmer, Neil J. Yeh, Robert W. TI Letter by Secemsky et al Regarding Article, "Relationship Between Femoral Vascular Closure Devices and Short-Term Mortality From 271845 Percutaneous Coronary Intervention Procedures Performed in the United Kingdom Between 2006 and 2011: A Propensity Score-Corrected Analysis From the British Cardiovascular Intervention Society" SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Letter C1 [Secemsky, Eric A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Wimmer, Neil J.] Christiana Care Hlth Syst, Dept Med, Div Cardiol, Newark, DE USA. [Yeh, Robert W.] Beth Israel Deaconess Med Ctr, Dept Med, Smith Ctr Outcomes Res Cardiol, Boston, MA 02215 USA. RP Secemsky, EA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. 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 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD SEP PY 2016 VL 9 IS 9 AR e004262 DI 10.1161/CIRCINTERVENTIONS.116.004262 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5YR UT WOS:000384459100016 ER PT J AU Haradhvala, NJ Kim, J Polak, P Lawrence, MS Getz, G AF Haradhvala, N. J. Kim, J. Polak, P. Lawrence, M. S. Getz, G. TI Tracking the Footprints of DNA Damage of Repair in Cancer Genomes. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 47th Annual Meeting of the Environmental-Mutagenesis-and-Genomics-Society CY SEP 24-28, 2016 CL Kansas City, MO SP Environm Mutagenesis & Genom Soc C1 [Haradhvala, N. J.; Lawrence, M. S.; Getz, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, J.; Polak, P.; Lawrence, M. S.; Getz, G.] Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2016 VL 57 SU 1 MA EG-31 BP S63 EP S63 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DW4BQ UT WOS:000383587400094 ER PT J AU Wong, TN Ramsingh, G Young, AL Klco, JM Miller, CA Petti, A Demeter, R Welch, JS Helton, NM Li, T Lamprecht, TL Fulton, RS Heath, S Ding, L Mardis, ER Westervelt, P DiPersio, JF Walter, MJ Graubert, TA Ley, TJ Wilson, RK Druley, TE Link, DC AF Wong, T. N. Ramsingh, G. Young, A. L. Klco, J. M. Miller, C. A. Petti, A. Demeter, R. Welch, J. S. Helton, N. M. Li, T. Lamprecht, T. L. Fulton, R. S. Heath, S. Ding, L. Mardis, E. R. Westervelt, P. DiPersio, J. F. Walter, M. J. Graubert, T. A. Ley, T. J. Wilson, R. K. Druley, T. E. Link, D. C. TI Cytotoxic Therapy Provides a Fitness Advantage to Rare HSPCs Harboring Somatic TP53 Mutations. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 47th Annual Meeting of the Environmental-Mutagenesis-and-Genomics-Society CY SEP 24-28, 2016 CL Kansas City, MO SP Environm Mutagenesis & Genom Soc C1 [Wong, T. N.; Welch, J. S.; Helton, N. M.; Heath, S.; Westervelt, P.; DiPersio, J. F.; Walter, M. J.; Ley, T. J.; Link, D. C.] Washington Univ, Dept Med, St Louis, MO USA. [Ramsingh, G.] USC, Los Angeles, CA USA. [Klco, J. M.; Lamprecht, T. L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Graubert, T. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, C. A.; Petti, A.; Demeter, R.; Li, T.; Fulton, R. S.; Ding, L.; Mardis, E. R.; Wilson, R. K.; Druley, T. E.] Washington Univ, McDonnell Genome Inst, St Louis, MO USA. [Young, A. L.; Druley, T. E.] Washington Univ, Dept Pediat, St Louis, MO 63130 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 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD SEP PY 2016 VL 57 SU 1 MA S59 BP S54 EP S54 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DW4BQ UT WOS:000383587400066 ER PT J AU Hu, YG Zhang, ZH Kashiwagi, M Yoshida, T Joshi, I Jena, N Somasundaram, R Emmanuel, AO Sigvardsson, M Fitamant, J El-Bardeesy, N Gounari, F Van Etten, RA Georgopoulos, K AF Hu, Yeguang Zhang, Zhihong Kashiwagi, Mariko Yoshida, Toshimi Joshi, Ila Jena, Nilamani Somasundaram, Rajesh Emmanuel, Akinola Olumide Sigvardsson, Mikael Fitamant, Julien El-Bardeesy, Nabeel Gounari, Fotini Van Etten, Richard A. Georgopoulos, Katia TI Superenhancer reprogramming drives a B-cell-epithelial transition and high-risk leukemia SO GENES & DEVELOPMENT LA English DT Article DE TEAD; YAP1; LHX2; PRC2; self-renewal ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANSCRIPTION FACTORS; SUPER-ENHANCERS; STEM-CELL; HISTONE MODIFICATIONS; GENETIC ALTERATIONS; SIGNALING PATHWAYS; T-CELLS; IKAROS; DIFFERENTIATION AB IKAROS is required for the differentiation of highly proliferative pre-B-cell precursors, and loss of IKAROS function indicates poor prognosis in precursor B-cell acute lymphoblastic leukemia (B-ALL). Here we show that IKAROS regulates this developmental stage by positive and negative regulation of superenhancers with distinct lineage affiliations. IKAROS defines superenhancers at pre-B-cell differentiation genes together with B-cell master regulators such as PAX5, EBF1, and IRF4 but is required for a highly permissive chromatin environment, a function that cannot be compensated for by the other transcription factors. IKAROS is also highly enriched at inactive enhancers of genes normally expressed in stem-epithelial cells. Upon IKAROS loss, expression of pre-B-cell differentiation genes is attenuated, while a group of extralineage transcription factors that are directly repressed by IKAROS and depend on EBF1 relocalization at their enhancers for expression is induced. LHX2, LMO2, and TEAD-YAP1, normally kept separate from native B-cell transcription regulators by IKAROS, now cooperate directly with them in a de novo superenhancer network with its own feed-forward transcriptional reinforcement. Induction of de novo superenhancers antagonizes Polycomb repression and superimposes aberrant stem epithelial cell properties in a B-cell precursor. This dual mechanism of IKAROS regulation promotes differentiation while safeguarding against a hybrid stem epithelial B-cell phenotype that underlies high-risk B-ALL. C1 [Hu, Yeguang; Zhang, Zhihong; Kashiwagi, Mariko; Yoshida, Toshimi; Joshi, Ila; Georgopoulos, Katia] Harvard Med Sch, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Jena, Nilamani; Van Etten, Richard A.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Dept Med, Irvine, CA 92868 USA. [Jena, Nilamani; Van Etten, Richard A.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Dept Biol Chem, Irvine, CA 92868 USA. [Somasundaram, Rajesh; Sigvardsson, Mikael] Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. [Emmanuel, Akinola Olumide; Gounari, Fotini] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Fitamant, Julien; El-Bardeesy, Nabeel] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu FU National Institutes of Health [R01CA162092, R21AI124326, R01CA090576, R01CA190964] FX We thank Dr. C. Benner for his advice and consultation on various applications of the HOMER software used throughout this project; Dr. K. White, Dr. J.M. Park, Dr. B. Morgan, Dr. T. Naito, and Dr. C. Benner for critical review of the manuscript; Dr. J. Drouin for anti-Tbx19 antibodies; and E. Wu and B. Czyzewski for mouse husbandry. This research was supported by National Institutes of Health grants R01CA162092 and R21AI124326 (K.G.), R01CA090576 (R.A.V.E.), and R01CA190964 (R.A.V.E. and K.G.). K.G. Is a Massachusetts General Hospital scholar supported by Dr. Jean de Gunzburg. High-throughput DNA sequencing was performed at the Bauer Center for Genomic Research, Harvard University, Cambridge. Y.H. performed the chromatin studies, the transcription factor knockdowns, and their effect on gene expression, cell cycle, cell adhesion, and clonogenicity. Z.Z. performed supporting protein studies. M.K., A.O.E., F.G., and K.G. performed ChIP and RNAseq data analysis and presentation. T.Y. performed gene expression studies on primary wild-type, IKDN, BCR-ABL1+, and IKDN-BCR-ABL1+ pre-B cells and data presentation. I.J. performed adhesion assays with large pre-B cells in wild-type, IKDN, and factor knockdown pre-B cells. N.J. generated and analyzed IKDN-BCR-ABLr pre-B cells. R.S. and M.S. aided with the Ebf1 knockdown studies. J.F. and N.E.B. aided with the Yap1 knockdown studies. R.A.V.E. and K.G. supervised the project and wrote the manuscript. NR 64 TC 3 Z9 3 U1 3 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2016 VL 30 IS 17 BP 1971 EP 1990 DI 10.1101/gad.283762.116 PG 20 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA DY3BA UT WOS:000384964600008 PM 27664237 ER PT J AU He, JF Liu, QG Christodoulou, AG Ma, C Lam, F Liang, ZP AF He, Jingfei Liu, Qiegen Christodoulou, Anthony G. Ma, Chao Lam, Fan Liang, Zhi-Pei TI Accelerated High-Dimensional MR Imaging With Sparse Sampling Using Low-Rank Tensors SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE High-dimensional MR imaging; low-rank tensor; partial separability; sparse regularization; sparse sampling ID PARTIALLY SEPARABLE FUNCTIONS; LEAST-SQUARES; DYNAMIC MRI; RECONSTRUCTION; MODEL; DECOMPOSITION; RESOLUTION; PRINCIPLES; SUPPORT AB High-dimensional MR imaging often requires long data acquisition time, thereby limiting its practical applications. This paper presents a low-rank tensor based method for accelerated high-dimensional MR imaging using sparse sampling. This method represents high-dimensional images as low-rank tensors (or partially separable functions) and uses this mathematical structure for sparse sampling of the data space and for image reconstruction from highly undersampled data. More specifically, the proposed method acquires two datasets with complementary sampling patterns, one for subspace estimation and the other for image reconstruction; image reconstruction from highly undersampled data is accomplished by fitting the measured data with a sparsity constraint on the core tensor and a group sparsity constraint on the spatial coefficients jointly using the alternating direction method of multipliers. The usefulness of the proposed method is demonstrated in MRI applications; it may also have applications beyond MRI. C1 [He, Jingfei] Nankai Univ, Dept Elect Informat & Opt Engn, Tianjin 300071, Peoples R China. [Liu, Qiegen] Nanchang Univ, Dept Elect Informat Engn, Nanchang 330031, Peoples R China. [Christodoulou, Anthony G.] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Christodoulou, Anthony G.] Cedars Sinai Med Ctr, Biomed Imaging Res Inst, Los Angeles, CA 90048 USA. [Ma, Chao] Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Nucl Med & Mol Imaging Div, Boston, MA 02129 USA. [Ma, Chao] Harvard Med Sch, Dept Radiol, Boston, MA 02129 USA. [Lam, Fan; Liang, Zhi-Pei] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Liang, Zhi-Pei] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. RP Liang, ZP (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA.; Liang, ZP (reprint author), Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. EM z-liang@illi-nois.edu FU Chinese Scholarship Council; National Natural Science Foundation of China [61362001]; [NIH-R01-EB013695-01]; [NIH-R21-EB021013-01]; [NIH-P41-EB002034-14A1] FX This work was supported in part by the following grants: NIH-R01-EB013695-01, NIH-R21-EB021013-01, and NIH-P41-EB002034-14A1. The work of J. He was supported by the Chinese Scholarship Council during his visit to University of Illinois at Urbana-Champaign. The work of Q. Liu was supported by the National Natural Science Foundation of China under 61362001, and the international postdoctoral exchange fellowship program. Asterisk indicates corresponding author. NR 62 TC 0 Z9 0 U1 11 U2 11 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 2016 VL 35 IS 9 BP 2119 EP 2129 DI 10.1109/TMI.2016.2550204 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA DY6VK UT WOS:000385266800012 ER PT J AU Coote, P Bermel, W Wagner, G Arthanari, H AF Coote, Paul Bermel, Wolfgang Wagner, Gerhard Arthanari, Haribabu TI Analytical optimization of active bandwidth and quality factor for TOCSY experiments in NMR spectroscopy SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE NMR spectroscopy; TOCSY; Pulse design; Optimization; Quality factor; Active bandwidth; Spin dynamics ID HOMONUCLEAR CROSS-POLARIZATION; COHERENCE-TRANSFER; ROTATING-FRAME AB Active bandwidth and global quality factor are the two main metrics used to quantitatively compare the performance of TOCSY mixing sequences. Active bandwidth refers to the spectral region over which at least 50 % of the magnetization is transferred via a coupling. Global quality factor scores mixing sequences according to the worst-case transfer over a range of possible mixing times and chemical shifts. Both metrics reward high transfer efficiency away from the main diagonal of a two-dimensional spectrum. They can therefore be used to design mixing sequences that will function favorably in experiments. Here, we develop optimization methods tailored to these two metrics, including precise control of off-diagonal cross peak buildup rates. These methods produce square shaped transfer efficiency profiles, directly matching the desirable properties that the metrics are intended to measure. The optimization methods are analytical, rather than numerical. The two resultant shaped pulses have significantly higher active bandwidth and quality factor, respectively, than all other known sequences. They are therefore highly suitable for use in NMR spectroscopy. We include experimental verification of these improved waveforms on small molecule and protein samples. C1 [Coote, Paul; Wagner, Gerhard; Arthanari, Haribabu] Harvard Med Sch, Boston, MA 02115 USA. [Bermel, Wolfgang] Bruker BioSpin GmbH, Silberstrifen 4, D-76287 Rheinstetten, Germany. [Arthanari, Haribabu] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Arthanari, H (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Arthanari, H (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_coote@hms.harvard.edu; hari@hms.harvard.edu FU NIH [GM047467, GM075879, P41-EB002026] FX This work is funded by NIH Grants GM047467, GM075879, and P41-EB002026 to GW. We thank Dr. O. Mechnich and Prof. H. Kessler for providing the 13C,15N labeled cyclic octapeptide hymenistatin. NR 24 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 EI 1573-5001 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2016 VL 66 IS 1 BP 9 EP 20 DI 10.1007/s10858-016-0051-z PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA DY6CZ UT WOS:000385195000002 PM 27515670 ER PT J AU Taft, CT Macdonald, A Creech, SK Monson, CM Murphy, CM AF Taft, Casey T. Macdonald, Alexandra Creech, Suzannah K. Monson, Candice M. Murphy, Christopher M. TI A Randomized Controlled Clinical Trial of the Strength at Home Men's Program for Partner Violence in Military Veterans SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Veterans and Military Issues; Violence/Aggression ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA; INTERVENTION; VALIDATION; REGRESSION; ABUSE; RATES AB Objective: We evaluated the efficacy of the Strength at Home Men's Program (SAH-M), a trauma-informed group intervention based on a social information processing model to end intimate partner violence (IPV) use in a sample of veterans/service members and their partners. To date, no randomized controlled trial has supported the efficacy of an IPV intervention in this population. Method: Participants included 135 male veterans/service members and 111 female partners. Recruitment was conducted from February 2010 through August 2013, and participation occurred within 2 Department of Veterans Affairs hospitals. Male participants completed an initial assessment that included diagnostic interviews and measures of physical and psychological IPV using the Revised Conflict Tactics Scales and were randomly assigned to an enhanced treatment as usual (ETAU) condition or SAH-M. Those randomized to SAH-M were enrolled in this 12-week group immediately after baseline. Those randomized to ETAU received clinical referrals and resources for mental health treatment and IPV services. All male participants were reassessed 3 and 6 months after baseline. Female partners completed phone assessments at the same intervals that were focused both on IPV and on the provision of safety information and clinical referrals. Results: Primary analyses using hierarchical linear modeling indicated significant time-by-condition effects such that SAH-M participants compared with ETAU participants evidenced greater eductions in physical and psychological IPV use (beta = -0.135 [SE = 0.061], P =.029; beta = -0.304 [SE = 0.135], P =.026; respectively). Additional analyses of a measure that disaggregated forms of psychological IPV showed that SAH-M, relative to ETAU, reduced controlling behaviors involving isolation and monitoring of the partner (beta = -0.072 [SE = 0.027], P =.010). Conclusions: Results provide support for the efficacy of SAH-M in reducing and ending IPV in male veterans and service members. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Taft, Casey T.; Macdonald, Alexandra] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.; Macdonald, Alexandra] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Creech, Suzannah K.] Brown Univ, Warren Alpert Med Sch, Providence VA Med Ctr, Providence, RI 02912 USA. [Creech, Suzannah K.] VHA VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. [Murphy, Christopher M.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 4, 150 South Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov FU Department of Veterans Afairs and Department of Defense FX This work was supported by grants from the Department of Veterans Afairs and Department of Defense and through the use of the facilities and resources of the Providence Veterans Afairs Medical Center. NR 26 TC 1 Z9 1 U1 5 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2016 VL 77 IS 9 BP 1168 EP 1175 DI 10.4088/JCP.15m10020 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DY0OQ UT WOS:000384796500001 PM 26613288 ER PT J AU Spencer, AE Biederman, J AF Spencer, Andrea E. Biederman, Joseph TI The Association Between PTSD and ADHD: Does the Association Reveal a PTSD-Somatoform Subtype? Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 [Spencer, Andrea E.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Spencer, Andrea E.] Harvard Med Sch, Boston, MA 02115 USA. RP Spencer, AE (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA.; Spencer, AE (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM aespencer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2016 VL 77 IS 9 BP E1150 EP E1150 DI 10.4088/JCP.16lr10630a PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DY0OQ UT WOS:000384796500018 PM 27780324 ER PT J AU Wong, GK Millar, D Penny, S Heather, JM Mistry, P Buettner, N Bryon, J Huissoon, AP Cobbold, M AF Wong, Gabriel K. Millar, David Penny, Sarah Heather, James M. Mistry, Punam Buettner, Nico Bryon, Jane Huissoon, Aarnoud P. Cobbold, Mark TI Accelerated Loss of TCR Repertoire Diversity in Common Variable Immunodeficiency SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR EXCISION CIRCLES; SELECTIVE IGA DEFICIENCY; T-CELL PHENOTYPES; DISEASE; ASSOCIATION; DISORDERS; OUTPUT; THYMUS AB Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab deficiencies, growing experimental data now suggest a global disruption of the entire adaptive immune response in a segment of patients. Oligoclonality of the TCR repertoire was previously demonstrated; however, the manner in which it relates to other B cell and T cell findings reported in CVID remains unclear. Using a combination approach of high-throughput TCR beta sequencing and multiparametric flow cytometry, we compared the TCR repertoire diversity between various subgroups of CVID patients according to their B cell immunophenotypes. Our data suggest that the reduction in repertoire diversity is predominantly restricted to those patients with severely reduced class-switched memory B cells and an elevated level of CD21(lo) B cells (Freiburg 1a), and may be driven by a reduced number of naive T cells unmasking underlying memory clonality. Moreover, our data indicate that this loss in repertoire diversity progresses with advancing age far exceeding the expected physiological rate. Radiological evidence supports the loss in thymic volume, correlating with the decrease in repertoire diversity. Evidence now suggests that primary thymic failure along with other well-described B cell abnormalities play an important role in the pathophysiology in Freiburg group 1a patients. Clinically, our findings emphasize the integration of combined B and T cell testing to identify those patients at the greatest risk for infection. Future work should focus on investigating the link between thymic failure and the severe reduction in class-switched memory B cells, while gathering longitudinal laboratory data to examine the progressive nature of the disease. C1 [Wong, Gabriel K.; Penny, Sarah; Mistry, Punam; Buettner, Nico] Univ Birmingham, Med Res Council Ctr Immune Regulat, Edgbaston B15 2TT, W Midlands, England. [Wong, Gabriel K.; Huissoon, Aarnoud P.] Birmingham Heartlands Hosp, West Midlands Primary Immunodeficiency Ctr, Birmingham B9 5SS, W Midlands, England. [Millar, David; Cobbold, Mark] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Millar, David; Cobbold, Mark] Harvard Med Sch, Dept Med, 13th St, Charlestown, MA 02129 USA. [Heather, James M.] UCL, Div Infect & Immun, London WC1E 6BT, England. [Bryon, Jane] Birmingham Womens Hosp, Reg Genet Lab, Birmingham B15 2TG, W Midlands, England. RP Cobbold, M (reprint author), Harvard Med Sch, Dept Med, 13th St, Charlestown, MA 02129 USA.; Cobbold, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St, Charlestown, MA 02129 USA. EM mcobbold@mgh.harvard.edu OI Heather, James/0000-0002-1783-5181; Wong, Gabriel/0000-0003-4987-4051 FU Wellcome Trust [099908] NR 33 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2016 VL 197 IS 5 BP 1642 EP 1649 DI 10.4049/jimmunol.1600526 PG 8 WC Immunology SC Immunology GA DY3OA UT WOS:000385002300013 PM 27481850 ER PT J AU Provine, NM Larocca, RA Aid, M Penaloza-MacMaster, P Badamchi-Zadeh, A Borducchi, EN Yates, KB Abbink, P Kirilova, M Ng'ang'a, D Bramson, J Haining, WN Barouch, DH AF Provine, Nicholas M. Larocca, Rafael A. Aid, Malika Penaloza-MacMaster, Pablo Badamchi-Zadeh, Alexander Borducchi, Erica N. Yates, Kathleen B. Abbink, Peter Kirilova, Marinela Ng'ang'a, David Bramson, Jonathan Haining, W. Nicholas Barouch, Dan H. TI Immediate Dysfunction of Vaccine-Elicited CD8(+) T Cells Primed in the Absence of CD4(+) T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC VIRAL-INFECTION; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HIV-1 ENV VACCINE; RESPONSES IN-VIVO; PROTECTIVE IMMUNITY; TRANSCRIPTION FACTOR; CTL RESPONSE; IPCAVD 001; MEMORY; EXHAUSTION AB CD4(+) T cell help is critical for optimal CD8(+) T cell memory differentiation and maintenance in many experimental systems. In addition, many reports have identified reduced primary CD8(+) T cell responses in the absence of CD4(+) T cell help, which often coincides with reduced Ag or pathogen clearance. In this study, we demonstrate that absence of CD4(+) T cells at the time of adenovirus vector immunization of mice led to immediate impairments in early CD8(+) T cell functionality and differentiation. Unhelped CD8(+) T cells exhibited a reduced effector phenotype, decreased ex vivo cytotoxicity, and decreased capacity to produce cytokines. This dysfunctional state was imprinted within 3 d of immunization. Unhelped CD8(+) T cells expressed elevated levels of inhibitory receptors and exhibited transcriptomic exhaustion and anergy profiles by gene set enrichment analysis. Dysfunctional, impaired effector differentiation also occurred following immunization of CD4(+) T cell-deficient mice with a poxvirus vector. This study demonstrates that following priming with viral vectors, CD4(+) T cell help is required to promote both the expansion and acquisition of effector functions by CD8(+) T cells, which is accomplished by preventing immediate dysfunction. C1 [Provine, Nicholas M.; Larocca, Rafael A.; Aid, Malika; Penaloza-MacMaster, Pablo; Badamchi-Zadeh, Alexander; Borducchi, Erica N.; Abbink, Peter; Kirilova, Marinela; Ng'ang'a, David; Barouch, Dan H.] Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yates, Kathleen B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Bramson, Jonathan] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada. [Bramson, Jonathan] McMaster Univ, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON L8S 4K1, Canada. [Bramson, Jonathan] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON L8S 4K1, Canada. [Haining, W. Nicholas] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Haining, W. Nicholas] Harvard Med Sch, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02139 USA. RP Barouch, DH (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 330 Brookline Ave E-CLS 1043, Boston, MA 02215 USA. EM dbarouch@bidmc.harvard.edu OI Assumpcao Larocca, Rafael/0000-0002-9995-1804 FU NIAID NIH HHS [T32 AI007245, T32 AI007387, U19 AI078526, U19 AI096040] NR 86 TC 1 Z9 1 U1 3 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2016 VL 197 IS 5 BP 1809 EP 1822 DI 10.4049/jimmunol.1600591 PG 14 WC Immunology SC Immunology GA DY3OA UT WOS:000385002300029 PM 27448585 ER PT J AU Boucard-Jourdin, M Kugler, D Ahanda, MLE This, S De Calisto, J Zhang, AL Mora, JR Stuart, LM Savill, J Lacy-Hulbert, A Paidassi, H AF Boucard-Jourdin, Mathilde Kugler, David Ahanda, Marie-Laure Endale This, Sebastien De Calisto, Jaime Zhang, Ailiang Mora, J. Rodrigo Stuart, Lynda M. Savill, John Lacy-Hulbert, Adam Paidassi, Helena TI beta 8 Integrin Expression and Activation of TGF-beta by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MESENTERIC LYMPH-NODES; ALPHA-V INTEGRINS; LAMINA-PROPRIA; RETINOIC-ACID; EPITHELIAL-CELLS; STEADY-STATE; VITAMIN-A AB Activation of TGF-beta by dendritic cells (DCs) expressing alpha v beta 8 integrin is essential for the generation of intestinal regulatory T cells (Tregs) that in turn promote tolerance to intestinal Ags. We have recently shown that alpha v beta 8 integrin is preferentially expressed by CD103 + DCs and confers their ability to activate TGF-beta and generate Tregs. However, how these DCs become specialized for this vital function is unknown. In this study, we show that beta 8 expression is controlled by a combination of factors that include DC lineage and signals derived from the tissue microenvironment and microbiota. Specifically, our data demonstrate that TGF-beta itself, along with retinoic acid and TLR signaling, drives expression of alpha v beta 8 in DCs. However, these signals only result in high levels of beta 8 expression in cells of the cDC1 lineage, CD8 alpha(+), or CD103(+)CD11b(-) DCs, and this is associated with epigenetic changes in the Itg beta 8 locus. Together, these data provide a key illustrative example of how microenvironmental factors and cell lineage drive the generation of regulatory alpha v beta 8-expressing DCs specialized for activation of TGF-beta to facilitate Treg generation. C1 [Boucard-Jourdin, Mathilde; Ahanda, Marie-Laure Endale; This, Sebastien; Paidassi, Helena] Univ Lyon, C1RI, F-69365 Lyon, France. [Boucard-Jourdin, Mathilde; Ahanda, Marie-Laure Endale; This, Sebastien; Paidassi, Helena] INSERM, U1111, F-69007 Lyon, France. [Boucard-Jourdin, Mathilde; Ahanda, Marie-Laure Endale; This, Sebastien; Paidassi, Helena] Ecole Normale Super Lyon, F-69007 Lyon, France. [Boucard-Jourdin, Mathilde; Ahanda, Marie-Laure Endale; This, Sebastien; Paidassi, Helena] Univ Lyon 1, Ctr Int Rech Infectiol, Lyon, France. [Boucard-Jourdin, Mathilde; Ahanda, Marie-Laure Endale; This, Sebastien; Paidassi, Helena] CNRS, UMR5308, F-69365 Lyon, France. [Kugler, David; Stuart, Lynda M.; Lacy-Hulbert, Adam] Benaroya Res Inst, Seattle, WA 98101 USA. [De Calisto, Jaime] Univ Mayor, Fac Ciencias, Ctr Genom & Bioinformat, Santiago 8580745, Chile. [Zhang, Ailiang; Savill, John] Univ Edinburgh, Queens Med Res Inst, Med Res Council Ctr Inflammat Res, Edinburgh EH16 4TJ, Midlothian, Scotland. [Mora, J. Rodrigo] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Paidassi, H (reprint author), Ctr Int Rech Infectiol, 21 Ave Tony Gamier, F-69365 Lyon, France. EM helena.paidassi@inserm.fr FU Medical Research Council [G0802069, G0901697]; NIDDK NIH HHS [R01 DK093695] NR 63 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2016 VL 197 IS 5 BP 1968 EP 1978 DI 10.4049/jimmunol.1600244 PG 11 WC Immunology SC Immunology GA DY3OA UT WOS:000385002300044 PM 27481847 ER PT J AU Chheda, ZS Sharma, RK Jala, VR Luster, AD Haribabu, B AF Chheda, Zinal S. Sharma, Rajesh K. Jala, Venkatakrishna R. Luster, Andrew D. Haribabu, Bodduluri TI Chemoattractant Receptors BLT1 and CXCR3 Regulate Antitumor Immunity by Facilitating CD8(+) T Cell Migration into Tumors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOTRIENE B-4 RECEPTORS; CXCR3-COGNATE CHEMOKINE PRODUCTION; LYMPHOCYTE TRAFFICKING; MELANOMA PATIENTS; CANCER CELLS; EXPRESSION; INFILTRATION; IMMUNOTHERAPY; THERAPY; INFLAMMATION AB Immunotherapies have shown considerable efficacy for the treatment of various cancers, but a multitude of patients remain unresponsive for various reasons, including poor homing of T cells into tumors. In this study, we investigated the roles of the leukotriene B4 receptor, BLT1, and CXCR3, the receptor for CXCL9, CXCL10, and CXCL11, under endogenous as well as vaccine-induced antitumor immune response in a syngeneic murine model of B16 melanoma. Significant accelerations in tumor growth and reduced survival were observed in both BLT1(-/-) and CXCR3(-/-) mice as compared with wild-type ( WT) mice. Analysis of tumor-infiltrating leukocytes revealed significant reduction of CD8 + T cells in the tumors of BLT1(-/-) and CXCR3(-/-) mice as compared with WT tumors, despite their similar frequencies in the periphery. Adoptive transfer of WT but not BLT1(-/-) or CXCR3(-/-) CTLs significantly reduced tumor growth in Rag2(-/-) mice, a function attributed to reduced infiltration of knockout CTLs into tumors. Cotransfer experiments suggested that WT CTLs do not facilitate the infiltration of knockout CTLs to tumors. Anti-programmed cell death-1 ( PD-1) treatment reduced the tumor growth rate in WT mice but not in BLT1(-/-) , CXCR3(-/-) , or BLT1(-/-) CXCR3(-/-) mice. The loss of efficacy correlated with failure of the knockout CTLs to infiltrate into tumors upon antiPD- 1 treatment, suggesting an obligate requirement for both BLT1 and CXCR3 in mediating anti-PD-1 based antitumor immune response. These results demonstrate a critical role for both BLT1 and CXCR3 in CTL migration to tumors and thus may be targeted to enhance efficacy of CTL-based immunotherapies. C1 [Chheda, Zinal S.; Sharma, Rajesh K.; Jala, Venkatakrishna R.; Haribabu, Bodduluri] Univ Louisville Hlth Sci, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. [Chheda, Zinal S.; Jala, Venkatakrishna R.; Haribabu, Bodduluri] Univ Louisville Hlth Sci, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Sharma, Rajesh K.] Univ Louisville Hlth Sci, Dept Med, Div Med Oncol, Louisville, KY 40202 USA. [Luster, Andrew D.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Cambridge, MA 02139 USA. RP Haribabu, B (reprint author), James Graham Brown Canc Ctr, 505 South Hancock St,Room 324,Ctr Bldg, Louisville, KY 40202 USA. EM H0bodd01@louisville.edu OI Bodduluri, Haribabu/0000-0002-8261-3294 FU NCI NIH HHS [R01 CA138623] NR 69 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2016 VL 197 IS 5 BP 2016 EP 2026 DI 10.4049/jimmunol.1502376 PG 11 WC Immunology SC Immunology GA DY3OA UT WOS:000385002300049 PM 27465528 ER PT J AU Lewis, A Kimberly, WT AF Lewis, Ariane Kimberly, W. Taylor TI A retrospective analysis of cerebrospinal fluid drainage volume in subarachnoid hemorrhage and the need for early or late ventriculoperitoneal shunt placement SO JOURNAL OF NEUROSURGICAL SCIENCES LA English DT Article DE Hydrocephalus; Subarachnoid hemorrhage; Cerebrospinal fluid; Drainage; Ventriculoperitoneal shunt ID EXTERNAL VENTRICULAR DRAINAGE; HYDROCEPHALUS; COMPLICATIONS; PREDICTORS; VASOSPASM; ANEURYSMS; TRIAL AB BACKGROUND: External ventricular drains (EVDs) are used to manage acute hydrocephalus and facilitate brain relaxation after subarachnoid hemorrhage (SAH). We conducted a retrospective study on the relationship between CSF drainage volume and requirement and timing (early vs. late) for ventriculoperitoneal shunt (VPS) placement after EVD removal. We also sought to examine what factors were associated with volume of CSF drainage. METHODS: We performed a retrospective analysis of SAH patients who had an EVD placed between January 2008 and June 2012 at Massachusetts General Hospital. Clinical and laboratory variables were abstracted from the medical record. RESULTS: Of 97 patients, 19 failed an EVD clamp trial and had an early VPS placed and 10 had their EVD removed but subsequently required late VPS placement. Average CSF drainage volume per day was highest in patients who required early VPS (median of 201 cc, interquartile range [IQR] 186-236) compared to those who did not require a VPS (median of 162cc, IQR 131-202) and those who required late VPS (median of 151cc, IQR 121-171) (P=0.002). There was a significant relationship between average CSF drainage volume per day and age (P=0.005) and sonographic vasospasm (P=0.006). After multivariate analysis, there was a significant relationship between VPS placement/timing and age (P=0.03) and average CSF output/day (P=<0.0001), and a trend towards significance with sonographic vasospasm (P=0.06). CONCLUSIONS: High CSF output is associated with early VPS placement. Prospective research on targeted CSF drainage volume is warranted. C1 [Lewis, Ariane] NYU, Dept Neurosurg, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. [Lewis, Ariane] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Lewis, A (reprint author), NYU, Langone Med Ctr, Div Neurocrit Care, Dept Neurol, 530 First Ave,HCC-5A, New York, NY 10016 USA. EM ariane.kansas.lewis@gmail.com FU Andrew David Heitman Neurovascular Research Foundation FX Ariane Lewis does not have any financial conflicts of interest. W. Taylor Kimberly receives support from the Andrew David Heitman Neurovascular Research Foundation. The Foundation had no role in study design, collection, analysis, interpretation of data, writing of the manuscript, or decision to submit the manuscript for publication. NR 29 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0390-5616 EI 1827-1855 J9 J NEUROSURG SCI JI J. Neurosurg. Sci. PD SEP PY 2016 VL 60 IS 3 BP 289 EP 295 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DY2UK UT WOS:000384947400002 PM 25516013 ER PT J AU Lucena-Araujo, AR Moran, JP VanderLaan, PA Dias-Santagata, D Folch, E Majid, A Kent, MS Gangadharan, SP Rangachari, D Huberman, MS Kobayashi, SS Costa, DB AF Lucena-Araujo, Antonio R. Moran, Jason P. VanderLaan, Paul A. Dias-Santagata, Dora Folch, Erik Majid, Adnan Kent, Michael S. Gangadharan, Sidharta P. Rangachari, Deepa Huberman, Mark S. Kobayashi, Susumu S. Costa, Daniel B. TI De novo ALK kinase domain mutations are uncommon in kinase inhibitor-naive ALK rearranged lung cancers SO LUNG CANCER LA English DT Article DE Mutation; Lung cancer; Adenocarcinoma; ALK; Kinase domain; Crizotinib ID TUMOR GENOTYPING TECHNIQUES; CRIZOTINIB RESISTANCE; IDENTIFICATION AB Introduction: Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinomas are responsive to the multitargeted ALK inhibitor crizotinib. One of the common mechanisms of resistance to crizotinib is the acquisition of ALK kinase domain mutations. However, the presence of ALK mutations in crizotinib-naive tumors has not been widely reported and it is unclear if de novo ALIC mutations affect the response to crizotinib. Methods: We analyzed preclinical models of ALIC rearranged lung cancers that were sensitive/resistant to ALK inhibitors, probed our institutional and other lung cancer databases for tumors with ALK kinase domain mutations, and evaluated tumor response to crizotinib. Results: ALK rearranged cell lines with ALK kinase domain mutations were heterogeneously less inhibited by increasing concentrations of crizotinib than cells driven solely by EML4-ALK fusions. Previous ALK rearranged lung cancer cohorts did not report ALK kinase mutations in inhibitor-naive tumors. We identified one TKI-naive ALK rearranged tumor with an ALK kinase domain mutation: ALIC-S1206F (mutations at ALK-S1206 shifted crizotinib inhibitory curves only minimally in preclinical models). The never smoker whose tumor harbored de novo EML4-ALK-E5;A20+ALK-S1206F only achieved a 4-month radiographic response to crizotinib 250 mg twice daily. Conclusions: Combining data from our and prior cohorts, ALK kinase domain mutations were uncommon events (<3% of cases) in ALK inhibitor-naive ALIC rearranged lung adenocarcinomas but their effect on intrinsic resistance to ALK inhibitors should be better evaluated. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Lucena-Araujo, Antonio R.; Moran, Jason P.; Folch, Erik; Majid, Adnan; Rangachari, Deepa; Huberman, Mark S.; Kobayashi, Susumu S.; Costa, Daniel B.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. [VanderLaan, Paul A.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. [Folch, Erik; Majid, Adnan; Kent, Michael S.; Gangadharan, Sidharta P.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. [Dias-Santagata, Dora] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Kobayashi, SS; Costa, DB (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. EM skobayas@bidmc.harvard.edu; dbcosta@bidmc.harvard.edu FU American Cancer Society [RSG 11-186]; National Cancer Institute [P50CA090578, R01CA169259, R21CA17830] FX This work was funded in part through an American Cancer Society grant RSG 11-186 (DBC), and National Cancer Institute grants P50CA090578 (DBC), R01CA169259 (SSK) and R21CA17830 (SSK). NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD SEP PY 2016 VL 99 BP 17 EP 22 DI 10.1016/j.lungcan.2016.06.006 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DY1NZ UT WOS:000384863000004 PM 27565908 ER PT J AU Karaa, A Kriger, J Grier, J Holbert, A Thompson, JLP Parikh, S Hirano, M AF Karaa, Amel Kriger, Joshua Grier, Johnston Holbert, Amy Thompson, John L. P. Parikh, Sumit Hirano, Michio TI Mitochondrial disease patients' perception of dietary supplements' use SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Mitochondria disease; Dietary supplements; Survey ID PEDIATRIC-PATIENTS; MULTIPLE VITAMINS; DISORDERS; TRIAL; UBIDECARENONE; MYOPATHIES; MANAGEMENT; CREATINE AB Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q(10), L-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2 weeks to 3 months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective interpretation of symptoms severity and supplements effect rather than real patients' experience. More extensive prospective studies will help further elucidate this topic. (C) 2016 Elsevier Inc. All rights reserved. C1 [Karaa, Amel] Harvard Univ, Massachusetts Gen Hosp, Genet Unit, Boston, MA 02114 USA. [Kriger, Joshua; Grier, Johnston; Thompson, John L. P.] Columbia Univ, Med Ctr, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Holbert, Amy] Univ S Florida, Hlth Informat Inst, Tampa, FL USA. [Parikh, Sumit] Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA. [Hirano, Michio] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. RP Karaa, A (reprint author), 185 Cambdrige St,Rm 2222, Boston, MA 02114 USA. EM akaraa@mgh.harvard.edu; jk3563@cumc.columbia.edu; jg3145@cumc.columbia.edu; amy.holbert@epi.usf.edu; jlt12@cumc.columbia.edu; parikhs@ccv.org; mh29@cumc.columbia.edu FU NIH [U54 NS078059]; NCATS - NIH Institute; NICHD - NIH Institute; NINDS - NIH Institute; ODS - NIH Institute; UMDF clinical Fellowship award [2013D000795] FX This North American Mitochondrial Disease Consortium (NAMDC) study is supported by NIH grant U54 NS078059. NAMDC is a part of the NCATS Rare Diseases Clinical Research Network (RDCRN) and is funded through a collaboration between NCATS, NICHD, NINDS and ODS co-funding NIH Institute(s). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR). AK was supported by a UMDF clinical Fellowship award (2013D000795). NR 20 TC 0 Z9 0 U1 4 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2016 VL 119 IS 1-2 SI SI BP 100 EP 108 DI 10.1016/j.ymgme.2016.07.005 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DX8IJ UT WOS:000384631000014 PM 27444792 ER PT J AU Hopkin, RJ Cabrera, G Charrow, J Lemay, R Martins, AM Mauer, M Ortiz, A Patel, MR Sims, K Waldek, S Warnock, DG Wilcox, WR AF Hopkin, Robert J. Cabrera, Gustavo Charrow, Joel Lemay, Roberta Martins, Ana Maria Mauer, Michael Ortiz, Alberto Patel, Manesh R. Sims, Katherine Waldek, Stephen Warnock, David G. Wilcox, William R. TI Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Fabry disease; Severe clinical events; Risk factors; Agalsidase beta ID GALACTOSIDASE-A GENE; NATURAL-HISTORY DATA; ALPHA-GALACTOSIDASE; MUTATIONS; INVOLVEMENT; MANAGEMENT; MORTALITY; STROKE; KIDNEY; IDENTIFICATION AB Background: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. Methods: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. Results: The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3 years and 3.2 years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free. Conclusions: Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. [Hopkin, Robert J.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Cabrera, Gustavo] Ctr Cardiovasc Bolivar, Buenos Aires, DF, Argentina. [Charrow, Joel] Ann & Robert H Lurie Childrens Hosp Chicago, Div Genet Birth Defects & Metab, Chicago, IL 60611 USA. [Lemay, Roberta] Sanofi Genzyme, Rare Dis, Strateg Epidemiol & Biostat, Cambridge, MA USA. [Martins, Ana Maria] Univ Fed Sao Paulo, Reference Ctr Inborn Errors Metab, Sao Paulo, Brazil. [Mauer, Michael] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Mauer, Michael] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Ortiz, Alberto] UAM, IIS Fdn Jimenez Diaz, Sch Med, Unidad Dialisis,IRSIN,REDINREN, Madrid, Spain. [Patel, Manesh R.] Duke Univ, Sch Med, Div Cardiovasc Med, Durham, NC 27706 USA. [Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sims, Katherine] Harvard Med Sch, Boston, MA USA. [Waldek, Stephen] Univ Sunderland, Sunderland SR2 7EE, Durham, England. [Warnock, David G.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA. [Wilcox, William R.] Emory Univ, Sch Med, Dept Human Genet, Div Med Genet, Atlanta, GA USA. RP Hopkin, RJ (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM rob.hopkin@cchmc.org; gustavo.h.cabrera@hotmail.com; jcharrow@northwestern.edu; Roberta.Lemay@genzyme.com; martins.anamaria@uol.com.br; mauer002@umn.edu; AOrtiz@fjd.es; patel017@mc.duke.edu; Sims@Helix.MGH.Harvard.edu; stephen.waldek@sunderland.ac.uk; dwarnock@uab.edu; william.wilcox@emory.edu OI Hopkin, Robert/0000-0003-0770-5516 FU Sanofi Genzyme; Fabry Registry FX This research was funded (statistical programming and medical writing support, and manuscript submission assistance; see "Acknowledgments" section) by Sanofi Genzyme, the sponsor of the Fabry Registry. The funder had a role in data collection and analysis. NR 43 TC 1 Z9 1 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2016 VL 119 IS 1-2 SI SI BP 151 EP 159 DI 10.1016/j.ymgme.2016.06.007 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DX8IJ UT WOS:000384631000020 PM 27510433 ER PT J AU Fietz, M AlSayed, M Burke, D Cohen-Pfeffer, J Cooper, JD Dvorakova, L Giugliani, R Izzo, E Jahnova, H Lukacs, Z Mole, SE de Halac, IN Pearce, DA Poupetova, H Schulz, A Specchio, N Xin, WN Miller, N AF Fietz, Michael AlSayed, Moeenaldeen Burke, Derek Cohen-Pfeffer, Jessica Cooper, Jonathan D. Dvorakova, Lenka Giugliani, Roberto Izzo, Emanuela Jahnova, Helena Lukacs, Zoltan Mole, Sara E. de Halac, Ines Noher Pearce, David A. Poupetova, Helena Schulz, Angela Specchio, Nicola Xin, Winnie Miller, Nicole TI Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Neuronal ceroid lipofuscinosis; Laboratory diagnosis; Lysosomal storage disorder; Expert recommendations; Neurodegeneration; Genetic cause of epilepsy ID TRIPEPTIDYL PEPTIDASE I; DRIED BLOOD SPOTS; BIOCHEMICAL-CHARACTERIZATION; CLINICAL-COURSE; BATTEN-DISEASE; MUTATIONS; EPILEPSY; PROTEIN; NCL; SEVERITY AB Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2-4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, orb) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Fietz, Michael] PathWest Lab Med WA, Dept Diagnost Genom, Nedlands, WA, Australia. [AlSayed, Moeenaldeen] Alfaisal Univ, King Faisal Specialist Hosp & Res Ctr, Dept Med Genet, Riyadh, Saudi Arabia. [Burke, Derek] Great Ormond St Hosp Sick Children, Camelia Botnar Labs, Chem Pathol, London, England. [Cohen-Pfeffer, Jessica; Izzo, Emanuela; Miller, Nicole] BioMarin Pharmaceut Inc, Novato, CA 94949 USA. [Cooper, Jonathan D.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England. [Dvorakova, Lenka; Jahnova, Helena; Poupetova, Helena] Charles Univ Prague, Gen Univ Hosp Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic. [Giugliani, Roberto] Univ Fed Rio Grande do Sul, INAGEMP, Dept Genet, Med Genet Serv,HCPA, Porto Alegre, RS, Brazil. [Lukacs, Zoltan] Univ Hamburg, Med Ctr, Newborn Screening & Metab Diagnost Unit, Hamburg, Germany. [Mole, Sara E.] UCL, UCL Inst Child Hlth, MRC Lab Mol Cell Biol, London, England. [de Halac, Ines Noher] Natl Univ Cordoba, Fac Ciencias Med, Cordoba, Argentina. [de Halac, Ines Noher] Natl Res Council CONICET, Cordoba, Argentina. [Pearce, David A.] Sanford Childrens Hlth Res Ctr, Sioux Falls, SD USA. [Schulz, Angela] Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Hamburg, Germany. [Specchio, Nicola] Bambino Gesu Pediat Hosp, Dept Neurosci, Rome, Italy. [Xin, Winnie] Harvard Med Sch, Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA USA. RP Miller, N (reprint author), BioMarin Pharmaceut Inc, Novato, CA 94949 USA. EM NMiller@bmrn.com OI Mole, Sara/0000-0003-4385-4957 FU BioMarin Pharmaceutical Inc. FX The authors thank all 18 respondents to the CLN2 Disease Expert Survey and all attendees of the CLN2 Expert Meeting, held May 2015 in Prague, Czech Republic, both of which were organized and supported by BioMarin Pharmaceutical Inc. The authors also thank Mitch Bailey, MS, Elaina Jurecki, MS, RD, and Renee Shediac, PhD, of BioMarin Pharmaceutical Inc. for review of the manuscript, and the Batten Disease Support and Research Association for sharing patient family survey information. This article was prepared with editorial assistance from Karl Zawadzki, PhD, of Health Interactions, which was funded by BioMarin Pharmaceutical Inc. NR 52 TC 0 Z9 0 U1 8 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2016 VL 119 IS 1-2 SI SI BP 160 EP 167 DI 10.1016/j.ymgme.2016.07.011 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DX8IJ UT WOS:000384631000021 PM 27553878 ER PT J AU Behjati, S Gundem, G Wedge, DC Roberts, ND Tarpey, PS Cooke, SL Van Loo, P Alexandrov, LB Ramakrishna, M Davies, H Nik-Zainal, S Hardy, C Latimer, C Raine, KM Stebbings, L Menzies, A Jones, D Shepherd, R Butler, AP Teague, JW Jorgensen, M Khatri, B Pillay, N Shlien, A Futreal, PA Badie, C McDermott, U Bova, GS Richardson, AL Flanagan, AM Stratton, MR Campbell, PJ AF Behjati, Sam Gundem, Gunes Wedge, David C. Roberts, Nicola D. Tarpey, Patrick S. Cooke, Susanna L. Van Loo, Peter Alexandrov, Ludmil B. Ramakrishna, Manasa Davies, Helen Nik-Zainal, Serena Hardy, Claire Latimer, Calli Raine, Keiran M. Stebbings, Lucy Menzies, Andy Jones, David Shepherd, Rebecca Butler, Adam P. Teague, Jon W. Jorgensen, Mette Khatri, Bhavisha Pillay, Nischalan Shlien, Adam Futreal, P. Andrew Badie, Christophe McDermott, Ultan Bova, G. Steven Richardson, Andrea L. Flanagan, Adrienne M. Stratton, Michael R. Campbell, Peter J. CA ICGC Prostate Grp TI Mutational signatures of ionizing radiation in second malignancies SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ANALYSIS; 21 BREAST CANCERS; INDUCED SARCOMAS; PROSTATE-CANCER; PAST EXPOSURE; RADIOTHERAPY; ANGIOSARCOMA; LYMPHOCYTES; MUTAGENESIS; INVERSIONS AB Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1-100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential. C1 [Behjati, Sam; Gundem, Gunes; Wedge, David C.; Roberts, Nicola D.; Tarpey, Patrick S.; Cooke, Susanna L.; Alexandrov, Ludmil B.; Ramakrishna, Manasa; Davies, Helen; Nik-Zainal, Serena; Hardy, Claire; Latimer, Calli; Raine, Keiran M.; Stebbings, Lucy; Menzies, Andy; Jones, David; Shepherd, Rebecca; Butler, Adam P.; Teague, Jon W.; Shlien, Adam; Futreal, P. Andrew; McDermott, Ultan; Stratton, Michael R.; Campbell, Peter J.] Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England. [Behjati, Sam] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England. [Wedge, David C.] Oxford Big Data Inst, Roosevelt Dr, Oxford OX3 7BN, England. [Wedge, David C.] Wellcome Trust Ctr Human Genet, Oxford Ctr Canc Gene Res, Roosevelt Dr, Oxford OX3 7BN, England. [Van Loo, Peter] Francis Crick Inst, London WC2A 3LY, England. [Van Loo, Peter] Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium. [Jorgensen, Mette; Pillay, Nischalan; Flanagan, Adrienne M.] UCL, Inst Canc, Huntley St, London WC1E 6BT, England. [Khatri, Bhavisha; Pillay, Nischalan; Flanagan, Adrienne M.] Royal Natl Orthopaed Hosp NHS Trust, Histopathol, Stanmore HA7 4LP, Middx, England. [Shlien, Adam] Hosp Sick Children, Lab Med, Dept Paediat, Toronto, ON M5G 1X8, Canada. [Futreal, P. Andrew] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Badie, Christophe] Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Radiat Effects Dept, Canc Mech & Biomarkers Grp, Didcot OX11 0RQ, Oxon, England. [Bova, G. Steven] Univ Tampere, BioMediTech, Inst Biosci & Med Technol, FI-33520 Tampere, Finland. [Bova, G. Steven] Tampere Univ Hosp, Fimlab Labs, FI-33520 Tampere, Finland. [Richardson, Andrea L.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Richardson, Andrea L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA. [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Hills Rd, Cambridge CB2 2XY, England. [Richardson, Andrea L.] Johns Hopkins Med, Sibley Mem Hosp, Washington, DC 20016 USA. RP Campbell, PJ (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.; Campbell, PJ (reprint author), Univ Cambridge, Dept Haematol, Hills Rd, Cambridge CB2 2XY, England. EM pc8@sanger.ac.uk OI Van Loo, Peter/0000-0003-0292-1949; McDermott, Ultan/0000-0001-9032-4700; Wedge, David/0000-0002-7572-3196; Martin, Sancha/0000-0001-6213-5259; Berney, Daniel/0000-0001-5474-8696; Badie, Christophe/0000-0003-4572-5008 FU Wellcome Trust [077012/Z/05/Z]; Skeletal Cancer Action Trust; Rosetrees Trust UK; Bone Cancer Research Trust; RNOH NHS Trust; National Institute for Health Research Health Protection Research Unit in Chemical and Radiation Hazards and Threats at Newcastle University; Public Health England; National Institute for Health Research; UCLH Biomedical Research Centre; CRUK UCL Experimental Cancer Centre; Wellcome Trust Intermediate Clinical Research Fellowships; Wellcome Trust Senior Clinical Research Fellowship FX This work was supported by funding from the Wellcome Trust (grant reference 077012/Z/05/Z), Skeletal Cancer Action Trust, Rosetrees Trust UK, Bone Cancer Research Trust, the RNOH NHS Trust, the National Institute for Health Research Health Protection Research Unit in Chemical and Radiation Hazards and Threats at Newcastle University in partnership with Public Health England. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England. Tissue was obtained from the RNOH Musculoskeletal Research Programme and Biobank, co-ordinated by Mrs Deidre Brooking and Mrs Ru Grinnell, Biobank staff, RNOH. Support was provided to AMF by the National Institute for Health Research, UCLH Biomedical Research Centre, and the CRUK UCL Experimental Cancer Centre. S.N.Z. and S.B. are personally funded through Wellcome Trust Intermediate Clinical Research Fellowships, P.J.C. through a Wellcome Trust Senior Clinical Research Fellowship. We are grateful to the patients for participating in this research and to the clinicians and support staff involved in their care. NR 42 TC 0 Z9 0 U1 12 U2 12 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 SEP PY 2016 VL 7 AR 12605 DI 10.1038/ncomms12605 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY6RQ UT WOS:000385256100001 PM 27615322 ER PT J AU Fu, Y Zhang, Z Sheehan, J Avnir, Y Ridenour, C Sachnik, T Sun, JS Hossain, MJ Chen, LM Zhu, Q Donis, RO Marasco, WA AF Fu, Ying Zhang, Zhen Sheehan, Jared Avnir, Yuval Ridenour, Callie Sachnik, Thomas Sun, Jiusong Hossain, M. Jaber Chen, Li-Mei Zhu, Quan Donis, Ruben O. Marasco, Wayne A. TI A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve SO NATURE COMMUNICATIONS LA English DT Article ID INFLUENZA-A VIRUS; STALK-SPECIFIC ANTIBODIES; HUMAN MONOCLONAL-ANTIBODY; LIVED PLASMA-CELLS; IN-VIVO; SOMATIC HYPERMUTATION; RECEPTOR-BINDING; EVOLUTION; ANTIGEN; VACCINE AB Understanding the natural evolution and structural changes involved in broadly neutralizing antibody (bnAb) development holds great promise for improving the design of prophylactic influenza vaccines. Here we report an haemagglutinin (HA) stem-directed bnAb, 3I14, isolated from human memory B cells, that utilizes a heavy chain encoded by the IGHV3-30 germline gene. MAb 3I14 binds and neutralizes groups 1 and 2 influenza A viruses and protects mice from lethal challenge. Analysis of VH and VL germline back-mutants reveals binding to H3 and H1 but not H5, which supports the critical role of somatic hypermutation in broadening the bnAb response. Moreover, a single VLD94N mutation improves the affinity of 3I14 to H5 by nearly 10-fold. These data provide evidence that memory B cell evolution can expand the HA subtype specificity. Our results further suggest that establishing an optimized memory B cell pool should be an aim of 'universal' influenza vaccine strategies. C1 [Fu, Ying; Zhang, Zhen; Sheehan, Jared; Avnir, Yuval; Sachnik, Thomas; Sun, Jiusong; Zhu, Quan; Marasco, Wayne A.] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & Virol, 450 Brookline Ave, Boston, MA 02115 USA. [Ridenour, Callie; Hossain, M. Jaber; Chen, Li-Mei; Donis, Ruben O.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Road Mail Stop G-16, Atlanta, GA 30333 USA. RP Marasco, WA (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & Virol, 450 Brookline Ave, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu FU National Institutes of Health (NIAID) [U01-AI074518] FX We thank Drs De-Kuan Chang and Xian-Chun Tang for technical support. This work was supported by National Institutes of Health (NIAID U01-AI074518) to W.A.M. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention or the Agency for Toxic Substances and Disease Registry. NR 54 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 SEP PY 2016 VL 7 AR 12780 DI 10.1038/ncomms12780 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY6RU UT WOS:000385256500010 PM 27619409 ER PT J AU Muzumdar, MD Dorans, KJ Chung, KM Robbins, R Tammela, T Gocheva, V Li, CMC Jacks, T AF Muzumdar, Mandar Deepak Dorans, Kimberly Judith Chung, Katherine Minjee Robbins, Rebecca Tammela, Tuomas Gocheva, Vasilena Li, Carman Man-Chung Jacks, Tyler TI Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers SO NATURE COMMUNICATIONS LA English DT Article ID PANCREATIC DUCTAL ADENOCARCINOMA; TUMOR-SUPPRESSOR GENE; ONCOGENIC K-RAS; LUNG-CANCER; MOSAIC ANALYSIS; DOUBLE MARKERS; INTRATUMORAL HETEROGENEITY; MUTANT P53; CELL; MOUSE AB Although it has become increasingly clear that cancers display extensive cellular heterogeneity, the spatial growth dynamics of genetically distinct clones within developing solid tumours remain poorly understood. Here we leverage mosaic analysis with double markers (MADM) to trace subclonal populations retaining or lacking p53 within oncogenic Kras-initiated lung and pancreatic tumours. In both models, p53 constrains progression to advanced adenocarcinomas. Comparison of lineage-related p53 knockout and wild-type clones reveals a minor role of p53 in suppressing cell expansion in lung adenomas. In contrast, p53 loss promotes both the initiation and expansion of low-grade pancreatic intraepithelial neoplasia (PanINs), likely through differential expression of the p53 regulator p19ARF. Strikingly, lineage-related cells are often dispersed in lung adenomas and PanINs, contrasting with more contiguous growth of advanced subclones. Together, these results support cancer type-specific suppressive roles of p53 in early tumour progression and offer insights into clonal growth patterns during tumour development. C1 [Muzumdar, Mandar Deepak; Dorans, Kimberly Judith; Chung, Katherine Minjee; Robbins, Rebecca; Tammela, Tuomas; Gocheva, Vasilena; Li, Carman Man-Chung; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave 75-453, Cambridge, MA 02139 USA. [Muzumdar, Mandar Deepak] Dana Farber Canc Inst, Boston, MA 02215 USA. [Muzumdar, Mandar Deepak] Harvard Med Sch, Boston, MA 02115 USA. [Li, Carman Man-Chung; Jacks, Tyler] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave 75-453, Cambridge, MA 02139 USA.; Jacks, T (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Jacks, T (reprint author), MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. EM tjacks@mit.edu FU Lustgarten Foundation; Howard Hughes Medical Institute; National Cancer Institute [P30-CA14051]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [KL2 TR001100]; NIH Pathway to Independence Award [K99]; Jane Coffin Childs Memorial Fund Postdoctoral Fellowship; Ludwig Center for Molecular Oncology Fund FX We thank P.-Y. Chen for critical reading of the manuscript; A. Li and K. Mercer for technical assistance; K. Cormier and C. Condon from the Hope Babette Tang (1983) Histology Facility for IHC support; J. Wyckoff from the Swanson Biotechnology Center Microscopy Core facility for technical assistance with confocal and multi-photon imaging; N.R. Kerper for help with CLARITY experiments; and A. Berns, A. Lowy, L. Luo and H. Zong for mice. This work was supported by the Lustgarten Foundation, the Howard Hughes Medical Institute and, in part, by a Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute. M.D.M. is supported by a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centres, or the National Institutes of Health. T.T. is supported by a NIH Pathway to Independence Award (K99). V.G. is supported by a Jane Coffin Childs Memorial Fund Postdoctoral Fellowship. C.M.L. is supported by the Ludwig Center for Molecular Oncology Fund. T.J. is a Howard Hughes Medical Institute Investigator, the David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar. NR 44 TC 1 Z9 1 U1 2 U2 2 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 SEP PY 2016 VL 7 AR 12685 DI 10.1038/ncomms12685 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DY3EC UT WOS:000384972600001 PM 27585860 ER PT J AU Schernthaner, G Groop, P Cooper, M Perkovic, V Hocher, B Kanasaki, K Sharma, K Stanton, R Toto, R Cescutti, J Gordat, M Meinicke, T Koitka-Weber, A Woerle, H Eynatten, M AF Schernthaner, G. Groop, P. Cooper, M. Perkovic, V Hocher, B. Kanasaki, K. Sharma, K. Stanton, R. Toto, R. Cescutti, J. Gordat, M. Meinicke, T. Koitka-Weber, A. Woerle, H. Eynatten, M. TI EFFECTS OF LINAGLIPTIN ON GLYCAEMIC CONTROL AND ALBUMINURIA IN TYPE 2 DIABETES - THE MARLINA-T2D (TM) TRIAL SO NEPHROLOGY LA English DT Meeting Abstract C1 [Schernthaner, G.] Rudolfstiftung Hosp, Dept Internal Med, Vienna, Austria. [Groop, P.] Biomedicum Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland. [Groop, P.; Cooper, M.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Perkovic, V] Univ Sydney, George Inst Global Hlth, Sydney, NSW, Australia. [Hocher, B.] Univ Potsdam, Inst Nutr Sci, Potsdam, Germany. [Kanasaki, K.] Kanazawa Med Univ, Uchinada, Ishikawa, Japan. [Sharma, K.] Univ Calif San Diego, Dept Med, Ctr Renal Translat Med, La Jolla, CA 92093 USA. [Stanton, R.] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Toto, R.] UT Southwestern Med Ctr, Dallas, TX USA. [Cescutti, J.; Gordat, M.] Boehringer Ingelheim GmbH & Co KG, Reims, France. [Meinicke, T.; Koitka-Weber, A.; Woerle, H.; Eynatten, M.] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 EI 1440-1797 J9 NEPHROLOGY JI Nephrology PD SEP PY 2016 VL 21 SU 2 BP 60 EP 60 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA DW4CV UT WOS:000383590600049 ER PT J AU Miao, H Chen, XG Yan, YW He, XX Hu, S Kong, J Wu, MQ Wei, YR Zhou, YW Wang, L Wang, K Qiu, BS AF Miao, Hui Chen, Xingui Yan, Yunwen He, Xiaoxuan Hu, Sheng Kong, Jian Wu, Meiqi Wei, Yarui Zhou, Yawen Wang, Lu Wang, Kai Qiu, Bensheng TI Functional connectivity change of brain default mode network in breast cancer patients after chemotherapy SO NEURORADIOLOGY LA English DT Article DE Default mode network; Breast cancer; Cognitive impairment; Chemotherapy; Attention deficit ID MILD COGNITIVE IMPAIRMENT; EXECUTIVE FUNCTIONS; WORKING-MEMORY; RESTING-STATE; RETROSPLENIAL CORTEX; SUSTAINED ATTENTION; SELECTIVE ATTENTION; ALZHEIMERS-DISEASE; WHITE-MATTER; SURVIVORS AB Complaint about attention disorders is common among breast cancer patients who have undergone chemotherapy, which may be associated with the default mode network (DMN). To validate this hypothesis, we investigated the DMN functional connectivity (FC) change and its relationship with the attention function in breast cancer patients (BC) using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-two BC treated with chemotherapy and 22 healthy controls (HC) were recruited into this study. The FC between the DMN's hubs and regions of the dorsal medial prefrontal cortex (dMPFC) and medial temporal lobe (MTL) subsystems was respectively calculated for each participant. The statistical result showed significantly lower connectivity in dMPFC and MTL subsystems in the BC group. In addition, the partial correlation analysis result indicated that the low connectivity of some brain regions in MTL subsystem was correlated with attention dysfunction following BC chemotherapy. These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy. C1 [Miao, Hui; He, Xiaoxuan; Hu, Sheng; Wu, Meiqi; Wei, Yarui; Zhou, Yawen; Wang, Lu; Qiu, Bensheng] Univ Sci & Technol China, Ctr Biomed Engn, Hefei, Anhui, Peoples R China. [Chen, Xingui; Wang, Kai] Anhui Med Univ, Dept Neurol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China. [Yan, Yunwen] Anhui Med Univ, Dept Breast Surg, Affiliated Hosp 1, Hefei, Anhui, Peoples R China. [Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Qiu, Bensheng] Anhui Comp Applicat Inst Tradit Chinese Med, Hefei 230038, Anhui, Peoples R China. RP Qiu, BS (reprint author), Univ Sci & Technol China, Ctr Biomed Engn, Hefei, Anhui, Peoples R China.; Wang, K (reprint author), Anhui Med Univ, Dept Neurol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China.; Qiu, BS (reprint author), Anhui Comp Applicat Inst Tradit Chinese Med, Hefei 230038, Anhui, Peoples R China. EM wangkai1964@126.com; bqiu@ustc.edu.cn FU National Science Foundation of China [81371537, 91432301]; Major State Basic Research Development Program of China (973 Program) [2013CB733803]; Fundamental Research Funds for the Central Universities of China [WK2070000033] FX This work was supported by National Science Foundation of China (Grant numbers: 81371537, 91432301), Major State Basic Research Development Program of China (973 Program) (Grant number: 2013CB733803) and the Fundamental Research Funds for the Central Universities of China (WK2070000033). NR 59 TC 1 Z9 1 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 EI 1432-1920 J9 NEURORADIOLOGY JI Neuroradiology PD SEP PY 2016 VL 58 IS 9 BP 921 EP 928 DI 10.1007/s00234-016-1708-8 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DY4JP UT WOS:000385065100010 PM 27278455 ER PT J AU Carter, BW Benveniste, MF Betancourt, SL de Groot, PM Lichtenberger, JP Amini, B Abbott, GF AF Carter, Brett W. Benveniste, Marcelo F. Betancourt, Sonia L. de Groot, Patricia M. Lichtenberger, John P., III Amini, Behrang Abbott, Gerald F. TI Imaging Evaluation of Malignant Chest Wall Neoplasms SO RADIOGRAPHICS LA English DT Article ID SOFT-TISSUE HEMANGIOMAS; NERVE SHEATH TUMORS; PATHOLOGICAL CORRELATION; RADIOLOGIC FINDINGS; SURGICAL-TREATMENT; CLINICAL-COURSE; FATTY TUMORS; DERMATOFIBROSARCOMA PROTUBERANS; BRONCHOGENIC-CARCINOMA; MULTIPLE-MYELOMA AB Neoplasms of the chest wall are uncommon lesions that represent approximately 5% of all thoracic malignancies. These tumors comprise a heterogeneous group of neoplasms that may arise from osseous structures or soft tissues, and they may be malignant or benign. More than 50% of chest wall neoplasms are malignancies and include tumors that may arise as primary malignancies or secondarily involve the chest wall by way of direct invasion or metastasis from intrathoracic or extrathoracic neoplasms. Although 20% of chest wall tumors may be detected at chest radiography, chest wall malignancies are best evaluated with cross-sectional imaging, principally multidetector computed tomography (CT) and magnetic resonance (MR) imaging, each of which has distinct strengths and limitations. Multidetector CT is optimal for depicting bone, muscle, and vascular structures, whereas MR imaging renders superior soft-tissue contrast and spatial resolution and is better for delineating the full extent of disease. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is not routinely performed to evaluate chest wall malignancies. The primary functions of PET/CT in this setting include staging of disease, evaluation of treatment response, and detection of recurrent disease. Ultrasonography has a limited role in the evaluation and characterization of superficial chest wall lesions; however, it can be used to guide biopsy and has been shown to depict chest wall invasion by lung cancer more accurately than CT. It is important that radiologists be able to identify the key multidetector CT and MR imaging features that can be used to differentiate malignant from benign chest lesions, suggest specific histologic tumor types, and ultimately guide patient treatment. (C) RSNA, 2016 . radiographics.rsna.org C1 [Carter, Brett W.; Benveniste, Marcelo F.; Betancourt, Sonia L.; de Groot, Patricia M.; Amini, Behrang] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Div Diagnost Imaging, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. [Lichtenberger, John P., III] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. [Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Carter, BW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Div Diagnost Imaging, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. EM bcarter2@mdanderson.org NR 75 TC 0 Z9 0 U1 5 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2016 VL 36 IS 5 BP 1285 EP 1306 DI 10.1148/rg.2016150208 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3YY UT WOS:000385036300004 PM 27494286 ER PT J AU Mittal, PK Camacho, JC Sahani, DV Kalb, B Harri, PA Master, V Kokabi, N Hartman, M Kitajima, HD Moreno, CC AF Mittal, Pardeep K. Camacho, Juan C. Sahani, Dushyant V. Kalb, Bobby Harri, Peter A. Master, Viraj Kokabi, Nima Hartman, Matthew Kitajima, Hiroumi D. Moreno, Courtney C. TI Hematospermia Evaluation at MR Imaging SO RADIOGRAPHICS LA English DT Article ID EJACULATORY DUCT OBSTRUCTION; GUIDED PROSTATE BIOPSY; SEMINAL-VESICLE CYST; ENDORECTAL MRI; HEMOSPERMIA; DIAGNOSIS; MANAGEMENT; HAEMATOSPERMIA; ETIOLOGY; COIL AB Hematospermia is a challenging and anxiety-provoking condition that can manifest as a single episode or recur over the course of weeks to months. It is usually a benign self-limiting condition in younger sexually active males without a history of risk factors such as cancer, urogenital malformations, bleeding disorders, and their associated symptoms. However, patients with recurrent, refractory and painful hematospermia with associated symptoms, such as fever, pain, or weight loss, require evaluation through clinical assessment and noninvasive investigations to rule out underlying pathologic conditions such as ejaculatory obstruction, infectious and inflammatory causes, malignancy, vascular malformations, and systemic disorders that increase the risk of bleeding, especially when presenting in older men. If these investigations are negative, the patient should be reassured and treated accordingly. In the recent past, magnetic resonance (MR) imaging has assumed a major role in the investigation of hematospermia due to its excellent soft-tissue contrast and multiplanar capabilities. In this review, we will discuss the potential causes of hematospermia and its diagnostic workup, including pathophysiology, anatomic considerations, the imaging appearance of associated pathologic conditions, and management. (C) RSNA, 2016 . radiographics.rsna.org C1 [Mittal, Pardeep K.; Camacho, Juan C.; Harri, Peter A.; Kokabi, Nima; Kitajima, Hiroumi D.; Moreno, Courtney C.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. [Master, Viraj] Emory Univ, Sch Med, Dept Urol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Kalb, Bobby] Univ Arizona, Sch Med, Dept Med Imaging, Tucson, AZ USA. [Hartman, Matthew] West Penn Allegheny Hlth Syst, Dept Radiol, Pittsburgh, PA USA. RP Mittal, PK (reprint author), Emory Univ, Sch Med, Dept Radiol & Imaging Sci, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM pmittal@emory.edu OI Mittal, Pardeep/0000-0002-3302-8590; Camacho, Juan/0000-0003-3182-5227 NR 72 TC 0 Z9 0 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2016 VL 36 IS 5 BP 1373 EP 1389 DI 10.1148/rg.2016150195 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3YY UT WOS:000385036300009 PM 27517360 ER PT J AU Kelil, T Keraliya, AR Howard, SA Krajewski, KM Braschi-Amirfarzan, M Hornick, JL Ramaiya, NH Tirumani, SH AF Kelil, Tatiana Keraliya, Abhishek R. Howard, Stephanie A. Krajewski, Katherine M. Braschi-Amirfarzan, Marta Hornick, Jason L. Ramaiya, Nikhil H. Tirumani, Sree Harsha TI Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for Radiologists SO RADIOGRAPHICS LA English DT Article ID TYROSINE-KINASE INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; TREATMENT-RELATED MORTALITY; RENAL-CELL CARCINOMA; PROGNOSTIC-FACTORS; COMPUTED-TOMOGRAPHY; TARGETED THERAPIES; PATHOLOGICAL CORRELATION; ASSOCIATION GUIDELINES; FOLLICULAR CARCINOMA AB Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 39-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer. Surgery is the mainstay of treatment, with radioactive iodine (RAI) therapy reserved for differentiated subtypes. Posttreatment surveillance of thyroid cancer is done with US of the thyroid bed as well as monitoring of tumor markers such as serum thyroglobulin and serum calcitonin. Computed tomography (CT), magnetic resonance imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography/CT are used in the follow-up of patients with negative iodine 131 imaging and elevated tumor markers. Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance. Treatment options for metastatic RAI-refractory thyroid cancer are limited. Currently, Food and Drug Administration-approved molecularly targeted therapies for metastatic RAI-refractory thyroid cancer, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target the vascular endothelial growth factor receptor and RET kinases. Imaging plays an important role in assessment of response to these therapies, which can be atypical owing to antiangiogenic effects. A wide spectrum of toxic effects is associated with the molecularly targeted therapies used in thyroid cancer and can be detected at restaging scans. (C) RSNA, 2016 . radiographics.rsna.org C1 [Kelil, Tatiana; Keraliya, Abhishek R.; Howard, Stephanie A.; Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H.; Tirumani, Sree Harsha] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Hornick, Jason L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Keraliya, Abhishek R.; Howard, Stephanie A.; Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H.; Tirumani, Sree Harsha] Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, Boston, MA USA. RP Tirumani, SH (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.; Tirumani, SH (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, Boston, MA USA. EM stirumani@partners.org NR 104 TC 0 Z9 0 U1 5 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2016 VL 36 IS 5 BP 1478 EP 1493 DI 10.1148/rg.2016150206 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3YY UT WOS:000385036300015 PM 27618325 ER PT J AU Hermann, A Stark, R Milad, MR Merz, CJ AF Hermann, A. Stark, R. Milad, M. R. Merz, C. J. TI Renewal of conditioned fear in a novel context is associated with hippocampal activation and connectivity SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE amygdala; extinction; fear conditioning; fMRI; hippocampus ID MEDIAL PREFRONTAL CORTEX; ANXIETY DISORDERS; EXTINCTION; HUMANS; AMYGDALA; MEMORY; RELAPSE AB Return of fear is a serious problem in exposure-based treatments of anxiety disorders. Renewal of the fear response may occur when re-encountering the conditioned stimulus within a novel context. Findings in rodents underpin the hippocampus' role in conditioned fear renewal in novel contexts, but it has yet to be investigated in humans. Forty-six healthy men took part in a 2-day, context-dependent, cued fear conditioning paradigm with fear acquisition, extinction learning (day 1) and extinction recall in the acquisition, extinction and a novel context one day later. Conditioned evaluative, skin conductance responses (SCRs) and blood-oxygen-level-dependent responses served as dependent variables. Context-dependent fear renewal was reflected in stronger conditioned SCRs. In the acquisition context, individuals with a higher renewal of conditioned SCRs showed stronger activation of the fear circuit. Hippocampal activation distinguished conditioned responding in the novel compared with the extinction context. Individuals with a stronger renewal of conditioned SCRs in the novel context showed increased effective connectivity of hippocampal activation foci with structures in the fear and extinction network. These results outline the pivotal role of the hippocampus and its connectivity in conditioned fear renewal in a novel context in humans and might have important implications for exposure therapy in anxiety disorders. C1 [Hermann, A.; Stark, R.] Univ Giessen, Dept Psychotherapy & Syst Neurosci, Otto Behaghel Str 10H, D-35394 Giessen, Germany. [Hermann, A.; Stark, R.] Univ Giessen, Bender Inst Neuroimaging, Otto Behaghel Str 10H, D-35394 Giessen, Germany. [Milad, M. R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Milad, M. R.] Harvard Med Sch, Charlestown, MA USA. [Merz, C. J.] Ruhr Univ Bochum, Dept Cognit Psychol, Inst Cognit Neurosci, Bochum, Germany. [Merz, C. J.] Univ Trier, Dept Biol & Clin Psychol, D-54286 Trier, Germany. RP Hermann, A (reprint author), Univ Giessen, Dept Psychotherapy & Syst Neurosci, Otto Behaghel Str 10H, D-35394 Giessen, Germany.; Hermann, A (reprint author), Univ Giessen, Bender Inst Neuroimaging, Otto Behaghel Str 10H, D-35394 Giessen, Germany. EM andrea.hermann@psychol.uni-giessen.de FU Justus Liebig University Giessen; German Research Foundation [HE 7013/1-1, ME 3831/4-1] FX This study was funded by a grant from the Justus Liebig University Giessen and from the German Research Foundation (HE 7013/1-1; ME 3831/4-1) to A. Hermann and C.J. Merz. NR 36 TC 1 Z9 1 U1 7 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD SEP PY 2016 VL 11 IS 9 BP 1411 EP 1421 DI 10.1093/scan/nsw047 PG 11 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA DW5ZY UT WOS:000383727400008 PM 27053767 ER PT J AU Gray, A Schloss, RS Yarmush, M AF Gray, Andrea Schloss, Rene S. Yarmush, Martin TI Donor variability among anti-inflammatory pre-activated mesenchymal stromal cells SO TECHNOLOGY LA English DT Article DE Immunomodulation; Interleukin 1 Beta; Macrophages; Mesenchymal Stromal Cells; Prostaglandin E2; Donor Variability ID NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR PRODUCTION; IN-VITRO EXPANSION; FACTOR-KAPPA-B; STEM-CELLS; BONE-MARROW; INTERFERON-GAMMA; TNF-ALPHA; IMMUNOSUPPRESSIVE PROPERTIES; MACROPHAGE ACTIVATION AB Therapeutic mesenchymal stromal cells (MSCs) are attractive in part due to their immunomodulatory properties, achieved by their paracrine secretion of factors including prostaglandin E2 (PGE2). Despite promising pre-clinical data, demonstrating clinical efficacy has proven difficult. The current studies were designed to develop approaches to pre-induce desired functions from naive MSCs and examine MSC donor variability, two factors contributing to this disconnect. MSCs from six human donors were pre-activated with interleukin 1 beta (IL-1 beta) at a concentration and duration identified as optimal or interferon gamma (IFN-gamma) as a comparator. Their secretion of PGE2 after pre-activation and secondary exposure to pro-inflammatory molecules was measured. Modulation of tumor necrosis factor alpha (TNF-alpha) secretion from M1 pro-inflammatory macrophages by co-cultured pre-activated MSCs was also measured. Our results indicated that pre-activation of MSCs with IL-1 beta resulted in upregulated PGE2 secretion post exposure. Pre-activation with IL-1 beta or IFN-gamma resulted in higher sensitivity to induction by secondary stimuli compared to no pre-activation. While IL-1 beta pre-activation led to enhanced MSC-mediated attenuation of macrophage TNF-alpha secretion, IFN-gamma pre-activation resulted in enhanced TNF-alpha secretion. Donor variability was noted in PGE2 secretion and upregulation and the level of improved or impaired macrophage modulation. C1 [Gray, Andrea; Schloss, Rene S.; Yarmush, Martin] Rutgers State Univ, Dept Biomed Engn, New Brunswick, NJ 08901 USA. [Yarmush, Martin] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Schloss, RS (reprint author), Rutgers State Univ, Dept Biomed Engn, New Brunswick, NJ 08901 USA. EM schloss@soemail.rutgers.edu NR 83 TC 0 Z9 0 U1 1 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 2339-5478 EI 2345-7740 J9 TECHNOLOGY JI Technology PD SEP PY 2016 VL 4 IS 3 BP 201 EP 215 DI 10.1142/S2339547816500084 PG 15 WC Engineering, Multidisciplinary SC Engineering GA DX5TE UT WOS:000384444100008 ER PT J AU Karimi, M Eslami, M Sahandi-Zangabad, P Mirab, F Farajisafiloo, N Shafaei, Z Ghosh, D Bozorgomid, M Dashkhaneh, F Hamblin, MR AF Karimi, Mahdi Eslami, Masoud Sahandi-Zangabad, Parham Mirab, Fereshteh Farajisafiloo, Negar Shafaei, Zahra Ghosh, Deepanjan Bozorgomid, Mahnaz Dashkhaneh, Fariba Hamblin, Michael R. TI pH-Sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID MESOPOROUS SILICA NANOPARTICLES; INTRACELLULAR DRUG-DELIVERY; INTERSTITIAL FLUID PRESSURE; BREAST-CANCER THERAPY; ORAL INSULIN DELIVERY; POLYMERIC MICELLES; ANTICANCER DRUGS; CONTROLLED-RELEASE; IN-VIVO; MAGNETIC NANOPARTICLES AB In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH-sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH-sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co-delivery of cargos, dual pH-sensitive nanocarriers, dual/multi stimuli-responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer's. In order to design an optimized system, it is necessary to understand the various pH-responsive micro/nanoparticles and the different mechanisms of pH-sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers. (C) 2016 Wiley Periodicals, Inc. C1 [Karimi, Mahdi; Sahandi-Zangabad, Parham] Iran Univ Med Sci, Fac Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Eslami, Masoud; Mirab, Fereshteh; Farajisafiloo, Negar] Sharif Univ Technol, Dept Mat Sci & Engn, Polymer Mat Res Grp, Tehran, Iran. [Sahandi-Zangabad, Parham] Sharif Univ Technol, Dept Mat Sci & Engn, Tehran, Iran. [Shafaei, Zahra] Kharazmi Univ, Fac Biol Sci, Dept Cell & Mol Biol, Tehran, Iran. [Ghosh, Deepanjan] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Bozorgomid, Mahnaz] Islamic Azad Univ Tehran, Dept Appl Chem, Cent Branch, Tehran, Iran. [Dashkhaneh, Fariba] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Med Nanotechnol, Tehran, Iran. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM hamblin@helix.mgh.harvard.edu OI Sahandi Zangabad, Parham /0000-0001-8316-6732 FU US NIH [R01AI050875] FX Michael R. Hamblin was supported by US NIH grant R01AI050875. NR 150 TC 4 Z9 4 U1 73 U2 78 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5116 EI 1939-0041 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD SEP-OCT PY 2016 VL 8 IS 5 BP 696 EP 716 DI 10.1002/wnan.1389 PG 21 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA DY3YJ UT WOS:000385034300004 PM 26762467 ER PT J AU Kulkarni, A Pandey, P Rao, P Mahmoud, A Goldman, A Sabbisetti, V Parcha, S Natarajan, SK Chandrasekar, V Dinulescu, D Roy, S Sengupta, S AF Kulkarni, Ashish Pandey, Prithvi Rao, Poomima Mahmoud, Ayaat Goldman, Aaron Sabbisetti, Venkata Parcha, Shashikanth Natarajan, Siva Kumar Chandrasekar, Vineethkrishna Dinulescu, Daniela Roy, Sudip Sengupta, Shiladitya TI Algorithm for Designing Nanoscale Supramolecular Therapeutics with Increased Anticancer Efficacy SO ACS NANO LA English DT Article DE cancer; supramolecular nanoparticles; molecular dynamics simulations; taxanes; drug delivery ID MOLECULAR-DYNAMICS SIMULATIONS; LIPID-BILAYER; COMPUTER-SIMULATION; ANTITUMOR EFFICACY; FORCE-FIELD; PHOSPHOLIPID-BILAYER; SELF-ORGANIZATION; NANOPARTICLE; PACLITAXEL; CANCER AB In the chemical world, evolution is mirrored in the origin of nanoscale supramolecular structures from molecular subunits. The complexity of function acquired in a supramolecular system over a molecular subunit can be harnessed in the treatment of cancer. However, the design of supramolecular nanostructures is hindered by a limited atomistic level understanding of interactions between building blocks. Here, we report the development of a computational algorithm, which we term Volvox after the first multicellular organism, that sequentially integrates quantum mechanical energy-state- and force-field-based models with large-scale all-atomistic explicit water molecular dynamics simulations to design stable nanoscale lipidic supramolecular structures. In one example, we demonstrate that Volvox enables the design of a nanoscale taxane supramolecular therapeutic. In another example, we demonstrate that Volvox can be extended to optimizing the ratio of excipients to form a stable nanoscale supramolecular therapeutic. The nanoscale taxane supramolecular therapeutic exerts greater antitumor efficacy than a clinically used taxane in vivo. Volvox can emerge as a powerful tool in the design of nanoscale supramolecular therapeutics for effective treatment of cancer. C1 [Kulkarni, Ashish; Goldman, Aaron; Sabbisetti, Venkata; Sengupta, Shiladitya] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Kulkarni, Ashish; Goldman, Aaron; Sengupta, Shiladitya] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kulkarni, Ashish; Rao, Poomima; Mahmoud, Ayaat; Goldman, Aaron; Parcha, Shashikanth; Natarajan, Siva Kumar; Chandrasekar, Vineethkrishna; Sengupta, Shiladitya] Brigham & Womens Hosp, Dept Med, Div Engn Med, 75 Francis St, Boston, MA 02115 USA. [Dinulescu, Daniela] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Goldman, Aaron] Harvard Digest Dis Ctr, Boston, MA 02115 USA. [Pandey, Prithvi; Roy, Sudip] India Innovat Res Ctr, Invictus Oncol, New Delhi 110092, India. [Sengupta, Shiladitya] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sengupta, S (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.; Sengupta, S (reprint author), Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA.; Sengupta, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Engn Med, 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 National Science Foundation [1541959]; DoD BCRP Collaborative Innovator Grant [W81XWH-09-1-0700]; NIH [1R01CA135242-01A2]; DoD Breakthrough Award [BC132168]; American Lung Association Innovation Award [LCD-259932-N]; Indo-U.S. Joint Center Grant from IUSSTF; American Cancer Society Postdoctoral Fellowship [122854-PF-12-226-01-CDD] FX The authors thank Prof. Erkki Ruoslahti (Sanford Burnham Prebys Medical Discovery Institute, University of California, Santa Barbara) for generously providing iRGD peptide. The cryo-TEM analysis was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation under NSF Award No. 1541959. CNS is part of Harvard University. 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-U.S. Joint Center Grant from IUSSTF. A.G is supported by an American Cancer Society Postdoctoral Fellowship (122854-PF-12-226-01-CDD). NR 70 TC 2 Z9 2 U1 15 U2 15 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 SEP PY 2016 VL 10 IS 9 BP 8154 EP 8168 DI 10.1021/acsnano.6b00241 PG 15 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DX5DF UT WOS:000384399300006 PM 27452234 ER PT J AU Yaremchuk, MJ AF Yaremchuk, Michael J. TI Commentary on: Alloplastic Augmentation of the Asian Face: A Review of 215 Patients SO AESTHETIC SURGERY JOURNAL LA English DT Editorial Material C1 [Yaremchuk, Michael J.] Harvard Med Sch, Surg, Boston, MA USA. [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Craniofacial Surg, Boston, MA 02114 USA. [Yaremchuk, Michael J.] Harvard Plast Surg Training Program, Boston, MA USA. RP Yaremchuk, MJ (reprint author), 170 Commonwealth Ave, Boston, MA 02116 USA. EM dr.y@dryaremchuk.com NR 4 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 1090-820X EI 1527-330X J9 AESTHET SURG J JI Aesthet. Surg. J. PD SEP PY 2016 VL 36 IS 8 BP 869 EP 871 DI 10.1093/asj/sjw034 PG 3 WC Surgery SC Surgery GA DW5SG UT WOS:000383706600008 PM 27010017 ER PT J AU Padua, D Mahurkar-Joshi, S Law, IKM Polytarchou, C Vu, JP Pisegna, JR Shih, D Iliopoulos, D Pothoulakis, C AF Padua, David Mahurkar-Joshi, Swapna Law, Ivy Ka Man Polytarchou, Christos Vu, John P. Pisegna, Joseph R. Shih, David Iliopoulos, Dimitrios Pothoulakis, Charalabos TI A long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an enhancer of inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE inflammatory bowel disease; ulcerative colitis; lncRNA; inflammation; interferon gamma ID BOWEL-DISEASE; PROSTATE-CANCER; CROHNS-DISEASE; TH1 CELLS; EXPRESSION; INTERFERON; TMEVPG1; PROGRESSION; ACTIVATION; THERAPY AB High-throughput technologies revealed new categories of genes, including the long noncoding RNAs (lncRNAs), involved in the pathogenesis of human disease; however, the role of lncRNAs in the ulcerative colitis (UC) has not been evaluated. Gene expression profiling was used to develop lncRNA signatures in UC samples. Jurkat T cells were activated by PMA/ionomycin subsequently interferon-gamma (IFNG) and tumor necrosis factor (TNF)-gamma protein levels were assessed by ELISA. Anti-sense molecules were designed to block IFNG-AS1 expression. A unique set of lncRNAs was differentially expressed between UC and control samples. Of these, IFNG-AS1 was among the highest statistically significant lncRNAs (fold change: 5.27, P value: 7.07E-06). Bioinformatic analysis showed that IFNG-AS1 was associated with the IBD susceptibility loci SNP rs7134599 and its genomic location is adjacent to the inflammatory cytokine IFNG. In mouse models of colitis, active colitis samples had increased colonic expression of this lncRNA. Utilizing the Jurkat T cell model, we found IFNG-AS1 to positively regulate IFNG expression. Novel lncRNA signatures differentiate UC patients with active disease, patients in remission, and control subjects. A subset of these lncRNAs was found to be associated with the clinically validated IBD susceptibility loci. IFNG-AS1 was one of these differentially expressed lncRNAs in UC patients and found to regulate the key inflammatory cytokine, IFNG, in CD4 T cells. Taking these findings together, our study revealed novel lncRNA signatures deregulated in UC and identified IFNG-AS1 as a novel regulator of IFNG inflammatory responses, suggesting the potential importance of noncoding RNA mechanisms on regulation of inflammatory bowel disease-related inflammatory responses. C1 [Padua, David; Mahurkar-Joshi, Swapna; Law, Ivy Ka Man; Iliopoulos, Dimitrios; Pothoulakis, Charalabos] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Polytarchou, Christos; Iliopoulos, Dimitrios] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Los Angeles, CA 90095 USA. [Polytarchou, Christos] Nottingham Trent Univ, Sch Sci & Technol, Nottingham, England. [Vu, John P.; Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA USA. [Vu, John P.; Pisegna, Joseph R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Shih, David] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA. RP Pothoulakis, C (reprint author), 675 Charles E Young Dr South,MRL RM 1240, Los Angeles, CA 90095 USA. EM cpothoulakis@mednet.ucla.edu FU NIH/NIDDK [T32 DK007180-41, R01 DK060729, P30 DK 41301] FX This research was supported by NIH/NIDDK T32 DK007180-41 grant (D. Padua), and R01 DK060729 (C. Pothoulakis). Support was also provided by NIH/NIDDK P30 DK 41301 Center Grant (D. Iliopoulos and C. Pothoulakis). NR 40 TC 0 Z9 0 U1 3 U2 3 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 SEP 1 PY 2016 VL 311 IS 3 BP G446 EP G457 DI 10.1152/ajpgi.00212.2016 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA DY0FL UT WOS:000384772600011 PM 27492330 ER PT J AU Rickard, JP Kish, T AF Rickard, Joshua P. Kish, Troy TI Systemic Intravenous Lidocaine for the Treatment of Complex Regional Pain Syndrome: A Case Report and Literature Review SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Review DE intravenous lidocaine; complex regional pain syndrome; pain; causalgia; aglodystrophy; reflex sympathetic dystrophy ID SYNDROME TYPE-I; MANAGEMENT; INFUSIONS; EFFICACY AB Complex regional pain syndrome (CRPS) was described in 1864 by Mitchell et al as a condition characterized by many unique symptoms. Although symptoms may differ from patient to patient, the most common complaints are painful swelling in upper or lower extremities or changes in the skin. CRPS has been given many different names since it was first mentioned in the literature in 1851. The most common alternative names include causalgia, aglodystrophy, and sympathetic dystrophy syndrome. This condition is generally diagnosed in older adults because of trauma, nerve damage, and coronary artery disease; however, there are cases of CRPS affecting the pediatric and young adult population. The fourth edition of the diagnostic and treatment guidelines of CRPS published by Harden et al in 2013 suggest many different pharmacologic treatment options for these patients. Intravenous lidocaine is used to block the sodium channels in neuronal membranes, thus stopping initiation and conduction of impulses associated with neuropathic and inflammatory pain. The use of regional intravenous lidocaine (by applying a tourniquet on the affected extremity) has been well-documented in the literature with a successful decrease in pain symptoms. A unique case of the use of systemic intravenous lidocaine will be presented. C1 [Rickard, Joshua P.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Kish, Troy] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA. RP Rickard, JP (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. EM josh.rickard90@gmail.com OI Rickard, Joshua/0000-0002-4447-1096 FU James J. Peters VA Medical Center, Bronx, NY FX Supported by the resources and by the use of facilities at the James J. Peters VA Medical Center, Bronx, NY. NR 10 TC 0 Z9 0 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1075-2765 EI 1536-3686 J9 AM J THER JI Am. J. Ther. PD SEP-OCT PY 2016 VL 23 IS 5 BP E1266 EP E1269 DI 10.1097/MJT.0000000000000345 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX5TY UT WOS:000384446400028 PM 26398854 ER PT J AU Brown, JC Harhay, MO Harhay, MN AF Brown, Justin C. Harhay, Michael O. Harhay, Meera N. TI The muscle quality index and mortality among males and females SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Physical function; Mobility; Aging; Physical activity; Muscle strength ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; 3RD NATIONAL-HEALTH; TO-STAND TEST; OLDER-ADULTS; BODY-COMPOSITION; FUNCTIONAL STATUS; ELDERLY-MEN; STRENGTH; MASS AB Purpose: The muscle quality index (MQI) was proposed as a measure to quantify age-related alterations in muscle function. It is unknown if the MQI predicts mortality. Methods: This was a population-based cohort study from the Third National Health and Nutrition Survey (NHANES III; 1988-1994). The MQI was quantified using a timed sit-to-stand test, body mass, and leg length. Vital status was obtained through the National Center for Health Statistics. We fit multivariable-adjusted regression models to estimate the hazard ratio (HR) and 95% confidence interval (CI) between the MQI and mortality. Results: During 14.6 years of follow-up, 3299 (73.1%) of 4510 study participants died. Lower MQI was associated with a higher risk of mortality (P-trend <.001). The multivariable-adjusted HR for mortality was 1.50 (95% CI, 1.15-1.96) for those in the lowest quintile of MQI compared to the highest quintile. The association between MQI and mortality was stronger among males (highest vs. lowest quintile of MQI, HR = 1.37 [95% CI, 1.00-1.87]; P-trend =.001) compared to females (highest vs. lowest quintile of MQI, HR = 1.27 (95% CI, 0.89-1.83); P-trend =.044; P-interaction =.005]. Conclusions: The MQI predicts mortality and may differ between males and females. Additional research examining the MQI is warranted. (C) 2016 Elsevier Inc. All rights reserved. C1 [Brown, Justin C.] Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave, Boston, MA 02115 USA. [Brown, Justin C.; Harhay, Michael O.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Harhay, Meera N.] Drexel Univ, Dept Med, Div Nephrol, Coll Med, Philadelphia, PA 19104 USA. RP Brown, JC (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave, Boston, MA 02115 USA. EM justinc_brown@dfci.harvard.edu FU National Cancer Institute [F31-CA192560, R21-CA182726, U54-CA155850]; National Heart, Lung, and Blood Institute [F31-HL127947]; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [F32-DK096758] FX Research reported in this publication was supported by the National Cancer Institute (F31-CA192560, R21-CA182726, U54-CA155850), National Heart, Lung, and Blood Institute (F31-HL127947) and the National Institute of Diabetes and Digestive and Kidney Diseases (F32-DK096758) of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 34 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2016 VL 26 IS 9 BP 648 EP 653 DI 10.1016/j.annepidem.2016.07.006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DX8HN UT WOS:000384628800008 PM 27480478 ER PT J AU Dagogo-Jack, I Shaw, AT AF Dagogo-Jack, I. Shaw, A. T. TI Crizotinib resistance: implications for therapeutic strategies SO ANNALS OF ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; CENTRAL-NERVOUS-SYSTEM; EPITHELIAL-MESENCHYMAL TRANSITION; ALK INHIBITOR RESISTANCE; POSITIVE NSCLC PATIENTS; EML4-ALK FUSION GENE; ACQUIRED-RESISTANCE; OLIGOPROGRESSIVE DISEASE; CONFER RESISTANCE; KINASE INHIBITORS AB Anaplastic lymphoma kinase-rearranged lung cancer is associated with significant response to crizotinib. However, resistance to crizotinib typically develops within 1-2 years. Preclinical studies and biopsies of resistant sites have demonstrated that diverse mechanisms underlie resistance. Insight into resistance mechanisms has facilitated development of next-generation inhibitors and led to therapeutic combination strategies, several of which are being tested in the clinic.In 2007, a chromosomal rearrangement resulting in a gene fusion leading to expression of a constitutively active anaplastic lymphoma kinase (ALK) fusion protein was identified as an oncogenic driver in non-small-cell lung cancer (NSCLC). ALK rearrangements are detected in 3%-7% of patients with NSCLC and are particularly enriched in younger patients with adenocarcinoma and a never or light smoking history. Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC. Despite dramatic and durable initial responses to crizotinib; however, the vast majority of patients will develop resistance within a few years. Diverse molecular mechanisms underlie resistance to crizotinib. This review will describe the clinical activity of crizotinib, review identified mechanisms of crizotinib resistance, and end with a survey of emerging therapeutic strategies aimed at overcoming crizotinib resistance. C1 [Dagogo-Jack, I.; Shaw, A. T.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA. EM ashaw1@partners.org NR 68 TC 3 Z9 3 U1 2 U2 2 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 SEP PY 2016 VL 27 SU 3 BP 42 EP 50 DI 10.1093/annonc/mdw305 PG 9 WC Oncology SC Oncology GA DW5SA UT WOS:000383706000006 ER PT J AU Kacmarek, RM Villar, J AF Kacmarek, Robert M. Villar, Jesus TI Noninvasive ventilatory management of the acute respiratory distress syndrome: a new era or just another tease! SO ANNALS OF TRANSLATIONAL MEDICINE LA English DT Editorial Material ID FLOW NASAL CANNULA; BERLIN DEFINITION; OXYGEN; PRESSURE; HELMET; ARDS C1 [Kacmarek, Robert M.] Harvard Med Sch, Dept Anesthesiol, Boston, MA USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St,Warren 1225, Boston, MA 02114 USA. [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St,Warren 1225, Boston, MA 02114 USA. EM rkacmarek@mgh.harvard.edu NR 18 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 2305-5839 EI 2305-5847 J9 ANN TRANSL MED JI ANN. TRANSL. MED. PD SEP PY 2016 VL 4 IS 18 AR 350 DI 10.21037/atm.2016.08.38 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DY0NP UT WOS:000384793800017 PM 27761454 ER PT J AU Dutta, P Hoyer, FF Sun, Y Iwamoto, Y Tricot, B Weissleder, R Magnani, JL Swirski, FK Nahrendorf, M AF Dutta, Partha Hoyer, Friedrich Felix Sun, Yuan Iwamoto, Yoshiko Tricot, Benoit Weissleder, Ralph Magnani, John L. Swirski, Filip K. Nahrendorf, Matthias TI E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; E-selectin; HSC; myelopoiesis; myocardial infarction ID LEUKOCYTE ADHESION MOLECULE; HEMATOPOIETIC STEM-CELLS; SOLUBLE E-SELECTIN; ATHEROSCLEROTIC LESIONS; MONOCYTES; MACROPHAGES; IDENTIFICATION; PROLIFERATION; EVENTS; RISK AB Objective Atherosclerosis is a chronic disease characterized by lipid accumulation in the arterial wall. After myocardial infarction (MI), atherosclerotic plaques are infiltrated by inflammatory myeloid cells that aggravate the disease and increase the risk of secondary myocardial ischemia. Splenic myelopoiesis provides a steady flow of myeloid cells to inflamed atherosclerotic lesions after MI. Therefore, targeting myeloid cell production in the spleen could ameliorate increased atherosclerotic plaque inflammation after MI. Approach and Results Here we show that MI increases splenic myelopoiesis by driving hematopoietic stem and progenitor cells into the cell cycle. In an atherosclerotic mouse model, E-selectin inhibition decreased hematopoietic stem and progenitor cell proliferation in the spleen after MI. This led to reduced extramedullary myelopoiesis and decreased myeloid cell accumulation in atherosclerotic lesions. Finally, we observed stable atherosclerotic plaque features, including smaller plaque size, reduced necrotic core area, and thicker fibrous cap after E-selectin inhibition. Conclusions Inhibiting E-selectin attenuated inflammation in atherosclerotic plaques, likely by reducing leukocyte recruitment into plaques and by mitigating hematopoietic stem and progenitor cell activation in the spleen of mice with MI. C1 [Dutta, Partha; Hoyer, Friedrich Felix; Sun, Yuan; Iwamoto, Yoshiko; Tricot, Benoit; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Dept Imaging, Ctr Syst Biol, Boston, MA USA. [Dutta, Partha; Hoyer, Friedrich Felix; Sun, Yuan; Iwamoto, Yoshiko; Tricot, Benoit; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Harvard Med Sch, Simches Res Bldg, Boston, MA USA. [Weissleder, Ralph] Harvard Med Sch, Dept Syst Biol, Boston, MA USA. [Magnani, John L.] GlycoMimetics Inc, Rockville, MD USA. RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU GlycoMimetics; National Institute of Health [R01-HL096576, R01-HL117829, R01-NS084863, K99-HL121076]; Deutsche Forschungsgemeinschaft [HO 5279/1-1] FX This work was funded in part by grants from GlycoMimetics, the National Institute of Health R01-HL096576, R01-HL117829, R01-NS084863 (M. Nahrendorf); K99-HL121076 (P. Dutta). F.F. Hoyer was funded by Deutsche Forschungsgemeinschaft (HO 5279/1-1). NR 33 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2016 VL 36 IS 9 BP 1802 EP 1808 DI 10.1161/ATVBAHA.116.307519 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DW3ZZ UT WOS:000383582900016 PM 27470513 ER PT J AU Lerchenmuller, C Heissenberg, J Damilano, F Bezzeridis, VJ Kramer, I Bochaton-Piallat, ML Hirschberg, K Busch, M Katus, HA Peppel, K Rosenzweig, A Busch, H Boerries, M Most, P AF Lerchenmueller, Carolin Heissenberg, Julian Damilano, Federico Bezzeridis, Vassilios J. Kraemer, Isabel Bochaton-Piallat, Marie-Luce Hirschberg, Kristof Busch, Martin Katus, Hugo A. Peppel, Karsten Rosenzweig, Anthony Busch, Hauke Boerries, Melanie Most, Patrick TI S100A6 Regulates Endothelial Cell Cycle Progression by Attenuating Antiproliferative Signal Transducers and Activators of Transcription 1 Signaling SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cell cycle; endothelium; protein inhibitors of activated STAT; S100A6 protein; human; STAT1 transcription factor ID CALCIUM-BINDING PROTEIN; NEGATIVE REGULATION; INTERFERON-GAMMA; STAT PROTEINS; GENE; IFITM1; ANGIOGENESIS; INHIBITION; EXPRESSION; RESPONSES AB Objective S100A6, a member of the S100 protein family, has been described as relevant for cell cycle entry and progression in endothelial cells. The molecular mechanism conferring S100A6's proliferative actions, however, remained elusive. Approach and Results Originating from the clinically relevant observation of enhanced S100A6 protein expression in proliferating endothelial cells in remodeling coronary and carotid arteries, our study unveiled S100A6 as a suppressor of antiproliferative signal transducers and activators of transcription 1 signaling. Discovery of the molecular liaison was enabled by combining gene expression time series analysis with bioinformatic pathway modeling in S100A6-silenced human endothelial cells stimulated with vascular endothelial growth factor A. This unbiased approach led to successful identification and experimental validation of interferon-inducible transmembrane protein 1 and protein inhibitors of activated signal transducers and activators of transcription as key components of the link between S100A6 and signal transducers and activators of transcription 1. Conclusions Given the important role of coordinated endothelial cell cycle activity for integrity and reconstitution of the inner lining of arterial blood vessels in health and disease, signal transducers and activators of transcription 1 suppression by S100A6 may represent a promising therapeutic target to facilitate reendothelialization in damaged vessels. C1 [Lerchenmueller, Carolin; Damilano, Federico; Rosenzweig, Anthony] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Damilano, Federico] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02114 USA. [Bezzeridis, Vassilios J.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA 02114 USA. [Lerchenmueller, Carolin; Heissenberg, Julian; Kraemer, Isabel; Busch, Martin; Most, Patrick] Univ Heidelberg Hosp, Mol & Translat Cardiol MTC, Dept Internal Med 3, Heidelberg, Germany. [Bochaton-Piallat, Marie-Luce] Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland. [Hirschberg, Kristof; Busch, Martin; Katus, Hugo A.; Most, Patrick] Heidelberg Univ, DZHK German Ctr Cardiovasc Res, Partner Site Heidelberg Mannheim, Bergheimer Str 58, D-69115 Heidelberg, Germany. [Peppel, Karsten; Most, Patrick] Jefferson Med Coll, Ctr Translat Med, Philadelphia, PA USA. [Busch, Hauke; Boerries, Melanie] Univ Freiburg, Syst Biol Cellular Microenvironm Grp, Inst Mol Med & Cell Res, Freiburg, Germany. [Busch, Hauke; Boerries, Melanie] German Canc Consortium DKTK, Freiburg, Germany. [Busch, Hauke; Boerries, Melanie] German Canc Res Ctr, Heidelberg, Germany. RP Lerchenmuller, C (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.; Boerries, M (reprint author), Univ Freiburg, Syst Biol Cellular Microenvironm, DKFZ Partner Side Freiburg, German Canc Consortium,Inst Mol Med & Cell Res, Stefan Meier Str 17, D-79104 Freiburg, Germany. EM clerchenmueller@mgh.harvard.edu; m.boerries@dkfz.de RI Busch, Hauke/R-6452-2016 OI Busch, Hauke/0000-0003-4763-4521 FU German Research Foundation (Deutsche Forschungsgemeinschaft); University Hospital Heidelberg; National Institutes of Health (NIH) [5T32HL007374-37]; German Center for Cardiovascular Research; German Ministry of Education and Research (BMBF) within e:Med consortium DeCaRe-Delineating Cardiac Regeneration; Harvard Catalyst; Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University; affiliated academic healthcare centers FX This work was funded by a research fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft) (C. Lerchenmuller), the Rahel Goitein-Straus stipend awarded by the University Hospital Heidelberg (C. Lerchenmuller), a National Institutes of Health (NIH) Institutional Training grant (5T32HL007374-37; F. Damilano), the German Center for Cardiovascular Research (P. Most and H. A. Katus), and the German Ministry of Education and Research (BMBF) within the e:Med consortium DeCaRe-Delineating Cardiac Regeneration (H. Busch and M. Boerries). This work was further conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. NR 41 TC 2 Z9 2 U1 2 U2 2 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 SEP PY 2016 VL 36 IS 9 BP 1854 EP 1867 DI 10.1161/ATVBAHA.115.306415 PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DW3ZZ UT WOS:000383582900022 PM 27386938 ER PT J AU Kolde, R Martens, K Lokk, K Laur, S Vilo, J AF Kolde, Raivo Martens, Kaspar Lokk, Kaie Laur, Sven Vilo, Jaak TI seqlm: an MDL based method for identifying differentially methylated regions in high density methylation array data SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 15th European Conference on Computational Biology (ECCB) CY SEP 03-07, 2016 CL The Hague, NETHERLANDS ID IDENTIFICATION; PACKAGE AB Motivation: One of the main goals of large scale methylation studies is to detect differentially methylated loci. One way is to approach this problem sitewise, i.e. to find differentially methylated positions (DMPs). However, it has been shown that methylation is regulated in longer genomic regions. So it is more desirable to identify differentially methylated regions (DMRs) instead of DMPs. The new high coverage arrays, like Illuminas 450k platform, make it possible at a reasonable cost. Few tools exist for DMR identification from this type of data, but there is no standard approach. Results: We propose a novel method for DMR identification that detects the region boundaries according to the minimum description length (MDL) principle, essentially solving the problem of model selection. The significance of the regions is established using linear mixed models. Using both simulated and large publicly available methylation datasets, we compare seqlm performance to alternative approaches. We demonstrate that it is both more sensitive and specific than competing methods. This is achieved with minimal parameter tuning and, surprisingly, quickest running time of all the tried methods. Finally, we show that the regional differential methylation patterns identified on sparse array data are confirmed by higher resolution sequencing approaches. C1 [Kolde, Raivo; Martens, Kaspar; Laur, Sven; Vilo, Jaak] Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia. [Kolde, Raivo] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Lokk, Kaie] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia. RP Kolde, R (reprint author), Univ Tartu, Inst Comp Sci, EE-50409 Tartu, Estonia.; Kolde, R (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM rkolde@gmail.com NR 21 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD SEP 1 PY 2016 VL 32 IS 17 BP 2604 EP 2610 DI 10.1093/bioinformatics/btw304 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA DX8VA UT WOS:000384666800055 PM 27187204 ER PT J AU Stocker, BK Koster, J Rahmann, S AF Stoecker, Bianca K. Koster, Johannes Rahmann, Sven TI SimLoRD: Simulation of Long Read Data SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 15th European Conference on Computational Biology (ECCB) CY SEP 03-07, 2016 CL The Hague, NETHERLANDS ID GENERATION AB Motivation: Third generation sequencing methods provide longer reads than second generation methods and have distinct error characteristics. While there exist many read simulators for second generation data, there is a very limited choice for third generation data. Results: We analyzed public data from Pacific Biosciences (PacBio) SMRT sequencing, developed an error model and implemented it in a new read simulator called SimLoRD. It offers options to choose the read length distribution and to model error probabilities depending on the number of passes through the sequencer. The new error model makes SimLoRD the most realistic SMRT read simulator available. C1 [Stoecker, Bianca K.; Rahmann, Sven] Univ Duisburg Essen, Inst Human Genet, Genome Informat, D-45147 Essen, Germany. [Koster, Johannes] Ctr Wiskunde & Informat, Life Sci, NL-1098 XG Amsterdam, Netherlands. [Koster, Johannes] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA 02215 USA. RP Rahmann, S (reprint author), Univ Duisburg Essen, Inst Human Genet, Genome Informat, D-45147 Essen, Germany. EM Bianca.Stoecker@uni-due.de; Sven.Rahmann@uni-due.de NR 5 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD SEP 1 PY 2016 VL 32 IS 17 BP 2704 EP 2706 DI 10.1093/bioinformatics/btw286 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA DX8VA UT WOS:000384666800071 PM 27166244 ER PT J AU de Souza, ALR Marra, K Gunn, J Samkoe, KS Kanick, SC Davis, SC Chapman, MS Maytin, EV Hasan, T Pogue, BW AF Ribeiro de Souza, Ana Luiza Marra, Kayla Gunn, Jason Samkoe, Kimberley S. Kanick, Stephen Chad Davis, Scott C. Chapman, M. Shane Maytin, Edward V. Hasan, Tayyaba Pogue, Brian W. TI Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE aminolevulinic acid; photodynamic; iron chelator; fractionation; protoporphyrin IX; dose ID TOPICAL 5-AMINOLEVULINIC ACID; BASAL-CELL CARCINOMA; IRON CHELATOR CP94; 2-FOLD ILLUMINATION SCHEMES; DELTA-AMINOLEVULINIC-ACID; HAIRLESS MOUSE SKIN; PROTOPORPHYRIN-IX; IN-VIVO; METHYL-AMINOLEVULINATE; PORPHYRIN SYNTHESIS AB Background: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides selective uptake and conversion of ALA into protoporphyrin IX (PpIX) in actinic keratosis and squamous cell carcinoma, yet large response variations in effect are common between individuals. The aim of this study was to compare pre-treatment strategies that increase the therapeutic effect, including fractionated light delivery during PDT (fPDT) and use of iron chelator desferrioxamine (DFO), separately and combined. Methods: Optical measurements of fluorescence were used to quantify PpIX produced, and the total amount of PpIX photobleached as an implicit measure of the photodynamic dose. In addition, measurements of white light reflectance were used to quantify changes in vascular physiology throughout the PDT treatment. Results: fPDT produced both a replenishment of PpIX and vascular re-oxygenation during a 2 h dark interval between the first and second PDT light fractions. The absolute photodynamic dose was increased 57% by fPDT, DFO and their combination, as compared with PDT group (from 0.7 to 1.1). Despite that light fractionation increased oedema and scab formation during the week after treatment, no significant difference in long-term survival has been observed between treatment groups. However, outcomes stratified on the basis of measured photodynamic dose showed a significant difference in long-term survival. Conclusions: The assessment of implicit photodynamic dose was a more significant predictor of efficacy for ALA-PDT skin cancer treatments than prescription of an enhanced treatment strategy, likely because of high individual variation in response between subjects. C1 [Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason; Samkoe, Kimberley S.; Kanick, Stephen Chad; Davis, Scott C.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Ribeiro de Souza, Ana Luiza] Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil. [Samkoe, Kimberley S.; Chapman, M. Shane; Pogue, Brian W.] Dartmouth Coll, Geisel Sch Med, Dept Surg, Lebanon, NH 03756 USA. [Maytin, Edward V.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA. [Hasan, Tayyaba] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.; Pogue, BW (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Surg, Lebanon, NH 03756 USA. EM brian.w.pogue@dartmouth.edu FU NIH research grant (USA) [P01 CA084203] FX This work was founded by CAPES-Proc no BEX 1376/14-4 (Brazil) and NIH research grant P01 CA084203 (USA). NR 50 TC 2 Z9 2 U1 7 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 2016 VL 115 IS 7 BP 805 EP 813 DI 10.1038/bjc.2016.267 PG 9 WC Oncology SC Oncology GA DX7NY UT WOS:000384576100007 PM 27575852 ER PT J AU Liu, MA Hshieh, T Condron, N Wadleigh, M Abel, GA Driver, JA AF Liu, Michael A. Hshieh, Tammy Condron, Nolan Wadleigh, Martha Abel, Gregory A. Driver, Jane A. TI Relationship between physician and patient assessment of performance status and survival in a large cohort of patients with haematologic malignancies SO BRITISH JOURNAL OF CANCER LA English DT Article DE medical oncology; haematologic malignancies; leukaemia; lymphoma; performance status; epidemiology ID CANCER; ONCOLOGISTS AB Background: Few studies have investigated the relationship between physician and patient-assessed performance status (PS) in blood cancers. Methods: Retrospective analysis among 1418 patients with haematologic malignancies seen at Dana-Farber Cancer Institute between 2007 and 2014. We analysed physician-patient agreement of Eastern Cooperative Oncology Group PS using weighted kappa-statistics and survival analysis. Results: Mean age was 58.6 years and average follow-up was 38 months. Agreement in PS was fair/moderate (weighted kappa = 0.41, 95% CI 0.37-0.44). Physicians assigned a better functional status (lower score) than patients (mean 0.60 vs 0.81), particularly when patients were young and the disease was aggressive. Both scores independently predicted survival, but physician scores were more accurate. Disagreements in score were associated with poorer survival when physicians rated PS better than patients, and were modified by age, sex and severity of disease. Conclusions: Physician-patient disagreements in PS score are common and have prognostic significance. C1 [Liu, Michael A.] Univ Arizona, Coll Med, 1501N Campbell Ave, Tucson, AZ 85724 USA. [Hshieh, Tammy; Driver, Jane A.] Brigham & Womens Hosp, Dept Med, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. [Hshieh, Tammy; Condron, Nolan; Wadleigh, Martha; Abel, Gregory A.; Driver, Jane A.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Driver, Jane A.] VA Boston Med Ctr, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. RP Driver, JA (reprint author), Brigham & Womens Hosp, Dept Med, Div Aging, 1620 Tremont St, Boston, MA 02120 USA.; Driver, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.; Driver, JA (reprint author), VA Boston Med Ctr, Geriatr Res Educ & Clin Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM jdriver@partners.org FU MSTAR Program (American Federation for Aging Research/NIH) [T35AG038027-05]; National Institute on Aging [T32AG000158]; Hartford Center of Excellence Award; Mary P. Murphy Fund for Hematologic Malignancies Research; Veterans' Administration Merit Review Award FX This research was funded by a grant from the MSTAR Program (American Federation for Aging Research/NIH Grant #T35AG038027-05; Michael Liu). TH was supported by Grant No. T32AG000158 from the National Institute on Aging and is supported by a Hartford Center of Excellence Award. GAA and NC are supported by the Mary P. Murphy Fund for Hematologic Malignancies Research. JAD is supported by a Veterans' Administration Merit Review Award. NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 2016 VL 115 IS 7 BP 858 EP 861 DI 10.1038/bjc.2016.260 PG 4 WC Oncology SC Oncology GA DX7NY UT WOS:000384576100013 PM 27552440 ER PT J AU Wasfy, JH Maddox, TM AF Wasfy, Jason H. Maddox, Thomas M. TI Worlds Apart: The Hype and Reality of Big Data to Improve Health Care SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Editorials; bioinformatics; heart failure; hospital readmission; myocardial infarction; problem solving; quality improvement ID PROFILING HOSPITAL PERFORMANCE; CAUSE READMISSION RATES C1 [Wasfy, Jason H.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Cardiol Sect, VA Eastern Colorado Hlth Care Syst, Denver, CO USA. RP Maddox, TM (reprint author), Univ Colorado, Sch Med, Cardiol Sect 111B, VA Eastern Colorado Hlth Care Syst, 1055 Clermont St, Denver, CO 80220 USA. EM tom.maddox@gmail.com NR 11 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 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2016 VL 9 IS 5 BP 495 EP 497 DI 10.1161/CIRCOUTCOMES.116.003150 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZL UT WOS:000384461300002 PM 27601457 ER PT J AU O'Brien, SM Cohen, DJ Rumsfeld, JS Brennan, JM Shahian, DM Dai, D Holmes, DR Hakim, RB Thourani, VH Peterson, ED Edwards, FH AF O'Brien, Sean M. Cohen, David J. Rumsfeld, John S. Brennan, J. Matthew Shahian, David M. Dai, David Holmes, David R. Hakim, Rosemarie B. Thourani, Vinod H. Peterson, Eric D. Edwards, Fred H. CA STS ACC TVT Registry TI Variation in Hospital Risk-Adjusted Mortality Rates Following Transcatheter Aortic Valve Replacement in the United States: A Report From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE aortic stenosis; case-mix adjustment; outcomes analysis; outcomes research; transcatheter aortic valve replacement ID RELIABILITY ADJUSTMENT; OUTCOMES; PERFORMANCE; SURGERY; MODELS AB Background The use of transcatheter aortic valve replacement (TAVR) to treat aortic stenosis in the United States is growing, yet little is known about the variation in procedural outcomes in community practice. We developed a TAVR in-hospital mortality risk model and used it to quantify variation in mortality rates across United States (US) TAVR centers. Methods and Results We analyzed data from 22248 TAVR procedures performed at 318 sites participating in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 to October 2014). A Bayesian hierarchical model was developed to estimate hospital-specific risk-adjusted mortality rates adjusting for 40 patient baseline factors. A total of 1130 in-hospital deaths (5.1%) were observed. Reliability-adjusted risk-adjusted mortality rate estimates ranged from 3.4% to 7.7% with an interquartile range of 4.8% to 5.4%. A patient's predicted odds of dying was 80% higher if treated by a hospital 1 standard deviation above the mean compared with a hospital 1 standard deviation below the mean (odds ratio =1.8; 95% credible interval, 1.4%-2.2%). Conclusions Risk modeling of TAVR in-hospital mortality revealed variation in risk-adjusted mortality rates during the US early commercial experience. Transcatheter Valve Therapy Registry analyses using this model will support research, feedback reporting, and the identification of factors associated with quality. C1 [O'Brien, Sean M.; Brennan, J. Matthew; Dai, David; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Holmes, David R.] Mayo Clin, Rochester, MN USA. [Hakim, Rosemarie B.] Ctr Medicare Serv, Baltimore, MD USA. [Hakim, Rosemarie B.] Ctr Medicaid Serv, Baltimore, MD USA. [Thourani, Vinod H.] Emory Univ, Sch Med, Atlanta, GA USA. [Edwards, Fred H.] Univ Florida, Jacksonville, FL USA. RP O'Brien, SM (reprint author), Duke Clin Res Inst, Duke Box 2721, Durham, NC 27715 USA. EM sean.m.obrien@duke.edu FU Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry is an initiative of the Society of Thoracic Surgeons; American College of Cardiology Foundation; American College of Cardiology Foundation's National Cardiovascular Data Registry; Society of Thoracic Surgeons FX The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry is an initiative of the Society of Thoracic Surgeons and the American College of Cardiology Foundation. This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry and the Society of Thoracic Surgeons. NR 25 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 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2016 VL 9 IS 5 BP 560 EP 565 DI 10.1161/CIRCOUTCOMES.116.002756 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZL UT WOS:000384461300011 PM 27625404 ER PT J AU Tanguturi, VK Temin, E Yeh, RW Thompson, RW Rao, SK Mallick, A Cavallo, E Ferris, TG Wasfy, JH AF Tanguturi, Varsha K. Temin, Elizabeth Yeh, Robert W. Thompson, Ryan W. Rao, Sandhya K. Mallick, Aditi Cavallo, Elena Ferris, Timothy G. Wasfy, Jason H. TI Clinical Interventions to Reduce Preventable Hospital Readmission After Percutaneous Coronary Intervention SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE episode of care; inpatient; myocardial infarction; percutaneous coronary intervention; readmission ID SHORT-TERM READMISSION; CARE; RATES AB Hospital readmissions are common and costly and, in some cases, may be related to problems with care processes. We sought to reduce readmissions after percutaneous coronary intervention (PCI) in a large tertiary care facility through programs to target vulnerabilities predischarge, after discharge, and during re-presentation to the emergency department. During initial hospitalization, we assessed patients' readmission risk with a validated risk score and used a discharge checklist to ensure access to appropriate medications and close follow-up for high-risk patients. We also developed patient education videos about chest discomfort and heart failure. After discharge, we established a new follow-up clinic with cardiology fellows. A computerized system was developed to automatically notify cardiologists when patients presented to the emergency department within 30 days of PCI to enhance patient access to cardiology care in the emergency department. Early cardiologist assessment and assistance with triage was encouraged, and the emergency department used a risk stratification algorithm derived from a local database of patients to triage patients presenting with chest discomfort after PCI. We tracked the number of patients readmitted after PCI to our hospital. With our interventions, from 2011 to 2015, the index hospital readmission rate has declined from 9.6% to 5.3%. This program could provide tangible structural changes that can be implemented in other healthcare centers, both reducing the cost of care and improving the quality of care for patients with PCI. C1 [Tanguturi, Varsha K.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. [Temin, Elizabeth] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Yeh, Robert W.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Smith Ctr Outcomes Res Cardiol, Boston, MA USA. [Thompson, Ryan W.; Mallick, Aditi] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Rao, Sandhya K.; Cavallo, Elena; Ferris, Timothy G.; Wasfy, Jason H.] Harvard Med Sch, Massachusetts Gen Phys Org, Boston, MA USA. RP Wasfy, JH (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 8-843,55 Fruit St, Boston, MA 02114 USA. EM jwasfy@mgh.harvard.edu NR 18 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 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2016 VL 9 IS 5 BP 600 EP 604 DI 10.1161/CIRCOUTCOMES.116.003086 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZL UT WOS:000384461300016 PM 27553598 ER PT J AU Greene, SJ Hernandez, AF Sun, JL Metra, M Butler, J Ambrosy, AP Ezekowitz, JA Starling, RC Teerlink, JR Schulte, PJ Voors, AA Armstrong, PW O'Connor, CM Mentz, RJ AF Greene, Stephen J. Hernandez, Adrian F. Sun, Jie-Lena Metra, Marco Butler, Javed Ambrosy, Andrew P. Ezekowitz, Justin A. Starling, Randall C. Teerlink, John R. Schulte, Phillip J. Voors, Adriaan A. Armstrong, Paul W. O'Connor, Christopher M. Mentz, Robert J. TI Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) SO CIRCULATION-HEART FAILURE LA English DT Article DE clinical trial; heart failure; patient discharge; quality of life ID OUTCOMES; DYSPNEA; CONDUCT; PREDICTORS; MANAGEMENT; TOLVAPTAN; PROPOSAL AB Background Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. Methods and Results We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled 1 patient, and median enrollment was 12 patients (interquartile range, 5-23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89-0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01-1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98-1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96-0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98-1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction P<0.01). Conclusions In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. C1 [Greene, Stephen J.; Hernandez, Adrian F.; Ambrosy, Andrew P.; O'Connor, Christopher M.; Mentz, Robert J.] Duke Univ, Med Ctr, Div Cardiol, 2301 Erwin Rd,Suite 7400, Durham, NC 27705 USA. [Hernandez, Adrian F.; Sun, Jie-Lena; Ambrosy, Andrew P.; Schulte, Phillip J.; O'Connor, Christopher M.; Mentz, Robert J.] Duke Clin Res Inst, Durham, NC USA. [Metra, Marco] Univ Brescia, Cardiol, I-25121 Brescia, Italy. [Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA. [Ezekowitz, Justin A.; Armstrong, Paul W.] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. RP Greene, SJ (reprint author), Duke Univ, Med Ctr, Div Cardiol, 2301 Erwin Rd,Suite 7400, Durham, NC 27705 USA. EM stephen.greene@duke.edu FU Scios Inc. (Mountain View, CA) FX Scios Inc. (Mountain View, CA) provided financial and material support for the ASCEND-HF trial. Database management and statistical analysis was performed by the Duke Clinical Research Institute. NR 23 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2016 VL 9 IS 9 AR UNSP e002986 DI 10.1161/CIRCHEARTFAILURE.116.002986 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZG UT WOS:000384460800003 ER PT J AU Hiremath, P Lawler, PR Ho, JE Correia, AW Abbasi, SA Kwong, RY Jerosch-Herold, M Ho, CY Cheng, SS AF Hiremath, Pranoti Lawler, Patrick R. Ho, Jennifer E. Correia, Andrew W. Abbasi, Siddique A. Kwong, Raymond Y. Jerosch-Herold, Michael Ho, Carolyn Y. Cheng, Susan TI Ultrasonic Assessment of Myocardial Microstructure in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy SO CIRCULATION-HEART FAILURE LA English DT Article DE echocardiography; hypertrophic cardiomyopathy; left ventricular hypertrophy; myocardium; sacromeres ID SPECKLE TRACKING ECHOCARDIOGRAPHY; TISSUE CHARACTERIZATION; INTEGRATED BACKSCATTER; DILATED CARDIOMYOPATHY; CYCLIC VARIATION; NONINVASIVE ASSESSMENT; STUNNED MYOCARDIUM; GRAY-LEVEL; FIBROSIS; HEART AB Background The noninvasive assessment of altered myocardium in patients with genetic mutations that are associated with hypertrophic cardiomyopathy (HCM) remains challenging. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy. Methods and Results We studied 3 groups of genotyped individuals: sarcomere mutation carriers with left ventricular hypertrophy (clinical HCM; n=36), mutation carriers with normal left ventricular wall thickness (subclinical HCM; n=28), and healthy controls (n=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including cardiac magnetic resonance measures of interstitial fibrosis (extracellular volume fraction), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation-adjusted analyses, the SIC was quantitatively different across subjects with overt HCM, subclinical HCM, and healthy controls (P<0.001). Compared with controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (P<0.001 for both). The SIC was significantly correlated with extracellular volume (r=0.72; P<0.01), with left ventricular mass and E velocity (r=0.45, -0.60, respectively; P<0.01 for both), and with serum NTproBNP levels (r=0.36; P<0.001). Conclusions Our findings suggest that the SIC could serve as a noninvasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and to evaluate the effects of interventions. C1 [Hiremath, Pranoti; Lawler, Patrick R.; Kwong, Raymond Y.; Ho, Carolyn Y.; Cheng, Susan] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [Jerosch-Herold, Michael] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. [Ho, Jennifer E.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Correia, Andrew W.] SessionM, Boston, MA USA. [Abbasi, Siddique A.] Brown Univ, Dept Med, Div Cardiol, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Ho, CY; Cheng, SS (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM cho@partners.org; scheng@rics.bwh.harvard.edu OI Lawler, Patrick/0000-0001-5155-5071 FU National Institutes of Health LRP; Ellison Foundation; [T32-HL007575]; [P20 HL101408]; [P50-HL112349]; [R00-HL107642]; [R01-HL131532]; [R01-HL134168] FX This work was supported by the National Institutes of Health LRP (Dr Lawler) and grants T32-HL007575 (Dr Lawler), P20 HL101408 (Dr C. Ho), P50-HL112349 (Dr C. Ho), R00-HL107642 (Dr Cheng), R01-HL131532 (Dr Cheng), R01-HL134168 (Dr Cheng), and the Ellison Foundation (Dr Cheng). NR 41 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2016 VL 9 IS 9 AR e003026 DI 10.1161/CIRCHEARTFAILURE.116.003026 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZG UT WOS:000384460800004 ER PT J AU Ibrahim, NE Gaggin, HK Konstam, MA Januzzi, JL AF Ibrahim, Nasrien E. Gaggin, Hanna K. Konstam, Marvin A. Januzzi, James L., Jr. TI Established and Emerging Roles of Biomarkers in Heart Failure Clinical Trials SO CIRCULATION-HEART FAILURE LA English DT Article DE biomarkers; heart failure; natriuretic peptides; precision medicine; retrospective study ID PRESERVED EJECTION FRACTION; BRAIN NATRIURETIC PEPTIDE; SURROGATE END-POINTS; VENTRICULAR SYSTOLIC DYSFUNCTION; ROSUVASTATIN MULTINATIONAL TRIAL; EMERGENCY-DEPARTMENT PRIDE; RANDOMIZED-TRIAL; PROGNOSTIC VALUE; THERAPY PROTECT; BLOCKER THERAPY AB The role of circulating biomarkers in heart failure clinical trials has evolved in recent decades. Increasing evidence behind the use of natriuretic peptides, emergence of novel biomarkers, and increased emphasis on targeting therapies toward physiological basis of disease (so-called precision medicine) have all contributed to the continued expansion of biomarker use in heart failure clinical trials. We will explore the advantages and pitfalls encountered through the use of biomarkers in clinical trials as an inclusion criterion, toxicity marker, and end point. We will also review their role in providing insights into the mechanism of action of therapeutics and guiding therapy in the management of patients with heart failure. C1 [Ibrahim, Nasrien E.; Gaggin, Hanna K.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gaggin, Hanna K.; Januzzi, James L., Jr.] Harvard Clin Res Inst, Boston, MA USA. [Konstam, Marvin A.] Tufts Med Ctr, Cardiovasc Ctr, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Dennis and Marilyn Barry Fellowship in Cardiology Research; Hutter Family Professorship FX Dr Ibrahim is supported by the Dennis and Marilyn Barry Fellowship in Cardiology Research. Dr Januzzi is supported, in part, by the Hutter Family Professorship. NR 63 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 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2016 VL 9 IS 9 AR e002598 DI 10.1161/CIRCHEARTFAILURE.115.002528 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZG UT WOS:000384460800001 ER PT J AU Schutt, RC Bhimiraj, A Estep, JD Guha, A Trachtenberg, BH Garami, Z AF Schutt, Robert C. Bhimiraj, Arvind Estep, Jerry D. Guha, Ashrith Trachtenberg, Barry H. Garami, Zsolt TI Deflation Timing Influences Intra-Aortic Balloon Pump-Mediated Carotid Blood Flow Reversal: A Case Report SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE carotid arteries; cerebral blood flow; heart failure; intra-aortic balloon pumping; ultrasonography C1 [Schutt, Robert C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schutt, Robert C.] Harvard Med Sch, Boston, MA USA. [Bhimiraj, Arvind; Estep, Jerry D.; Guha, Ashrith; Trachtenberg, Barry H.; Garami, Zsolt] Houston Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. RP Schutt, RC (reprint author), 1 Emerson Pl,5P, Boston, MA 02114 USA. EM rschutt@mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2016 VL 9 IS 9 AR e003474 DI 10.1161/CIRCHEARTFAILURE.116.003474 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX5ZG UT WOS:000384460800010 ER PT J AU Flores-Blanco, PJ Lopez-Cuenca, A Januzzi, JL Marin, F Sanchez-Martinez, M Quintana-Giner, M Romero-Aniorte, AI Valdos, M Manzano-Fernandez, S AF Flores-Blanco, Pedro J. Lopez-Cuenca, Angel Januzzi, James L. Marin, Francisco Sanchez-Martinez, Marianela Quintana-Giner, Miriam Romero-Aniorte, Ana I. Valdes, Mariano Manzano-Fernandez, Sergio TI Comparison of Risk Prediction With the CKD- EPI and MDRD Equations in Non-ST-Segment Elevation Acute Coronary Syndrome SO CLINICAL CARDIOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; SERUM CYSTATIN-C; DECOMPENSATED HEART-FAILURE; ESTIMATING RENAL-FUNCTION; BETA-TRACE PROTEIN; EPIDEMIOLOGY COLLABORATION; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ESTIMATING GFR AB Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (GFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. Hypothesis: New CKD-EPI equations improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and provide complementary information to the Global Registry of Acute Coronary Events (GRACE) risk score. Methods: We studied 350 subjects (mean age, 68 +/- 12 years; 70% male) with NSTE-ACS. Estimated GFR was calculated using the MDRD and new CKD-EPI equations based on serum creatinine (SCr) and/or cystatin C (CysC) concentrations obtained within 48 hours of hospital admission. The primary endpoint was all-cause death during follow-up. Results: Over the study period (median, 648 days [interquartile range, 236-1042 days]), 31 patients died (0.05% events per person-year). Decedents had poorer renal-function parameters (P < 0.001). Both CysC-based CKD-EPI equations had the highest areas under the receiver operating characteristic curve for the prediction of all-cause mortality. After multivariate adjustment, only CysC-based CKD-EPI equations were independent predictors of all-cause mortality (CKD-EPISCr-CysC, per mL/min/1.73 m(2): hazard ratio: 0.975, 95% confidence interval: 0.956-0.994, P = 0.009; CKD-EPICysC, per mL/min/1.73 m(2:) hazard ratio: 0.976, 95% confidence interval: 0.959-0.993, P = 0.005). Reclassification analyses showed that only CysC-based CKD-EPI equations improved predictive accuracy of the GRACE risk score. Conclusions: In patients with NSTE-ACS, CysC-based CKD-EPI equations improved clinical risk stratification for mortality and added complementary prognostic information to the GRACE risk score. C1 [Flores-Blanco, Pedro J.; Marin, Francisco; Sanchez-Martinez, Marianela; Quintana-Giner, Miriam; Romero-Aniorte, Ana I.; Valdes, Mariano; Manzano-Fernandez, Sergio] Hosp Univ Virgen de la Arrixaca, Dept Cardiol, Murcia, Spain. [Lopez-Cuenca, Angel] Hosp Vega Lorenzo Guirao, Dept Cardiol, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Marin, Francisco; Valdes, Mariano; Manzano-Fernandez, Sergio] Univ Murcia, Sch Med, Dept Cardiol, Murcia, Spain. RP Flores-Blanco, PJ (reprint author), Univ Murcia, Sch Med, Univ Hosp Virgen de la Arrixaca, Div Cardiol, Carretera Madrid Cartagena S-N, Murcia 30120, Spain. EM pedrofb1986@gmail.com OI Flores-Blanco, Pedro J/0000-0002-6394-9841 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 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD SEP PY 2016 VL 39 IS 9 BP 507 EP 515 DI 10.1002/clc.22556 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DY0UO UT WOS:000384811900003 PM 27249221 ER PT J AU Zhang, ZW Yang, YJ Ng, CY Wang, DD Wang, JL Li, GP Liu, T AF Zhang, Zhiwei Yang, Yajuan Ng, Chee Yuan Wang, Dandan Wang, Jianlong Li, Guangping Liu, Tong TI Meta-analysis of Vitamin D Deficiency and Risk of Atrial Fibrillation SO CLINICAL CARDIOLOGY LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; 25-HYDROXYVITAMIN D; ELECTRICAL CARDIOVERSION; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; SEASONAL-VARIATION; REACTIVE PROTEIN; HEART-FAILURE; ASSOCIATION AB Background: There are accumulating studies investigating the association between vitamin D status and the risk of atrial fibrillation (AF). However, the results in these studies were inconsistent in regard to the role of vitamin D deficiency in predicting the development of AF. Hypothesis: Vitamin D deficiency is associated increased risk of AF. Methods: Using PubMed and Embase databases, we searched for records published before March 2016. Additionally, a manual search was conducted using all review articles on this topic. Of the 587 initially identified records, 8 studies with a total of 27 307 patients were finally analyzed. Results: In the categorical variable analysis, vitamin D deficiency was associated with the occurrence of AF (odds ratio: 1.31, 95% confidence interval: 1.06-1.62, P = 0.01). In the continuous variable analysis, higher vitamin D levels appear to protect against the development of AF (odds ratio: 0.92, 95% confidence interval: 0.87-0.97, P = 0.002). However, the association is weak on the pooled analysis of prospective cohort studies focused on new-onset AF (P = 0.07 and 0.04), whereas the pooled analysis of case-control studies mainly assessing for chronic AF strongly support such an association (both P < 0.0001). Conclusions: Vitamin D deficiency modestly increases the risk of AF. Further studies are needed to determine the if there is a direct causal relationship between vitamin D levels and AF and whether vitamin D supplements will prevent new-onset AF. C1 [Zhang, Zhiwei; Yang, Yajuan; Wang, Dandan; Wang, Jianlong; Li, Guangping; Liu, Tong] Tianjin Med Univ, Hosp 2, Tianjin Key Lab Ion Mol Funct Cardiovasc Dis, Dept Cardiol,Tianjin Inst Cardiol, Tianjin 300211, Peoples R China. [Ng, Chee Yuan] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Liu, T (reprint author), Tianjin Med Univ, Hosp 2, Tianjin Key Lab Ion Mol Funct Cardiovasc Dis, Dept Cardiol,Tianjin Inst Cardiol, Tianjin 300211, Peoples R China. EM liutongdoc@126.com FU National Natural Science Foundation of China [81270245, 81570298] FX This work was supported by grants (81270245 and 81570298 to T.L.) from the National Natural Science Foundation of China. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 37 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD SEP PY 2016 VL 39 IS 9 BP 537 EP 543 DI 10.1002/clc.22563 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DY0UO UT WOS:000384811900007 PM 27556176 ER PT J AU Schalock, PC Crawford, G Nedorost, S Scheinman, PL Atwater, AR Mowad, C Brod, B Ehrlich, A Watsky, KL Sasseville, D Silvestri, D Worobec, SM Elliott, JF Honari, G Powell, DL Taylor, J DeKoven, J AF Schalock, Peter C. Crawford, Glen Nedorost, Susan Scheinman, Pamela L. Atwater, Amber Reck Mowad, Christen Brod, Bruce Ehrlich, Alison Watsky, Kalman L. Sasseville, Denis Silvestri, Dianne Worobec, Sophie M. Elliott, John F. Honari, Golara Powell, Douglas L. Taylor, James DeKoven, Joel TI Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society SO DERMATITIS LA English DT Review ID TOTAL HIP-ARTHROPLASTY; NUSS PROCEDURE; DIAGNOSTIC ALGORITHM; ORTHOPEDIC IMPLANTS; SURGICAL IMPLANTS; PECTUS EXCAVATUM; NO ASSOCIATION; HIGH-FREQUENCY; IN-VITRO; T-CELL AB The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion-based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantationmorbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient. C1 [Schalock, Peter C.] Harvard Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Crawford, Glen; Brod, Bruce] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Nedorost, Susan] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Scheinman, Pamela L.] Harvard Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA USA. [Atwater, Amber Reck] Duke Univ, Med Ctr, Duke Dermatol, Durham, NC USA. [Mowad, Christen] Geisinger Hlth Syst, Dept Dermatol, Danville, PA USA. [Ehrlich, Alison] George Washington Univ, Dept Dermatol, Washington, DC USA. [Watsky, Kalman L.] Yale Univ, Sch Med, New Haven, CT USA. [Sasseville, Denis] McGill Univ, Ctr Hlth, Div Dermatol, Montreal, PQ, Canada. [Silvestri, Dianne] UMass Mem Med Ctr, Div Dermatol, Worcester, MA USA. [Worobec, Sophie M.] Univ Illinois, Chicago, IL USA. [Elliott, John F.] Univ Alberta, Div Dermatol, Dept Med, Edmonton, AB, Canada. [Elliott, John F.] Univ Alberta, Div Dermatol, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. [Honari, Golara] Stanford Univ, Dept Dermatol, Palo Alto, CA 94304 USA. [Powell, Douglas L.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Taylor, James] Cleveland Clin, Dermatol Plast Surg Inst, Cleveland, OH 44106 USA. [DeKoven, Joel] Univ Toronto, Dept Med Dermatol, Toronto, ON M5S 1A1, Canada. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR622,55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com OI Ehrlich, Alison/0000-0002-4062-5289 NR 59 TC 2 Z9 2 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD SEP-OCT PY 2016 VL 27 IS 5 BP 241 EP 247 DI 10.1097/DER.0000000000000210 PG 7 WC Dermatology SC Dermatology GA DX7OM UT WOS:000384577700002 PM 27649347 ER PT J AU Goldenberg, A Mousdicas, N Silverberg, N Powell, D Pelletier, JL Silverberg, JI Zippin, J Fonacier, L Tosti, A Lawley, L Chang, MW Scheman, A Kleiner, G Williams, J Watsky, K Dunnick, CA Frederickson, R Matiz, C Chaney, K Estes, TS Botto, N Draper, M Kircik, L Lugo-Somolinos, A Machler, B Jacob, SE AF Goldenberg, Alina Mousdicas, Nico Silverberg, Nanette Powell, Douglas Pelletier, Janice L. Silverberg, Jonathan I. Zippin, Jonathan Fonacier, Luz Tosti, Antonella Lawley, Leslie Chang, Mary Wu Scheman, Andrew Kleiner, Gary Williams, Judith Watsky, Kalman Dunnick, Cory A. Frederickson, Rachel Matiz, Catalina Chaney, Keri Estes, Tracy S. Botto, Nina Draper, Michelle Kircik, Leon Lugo-Somolinos, Aida Machler, Brian Jacob, Sharon E. TI Pediatric Contact Dermatitis Registry Inaugural Case Data SO DERMATITIS LA English DT Article AB Background: Little is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. Objective: The aim was to quantify patch test results from providers evaluating US children. Methods: The study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015-2016). Results: One thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). Conclusions: This US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products. C1 [Goldenberg, Alina] Univ Calif San Diego, Dept Dermatol, La Jolla, CA 92093 USA. [Mousdicas, Nico] Indiana Univ Hlth, Dept Dermatol, Indianapolis, IN USA. [Silverberg, Nanette] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Powell, Douglas] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Pelletier, Janice L.] Eastern Maine Med Ctr, Dept Pediat, Bangor, ME USA. [Pelletier, Janice L.] Univ Vermont, Coll Med, Burlington, VT USA. [Silverberg, Jonathan I.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol Prevent Med & Med Social Sci, Chicago, IL 60611 USA. [Zippin, Jonathan] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Fonacier, Luz] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [Fonacier, Luz] Winthrop Univ Hosp, Allergy & Immunol Training Program, Mineola, NY 11501 USA. [Tosti, Antonella] Univ Miami, Dept Dermatology& Cutaneous Surg, Coral Gables, FL USA. [Lawley, Leslie] Emory Univ, Sch Med, Dept Dermatol & Pediat, Atlanta, GA USA. [Chang, Mary Wu] Univ Connecticut, Sch Med, Dept Dermatol & Pediat, Farmington, CT USA. [Scheman, Andrew] Northwestern Univ, Dermatol Clin, Chicago, IL USA. [Kleiner, Gary] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Williams, Judith] Eastern Virginia Med Sch, Dept Pediat & Dermatol, Childrens Specialty Grp, Norfolk, VA 23501 USA. [Watsky, Kalman] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Dunnick, Cory A.] Univ Colorado Denver, Dept Dermatol, Denver, CO USA. [Dunnick, Cory A.] Denver VAMC, Denver, CO USA. [Frederickson, Rachel] Vanguard Skin Specialists, Colorado Springs, CO USA. [Matiz, Catalina] Univ Calif San Diego, Dept Dermatol, San Diego, CA 92103 USA. [Chaney, Keri] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Estes, Tracy S.] Asthma & Allergy Care Delaware, Newark, DE USA. [Botto, Nina] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Draper, Michelle] Everett Clin, Dept Dermatol, Everett, WA USA. [Kircik, Leon] Phys Skin Care PLLC, Louisville, KY USA. [Kircik, Leon] DermResearch PLLC, Louisville, KY USA. [Kircik, Leon] KY, New York, NY USA. [Kircik, Leon] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lugo-Somolinos, Aida] Univ N Carolina, Dept Dermatol, Chapel Hill, NC USA. [Machler, Brian] NYU Ronald O Perelman Sch Med, Dept Dermatol, New York, NY USA. [Jacob, Sharon E.] Loma Linda Univ, Dept Dermatol, Loma Linda, CA 92350 USA. RP Jacob, SE (reprint author), Loma Linda Univ, Dept Dermatol, Fac Med Off, 11370 Anderson St,Suite 2600, Loma Linda, CA 92350 USA. EM sjacob@contactderm.net FU Society of Pediatric Dermatology Pilot Project Grant FX The provider registry component portion of this study was funded in part by a Society of Pediatric Dermatology Pilot Project Grant. S.E.J. and A.G. were directly involved in the design, data collection and analysis, conduction of the study, and IRB approvals and preliminary manuscript preparation. The other authors were directly involved in self-reporting their deidentified patch test results and in the preparation and final review of the manuscript. Coauthorship was granted to the investigators who entered more than 15 cases within 1 year of data collection. NR 13 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD SEP-OCT PY 2016 VL 27 IS 5 BP 293 EP 302 DI 10.1097/DER.0000000000000214 PG 10 WC Dermatology SC Dermatology GA DX7OM UT WOS:000384577700010 PM 27649353 ER PT J AU Hamada, T Nakai, Y Isayama, H Yasunaga, H Matsui, H Takahara, N Mizuno, S Kogure, H Matsubara, S Yamamoto, N Tada, M Koike, K AF Hamada, Tsuyoshi Nakai, Yousuke Isayama, Hiroyuki Yasunaga, Hideo Matsui, Hiroki Takahara, Naminatsu Mizuno, Suguru Kogure, Hirofumi Matsubara, Saburo Yamamoto, Natsuyo Tada, Minoru Koike, Kazuhiko TI Progression-free survival as a surrogate for overall survival in first-line chemotherapy for advanced pancreatic cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Drug therapy; End-point determination; Pancreatic neoplasms; Survival; Treatment outcome ID PHASE-III TRIAL; GEMCITABINE PLUS PLACEBO; METASTATIC COLORECTAL-CANCER; COOPERATIVE-ONCOLOGY-GROUP; INDIVIDUAL PATIENT DATA; END-POINT DEFINITIONS; DOUBLE-BLIND; RANDOMIZED-TRIAL; COMPARING GEMCITABINE; TUMOR RESPONSE AB Background: Overall survival (OS), as the primary end-point in first-line chemotherapy trials, requires a prolonged follow-up time and may be confounded by subsequent regimens. This study aimed to evaluate the correlation between OS and surrogate end-points (progression-free survival [PFS], response rate and disease control rate), and to identify a potential surrogate for OS in advanced pancreatic cancer. Methods: Based on an electronic search, we identified randomized controlled phase II and III trials of first-line chemotherapy for advanced pancreatic cancer. Correlation analyses were performed between surrogate end-points and OS, and between improvements in surrogates and those in OS. Results: Fifty trials (II/II-III/III, 17/2/31) with 111 treatment arms were identified, and 15,906 patients were analysed. PFS was most strongly correlated with OS (correlation coefficient, 0.76). Weighted linear regression models revealed the greatest determinant coefficient of 0.84 between the hazard ratio (HR) of the experimental arms compared with the control arms of PFS and that of OS. The approximate equation was log HROS = 0.01 + 0.77 x log HRPFS, indicating that risk reduction of OS via chemotherapy would translate into a 77% risk reduction of PFS. The surrogacy of PFS for OS was robust throughout our subgroup analyses: e.g., biologic versus non-biologic regimens, locally advanced versus metastatic disease. Conclusions: The surrogacy of PFS for OS in pancreatic cancer was validated. Therefore, the use of PFS as the primary end-point in clinical trials could facilitate the early introduction of new effective chemotherapy regimens into clinical practice. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Hamada, Tsuyoshi; Nakai, Yousuke; Isayama, Hiroyuki; Takahara, Naminatsu; Mizuno, Suguru; Kogure, Hirofumi; Matsubara, Saburo; Yamamoto, Natsuyo; Tada, Minoru; Koike, Kazuhiko] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. [Hamada, Tsuyoshi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Hamada, Tsuyoshi] Harvard Med Sch, Boston, MA USA. [Yasunaga, Hideo; Matsui, Hiroki] Univ Tokyo, Sch Publ Hlth, Dept Clin Epidemiol & Hlth Econ, Tokyo, Japan. RP Isayama, H (reprint author), Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM hamada-tky@umin.ac.jp; ynakai-tky@umin.ac.jp; isayama-tky@umin.ac.jp; yasunagah-tky@umin.ac.jp; ptmatsui-tky@umin.ac.jp; naminatsu.takahara@gmail.com; smizuno-tky@umin.ac.jp; kogureh-tky@umin.ac.jp; sab-tky@umin.net; natsuyoy-gi@umin.ac.jp; mtada-tky@umin.ac.jp; kkoike-tky@umin.ac.jp NR 80 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 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2016 VL 65 BP 11 EP 20 DI 10.1016/j.ejca.2016.05.016 PG 10 WC Oncology SC Oncology GA DU5BP UT WOS:000382227300002 PM 27451020 ER PT J AU Ruiz-Morales, JM Swierkowski, M Wells, JC Fraccon, AP Pasini, F Donskov, F Bjarnason, GA Lee, JL Sim, HW Sliwczynsk, A Ptak-Chmielewska, A Teter, Z Beuselinck, B Wood, LA Yuasa, T Pezaro, C Rini, BI Szczylik, C Choueiri, TK Heng, DYC AF Ruiz-Morales, Jose Manuel Swierkowski, Marcin Wells, J. Connor Fraccon, Anna Paola Pasini, Felice Donskov, Frede Bjarnason, Georg A. Lee, Jae-Lyun Sim, Hao-Wen Sliwczynsk, Andrzej Ptak-Chmielewska, Aneta Teter, Zbigniew Beuselinck, Benoit Wood, Lori A. Yuasa, Takeshi Pezaro, Carmel Rini, Brian I. Szczylik, Cezary Choueiri, Toni K. Heng, Daniel Y. C. TI First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Carcinoma; Renal cell; Sunitinib; Pazopanib; Vascular endothelial growth factor receptor ID INDIVIDUALIZED SUNITINIB; DOUBLE-BLIND; PHASE-II; SCHEDULE; OUTCOMES; THERAPY; TRIAL AB Background: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. Patients and methods: We used the International mRCC Database Consortium (IMDC) to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS (OS2) and second-line PFS (PFS2) were also evaluated. Results: We obtained data from 7438 patients with mRCC treated with either first-line SU (n = 6519) or PZ (n = 919) with an overall median follow-up of 40.4 months (95% confidence interval [CI] 39.2-42.1). There were no significant differences in IMDC prognostic groups (p = 0.36). There was no OS difference between SU and PZ (22.3 versus 22.6 months, respectively, p = 0.65). When adjusted for IMDC criteria, the hazard ratio (HR) of death for PZ versus SU was 1.03 (95% CI 0.92-1.17, p = 0.58). There was no PFS difference between SU and PZ (8.4 versus 8.3 months, respectively, p = 0.17). When adjusted for IMDC criteria, the HR for PFS for PZ versus SU was 1.08 (95% CI 0.981-1.19, p = 0.12). There was no difference in RR between SU and PZ (30% versus 28%, respectively, p = 0.15). We also found no difference in any second-line treatment between either post-SU or post-PZ groups for OS2 (13.1 versus 11 months, p = 0.27) and PFS2 (3.7 versus 5.0 months, p = 0.07). Conclusions: We confirmed in real-world practice that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Ruiz-Morales, Jose Manuel; Wells, J. Connor; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Ruiz-Morales, Jose Manuel] Hosp Med Sur, Mexico City, DF, Mexico. [Swierkowski, Marcin; Szczylik, Cezary] Mil Inst Med, Dept Oncol, Warsaw, Poland. [Fraccon, Anna Paola] Casa Cura Pederzoli, Dept Oncol, Peschiera Del Garda, Italy. [Pasini, Felice] Osped S Maria Misericordia, Dept Med Oncol, Rovigo, Italy. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark. [Bjarnason, Georg A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lee, Jae-Lyun] Univ Ulsan, Dept Oncol, Asan Med Ctr, Coll Med, Seoul, South Korea. [Sim, Hao-Wen] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Sliwczynsk, Andrzej] Med Univ Lodz, Dept Hlth Qual, Lodz, Poland. [Ptak-Chmielewska, Aneta] Warsaw Sch Econ, Inst Stat & Demog, Warsaw, Poland. [Teter, Zbigniew] Natl Hlth Fund, Warsaw, Poland. [Beuselinck, Benoit] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. [Wood, Lori A.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Yuasa, Takeshi] Japanese Fdn Canc Res, Dept Urol, Canc Inst Hosp, Tokyo, Japan. [Pezaro, Carmel] Monash Univ, Eastern Hlth Clin Sch, Clayton, Vic 3800, Australia. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heng, DYC (reprint author), Univ Calgary, Alberta Hlth Serv Canc Care, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca NR 14 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 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2016 VL 65 BP 102 EP 108 DI 10.1016/j.ejca.2016.06.016 PG 7 WC Oncology SC Oncology GA DU5BP UT WOS:000382227300011 PM 27487293 ER PT J AU Law, CCY Sasidharan, S Rodrigues, R Nguyen, DD Sauk, J Garber, J Giallourakis, C Xavier, R Khalili, H Yajnik, V Ananthakrishnan, AN AF Law, Cindy C. Y. Sasidharan, Saranya Rodrigues, Rodrigo Nguyen, Deanna D. Sauk, Jenny Garber, John Giallourakis, Cosmas Xavier, Ramnik Khalili, Hamed Yajnik, Vijay Ananthakrishnan, Ashwin N. TI Impact of Specialized Inpatient IBD Care on Outcomes of IBD Hospitalizations: A Cohort Study SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE infliximab; hospitalization; surgery; high-dose; accelerated induction ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; ULCERATIVE-COLITIS; UNITED-STATES; NATIONWIDE ANALYSIS; BIOLOGICAL THERAPY; SURGERY; VOLUME; MANAGEMENT; MORTALITY AB Background: The management of inflammatory bowel diseases (IBDs; Crohn's disease, ulcerative colitis) is increasingly complex. Specialized care has been associated with improved ambulatory IBD outcomes. Aims: To examine if the implementation of specialized inpatient IBD care modified short-term and long-term clinical outcomes in IBD-related hospitalizations. Methods: This retrospective cohort study included IBD patients hospitalized between July 2013 and April 2015 at a single tertiary referral center where a specialized inpatient IBD care model was implemented in July 2014. In-hospital medical and surgical outcomes as well as postdischarge outcomes at 30 and 90 days were analyzed along with measures of quality of in-hospital care. Effect of specialist IBD care was examined on multivariate analysis. Results: A total of 408 IBD-related admissions were included. With implementation of specialized IBD inpatient care, we observed increased frequency of use of high-dose biologic therapy for induction (26% versus 9%, odds ratio 5.50, 95% confidence interval 1.30-23.17) and higher proportion of patients in remission at 90 days after discharge (multivariate odds ratio 1.60, 95% confidence interval 0.99-2.69). Although there was no difference in surgery by 90 days, among those who underwent surgery, early surgery defined as in-hospital or within 30 days of discharge, was more common in the study period (71%) compared with the control period (46%, multivariate odds ratio 2.73, 95% confidence interval 1.22-6.12). There was no difference in length of stay between the 2 years. Conclusions: Implementation of specialized inpatient IBD care beneficially impacted remission and facilitated early surgical treatment. C1 [Law, Cindy C. Y.; Nguyen, Deanna D.; Sauk, Jenny; Garber, John; Giallourakis, Cosmas; Xavier, Ramnik; Khalili, Hamed; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. [Law, Cindy C. Y.] Univ Ottawa, Ottawa, ON, Canada. [Sasidharan, Saranya] Boston Med Ctr, Boston, MA USA. [Rodrigues, Rodrigo] North Shore Community Hlth Ctr, Salem, MA USA. [Nguyen, Deanna D.; Sauk, Jenny; Garber, John; Giallourakis, Cosmas; Xavier, Ramnik; Khalili, Hamed; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU AGA Student Research Fellowship Award; National Institutes of Health [K23 DK097142]; American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; National Institutes of Health (NIH) [P30 DK043351]; Cubist; Amgen; Abbvie; NPS; Janssen Pharmaceuticals; UCB FX Supported by the AGA Student Research Fellowship Award. A. N. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). Khalili is supported by a career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). This work is also supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases.; A. N. Ananthakrishnan has served on the scientific advisory boards for Abbvie, Exact Sciences, and Cubist pharmaceuticals and has received grant support from Cubist and Amgen. H. Khalili has received consultant fee from Abbvie. V. Yajnik has received consulting fees from NPS, Janssen Pharmaceuticals, and UCB. The remaining authors have no conflict of interest to disclose. NR 34 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 SEP PY 2016 VL 22 IS 9 BP 2149 EP 2157 DI 10.1097/MIB.0000000000000870 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX6AS UT WOS:000384464800020 PM 27482978 ER PT J AU Vaughn, BP Vatanen, T Allegretti, JR Bai, AP Xavier, RJ Korzenik, J Gevers, D Ting, A Robson, SC Moss, AC AF Vaughn, Byron P. Vatanen, Tommi Allegretti, Jessica R. Bai, Aiping Xavier, Ramnik J. Korzenik, Joshua Gevers, Dirk Ting, Amanda Robson, Simon C. Moss, Alan C. TI Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; Clinical Trials; microbiology of IBD ID INFLAMMATORY-BOWEL-DISEASE; RECURRENT CLOSTRIDIUM-DIFFICILE; RANDOMIZED CONTROLLED-TRIAL; REGULATORY T-CELLS; ULCERATIVE-COLITIS; FUNCTIONAL ANNOTATION; NLRP3 INFLAMMASOME; ESCHERICHIA-COLI; INFECTION; EXPRESSION AB Background: The microbiota in the lumen of patients with Crohn's disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD. Methods: We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed by colonoscopy. Recipients' microbial diversity, mucosal T-cell phenotypes, and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks. Results: Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (Harvey-Bradshaw Index decrease >3) following FMT. Fifteen subjects had sufficient pre/postfecal samples for analysis. A significant increase in microbial diversity occurred after FMT (P = 0.02). This was greater in clinical responders than nonresponders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition toward their donor's profile as assessed by the Bray-Curtis index at 4 weeks (P = 0.003). An increase in regulatory T cells (CD4(+)CD25(+)CD127lo) was also noted in recipients' lamina propria following FMT. No serious adverse events were noted over the 26-week study period. Conclusions: In this open-label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed before randomized clinical trials of FMT in CD. C1 [Vaughn, Byron P.; Bai, Aiping; Ting, Amanda; Robson, Simon C.; Moss, Alan C.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Boston, MA USA. [Vatanen, Tommi; Xavier, Ramnik J.; Gevers, Dirk] Broad Inst MIT & Harvard, Cambridge, MA USA. [Vatanen, Tommi] Aalto Univ, Sch Sci, Dept Comp Sci, Espoo, Finland. [Allegretti, Jessica R.; Korzenik, Joshua] Brigham & Womens Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02115 USA. [Allegretti, Jessica R.; Xavier, Ramnik J.; Korzenik, Joshua] Harvard Med Sch, Boston, MA USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Gevers, Dirk] Janssen R&D, Janssen Human Microbiome Inst, Cambridge, MA USA. [Vaughn, Byron P.] Univ Minnesota, Div Gastroenterol Hepatol & Nutr, Minneapolis, MN 55455 USA. [Gevers, Dirk] Janssen Human Microbiome Inst, Cambridge, MA USA. RP Moss, AC (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. EM amoss@bidmc.harvard.edu FU Leona and Harry Helmsley Charitable Trust; NIH [K23DK084338, 5T32DK007760-14]; Takeda; Pfizer; CTI; Dainippon; Helmsley Trust/HITI; Theravance FX Project support from grant to the Harvard Institute of Translational Immunology (HITI) from the Leona and Harry Helmsley Charitable Trust (A.C.M.). A. C. Moss is supported by NIH grant K23DK084338. B. P. Vaughn is supported by NIH grant 5T32DK007760-14.; B. P. Vaughn has no conflicts of interest to report and is currently affiliated with the University of Minnesota, Division of Gastroenterology Hepatology and Nutrition. D. Gevers is currently an employee of Janssen Human Microbiome Institute. J. Korzenik has consulted for Janssen Abbvie and research support from Takeda and Pfizer. S. C. Robson has research support from NIH, Pfizer, CTI, Dainippon and Helmsley Trust/HITI, has consulted for PureTech, and has Royalties from eBioscience, Bioloegend, Merck, Sharp & Dohme and Mersana. A. C. Moss has consulted for Janssen, Abbott, UCB, Roche, Seres and Bayer, and received research support (to BIDMC) from Pfizer and Theravance. The remaining authors have no conflicts of interest to disclose. NR 40 TC 2 Z9 2 U1 15 U2 15 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 SEP PY 2016 VL 22 IS 9 BP 2182 EP 2190 DI 10.1097/MIB.0000000000000893 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX6AS UT WOS:000384464800024 PM 27542133 ER PT J AU Cholapranee, A Ananthakrishnan, AN AF Cholapranee, Aurada Ananthakrishnan, Ashwin N. TI Environmental Hygiene and Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE hygiene; Crohn's disease; ulcerative colitis; farm; pets; inflammatory bowel disease; toilet ID ONSET CROHNS-DISEASE; ULCERATIVE-COLITIS; ALLERGIC DISEASES; CHILDHOOD HYGIENE; DOMESTIC HYGIENE; HYPOTHESIS; ASSOCIATION; EPIDEMIOLOGY; MULTICENTER; AUTOIMMUNE AB Background: According to the hygiene hypothesis, individuals raised in a sanitary environment have a higher risk of developing inflammatory bowel diseases (IBD). However, results have been inconsistent. We conducted this systematic review of factors related to environmental hygiene and risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Methods: A systematic search was performed on MEDLINE between 1980 and 2015 to identify studies of the association between IBD and contact with pets and farm animals, number of siblings, bedroom sharing in childhood, and access to personal toilet and hot water. Random-or fixed-effect meta-analyses were performed, and analysis further stratified based on ethnicity of the included cohort. Results: A total of 29 relevant studies were included. Having a pet (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.63-0.88) and contact with farm animals was inversely associated with risk of IBD (OR, 0.45; 95% CI, 0.31-0.60). However, the strength of association with farm animals was statistically stronger in non-white cohorts (OR, 0.27; 95% CI, 0.02-0.53) than in white cohorts (OR, 0.55; 95% CI, 0.45-0.65) (P = 0.028). Access to toilet (OR, 0.71; 95% CI, 0.56-0.85) and hot water (OR, 0.67; 95% CI, 0.44-0.89) was inversely associated with UC in non-white populations but not whites. Having more than 2 siblings was inversely associated with risk of CD. Conclusions: Several factors pertaining to reduced environmental hygiene are inversely associated with risk of IBD. However, underlying ethnicity influences susceptibility to the effect of these factors. C1 [Cholapranee, Aurada] Montefiore Med Ctr, Dept Internal Med, New York, NY USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU U.S. National Institutes of Health [K23 DK097142] FX Supported by funding from the U.S. National Institutes of Health (K23 DK097142 to A.N.A.). NR 51 TC 1 Z9 1 U1 7 U2 7 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 SEP PY 2016 VL 22 IS 9 BP 2191 EP 2199 DI 10.1097/MIB.0000000000000852 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX6AS UT WOS:000384464800025 PM 27482977 ER PT J AU DePasse, J Celi, LA AF DePasse, Jacqueline Celi, Leo Anthony TI Collaboration, capacity building and co-creation as a new mantra in global health SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Editorial Material C1 [DePasse, Jacqueline] Massachusetts Gen Hopsital, Dept Med, 15 Parkman St, Boston, MA 02214 USA. [Celi, Leo Anthony] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave,E25-505, Cambridge, MA 02139 USA. [Celi, Leo Anthony] BIDMC, Div Pulm Crit Care & Sleep Med, 330 Brookline Ave, Boston, MA 02215 USA. RP DePasse, J (reprint author), Massachusetts Gen Hopsital, Dept Med, 15 Parkman St, Boston, MA 02214 USA. EM jwdepasse@partners.org OI DePasse, Jacqueline/0000-0003-2811-5312 NR 6 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 EI 1464-3677 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD SEP 1 PY 2016 VL 28 IS 4 BP 536 EP 537 DI 10.1093/intqhc/mzt077 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX8ST UT WOS:000384660300016 PM 24225268 ER PT J AU Livorsi, D Knobloch, MJ Blue, LA Swafford, K Maze, L Riggins, K Hayward, T Safdar, N AF Livorsi, D. Knobloch, M. J. Blue, L. A. Swafford, K. Maze, L. Riggins, K. Hayward, T. Safdar, N. TI A rapid assessment of barriers and facilitators to safety culture in an intensive care unit SO INTERNATIONAL NURSING REVIEW LA English DT Article DE Safety Culture; ICU ID PATIENT SAFETY AB The Hospital Survey on Patient Safety was used to identify opportunities for safety culture improvement in a 30-bed intensive care unit. Based on the survey results, a core team decided to focus on three safety domains: reporting errors, approachability of authority figures and handovers. The project team subsequently interviewed 39 intensive care unit staff members, gathering information on these three domains that will inform future safety efforts. Numerous barriers and facilitators to improvement were described. This mixed-methods approach could be applied in other hospitals seeking to quickly yet thoroughly understand how their safety culture can be improved. Developing local strategies to reduce these barriers may promote a safer patient experience at our hospital. C1 [Livorsi, D.] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA 52246 USA. [Knobloch, M. J.; Safdar, N.] Univ Wisconsin, Sch Med, Madison, WI USA. [Blue, L. A.] Sidney & Lois Eskenazi Hosp, Patient Care Serv, Indianapolis, IN USA. [Swafford, K.; Maze, L.; Riggins, K.] Sidney & Lois Eskenazi Hosp, Indianapolis, IN USA. [Hayward, T.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA. [Safdar, N.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Livorsi, D.] Iowa City VAMC, Antimicrobial Stewardship, Iowa City, IA 52246 USA. RP Livorsi, D (reprint author), Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA 52246 USA.; Livorsi, D (reprint author), Iowa City VAMC, Antimicrobial Stewardship, Iowa City, IA 52246 USA. EM daniel-livorsi@uiowa.edu FU Health Research and Educational Trust FX This project was funded by a grant from the Health Research and Educational Trust as part of the Project Protect Fellowship. NR 12 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-8132 EI 1466-7657 J9 INT NURS REV JI Int. Nurs. Rev. PD SEP PY 2016 VL 63 IS 3 BP 372 EP 376 DI 10.1111/inr.12254 PG 5 WC Nursing SC Nursing GA DY0VD UT WOS:000384813400013 PM 27250081 ER PT J AU Jena, AB Olenski, AR Blumenthal, DM AF Jena, Anupam B. Olenski, Andrew R. Blumenthal, Daniel M. TI Sex Differences in Physician Salary in US Public Medical Schools SO JAMA INTERNAL MEDICINE LA English DT Article ID CONTROLLABLE LIFE-STYLE; ACADEMIC MEDICINE; GENDER-DIFFERENCES; CAREER-DEVELOPMENT; FEMALE PHYSICIANS; SPECIALTY CHOICE; WOMEN PHYSICIANS; MEN; PRODUCTIVITY; FACULTY AB IMPORTANCE Limited evidence exists on salary differences between male and female academic physicians, largely owing to difficulty obtaining data on salary and factors influencing salary. Existing studies have been limited by reliance on survey-based approaches to measuring sex differences in earnings, lack of contemporary data, small sample sizes, or limited geographic representation. OBJECTIVE To analyze sex differences in earnings among US academic physicians. DESIGN, SETTING, AND PARTICIPANTS Freedom of Information laws mandate release of salary information of public university employees in several states. In 12 states with salary information published online, salary data were extracted on 10 241 academic physicians at 24 public medical schools. These data were linked to a unique physician database with detailed information on sex, age, years of experience, faculty rank, specialty, scientific authorship, National Institutes of Health funding, clinical trial participation, and Medicare reimbursements (proxy for clinical revenue). Sex differences in salary were estimated after adjusting for these factors. EXPOSURES Physician sex. MAIN OUTCOMES AND MEASURES Annual salary. RESULTS Among 10 241 physicians, female physicians (n = 3549) had lower mean (SD) unadjusted salaries than male physicians ($206 641 [$88 238] vs $257 957 [$ 137 202]; absolute difference, $51 315 [95% CI, $46 330-$ 56 301]). Sex differences persisted after multivariable adjustment ($227 783 [95% CI, $224 117-$231 448] vs $247 661 [95% CI, $245 065-$250 258] with an absolute difference of $19 878 [95% CI, $15 261-$24 495]). Sex differences in salary varied across specialties, institutions, and faculty ranks. For example, adjusted salaries of female full professors ($250 971 [95% CI, $242 307-$259 635]) were comparable to those of male associate professors ($247 212 [95% CI, $241 850-$252 575]). Among specialties, adjusted salaries were highest in orthopedic surgery ($ 358 093 [95% CI, $344 354-$371 831]), surgical subspecialties ($318 760 [95% CI, $311 030-$326 491]), and general surgery ($302 666 [95% CI, $294 060-$311 272]) and lowest in infectious disease, family medicine, and neurology (mean income, <$200 000). Years of experience, total publications, clinical trial participation, and Medicare payments were positively associated with salary. CONCLUSIONS AND RELEVANCE Among physicians with faculty appointments at 24 US public medical schools, significant sex differences in salary exist even after accounting for age, experience, specialty, faculty rank, and measures of research productivity and clinical revenue. C1 [Jena, Anupam B.; Olenski, Andrew R.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Blumenthal, Daniel M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Blumenthal, Daniel M.] Harvard Med Sch, Boston, MA USA. RP Jena, AB (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU Early Independence Award from the National Institutes of Health [1DP5OD017897-01] FX Funding was received through grant 1DP5OD017897-01, an Early Independence Award from the National Institutes of Health (Dr Jena). NR 38 TC 11 Z9 11 U1 4 U2 4 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 SEP PY 2016 VL 176 IS 9 BP 1294 EP 1304 DI 10.1001/jamainternmed.2016.3284 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DX2MR UT WOS:000384204800015 PM 27400435 ER PT J AU Gellad, WF Good, CB AF Gellad, Walid F. Good, Chester B. TI Prescription of Brand-Name Medications When Generic Alternatives Are Available-Patently Unfair SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Gellad, Walid F.; Good, Chester B.] Univ Pittsburgh, Div Gen Med, Pittsburgh, PA USA. [Gellad, Walid F.; Good, Chester B.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA USA. [Gellad, Walid F.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Good, Chester B.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. RP Gellad, WF (reprint author), Univ Pittsburgh, Div Gen Internal Med, Univ Dr,Bldg 151C, Pittsburgh, PA 15240 USA. EM walid.gellad@pitt.edu 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2016 VL 176 IS 9 BP 1323 EP 1324 DI 10.1001/jamainternmed.2016.3389 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DX2MR UT WOS:000384204800020 PM 27367570 ER PT J AU Schwamm, LH AF Schwamm, Lee H. TI Admitting the Patient With Acute Stroke to the Right House-Lessons From the Sorting Hat of Hogwarts SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; GUIDELINES-STROKE; OUTCOMES; PERFORMANCE; PROGRAM C1 [Schwamm, Lee H.] Harvard Med Sch, Massachusetts Gen Hosp, Stroke Serv, 55 Fruit St,Ste ACC720, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Stroke Serv, 55 Fruit St,Ste ACC720, Boston, MA 02114 USA. EM lschwamm@mgh.harvard.edu NR 9 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 SEP PY 2016 VL 176 IS 9 BP 1368 EP 1370 DI 10.1001/jamainternmed.2016.3930 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DX2MR UT WOS:000384204800029 PM 27454422 ER PT J AU Lakin, JR Block, SD Billings, JA Koritsanszky, LA Cunningham, R Wichmann, L Harvey, D Lamey, J Bernacki, RE AF Lakin, Joshua R. Block, Susan D. Billings, J. Andrew Koritsanszky, Luca A. Cunningham, Rebecca Wichmann, Lisa Harvey, Doreen Lamey, Jan Bernacki, Rachelle E. TI Improving Communication About Serious Illness in Primary Care SO JAMA INTERNAL MEDICINE LA English DT Review ID TERMINALLY-ILL PATIENTS; OF-LIFE CARE; PALLIATIVE CARE; GENERAL-PRACTITIONERS; CANCER-PATIENTS; DISCUSSING PROGNOSIS; FAMILY PHYSICIANS; END; INVOLVEMENT; PREFERENCES AB IMPORTANCE The Institute of Medicine recently called for systematic improvements in clinician-led conversations about goals, values, and care preferences for patients with serious and life-threatening illnesses. Studies suggest that these conversations are associated with improved outcomes for patients and their families, enhanced clinician satisfaction, and lower health care costs; however, the role of primary care clinicians in driving conversations about goals and priorities in serious illness is not well defined. OBJECTIVE To present a review of a structured search of the evidence base about communication in serious illness in primary care. EVIDENCE REVIEW MEDLINE was searched, via PubMed, on January 19, 2016, finding 911 articles; 126 articles were reviewed and selected titles were added from bibliography searches. FINDINGS Review of the literature informed 2 major topic areas: the role of primary care in communication about serious illness and clinician barriers and system failures that interfere with effective communication. Literature regarding the role that primary care plays in communication focused primarily on the ambiguity about whether primary care clinicians or specialists are responsible for initiating conversations, the benefits of primary care clinicians and specialists conducting conversations, and the quantity and quality of discussions. Timely and effective communication about serious illness in primary care is hampered by key clinician barriers, which include deficits in knowledge, skills, and attitudes; discomfort with prognostication; and lack of clarity about the appropriate timing and initiation of conversations. Finally, system failures in coordination, documentation, feedback, and quality improvement contribute to lack of conversations. CONCLUSIONS AND RELEVANCE Clinician and system barriers will challenge primary care clinicians and institutions to meet the needs of patients with serious illness. Ensuring that conversations about goals and values occur at the appropriate time for seriously ill patients will require improved training, validation, and dissemination of patient selection tools, systems for conducting and revisiting conversations, accessible documentation, and incentives for measurement, feedback, and continuous improvement. C1 [Lakin, Joshua R.; Block, Susan D.; Bernacki, Rachelle E.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,Mailbox D-216A, Boston, MA 02215 USA. [Lakin, Joshua R.; Block, Susan D.; Bernacki, Rachelle E.] Brigham & Womens Hosp, Div Palliat Med, 75 Francis St, Boston, MA 02115 USA. [Lakin, Joshua R.; Block, Susan D.; Billings, J. Andrew; Koritsanszky, Luca A.; Bernacki, Rachelle E.] Brigham & Womens Hosp, Ariadne Labs, 75 Francis St, Boston, MA 02115 USA. [Lakin, Joshua R.; Block, Susan D.; Billings, J. Andrew; Koritsanszky, Luca A.; Bernacki, Rachelle E.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Lakin, Joshua R.; Block, Susan D.; Cunningham, Rebecca; Bernacki, Rachelle E.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. [Billings, J. Andrew] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA. [Wichmann, Lisa; Harvey, Doreen] Brigham & Womens Hosp, Dept Care Coordinat, 75 Francis St, Boston, MA 02115 USA. [Lamey, Jan] Brigham & Womens Phys Org, Dept Med Management, Boston, MA USA. [Bernacki, Rachelle E.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. RP Lakin, JR (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,Mailbox D-216A, Boston, MA 02215 USA. EM jlakin@partners.org NR 60 TC 1 Z9 1 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD SEP PY 2016 VL 176 IS 9 BP 1380 EP 1387 DI 10.1001/jamainternmed.2016.3212 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DX2MR UT WOS:000384204800032 PM 27398990 ER PT J AU Wentland, C Hersh, C Sally, S Fracchia, MS Hardy, S Liu, B Garcia, JA Hartnick, CJ AF Wentland, Carissa Hersh, Cheryl Sally, Sarah Fracchia, M. Shannon Hardy, Steven Liu, Bob Garcia, Jordan A. Hartnick, Christopher J. TI Modified Best-Practice Algorithm to Reduce the Number of Postoperative Videofluoroscopic Swallow Studies in Patients With Type 1 Laryngeal Cleft Repair SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ENDOSCOPIC REPAIR; MANAGEMENT; DIAGNOSIS AB IMPORTANCE There is no consensus as to the timing of videofluoroscopic swallow studies (VFSSs) in determining resolving aspiration after laryngeal cleft repair. There is a growing literature on the effect of radiation exposure in children. OBJECTIVE To modify a previously published best-practice algorithm based on a literature review and our clinical experience to maintain the quality of care provided after successful type 1 laryngeal cleft repair, while reducing the total number of postoperative VFSSs by 10% or greater. DESIGN, SETTING, AND PARTICIPANTS The previously published algorithm was modified by a multidisciplinary group at a tertiary care academic medical center (Massachusetts Eye and Ear) and was prospectively applied to 31 children who underwent type 1 laryngeal cleft repair from January 1, 2013, to February 28, 2015. MAIN OUTCOMES AND MEASURES The number of VFSSs obtained in the first 7 months after surgery was compared with the peer-reviewed literature and with a retrospective cohort of 27 patients who underwent type 1 laryngeal cleft repair from January 1, 2008, to December 31, 2012. RESULTS The study cohort comprised 31 patients. Their ages ranged from 10 to 48 months, with a mean (SD) age of 23.94 (9.93) months, and 19% (6 of 31) were female. The mean (SD) number of postoperative VFSSs per patient before and after implementation of the algorithm was 1.22 (0.42) and 1.03 (0.55), respectively. The use of the algorithm reduced the number of VFSSs by 0.19 (95% CI, -0.07 to 0.45). This reduction in radiation exposure is equivalent to 1.47 chest radiographs per child per course of care. Surgical success was 87%(27 of 31) compared with our group's previously published success rate of 78%(21 of 27) (absolute difference, 0.09; 95% CI, -0.17 to 0.34). CONCLUSIONS AND RELEVANCE This modified algorithm to help guide decisions on when and how often to obtain VFSSs after type 1 laryngeal cleft repair can limit patients' radiation exposure, while maintaining high surgical success rates. C1 [Wentland, Carissa; Hartnick, Christopher J.] Massachusetts Eye & Ear, Pediat Otolaryngol Serv, 243 Charles St, Boston, MA 02114 USA. [Hersh, Cheryl; Sally, Sarah] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. [Fracchia, M. Shannon] Massachusetts Gen Hosp, Pediat Pulmonol Serv, Boston, MA 02114 USA. [Hardy, Steven] Massachusetts Gen Hosp, Pediat Gastroenterol Serv, Boston, MA 02114 USA. [Liu, Bob] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Garcia, Jordan A.] Harvard Med Sch, Massachusetts Eye & Ear, Dept Otolaryngol ENT, Boston, MA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear, Pediat Otolaryngol Serv, 243 Charles St, Boston, MA 02114 USA. EM christopher_hartnick@meei.harvard.edu NR 20 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 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD SEP PY 2016 VL 142 IS 9 BP 851 EP 856 DI 10.1001/jamaoto.2016.1252 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DX7PX UT WOS:000384581800006 PM 27356238 ER PT J AU Weinrauch, LA Bayliss, G Segal, AR Liu, JK Wisniewski, E D'Elia, JA AF Weinrauch, Larry A. Bayliss, George Segal, Alissa R. Liu, Jiankang Wisniewski, Eric D'Elia, John A. TI Renal Function Alters Antihypertensive Regimens in Type 2 Diabetic Patients SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID TREATMENT-RESISTANT HYPERTENSION; ANGIOTENSIN-CONVERTING ENZYME; LIPID-LOWERING TREATMENT; CHRONIC KIDNEY-DISEASE; ATTACK TRIAL ALLHAT; HIGH-BLOOD-PRESSURE; UNITED-STATES; GLUCOSE CONTROL; POTENTIAL ROLE; PREVALENCE AB To determine the prevalence of multidrug antihypertensive therapy (MDAT), records were evaluated for patients with both type 2 diabetes and hypertension during a 5-year period at Joslin Diabetes Center. Hypertension control was defined as requiring multiple drugs if three or more antihypertensive drugs were used, one of which must be a diuretic (unless patient is receiving dialysis), or use of four or more antihypertensive drugs, one of which a diuretic (unless patient is receiving dialysis) was established. The objective was to determine the prevalence of multidrug requirement for hypertensive therapy in relationship to four levels of renal function estimated by the Modification of Diet in Renal Disease formula for glomerular filtration rate (GFR). Among 10,151 patients, mean estimated GFR was 80mL/min. Using standard (ASN) classification for renal function, we noted the following breakdown of MDAT use: [GRAPHICS] Prevalence of multidrug antihypertensive therapy is markedly increased in the presence of reduced renal function. (C) 2016 Wiley Periodicals, Inc. C1 [Weinrauch, Larry A.; Segal, Alissa R.; Wisniewski, Eric; D'Elia, John A.] Joslin Diabet Ctr, Kidney & Hypertens Sect, Boston, MA 02215 USA. [Bayliss, George] Brown Univ, Rhode Isl Hosp, Div Kidney Dis & Hypertens, Alpert Med Sch, Providence, RI 02903 USA. [Weinrauch, Larry A.; Liu, Jiankang] Brigham & Womens Hosp, Div Cardiovasc, Clin End Points Sect, 75 Francis St, Boston, MA 02115 USA. RP Weinrauch, LA (reprint author), 521 Mt Auburn St,Suite 204, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu NR 32 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD SEP PY 2016 VL 18 IS 9 BP 878 EP 883 DI 10.1111/jch.12776 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX9WF UT WOS:000384747000009 PM 26932730 ER PT J AU Billington, M Kandalaft, OR Aisiku, IP AF Billington, Michael Kandalaft, Osama R. Aisiku, Imoigele P. TI Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management SO JOURNAL OF CLINICAL MEDICINE LA English DT Review DE epilepsy; Status Epilepticus (SE); generalized convulsive status epilepticus (GCSE); Anti-Epileptic Drugs (AEDs); benzodiazepines ID CONVULSIVE STATUS EPILEPTICUS; REFRACTORY STATUS EPILEPTICUS; HOSPITAL STATUS EPILEPTICUS; SEIZURE PATIENTS; MORTALITY; PATHOPHYSIOLOGY; DIAZEPAM; EPIDEMIOLOGY; POPULATION; LORAZEPAM AB Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second-and third-line pharmacological agents. C1 [Billington, Michael] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Kandalaft, Osama R.; Aisiku, Imoigele P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Aisiku, IP (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mbillington@partners.org; okandalaft@partners.org; iaisiku@bwh.harvard.edu OI Aisiku, Imoigele/0000-0003-1041-3768 NR 47 TC 0 Z9 0 U1 2 U2 2 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2077-0383 J9 J CLIN MED JI J. Clin. Med. PD SEP PY 2016 VL 5 IS 9 AR 74 DI 10.3390/jcm5090074 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DX9EZ UT WOS:000384697700001 ER PT J AU Song, BJ Ramanathan, M Morales, E Law, SK Giaconi, JA Coleman, AL Caprioli, J AF Song, Brian J. Ramanathan, Meera Morales, Esteban Law, Simon K. Giaconi, JoAnn A. Coleman, Anne L. Caprioli, Joseph TI Trabeculectomy and Combined Phacoemulsification-Trabeculectomy: Outcomes and Risk Factors for Failure in Primary Angle Closure Glaucoma SO JOURNAL OF GLAUCOMA LA English DT Article DE primary angle closure glaucoma; trabeculectomy; intraocular pressure; cataract ID INTRAOCULAR-PRESSURE CONTROL; MITOMYCIN-C; CATARACT-EXTRACTION; SURGERY; IMPLANTATION; LASER AB Purpose: To evaluate tonometric outcomes of patients with primary angle closure glaucoma (PACG) who have undergone trabeculectomy with mitomycin C (MMC) with and without concurrent phacoemulsification and to identify risk factors for postoperative failure. Patients and Methods: Retrospective cohort study of 44 eyes of 33 phakic patients who underwent trabeculectomy with MMC with or without combined phacoemulsification for PACG. The primary endpoint was qualified tonometric success at 12 months according to predefined criteria. LogMAR visual acuity, number of glaucoma medications, and postoperative complications were also evaluated. Cox proportional hazard regression analysis was performed to identify potential risk factors for trabeculectomy failure. Results: Mean intraocular pressure (IOP) decreased from 21.3+/-7.9 to 12.2+/-3.9mm Hg at 12 months (P<0.001) in all patients. A significant reduction in mean number of glaucoma medications (P<0.001) was also seen. There was no change in logMAR visual acuity (P=0.39) after 12 months. There were no significant intergroup differences in mean IOP (P=0.42), number of glaucoma medications (P=0.85), or logMAR visual acuity (P=0.42) between the trabeculectomy versus combined surgery groups after 12 months. Increased age, greater baseline IOP, limbus-based conjunctival flaps, and MMC duration >1 minute were associated with decreased risk of surgical failure. Concurrent phacoemulsification at the time of trabeculectomy did not alter tonometric success or rate of complications. Conclusions: In phakic patients with PACG, trabeculectomy with MMC significantly reduces IOP and number of glaucoma medications at 12 months without change in visual acuity. However, success rates are modest when based on more demanding tonometric criteria. C1 [Song, Brian J.; Ramanathan, Meera; Morales, Esteban; Law, Simon K.; Giaconi, JoAnn A.; Coleman, Anne L.; Caprioli, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Song, Brian J.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Ramanathan, Meera] Banner Good Samaritan Med Ctr, Dept Med, Phoenix, AZ USA. RP Song, BJ (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM brian_song@meei.harvard.edu FU Research to Prevent Blindness Inc. FX Supported by an unrestricted departmental grant from Research to Prevent Blindness Inc. NR 26 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD SEP PY 2016 VL 25 IS 9 BP 763 EP 769 DI 10.1097/IJG.0000000000000493 PG 7 WC Ophthalmology SC Ophthalmology GA DX6VB UT WOS:000384521100018 PM 27513900 ER PT J AU Cagney, DN Alexander, BM Hodi, FS Buchbinder, EI Ott, PA Aizer, AA AF Cagney, Daniel N. Alexander, Brian M. Hodi, F. Stephen Buchbinder, Elizabeth I. Ott, Patrick A. Aizer, Ayal A. TI Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Melanoma; Target therapy; Intracranial disease ID WHOLE-BRAIN RADIOTHERAPY; STAGE-IV MELANOMA; SURGICAL RESECTION; MEK INHIBITION; SOLID TUMORS; VEMURAFENIB; SURVIVAL; CANCER; RADIOSURGERY; DABRAFENIB AB Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care. C1 [Cagney, Daniel N.; Alexander, Brian M.; Aizer, Ayal A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Hodi, F. Stephen; Buchbinder, Elizabeth I.; Ott, Patrick A.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Cagney, DN (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM dcagney@lroc.harvard.edu FU Richard Steevens Scholarship FX D. N. Cagney, reports contribution made by Richard Steevens Scholarship 2015. B. M. Alexander reports consulting for Amgen, Abbvie, and Precision Health Economics. F. S. Hodi reports receiving clinical trial support to his institution from Bristol-Myers Squibb as well as consulting for Merck, Genentech, Synta. E. I. Buchbinder reports receiving clinical trial support to her institution from Bristol-Myers Squibb. P. A. Ott reports receiving clinical trial support to his institution from Bristol-Myers Squibb, Merck, and Armo Biosciences as well as consulting for Amgen, Bristol-Myers Squibb, and Alexion. NR 26 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2016 VL 129 IS 3 BP 389 EP 393 DI 10.1007/s11060-016-2196-8 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DX7JU UT WOS:000384563800001 ER PT J AU Mi, Z Halfter, W Abrahamson, EE Klunk, WE Mathis, CA Mufson, EJ Ikonomovic, MD AF Mi, Zhiping Halfter, Willi Abrahamson, Eric E. Klunk, William E. Mathis, Chester A. Mufson, Elliott J. Ikonomovic, Milos D. TI Tenascin-C Is Associated with Cored Amyloid-beta Plaques in Alzheimer Disease and Pathology Burdened Cognitively Normal Elderly SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE beta-amyloid; Alzheimer disease; Astrocytes; Extracellular matrix; Inflammation; Microglia; Tau; Tenascin ID GLYCOGEN-SYNTHASE KINASE-3-BETA; PITTSBURGH COMPOUND-B; EXTRACELLULAR-MATRIX; NEUROFIBRILLARY TANGLES; SULFATE PROTEOGLYCANS; NEURITIC PLAQUES; A-BETA; NEUROPATHOLOGIC ASSESSMENT; FIBRIL FORMATION; TAU-PROTEIN AB Tenascin-C (TN-C) is an extracellular matrix glycoprotein linked to inflammatory processes in pathological conditions including Alzheimer disease (AD). We examined the distribution of TN-C immunoreactivity (ir) in relation to amyloid-beta (A beta) plaques and vascular A beta deposits in autopsy brain tissues from 14 patients with clinical and neuropathological AD and 10 aged-matched controls with no cognitive impairment; 5 of the controls had A beta plaques and 5 did not. TN-C ir was abundant in cortical white matter and subpial cerebral gray matter in all cases, whereas TN-C ir was weak in blood vessels. In all cases with A beta plaques but not in plaque-free controls, TN-C ir was detected as large (> 100 mm in diameter) diffuse extracellular deposits in cortical grey matter. TN-C plaques completely overlapped and surrounded cored A beta plaques labeled with X-34, a fluorescent derivative of Congo red, and they were associated with reactive astrocytes astrocytes, microglia and phosphorylated tau-containing dystrophic neurites. Diffuse A beta plaques lacking amyloid cores, reactive glia or dystrophic neurites showed no TN-C ir. In cases with cerebral amyloid angiopathy, TN-C ir in vessel walls did not spread into the surrounding neuropil. These results suggest a role for TN-C in A beta plaque pathogenesis and its potential as a biomarker and therapy target. C1 [Mi, Zhiping; Abrahamson, Eric E.; Klunk, William E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Halfter, Willi] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. [Klunk, William E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Mi, Zhiping; Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mufson, Elliott J.] Barrow Neurol Inst, Dept Neurobiol, Pittsburgh, PA USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, BST South, 200 Lothrop St,Room S521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu FU NIA NIH HHS [P01 AG025204, P50 AG005133] NR 72 TC 2 Z9 2 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2016 VL 75 IS 9 BP 868 EP 876 DI 10.1093/jnen/nlw062 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DX8WJ UT WOS:000384671300005 PM 27444354 ER PT J AU Piel, J AF Piel, Jennifer TI Informed Consent in Right-To-Try Cases SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material ID EXPANDED ACCESS C1 [Piel, Jennifer] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Piel, Jennifer] VA Puget Sound Hlth Care Syst, 1660 South Columbian Way, Seattle, WA 98108 USA. RP Piel, J (reprint author), VA Puget Sound Hlth Care Syst, 1660 South Columbian Way, Seattle, WA 98108 USA. EM jennifer.piel@va.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 EI 1943-3662 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PD SEP 1 PY 2016 VL 44 IS 3 BP 290 EP 296 PG 7 WC Law; Psychiatry SC Government & Law; Psychiatry GA DX6SB UT WOS:000384512300001 PM 27644860 ER PT J AU Tregouet, DA Delluc, A Roche, A Derbois, C Olaso, R Germain, M de Andrade, M Tang, W Chasman, DI Vlieg, AV Reitsma, PH Kabrhel, C Smith, N Morange, PE AF Tregouet, D. A. Delluc, A. Roche, A. Derbois, C. Olaso, R. Germain, M. de Andrade, M. Tang, W. Chasman, D. I. Vlieg, A. van Hylckama Reitsma, P. H. Kabrhel, C. Smith, N. Morange, P. E. TI Is there still room for additional common susceptibility alleles for venous thromboembolism? SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE genetic polymorphisms; genome-wide association study; meta-analysis; risk factors; venous thromboembolism ID GENOME-WIDE ASSOCIATION; LOCI; INDIVIDUALS AB Background: Through a meta-analysis of 12 genome-wide association studies, the International Network against VENous Thrombosis (INVENT) consortium identified two novel susceptibility loci for venous thromboembolism (VTE). This project has also generated other candidates that need to be confirmed. Objectives: To assess the association with VTE of common single-nucleotide polymorphisms (SNPs) that demonstrated strong statistical, but not genome-wide, significance in the INVENT cohorts. Patients/methods: Eleven SNPs were genotyped and tested for association with VTE in three case-control studies totaling 3019 patients and 2605 healthy individuals. Results and conclusions: None of the tested SNPs showed evidence for association with VTE. Different strategies are needed to decipher the whole spectrum of common and rare genetic variations associated with VTE risk. C1 [Tregouet, D. A.; Germain, M.] Univ Paris 04, Team Genom & Pathophysiol Cardiovasc Dis, INSERM, Univ Paris 06,UMR S 1166, Paris, France. [Tregouet, D. A.; Germain, M.] ICAN Inst Cardiometab & Nutr, Paris, France. [Delluc, A.] Univ Brest, EA3878, Brest, France. [Delluc, A.] Univ Brest, CIC1412, Brest, France. [Roche, A.] Hop Europeen Georges Pompidou, AP HP, Serv Pneumol & Soins Intensifs Resp, Paris, France. [Roche, A.] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Roche, A.] Inserm UMR S1140, Paris, France. [Derbois, C.; Olaso, R.] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France. [de Andrade, M.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. [Tang, W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Chasman, D. I.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chasman, D. I.] Harvard Med Sch, Boston, MA USA. [Vlieg, A. van Hylckama] Leiden Univ, Med Ctr, Dept Thrombosis & Hemostasis, Dept Clin Epidemiol, Leiden, Netherlands. [Reitsma, P. H.] Leiden Univ, Med Ctr, Dept Thrombosis & Hemostasis, Einthoven Lab Expt Vasc Med, Leiden, Netherlands. [Kabrhel, C.] Harvard Med Sch, Massachusetts Gen Hosp, Channing Network Med, Dept Emergency Med, Boston, MA USA. [Smith, N.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, N.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Smith, N.] VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Morange, P. E.] Aix Marseille Univ, La Timone Hosp, Haematol Lab, Marseille, France. [Morange, P. E.] Aix Marseille Univ, Nutr Obes & Risk Thrombosis, Unite Mixte Rech St UMR S 1062, INSERM, Marseille, France. RP Tregouet, DA (reprint author), INSERM UMR S 1166, Room 405,4th Floor,91 Blvd Hop, F-75013 Paris, France. EM david.tregouet@upmc.fr RI van Hylckama Vlieg, Astrid/A-3323-2017; OI Kabrhel, Christopher/0000-0002-8699-7176 FU NHLBI [R01HL116854, 1R01HL116854]; GenMed LABEX [ANR-10-LABX-0013]; French Clinical Research Infrastructure Network on Venous Thrombo-Embolism (F-CRIN INNOVTE); ICAN Institute for Cardiometabolism and Nutrition [ANR-10-IAHU-05] FX This work was conducted as part of the INVENT consortium; a list of contributors is given in the Appendix. This study received grant support from NHLBI R01HL116854 and NHLBI 1R01HL116854. This work was partially supported by the GenMed LABEX (ANR-10-LABX-0013), the French Clinical Research Infrastructure Network on Venous Thrombo-Embolism (F-CRIN INNOVTE), and the ICAN Institute for Cardiometabolism and Nutrition (ANR-10-IAHU-05). We thank C. Dulary and F. Dos Santos for their technical support in genotyping MARTHA12, FARIVE and EDITH samples. NR 5 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2016 VL 14 IS 9 BP 1798 EP 1802 DI 10.1111/jth.13392 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DY0ZL UT WOS:000384824600017 PM 27326655 ER PT J AU Gao, F McDaniel, J Chen, EY Rockwell, H Lynes, MD Tseng, YH Sarangarajan, R Narain, NR Kiebish, MA AF Gao, Fei McDaniel, Justice Chen, Emily Y. Rockwell, Hannah Lynes, Matthew D. Tseng, Yu-Hua Sarangarajan, Rangaprasad Narain, Niven R. Kiebish, Michael A. TI Monoacylglycerol Analysis Using MS/MSALL Quadruple Time of Flight Mass Spectrometry SO METABOLITES LA English DT Article DE monoacyglycerols; MS/MSALL; mass spectrometry; QTOF; acylglycerols ID BROWN ADIPOSE-TISSUE; DATA-INDEPENDENT ACQUISITION; SHOTGUN LIPIDOMICS; BIOLOGICAL SAMPLES; CRUDE EXTRACTS; FATTY-ACIDS; IDENTIFICATION; 2-ARACHIDONOYLGLYCEROL; QUANTIFICATION; RECEPTOR AB Monoacylglycerols (MAGs) are structural and bioactive metabolites critical for biological function. Development of facile tools for measuring MAG are essential to understand its role in different diseases and various pathways. A data-independent acquisition method, MS/MSALL, using electrospray ionization (ESI) coupled quadrupole time of flight mass spectrometry (MS), was utilized for the structural identification and quantitative analysis of individual MAG molecular species. Compared with other acylglycerols, diacylglycerols (DAG) and triacylglycerols (TAG), MAG characteristically presented as a dominant protonated ion, [M + H](+), and under low collision energy as fatty acid-like fragments due to the neutral loss of the glycerol head group. At low concentrations (<10 pmol/mu L), where lipid-lipid interactions are rare, there was a strong linear correlation between ion abundance and MAG concentration. Moreover, using the MS/MSALL method the major MAG species from human plasma and mouse brown and white adipose tissues were quantified in less than 6 min. Collectively, these results demonstrate that MS/MSALL analysis of MAG is an enabling strategy for the direct identification and quantitative analysis of low level MAG species from biological samples with high throughput and sensitivity. C1 [Gao, Fei; McDaniel, Justice; Chen, Emily Y.; Rockwell, Hannah; Sarangarajan, Rangaprasad; Narain, Niven R.; Kiebish, Michael A.] BERG LLC, 500 Old Connecticut Path,Bldg B,3rd Floor, Framingham, MA 01701 USA. [Lynes, Matthew D.; Tseng, Yu-Hua] Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA. RP Kiebish, MA (reprint author), BERG LLC, 500 Old Connecticut Path,Bldg B,3rd Floor, Framingham, MA 01701 USA. EM Fei.Gao@Berghealth.com; Justice.McDaniel@Berghealth.com; Emily.Chen@Berghealth.com; Hannah.Rockwell@Berghealth.com; Matthew.lynes@joslin.harvard.edu; yu-hua.tseng@joslin.harvard.edu; Rangaprasad.Sarangarajan@Berghealth.com; Niven.Narain@Berghealth.com; Michael.Kiebish@BergHealth.com NR 34 TC 1 Z9 1 U1 3 U2 3 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2218-1989 J9 METABOLITES JI Metabolites PD SEP PY 2016 VL 6 IS 3 AR 25 DI 10.3390/metabo6030025 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX3HV UT WOS:000384265100006 ER PT J AU Wang, ZB Ma, XS Hu, MW Jiang, ZZ Meng, TG Dong, MZ Fan, LH Ouyang, YC Snapper, SB Schatten, H Sun, QY AF Wang, Zhen-Bo Ma, Xue-Shan Hu, Meng-Wen Jiang, Zong-Zhe Meng, Tie-Gang Dong, Ming-Zhe Fan, Li-Hua Ouyang, Ying-Chun Snapper, Scott B. Schatten, Heide Sun, Qing-Yuan TI Oocyte-specific deletion of N-WASP does not affect oocyte polarity, but causes failure of meiosis II completion SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE N-WASP; oocyte; polarity; meiosis II; cytokinesis ID MOUSE OOCYTES; ARP2/3 COMPLEX; ACTIN-FILAMENTS; MEIOTIC SPINDLE; CHROMOSOME SEGREGATION; INVADOPODIUM FORMATION; ASYMMETRIC DIVISION; FAMILY PROTEINS; CDC42; ACTIVATION AB There is an unexplored physiological role of N-WASP (neural Wiskott-Aldrich syndrome protein) in oocyte maturation that prevents completion of second meiosis. In mice, N-WASP deletion did not affect oocyte polarity and asymmetric meiotic division in first meiosis, but did impair midbody formation and second meiosis completion. N-WASP regulates actin dynamics and participates in various cell activities through the RHO-GTPase-Arp2/3 (actin-related protein 2/3 complex) pathway, and specifically the Cdc42 (cell division cycle 42)-N-WASP-Arp2/3 pathway. Differences in the functions of Cdc42 have been obtained from in vitro compared to in vivo studies. By conditional knockout of N-WASP in mouse oocytes, we analyzed its in vivo functions by employing a variety of different methods including oocyte culture, immunofluorescent staining and live oocyte imaging. Each experiment was repeated at least three times, and data were analyzed by paired-samples t-test. Oocyte-specific deletion of N-WASP did not affect the process of oocyte maturation including spindle formation, spindle migration, polarity establishment and maintenance, and homologous chromosome or sister chromatid segregation, but caused failure of cytokinesis completion during second meiosis (P < 0.001 compared to control). Further analysis showed that a defective midbody may be responsible for the failure of cytokinesis completion. The present study did not include a detailed analysis of the mechanisms underlying the results, which will require more extensive further investigations. N-WASP may play an important role in mediating and co-ordinating the activity of the spindle (midbody) and actin (contractile ring constriction) when cell division occurs. The findings are important for understanding the regulation of oocyte meiosis completion and failures in this process that affect oocyte quality. None. This work was supported by the National Basic Research Program of China (No. 2012CB944404) and the National Natural Science Foundation of China (Nos 30930065, 31371451, 31272260 and 31530049). There are no potential conflicts of interests. C1 [Wang, Zhen-Bo; Ma, Xue-Shan; Hu, Meng-Wen; Jiang, Zong-Zhe; Meng, Tie-Gang; Dong, Ming-Zhe; Fan, Li-Hua; Ouyang, Ying-Chun; Sun, Qing-Yuan] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, 1 Beichen West Rd, Beijing 100101, Peoples R China. [Wang, Zhen-Bo; Meng, Tie-Gang; Fan, Li-Hua; Sun, Qing-Yuan] Univ Chinese Acad Sci, Beijing 100101, Peoples R China. [Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Snapper, Scott B.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Schatten, Heide] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. RP Sun, QY (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, 1 Beichen West Rd, Beijing 100101, Peoples R China. EM sunqy@ioz.ac.cn FU National Basic Research Program of China [2012CB944404]; National Natural Science Foundation of China [30930065, 31371451, 31272260, 31530049] FX The National Basic Research Program of China (No. 2012CB944404) and the National Natural Science Foundation of China (Nos 30930065, 31371451, 31272260 and 31530049). NR 33 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 EI 1460-2407 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD SEP PY 2016 VL 22 IS 9 BP 613 EP 621 DI 10.1093/molehr/gaw046 PG 9 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA DW5UA UT WOS:000383711200002 PM 27401749 ER PT J AU Rabin, JS Olsen, RK Gilboa, A Buchsbaum, BR Rosenbaum, RS AF Rabin, Jennifer S. Olsen, Rosanna K. Gilboa, Asaf Buchsbaum, Bradley R. Rosenbaum, R. Shayna TI Using fMRI to understand event construction in developmental amnesia SO NEUROPSYCHOLOGIA LA English DT Article DE Developmental amnesia; Case study; fMRI; Hippocampus; Autobiographical memory; Imagining ID MEDIAL-TEMPORAL-LOBE; AUTOBIOGRAPHICAL MEMORY RETRIEVAL; BRAINS DEFAULT NETWORK; EPISODIC MEMORY; HIPPOCAMPAL DAMAGE; COUNTERFACTUAL THINKING; FUNCTIONAL NEUROANATOMY; COGNITIVE NEUROSCIENCE; FUTURE THINKING; SEMANTIC MEMORY AB Recently, neuroimaging and patient-lesion methods have been combined to explain anomalies such as patients' intact performance on tasks on which they would be predicted to perform poorly. In some cases, preserved performance has been attributed to activation of residual tissue within the damaged region. However, activation of remnant tissue can also occur in relation to impaired performance and, thus, may not necessarily correspond to successful recruitment. To constrain these neuroimaging interpretations, what is needed is a paradigm with closely matched conditions that yields intact and impaired performance in the same patient. We investigated this in H.C., an amnesic person with congenital abnormalities of the hippocampus and its connections, who was scanned during remembering and imagining, abilities known to depend on the hippocampus. Specifically, we examined whether differences in activation and/or functional connectivity would explain H.C.'s compromised ability to construct events relating to herself in autobiographical memory (SELF condition) and events relating to personally familiar others (FAMILIAR condition) versus her intact ability to construct events relating to unknown others (UNFAMILIAR condition). Despite behavioral dissociations in H.C., the pattern of activation and functional connectivity supporting her performance was strikingly similar to that of controls across conditions. Most notably, like controls, H.C. showed robust hippocampal activation and functional connectivity to the hippocampus, both when her performance was intact and impaired. Across all conditions, H.C. activated several extra-hippocampal regions to a greater extent than did controls, and modest differences were observed in functional connectivity between extra-hippocampal regions. Taken together, these findings urge caution when drawing conclusions about the functional integrity of a structurally compromised brain region even when it is activated and/or co-activated with other regions. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Rabin, Jennifer S.; Rosenbaum, R. Shayna] York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. [Olsen, Rosanna K.; Gilboa, Asaf; Buchsbaum, Bradley R.; Rosenbaum, R. Shayna] Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Olsen, Rosanna K.; Gilboa, Asaf; Buchsbaum, Bradley R.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Gilboa, Asaf; Rosenbaum, R. Shayna] Heart & Stroke Fdn Canadian Partnership Stroke Re, Toronto, ON, Canada. RP Rosenbaum, RS (reprint author), York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada.; Rabin, JS (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. FU Canadian Institutes of Health Research (CIHR) [MOP 93535]; NSERC [405649]; Focus on Stroke Doctoral Research Award FX This paper is dedicated to Morris Moscovitch in honor of his festschrift. Morris' work emphasizes the value of studying single neurological cases along with the importance of showing the human side of patient research. In that spirit, we thank H.C. and other individuals with memory impairment for their involvement in research and the invaluable contributions that they make to memory theory. The research reported in this paper was funded by a Canadian Institutes of Health Research (CIHR) Operating Grant MOP 93535 and New Investigator Award to R.S.R. A.G. acknowledges NSERC grant 405649, and J.S.R. acknowledges a Focus on Stroke Doctoral Research Award. NR 74 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 2016 VL 90 SI SI BP 261 EP 273 DI 10.1016/j.neuropsychologia.2016.07.036 PG 13 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA DY0MK UT WOS:000384790700025 PM 27477629 ER PT J AU Tan-Shalaby, JL Carrick, J Edinger, K Genovese, D Liman, AD Passero, VA Shah, RB AF Tan-Shalaby, Jocelyn L. Carrick, Jennifer Edinger, Krystal Genovese, Dana Liman, Andrew D. Passero, Vida A. Shah, Rashmikant B. TI Modified Atkins diet in advanced malignancies-final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System (vol 13, 52, 2016) SO NUTRITION & METABOLISM LA English DT Correction C1 [Tan-Shalaby, Jocelyn L.; Carrick, Jennifer; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.; Shah, Rashmikant B.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Tan-Shalaby, Jocelyn L.; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Tan-Shalaby, JL (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.; Tan-Shalaby, JL (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM jocelyn.tan@va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-7075 J9 NUTR METAB JI Nutr. Metab. PD SEP 1 PY 2016 VL 13 AR 61 DI 10.1186/s12986-016-0120-z PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DX7QQ UT WOS:000384584000001 PM 27594893 ER PT J AU Pandol, SJ Forsmark, CE Hart, PA AF Pandol, Stephen J. Forsmark, Chris E. Hart, Phil A. CA Consortium Study Chronic Pancreati TI Acceleration of our understanding of recurrent acute and chronic pancreatitis SO PANCREATOLOGY LA English DT Editorial Material ID FIBROSIS; RISK C1 [Pandol, Stephen J.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Pandol, Stephen J.] US Dept Vet Affairs, Los Angeles, CA 90024 USA. [Forsmark, Chris E.] Univ Florida, Gainesville, FL USA. [Hart, Phil A.] Ohio State Univ, Div Gastroenterol Hepatol & Nutr, Wexner Med Ctr, Columbus, OH 43210 USA. RP Pandol, SJ (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.; Pandol, SJ (reprint author), US Dept Vet Affairs, Los Angeles, CA 90024 USA. EM Stephen.Pandol@cshs.org RI Hart, Phil/A-9842-2016 OI Hart, Phil/0000-0003-4346-6196 FU NIDDK NIH HHS [U01 DK108314] NR 12 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD SEP-OCT PY 2016 VL 16 IS 5 BP 692 EP 693 DI 10.1016/j.pan.2016.08.002 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY0KM UT WOS:000384785700002 PM 27542963 ER PT J AU Fagenholz, PJ Thabet, A Mueller, PR Forcione, DG AF Fagenholz, Peter J. Thabet, Ashraf Mueller, Peter R. Forcione, David G. TI Combined endoscopic trangastric drainage and video assisted retroperitoneal pancreatic debridement - The best of both worlds for extensive pancreatic necrosis with enteric fistulae SO PANCREATOLOGY LA English DT Article DE Pancreatitis; Debridement; Endoscopy; Video-assisted surgery; Digestive system fistula ID STEP-UP APPROACH; NECROTIZING PANCREATITIS AB Enteric fistula is a serious complication of necrotizing pancreatitis. Endoscopic transluminal drainage and necrosectomy can significantly reduce the incidence of enterocutaneous fistula after pancreatic debridement. However, endoscopic necrosectomy may not be well-suited to debridement of necrosis that tracks laterally to the paracolic gutters, which is often more efficiently addressed by video-assisted retroperitoneal debridement (VARD). We report the combined use of endoscopic transgastric drainage and VARD for treatment of a 76 year old man with severe necrotizing acute pancreatitis complicated by infected, walled-off pancreatic necrosis. Computed tomography showed laterally tracking pancreatic necrosis and flouroscopic drain injection after percutaneous drainage demonstrated with fistulas to the stomach, duodenum, and colon. The infection and fistulas resolved completely. This approach combined the major advantage of VARD with the major advantage of endoscopic transluminal drainage. We are not aware of any reports of combining these techniques and believe the combination offers a minimally invasive approach for patients with extensive necrosis and a high likelihood of enteric or pancreatic fistulas. (C) 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved. C1 [Fagenholz, Peter J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Thabet, Ashraf; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Forcione, David G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Fagenholz, Peter J.; Thabet, Ashraf; Mueller, Peter R.; Forcione, David G.] Harvard Med Sch, Boston, MA USA. RP Fagenholz, PJ (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM pfagenholz@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD SEP-OCT PY 2016 VL 16 IS 5 BP 788 EP 790 DI 10.1016/j.pan.2016.06.009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY0KM UT WOS:000384785700017 PM 27344627 ER PT J AU Lopez, I Zapata, L Sosa, JJ Rodgers, C Ruiz, M Oh, S Hynan, LS Kimball, AB Pandya, AG AF Lopez, Isha Zapata, Lucio Sosa, Juan Jesus Rodgers, Clifford Ruiz, Maria Oh, Susan Hynan, Linda S. Kimball, Alexa B. Pandya, Amit G. TI Acne Knowledge of Hispanic Parents of Teenagers with Mild to Moderate Acne SO PEDIATRIC DERMATOLOGY LA English DT Article AB We performed a cross-sectional study of Hispanic and non-Hispanic parents of children with acne using a survey designed to determine their level of awareness of acne and its treatment; 82% of Hispanic parents and 40% of non-Hispanic parents agreed that a health care provider should treat mild acne (p < 0.001). Hispanic parents of adolescents with acne agreed more frequently than non-Hispanic parents that children with mild and moderate acne should be taken to a health care provider for treatment, but they tended not to visit health care providers. Future studies should aim to determine the reasons for this discrepancy, after which culturally sensitive educational programs can be developed to address this disparity. C1 [Lopez, Isha; Zapata, Lucio; Sosa, Juan Jesus; Rodgers, Clifford; Ruiz, Maria; Oh, Susan; Pandya, Amit G.] Univ Texas Southwestern Med Ctr, Dept Dermatol, Dallas, TX USA. [Hynan, Linda S.] Univ Texas Southwestern Med Ctr, Dept Clin Sci Biostat, Dallas, TX USA. [Hynan, Linda S.] Univ Texas Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Lopez, I (reprint author), Univ Texas Southwestern Dallas, Dept Dermatol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Isha.e.lopez@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2016 VL 33 IS 5 BP E292 EP E293 DI 10.1111/pde.12934 PG 2 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA DW4OH UT WOS:000383622200013 PM 27397689 ER PT J AU Burgo-Black, AL Brown, JL Boyce, RM Hunt, SC AF Burgo-Black, A. Lucile Brown, Jeffrey L. Boyce, Ross M. Hunt, Stephen C. TI The Importance of Taking a Military History SO PUBLIC HEALTH REPORTS LA English DT Article DE veteran's health; military culture training; deployment health ID CARE; VETERANS; IRAQ; AFGHANISTAN; FAMILIES C1 [Burgo-Black, A. Lucile] Yale Univ, Sch Med, New Haven, CT USA. [Burgo-Black, A. Lucile] VA Connecticut Healthcare Syst, West Haven, CT USA. [Burgo-Black, A. Lucile; Hunt, Stephen C.] Vet Hlth Adm, Postdeployment Integrated Care Initiat, Patient Care Serv, Washington, DC USA. [Brown, Jeffrey L.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Brown, Jeffrey L.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. [Boyce, Ross M.] Univ North Carolina Chapel Hill, Div Infect Dis, Chapel Hill, NC USA. [Hunt, Stephen C.] Univ Washington, Dept Med, Seattle, WA USA. [Hunt, Stephen C.] VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Burgo-Black, AL (reprint author), Yale Univ, VA Connecticut Healthcare Syst, Gen Internal Med Primary Care, 20 Kenter Pl, New Haven, CT 06515 USA. EM lucille.burgo@va.gov NR 20 TC 0 Z9 0 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0033-3549 EI 1468-2877 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2016 VL 131 IS 5 BP 711 EP 713 DI 10.1177/0033354916660073 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DX3LT UT WOS:000384275300010 PM 28123212 ER PT J AU Cypel, YS Hamlett-Berry, K Barth, SK Christofferson, DE Davey, VJ Eber, S Schneiderman, AI Bossarte, RM AF Cypel, Yasmin S. Hamlett-Berry, Kim Barth, Shannon K. Christofferson, Dana E. Davey, Victoria J. Eber, Stephanie Schneiderman, Aaron I. Bossarte, Robert M. TI Cigarette Smoking and Sociodemographic, Military, and Health Characteristics of Operation Enduring Freedom and Operation Iraqi Freedom Veterans: 2009-2011 National Health Study for a New Generation of US Veterans SO PUBLIC HEALTH REPORTS LA English DT Article DE veterans; cigarettes; smoking; OEF/OIF; Operation Iraqi Freedom; Operation Enduring Freedom; health; Afghanistan; Iraq ID POSTTRAUMATIC-STRESS-DISORDER; POPULATION-BASED COHORT; GENDER-DIFFERENCES; NICOTINE DEPENDENCE; SUBSTANCE USE; TOBACCO USE; AIR-FORCE; AFGHANISTAN; PREVALENCE; PERSONNEL AB Objective: We examined the sociodemographic, military, and health characteristics of current cigarette smokers, former smokers, and nonsmokers among Operation Enduring Freedom (OEF) / Operation Iraqi Freedom (OIF) veterans and estimated smoking prevalence to better understand cigarette use in this population. Methods: We analyzed data from the US Department of Veterans Affairs (VA) 2009-2011 National Health Study for a New Generation of US Veterans. On the basis of a stratified random sample of 60 000 OEF/OIF veterans, we sought responses to a 72-item questionnaire via mail, telephone, or Internet. Cigarette smoking status was based on self-reported cigarette use in the past year. We used multinomial logistic regression to evaluate associations between smoking status and sociodemographic, military, and health characteristics. Results: Among 19 911 veterans who provided information on cigarette smoking, 5581 were current smokers (weighted percentage: 32.5%, 95% confidence interval [CI]: 31.7-33.2). Current smokers were more likely than nonsmokers or former smokers to be younger, to have less education or income, to be separated/divorced or never married/single, and to have served on active duty or in the army. Comparing current smokers and nonsmokers, some significant associations from adjusted analyses included the following: having a Mental Component Summary score (a measure of overall mental health) above the mean of the US population relative to below the mean (adjusted odds ratio [aOR] = 0.81, 95% CI: 0.73-0.90); having physician diagnosed depression (aOR = 1.52, 95% CI: 1.33-1.74), respiratory conditions (aOR = 1.16, 95% CI: 1.04-1.30), or repeated seizures/blackouts/convulsions (aOR = 1.80, 95% CI: 1.22-2.67); heavy alcohol use vs never use (aOR = 5.49, 95% CI: 4.57-6.59); a poor vs excellent perception of overall health (aOR = 3.79, 95% CI: 2.60-5.52); and being deployed vs nondeployed (aOR = 0.87, 95% CI: 0.78-0.96). Using health care services from the VA protected against current smoking. Conclusion: Mental and physical health, substance use, and military service characteristics shape cigarette-smoking patterns in OEF/OIF veterans. C1 [Cypel, Yasmin S.; Barth, Shannon K.; Eber, Stephanie; Schneiderman, Aaron I.; Bossarte, Robert M.] US Dept Vet Affairs, Vet Hlth Adm, Off Patient Care Serv, Postdeployment Hlth Serv, Washington, DC USA. [Hamlett-Berry, Kim; Christofferson, Dana E.] US Dept Vet Affairs, Vet Hlth Adm, Off Patient Care Serv, Mental Hlth Serv, Washington, DC USA. [Davey, Victoria J.] US Dept Vet Affairs, Vet Hlth Adm, Off Res & Dev, Washington, DC USA. RP Cypel, YS (reprint author), US Dept Vet Affairs, Vet Hlth Adm, Postdeployment Hlth Serv 10P4Q, 810 Vermont Ave NW, Washington, DC 20420 USA. EM yasmin.cypel@va.gov FU VA Post-Deployment Health Services, Epidemiology Program FX This study was funded by the VA Post-Deployment Health Services, Epidemiology Program. The views expressed in this article are solely those of the authors and do not necessarily reflect the position or policy of the VA or the US government. NR 67 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0033-3549 EI 1468-2877 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2016 VL 131 IS 5 BP 714 EP 727 DI 10.1177/0033354916664864 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DX3LT UT WOS:000384275300011 PM 28123213 ER PT J AU Treger, R Hanna, RM Lee, BM Lopez, EA Wilson, J Corry, D AF Treger, Richard Hanna, Ramy M. Lee, Brian M. Lopez, Eduardo A. Wilson, James Corry, Dalila TI Delayed clearance of hepatitis B surface antigen and development of hepatitis B surface antibody in a chronic hemodialysis patient SO SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION LA English DT Article ID VIRUS INFECTION; NATURAL-HISTORY; CIRRHOSIS; DISEASE; SEROCONVERSION; VACCINATION; LOAD AB The introduction of hepatitis B vaccination and infection control in 1977 has greatly decreased the prevalence of hepatitis B. Currently, approximately 2.8% of the end-stage renal disease population is hepatitis B positive with a presence in 27.7% of the USA hemodialysis (HD) units according to the Dialysis Outcomes and Practice Patterns Study data. The behavior of hepatitis B infection differs significantly between immunocompetent and immunosuppressed hosts. Immunosuppressed hosts present more subtly with complications of chronic hepatitis B infection, being more challenging to detect. It is also well known that patients with chronic infection on HD have a small chance of clearing the virus. We report here a case of a hepatitis B positive HD patient who underwent spontaneous delayed serological clearance of hepatitis B surface antigen and development of immunity via appearance of hepatitis B surface antibody. This is a rare occurrence, and the few similar reported cases will be discussed. C1 [Treger, Richard; Corry, Dalila] Greater Los Angeles Vet Affairs Healthcare Syst, Div Nephrol, Los Angeles, CA USA. [Treger, Richard; Hanna, Ramy M.; Lee, Brian M.; Wilson, James; Corry, Dalila] UCLA, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Treger, Richard; Hanna, Ramy M.; Lee, Brian M.; Wilson, James; Corry, Dalila] Olive View UCLA Med Ctr, Div Nephrol, Los Angeles, CA USA. [Hanna, Ramy M.] Cedars Sinai Med Ctr, Dept Med, Div Nephrol, Los Angeles, CA 90048 USA. [Lopez, Eduardo A.] Kaiser Permanente Panorama City, Dept Nephrol, Los Angeles, CA USA. [Wilson, James] UCLA, David Geffen Sch Med, Director UCLA Stone Ctr, Surg Consultat Nephrol, Los Angeles, CA 90095 USA. RP Hanna, RM (reprint author), Cedars Sinai Med Ctr, Off Towers,8635 West Third St,Suite 495, Los Angeles, CA 90048 USA. EM rhannamd81@yahoo.com OI Hanna, Ramy/0000-0003-1807-8909 NR 22 TC 0 Z9 0 U1 1 U2 1 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1319-2442 EI 2320-3838 J9 SAUDI J KIDNEY DIS T JI Saudi J. Kidney Dis. Transplant. PD SEP-OCT PY 2016 VL 27 IS 5 BP 1047 EP 1051 DI 10.4103/1319-2442.190886 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA DX7JL UT WOS:000384562800028 PM 27752020 ER PT J AU Aronow, HD Kennedy, KF Wayangankar, SA Katzen, BT Schneider, PA Abou-Chebl, A Rosenfield, KA AF Aronow, Herbert D. Kennedy, Kevin F. Wayangankar, Siddharth A. Katzen, Barry T. Schneider, Peter A. Abou-Chebl, Alex Rosenfield, Kenneth A. TI Prescription of Guideline-Based Medical Therapies at Discharge After Carotid Artery Stenting and Endarterectomy: An NCDR Analysis SO STROKE LA English DT Article DE carotid endarterectomy; carotid stenosis; carotid stent; drug therapy; stroke ID VASCULAR-SURGERY; INTERVENTIONAL-RADIOLOGY; WRITING COMMITTEE; TASK-FORCE; STENOSIS; DISEASE; ANGIOGRAPHY; PREVENTION; MANAGEMENT; INITIATION AB Background and Purpose Carotid artery revascularization was previously found to incrementally reduce stroke risk among patients with carotid stenosis treated with medical therapy. However, the frequency with which optimal medical therapies are used at discharge after carotid endarterectomy (CEA) and carotid artery stenting (CAS) is not known, and the influence of patient, operator, and hospital characteristics on the likelihood of prescription is poorly understood. Methods In a retrospective cohort study of 23112 patients undergoing CAS or CEA between January 2007 and June 2012 at US hospitals participating in the CARE registry (Carotid Artery Revascularization and Endarterectomy), we examined antiplatelet therapy and statin utilization at discharge. Hierarchical multivariable logistic regression was used in adjusted analyses. Results Antiplatelet agents and statins were prescribed at discharge in 99% and 78%, respectively, after CAS and 93% and 75%, respectively, after CEA. After adjustment, antiplatelet therapy was more often prescribed after CAS than CEA (odds ratio 2.4 [95% confidence interval 1.68-3.45]), but statin prescription was equally likely (odds ratio 1.11 [95% confidence interval 0.84-1.49]). Operator specialty (medical>radiology/surgery) and hospital community setting (suburban>urban>rural) independently predicted antiplatelet and statin agent use at discharge, whereas hospital geographic location (Northeast>Midwest/South>West) predicted use of statins but not antiplatelet therapy at discharge. Conclusions US antiplatelet agent and statin discharge prescription rates were suboptimal after both CAS and CEA and varied by revascularization modality, operating physician specialty, and hospital characteristics. Improved and more uniform utilization after these procedures will be critical to the success of comprehensive stroke risk reduction efforts. C1 [Aronow, Herbert D.] Brown Univ, Warren Alpert Med Sch, Cardiovasc Inst, Providence, RI USA. [Kennedy, Kevin F.] Mid Amer Heart Inst, Kansas City, MO USA. [Wayangankar, Siddharth A.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Katzen, Barry T.] Miami Cardiac & Vasc Inst, Miami, FL USA. [Schneider, Peter A.] Kaiser Permanente, Med Ctr, Honolulu, HI USA. [Abou-Chebl, Alex] Baptist Hlth, Louisville, KY USA. [Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Aronow, HD (reprint author), 593 Eddy St,RIH APC 730, Providence, RI 02903 USA. EM herbert.aronow@lifespan.org FU Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; American Academy of Neurology; American Association of Neurological Surgeons/Congress of Neurological Surgeons; Society for Vascular Medicine; Society of Vascular and Interventional Neurology; ACCF's NCDR FX The CARE Registry is an initiative of the American College of Cardiology Foundation (ACCF) with partnering support from the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, American Academy of Neurology, American Association of Neurological Surgeons/Congress of Neurological Surgeons, Society for Vascular Medicine, and the Society of Vascular and Interventional Neurology. This research was supported by the ACCF's NCDR. The NCDR CARE Registry Research & Publications Committee reviewed and approved the design and conduct of the study; collection, management, analysis, and interpretation of the data. This committee was not involved in preparation of the article but did participate in its review and approval. NR 20 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 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2016 VL 47 IS 9 BP 2339 EP 2346 DI 10.1161/STROKEAHA.116.012981 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DW3RD UT WOS:000383559300039 PM 27507868 ER PT J AU Arora, R Salamon, E Katz, JM Cox, M Saver, JL Bhatt, DL Fonarow, GC Peterson, ED Smith, EE Schwamm, LH Xian, Y Libman, RB AF Arora, Rohan Salamon, Elliott Katz, Jeffrey M. Cox, Margueritte Saver, Jeffrey L. Bhatt, Deepak L. Fonarow, Gregg C. Peterson, Eric D. Smith, Eric E. Schwamm, Lee H. Xian, Ying Libman, Richard B. TI Use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients >= 90 Years of Age SO STROKE LA English DT Article DE hospices; hospital mortality; stroke; thrombolytic therapy; tissue-type plasminogen activator ID PLASMINOGEN-ACTIVATOR; GUIDELINES-STROKE; NONAGENARIANS; ASSOCIATION; MANAGEMENT; MORTALITY; CARE AB Background and Purpose Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged 90 years. Methods We analyzed data from the Get With The Guidelines-Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged 90 and 3 younger age groups (18-64, 65-79, and 80-89 years). Results Among 35708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were 90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged 90 years (67.4% versus 84.1% in 18-89-year olds; P<0.0001). Discharge outcomes among individuals aged 90 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged 90 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds. Conclusions The use of intravenous tPA among those aged 90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower. C1 [Arora, Rohan; Salamon, Elliott; Katz, Jeffrey M.; Libman, Richard B.] Hofstra Northwell Sch Med, Dept Neurol, Hempstead, NY USA. [Cox, Margueritte] Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC USA. [Peterson, Eric D.] Duke Clin Res Inst, Dept Med, Div Cardiol, Durham, NC USA. [Xian, Ying] Duke Clin Res Inst, Dept Neurol, Durham, NC USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Bhatt, Deepak L.] Womens Heart & Vasc Ctr, Boston, MA USA. [Bhatt, Deepak L.] Harvard Med Sch, Boston, MA USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Saver, JL (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Comprehens Stroke Ctr, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM jsaver@mednet.ucla.edu FU Medtronic; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; Janseen Pharmaceutical Company of Johnson Johnson; Janseen Pharmaceutical Company of AHA Pharmaceutical Roundtable FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke 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. NR 20 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 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2016 VL 47 IS 9 BP 2347 EP 2354 DI 10.1161/STROKEAHA.116.012241 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DW3RD UT WOS:000383559300040 PM 27491734 ER PT J AU Charidimou, A Pasi, M Fiorelli, M Shams, S von Kummer, R Pantoni, L Rost, N AF Charidimou, Andreas Pasi, Marco Fiorelli, Marco Shams, Sara von Kummer, Ruediger Pantoni, Leonardo Rost, Natalia TI Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke A Meta-Analysis (v1) SO STROKE LA English DT Article DE cerebral small vessel disease; intracerebral hemorrhage; leukoaraiosis; thrombolysis; white matter hyperintensities ID WHITE-MATTER LESIONS; TISSUE-PLASMINOGEN ACTIVATOR; INTRACEREBRAL HEMORRHAGE; RISK-FACTOR; MICROBLEEDS; AGE; CT; ASSOCIATION; SEVERITY; COHORT AB Background and Purpose We performed a meta-analysis to assess whether leukoaraiosis on brain computed tomographic scans of acute ischemic stroke patients treated with intravenous thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at 3 to 6 months after stroke, or both. Methods We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin Score >2. Results Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95% confidence interval [CI], 1.17-2.06; P=0.002) and severe leukoaraiosis (OR, 2.53; 95% CI, 1.92-3.34; P<0.0001) compared with patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976; adjusted OR, 1.75; 95% CI, 1.35-2.27; P<0.0001). OR for leukoaraiosis and poor 3- to 6-month outcome was 2.02 (95% CI, 1.54-2.65; P<0.0001), with significant statistical heterogeneity (I-2, 75.7%; P=0.002). In adjusted analyses, leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR, 1.61; 95% CI, 1.44-1.79; P<0.0001). In post hoc analyses, including only leukoaraiosis patients in randomized controlled trials (IST-3 [third International Stroke Trial], NINDS [National Institute of Neurological Disorders and Stroke], ECASS-1-2 [European Cooperative Acute Stroke Study]; n=2234), tissue-type plasminogen activator versus control was associated with higher sICH risk (OR, 5.50; 95% CI, 2.49-12.13), but lower poor outcome risk (OR, 0.75; 95% CI, 0.60-0.95). Conclusions Leukoaraiosis might increase post-intravenous thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk, intravenous tissue-type plasminogen activator treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding intravenous thrombolysis. C1 [Charidimou, Andreas; Pasi, Marco; Rost, Natalia] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Charidimou, Andreas; Pasi, Marco; Rost, Natalia] Harvard Med Sch, 175 Cambridge St, Boston, MA 02114 USA. [Fiorelli, Marco] Univ Roma La Sapienza, Dept Neurol & Psychiat, Viale Univ 30, Rome, Italy. [Shams, Sara] Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden. [von Kummer, Ruediger] Dresden Univ, Stroke Ctr, Inst Diagnost & Intervent Neuroradiol, Dresden, Germany. [Pasi, Marco; Pantoni, Leonardo] Univ Florence, NEUROFARBA Dept, Neurosci Sect, I-50121 Florence, Italy. RP Charidimou, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Clin Neurol, 175 Cambridge St, Boston, MA 02114 USA. EM andreas.charidimou.09@ucl.ac.uk FU NIH-NINDS [R01 NS082285, R01 NS086905] FX R. von Kummer reports personal fees from Boehringer Ingelheim during the conduct of ECASS-1-2, H. Lundbeck A/S, Covidien, Brainsgate, and Penumbra, Inc outside the submitted work. N. Rost is in part supported by NIH-NINDS R01 NS082285 and R01 NS086905. NR 31 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2016 VL 47 IS 9 BP 2364 EP 2372 DI 10.1161/STROKEAHA.116.014096 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DW3RD UT WOS:000383559300043 PM 27491738 ER PT J AU Delaney, M Stark, PC Suh, M Triulzi, DJ Hess, JR Steiner, ME Stowell, CP Sloan, SR AF Delaney, M. Stark, P. C. Suh, M. Triulzi, D. J. Hess, J. R. Steiner, M. E. Stowell, C. P. Sloan, S. R. TI Massive Transfusion in Cardiac Surgery: The Impact of Blood Component Ratios on Clinical Outcomes and Survival SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting CY OCT 22-25, 2016 CL Orlando, FL SP AABB C1 [Delaney, M.] Bloodworks NW, Med, Seattle, WA USA. [Delaney, M.; Hess, J. R.] Univ Washington, Lab Med, Seattle, WA 98195 USA. [Stark, P. C.; Suh, M.] New England Res Inst, Data Coordinating Ctr, 9 Galen St, Watertown, MA 02172 USA. [Triulzi, D. J.] Univ Pittsburgh, Pathol, Pittsburgh, PA USA. [Triulzi, D. J.] Inst Transfus Med, Pittsburgh, PA USA. [Hess, J. R.] Harborview Med Ctr, Seattle, WA USA. [Steiner, M. E.] Univ Minnesota, Minneapolis, MN USA. [Stowell, C. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stowell, C. P.; Sloan, S. R.] Harvard Med Sch, Boston, MA USA. [Sloan, S. R.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD SEP PY 2016 VL 56 SU 4 SI SI MA P1-030A BP 3A EP 3A DI 10.1111/trf.13807 PG 1 WC Hematology SC Hematology GA DX8NS UT WOS:000384646400002 ER PT J AU Mack, J Mansfield, P Haspel, RL Horn, T Keller, JA Keller, MA AF Mack, J. Mansfield, P. Haspel, R. L. Horn, T. Keller, J. A. Keller, M. A. TI A Novel JK*A Allele in a Jk(a-b-) Patient with Anti-Jk3 and Anti-Jka SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting CY OCT 22-25, 2016 CL Orlando, FL SP AABB C1 [Mack, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mansfield, P.] Amer Red Cross, Immunohematol Reference Lab, Philadelphia, PA USA. [Haspel, R. L.] Beth Israel Deaconess Med Ctr, Pathol, Boston, MA 02215 USA. [Horn, T.; Keller, J. A.; Keller, M. A.] Amer Red Cross, Natl Mol Lab, Philadelphia, PA 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 SEP PY 2016 VL 56 SU 4 SI SI MA SP324 BP 156A EP 156A PG 1 WC Hematology SC Hematology GA DX8NS UT WOS:000384646400428 ER PT J AU Horn, T Keller, JA Pucillo, TM Iqbal, J Mansfield, P Keller, MA AF Horn, T. Keller, J. A. Pucillo, T. M. Iqbal, J. Mansfield, P. Keller, M. A. TI Novel RHCE*ce Alleles Containing c.307T Cause C Typing Discrepancies SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting CY OCT 22-25, 2016 CL Orlando, FL SP AABB C1 [Horn, T.; Keller, J. A.; Keller, M. A.] Amer Red Cross, Natl Mol Lab, Philadelphia, PA USA. [Pucillo, T. M.] Amer Red Cross, Immunohematol Reference Lab, Baltimore, MD USA. [Mansfield, P.] Amer Red Cross, Immunohematol Reference Lab, Philadelphia, PA USA. [Iqbal, J.] Vet Affairs Greater Los Angeles Healthcare Syst, Pathol & Lab Med, Los Angeles, CA 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 SEP PY 2016 VL 56 SU 4 SI SI MA SP334 BP 159A EP 159A PG 1 WC Hematology SC Hematology GA DX8NS UT WOS:000384646400438 ER PT J AU Dumas, O Varraso, R Gillman, MW Field, AE Camargo, CA AF Dumas, O. Varraso, R. Gillman, M. W. Field, A. E. Camargo, C. A., Jr. TI Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma SO ALLERGY LA English DT Article DE allergy; childhood asthma; developmental origins of health and disease; gestational weight gain; maternal obesity ID PREPREGNANCY OBESITY; CHILDHOOD ASTHMA; BIRTH COHORT; EARLY-LIFE; PREGNANCY; CHILDREN; DISEASE; GENDER; RISK; DETERMINANTS AB BackgroundSparse data are available on the relationship between prenatal exposures and asthma during later childhood. In a longitudinal study of adolescents and their mothers, we examined the association of (i) maternal prepregnancy body mass index (BMI) and (ii) gestational weight gain (GWG), with incidence of allergic and nonallergic asthma in offspring. MethodsAnalyses were conducted using data from 12 963 children aged 9-14 years at enrolment in the Growing Up Today Study, and their mothers, who are participants in the Nurses' Health Study II. Physician-diagnosed asthma and allergies were assessed by questionnaires sent regularly to participants and their mothers. Logistic regression was used to evaluate associations of maternal BMI and GWG with offspring asthma, overall and by subtype. ResultsPhysician-diagnosed asthma during childhood or adolescence was reported by 2694 children (21%). Maternal prepregnancy overweight (OR: 1.19, 95% CI: 1.03-1.38) and obesity (1.34, 1.08-1.68) were associated with offspring asthma. In asthma subtype analyses, the association was seen only for asthma onset before age 12 years. Moreover, the association of maternal obesity with nonallergic asthma was observed in boys (2.39, 1.40-4.09) and not in girls (0.96, 0.50-1.85; P-interaction = 0.03); the opposite pattern was suggested for allergic asthma. With regard to GWG, an association was suggested between gains of <15 lb and higher risk of offspring asthma (1.28, 0.98-1.66), without clear allergy- or sex-related patterns. ConclusionThe relation of several prenatal factors to risk of childhood asthma supports the early origins hypothesis for asthma. The observed allergy- and sex-specific patterns suggest multiple etiologic pathways. C1 [Dumas, O.; Field, A. E.; Camargo, C. A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Dumas, O.; Field, A. E.; Camargo, C. A., Jr.] Harvard Med Sch, Boston, MA USA. [Dumas, O.; Camargo, C. A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Suite 920, Boston, MA 02114 USA. [Dumas, O.; Varraso, R.] VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, INSERM, Villejuif, France. [Dumas, O.; Varraso, R.] Univ Versailles St Quentin En Yvelines, UVSQ, UMR S 1168, Montigny Le Bretonneux, France. [Gillman, M. W.] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Gillman, M. W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Field, A. E.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA USA. [Field, A. E.; Camargo, C. A., Jr.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Suite 920, Boston, MA 02114 USA. EM ccamargo@partners.org RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU National Institutes of Health [R01 HL84401, UM1 CA176726] FX National Institutes of Health R01 HL84401, UM1 CA176726. NR 45 TC 1 Z9 1 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2016 VL 71 IS 9 BP 1295 EP 1304 DI 10.1111/all.12876 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DS7DC UT WOS:000380942000007 PM 26969855 ER PT J AU Zhou, L Dhopeshwarkar, N Blumenthal, KG Goss, F Topaz, M Slight, SP Bates, DW AF Zhou, L. Dhopeshwarkar, N. Blumenthal, K. G. Goss, F. Topaz, M. Slight, S. P. Bates, D. W. TI Drug allergies documented in electronic health records of a large healthcare system SO ALLERGY LA English DT Article DE adverse drug event; drug allergy; drug hypersensitivity; electronic health records; safety ID EMERGENCY-DEPARTMENT VISITS; UNITED-STATES; HOSPITALIZED-PATIENTS; PRESCRIBING-PATTERNS; INTOLERANCE SYNDROME; ANAPHYLAXIS; RISK; EPIDEMIOLOGY; PREVALENCE; POPULATION AB BackgroundThe prevalence of drug allergies documented in electronic health records (EHRs) of large patient populations is understudied. ObjectiveWe aimed to describe the prevalence of common drug allergies and patient characteristics documented in EHRs of a large healthcare network over the last two decades. MethodsDrug allergy data were obtained from EHRs of patients who visited two large tertiary care hospitals in Boston from 1990 to 2013. The prevalence of each drug and drug class was calculated and compared by sex and race/ethnicity. The number of allergies per patient was calculated and the frequency of patients having 1, 2, 3..., or 10+ drug allergies was reported. We also conducted a trend analysis by comparing the proportion of each allergy to the total number of drug allergies over time. ResultsAmong 1 766 328 patients, 35.5% of patients had at least one reported drug allergy with an average of 1.95 drug allergies per patient. The most commonly reported drug allergies in this population were to penicillins (12.8%), sulfonamide antibiotics (7.4%), opiates (6.8%), and nonsteroidal anti-inflammatory drugs (NSAIDs) (3.5%). The relative proportion of allergies to angiotensin-converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors (statins) have more than doubled since early 2000s. Drug allergies were most prevalent among females and white patients except for NSAIDs, ACE inhibitors, and thiazide diuretics, which were more prevalent in black patients. ConclusionFemales and white patients may be more likely to experience a reaction from common medications. An increase in reported allergies to ACE inhibitors and statins is noteworthy. C1 [Zhou, L.; Dhopeshwarkar, N.; Topaz, M.; Slight, S. P.; Bates, D. W.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Zhou, L.] Partners HealthCare Syst, Clin Informat, Partners ECare, Boston, MA USA. [Zhou, L.; Topaz, M.; Bates, D. W.] Harvard Med Sch, Boston, MA USA. [Blumenthal, K. G.] Massachusetts Gen Hosp, Allergy & Immunol, Boston, MA 02114 USA. [Goss, F.] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Slight, S. P.] Univ Durham, Div Pharm, Sch Med Pharm & Hlth, Durham, England. RP Zhou, L (reprint author), Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. EM lzhou2@partners.org FU Agency for Healthcare Research and Quality (AHRQ) [R01HS022728] FX This study was funded by the Agency for Healthcare Research and Quality (AHRQ) grant R01HS022728. NR 38 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2016 VL 71 IS 9 BP 1305 EP 1313 DI 10.1111/all.12881 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA DS7DC UT WOS:000380942000008 PM 26970431 ER PT J AU Grant, CC Crane, J Mitchell, EA Sinclair, J Stewart, A Milne, T Knight, J Gilchrist, C Camargo, CA AF Grant, C. C. Crane, J. Mitchell, E. A. Sinclair, J. Stewart, A. Milne, T. Knight, J. Gilchrist, C. Camargo, C. A., Jr. TI Vitamin D supplementation during pregnancy and infancy reduces aeroallergen sensitization: a randomized controlled trial SO ALLERGY LA English DT Article DE asthma; infant; pregnancy; supplementation; Vitamin D; 25-hydroxyvitamin D ID HOUSE-DUST MITE; SERUM 25-HYDROXYVITAMIN D; NEW-ZEALAND; RISK-FACTORS; ASTHMA; CHILDREN; CHILDHOOD; PREVENTION; ALLERGEN; COHORT AB BackgroundVitamin D has immune-modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations. MethodsA randomized, double-blind, placebo-controlled parallel-group trial. We assigned pregnant women, from 27-week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum-specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough. ResultsSpecific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der-f1, Der-f2) and Dermatophagoides pteronyssinus (Der-p1, Der-p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der-f1 (18%, 10%, 2%), Der-f2 (14%, 3%, 2%), Der-p1 (19%, 14%, 3%) and Der-p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses. ConclusionsVitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed. C1 [Grant, C. C.; Mitchell, E. A.; Milne, T.; Gilchrist, C.] Univ Auckland, Dept Paediat Child Youth Hlth, Auckland, New Zealand. [Grant, C. C.; Sinclair, J.] Starship Childrens Hosp, Auckland, New Zealand. [Crane, J.] Univ Otago, Med, Wellington, New Zealand. [Stewart, A.; Knight, J.] Univ Auckland, Epidemiol & Biostat, Auckland, New Zealand. [Camargo, C. A., Jr.] Harvard Med Sch, Emergency Med, Massachusetts Gen Hosp, Boston, MA USA. RP Grant, CC (reprint author), Univ Auckland, Dept Paediat Child & Youth Hlth, Fac Med & Hlth Sci, Private Bag 92019,Wellesley St, Auckland 1142, New Zealand. EM cc.grant@auckland.ac.nz OI Knight, Andrew/0000-0001-5268-8263; Grant, Cameron/0000-0002-4032-7230; Gilchrist, Catherine/0000-0002-7467-7933 NR 48 TC 5 Z9 5 U1 7 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD SEP PY 2016 VL 71 IS 9 BP 1325 EP 1334 DI 10.1111/all.12909 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA DS7DC UT WOS:000380942000010 PM 27060679 ER PT J AU Guo, MH Dauber, A Lippincott, MF Chan, YM Salem, RM Hirschhorn, JN AF Guo, Michael H. Dauber, Andrew Lippincott, Margaret F. Chan, Yee-Ming Salem, Rany M. Hirschhorn, Joel N. TI Determinants of Power in Gene-Based Burden Testing for Monogenic Disorders SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; RARE-VARIANT ASSOCIATION; EXOME VARIANTS; DISEASES; LINKAGE; RISK; FRAMEWORK; COMMON AB Whole-exome sequencing has enabled new approaches for discovering genes associated with monogenic disorders. One such approach is gene-based burden testing, in which the aggregate frequency of "qualifying variants" is compared between case and control subjects for each gene. Despite substantial successes of this approach, the genetic causes for many monogenic disorders remain unknown or only partially known. It is possible that particular genetic architectures lower rates of discovery, but the influence of these factors on power has not been rigorously evaluated. Here, we leverage large-scale exome-sequencing data to create an empirically based simulation framework to evaluate the impact of key parameters (background variation rates, locus heterogeneity, mode of inheritance, penetrance) on power in gene-based burden tests in the context of monogenic disorders. Our results demonstrate that across genes, there is a wide range in sample sizes needed to achieve power due to differences in the background rate of rare variants in each gene. Increasing locus heterogeneity results in rapid increases in sample sizes needed to achieve adequate power, particularly when individual genes contribute to less than 5% of cases under a dominant model. Interestingly, incomplete penetrance as low as 10% had little effect on power due to the low prevalence of monogenic disorders. Our results suggest that moderate incomplete penetrance is not an obstacle in this gene-based burden testing approach but that dominant disorders with high locus heterogeneity will require large sample sizes. Our simulations also provide guidance on sample size needs and inform study design under various genetic architectures. C1 [Guo, Michael H.; Chan, Yee-Ming; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Guo, Michael H.; Salem, Rany M.; Hirschhorn, Joel N.] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Guo, Michael H.; Salem, Rany M.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Guo, Michael H.; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Dauber, Andrew] Cincinnati Childrens Hosp Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. [Lippincott, Margaret F.; Chan, Yee-Ming] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. [Lippincott, Margaret F.; Chan, Yee-Ming] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. RP Hirschhorn, JN (reprint author), Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA.; Hirschhorn, JN (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Hirschhorn, JN (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Hirschhorn, JN (reprint author), Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. EM joelh@broadinstitute.org FU NIH-NIDDK [R01DK075787]; NIH-NICHD [K23HD073351, P50 HD028138]; DDCF [2013110]; NIH-NHLBI [1K99HL122515-01A1] FX We thank members of the J.N.H. lab for insightful feedback. We thank Monkol Lek and Daniel MacArthur and the ExAC consortium for joint variant calling of the exome-sequencing data used throughout this paper. M.H.G. and J.N.H. are supported by NIH-NIDDK award R01DK075787. A.D. was supported by NIH-NICHD award K23HD073351. Y.-M.C. was supported by DDCF grant 2013110. M.F.L. was supported by NIH-NICHD award P50 HD028138. R.M.S. was support by NIH-NHLBI award 1K99HL122515-01A1. NR 38 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP 1 PY 2016 VL 99 IS 3 BP 527 EP 539 DI 10.1016/j.ajhg.2016.06.031 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA DV7KM UT WOS:000383114800001 PM 27545677 ER PT J AU Muona, M Ishimura, R Laari, A Ichimura, Y Linnankivi, T Keski-Filppula, R Herva, R Rantala, H Paetau, A Poyhonen, M Obata, M Uemura, T Karhu, T Bizen, N Takebayashi, H McKee, S Parker, MJ Akawi, N McRae, J Hurles, ME Kuismin, O Kurki, MI Anttonen, AK Tanaka, K Palotie, A Waguri, S Lehesjoki, AE Komatsus, M AF Muona, Mikko Ishimura, Ryosuke Laari, Anni Ichimura, Yoshinobu Linnankivi, Tarja Keski-Filppula, Riikka Herva, Riitta Rantala, Heikki Paetau, Anders Poyhonen, Minna Obata, Miki Uemura, Takefumi Karhu, Thomas Bizen, Norihisa Takebayashi, Hirohide McKee, Shane Parker, Michael J. Akawi, Nadia McRae, Jeremy Hurles, Matthew E. Kuismin, Outi Kurki, Mitja I. Anttonen, Anna-Kaisa Tanaka, Keiji Palotie, Aarno Waguri, Satoshi Lehesjoki, Anna-Elina Komatsus, Masaaki CA DDD Study TI Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DNA-SEQUENCING DATA; FOLD MODIFIER; DISCOVERY; DISRUPTION; FRAMEWORK; SYSTEM; MICE AB The ubiquitin fold modifier 1 (UFM1) cascade is a recently identified evolutionarily conserved ubiquitin-like modification system whose function and link to human disease have remained largely uncharacterized. By using exome sequencing in Finnish individuals with severe epileptic syndromes, we identified pathogenic compound heterozygous variants in UBAS, encoding an activating enzyme for UFM1, in two unrelated families. Two additional individuals with biallelic UBAS variants were identified from the UK-based Deciphering Developmental Disorders study and one from the Northern Finland Intellectual Disability cohort. The affected individuals (n = 9) presented in early infancy with severe irritability, followed by dystonia and stagnation of development. Furthermore, the majority of individuals display postnatal microcephaly and epilepsy and develop spasticity. The affected individuals were compound heterozygous for a missense substitution, c.1111G>A (p.A1a371Thr; allele frequency of 0.28% in Europeans), and a nonsense variant or c.164G>A that encodes an amino acid substitution p.Arg5SHis, but also affects splicing by facilitating exon 2 skipping, thus also being in effect a loss-of-function allele. Using an in vitro thioester formation assay and cellular analyses, we show that the p.A1a371Thr variant is hypomorphic with attenuated ability to transfer the activated UFM1 to UFC1. Finally, we show that the CNS-specific knockout of Ufml in mice causes neonatal death accompanied by microcephaly and apoptosis in specific neurons, further suggesting that the UFM1 system is essential for CNS development and function. Taken together, our data imply that the combination of a hypomorphic p.A1a371Thr variant in trans with a loss-of-function allele in UBAS underlies a severe infantile-onset encephalopathy. C1 [Muona, Mikko; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland. [Muona, Mikko; Laari, Anni; Anttonen, Anna-Kaisa; Lehesjoki, Anna-Elina] Folkhalsan Inst Genet, Helsinki 00290, Finland. [Muona, Mikko; Laari, Anni; Karhu, Thomas; Anttonen, Anna-Kaisa; Lehesjoki, Anna-Elina] Univ Helsinki, Ctr Neurosci, FIN-00290 Helsinki, Finland. [Muona, Mikko; Laari, Anni; Karhu, Thomas; Anttonen, Anna-Kaisa; Lehesjoki, Anna-Elina] Univ Helsinki, Res Programs Unit, Mol Neurol, FIN-00290 Helsinki, Finland. [Ishimura, Ryosuke; Ichimura, Yoshinobu; Obata, Miki; Komatsus, Masaaki] Niigata Univ, Grad Sch Med & Dent Sci, Dept Biochem, Chuo Ku, Niigata 9518510, Japan. [Ishimura, Ryosuke; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 1568506, Japan. [Linnankivi, Tarja] Univ Helsinki, Childrens Hosp, Dept Child Neurol, FIN-00290 Helsinki, Finland. [Linnankivi, Tarja; Poyhonen, Minna] Helsinki Univ Hosp, Helsinki 00290, Finland. [Keski-Filppula, Riikka; Rantala, Heikki; Kuismin, Outi] Univ Oulu, PEDEGO Res Unit, Oulu 90014, Finland. [Keski-Filppula, Riikka; Rantala, Heikki; Kuismin, Outi] Univ Oulu, Med Res Ctr Oulu, Oulu 90014, Finland. [Keski-Filppula, Riikka; Kuismin, Outi] Oulu Univ Hosp, Dept Clin Genet, Oulu 90029, Finland. [Herva, Riitta] Oulu Univ Hosp, Dept Pathol, Canc & Translat Med Res Unit, Med Res Ctr Oulu, Oulu 90014, Finland. [Herva, Riitta] Univ Oulu, Oulu 90014, Finland. [Rantala, Heikki] Oulu Univ Hosp, Dept Children & Adolescents, Div Paediat Neurol, Oulu 90029, Finland. [Paetau, Anders] Univ Helsinki, Dept Pathol, Haartmaninkatu 3, FIN-00290 Helsinki, Finland. [Paetau, Anders] Helsinki Univ Cent Hosp, Helsinki 00290, Finland. [Poyhonen, Minna; Anttonen, Anna-Kaisa] Univ Helsinki, Med & Clin Genet, FIN-00290 Helsinki, Finland. [Uemura, Takefumi; Waguri, Satoshi] Fukushima Med Univ, Sch Med, Dept Anat & Histol, Fukushima 9601295, Japan. [Bizen, Norihisa; Takebayashi, Hirohide] Niigata Univ, Grad Sch Med & Dent Sci, Div Neurobiol & Anat, Chuo Ku, Niigata 9518510, Japan. [McKee, Shane] Belfast City Hosp, Dept Med Genet, Belfast BT9 7AB, Antrim, North Ireland. [Parker, Michael J.] Sheffield Childrens Hosp NHS Fdn Trust, Western Bank, Sheffield S10 2TH, S Yorkshire, England. [Akawi, Nadia; McRae, Jeremy; Hurles, Matthew E.; Palotie, Aarno] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England. [Kurki, Mitja I.] Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio 70029, Finland. [Kurki, Mitja I.; Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Kurki, Mitja I.; Palotie, Aarno] Harvard Med Sch, Boston, MA 02114 USA. [Kurki, Mitja I.; Palotie, Aarno] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02141 USA. [Palotie, Aarno] Broad Inst Harvard & Massachusetts Inst Technol, Stanley Ctr Psychiat Res, Cambridge, MA 02141 USA. [Palotie, Aarno] Harvard Med Sch, Program Genet & Genom Biol & Biomed Sci, Boston, MA 02114 USA. [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. [Muona, Mikko] Blueprint Genet, Helsinki 00290, Finland. RP Lehesjoki, AE (reprint author), Folkhalsan Inst Genet, Helsinki 00290, Finland.; Lehesjoki, AE (reprint author), Univ Helsinki, Ctr Neurosci, FIN-00290 Helsinki, Finland.; Lehesjoki, AE (reprint author), Univ Helsinki, Res Programs Unit, Mol Neurol, FIN-00290 Helsinki, Finland.; Komatsus, M (reprint author), Niigata Univ, Grad Sch Med & Dent Sci, Dept Biochem, Chuo Ku, Niigata 9518510, Japan. EM anna-elina.lehesjoki@helsinki.fi; komatsu-ms@med.niigata-u.ac.jp NR 31 TC 1 Z9 1 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP 1 PY 2016 VL 99 IS 3 BP 683 EP 694 DI 10.1016/j.ajhg.2016.06.020 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA DV7KM UT WOS:000383114800013 PM 27545674 ER PT J AU Kim, JH Shinde, DN Reijnders, MRF Hauser, NS Belmonte, RL Wilson, GR Bosch, DGM Bubulya, PA Shashi, V Petrovski, S Stone, JK Park, EY Veltman, JA Sinnema, M Stumpel, CTRM Draaisma, JM Nicolai, J Yntema, HG Lindstrom, K de Vries, BBA Jewett, T Santoro, SL Vogt, J Bachman, KK Seeley, AH Krokosky, A Turner, C Rohena, L Hempel, M Kortum, F Lessel, D Neu, A Strom, TM Wieczorek, D Bramswig, N Laccone, FA Behunova, J Rehder, H Gordon, CT Rio, M Romana, S Tang, S El-Khechen, D Cho, MT McWalter, K Douglas, G Baskin, B Begtrup, A Funari, T Schoch, K Stegmann, APA Stevens, SJC Zhang, DE Traver, D Yao, X MacArthur, DG Brunner, HG Mancini, GM Myers, RM Owen, LB Lim, ST Stachura, DL Vissers, LELM Ahn, EYE AF Kim, Jung-Hyun Shinde, Deepali N. Reijnders, Margot R. F. Hauser, Natalie S. Belmonte, Rebecca L. Wilson, Gregory R. Bosch, Danielle G. M. Bubulya, Paula A. Shashi, Vandana Petrovski, Slave Stone, Joshua K. Park, Eun Young Veltman, Joris A. Sinnema, Margje Stumpel, Connie T. R. M. Draaisma, Jos M. Nicolai, Joost Yntema, Helger G. Lindstrom, Kristin de Vries, Bert B. A. Jewett, Tamison Santoro, Stephanie L. Vogt, Julie Bachman, Kristine K. Seeley, Andrea H. Krokosky, Alyson Turner, Clesson Rohena, Luis Hempel, Maja Kortuem, Fanny Lessel, Davor Neu, Axel Strom, Tim M. Wieczorek, Dagmar Bramswig, Nuria Laccone, Franco A. Behunova, Jana Rehder, Helga Gordon, Christopher T. Rio, Marlene Romana, Serge Tang, Sha El-Khechen, Dima Cho, Megan T. McWalter, Kirsty Douglas, Ganka Baskin, Berivan Begtrup, Amber Funari, Tara Schoch, Kelly Stegmann, Alexander P. A. Stevens, Servi J. C. Zhang, Dong-Er Traver, David Yao, Xu MacArthur, Daniel G. Brunner, Han G. Mancini, Grazia M. Myers, Richard M. Owen, Laurie B. Lim, Ssang-Taek Stachura, David L. Vissers, Lisenka E. L. M. Ahn, Eun-Young Erin CA Univ Washington Deciphering Dev Disorders Study TI De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CELL-CYCLE PROGRESSION; MENTAL-RETARDATION; STEM-CELLS; WDR62; MALFORMATIONS; SCHIZOPHRENIA; NETWORK; DISEASE; PROTEIN; AUTISM AB The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development. C1 [Kim, Jung-Hyun; Stone, Joshua K.; Park, Eun Young; Owen, Laurie B.; Ahn, Eun-Young Erin] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA. [Shinde, Deepali N.; Tang, Sha; El-Khechen, Dima] Ambry Genet, Aliso Viejo, CA 92656 USA. [Reijnders, Margot R. F.; Bosch, Danielle G. M.; Veltman, Joris A.; Yntema, Helger G.; de Vries, Bert B. A.; Brunner, Han G.; Vissers, Lisenka E. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Hauser, Natalie S.] Valley Childrens Hosp, Med Genet & Metab, Madera, CA 93636 USA. [Belmonte, Rebecca L.; Wilson, Gregory R.; Stachura, David L.] Calif State Univ Chico, Dept Biol Sci, Chico, CA 95929 USA. [Bubulya, Paula A.] Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. [Shashi, Vandana; Schoch, Kelly] Duke Univ, Sch Med, Div Med Genet, Dept Pediat, Durham, NC 27710 USA. [Petrovski, Slave] Univ Melbourne, Dept Med, Austin Hosp, Parkville, Vic 3010, Australia. [Petrovski, Slave] Royal Melbourne Hosp, Parkville, Vic 3010, Australia. [Petrovski, Slave] Columbia Univ, Inst Genom Med, New York, NY 10027 USA. [Veltman, Joris A.; Sinnema, Margje; Stumpel, Connie T. R. M.; Stegmann, Alexander P. A.; Stevens, Servi J. C.; Brunner, Han G.] Maastricht Univ, Med Ctr, Dept Clin Genet, NL-6202 AZ Maastricht, Netherlands. [Veltman, Joris A.; Sinnema, Margje; Stumpel, Connie T. R. M.; Stegmann, Alexander P. A.; Stevens, Servi J. C.; Brunner, Han G.] Maastricht Univ, Med Ctr, Sch Oncol & Dev Biol GROW, NL-6202 AZ Maastricht, Netherlands. [Draaisma, Jos M.] Radboudumc Amalia Childrens Hosp, Dept Pediat, NL-6500 HB Nijmegen, Netherlands. [Nicolai, Joost] Maastricht Univ, Med Ctr, Dept Neurol, NL-6299 HX Maastricht, Netherlands. [Lindstrom, Kristin] Phoenix Childrens Hosp, Div Genet & Metab, Phoenix, AZ 85016 USA. [Jewett, Tamison] Wake Forest Sch Med, Sect Med Genet, Dept Pediat, Winston Salem, NC 27157 USA. [Santoro, Stephanie L.] Nationwide Childrens Hosp, Columbus, OH 43205 USA. [Santoro, Stephanie L.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Vogt, Julie] Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England. [Deciphering Dev Disorders Study] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Bachman, Kristine K.; Seeley, Andrea H.] Geisinger Med Ctr, Danville, PA 17822 USA. [Krokosky, Alyson; Turner, Clesson] Walter Reed Natl Mil Med Ctr, Div Genet, Dept Pediat, Bethesda, MD 20889 USA. [Rohena, Luis] San Antonio Mil Med Ctr, Div Genet, Dept Pediat, Ft Sam Houston, TX 78234 USA. [Rohena, Luis] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Hempel, Maja; Kortuem, Fanny; Lessel, Davor] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany. [Neu, Axel] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, D-20246 Hamburg, Germany. [Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Strom, Tim M.] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. [Wieczorek, Dagmar] Univ Dusseldorf, Inst Human Genet, Univ Clin Dusseldorf, D-40225 Dusseldorf, Germany. [Wieczorek, Dagmar; Bramswig, Nuria] Univ Duisburg Essen, Univ Clin Essen, Inst Human Genet, D-45147 Essen, Germany. [Laccone, Franco A.; Behunova, Jana; Rehder, Helga] Med Univ Vienna, Inst Med Genet, Waehringer Str 10, A-1090 Vienna, Austria. [Gordon, Christopher T.] INSERM, UMR 1163, Inst Imagine, Lab Embryol & Genet Congenital Malformat, F-75015 Paris, France. [Gordon, Christopher T.] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, France. [Rio, Marlene] Hop Necker Enfants Malad, Dept Genet, F-75015 Paris, France. [Romana, Serge] Hop Necker Enfants Malad, Serv Cytogenet, F-75015 Paris, France. [Romana, Serge] Paris Descartes Sorbonne Paris Cite Univ, Inst Imagine, F-75015 Paris, France. [Cho, Megan T.; McWalter, Kirsty; Douglas, Ganka; Baskin, Berivan; Begtrup, Amber; Funari, Tara] GeneDx Inc, 205 Perry Pkwy, Gaithersburg, MD 20877 USA. [Zhang, Dong-Er; Yao, Xu] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Zhang, Dong-Er] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Zhang, Dong-Er; Traver, David] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [MacArthur, Daniel G.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [MacArthur, Daniel G.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Mancini, Grazia M.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3015 CN Rotterdam, Netherlands. [Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Lim, Ssang-Taek; Ahn, Eun-Young Erin] Univ S Alabama, Dept Biochem & Mol Biol, Coll Med, Mobile, AL 36688 USA. RP Ahn, EYE (reprint author), Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36604 USA.; Vissers, LELM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.; Ahn, EYE (reprint author), Univ S Alabama, Dept Biochem & Mol Biol, Coll Med, Mobile, AL 36688 USA. EM lisenka.vissers@radboudumc.nl; eahn@health.southalabama.edu RI Veltman, Joris/F-5128-2010; Gordon, Christopher/F-1267-2017 OI Veltman, Joris/0000-0002-3218-8250; Gordon, Christopher/0000-0002-9300-8399 FU National Human Genome Research Institute; National Heart, Lung, and Blood Institute [1U54HG006493]; Radboudumc Genomics Technology Center for family-based sequencing; NIH [CA190688, CA185818, GM084407]; University of South Alabama Mitchell Cancer Institute; Ohio Board of Regents; California State University Chico Internal Research Grant; Stichting ODAS [5781251]; Dutch Organization for Health Research and Development [912-12-109]; Wellcome Trust; Vereniging Bartimeus-Sonneheerdt FX We are deeply grateful to all individuals and their families for participating in this study. We thank Dr. Michael Markey (Wright State University) for transcript splicing analysis, Dr. David Goldstein, Jennifer Sullivan, and Nicole Walley (Duke University) for their help in collecting clinical information, Petra de Vries (Radboudumc) and Hermann-Josef Ludecke (University Duisburg-Essen) for technical support, and Dr. Christian Gilissen (Radboudumc) for bioinformatic support. We thank the University of Washington Center for Mendelian Genomics (funded by the National Human Genome Research Institute and National Heart, Lung, and Blood Institute grant 1U54HG006493 to Drs. Debbie Nickerson, Jay Shendure, and Michael Bamshad) and the Radboudumc Genomics Technology Center for family-based sequencing. This work was supported by NIH grants (CA190688 and CA185818 to E.-Y.E.A. and GM084407 to P.A.B.), a start-up fund from the University of South Alabama Mitchell Cancer Institute (to E.-Y.E.A.), the Ohio Board of Regents (to P.A.B.), a California State University Chico Internal Research Grant (to D.L.S.), grants from Stichting ODAS and Vereniging Bartimeus-Sonneheerdt (5781251 to B.B.A.d.V. and D.G.M.B.), and a grant from the Dutch Organization for Health Research and Development (912-12-109 to B.B.A.d.V. and J.A.V.). This study used data generated by the DECIPHER Consortium. A full list of centers who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email at decipher@sanger.ac.uk. Funding for the DECIPHER project was provided by the Wellcome Trust. NR 35 TC 0 Z9 0 U1 4 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP 1 PY 2016 VL 99 IS 3 BP 711 EP 719 DI 10.1016/j.ajhg.2016.06.029 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DV7KM UT WOS:000383114800016 PM 27545680 ER PT J AU Browns, DW Damato, AL Sutlief, S Morcovescu, S Park, SJ Reiff, J Shih, A Scanderbeg, DJ AF Browns, Derek W. Damato, Antonio L. Sutlief, Steven Morcovescu, Serban Park, Sang-June Reiff, Jay Shih, Allen Scanderbeg, Daniel J. TI A consensus-based, process commissioning template for high-dose-rate gynecologic treatments SO BRACHYTHERAPY LA English DT Article DE HDR; GYN; Commissioning; Standardization; Process ID RADIATION-THERAPY; TREATMENT DELIVERY; CERVICAL-CANCER; BRACHYTHERAPY AB PURPOSE: There is a lack of prescriptive, practical information for those doing the work of commissioning high-dose-rate (HDR) gynecologic (GYN) treatment equipment. The purpose of this work is to develop a vendor-neutral, consensus-based, commissioning template to improve standardization of the commissioning process. METHODS AND MATERIALS: A series of commissioning procedures and tests specific to HDR GYN treatments were compiled within one institution. The list of procedures and tests was then sent to five external reviewers at clinics engaged in HDR GYN treatments. External reviewers were asked to (1) suggest deletions, additions, and improvements/modifications to descriptions, (2) link the procedures and tests to common, severe failure modes based on their effectiveness at mitigating those failure modes, and (3) rank the procedures and tests based on perceived level of importance. RESULTS: External reviewers suggested the addition of 14 procedures and tests. The final template consists of 67 procedures and tests. "Treatment process" and "staff training" sections were identified as mitigating the highest number of commonly reported failure modes. The mean perceived importance for all procedures and tests was 4.4 of 5, and the mean for each section ranged from 3.6 to 4.8. Sections of the template that were identified as mitigating the highest number of commonly reported failure modes were not assigned the highest perceived importance. CONCLUSION: The commissioning template developed here provides a standardized approach to process and equipment commissioning. The discord between perceived importance and mitigation of the highest number of failure modes suggests that increased focus should be placed on procedures and tests in "treatment process" and "staff training" sections. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Browns, Derek W.; Sutlief, Steven; Scanderbeg, Daniel J.] Univ Calif San Diego, Deparment Radiat Med & Appl Sci, La Jolla, CA USA. [Damato, Antonio L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Damato, Antonio L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Morcovescu, Serban] Texas Oncol, Denton, TX USA. [Park, Sang-June] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA. [Reiff, Jay] Drexel Univ, Coll Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Shih, Allen] Kaiser Permanente Santa Clara, Canc Treatment Ctr, Santa Clara, CA USA. RP Browns, DW (reprint author), Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA. EM d7brown@ucsd.edu OI Sutlief, Steven/0000-0001-9369-9153 NR 22 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 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD SEP-OCT PY 2016 VL 15 IS 5 BP 570 EP 577 DI 10.1016/j.brachy.2016.05.003 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DX0FS UT WOS:000384037800006 PM 27364873 ER PT J AU Scarlett, UK Chang, DC Murtagh, TJ Flaherty, KT AF Scarlett, Uciane K. Chang, Dennis C. Murtagh, Thomas J. Flaherty, Keith T. TI High-Throughput Testing of Novel-Novel Combination Therapies for Cancer: An Idea Whose Time Has Come SO CANCER DISCOVERY LA English DT Editorial Material ID CHEMOTHERAPY AB Combination therapies are essential to address the genetic complexity, plasticity, and heterogeneity of tumors and to overcome resistance mechanisms that confound single-agent approaches, and are a paradigm that became well established in the era of conventional cytotoxic chemotherapies. Today, we are well equipped to address many of the scientific, clinical, and collaboration challenges that have existed historically; however, the pace of testing rational combinations is modest. Our analysis shows that the volume of clinical trials testing multiple investigational pipeline agents ("novel-novel" combinations) is dismally low, as out of approximately 1,500 phase I to III investigational combination trials initiated in 2014-2015, only 80 were for novel-novel combinations, and only 9 of those involved more than one company. The Collaborative Novel-Novel Combination Therapies (CoNNCT) initiative aims to alleviate this bottleneck by developing a new, faster paradigm for early investigation of scientifically informed, novel-novel drug combinations. The initiative kicked off on March 7, 2016, when representatives from top academic centers, biopharma, nonprofits, the FDA, and other groups gathered to define an actionable path forward. (C) 2016 AACR. C1 [Scarlett, Uciane K.; Chang, Dennis C.; Murtagh, Thomas J.] Clarion Healthcare LLC, Boston, MA USA. [Flaherty, Keith T.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Scarlett, UK (reprint author), Clarion Healthcare, Financial Ctr 1, Suite 1610, Boston, MA 02111 USA. EM uscarlett@clarionhealthcare.com NR 17 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD SEP PY 2016 VL 6 IS 9 BP 956 EP 962 DI 10.1158/2159-8290.CD-16-0440 PG 7 WC Oncology SC Oncology GA DW0TT UT WOS:000383356400021 PM 27587468 ER PT J AU Mishra, A La Perle, K Kwiatkowski, S Sullivan, LA Sams, GH Johns, J Curphey, DP Wen, J McConnell, K Qi, J Wong, H Russo, G Zhang, JY Marcucci, G Bradner, JE Porcu, P Caligiuri, MA AF Mishra, Anjali La Perle, Krista Kwiatkowski, Sonya Sullivan, Laura A. Sams, Gregory H. Johns, Jessica Curphey, Douglas P. Wen, Jing McConnell, Kathleen Qi, Jun Wong, Henry Russo, Giandomenico Zhang, Jianying Marcucci, Guido Bradner, James E. Porcu, Pierluigi Caligiuri, Michael A. TI Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma SO CANCER DISCOVERY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; DNA METHYLATION; HDAC INHIBITORS; NATURAL-KILLER; CANCER; EXPRESSION; INTERLEUKIN-15 AB Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15. Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotypespecific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL. SIGNIFICANCE: To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. C) 2016 AACR. C1 [Mishra, Anjali; Wong, Henry] Ohio State Univ, Dept Internal Med, Div Dermatol, Columbus, OH 43210 USA. [Mishra, Anjali; La Perle, Krista; Kwiatkowski, Sonya; Sullivan, Laura A.; Sams, Gregory H.; Johns, Jessica; Curphey, Douglas P.; Wen, Jing; McConnell, Kathleen; Wong, Henry; Porcu, Pierluigi; Caligiuri, Michael A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Mishra, Anjali; La Perle, Krista; Kwiatkowski, Sonya; Sullivan, Laura A.; Sams, Gregory H.; Johns, Jessica; Curphey, Douglas P.; Wen, Jing; McConnell, Kathleen; Wong, Henry; Porcu, Pierluigi; Caligiuri, Michael A.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [La Perle, Krista] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA. [Qi, Jun; Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Russo, Giandomenico] Ist Ricovero & Cura Carattere Sci, Ist Dermopat Immacolata, Rome, Italy. [Zhang, Jianying] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Marcucci, Guido] City Hope Med Ctr, Beckman Res Inst, Norbert Gehr & Family Leukemia Ctr, Div Hematopoiet Stem Cell & Leukemia Res, Duarte, CA USA. [Caligiuri, Michael A.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. RP Mishra, A; Porcu, P; Caligiuri, MA (reprint author), Ohio State Univ, 460 West 10th Ave,Suite D920, Columbus, OH 43210 USA. EM Pierluigi.Porcu@osumc.edu; Michael.Caligiuri@osumc.edu FU Galderma FX H. Wong is a consultant/advisory board member for Actelion and Seattle Genetics. J.E. Bradner is President at Novartis Institute of BioMedical Research. P. Porcu reports receiving a commercial research grant from Galderma. No potential conflicts of interest were disclosed by the other authors. NR 86 TC 3 Z9 3 U1 3 U2 3 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 SEP PY 2016 VL 6 IS 9 BP 986 EP 1005 DI 10.1158/2159-8290.CD-15-1297 PG 20 WC Oncology SC Oncology GA DW0TT UT WOS:000383356400024 PM 27422033 ER PT J AU Zhang, HK Qi, J Reyes, JM Li, L Rao, PK Li, FG Lin, CY Perry, JA Lawlor, MA Federation, A De Raedt, T Li, YY Liu, Y Duarte, MA Zhang, YX Herter-Sprie, GS Kikuchi, E Carretero, J Perou, CM Reibel, JB Paulk, J Bronson, RT Watanabe, H Brainson, CF Kim, CF Hammerman, PS Brown, M Cichowski, K Long, H Bradner, JE Wong, KK AF Zhang, Haikuo Qi, Jun Reyes, Jaime M. Li, Lewyn Rao, Prakash K. Li, Fugen Lin, Charles Y. Perry, Jennifer A. Lawlor, Matthew A. Federation, Alexander De Raedt, Thomas Li, Yvonne Y. Liu, Yan Duarte, Melissa A. Zhang, Yanxi Herter-Sprie, Grit S. Kikuchi, Eiki Carretero, Julian Perou, Charles M. Reibel, Jacob B. Paulk, Joshiawa Bronson, Roderick T. Watanabe, Hideo Brainson, Christine Fillmore Kim, Carla F. Hammerman, Peter S. Brown, Myles Cichowski, Karen Long, Henry Bradner, James E. Wong, Kwok-Kin TI Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer SO CANCER DISCOVERY LA English DT Article ID ZESTE HOMOLOG 2; GROUP PROTEIN EZH2; B-CELL LYMPHOMAS; SELECTIVE-INHIBITION; HISTONE METHYLTRANSFERASE; SUPER-ENHANCERS; BREAST-CANCER; EXPRESSION; MUTATIONS; GENE AB As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non-small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS - and EGFR - mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a potent open-source EZH2 inhibitor, JQEZ5, that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer. SIGNIFICANCE: EZH2 overexpression induces murine lung cancers that are similar to human NSCLC with high EZH2 expression and low levels of phosphorylated AKT and ERK, implicating biomarkers for EZH2 inhibitor sensitivity. Our EZH2 inhibitor, JQEZ5, promotes regression of these tumors, revealing a potential role for anti-EZH2 therapy in lung cancer. (C) 2016 AACR. C1 [Zhang, Haikuo; Qi, Jun; Reyes, Jaime M.; Lin, Charles Y.; Perry, Jennifer A.; Lawlor, Matthew A.; Federation, Alexander; Li, Yvonne Y.; Liu, Yan; Zhang, Yanxi; Herter-Sprie, Grit S.; Kikuchi, Eiki; Reibel, Jacob B.; Paulk, Joshiawa; Watanabe, Hideo; Hammerman, Peter S.; Bradner, James E.; Wong, Kwok-Kin] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Zhang, Haikuo; Qi, Jun; De Raedt, Thomas; Li, Yvonne Y.; Liu, Yan; Zhang, Yanxi; Herter-Sprie, Grit S.; Kikuchi, Eiki; Reibel, Jacob B.; Watanabe, Hideo; Hammerman, Peter S.; Brown, Myles; Cichowski, Karen; Bradner, James E.; Wong, Kwok-Kin] Harvard Med Sch, Dept Med, Boston, MA USA. [Li, Lewyn; Rao, Prakash K.; Li, Fugen; Duarte, Melissa A.; Brown, Myles; Long, Henry] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [De Raedt, Thomas; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Genet Div, 75 Francis St, Boston, MA 02115 USA. [Carretero, Julian] Univ Valencia, Dept Physiol, Burjassot, Spain. [Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Bronson, Roderick T.] Harvard Med Sch, Dept Microbiol & Immunol, Div Immunol, Boston, MA USA. [Brainson, Christine Fillmore; Kim, Carla F.] Boston Childrens Hosp, Stem Cell Program, Boston, MA USA. [Brainson, Christine Fillmore; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA USA. [Brainson, Christine Fillmore; Kim, Carla F.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA USA. RP Wong, KK (reprint author), Harvard Med Sch, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Ctr Thorac Oncol, 450 Brookline Ave,LC 4115, Boston, MA 02215 USA.; Bradner, JE (reprint author), Harvard Med Sch, Dana Farber Canc Inst, 450 Brookline Ave,LC 2210, Boston, MA 02215 USA. EM james_bradner@dfci.harvard.edu; kwong1@partners.org RI Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; wong, kwok kin/0000-0001-6323-235X FU Deutsche Forschungsgemeinschaft [HE 6897/1-1]; NIH/NCI [1R01CA195740-01, P01CA120964, 5R01CA163896-04, 5R01CA140594-07, 5R01CA122794-10, 5R01CA166480-04]; Gross-Loh Family Fund for Lung Cancer Research at Dana-Farber Cancer Institute; Susan Spooner Family Lung Cancer Research Fund at Dana-Farber Cancer Institute; Burroughs-Wellcome Fund; William Lawrence and Blanche Hughes Foundation; Leukemia and Lymphoma Society SCOR grant FX G.S. Herter-Sprie was supported by the Deutsche Forschungsgemeinschaft (HE 6897/1-1). K.-K. Wong and C.M. Perou are supported by NIH/NCI 1R01CA195740-01. K.-K. Wong is also supported by NIH/NCI P01CA120964, 5R01CA163896-04, 5R01CA140594-07, 5R01CA122794-10, and 5R01CA166480-04 grants and the Gross-Loh Family Fund for Lung Cancer Research and Susan Spooner Family Lung Cancer Research Fund at Dana-Farber Cancer Institute. J.E. Bradner is supported by the Burroughs-Wellcome Fund, the William Lawrence and Blanche Hughes Foundation, and a Leukemia and Lymphoma Society SCOR grant. NR 53 TC 5 Z9 5 U1 7 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 SEP PY 2016 VL 6 IS 9 BP 1006 EP 1021 DI 10.1158/2159-8290.CD-16-0164 PG 16 WC Oncology SC Oncology GA DW0TT UT WOS:000383356400025 PM 27312177 ER PT J AU Kar, SP Beesley, J Al Olama, AA Michailidou, K Tyrer, J Kote-Jarai, ZA Lawrenson, K Lindstrom, S Ramus, SJ Thompson, DJ Kibel, AS Dansonka-Mieszkowska, A Michael, A Dieffenbach, AK Gentry-Maharaj, A Whittemore, AS Wolk, A Monteiro, A Peixoto, A Kierzek, A Cox, A Rudolph, A Gonzalez-Neira, A Wu, AH Lindblom, A Swerdlow, A Ziogas, A Ekici, AB Burwinkel, B Karlan, BY Nordestgaard, BG Blomqvist, C Phelan, C McLean, C Pearce, CL Vachon, C Cybulski, C Slavov, C Stegmaier, C Maier, C Ambrosone, CB Hogdall, CK Teerlink, CC Kang, D Tessier, DC Schaid, DJ Stram, DO Cramer, DW Neal, DE Eccles, D Flesch-Janys, D Edwards, DRV Wokozorczyk, D Levine, DA Yannoukakos, D Sawyer, EJ Bandera, EV Poole, EM Goode, EL Khusnutdinova, E Hogdall, E Song, FJ Bruinsma, F Heitz, F Modugno, F Hamdy, FC Wiklund, F Giles, GG Olsson, H Wildiers, H Ulmer, HU Pandha, H Risch, HA Darabi, H Salvesen, HB Nevanlinna, H Gronberg, H Brenner, H Brauch, H Anton-Culver, H Song, HL Lim, HY McNeish, I Campbell, I Vergote, I Gronwald, J Lubinski, J Stanford, JL Bentez, J Doherty, JA Permuth, JB Chang-Claude, J Donovan, JL Dennis, J Schildkraut, JM Schleutker, J Hopper, JL Kupryjanczyk, J Park, JY Figueroa, J Clements, JA Knight, JA Peto, J Cunningham, JM Pow-Sang, J Batra, J Czene, K Lu, KH Herkommer, K Khaw, KT Matsuo, K Muir, K Offitt, K Chen, KX Moysich, KB Aittomaki, K Odunsi, K Kiemeney, LA Massuger, LFAG Fitzgerald, LM Cook, LS Cannon-Albright, L Hooning, MJ Pike, MC Bolla, MK Luedeke, M Teixeira, MR Goodman, MT Schmidt, MK Riggan, M Aly, M Rossing, MA Beckmann, MW Moisse, M Sanderson, M Southey, MC Jones, M Lush, M Hildebrandt, MAT Hou, MF Schoemaker, MJ Garcia-Closas, M Bogdanova, N Rahman, N Le, ND Orr, N Wentzensen, N Pashayan, N Peterlongo, P Guenel, P Brennan, P Paulo, P Webb, PM Broberg, P Fasching, PA Devilee, P Wang, Q Cai, QY Li, QY Kaneva, R Butzow, R Kopperud, RK Schmutzler, RK Stephenson, RA MacInnis, RJ Hoover, RN Winqvist, R Ness, R Milne, RL Travis, RC Benlloch, S Olson, SH McDonnell, SK Tworoger, SS Maia, SA Berndt, S Lee, SC Teo, SH Thibodeau, SN Bojesen, SE Gapstur, SM Kjaer, SK Pejovic, T Tammela, TLJ Dork, T Bruning, T Wahlfors, T Key, TJ Edwards, TL Menon, U Hamann, U Mitev, V Kosma, VM Setiawan, VW Kristensen, V Arndt, V Vogel, W Zheng, W Sieh, W Blot, WJ Kluzniak, W Shu, XO Gao, YT Schumacher, F Freedman, ML Berchuck, A Dunning, AM Simard, J Haiman, CA Spurdle, A Sellers, TA Hunter, DJ Henderson, BE Kraft, P Chanock, SJ Couch, FJ Hall, P Gayther, SA Easton, DF Chenevix-Trench, G Eeles, R Pharoah, PDP Lambrechts, D AF Kar, Siddhartha P. Beesley, Jonathan Al Olama, Ali Amin Michailidou, Kyriaki Tyrer, Jonathan Kote-Jarai, Zsofi A. Lawrenson, Kate Lindstrom, Sara Ramus, Susan J. Thompson, Deborah J. Kibel, Adam S. Dansonka-Mieszkowska, Agnieszka Michael, Agnieszka Dieffenbach, Aida K. Gentry-Maharaj, Aleksandra Whittemore, Alice S. Wolk, Alicja Monteiro, Alvaro Peixoto, Ana Kierzek, Andrzej Cox, Angela Rudolph, Anja Gonzalez-Neira, Anna Wu, Anna H. Lindblom, Annika Swerdlow, Anthony Ziogas, Argyrios Ekici, Arif B. Burwinkel, Barbara Karlan, Beth Y. Nordestgaard, Borge G. Blomqvist, Carl Phelan, Catherine McLean, Catriona Pearce, Celeste Leigh Vachon, Celine Cybulski, Cezary Slavov, Chavdar Stegmaier, Christa Maier, Christiane Ambrosone, Christine B. Hogdall, Claus K. Teerlink, Craig C. Kang, Daehee Tessier, Daniel C. Schaid, Daniel J. Stram, Daniel O. Cramer, Daniel W. Neal, David E. Eccles, Diana Flesch-Janys, Dieter Edwards, Digna R. Velez Wokozorczyk, Dominika Levine, Douglas A. Yannoukakos, Drakoulis Sawyer, Elinor J. Bandera, Elisa V. Poole, Elizabeth M. Goode, Ellen L. Khusnutdinova, Elza Hogdall, Estrid Song, Fengju Bruinsma, Fiona Heitz, Florian Modugno, Francesmary Hamdy, Freddie C. Wiklund, Fredrik Giles, Graham G. Olsson, Hakan Wildiers, Hans Ulmer, Hans-Ulrich Pandha, Hardev Risch, Harvey A. Darabi, Hatef Salvesen, Helga B. Nevanlinna, Heli Gronberg, Henrik Brenner, Hermann Brauch, Hiltrud Anton-Culver, Hoda Song, Honglin Lim, Hui-Yi McNeish, Iain Campbell, Ian Vergote, Ignace Gronwald, Jacek Lubinski, Jan Stanford, Janet L. Bentez, Javier Doherty, Jennifer A. Permuth, Jennifer B. Chang-Claude, Jenny Donovan, Jenny L. Dennis, Joe Schildkraut, Joellen M. Schleutker, Johanna Hopper, John L. Kupryjanczyk, Jolanta Park, Jong Y. Figueroa, Jonine Clements, Judith A. Knight, Julia A. Peto, Julian Cunningham, Julie M. Pow-Sang, Julio Batra, Jyotsna Czene, Kamila Lu, Karen H. Herkommer, Kathleen Khaw, Kay-Tee Matsuo, Keitaro Muir, Kenneth Offitt, Kenneth Chen, Kexin Moysich, Kirsten B. Aittomaki, Kristiina Odunsi, Kunle Kiemeney, Lambertus A. Massuger, Leon F. A. G. Fitzgerald, Liesel M. Cook, Linda S. Cannon-Albright, Lisa Hooning, Maartje J. Pike, Malcolm C. Bolla, Manjeet K. Luedeke, Manuel Teixeira, Manuel R. Goodman, Marc T. Schmidt, Marjanka K. Riggan, Marjorie Aly, Markus Rossing, Mary Anne Beckmann, Matthias W. Moisse, Matthieu Sanderson, Maureen Southey, Melissa C. Jones, Michael Lush, Michael Hildebrandt, Michelle A. T. Hou, Ming-Feng Schoemaker, Minouk J. Garcia-Closas, Montserrat Bogdanova, Natalia Rahman, Nazneen Le, Nhu D. Orr, Nick Wentzensen, Nicolas Pashayan, Nora Peterlongo, Paolo Guenel, Pascal Brennan, Paul Paulo, Paula Webb, Penelope M. Broberg, Per Fasching, Peter A. Devilee, Peter Wang, Qin Cai, Qiuyin Li, Qiyuan Kaneva, Radka Butzow, Ralf Kopperud, Reidun Kristin Schmutzler, Rita K. Stephenson, Robert A. MacInnis, Robert J. Hoover, Robert N. Winqvist, Robert Ness, Roberta Milne, Roger L. Travis, Ruth C. Benlloch, Sara Olson, Sara H. McDonnell, Shannon K. Tworoger, Shelley S. Maia, Sofi A. Berndt, Sonja Lee, Soo Chin Teo, Soo-Hwang Thibodeau, Stephen N. Bojesen, Stig E. Gapstur, Susan M. Kjaer, Susanne Krueger Pejovic, Tanja Tammela, Teuvo L. J. Doerk, Thilo Bruening, Thomas Wahlfors, Tiina Key, Tim J. Edwards, Todd L. Menon, Usha Hamann, Ute Mitev, Vanio Kosma, Veli-Matti Setiawan, Veronica Wendy Kristensen, Vessela Arndt, Volker Vogel, Walther Zheng, Wei Sieh, Weiva Blot, William J. Kluzniak, Wojciech Shu, Xiao-Ou Gao, Yu-Tang Schumacher, Fredrick Freedman, Matthew L. Berchuck, Andrew Dunning, Alison M. Simard, Jacques Haiman, Christopher A. Spurdle, Amanda Sellers, Thomas A. Hunter, David J. Henderson, Brian E. Kraft, Peter Chanock, Stephen J. Couch, Fergus J. Hall, Per Gayther, Simon A. Easton, Douglas F. Chenevix-Trench, Georgia Eeles, Rosalind Pharoah, Paul D. P. Lambrechts, Diether CA ABCTB Investigators AOCS Study Grp Australian Canc APCB BioResource KConFab Investigators NBCS Investigators GENICA Network PRACTICAL Consortium TI Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types SO CANCER DISCOVERY LA English DT Article ID TRAIL-INDUCED APOPTOSIS; PASSENGER COMPLEX CPC; BIOLOGICAL PATHWAYS; ENRICHMENT ANALYSIS; DEATH RECEPTORS; RISK LOCI; VARIANTS; CELLS; GENE; POPULATION AB Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10 -8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. (C) 2016 AACR. C1 [Kar, Siddhartha P.; Al Olama, Ali Amin; Michailidou, Kyriaki; Thompson, Deborah J.; Dennis, Joe; Bolla, Manjeet K.; Lush, Michael; Wang, Qin; Benlloch, Sara; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Beesley, Jonathan; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Herston, Qld, Australia. [Tyrer, Jonathan; Song, Honglin; Pashayan, Nora; Dunning, Alison M.; Easton, Douglas F.; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Kote-Jarai, Zsofi A.; Eeles, Rosalind] Inst Canc Res, Sutton, Surrey, England. [Lawrenson, Kate; Ramus, Susan J.; Wu, Anna H.; Stram, Daniel O.; Setiawan, Veronica Wendy; Schumacher, Fredrick; Haiman, Christopher A.; Henderson, Brian E.; Gayther, Simon A.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Lindstrom, Sara; Hunter, David J.; Kraft, Peter] Harvard Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA. [ABCTB Investigators] Univ Sydney, Westmead Millennium Inst, Australian Breast Canc Tissue Bank ABCTB Investig, Sydney, NSW, Australia. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol & Lab Diagnost, Warsaw, Poland. [Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta] Inst Oncol, Warsaw, Poland. [Michael, Agnieszka; Kierzek, Andrzej; Pandha, Hardev] Univ Surrey, Guildford, Surrey, England. [Dieffenbach, Aida K.; Brenner, Hermann; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Dieffenbach, Aida K.; Brenner, Hermann; Brauch, Hiltrud] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Womens Canc, London, England. [Whittemore, Alice S.; Sieh, Weiva] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Wolk, Alicja] Karolinska Inst, Dept Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Monteiro, Alvaro; Phelan, Catherine; Permuth, Jennifer B.; Park, Jong Y.; Pow-Sang, Julio; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Peixoto, Ana; Teixeira, Manuel R.; Paulo, Paula; Maia, Sofi A.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England. [Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Gonzalez-Neira, Anna; Bentez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Madrid, Spain. [Gonzalez-Neira, Anna; Bentez, Javier] Spanish Natl Genotyping Ctr CEGEN, Madrid, Spain. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk J.; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London, England. [Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London, England. Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr, Brisbane, Qld, Australia. [APCB BioResource] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia. 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[Ulmer, Hans-Ulrich; Hamann, Ute] Frauenklin Stadtklin Baden Baden, Baden Baden, Germany. [Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Salvesen, Helga B.; Kopperud, Reidun Kristin] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway. [Salvesen, Helga B.; Kopperud, Reidun Kristin] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, Bergen, Norway. [Nevanlinna, Heli] Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland. [Brenner, Hermann] Natl Ctr Tumor Dis NCT, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Heidelberg, Germany. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Lim, Hui-Yi] H Lee Moffitt Canc Ctr & Res Inst, Biostat Program, Tampa, FL USA. [McNeish, Iain] Univ Glasgow, Inst Canc Sci, Beatson Inst Canc Res, Wolfson Wohl Canc Res Ctr, Glasgow, Lanark, Scotland. [Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, St Andrews Pl, East Melbourne, Vic, Australia. [Campbell, Ian; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic, Australia. [Vergote, Ignace] Katholieke Univ Leuven, Univ Hosp Leuven, Leuven Canc Inst, Dept Gynaecol Oncol, Leuven, Belgium. [Stanford, Janet L.; Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA. [Stanford, Janet L.; Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Dept Epidemiol, Hanover, NH USA. [Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA. [Schleutker, Johanna; Wahlfors, Tiina] Univ Turku, Dept Med Biochem, Turku, Finland. [Schleutker, Johanna; Wahlfors, Tiina] Univ Turku, Genet Inst Biomed, Turku, Finland. [Schleutker, Johanna] Univ Tampere, BioMediTech, Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. [Hopper, John L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [Figueroa, Jonine; Garcia-Closas, Montserrat; Wentzensen, Nicolas; Hoover, Robert N.; Berndt, Sonja; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Australian Prostate Canc Res Ctr, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia. [Clements, Judith A.; Batra, Jyotsna] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada. [Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England. [Cunningham, Julie M.; Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Herkommer, Kathleen] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, Munich, Germany. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Nagoya, Aichi, Japan. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England. [Offitt, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, Dept Canc Biol & Genet, 1275 York Ave, New York, NY 10021 USA. [Offitt, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Aittomaki, Kristiina] Helsinki Univ Hosp, Dept Clin Genet, Helsinki, Finland. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radbond Inst Hlth Sci, Nijmegen, Netherlands. [Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, Nijmegen, Netherlands. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cannon-Albright, Lisa] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. [Hooning, Maartje J.] Erasmus MC, Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Pike, Malcolm C.; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal. [Goodman, Marc T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA. [Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Riggan, Marjorie; Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Aly, Markus] Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Obstet & Gynaecol, Erlangen, Germany. Katholieke Univ Leuven, VIB Vesalius Res Ctr, Leuven, Belgium. [Sanderson, Maureen] Meharry Med Coll, Dept Family & Community Med, Nashville, TN 37208 USA. [Hildebrandt, Michelle A. T.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. 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[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA. [Li, Qiyuan] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02115 USA. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Kaneva, Radka; Mitev, Vanio] Med Univ, Mol Med Ctr, Dept Med Chem & Biochem, Sofia, Bulgaria. [Butzow, Ralf] Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland. [Schmutzler, Rita K.] Univ Hosp Cologne, CIO, Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.] Univ Cologne, CMMC, Cologne, Germany. [Stephenson, Robert A.] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA. [Winqvist, Robert] Univ Oulu, Bioctr Oulu, Lab Canc Genet & Tumor Biol Canc Res & Translat M, Oulu, Finland. 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[Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland. [Tammela, Teuvo L. J.] Tampere Univ, Sch Med, Tampere, Finland. [Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany. [Bruening, Thomas] Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany. [Edwards, Todd L.] Vanderbilt Univ, Dept Med, Vanderbilt Genet Inst, Vanderbilt Epidemiol Ctr,Div Epidemiol, Nashville, TN USA. [Kosma, Veli-Matti] Univ Eastern Finland, Inst Clin Med, Dept Pathol & Forens Med, Kuopio, Finland. [Kosma, Veli-Matti] Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland. [Kristensen, Vessela] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway. [Kristensen, Vessela] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Oslo, Norway. [Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway. [Vogel, Walther] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Blot, William J.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Genom Ctr, Quebec City, PQ, Canada. [Spurdle, Amanda] QIMR Berghofer Med Res Inst, Mol Canc Epidemiol Lab, Herston, Qld, Australia. [Eeles, Rosalind] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England. [Eeles, Rosalind] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England. RP Kar, SP (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. EM sk718@medschl.cam.ac.uk RI Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013; Bruning, Thomas/G-8120-2015; Dork, Thilo/J-8620-2012; Khusnutdinova, Elza/A-4810-2013; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; salvesen, Helga/C-1187-2017; OI Dunning, Alison Margaret/0000-0001-6651-7166; Clements, Judith/0000-0001-6026-1964; Zheng, Wei/0000-0003-1226-070X; Bruning, Thomas/0000-0001-9560-5464; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; salvesen, Helga/0000-0002-4438-8831; Moisse, Matthieu/0000-0001-8880-9311; Yannoukakos, Drakoulis/0000-0001-7509-3510 FU Cancer Research UK [C1287/A12014, C5047/A7357, C5047/A3354, C5047/A10692, C16913/A6135, C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C8197/A16565]; European Community [223175 (HEALTH-F2-2009-223175)]; NIH [CA128978]; Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; U.S. Department of Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund FX The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK (C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC). Funding for the Collaborative Oncological Gene-Environment Study (COGS) infrastructure came from the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the NIH (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the U.S. Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented in the Supplementary Financial Support. NR 84 TC 6 Z9 6 U1 16 U2 16 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 SEP PY 2016 VL 6 IS 9 BP 1052 EP 1067 DI 10.1158/2159-8290.CD-15-1227 PG 16 WC Oncology SC Oncology GA DW0TT UT WOS:000383356400028 PM 27432226 ER PT J AU Child, K Holbrook, E Schwob, J Jang, W AF Child, Kevin Holbrook, Eric Schwob, James Jang, Woochan TI Accelerated Olfactory Aging in Transgenic Mice Recapitulates Aging Human Olfactory Epithelium SO CHEMICAL SENSES LA English DT Meeting Abstract CT 38th Annual Meeting of the Association-for-Chemoreception-Sciences (AChemS) CY APR 20-23, 2016 CL Bonita Springs, FL SP Assoc Chemorecept Sci C1 [Child, Kevin] Tufts Univ, Sackler Sch Biomed Sci, Boston, MA 02111 USA. [Holbrook, Eric] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Schwob, James; Jang, Woochan] Tufts Univ, Dept Dev Mol & Chem Biol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X EI 1464-3553 J9 CHEM SENSES JI Chem. Senses PD SEP PY 2016 VL 41 IS 7 MA 106 BP E26 EP E26 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA DW7TH UT WOS:000383854300067 ER PT J AU Kalil, AC Metersky, ML Klompas, M Muscedere, J Sweeney, DA Palmer, LB Napolitano, LM O'Grady, NP Bartlett, JG Carratala, J El Solh, AA Ewig, S Fey, PD File, TM Restrepo, MI Roberts, JA Waterer, GW Cruse, P Knight, SL Brozek, JL AF Kalil, Andre C. Metersky, Mark L. Klompas, Michael Muscedere, John Sweeney, Daniel A. Palmer, Lucy B. Napolitano, Lena M. O'Grady, Naomi P. Bartlett, John G. Carratala, Jordi El Solh, Ali A. Ewig, Santiago Fey, Paul D. File, Thomas M., Jr. Restrepo, Marcos I. Roberts, Jason A. Waterer, Grant W. Cruse, Peggy Knight, Shandra L. Brozek, Jan L. TI Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CONSENSUS; COLISTIN AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews. C1 [Kalil, Andre C.] Univ Nebraska Med Ctr, Div Infect Dis, Dept Internal Med, Omaha, NE 68198 USA. [Metersky, Mark L.] Univ Connecticut, Sch Med, Div Pulm & Crit Care Med, Farmington, CT USA. [Klompas, Michael] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Klompas, Michael] Harvard Med Sch, Boston, MA USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Muscedere, John] Queens Univ, Dept Med, Crit Care Program, Kingston, ON, Canada. [Sweeney, Daniel A.] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, San Diego, CA 92103 USA. [Palmer, Lucy B.] SUNY Stony Brook, Dept Med, Div Pulm Crit Care & Sleep Med, Stony Brook, NY 11794 USA. [Napolitano, Lena M.] Univ Michigan, Dept Surg, Div Trauma Crit Care & Emergency Surg, Ann Arbor, MI 48109 USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. [Bartlett, John G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Carratala, Jordi] Univ Barcelona, Dept Infect Dis, Hosp Univ Bellvitge, Bellvitge Biomed Res Inst,Spanish Network Res Inf, E-08007 Barcelona, Spain. [El Solh, Ali A.] SUNY Buffalo, Vet Affairs Western New York Healthcare Syst, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY USA. [Ewig, Santiago] EVK Herne, Dept Resp & Infect Dis, Thoraxzentrum Ruhrgebiet, Herne, Germany. [Ewig, Santiago] Augusta Kranken Anstalt Bochum, Bochum, Germany. [Fey, Paul D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [File, Thomas M., Jr.] Summa Hlth Syst, Akron, OH USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Roberts, Jason A.] Univ Queensland, Burns Trauma & Crit Care Res Ctr, Brisbane, Qld 4072, Australia. [Roberts, Jason A.] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Waterer, Grant W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia. [Cruse, Peggy; Knight, Shandra L.] Natl Jewish Hlth, Lib Serv, Denver, CO USA. [Cruse, Peggy; Knight, Shandra L.] Natl Jewish Hlth, Knowledge Serv, Denver, CO USA. [Brozek, Jan L.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Brozek, Jan L.] McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Div Infect Dis, Dept Internal Med, Omaha, NE 68198 USA. EM akalil@unmc.edu FU IDSA; ATS FX The IDSA and the ATS provided meeting facilities for face-to-face meetings, financial support for conference calls, and administrative support. Industry funding to support guideline development was not permitted. NR 6 TC 6 Z9 6 U1 11 U2 11 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 SEP 1 PY 2016 VL 63 IS 5 BP 575 EP 582 DI 10.1093/cid/ciw504 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DW7TZ UT WOS:000383856300002 PM 27521441 ER PT J AU Van Hise, NW Bryant, AM Hennessey, EK Crannage, AJ Khoury, JA Manian, FA AF Van Hise, Nicholas W. Bryant, Alex M. Hennessey, Erin K. Crannage, Andrew J. Khoury, Jad A. Manian, Farrin A. TI Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE prophylaxis; Clostridium difficile; vancomycin; antimicrobial agents ID DIARRHEA; DISEASE; RISK AB We compared rates of recurrent Clostridium difficile infection in patients receiving or not receiving oral vancomycin prophylaxis with systemic antimicrobial therapy. The incidence of C. difficile infection was significantly lower in patients receiving prophylaxis (4.2% vs 26.6% in those without prophylaxis; odds ratio, 0.12; 95% confidence interval, .04-.4; P < .001). C1 [Van Hise, Nicholas W.] Edward Elmhurst Hosp, Dept Pharm, Naperville, IL USA. [Bryant, Alex M.; Hennessey, Erin K.; Crannage, Andrew J.] Mercy Hosp, Dept Pharm, St Louis, MO USA. [Khoury, Jad A.] Mercy Hosp, Dept Med, St Louis, MO USA. [Hennessey, Erin K.; Crannage, Andrew J.] St Louis Coll Pharm, St Louis, MO USA. [Manian, Farrin A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Van Hise, NW (reprint author), 2304 Modaff Rd, Naperville, IL 60565 USA. EM nicholas.vanhise@gmail.com NR 9 TC 4 Z9 4 U1 2 U2 3 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 SEP 1 PY 2016 VL 63 IS 5 BP 651 EP 653 DI 10.1093/cid/ciw401 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DW7TZ UT WOS:000383856300013 PM 27318333 ER PT J AU Kalil, AC Metersky, ML Klompas, M Muscedere, J Sweeney, DA Palmer, LB Napolitano, LM O'Grady, NP Bartlett, JG Carratala, J El Solh, AA Ewig, S Fey, PD File, TM Restrepo, MI Roberts, JA Waterer, GW Cruse, P Knight, SL Brozek, JL AF Kalil, Andre C. Metersky, Mark L. Klompas, Michael Muscedere, John Sweeney, Daniel A. Palmer, Lucy B. Napolitano, Lena M. O'Grady, Naomi P. Bartlett, John G. Carratala, Jordi El Solh, Ali A. Ewig, Santiago Fey, Paul D. File, Thomas M., Jr. Restrepo, Marcos I. Roberts, Jason A. Waterer, Grant W. Cruse, Peggy Knight, Shandra L. Brozek, Jan L. TI Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE-UNIT; RESISTANT STAPHYLOCOCCUS-AUREUS; CRITICALLY-ILL PATIENTS; GRAM-NEGATIVE BACTERIA; COMBINATION ANTIBIOTIC-THERAPY; RANDOMIZED CONTROLLED-TRIAL; DE-ESCALATION THERAPY; PSEUDOMONAS-AERUGINOSA BACTEREMIA; RESPIRATORY-TRACT INFECTIONS; PROTECTED SPECIMEN BRUSH AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews. C1 [Kalil, Andre C.] Univ Nebraska Med Ctr, Div Infect Dis, Dept Internal Med, Omaha, NE 68198 USA. [Metersky, Mark L.] Univ Connecticut, Sch Med, Div Pulm & Crit Care Med, Farmington, CT USA. [Klompas, Michael] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Klompas, Michael] Harvard Med Sch, Boston, MA USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Muscedere, John] Queens Univ, Dept Med, Crit Care Program, Kingston, ON, Canada. [Sweeney, Daniel A.] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, San Diego, CA 92103 USA. [Palmer, Lucy B.] SUNY Stony Brook, Dept Med, Div Pulm Crit Care & Sleep Med, Stony Brook, NY 11794 USA. [Napolitano, Lena M.] Univ Michigan, Dept Surg, Div Trauma Crit Care & Emergency Surg, Ann Arbor, MI 48109 USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Bartlett, John G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Carratala, Jordi] Univ Barcelona, Spanish Network Res Infect Dis, Bellvitge Biomed Res Inst, Dept Infect Dis,Hosp Univ Bellvitge, E-08007 Barcelona, Spain. [El Solh, Ali A.] SUNY Buffalo, Dept Med, Div Pulm Crit Care & Sleep Med, Vet Affairs Western New York Healthcare Syst, New York, NY USA. [Ewig, Santiago] EVK Herne, Thoraxzentrum Ruhrgebiet, Dept Resp & Infect Dis, Herne, Germany. [Ewig, Santiago] Augusta Kranken Anstalt Bochum, Bochum, Germany. [Fey, Paul D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [File, Thomas M., Jr.] Summa Hlth Syst, Akron, OH USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX USA. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Roberts, Jason A.] Univ Queensland, Burns Trauma & Crit Care Res Ctr, Brisbane, Qld 4072, Australia. [Roberts, Jason A.] Royal Brisbane & Womens Hosp, Herston, Qld, Australia. [Waterer, Grant W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia. [Cruse, Peggy; Knight, Shandra L.] Natl Jewish Hlth, Lib Serv, Denver, CO USA. [Cruse, Peggy; Knight, Shandra L.] Natl Jewish Hlth, Knowledge Serv, Denver, CO USA. [Brozek, Jan L.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Brozek, Jan L.] McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Div Infect Dis, Dept Internal Med, Omaha, NE 68198 USA. EM akalil@unmc.edu FU IDSA; ATS FX The IDSA and the ATS provided meeting facilities for face-to-face meetings, financial support for conference calls, and administrative support. Industry funding to support guideline development was not permitted. NR 364 TC 38 Z9 41 U1 5 U2 5 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 SEP 1 PY 2016 VL 63 IS 5 BP E61 EP E111 DI 10.1093/cid/ciw353 PG 51 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DW7TZ UT WOS:000383856300001 PM 27418577 ER PT J AU Mangla, S Goldin, AH Singal, G Hornick, JL Blatman, KSH Burakoff, R Chan, WW AF Mangla, Shikha Goldin, Alison H. Singal, Gaurav Hornick, Jason L. Blatman, Karen S. Hsu Burakoff, Robert Chan, Walter W. TI Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Eosinophilic esophagitis; Eosinophil counts; Esophageal rings; Erosions; Food impaction ID DISEASE AB Background and Aims Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. Methods This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with >= 15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). 400 patients (42 +/- 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (beta-coefficient = 0.01, p = 0.04) remained associated with food impaction. Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings). C1 [Mangla, Shikha; Goldin, Alison H.; Burakoff, Robert; Chan, Walter W.] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. [Singal, Gaurav] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Blatman, Karen S. Hsu] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. [Mangla, Shikha; Goldin, Alison H.; Singal, Gaurav; Hornick, Jason L.; Blatman, Karen S. Hsu; Burakoff, Robert; Chan, Walter W.] Harvard Med Sch, Boston, MA 02115 USA. RP Chan, WW (reprint author), Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA.; Chan, WW (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM wwchan@partners.org NR 20 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2016 VL 61 IS 9 BP 2578 EP 2584 DI 10.1007/s10620-016-4190-6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DU1TP UT WOS:000381992700017 PM 27193561 ER PT J AU Taleban, S Stewart, KO Li, DK Singh, P Pardi, DS Sturgeon, HC Yajnik, V Xavier, RJ Ananthakrishnan, AN Khalili, H AF Taleban, Sasha Stewart, Kathleen O. Li, Darrick K. Singh, Prashant Pardi, Darrell S. Sturgeon, Holly C. Yajnik, Vijay Xavier, Ramnik J. Ananthakrishnan, Ashwin N. Khalili, Hamed TI Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn's Disease Phenotypes SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Crohn's disease; Ulcerative colitis; Quality of life; Inflammatory bowel disease ID INFLAMMATORY-BOWEL-DISEASE; C-REACTIVE PROTEIN; ENDOSCOPIC REMISSION; FECAL CALPROTECTIN; OLMSTED COUNTY; CHARM TRIAL; IBD; ADALIMUMAB; RECOMMENDATIONS; QUESTIONNAIRE AB Clinical activity and quality of life (QOL) indices assess disease activity in Crohn's disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. We used a prospective registry to identify CD and UC patients aeyen18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey-Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and -0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes. C1 [Taleban, Sasha] Univ Arizona, Coll Med, Div Gastroenterol, Tucson, AZ 85724 USA. [Taleban, Sasha] Univ Arizona, Dept Med, Ctr Aging, Tucson, AZ 85724 USA. [Stewart, Kathleen O.; Sturgeon, Holly C.; Yajnik, Vijay; Xavier, Ramnik J.; Ananthakrishnan, Ashwin N.; Khalili, Hamed] Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Li, Darrick K.; Singh, Prashant] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pardi, Darrell S.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Xavier, Ramnik J.] Broad Inst, Cambridge, MA 02124 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Khalili, Hamed] Harvard Med Sch, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Khalili, Hamed] Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. [Taleban, Sasha] Banner Univ, Med Ctr, Gastroenterol Sect, 1501 N Campbell Ave, Tucson, AZ 85724 USA. RP Taleban, S (reprint author), Univ Arizona, Coll Med, Div Gastroenterol, Tucson, AZ 85724 USA.; Taleban, S (reprint author), Univ Arizona, Dept Med, Ctr Aging, Tucson, AZ 85724 USA.; Khalili, H (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.; Khalili, H (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA.; Khalili, H (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.; Taleban, S (reprint author), Banner Univ, Med Ctr, Gastroenterol Sect, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM staleban@yahoo.com; hkhalili@mgh.harvard.edu FU American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; National Institutes of Health [K23 DK097142] FX This work is supported by a career development award from the American Gastroenterological Association (AGA) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681 to HK) along with a grant from the National Institutes of Health (K23 DK097142 to ANN). NR 46 TC 1 Z9 2 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 SEP PY 2016 VL 61 IS 9 BP 2627 EP 2635 DI 10.1007/s10620-016-4180-8 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DU1TP UT WOS:000381992700023 PM 27142671 ER PT J AU Pauls, Q Durkalski-Mauldin, V Brawman-Mintzer, O Lawrence, C Whichard, R Cotton, PB AF Pauls, Qi Durkalski-Mauldin, Valerie Brawman-Mintzer, Olga Lawrence, Chris Whichard, Rebekah Cotton, Peter B. TI Duloxetine for the Treatment of Patients with Suspected Sphincter of Oddi Dysfunction: A Pilot Study SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Sphincter of Oddi dysfunction; Abdominal pain; Biliary disease; Pharmacotherapy ID IRRITABLE-BOWEL-SYNDROME; FINDINGS TYPE-I; ABDOMINAL-PAIN; DISORDERS; PRESENTATIONS; DISABILITY; PLACEBO; TRIAL AB To examine the tolerability and efficacy of duloxetine in patients with suspected sphincter of Oddi dysfunction (SOD). An open-label, single-center, 12-week trial of duloxetine 60 mg once daily was conducted in 20 patients with suspected SOD. All patients were evaluated by expert pancreato-biliary specialists. The primary outcome measure was a Patient Global Impression of Change (PGIC) scale. Secondary measures included the pain burden, assessed by the Recurrent Abdominal Pain Intensity and Disability scale, the Short-Form Health Survey, and the Hospital Anxiety and Depression Scale. A positive clinical response was defined as a PGIC score of much or very much improved at 3 months and was estimated using a two-sided 90 % confidence interval. The primary outcome was analyzed using a one-sample binomial test at a significance level of 0.10. Of the 20 screened patients, 18 were enrolled; 14 completed at least one post-baseline evaluation; and 10 patients completed the third month endpoint visit. Patients missing the third month visit were considered non-responders for the primary outcome. Response rates were 90 % for study completers (n = 10; 90 % CI 74-100; p = 0.02) and 64 % for patients who completed at least one post-baseline evaluation (n = 14; 90 % CI 43-85; p = 0.42). Seven patients did not complete the study due to adverse events (mostly fatigue and nausea). Duloxetine showed an indication of efficacy in the treatment of pain in patients with suspected SOD, but adverse events limited its use. These preliminary, open-label results justify definitive placebo-controlled trials. C1 [Pauls, Qi; Durkalski-Mauldin, Valerie] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Lawrence, Chris; Whichard, Rebekah; Cotton, Peter B.] Med Univ South Carolina, Ctr Digest Dis, Suite 249,MSC 702,114 Doughty St, Charleston, SC 29425 USA. [Brawman-Mintzer, Olga] Med Univ South Carolina, Dept Psychiat, Charleston, SC USA. [Brawman-Mintzer, Olga] Ralph H Johnson VAMC, Charleston, SC USA. RP Cotton, PB (reprint author), Med Univ South Carolina, Ctr Digest Dis, Suite 249,MSC 702,114 Doughty St, Charleston, SC 29425 USA. EM Petercotto@gmail.com FU Lilly Pharmaceuticals, USA FX The study was investigator-initiated and funded by an unrestricted research grant from Lilly Pharmaceuticals, USA. Lilly had no input on the design and management of the study or on the analysis of the data. NR 15 TC 2 Z9 2 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 SEP PY 2016 VL 61 IS 9 BP 2704 EP 2709 DI 10.1007/s10620-016-4187-1 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DU1TP UT WOS:000381992700031 PM 27165434 ER PT J AU Pectasides, E Miksad, R Pyatibrat, S Srivastava, A Bullock, A AF Pectasides, Eirini Miksad, Rebecca Pyatibrat, Sergey Srivastava, Amogh Bullock, Andrea TI Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases: A Case Report and Review of the Literature SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Metastatic hepatocellular carcinoma; Spontaneous regression ID BONE METASTASIS; CANCER; CELLS; INTERLEUKIN-18; THROMBUS AB Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. Here we present a case of spontaneous regression of metastatic HCC. A 53-year-old man with hepatitis C and alcoholic cirrhosis was found to have a large liver mass consistent with HCC based on its radiographic features. Imaging also revealed left portal and hepatic vein thrombosis, as well as multiple lung nodules concerning for metastases. Approximately 2 months after the initial diagnosis, both the primary liver lesion and the lung metastases decreased in size and eventually resolved without any intervention. Thereafter, the left hepatic vein thrombus progressed into the inferior vena cava and the right atrium, and the patient died due to right heart failure. In this case report and literature review, we discuss the potential mechanisms for and review the literature on spontaneous regression of metastatic HCC. C1 [Pectasides, Eirini] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pectasides, Eirini; Miksad, Rebecca; Bullock, Andrea] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pyatibrat, Sergey] Univ Ottawa, Ottawa, ON, Canada. [Srivastava, Amogh] Metrowest Radiol Associates, Framingham, MA USA. RP Bullock, A (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM abullock@bidmc.harvard.edu NR 38 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2016 VL 61 IS 9 BP 2749 EP 2754 DI 10.1007/s10620-016-4141-2 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DU1TP UT WOS:000381992700036 PM 27038447 ER PT J AU Sever, S White, DL Garcia, JM AF Sever, Sakine White, Donna L. Garcia, Jose M. TI Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review SO ENDOCRINE-RELATED CANCER LA English DT Review DE ghrelin; cancer; tumor growth; metastasis; in vivo; cachexia ID GH REPLACEMENT THERAPY; IGF-BINDING PROTEIN-3; GROWTH-FACTOR (IGF)-I; HELICOBACTER-PYLORI INFECTION; PLASMA GHRELIN CONCENTRATION; PRADER-WILLI-SYNDROME; CELL LUNG-CANCER; BREAST-CANCER; CIRCULATING GHRELIN; COLORECTAL-CANCER AB Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown high expression of ghrelin in cancer tissue, although its role including its impact in cancer risk and progression has not been established. We performed a systematic literature review to identify peer-reviewed human or animal in vivo original research studies of ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants and the risk, presence, or growth of cancer using structured searches in PubMed database as well as secondary searches of article reference lists, additional reviews and meta-analyses. Overall, 45 (73.8%) of the 61 studies reviewed, including all 11 involving exogenous ghrelin/ghrelin-receptor agonist treatment, reported either a null (no statistically significant difference) or inverse association of ghrelin/ghrelin-receptor agonists or ghrelin genetic variants with cancer risk, presence or growth; 10 (16.7%) studies reported positive associations; and 6 (10.0%) reported both negative or null and positive associations. Differences in serum ghrelin levels in cancer cases vs controls (typically lower) were reported for some but not all cancers. The majority of in vivo studies showed a null or inverse association of ghrelin with risk and progression of most cancers, suggesting that ghrelin/ghrelin-receptor agonist treatment may have a favorable safety profile to use for cancer cachexia. Additional large-scale prospective clinical trials as well as basic bioscientific research are warranted to further evaluate the safety and benefits of ghrelin treatment in patients with cancer. C1 [Sever, Sakine; Garcia, Jose M.] Baylor Coll Med, Div Endocrinol Diabet & Metab, Alkek Bldg Biomedical Res, Houston, TX 77030 USA. [White, Donna L.] Baylor Coll Med, Med Ctr, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [White, Donna L.] Michael E DeBakey VA Med Ctr, Sect Hlth Serv Res IQuESt, Clin Epidemiol & Comparat Effectiveness Program, HSR&D Ctr Innovat 152, Houston, TX USA. [White, Donna L.] Baylor Coll Med, Texas Med Ctr, Ctr Digest Dis, Houston, TX 77030 USA. [White, Donna L.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA. [White, Donna L.; Garcia, Jose M.] Michael E DeBakey VA Med Ctr, CTRID, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Garcia, Jose M.] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. [Garcia, Jose M.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Garcia, Jose M.] Univ Washington, Seattle, WA 98195 USA. RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Alkek Bldg Biomedical Res, Houston, TX 77030 USA.; Garcia, JM (reprint author), Michael E DeBakey VA Med Ctr, CTRID, Houston, TX 77030 USA.; Garcia, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.; Garcia, JM (reprint author), Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA.; Garcia, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.; Garcia, JM (reprint author), Univ Washington, Seattle, WA 98195 USA. EM jose.garcia@va.gov FU National Institute of Diabetes Digestive and Kidney Diseases [R03 DK095082]; Michael E DeBakey Veterans Affairs Health Services Research Center of Innovations [CIN13-413]; Aeterna Zentaris (USA); Helsinn Therapeutics (USA); Department of Veterans Affairs (MERIT grants) [I01-BX000507, I01 CX000174]; Aeterna Zentaris; Department of Veterans Affairs (NIA) [T32AG000183, AG040583] FX D L White receives research support from the National Institute of Diabetes Digestive and Kidney Diseases (R03 DK095082, PI: White) and the Michael E DeBakey Veterans Affairs Health Services Research Center of Innovations (CIN13-413). J M Garcia has received consulting or advisory fees from Aeterna Zentaris and Helsinn Therapeutics (USA), and research grants from the Department of Veterans Affairs (MERIT grants I01-BX000507 and I01 CX000174, and the NIA T32AG000183 and AG040583), Aeterna Zentaris, and Helsinn Therapeutics (USA). Support for developing this manuscript was provided by Helsinn Therapeutics. NR 140 TC 2 Z9 2 U1 1 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2016 VL 23 IS 9 BP R393 EP R409 DI 10.1530/ERC-16-0130 PG 17 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA DX2HX UT WOS:000384190100003 PM 27552970 ER PT J AU Hogan, MF Meier, DT Zraika, S Templin, AT Mellati, M Hull, RL Leissring, MA Kahn, SE AF Hogan, Meghan F. Meier, Daniel T. Zraika, Sakeneh Templin, Andrew T. Mellati, Mahnaz Hull, Rebecca L. Leissring, Malcolm A. Kahn, Steven E. TI Inhibition of Insulin-Degrading Enzyme Does Not Increase Islet Amyloid Deposition in Vitro SO ENDOCRINOLOGY LA English DT Article ID BETA-CELL APOPTOSIS; FIBRIL FORMATION; TRANSGENIC MICE; PANCREATIC-ISLETS; POLYPEPTIDE; DEGRADATION; SECRETION; AMYLIN; MOUSE; PATHOPHYSIOLOGY AB Islet amyloid deposition in human type 2 diabetes results in beta-cell loss. These amyloid deposits contain the unique amyloidogenic peptide human islet amyloid polypeptide (hIAPP), which is also a known substrate of the protease insulin-degrading enzyme (IDE). Whereas IDE inhibition has recently been demonstrated to improve glucose metabolism in mice, inhibiting it has also been shown to increase cell death when synthetic hIAPP is applied exogenously to a beta-cell line. Thus, we wanted to determine whether a similar deleterious effect is observed when hIAPP is endogenously produced and secreted from islets. To address this issue, we cultured hIAPP transgenic mouse islets that have the propensity to form amyloid for 48 and 144 hours in 16.7 mM glucose in the presence and absence of the IDE inhibitor 1. At neither time interval did IDE inhibition increase amyloid formation or beta-cell loss. Thus, the inhibition of IDE may represent an approach to improve glucose metabolism in human type 2 diabetes, without inducing amyloid deposition and its deleterious effects. C1 [Hogan, Meghan F.; Meier, Daniel T.; Zraika, Sakeneh; Templin, Andrew T.; Mellati, Mahnaz; Hull, Rebecca L.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Hogan, Meghan F.; Meier, Daniel T.; Zraika, Sakeneh; Templin, Andrew T.; Mellati, Mahnaz; Hull, Rebecca L.; Kahn, Steven E.] Univ Washington, Seattle, WA 98108 USA. [Leissring, Malcolm A.] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA 92697 USA. RP Hogan, MF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, 1660 South Columbian Way 151, Seattle, WA 98108 USA. EM mfhogan@uw.edu OI Kahn, Steven/0000-0001-7307-9002 FU Department of Veterans Affairs Grant [BX001060]; Veterans Affairs Puget Sound Health Care System (Seattle, WA); National Institutes of Health [P30DK017047, 5T32HL007028, T32DK007247]; Swiss National Foundation Fellowship; Dick and Julia McAbee Endowed Fellowship FX This work was supported, in whole or in part, by Department of Veterans Affairs Grant BX001060; Veterans Affairs Puget Sound Health Care System (Seattle, WA) and National Institutes of Health Grants P30DK017047 (to the University of Washington Diabetes Research Center), Grant 5T32HL007028 (to M.F.H.), and T32DK007247 (to A.T.T.); Swiss National Foundation Fellowship (to D.T.M.); and Dick and Julia McAbee Endowed Fellowship (to D.T.M.). NR 31 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2016 VL 157 IS 9 BP 3462 EP 3468 DI 10.1210/en.2016-1410 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX1NA UT WOS:000384132900022 PM 27404391 ER PT J AU Baliram, R Latif, R Morshed, SA Zaidi, M Davies, TF AF Baliram, R. Latif, R. Morshed, S. A. Zaidi, M. Davies, T. F. TI T-3 Regulates a Human Macrophage-Derived TSH-beta Splice Variant: Implications for Human Bone Biology SO ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; MONOCYTIC LEUKEMIA-CELLS; THP-1 CELLS; POSTMENOPAUSAL WOMEN; DENDRITIC CELLS; DIFFERENTIATION; THYROTROPIN; ALPHA; GENE; OSTEOBLASTOGENESIS AB TSH and thyroid hormones (T-3 and T-4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-beta splice variant (TSH-beta v) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblas-togenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-beta variant in human macrophages. Real-time PCR analyses using human TSH-beta-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-beta v previously reported. We then examined TSH-beta v regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T-3 showed a 14-fold induction of human TSH-beta v mRNA and variant protein. Furthermore, these human TSH-beta v-positive cells, induced by T-3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-beta v, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors. C1 [Baliram, R.; Latif, R.; Morshed, S. A.; Davies, T. F.] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel Med Ctr, Thyroid Res Unit, New York, NY 10029 USA. [Baliram, R.; Latif, R.; Zaidi, M.; Davies, T. F.] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel Med Ctr, Mt Sinai Bone Program, New York, NY 10029 USA. [Baliram, R.] James J Peters Vet Affairs Med Ctr, Res Bldg Room 2F-28,130 West Kingsbridge Rd, Bronx, NY 10468 USA. RP Baliram, R (reprint author), James J Peters Vet Affairs Med Ctr, Res Bldg Room 2F-28,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM annie.baliram@mssm.edu FU National Institutes of Health [DK069713, DK052464]; Veterans Affairs Merit Review Program FX This work was supported in part by Grants DK069713 and DK052464 from the National Institutes of Health (to T.F.D.) and the Veterans Affairs Merit Review Program (to T.F.D.). NR 34 TC 2 Z9 2 U1 3 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2016 VL 157 IS 9 BP 3658 EP 3667 DI 10.1210/en.2015-1974 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX1NA UT WOS:000384132900038 PM 27300765 ER PT J AU Verrier, RL Nearing, BD Olin, B Boon, P Schachter, SC AF Verrier, Richard L. Nearing, Bruce D. Olin, Bryan Boon, Paul Schachter, Steven C. TI Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Sudden unexpected death in epilepsy; T-wave alternans; Biomarker; Risk reduction ID SUDDEN UNEXPECTED DEATH; MYOCARDIAL-INFARCTION; FOCAL EPILEPSY; HEART-FAILURE; SEIZURE; RISK; REPOLARIZATION; MECHANISMS; PREVENTION; MORTALITY AB Objective: Reports of cardiac arrhythmias and cardiac pathology at postmortem examination of patients with epilepsy suggest a possible cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans (TWA) is an established marker of cardiac electrical instability and risk for sudden death in patients with cardiovascular disease. We determined the TWA level before vagus nerve stimulation (VNS) system implantation and subsequently the effect of VNS on TWA in patients with drug-resistant epilepsy. Methods: Patients (n = 28) from the Seizure Detection and Automatic Magnet Mode Performance Study (E-36), a clinical trial of the AspireSR (R) VNS Therapy System (R) (NCT01325623), were monitored with ambulatory electrocardiograms (ECGs) similar to 2 weeks before de novo VNS system implantation and following 2- to 4-week VNS titration during a protocol-specified 3- to 5-day epilepsy monitoring unit stay with concurrent EEG/ECG recordings. The TWA level was assessed interictally by the Modified Moving Average (MMA) method. Results: At preimplantation baseline, TWA was elevated above the 47-mu V abnormality cutpoint in 23 (82%) patients with drug-resistant epilepsy. In 16 (70%) patients, TWA level was reduced during VNS treatment to <47 mu V, thereby converting positive TWA test results to negative. Peak TWA level in all 28 patients improved (group mean, 43%, from 72 +/- 4.3 to 41 +/- 2.3 mu V; p < 0.0001). Vagus nerve stimulation was not associated with reduced heart rate (77 +/- 1.4 to 75 +/- 1.4 beats/min; p = 0.18). Heart rate variability was unchanged. Significance: These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Verrier, Richard L.; Nearing, Bruce D.; Schachter, Steven C.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Olin, Bryan] LivaNova PLC, Houston, TX USA. [Boon, Paul] Ghent Univ Hosp, Study Grp E 36, Ghent, Belgium. [Schachter, Steven C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schachter, Steven C.] Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Verrier, RL (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU LivaNova, Inc. [VERR004] FX This study was funded by a grant VERR004 from LivaNova, Inc. to Beth Israel Deaconess Medical Center (BIDMC), RL Verrier, P.I. NR 39 TC 0 Z9 0 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD SEP PY 2016 VL 62 BP 85 EP 89 DI 10.1016/j.yebeh.2016.06.016 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DX5AP UT WOS:000384392500016 PM 27450311 ER PT J AU Moura, LMVR Carneiro, TS Thorn, EL Seitz, MP Hsu, J Cole, AJ Vickrey, BG Hoch, DB AF Moura, Lidia M. V. R. Carneiro, Thiago S. Thorn, Emily L. Seitz, Michael P. Hsu, John Cole, Andrew J. Vickrey, Barbara G. Hoch, Daniel B. TI Patient perceptions of physician-documented quality care in epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy/seizures; Health services research; Quality of life; Clinical neurology; Patient experience; Outcome research ID CLINICAL-PRACTICE; REPORTED OUTCOMES; PHONE SURVEY; SATISFACTION; ADHERENCE; RECOMMENDATION; ASSOCIATION; EXPERIENCE; ADULTS AB Objective: The aim of this study was to compare physician encounter documentation with patient perceptions of quality of epilepsy care and examine the association between quality and patient assessment of provider communication. Methods: We identified 505 adult patients with epilepsy aged 18 years or older over a 3-year period in two large academic medical centers. We abstracted individual, clinical, and care measures from 2723 electronic clinical notes written by physicians. We then randomly selected 245 patients for a phone interview. We compared patient perceptions of care with the documented care for several established epilepsy quality measures. We also explored the association of patient's perception of provider communication with provider documentation of key encounter interventions. Results: There were 88 patients (36%) who completed the interviews. Fifty-seven (24%) refused to participate, and 100 (40%) could not be contacted. Participants and nonparticipants were comparable in their demographic and clinical characteristics; however, participants were more often seen by epilepsy specialists than nonparticipants (75% vs. 61.9%, p < 0.01). Quality scores based on patient perceptions differed from those determined by assessing the documentation in the medical record for several quality measures, e.g., documentation of side effects of antiseizure therapy (p = 0.05), safety counseling (p < 0.01), and counseling for women of childbearing potential with epilepsy (McNemar's p = 0.03; intraclass correlation coefficient, ICC = 0.07). There was a significant, positive association between patient-reported counseling during the encounter (e.g., personalized safety counseling) and patient-reported scores of provider communication (p = 0.05). Conclusions: The association between the patient's recollection of counseling during the visit and his/her positive perception of the provider's communication skills highlights the importance of spending time counseling patients about their epilepsy and not just determining if seizures are controlled. (C) 2016 Elsevier Inc. All rights reserved. C1 [Moura, Lidia M. V. R.; Carneiro, Thiago S.; Thorn, Emily L.; Seitz, Michael P.; Cole, Andrew J.; Hoch, Daniel B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hsu, John] Massachusetts Gen Hosp, Dept Med, Mongan Inst, Boston, MA 02114 USA. [Hsu, John] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. [Vickrey, Barbara G.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. RP Moura, LMVR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Wang 739D, Boston, MA 02114 USA. EM lidia.moura@mgh.harvard.edu; tcarneiro@mgh.harvard.edu; ethorn@mgh.harvard.edu; mseitz@mgh.harvard.edu; john.hsu@mgh.harvard.edu; cole.andrew@mgh.harvard.edu; barbara.vickrey@mssm.edu; dhoch@mgh.harvard.edu FU National Institutes of Health; Clinical Research Fellowship - American Academy of Neurology; American Brain Foundation FX The authors acknowledge Hui Zheng, Ph.D. for statistical consultation through the Harvard Catalyst Biostatistical Consulting Program, funded by the National Institutes of Health. The first author is the recipient of The 2015 Clinical Research Fellowship, sponsored by American Academy of Neurology and American Brain Foundation, to conduct this study. NR 37 TC 1 Z9 1 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD SEP PY 2016 VL 62 BP 90 EP 96 DI 10.1016/j.yebeh.2016.06.024 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DX5AP UT WOS:000384392500017 PM 27450312 ER PT J AU Pieters, HC Iwaki, T Vickrey, BG Mathern, GW Baca, CB AF Pieters, Huibrie C. Iwaki, Tomoko Vickrey, Barbara G. Mathern, Gary W. Baca, Christine B. TI "It was five years of hell": Parental experiences of navigating and processing the slow and arduous time to pediatric resective epilepsy surgery SO EPILEPSY & BEHAVIOR LA English DT Article DE Parent; Pediatric; Epilepsy surgery; Decision-making; Proxy report; Patient empowerment ID MEDICALLY REFRACTORY EPILEPSY; SHARED DECISION-MAKING; IMPROVED OUTCOMES; ONSET EPILEPSY; PEER SUPPORT; CHILDREN; NEUROLOGISTS; ATTITUDES; CARE; HEMISPHERECTOMY AB Objective: Children with medically refractory epilepsy stand to benefit from surgery and live a life free of seizures. However, a large proportion of potentially eligible children do not receive a timely referral for a surgical evaluation. We aimed to describe experiences during the arduous time before the referral and the parent-reported facilitators that helped them move forward through this slow time. Methods: Individual semi-structured interviews with 37 parents of children who had previously undergone epilepsy surgery at UCLA (2006-2011) were recorded, transcribed, and systematically analyzed by two independent coders using thematic analysis. Clinical data were extracted from medical records. Results: Parents, 41.3 years of age on average, were mostly Caucasian, English-speaking, mothers, married, and employed. The mean age at surgery for children was 8.2 years with a mean time from epilepsy onset to surgery of 5.4 years. Parental decision-making was facilitated when parents eventually received a presurgical referral and navigated to a multidisciplinary team that they trusted to care for their child with medically refractory epilepsy. Four themes described the experiences that parents used to feel a sense of moving forward. The first theme, processing, involved working through feelings and was mostly done alone. The second theme, navigating the complex unknowns of the health-care system, was more active and purposeful. Processing co-occurred with navigating in a fluid intersection, the third theme, which was evidenced by deliberate actions. The fourth theme, facilitators, explained helpful ways of processing and navigating; parents utilized these mechanisms to turn vulnerable times following the distress of their child's diagnosis into an experience of productivity. Significance: To limit parental distress and remediate the slow and arduous journey to multidisciplinary care at a comprehensive epilepsy center for a surgical evaluation, we suggest multi-pronged interventions to modify barriers associated with parents, providers, and health-care systems. Based on the facilitators that moved parents of our sample forward, we provide practical suggestions such as increased peer support, developing the role of patient navigators and communication strategies with parents before, during, and after referral to a comprehensive epilepsy center and presurgical evaluation. Published by Elsevier Inc. C1 [Pieters, Huibrie C.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Iwaki, Tomoko] NYU, Silver Sch Social Work, New York, NY USA. [Vickrey, Barbara G.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Mathern, Gary W.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Baca, Christine B.] Univ Calif Los Angeles, Dept Neurol, 710 Westwood Blvd,C-249, Los Angeles, CA 90024 USA. [Baca, Christine B.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. RP Baca, CB (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Blvd,C-249, Los Angeles, CA 90024 USA. EM cbower@mednet.ucla.edu FU Epilepsy Foundation grant [213971]; National Cancer Institute; UCLA Faculty Career Development Award for Assistant Professors [R21CA167218-02]; NIH [U54 N5081764, RO1 NS38992]; UniHealth Foundation; California Community Foundation; Veterans Administration Health Services Research and Development (VA HSRD) [IIR-12-337-3] FX This project was funded by an Epilepsy Foundation grant (PI Baca: 213971).; Dr. Pieters is supported by a grant from the National Cancer Institute and UCLA Faculty Career Development Award for Assistant Professors (R21CA167218-02).; Dr. Vickrey receives support from NIH U54 N5081764, UniHealth Foundation, and the California Community Foundation.; Dr. Mathern is the Davies/Crandall endowed chair for epilepsy research at UCLA and is co-editor-in-chief of Epilepsia and Epilepsia Open and is on the editorial board of Neurology. He receives funding from NIH RO1 NS38992.; Dr. Baca is a co-investigator on grant from the Veterans Administration Health Services Research and Development (VA HSR&D IIR-12-337-3) and is the PI for the AES/EF Junior Investigator Research Award. NR 43 TC 1 Z9 1 U1 3 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 SEP PY 2016 VL 62 BP 276 EP 284 DI 10.1016/j.yebeh.2016.07.019 PG 9 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DX5AP UT WOS:000384392500047 PM 27521720 ER PT J AU Tenhola, S Voutilainen, R Reyes, M Toiviainen-Salo, S Juppner, H Makitie, O AF Tenhola, Sirpa Voutilainen, Raimo Reyes, Monica Toiviainen-Salo, Sanna Juppner, Harald Makitie, Outi TI Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CALCIUM-SENSING RECEPTOR; HYPOPARATHYROIDISM; HYPERCALCEMIA AB Objective: Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and inappropriately low PTH concentrations. ADH type 1 is caused by activating mutations in the calcium-sensing receptor (CASR), a G-protein-coupled receptor signaling through alpha(11) (G alpha(11)) and alpha(q) (G alpha(q)) subunits. Heterozygous activating mutations in GNA11, the gene encoding G alpha(11), underlie ADH type 2. This study describes disease characteristics in a family with ADH caused by a gain-of-function mutation in GNA11. Design: A three-generation family with seven members (3 adults, 4 children) presenting with ADH. Methods: Biochemical parameters of calcium metabolism, clinical, genetic and brain imaging findings were analyzed. Results: Sanger sequencing revealed a heterozygous GNA11 missense mutation (c. 1018G>A, p.V340M) in all seven hypocalcemic subjects, but not in the healthy family members (n = 4). The adult patients showed clinical symptoms of hypocalcemia, while the children were asymptomatic. Plasma ionized calcium ranged from 0.95 to 1.14 mmol/L, yet plasma PTH was inappropriately low for the degree of hypocalcemia. Serum 25OHD was normal. Despite hypocalcemia 1,25(OH)(2)D and urinary calcium excretion were inappropriately in the reference range. None of the patients had nephrocalcinosis. Two adults and one child (of the two MRI scanned children) had distinct intracranial calcifications. All affected subjects had short stature (height S.D. scores ranging from -3.4 to -2.3 vs -0.5 in the unaffected children). Conclusions: The identified GNA11 mutation results in biochemical abnormalities typical for ADH. Additional features, including short stature and early intracranial calcifications, cosegregated with the mutation. These findings may indicate a wider role for G alpha(11) signaling besides calcium regulation. C1 [Tenhola, Sirpa] Kymenlaakso Cent Hosp, Dept Pediat, Kotka, Finland. [Tenhola, Sirpa; Voutilainen, Raimo] Kuopio Univ Hosp, Dept Pediat, Kuopio, Finland. [Tenhola, Sirpa; Voutilainen, Raimo] Univ Eastern Finland, Kuopio, Finland. [Reyes, Monica; Juppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Reyes, Monica; Juppner, Harald] Harvard Med Sch, Boston, MA USA. [Toiviainen-Salo, Sanna] Univ Helsinki, HUS Med Imaging Ctr, Dept Radiol, Helsinki, Finland. [Toiviainen-Salo, Sanna; Makitie, Outi] Helsinki Univ Hosp, Helsinki, Finland. [Makitie, Outi] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Makitie, Outi] Folkhalsan Inst Genet, Helsinki, Finland. [Makitie, Outi] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Makitie, Outi] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. RP Makitie, O (reprint author), Univ Helsinki, Childrens Hosp, Helsinki, Finland.; Makitie, O (reprint author), Folkhalsan Inst Genet, Helsinki, Finland.; Makitie, O (reprint author), Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.; Makitie, O (reprint author), Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. EM outi.makitie@helsinki.fi FU Kuopio University Hospital; Academy of Finland; Sigrid Juselius Foundation; Folkhalsan Research Foundation; Foundation for Pediatric Research; Novo Nordisk Foundation; Helsinki University Hospital research funds; Swedish Research Council; Swedish Childhood Cancer Foundation; NIDDK grants [R01DK46718-20, PO1DK11794] FX This study was financially supported by Kuopio University Hospital, the Academy of Finland, the Sigrid Juselius Foundation, the Folkhalsan Research Foundation, Foundation for Pediatric Research, the Novo Nordisk Foundation, the Helsinki University Hospital research funds, the Swedish Research Council, the Swedish Childhood Cancer Foundation, through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and through NIDDK grants to H J (R01DK46718-20 and PO1DK11794 (subproject IV)). NR 15 TC 4 Z9 4 U1 1 U2 1 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 SEP PY 2016 VL 175 IS 3 BP 211 EP 218 DI 10.1530/EJE-16-0109 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX2IO UT WOS:000384192100011 PM 27334330 ER PT J AU ElSalhy, M Soderling, E Honkala, E Fontana, M Flannagan, S Kokaras, A Paster, BJ Varghese, A Honkala, S AF ElSalhy, M. Soderling, E. Honkala, E. Fontana, M. Flannagan, S. Kokaras, A. Paster, B. J. Varghese, A. Honkala, S. TI Salivary microbiota and caries occurrence in Mutans Streptococci-positive school children SO EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY LA English DT Article DE Cartes prevalence; Children With mixed dentition; Salivary microbiota ID EARLY-CHILDHOOD CARIES; DENTAL-CARIES; RISK; DENTITION; SCHOOLCHILDREN; BACTERIA AB Aim To compare the composition of the salivary microbiota. in caries-affected vs. caries-free mutans streptococci (MS)-positive children with mixed dentition. Methods Twenty eight healthy, 11-12-year-old schoolchildren with high MS counts (>10(5)CFU/mL) were included in this study. The children were screened with the Dentocult (R) SM Strip Mutans test (Orion Diagnostica, Espoo, Finland) and examined using the International Caries Detection and Assessment System (ICDAS). The microbial composition of the saliva was assessed using the Human Oral Microbe Identification Microarray (HOMIM). Microbial differences between caries-affected (n=18) and caries-free children (n=10) were compared by Mann-Whitney analysis. Results The microbiota of the caries-affected vs. caries free children was rather similar. Abiotrophia defectiva and Actinomyces meyeri/A. odontolyticus were significantly higher in caries-affected than in caries-free children (p=0.006, 0.046, respectively). Shuttleworthia satelles was significantly higher in caries-free compared to caries-affected children (p=0.031). A. defectiva and A. meyeri/A. odontolyticus correlated positively with caries severity measured by ICDAS Caries Index (p = 0.494, 0.454, 0.400 respectively) while S. satelles was negatively correlated with caries severity (p= -0.489). Conclusions Salivary A. defectiva and A. meyeri/A. odontolyticus and are associated with caries occurrence in MS-positive children with mixed dentition. C1 [ElSalhy, M.; Honkala, E.; Varghese, A.; Honkala, S.] Kuwait Univ, Fac Dent, Kuwait, Kuwait. [ElSalhy, M.; Soderling, E.] Univ Turku, Inst Dent, SF-20500 Turku, Finland. [Fontana, M.; Flannagan, S.] Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA. [Kokaras, A.; Paster, B. J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, B. J.] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. RP ElSalhy, M (reprint author), Kuwait Univ, Fac Dent, Kuwait, Kuwait.; ElSalhy, M (reprint author), Univ Turku, Inst Dent, SF-20500 Turku, Finland. EM alsalhy1@hotmail.com FU Kuwait University [DD02/10, GD01/11, SRUL02/13]; Kuwait Foundation for the Advancement of Sciences [2011-5502-01]; Alberta Innovates-Health Solutions (AIHS) Clinician Fellowship [RES0027148]; Honorary Izaak Walton Killam Memorial Scholarship FX This study was supported by Kuwait University grants DD02/10, GD01/11, SRUL02/13 and by Kuwait Foundation for the Advancement of Sciences under project code: 2011-5502-01. M. ElSalhy is supported through Alberta Innovates-Health Solutions (AIHS) Clinician Fellowship (RES0027148) and the Honorary Izaak Walton Killam Memorial Scholarship. NR 30 TC 0 Z9 0 U1 2 U2 2 PU ARIESDUE SRL PI CARIMATE PA VIA AIROLDI, CARIMATE, 11-22060, ITALY SN 1591-996X EI 2035-648X J9 EUR J PAEDIATR DENT JI Eur. J. Paediatr. Dent. PD SEP PY 2016 VL 17 IS 3 BP 188 EP 192 PG 5 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA DX1WA UT WOS:000384156500004 PM 27759406 ER PT J AU Beitler, JJ Quon, H Jones, CU Salama, JK Busse, PM Cooper, JS Koyfman, SA Ridge, JA Saba, NF Siddiqui, F Smith, RV Worden, F Yao, M Yom, SS AF Beitler, Jonathan J. Quon, Harry Jones, Christopher U. Salama, Joseph K. Busse, Paul M. Cooper, Jay S. Koyfman, Shlomo A. Ridge, John A. Saba, Nabil F. Siddiqui, Farzan Smith, Richard V. Worden, Francis Yao, Min Yom, Sue S. CA Expert Panel Radiation Oncology-He TI ACR Appropriateness Criteria (R) Locoregional therapy for resectable oropharyngeal squamous cell carcinomas SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE oropharyngeal cancer; human papillomavirus (HPV); tonsillar cancer; base of tongue cancer; transoral robotic surgery (TORS) ID LOCALLY ADVANCED HEAD; INTENSITY-MODULATED RADIOTHERAPY; QUALITY-OF-LIFE; TRANSORAL LATERAL OROPHARYNGECTOMY; ADVANCED NASOPHARYNGEAL CARCINOMA; PROSPECTIVE RANDOMIZED-TRIAL; PHASE-III TRIAL; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; RADIATION-THERAPY AB Background. There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC. Methods. The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use. Results. A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC. Conclusion. T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. (C) 2016 American College of Radiology. C1 [Beitler, Jonathan J.] Emory Univ, Sch Med, Atlanta, GA USA. [Quon, Harry] Johns Hopkins Univ, Baltimore, MD USA. [Jones, Christopher U.] Radiol Associates Sacramento, Sacramento, CA USA. [Salama, Joseph K.] Duke Univ, Med Ctr, Durham, NC USA. [Busse, Paul M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cooper, Jay S.] Maimonides Canc Ctr, Brooklyn, NY USA. [Koyfman, Shlomo A.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Ridge, John A.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Ridge, John A.; Smith, Richard V.] Amer Coll Surg, Philadelphia, PA USA. [Saba, Nabil F.] Emory Univ, Atlanta, GA 30322 USA. [Saba, Nabil F.; Worden, Francis] Amer Soc Clin Oncol, Atlanta, GA USA. [Siddiqui, Farzan] Henry Ford Hosp, Detroit, MI 48202 USA. [Smith, Richard V.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Worden, Francis] Univ Michigan, Ann Arbor, MI 48109 USA. [Yao, Min] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Yom, Sue S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Beitler, JJ (reprint author), Emory Univ, Dept Radiat Oncol, Sch Med, 550 Peachtree St NE, Atlanta, GA 30308 USA. EM publications@acr.org NR 90 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD SEP PY 2016 VL 38 IS 9 BP 1299 EP 1309 DI 10.1002/hed.24447 PG 11 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA DX0OD UT WOS:000384061700005 PM 27330003 ER PT J AU Moy, AP Arora, K Deshpande, V AF Moy, Andrea P. Arora, Kshitij Deshpande, Vikram TI Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma SO HISTOPATHOLOGY LA English DT Article DE albumin; bile duct adenoma; BRAF; in-situ hybridization ID IN-SITU-HYBRIDIZATION; MEYENBURG COMPLEX; BILIARY-TRACT; PATHOGENESIS; CARCINOMA; LIVER; IMMUNOHISTOCHEMISTRY; HAMARTOMA; MUTATIONS; RNA AB AimsBile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. Methods and resultsWe studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity ofexpression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. ConclusionsDiagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH. C1 [Deshpande, Vikram] Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 256, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,Warren 256, Boston, MA 02114 USA. EM vikramdirdeshpande@gmail.com FU Affymetrix, CA, USA FX The study was supported in part by a sponsored research agreement between the authors' institution and Affymetrix, CA, USA. This work was presented in abstract form at the 103rd United States and Canadian Academy of Pathology Annual Meeting in San Diego, CA, USA in March 2014. The study was approved by the IRB (2015P002328). The IRB has waived the requirement for individual patient consent. NR 22 TC 2 Z9 2 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 SEP PY 2016 VL 69 IS 3 BP 423 EP 430 DI 10.1111/his.12942 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DV3UE UT WOS:000382848200006 PM 26841202 ER PT J AU Kamionek, M Moghaddam, PA Sakhdari, A Kovach, AE Welch, M Meng, XL Dresser, K Tomaszewicz, K Cosar, EF Mark, EJ Fraire, AE Hutchinson, L AF Kamionek, Michal Moghaddam, Parnian Ahmadi Sakhdari, Ali Kovach, Alexandra E. Welch, Matthew Meng, Xiuling Dresser, Karen Tomaszewicz, Keith Cosar, Ediz F. Mark, Eugene J. Fraire, Armando E. Hutchinson, Lloyd TI Mutually exclusive extracellular signal-regulated kinase pathway mutations are present in different stages of multi-focal pulmonary Langerhans cell histiocytosis supporting clonal nature of the disease SO HISTOPATHOLOGY LA English DT Article DE clonal neoplasm; ERK pathway; natural history; pathogenesis; PLCH ID CONFER RESISTANCE; SOMATIC MUTATIONS; MAP2K1; CANCER AB AimsPulmonary Langerhans cell histiocytosis (PLCH) is an idiopathic cigarette smoking-related disorder of the lung. Molecular changes in cellular or fibrotic stages of PLCH have not been investigated. We studied the prevalence of extracellular signal-regulated kinase (ERK) pathway mutations in different PLCH stages and other non-PLCH smoking-related lung diseases. Methods and resultsThe cohort included 28 PLCH with cellular (n = 10), mixed cellular/fibrotic (n = 4) and fibrotic histology (n = 14). Seven cases had concurrent multi-focal/multi-lobar tumours. Respiratory bronchiolitis interstitial lung disease (RB-ILD, n = 2), desquamative interstitial pneumonia (DIP, n = 4) and mixed RB-ILD/DIP (n = 2) were included for comparison. BRAF(V600E)immunohistochemistry, next-generation sequencing (NGS) and peptide nucleic acid (PNA) clamp polymerase chain reaction (PCR) with high analytical sensitivity (<0.1-0.2%) were used to analyse RAS, BRAF and MAP2K1 genes. Of 26 cases with gene mutation data, BRAF(V600E) was identified in eight of 12 (67%) cellular cases and in one of 14 (7%) fibrotic cases. MAP2K1 or KRAS mutations were observed in four of 14 (29%) fibrotic cases and three of the 12 (25%) cellular cases. Multi-focal/multi-lobar specimens carried identical BRAF (n = 5) or non-hotspot MAP2K1 (n = 2) mutations. The other smoking-related disorders were negative for mutations. Patients with cellular lesions or BRAF mutation were significantly younger than patients with fibrotic or BRAF wild-type PLCH. ConclusionThe presence of identical but mutually exclusive ERK pathway mutations in multi-focal PLCH supports a neoplastic/clonal origin for this disease. Patient age and mutation type differed between cellular and fibrotic histology and may indicate a natural progression or a mutation-specific pathogenicity. C1 [Kamionek, Michal; Kovach, Alexandra E.; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moghaddam, Parnian Ahmadi; Sakhdari, Ali; Welch, Matthew; Meng, Xiuling; Dresser, Karen; Tomaszewicz, Keith; Cosar, Ediz F.; Fraire, Armando E.; Hutchinson, Lloyd] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. RP Hutchinson, L (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. EM Lloyd.Hutchinson@umassmemorial.org NR 31 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 SEP PY 2016 VL 69 IS 3 BP 499 EP 509 DI 10.1111/his.12955 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA DV3UE UT WOS:000382848200014 PM 26915300 ER PT J AU Shu, YL Tao, Y Wang, ZM Tang, Y Li, HW Dai, P Gao, GP Chen, ZY AF Shu, Yilai Tao, Yong Wang, Zhengmin Tang, Yong Li, Huawei Dai, Pu Gao, Guangping Chen, Zheng-Yi TI Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes SO HUMAN GENE THERAPY LA English DT Article ID IN-VIVO DELIVERY; GENE-THERAPY; HEARING-LOSS; MOUSE MODEL; SCALA MEDIA; GUINEA-PIG; COCHLEA; VIRUS; TRANSDUCTION; DEAFNESS AB The mammalian inner ear consists of diverse cell types with important functions. Gene mutations in these diverse cell types have been found to underlie different forms of genetic hearing loss. Targeting these mutations for gene therapy development represents a future therapeutic strategy to treat hearing loss. Adeno-associated viral (AAV) vectors have become the vector of choice for gene delivery in animal models in vivo. To identify AAV vectors that target inner ear cell subtypes, we systemically screened 12 AAV vectors with different serotypes (AAV1, 2, 5, 6, 6.2, 7, 8, 9, rh. 8, rh. 10, rh. 39, and rh. 43) that carry a reporter gene GFP in neonatal and adult mice by microinjection in vivo. We found that most AAVs infect both neonatal and adult inner ear, with different specificities and expression levels. The inner ear cochlear sensory epithelial region, which includes auditory hair cells and supporting cells, is most frequently targeted for gene delivery. Expression of the transgene is sustained, and neonatal inner ear delivery does not adversely affect hearing. Adult inner ear injection of AAV has a similar infection pattern as the younger inner ear, with the exception that outer hair cell death caused by the injection procedure can lead to hearing loss. In the adult, more so than in the neonatal mice, cell types infected and efficiency of infection are correlated with the site of injection. Most infected cells survive in neonatal and adult inner ears. The study adds to the list of AAV vectors that transduce the mammalian inner ear efficiently, providing the tools that are important to study inner ear gene function and for the development of gene therapy to treat hearing loss. C1 [Shu, Yilai; Tao, Yong; Tang, Yong; Chen, Zheng-Yi] Harvard Med Sch, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Shu, Yilai; Tao, Yong; Tang, Yong; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. [Shu, Yilai; Wang, Zhengmin; Li, Huawei] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai, Peoples R China. [Shu, Yilai; Wang, Zhengmin; Li, Huawei] Natl Hlth & Family Planning Commiss, Key Lab Hearing Med, Shanghai, Peoples R China. [Tang, Yong] Peoples Hosp Jilin Prov, Dept Ear Nose & Throat, Changchun, Jilin Province, Peoples R China. [Dai, Pu] Chinese Peoples Liberat Army Gen Hosp, Dept Otolaryngol, Beijing, Peoples R China. [Gao, Guangping] Univ Massachusetts, Sch Med, Horae Gene Therapy Ctr, Worcester, MA USA. [Gao, Guangping] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA USA. [Gao, Guangping] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China. RP Chen, ZY (reprint author), Harvard Med Sch, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.; Chen, ZY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM zheng-yi_chen@meei.harvard.edu FU U.S. National Institutes of Health [R01 DC006908]; Frederick and Ines Yeatts Hair Cell Regeneration Grant; National Nature Science Foundation of China [NSFC81300824]; Science and Technology Commission of Shanghai Municipality [15pj1401000] FX Z.-Y.C. was supported by U.S. National Institutes of Health (R01 DC006908). Y.S., Y.T., and Y.T. were supported by the Frederick and Ines Yeatts Hair Cell Regeneration Grant and Y.S. by the National Nature Science Foundation of China (NSFC81300824) and Science and Technology Commission of Shanghai Municipality (15pj1401000). NR 34 TC 1 Z9 1 U1 13 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2016 VL 27 IS 9 BP 687 EP 699 DI 10.1089/hum.2016.053 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DW9IE UT WOS:000383970300005 PM 27342665 ER PT J AU Perez-Pinera, P Chen, ZY AF Perez-Pinera, Pablo Chen, Zheng-Yi TI Biomedical applications of gene editing SO HUMAN GENETICS LA English DT Editorial Material C1 [Perez-Pinera, Pablo] Univ Illinois, Dept Bioengn, Digital Comp Lab 1270, MC-278,1304 West Springfield Ave, Urbana, IL 61801 USA. [Perez-Pinera, Pablo] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. [Chen, Zheng-Yi] Harvard Med Sch, Dept Otolaryngol, Boston, MA 02114 USA. [Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Perez-Pinera, P (reprint author), Univ Illinois, Dept Bioengn, Digital Comp Lab 1270, MC-278,1304 West Springfield Ave, Urbana, IL 61801 USA.; Perez-Pinera, P (reprint author), Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.; Chen, ZY (reprint author), Harvard Med Sch, Dept Otolaryngol, Boston, MA 02114 USA.; Chen, ZY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM pablo@illinois.edu; Zheng-Yi_Chen@meei.harvard.edu NR 11 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2016 VL 135 IS 9 SI SI BP 967 EP 969 DI 10.1007/s00439-016-1723-1 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA DX2TN UT WOS:000384223800001 PM 27535845 ER PT J AU Papazian, L Corley, A Hess, D Fraser, JF Frat, JP Guitton, C Jaber, S Maggiore, SM Nava, S Rello, J Ricard, JD Stephan, F Trisolini, R Azoulay, E AF Papazian, Laurent Corley, Amanda Hess, Dean Fraser, John F. Frat, Jean-Pierre Guitton, Christophe Jaber, Samir Maggiore, Salvatore M. Nava, Stefano Rello, Jordi Ricard, Jean-Damien Stephan, Francois Trisolini, Rocco Azoulay, Elie TI Use of high-flow nasal cannula oxygenation in ICU adults: a narrative review SO INTENSIVE CARE MEDICINE LA English DT Review DE High-flow nasal cannula oxygenation; Oxygen therapy; Acute respiratory failure; Bronchoscopy; Aerosol; Non-invasive ventilation ID ACUTE RESPIRATORY-FAILURE; POSITIVE-PRESSURE VENTILATION; INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; CARDIAC SURGICAL-PATIENTS; CRITICALLY-ILL PATIENTS; EXPIRATORY LUNG-VOLUME; NONINVASIVE VENTILATION; AIRWAY PRESSURE; FIBEROPTIC BRONCHOSCOPY AB Oxygen therapy can be delivered using low-flow, intermediate-flow (air entrainment mask), or high-flow devices. Low/intermediate-flow oxygen devices have several drawbacks that cause critically ill patients discomfort and translate into suboptimal clinical results. These include limitation of the FiO(2) (due to the high inspiratory flow often observed in patients with respiratory failure), and insufficient humidification and warming of the inspired gas. High-flow nasal cannula oxygenation (HFNCO) delivers oxygen flow rates of up to 60 L/min and over the last decade its effect on clinical outcomes has widely been evaluated, such as in the improvement of respiratory distress, the need for intubation, and mortality. Mechanisms of action of HFNCO are complex and not limited to the increased oxygen flow rate. The main aim of this review is to guide clinicians towards evidence-based clinical practice guidelines. It summarizes current knowledge about HFNCO use in ICU patients and the potential areas of uncertainties. For instance, it has been recently suggested that HFNCO could improve the outcome of patients with hypoxemic acute respiratory failure. In other settings, research is ongoing and additional evidence is needed. For instance, if intubation is required, studies suggest that HFNCO may help to improve preoxygenation and can be used after extubation. Likewise, HFNCO might be used in obese patients, or to prevent respiratory deterioration in hypoxemic patients requiring bronchoscopy, or for the delivery of aerosol therapy. However, areas for which conclusive data exist are limited and interventions using standardized HFNCO protocols, comparators, and relevant clinical outcomes are warranted. C1 [Papazian, Laurent] Hop Nord Marseille, Assistance Publ Hop Marseille, Reanimat Detresses Resp & Infect Severes, Chemin Bourrely, F-13015 Marseille, France. [Papazian, Laurent] Aix Marseille Univ, URMITE UMR CNRS 7278, Fac Med, F-13005 Marseille, France. [Corley, Amanda; Fraser, John F.] Prince Charles Hosp, Crit Care Res Grp, Brisbane, Qld, Australia. [Corley, Amanda; Fraser, John F.] Univ Queensland, Brisbane, Qld, Australia. [Hess, Dean] Massachusetts Gen Hosp, Resp Care Dept, Boston, MA 02114 USA. [Hess, Dean] Harvard Med Sch, Dept Anesthesia, Boston, MA USA. [Frat, Jean-Pierre] CHU Poitiers, Reanimat Med, Poitiers, France. [Frat, Jean-Pierre] Univ Poitiers, INSERM, CIC 1402, Poitiers, France. [Guitton, Christophe] Univ Hosp Nantes, Hotel Dieu, Med ICU, Nantes, France. [Jaber, Samir] St Eloi Univ Hosp, Res Unit INSERM U1046, Dept Crit Care Med & Anesthesiol DAR B, 80 Ave Augustin Fliche, F-34295 Montpellier, France. [Jaber, Samir] Montpellier Sch Med, 80 Ave Augustin Fliche, F-34295 Montpellier, France. [Maggiore, Salvatore M.] Univ Gabriele dAnnunzio Chieti Pescara, Policlin SS Annunziata, Dept Anesthesiol & Crit Care Med, Via Vestini 31, I-66100 Chieti, Italy. [Nava, Stefano] Univ Bologna, Malpighi Hosp, Sch Med Resp & Crit Care, Dept Specialist Diagnost & Expt Med, Bologna, Italy. [Rello, Jordi] Univ Autonoma Barcelona, CIBERES, Dept Med, Ps Vall dHebron 119,Anexe AG-5a Planta, Barcelona 08035, Spain. [Ricard, Jean-Damien] Hop Louis Mourier, AP HP, Serv Reanimat Medicochirurg, 178 Rue Renouillers, F-92700 Colombes, France. [Ricard, Jean-Damien] INSERM, IAME, UMR 1137, F-75018 Paris, France. [Ricard, Jean-Damien] Univ Paris Diderot, Sorbonne Paris Cite, IAME, UMR 1137, F-75018 Paris, France. [Stephan, Francois] Hop Marie Lannelongue, Serv Reanimat Adulte, 133 Ave Resistance, F-92350 Le Plessis Robinson, France. [Trisolini, Rocco] Malpighi Bologna Hosp, Intervent Pulmol, Bologna, Italy. [Azoulay, Elie] Paris Diderot Univ, Hop St Louis, AP HP, Sorbonne Paris Cite,Serv Reanimat Med, Paris, France. RP Papazian, L (reprint author), Hop Nord Marseille, Assistance Publ Hop Marseille, Reanimat Detresses Resp & Infect Severes, Chemin Bourrely, F-13015 Marseille, France.; Papazian, L (reprint author), Aix Marseille Univ, URMITE UMR CNRS 7278, Fac Med, F-13005 Marseille, France. EM laurent.papazian@ap-hm.fr FU Fisher and Paykel Healthcare FX Amanda Corley: unrestricted grant and travel expenses from Fisher and Paykel Healthcare; John F. Fraser: unrestricted grant and travel expenses from Fisher and Paykel Healthcare; Dean Hess: Philipps, Respironics, Bayer, Merck, Up To Date, McGraw-Hill, Jones and Bartlett, and the American Board of Internal Medicine; Jean-Damien Ricard: travel expenses from Fisher and Paykel Healthcare; Jean-Pierre Frat: travel expenses from Fisher and Paykel Healthcare; Stefano Nava: grant from Fisher and Paykel Healthcare; Salvatoire M. Maggiore: unrestricted research grant from Fisher and Paykel Healthcare; Francois Stephan: lecture fees from Fisher and Paykel Healthcare. NR 84 TC 13 Z9 13 U1 5 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2016 VL 42 IS 9 BP 1336 EP 1349 DI 10.1007/s00134-016-4277-8 PG 14 WC Critical Care Medicine SC General & Internal Medicine GA DU2IJ UT WOS:000382034200005 PM 26969671 ER PT J AU Beitler, JR Sands, SA Loring, SH Owens, RL Malhotra, A Spragg, RG Matthay, MA Thompson, BT Talmor, D AF Beitler, Jeremy R. Sands, Scott A. Loring, Stephen H. Owens, Robert L. Malhotra, Atul Spragg, Roger G. Matthay, Michael A. Thompson, B. Taylor Talmor, Daniel TI Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria SO INTENSIVE CARE MEDICINE LA English DT Article DE Acute respiratory distress syndrome; Acute lung injury; Ventilator-induced lung injury; Respiratory mechanics; Mechanical ventilation; Patient-ventilator dyssynchrony ID RESPIRATORY-DISTRESS-SYNDROME; PATIENT-VENTILATOR ASYNCHRONY; LUNG-PROTECTIVE VENTILATION; ASSIST-CONTROL MODE; MECHANICAL VENTILATION; INJURY; PRESSURE; ENTRAINMENT; MORTALITY; FREQUENCY AB Breath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS. Airway flow and pressure were recorded continuously for up to 72 h in 33 patients with ARDS receiving volume-preset assist-control ventilation. The flow-time waveform was integrated to calculate tidal volume breath-by-breath. The BREATHE criteria considered five domains in evaluating for breath stacking dyssynchrony: ventilator cycling, interval expiratory volume, cumulative inspiratory volume, expiratory time, and inspiratory time. The observed tidal volume of BREATHE stacked breaths was 11.3 (9.7-13.3) mL/kg predicted body weight, significantly higher than the preset volume [6.3 (6.0-6.8) mL/kg; p < 0.001]. BREATHE identified more high-volume breaths (aeyen2 mL/kg above intended volume) than the other existing objective criteria for breath stacking [27 (7-59) vs 19 (5-46) breaths/h; p < 0.001]. Agreement between BREATHE and visual waveform inspection was high (raw agreement 96.4-98.1 %; phi 0.80-0.92). Breath stacking dyssynchrony was near-completely eliminated during neuromuscular blockade [0 (0-1) breaths/h; p < 0.001]. The BREATHE criteria provide an objective definition of breath stacking dyssynchrony emphasizing occult exposure to high tidal volumes. BREATHE identified high-volume breaths missed by other methods for quantifying this dyssynchrony. Neuromuscular blockade prevented breath stacking dyssynchrony, assuring provision of the intended lung-protective strategy. C1 [Beitler, Jeremy R.; Owens, Robert L.; Malhotra, Atul; Spragg, Roger G.] Univ Calif San Diego, Div Pulm & Crit Care Med, 200 West Arbor Dr,8409, San Diego, CA 92103 USA. [Sands, Scott A.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. [Sands, Scott A.] Harvard Med Sch, Boston, MA USA. [Sands, Scott A.] The Alfred, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia. [Sands, Scott A.] The Alfred, Cent Clin Sch, Melbourne, Vic, Australia. [Sands, Scott A.] Monash Univ, Melbourne, Vic, Australia. [Loring, Stephen H.; Talmor, Daniel] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA USA. [Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Beitler, JR (reprint author), Univ Calif San Diego, Div Pulm & Crit Care Med, 200 West Arbor Dr,8409, San Diego, CA 92103 USA. EM jbeitler@ucsd.edu FU National Heart, Lung, and Blood Institute [T32-HL007633, K24-HL132105, R01-HL085188, UM1-HL108724]; National Health and Medical Research Council of Australia [1053201]; American Heart Association [11POST7360012, 15SDG25890059] FX This project was supported in part by grants from the National Heart, Lung, and Blood Institute (Dr. Beitler: T32-HL007633; Dr. Malhotra: K24-HL132105, R01-HL085188; Dr. Talmor: UM1-HL108724), National Health and Medical Research Council of Australia (Dr. Sands: 1053201), and American Heart Association (Dr. Sands: 11POST7360012, 15SDG25890059). NR 37 TC 5 Z9 5 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2016 VL 42 IS 9 BP 1427 EP 1436 DI 10.1007/s00134-016-4423-3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA DU2IJ UT WOS:000382034200013 PM 27342819 ER PT J AU Fang, A Siev, J Minichiello, WE Baer, L AF Fang, Angela Siev, Jedidiah Minichiello, William E. Baer, Lee TI Association Between Scrupulosity and Personality Characteristics in Individuals With Obsessive-Compulsive Symptoms SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article DE neuroticism; obsessive-compulsive disorder; obsessive-compulsive personality disorder; personality; scrupulosity ID BEHAVIOR-THERAPY; PENN INVENTORY; 5-FACTOR MODEL; OCI-R; DISORDER; ANXIETY; SAMPLE; DIMENSIONS; PERFECTIONISM; VALIDATION AB Scrupulosity is a subtype of obsessive-compulsive disorder (OCD) defined by religious or moral fears. Although the relationship between personality and OCD has been extensively studied, it remains unclear how personality relates specifically to religious obsessions and scrupulous fears. In the current study, we examined the association between scrupulosity and personality characteristics, including the Five Factor Model (FFM) and obsessive-compulsive personality disorder (OCPD), in a sample of individuals with self-reported obsessive-compulsive (OC) symptoms. Seventy-nine participants completed an anonymous online survey. FFM traits did not, but OCPD traits did, explain a significant amount of variance in scrupulosity. We also replicated previous findings showing that individuals with greater OC symptoms score lower on Extraversion and higher on Neuroticism. These findings suggest that scrupulous symptoms may not be specifically linked with any of the FFM personality factors, but may be associated with OCPD. Findings are discussed in the context of cognitive-behavioral theory and practice. C1 [Fang, Angela; Minichiello, William E.; Baer, Lee] Harvard Med Sch, Massachusetts Gen Hosp, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. [Siev, Jedidiah] Nova Southeastern Univ, Ft Lauderdale, FL USA. RP Fang, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM afang@partners.org NR 43 TC 0 Z9 0 U1 4 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 1937-1209 EI 1937-1217 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD SEP PY 2016 VL 9 IS 3 BP 245 EP 259 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DW4UB UT WOS:000383637400005 ER PT J AU Lanthier, S Strbian, D Putaala, J Letourneau-Guillon, L Ferro, JM Calabrese, LH Frosch, MP Seifert-Held, T Hietaharju, A Geraldes, R Mackey, A Poppe, AY Singhal, AB Dubuc, V AF Lanthier, Sylvain Strbian, Daniel Putaala, Jukka Letourneau-Guillon, Laurent Ferro, Jose M. Calabrese, Leonard H. Frosch, Matthew P. Seifert-Held, Thomas Hietaharju, Aki Geraldes, Ruth Mackey, Ariane Poppe, Alexandre Y. Singhal, Aneesh B. Dubuc, Veronique TI The International Study on Primary Angiitis of the Central Nervous System (INTERSPACE) - a Call to the World SO INTERNATIONAL JOURNAL OF STROKE LA English DT Meeting Abstract C1 [Lanthier, Sylvain; Letourneau-Guillon, Laurent; Poppe, Alexandre Y.] CHUM Univ Montreal, Montreal, PQ, Canada. [Strbian, Daniel] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Putaala, Jukka; Ferro, Jose M.; Geraldes, Ruth] Hosp Santa Maria, Lisbon, Portugal. [Calabrese, Leonard H.] Cleveland Clin, Cleveland, OH 44106 USA. [Frosch, Matthew P.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Azienda Osped ASMN Ist Ricovero & Cura Carattere, Reggio Emilia, Italy. [Seifert-Held, Thomas] Med Univ Graz, Graz, Austria. [Hietaharju, Aki] Tampere Univ Hosp, Tampere, Finland. [Mackey, Ariane] CHUQ Laval Hosp Quebec, Quebec City, PQ, Canada. [Dubuc, Veronique] Sacre Coeur Hosp Montreal, Montreal, PQ, Canada. 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD SEP PY 2016 VL 11 SU 2 MA P5.02 BP 87 EP 87 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DW9CL UT WOS:000383952400246 ER PT J AU Ratushny, V Kraft, S Moschella, SL Duncan, LM Lawrence, DP Tsao, H AF Ratushny, Vladimir Kraft, Stefan Moschella, Samuel L. Duncan, Lyn M. Lawrence, Donald P. Tsao, Hensin TI A Symmetric Eczematous Eruption Harboring Thousands of Melanocytic Lesions SO JAMA DERMATOLOGY LA English DT Article ID METASTATIC MELANOMA; BRAF MUTATIONS; NEVI AB IMPORTANCE The abrupt appearance of melanocytic lesions is a unique phenomenon that can occur in the setting of eruptive nevi or epidermotropic melanoma metastases. OBJECTIVE To examine the immunohistochemical and genetic mutative features of a novel case of an eczematous reaction followed by the abrupt appearance of melanocytic lesions. DESIGN, SETTING, AND PARTICIPANT Case report of a 48-year-old woman with no significant medical history who first presented with an eczematous dermatitis on her torso, extremities, and buttocks and who subsequently developed thousands of pinpoint, histologically atypical melanocytic tumors and invasive melanoma within the areas of inflammation. MAIN OUTCOMES AND MEASURES Immunohistochemical and mutational analyses of the patient's melanocytic tumors were conducted. RESULTS Mutational analysis of the pigmented lesions did not identify any activating mutations in BRAF, PTEN, NRAS, KRAS, and HRAS. Immunohistochemical analyses of 9 biopsied pigmented lesions all showed normal expression of the tumor suppressors p16 and PTEN and no expression of mutated BRAF V600E protein. CONCLUSIONS AND RELEVANCE To our knowledge, this is a previously unreported eruption comprising 2 distinct components: an eczematous reaction and a wave of melanocytic proliferations within the inflammatory regions. Possible explanations for this patient's condition, include immune stimulation leading to nevogenesis, benign "nevic" metastases, eruptive nevi, and epidermotropic metastatic melanoma. C1 [Ratushny, Vladimir; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. [Ratushny, Vladimir; Kraft, Stefan; Duncan, Lyn M.; Lawrence, Donald P.; Tsao, Hensin] Harvard Med Sch, Boston, MA USA. [Kraft, Stefan; Duncan, Lyn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moschella, Samuel L.] Lahey Hosp & Med Ctr, Dept Dermatol, Burlington, MA USA. [Lawrence, Donald P.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. EM htsao@mgh.harvard.edu FU National Cancer Institute [1K24 CA149202] FX This study was supported in part by grant 1K24 CA149202 from the National Cancer Institute. NR 8 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 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD SEP PY 2016 VL 152 IS 9 BP 1021 EP 1024 DI 10.1001/jamadermatol.2016.1150 PG 4 WC Dermatology SC Dermatology GA DX4EA UT WOS:000384332800015 PM 27192392 ER PT J AU Tollefson, TT Shaye, D AF Tollefson, Travis T. Shaye, David TI Expanding Roles and Broader Goals for Global Surgery SO JAMA FACIAL PLASTIC SURGERY LA English DT Editorial Material ID SURGICAL RECONSTRUCTION; EPIDEMIOLOGY; DEFORMITIES; ZIMBABWE; DISEASE; BURDEN; PALATE C1 [Tollefson, Travis T.] Univ Calif Davis, Med Ctr, Dept Otolaryngol Head & Neck Surg, 2521 Stockton Blvd,Ste 7200, Sacramento, CA 95817 USA. [Shaye, David] Harvard Med Sch, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Tollefson, TT (reprint author), Univ Calif Davis, Med Ctr, Dept Otolaryngol Head & Neck Surg, 2521 Stockton Blvd,Ste 7200, Sacramento, CA 95817 USA. EM tttollefson@ucdavis.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 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD SEP-OCT PY 2016 VL 18 IS 5 BP 361 EP 362 DI 10.1001/jamafacial.2016.0477 PG 3 WC Surgery SC Surgery GA DX3TC UT WOS:000384295300008 PM 27281013 ER PT J AU Kiyohara, N Badger, C Tjoa, T Wong, B AF Kiyohara, Nicole Badger, Christopher Tjoa, Tjoson Wong, Brian TI A Comparison of Over-the-Counter Mechanical Nasal Dilators A Systematic Review SO JAMA FACIAL PLASTIC SURGERY LA English DT Review ID AIR-FLOW; STRIP; NOSE; EXERCISE; DILATION; TRIAL AB IMPORTANCE The internal nasal valve is the narrowest part of the nasal airway and a common site of inspiratory collapse and obstruction of nasal airflow. Over-the-counter mechanical nasal dilators are an alternative to surgical intervention that attempts to improve airflow through the internal nasal valve. OBJECTIVE To determine the efficacy of over-the-counter mechanical nasal dilators and classify these products by mechanism. EVIDENCE REVIEW A database of 33 available over-the-counter mechanical nasal dilators was generated via a PubMed search as well as an internet search via Amazon.com and Google, conducted from April 1, 2013, through December 31, 2015. Products determined to be unavailable or discontinued were excluded from the database. Of the devices examined in published literature, efficacy was based on objective measures, such as measured airflow, the cross-sectional area of the nasal valve, and changes in resistance. Measures of reported sleep quality or patient perception were excluded. FINDINGS An analysis of each product's mechanism revealed 4 broad classes: external nasal dilator strips, nasal stents, nasal clips, and septal stimulators. A review demonstrated 5 studies supporting the use of external nasal dilator strips, 4 studies supporting the use of nasal clips, 1 study supporting the use of nasal stents, and no studies supporting the use of septal stimulators. CONCLUSIONS AND RELEVANCE Our findings suggest that external nasal dilator strips and nasal clips effectively relieve obstruction of the internal nasal valve and may be an alternative to surgical intervention in some patients. C1 [Kiyohara, Nicole; Badger, Christopher] Univ Calif Irvine, Sch Med, 1002 Hlth Sci Rd, Irvine, CA 92612 USA. [Kiyohara, Nicole; Badger, Christopher; Wong, Brian] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92717 USA. [Kiyohara, Nicole; Badger, Christopher; Wong, Brian] Univ Calif Irvine, Med Clin, Irvine, CA 92717 USA. [Tjoa, Tjoson] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Wong, Brian] Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, Orange, CA 92668 USA. [Wong, Brian] Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, Irvine, CA 92717 USA. [Wong, Brian] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92717 USA. RP Badger, C (reprint author), Univ Calif Irvine, Sch Med, 1002 Hlth Sci Rd, Irvine, CA 92612 USA. EM badgerc@uci.edu NR 21 TC 1 Z9 1 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD SEP-OCT PY 2016 VL 18 IS 5 BP 385 EP 389 DI 10.1001/jamafacial.2016.0291 PG 5 WC Surgery SC Surgery GA DX3TC UT WOS:000384295300012 PM 27367589 ER PT J AU Weintraub, D Kales, HC Marras, C AF Weintraub, Daniel Kales, Helen C. Marras, Connie TI The Danger of Not Treating Parkinson Disease Psychosis Reply SO JAMA NEUROLOGY LA English DT Letter ID MORTALITY C1 [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kales, Helen C.] Ctr Clin Management Res, Dept Vet Affairs Hlth Serv Res & Dev, Ann Arbor, MI USA. [Kales, Helen C.] Vet Affairs Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Kales, Helen C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Marras, Connie] Univ Toronto, TorontoWestern Hosp, Edmond J Safra Program Parkinsons Dis, Morton & Gloria Shulman Movement Disorder Ctr, Toronto, ON, Canada. RP Weintraub, D (reprint author), Univ Penn, Perelman Sch Med, 3615 Chestnut St,Ste 330, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD SEP PY 2016 VL 73 IS 9 BP 1156 EP 1157 DI 10.1001/jamaneurol.2016.2274 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DX2MV UT WOS:000384205200026 PM 27400239 ER PT J AU Deiner, MS Lietman, TM McLeod, SD Chodosh, J Porco, TC AF Deiner, Michael S. Lietman, Thomas M. McLeod, Stephen D. Chodosh, James Porco, Travis C. TI Surveillance Tools Emerging From Search Engines and Social Media Data for Determining Eye Disease Patterns SO JAMA OPHTHALMOLOGY LA English DT Article ID PUBLIC-HEALTH SURVEILLANCE; UNITED-STATES; CONJUNCTIVITIS; EPIDEMIOLOGY AB IMPORTANCE Internet-based search engine and social media data may provide a novel complementary source for better understanding the epidemiologic factors of infectious eye diseases, which could better inform eye health care and disease prevention. OBJECTIVE To assess whether data from internet-based social media and search engines are associated with objective clinic-based diagnoses of conjunctivitis. DESIGN, SETTING, AND PARTICIPANTS Data from encounters of 4143 patients diagnosed with conjunctivitis from June 3, 2012, to April 26, 2014, at the University of California San Francisco (UCSF) Medical Center, were analyzed using Spearman rank correlation of each weekly observation to compare demographics and seasonality of nonallergic conjunctivitis with allergic conjunctivitis. Data for patient encounters with diagnoses for glaucoma and influenza were also obtained for the same period and compared with conjunctivitis. Temporal patterns of Twitter and Google web search data, geolocated to the United States and associated with these clinical diagnoses, were compared with the clinical encounters. The a priori hypothesis was that weekly internet-based searches and social media posts about conjunctivitis may reflect the true weekly clinical occurrence of conjunctivitis. MAIN OUTCOMES AND MEASURES Weekly total clinical diagnoses at UCSF of nonallergic conjunctivitis, allergic conjunctivitis, glaucoma, and influenza were compared using Spearman rank correlation with equivalent weekly data on Tweets related to disease or disease-related keyword searches obtained from Google Trends. RESULTS Seasonality of clinical diagnoses of nonallergic conjunctivitis among the 4143 patients (2364 females [57.1%] and 1776 males [42.9%]) with 5816 conjunctivitis encounters at UCSF correlated strongly with results of Google searches in the United States for the term pink eye (rho, 0.68 [95% CI, 0.52 to 0.78]; P < .001) and correlated moderately with Twitter results about pink eye (rho, 0.38 [95% CI, 0.16 to 0.56]; P < .001) and with clinical diagnosis of influenza (rho, 0.33 [95% CI, 0.12 to 0.49]; P < .001), but did not significantly correlate with seasonality of clinical diagnoses of allergic conjunctivitis diagnosis at UCSF (rho, 0.21 [95% CI, -0.02 to 0.42]; P = .06) or with results of Google searches in the United States for the term eye allergy (rho, 0.13 [95% CI, -0.06 to 0.32]; P = .19). Seasonality of clinical diagnoses of allergic conjunctivitis at UCSF correlated strongly with results of Google searches in the United States for the term eye allergy (rho, 0.44 [95% CI, 0.24 to 0.60]; P < .001) and eye drops (rho, 0.47 [95% CI, 0.27 to 0.62]; P < .001). CONCLUSIONS AND RELEVANCE Internet-based search engine and social media data may reflect the occurrence of clinically diagnosed conjunctivitis, suggesting that these data sources can be leveraged to better understand the epidemiologic factors of conjunctivitis. C1 [Deiner, Michael S.; Lietman, Thomas M.; McLeod, Stephen D.; Porco, Travis C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Lietman, Thomas M.; McLeod, Stephen D.; Porco, Travis C.] Univ Calif San Francisco, FI Proctor Fdn, 513 Parnassus,Med Sci Room S334, San Francisco, CA 94143 USA. [Lietman, Thomas M.; Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Lietman, Thomas M.] Univ Calif San Francisco, Global Hlth Sci, San Francisco, CA 94143 USA. [Chodosh, James] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Porco, TC (reprint author), Univ Calif San Francisco, FI Proctor Fdn, 513 Parnassus,Med Sci Room S334, San Francisco, CA 94143 USA. EM travis.porco@ucsf.edu FU National Institutes of Health-National Eye Institute (NIH-NEI) [1R01EY024608-01A1]; NIH-NEI [EY002162]; Research to Prevent Blindness, through the University of California San Francisco Information Technology Enterprise Information Analytics Department's Research Data Browser and Clinical Data Research Consultation Services; NIH-National Institute of General Medical Sciences Models of Infectious Disease Agent Study Program [1-U01-GM087728] FX This work was supported in part by grant 1R01EY024608-01A1 from the National Institutes of Health-National Eye Institute (NIH-NEI), grant EY002162 (Core Grant for Vision Research) from the NIH-NEI, an unrestricted grant from Research to Prevent Blindness, through the University of California San Francisco Information Technology Enterprise Information Analytics Department's Research Data Browser and Clinical Data Research Consultation Services, and grant 1-U01-GM087728 from the NIH-National Institute of General Medical Sciences Models of Infectious Disease Agent Study Program (Dr Porco). NR 28 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD SEP PY 2016 VL 134 IS 9 BP 1024 EP 1030 DI 10.1001/jamaophthalmol.2016.2267 PG 7 WC Ophthalmology SC Ophthalmology GA DW9NY UT WOS:000383988800017 PM 27416554 ER PT J AU Gilbert, AL Thanos, A Pineda, R AF Gilbert, Aubrey L. Thanos, Aristomenis Pineda, Roberto TI Persistent Blurry Vision After a Routine Eye Examination SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID WEILL-MARCHESANI-SYNDROME; ANGLE-CLOSURE GLAUCOMA; MICROSPHEROPHAKIA C1 [Gilbert, Aubrey L.; Thanos, Aristomenis; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. RP Gilbert, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM aubrey_gilbert@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD SEP PY 2016 VL 134 IS 9 BP 1065 EP 1066 DI 10.1001/jamaophthalmol.2016.0812 PG 2 WC Ophthalmology SC Ophthalmology GA DW9NY UT WOS:000383988800028 PM 27389836 ER PT J AU Oberg, AS D'Onofrio, BM Rickert, ME Hernandez-Diaz, S Ecker, JL Almqvist, C Larsson, H Lichtenstein, P Bateman, BT AF Oberg, Anna Sara D'Onofrio, Brian M. Rickert, Martin E. Hernandez-Diaz, Sonia Ecker, Jeffrey L. Almqvist, Catarina Larsson, Henrik Lichtenstein, Paul Bateman, Brian T. TI Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders SO JAMA PEDIATRICS LA English DT Article ID POPULATION; OXYTOCIN; DESIGNS AB IMPORTANCE Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence. OBJECTIVE To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction). DESIGN, SETTING, AND PARTICIPANTS Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year. EXPOSURES Induction of labor. MAIN OUTCOMES AND MEASURES Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings. RESULTS The full cohort included 1 362 950 births, of which 22 077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10). CONCLUSIONS AND RELEVANCE In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor. C1 [Oberg, Anna Sara; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. [Oberg, Anna Sara; Almqvist, Catarina; Larsson, Henrik; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [D'Onofrio, Brian M.; Rickert, Martin E.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Ecker, Jeffrey L.] Harvard Med Sch, Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA USA. [Almqvist, Catarina] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden. [Bateman, Brian T.] Harvard Med Sch, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Bateman, Brian T.] Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA USA. RP Oberg, AS (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM oberg@hsph.harvard.edu FU Swedish Initiative for Research on Microdata in the Social and Medical Sciences [SIMSAM] from Swedish Research Council [340-2013-5867]; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development [K08HD075831, R01HD061817]; International Postdoctoral grant from Swedish Research Council [2012-34] FX This study was supported by grants 2012-34 (International Postdoctoral grant) and 340-2013-5867 (Swedish Initiative for Research on Microdata in the Social and Medical Sciences [SIMSAM]) from the Swedish Research Council and grants K08HD075831 and R01HD061817 from the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development. NR 26 TC 1 Z9 1 U1 9 U2 9 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 SEP PY 2016 VL 170 IS 9 AR e160965 DI 10.1001/jamapediatrics.2016.0965 PG 7 WC Pediatrics SC Pediatrics GA DX2PL UT WOS:000384212700001 PM 27454803 ER PT J AU McDougle, CJ AF McDougle, Christopher J. TI Atypical Antipsychotic-Induced Weight Gain in Children and Adolescents Sometimes Less Is More SO JAMA PSYCHIATRY LA English DT Editorial Material ID AUTISTIC DISORDER; ZIPRASIDONE; TOPIRAMATE C1 [McDougle, Christopher J.] Harvard Med Sch, Lurie Ctr Autism, Massachusetts Gen Hosp, One Maguire Rd, Lexington, MA 02421 USA. RP McDougle, CJ (reprint author), Harvard Med Sch, Lurie Ctr Autism, Massachusetts Gen Hosp, One Maguire Rd, Lexington, MA 02421 USA. EM cmcdougle@partners.org NR 8 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 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD SEP PY 2016 VL 73 IS 9 BP 899 EP 901 DI 10.1001/jamapsychiatry.2016.1213 PG 3 WC Psychiatry SC Psychiatry GA DW9PB UT WOS:000383992300005 PM 27556412 ER PT J AU Anagnostou, E Aman, MG Handen, BL Sanders, KB Shui, A Hollway, JA Brian, J Arnold, LE Capano, L Hellings, JA Butter, E Mankad, D Tumuluru, R Kettel, J Newsom, CR Hadjiyannakis, S Peleg, N Odrobina, D McAuliffe-Bellin, S Zakroysky, P Marler, S Wagner, A Wong, T Macklin, EA Veenstra-VanderWeele, J AF Anagnostou, Evdokia Aman, Michael G. Handen, Benjamin L. Sanders, Kevin B. Shui, Amy Hollway, Jill A. Brian, Jessica Arnold, L. Eugene Capano, Lucia Hellings, Jessica A. Butter, Eric Mankad, Deepali Tumuluru, Rameshwari Kettel, Jessica Newsom, Cassandra R. Hadjiyannakis, Stasia Peleg, Naomi Odrobina, Dina McAuliffe-Bellin, Sarah Zakroysky, Pearl Marler, Sarah Wagner, Alexis Wong, Taylor Macklin, Eric A. Veenstra-VanderWeele, Jeremy TI Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID ABERRANT BEHAVIOR CHECKLIST; PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; WEIGHT-GAIN; GASTROINTESTINAL SYMPTOMS; DOUBLE-BLIND; PEDIATRIC PSYCHOPHARMACOLOGY; CHILDREN; RISPERIDONE; ADOLESCENTS AB IMPORTANCE Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. OBJECTIVE To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. DESIGN, SETTING, AND PARTICIPANTS A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. INTERVENTIONS Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. MAIN OUTCOMES AND MEASURES The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. RESULTS Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005). CONCLUSIONS AND RELEVANCE Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. C1 [Anagnostou, Evdokia; Brian, Jessica; Capano, Lucia; Mankad, Deepali; Peleg, Naomi; Odrobina, Dina] Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, 150 Kilgour Rd, Toronto, ON M4G 1R8, Canada. [Anagnostou, Evdokia; Brian, Jessica; Capano, Lucia; Mankad, Deepali] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Aman, Michael G.; Hollway, Jill A.; Arnold, L. Eugene; Hellings, Jessica A.; Wagner, Alexis; Wong, Taylor] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Handen, Benjamin L.; Tumuluru, Rameshwari; Kettel, Jessica; McAuliffe-Bellin, Sarah] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sanders, Kevin B.; Marler, Sarah] Vanderbilt Univ, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Shui, Amy; Zakroysky, Pearl; Macklin, Eric A.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Butter, Eric] Nationwide Childrens Hosp, Dept Psychol, Columbus, OH USA. [Butter, Eric] Ohio State Univ, Dept Pediat & Psychol, Columbus, OH 43210 USA. [Newsom, Cassandra R.] Vanderbilt Univ, Dept Pediat, Nashville, TN USA. [Hadjiyannakis, Stasia] Univ Ottawa, CHEO Res Inst, Dept Pediat, Ottawa, ON, Canada. [Macklin, Eric A.] Harvard Med Sch, Dept Med, Boston, MA USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Dept Psychiat, New York, NY USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Sackler Inst Dev Psychobiol, New York, NY USA. [Veenstra-VanderWeele, Jeremy] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Veenstra-VanderWeele, Jeremy] New York Presbyterian Hosp, Ctr Autism & Developing Brain, White Plains, NY USA. RP Anagnostou, E (reprint author), Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, 150 Kilgour Rd, Toronto, ON M4G 1R8, Canada. EM eanagnostou@hollandbloorview.ca FU HRSA of the US Department of Health and Human Services (HHS)-Autism Intervention Research Network on Physical Health [UA3 MC11054] FX This project is/was funded by the HRSA of the US Department of Health and Human Services (HHS) under cooperative agreement grant UA3 MC11054-Autism Intervention Research Network on Physical Health. Ranbaxy Laboratories Ltd donated both metformin and placebo for the purposes of this study. NR 43 TC 3 Z9 3 U1 9 U2 9 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 SEP PY 2016 VL 73 IS 9 BP 928 EP 937 DI 10.1001/jamapsychiatry.2016.1232 PG 10 WC Psychiatry SC Psychiatry GA DW9PB UT WOS:000383992300010 PM 27556593 ER PT J AU Huybrechts, KF Hernandez-Diaz, S Patorno, E Desai, RJ Mogun, H Dejene, SZ Cohen, JM Panchaud, A Cohen, L Bateman, BT AF Huybrechts, Krista F. Hernandez-Diaz, Sonia Patorno, Elisabetta Desai, Rishi J. Mogun, Helen Dejene, Sara Z. Cohen, Jacqueline M. Panchaud, Alice Cohen, Lee Bateman, Brian T. TI Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations SO JAMA PSYCHIATRY LA English DT Article ID ATYPICAL ANTIPSYCHOTICS; EXPOSURE; COHORT; SCORES; DRUGS AB IMPORTANCE The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. OBJECTIVE To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. DESIGN, SETTING, AND PARTICIPANTS This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. EXPOSURES Use of APs during the first trimester, the etiologically relevant period for organogenesis. MAIN OUTCOMES AND MEASURES Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. RESULTS Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4-33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5-48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6-54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24-1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81-1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96-1.16) for atypical APs and 0.90 (95% CI, 0.62-1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81) was found for risperidone that was independent of measured confounders. CONCLUSIONS AND RELEVANCE Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study. C1 [Huybrechts, Krista F.; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Dejene, Sara Z.; Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. [Huybrechts, Krista F.; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Dejene, Sara Z.; Bateman, Brian T.] Harvard Med Sch, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. [Hernandez-Diaz, Sonia; Cohen, Jacqueline M.; Panchaud, Alice] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Cohen, Lee] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Harvard Med Sch, Boston, MA 02114 USA. RP Huybrechts, KF (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA.; Huybrechts, KF (reprint author), Harvard Med Sch, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM khuybrechts@bwh.harvard.edu OI panchaud, alice/0000-0001-6086-2401 FU NIMH [R01 MH100216, K01MH099141]; National Institute of Child Health and Human Development [K08HD075831]; Swiss National Science Foundation [P3SMP3-158808/1] FX This study was supported by grant R01 MH100216 from the NIMH, career development grant K01MH099141 from the NIMH (Dr Huybrechts), career development grant K08HD075831 from the National Institute of Child Health and Human Development (Dr Bateman), and grant P3SMP3-158808/1 from the Swiss National Science Foundation (Dr Panchaud). NR 16 TC 3 Z9 3 U1 0 U2 0 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 SEP PY 2016 VL 73 IS 9 BP 938 EP 946 DI 10.1001/jamapsychiatry.2016.1520 PG 9 WC Psychiatry SC Psychiatry GA DW9PB UT WOS:000383992300011 PM 27540849 ER PT J AU Yule, S Sacks, GD Maggard-Gibbons, M AF Yule, Steven Sacks, Greg D. Maggard-Gibbons, Melinda TI Innovative Approaches for Modifying Surgical Culture SO JAMA SURGERY LA English DT Editorial Material ID NONTECHNICAL SKILLS; IMPLEMENTATION; INFECTIONS; MORTALITY; PROGRAM C1 [Yule, Steven] Brigham & Womens Hosp, STRATUS Ctr Med Simulat, 75 Francis St, Boston, MA 02115 USA. [Yule, Steven] Harvard Med Sch, Boston, MA USA. [Sacks, Greg D.; Maggard-Gibbons, Melinda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,CHS 72-215, Los Angeles, CA 90095 USA. [Sacks, Greg D.; Maggard-Gibbons, Melinda] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Maggard-Gibbons, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,CHS 72-215, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu NR 9 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD SEP PY 2016 VL 151 IS 9 BP 791 EP 792 DI 10.1001/jamasurg.2016.0425 PG 2 WC Surgery SC Surgery GA DX1IO UT WOS:000384120400005 PM 27168456 ER PT J AU Engineer, LD Winters, BD Weston, CM Zhang, A Sharma, R Bass, E Jones, D Rosen, A Yoon, FB Borzecki, A Dy, SM AF Engineer, Lilly D. Winters, Bradford D. Weston, Christine M. Zhang, Allen Sharma, Ritu Bass, Eric Jones, David Rosen, Amy Yoon, Frank B. Borzecki, Ann Dy, Sydney M. TI Hospital Characteristics and the Agency for Healthcare Research and Quality Inpatient Quality Indicators: A Systematic Review SO JOURNAL FOR HEALTHCARE QUALITY LA English DT Review DE Quality; Quality Indicators; IQIs; Hospital characteristics; Systematic Review; Performance; Improvement; Hospital performance; Hospital quality ID DUTY HOUR REFORM; PATIENT OUTCOMES; 30-DAY MORTALITY; OF-CARE; VOLUME AB Background: The Agency for Healthcare Research and Quality Inpatient Quality Indicators (IQIs) include inpatient mortality for selected procedures and medical conditions. They have assumed an increasingly prominent role in hospital comparisons. Healthcare delivery and policy-related decisions need to be driven by reliable research that shows associations between hospital characteristics and quality of inpatient care delivered. Objectives: To systematically review the literature on associations between hospital characteristics and IQIs. Methods: We systematically searched PubMed and gray literature (2000-2012) for studies relevant to 14 hospital characteristics and 17 IQIs. We extracted data for study characteristics, IQIs analyzed, and hospital characteristics (e.g., teaching status, bed size, patient volume, rural vs. urban location, and nurse staffing). Results: We included 16 studies, which showed few significant associations. Four hospital characteristics (higher hospital volume, higher nurse staffing, urban vs. rural status, and higher hospital financial resources) had statistically significant associations with lower mortality and selected IQIs in approximately half of the studies. For example, there were no associations between nurse staffing and four IQIs; however, approximately 50% of studies showed a statistically significant relationship between nurse staffing and lower mortality for six IQIs. For two hospital characteristics-higher bed size and disproportionate share percentage-all statistically significant associations had higher mortality. Five hospital characteristics (teaching status, system affiliation, ownership, minority-serving hospitals, and electronic health record status) had some studies with significantly positive and some with significantly negative associations, and many studies with no association. Conclusions: We found few associations between hospital characteristics and mortality IQIs. Differences in study methodology, coding across hospitals, and hospital case-mix adjustment may partly explain these results. Ongoing research will evaluate potential mechanisms for the identified associations. C1 [Engineer, Lilly D.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21218 USA. [Engineer, Lilly D.] Johns Hopkins Univ, Dept Hlth Policy, Baltimore, MD 21218 USA. [Engineer, Lilly D.] Johns Hopkins Univ, Dept Management, Baltimore, MD 21218 USA. [Engineer, Lilly D.; Dy, Sydney M.] Armstrong Inst Patient Safety & Qual, Baltimore, MD 21201 USA. [Engineer, Lilly D.] Dept Hlth Policy & Management, Baltimore, MD USA. [Winters, Bradford D.] Johns Hopkins Univ, Sch Med, Crit Care Med Anesthesiol Neurol Neurosurg & Surg, Baltimore, MD 21218 USA. [Winters, Bradford D.] Johns Hopkins Univ, Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD 21218 USA. [Weston, Christine M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Weston, Christine M.] Ctr Hlth Serv & Outcomes Res, Baltimore, MD USA. [Zhang, Allen] Johns Hopkins Univ, Evidence Based Practice Ctr JHU EPC, Baltimore, MD 21218 USA. [Sharma, Ritu] JHU Evidence Based Practice Ctr, Baltimore, MD USA. [Bass, Eric] JHU, Med Hlth Policy & Management & Epidemiol, Baltimore, MD USA. [Bass, Eric; Dy, Sydney M.] Johns Hopkins Evidence Based Practice Ctr, Baltimore, MD USA. [Jones, David] Math Policy Res, Hlth Res, Princeton, NJ USA. [Rosen, Amy] VA Boston Healthcare Syst, CHOIR, Boston, MA USA. [Rosen, Amy] Boston Univ, Sch Med, Surg, Boston, MA 02215 USA. [Yoon, Frank B.] Math Policy Res, Data Sci & Stat, Princeton, NJ USA. [Yoon, Frank B.] Harvard Med Sch, Hlth Care Policy, Boston, MA USA. [Borzecki, Ann] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Borzecki, Ann] Boston Univ, Sch Med, Boston, MA 02215 USA. [Borzecki, Ann] Ctr Hlth Org & Implementat Res, Boston, MA USA. [Dy, Sydney M.] Johns Hopkins Univ, Hlth Policy & Management Oncol & Med, Baltimore, MD 21218 USA. RP Engineer, LD (reprint author), Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21218 USA.; Engineer, LD (reprint author), Johns Hopkins Univ, Dept Hlth Policy, Baltimore, MD 21218 USA.; Engineer, LD (reprint author), Johns Hopkins Univ, Dept Management, Baltimore, MD 21218 USA.; Engineer, LD (reprint author), Armstrong Inst Patient Safety & Qual, Baltimore, MD 21201 USA.; Engineer, LD (reprint author), Dept Hlth Policy & Management, Baltimore, MD USA. EM lengine1@jhu.edu NR 26 TC 1 Z9 1 U1 12 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1062-2551 EI 1945-1474 J9 J HEALTHC QUAL JI J. Healthc. Qual. PD SEP-OCT PY 2016 VL 38 IS 5 BP 304 EP 313 DI 10.1097/JHQ.0000000000000015 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DX2ER UT WOS:000384180800008 PM 26562350 ER PT J AU Servetas, SL Carpenter, BM Haley, KP Gilbreath, JJ Gaddy, JA Merrell, DS AF Servetas, Stephanie L. Carpenter, Beth M. Haley, Kathryn P. Gilbreath, Jeremy J. Gaddy, Jennifer A. Merrell, D. Scott TI Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FERRIC UPTAKE REGULATOR; HUMAN GASTRIC-MUCOSA; HP0165-HP0166 2-COMPONENT SYSTEM; COMPLETE GENOME SEQUENCE; ABIOTIC SURFACES; MOLECULAR CHARACTERIZATION; MEMBRANE-VESICLES; ACID ACCLIMATION; GENE-EXPRESSION; FUR AB Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, Delta nikR Delta arsS, and Delta fur Delta nikR Delta arsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. C1 [Servetas, Stephanie L.; Carpenter, Beth M.; Gilbreath, Jeremy J.; Merrell, D. Scott] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Haley, Kathryn P.; Gaddy, Jennifer A.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Gaddy, Jennifer A.] US Dept Vet Affairs, Tennessee Valley Hlth Care Syst, Nashville, TN USA. [Carpenter, Beth M.] Univ Maryland, Univ Coll, Nat Sci Biotechnol Environm Management & Lab Mana, Adelphi, MD USA. [Gilbreath, Jeremy J.] BioFire Diagnost, Salt Lake City, UT USA. RP Merrell, DS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM douglas.merrell@usuhs.edu FU HHS \ National Institutes of Health (NIH) [T32-AI095202, P30DK058404]; U.S. Department of Veterans Affairs (VA) [1IK2BX001701]; U.S. Department of Defense (DOD); Henry M. Jackson Foundation (HJF) FX This work, including the efforts of D. Scott Merrell, was funded by HHS vertical bar National Institutes of Health (NIH). This work, including the efforts of Kathryn P. Haley and Jennifer A. Gaddy, was funded by HHS vertical bar National Institutes of Health (NIH) (T32-AI095202 and P30DK058404). This work, including the efforts of Kathryn P. Haley and Jennifer A. Gaddy, was funded by U.S. Department of Veterans Affairs (VA) (1IK2BX001701). This work, including the efforts of D. Scott Merrell, was funded by U.S. Department of Defense (DOD). This work, including the efforts of Stephanie L. Servetas, was funded by Henry M. Jackson Foundation (HJF). NR 72 TC 1 Z9 1 U1 4 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2016 VL 198 IS 18 BP 2536 EP 2548 DI 10.1128/JB.00324-16 PG 13 WC Microbiology SC Microbiology GA DX4IB UT WOS:000384343300018 PM 27432830 ER PT J AU Reeves, GR Gupta, S Forman, DE AF Reeves, Gordon R. Gupta, Shuchita Forman, Daniel E. TI Evolving Role of Exercise Testing in Contemporary Cardiac Rehabilitation SO JOURNAL OF CARDIOPULMONARY REHABILITATION AND PREVENTION LA English DT Review DE cardiac rehabilitation; exercise testing; functional assessment ID 6-MINUTE WALK TEST; AMERICAN-HEART-ASSOCIATION; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; PEAK OXYGEN-UPTAKE; OLDER-ADULTS; ELDERLY-PATIENTS; SCIENTIFIC STATEMENT; CARDIOVASCULAR PREVENTION; THERAPEUTIC INTERVENTIONS AB Symptom-limited (maximal) exercise testing before cardiac rehabilitation (CR) was once an unambiguous standard of care. In particular, it served as an important screen for residual ischemia and instability before initiating a progressive exercise training regimen. However, improved revascularization and therapy for coronary heart disease has led many clinicians to downplay this application of exercise testing, especially because such testing is also a potential encumbrance to CR enrollment (delaying ease and efficiency of enrollment after procedures and hospitalizations) and patient burden (eg, added costs, logistic hassle, and anxiety). Nonetheless, exercise testing has enduring value for CR, especially because it reveals dynamic physiological responses as well as ischemia, arrhythmias, and symptoms pertinent to exercise prescription and training and to overall stability and prognosis. Moreover, as indications for CR have expanded, the value of exercise testing and functional assessment is more relevant than ever in the growing population of eligible patients, including those with heart failure, valvular heart disease, and posttransplantation, especially as current patients also tend to be more clinically complex, with advanced ages, multimorbidity, frailty, and obesity. This review focuses on the appropriate use of exercise testing in the CR setting. Graded exercise tests, cardiopulmonary exercise tests, submaximal walking tests, and other functional assessments (strength, frailty) for CR are discussed. C1 [Reeves, Gordon R.; Gupta, Shuchita] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Med, Philadelphia, PA 19107 USA. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Div Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Div Geriatr, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Forman, DE (reprint author), Geriatr Cardiol Sect, 3471 Fifth Ave,Ste 500, Pittsburgh, PA 15213 USA. EM formand@pitt.edu FU NIA [P30 AG024827, R01AG045551]; VA RRD [F0834-R] FX Dr Forman is supported in part from NIA grant P30 AG024827 and VA RR&D F0834-R. Dr Reeves is supported in part from NIA grant R01AG045551. NR 72 TC 1 Z9 2 U1 8 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-7501 EI 1932-751X J9 J CARDIOPULM REHABIL JI J. Cardiopulm. Rehabil. Prev. PD SEP-OCT PY 2016 VL 36 IS 5 BP 309 EP 319 DI 10.1097/HCR.0000000000000176 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX1HN UT WOS:000384117600001 PM 27120040 ER PT J AU Shah, AK Bilko, A Takayesu, JK AF Shah, Aakash Kaushik Bilko, Andrey Takayesu, James Kimo TI EPIDURAL STEROID INJECTION COMPLICATED BY INTRATHECAL ENTRY, PNEUMOCEPHALUS, AND CHEMICAL MENINGITIS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE intrathecal injection; pneumocephalus; chemical meningitis; epidural steroid injection; epidural intervention; headache ID AIR; RESISTANCE AB Background: Epidural steroid injections are frequently used to treat back and extremity pain. The procedure is generally safe, with a low rate of adverse events, including intrathecal entry, pneumocephalus, and chemical meningitis. Case Report: We report a case of a 45-year-old woman who presented to the emergency department (ED) with headache, nausea, vomiting, and photophobia after a lumbar epidural steroid injection. She was afebrile and had an elevated white blood cell count. A non-contrast computed tomography scan of the head revealed pneumocephalus within the subarachnoid space and lateral ventricles. The patient was admitted to the ED observation unit for pain control and subsequently developed a marked leukocytosis and worsening meningismus. A lumbar puncture was performed yielding cerebrospinal fluid (CSF) consistent with meningitis (1,000 total nucleated cells, 89% neutrophils, 85 mg/dL total protein, and no red blood cells). Gram stain revealed no bacteria. The patient was admitted on empiric vancomycin and ceftriaxone. Antibiotics were discontinued at 48 h when CSF cultures remained negative and the patient was clinically asymptomatic. Why Should an Emergency Physician Be Aware of This?: Emergency physicians should consider intrathecal entry and pneumocephalus in patients who present with a headache after an epidural intervention. The management of pneumocephalus includes supportive therapies, appropriate positioning, and supplemental oxygen. These symptoms can be accompanied by fever, leukocytosis, and markedly inflammatory CSF findings consistent with bacterial or chemical meningitis. Empiric treatment with broad-spectrum antibiotics should be initiated until CSF culture results are available. (C) 2016 Elsevier Inc. All rights reserved. C1 [Shah, Aakash Kaushik; Takayesu, James Kimo] Massachusetts Gen Hosp, Dept Emergency Med, 5 Emerson Pl, Boston, MA 02114 USA. [Shah, Aakash Kaushik; Takayesu, James Kimo] Harvard Med Sch, 5 Emerson Pl, Boston, MA 02114 USA. [Bilko, Andrey] Penn State Milton S Hershey Med Ctr, Dept Anesthesiol, Hershey, PA USA. [Bilko, Andrey] Penn State Coll Med, Hershey, PA USA. RP Shah, AK (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 5 Emerson Pl, Boston, MA 02114 USA.; Shah, AK (reprint author), Harvard Med Sch, 5 Emerson Pl, Boston, MA 02114 USA. 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 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD SEP PY 2016 VL 51 IS 3 BP 265 EP 268 DI 10.1016/j.jemermed.2016.05.040 PG 4 WC Emergency Medicine SC Emergency Medicine GA DX0VK UT WOS:000384083900023 PM 27381953 ER PT J AU Verfaellie, M Lee, LO Lafleche, G Spiro, A AF Verfaellie, Mieke Lee, Lewina O. Lafleche, Ginette Spiro, Avron TI Self-Reported Sleep Disturbance Mediates the Relationship Between PTSD and Cognitive Outcome in Blast-Exposed OEF/OIF Veterans SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE blast injuries; cognition; mediation; posttraumatic stress disorder; sleep; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; CLOSED-HEAD INJURY; NEUROPSYCHOLOGICAL OUTCOMES; COMBAT VETERANS; STRUCTURAL MODELS; VIETNAM VETERANS; PHYSICAL HEALTH; QUALITY INDEX; US VETERANS AB Objectives: To examine the contribution of sleep disturbance to cognitive performance following blast exposure. Design: Correlational research evaluating self-reported sleep disturbance as a mediator of the association between the primary blast-related comorbidities of mild traumatic brain injury (mTBI) and posttraumatic stress disorder and cognitive outcome. Participants: One hundred sixty Operation Enduring Freedom/Operation Iraqi Freedom Veterans with a history of blast exposure assigned to 1 of 3 groups (no TBI, mTBI without loss of consciousness, and mTBI with loss of consciousness). Main Outcome Measures: Neuropsychological measures and self-report of sleep disturbance. Results: Increased posttraumatic stress disorder symptomatology was associated with worse performance inmultiple cognitive domains. This association was mediated in part by self-reported sleep disturbance. Traumatic brain injury with loss of consciousness was associated with lower manual dexterity, but this association was not mediated by sleep disturbance. Conclusions: Our results highlight the importance of sleep disturbance as a factor contributing to cognitive outcome in individuals with posttraumatic stress disorder symptoms. They point to the importance of considering sleep problems in the diagnosis and treatment of cognitive deficits in veterans with blast exposure. C1 [Verfaellie, Mieke; Lafleche, Ginette] VA Boston Healthcare Syst, Memory Disorders Res Ctr, 151-A,150 South Huntington Ave, Boston, MA 02130 USA. [Verfaellie, Mieke; Lee, Lewina O.; Lafleche, Ginette; Spiro, Avron] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lee, Lewina O.; Spiro, Avron] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Lee, Lewina O.; Spiro, Avron] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 151-A,150 South Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu FU Merit Review grants - Clinical Science Research and Development Service and Rehabilitation Research and Development Service of the Department of Veterans Affairs; Clinical Science Research and Development Service of the Department of Veterans Affairs FX The research was supported by Merit Review grants awarded by the Clinical Science Research and Development Service and Rehabilitation Research and Development Service of the Department of Veterans Affairs to Dr Verfaellie. Drs Verfaellie and Spiro are supported by the Clinical Science Research and Development Service of the Department of Veterans Affairs. The contents do not represent the views of the U.S. Department of Veterans Affairs or the US Government. NR 93 TC 1 Z9 1 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2016 VL 31 IS 5 BP 309 EP 319 DI 10.1097/HTR.0000000000000197 PG 11 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DX2ZY UT WOS:000384243600009 PM 26580692 ER PT J AU Yee, MK Seichepine, DR Janulewicz, PA Sullivan, KA Proctor, SP Krengel, MH AF Yee, Megan K. Seichepine, Daniel R. Janulewicz, Patricia A. Sullivan, Kimberly A. Proctor, Susan P. Krengel, Maxine H. TI Self-Reported Traumatic Brain Injury, Health and Rate of Chronic Multisymptom Illness in Veterans From the 1990-1991 Gulf War SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE chronic multisymptom illness; Gulf War; traumatic brain injury ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; NEURON-SPECIFIC ENOLASE; US ARMY VETERANS; PSYCHIATRIC-DISORDERS; FOLLOW-UP; SERUM CONCENTRATIONS; BIOCHEMICAL MARKERS; CARE UTILIZATION; DAMAGE S-100B AB Background: Traumatic brain injury (TBI) was not considered to be common in the 1990-1991 Gulf War (GW). Therefore, the relationship between TBI and chronic health symptoms experienced by GW veterans is unknown. Health symptoms reported by veterans deployed more recently to this region (Operations Enduring and Iraqi Freedom) are similar to those of GW veterans and have been primarily attributed to TBI. Objective: To examine the relationships among self-reported TBI, health symptoms, chronic multisymptom illness (CMI), and health-related quality of life among GW veterans. Participants: Participants included 1 274 GW veterans from the Devens Cohort Study, 156 of whom self-reported a history of TBI (12.2% of the sample). Design: Cross-sectional retrospective analysis of existing survey data. Main Measures: A 52-item health symptom checklist and the RAND 36-Item Health short Form Survey. Results: Self-reported TBI in GW Veterans is related to increased rates of health symptoms, CMI, and poorer health-related quality of life. Conclusions: Gulf War veterans' self-reported exposure to TBI is related to increased rates of chronic health symptoms and CMI, which interfere with everyday activities of daily living. C1 [Yee, Megan K.; Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, 150 S Huntington Ave,D12-87, Boston, MA 02130 USA. [Krengel, Maxine H.] VA Boston Healthcare Syst, Psychol Res, Boston, MA 02130 USA. [Yee, Megan K.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Seichepine, Daniel R.] Univ New Hampshire, Div Social Sci, Manchester, NH USA. [Janulewicz, Patricia A.; Sullivan, Kimberly A.; Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Proctor, Susan P.] US Army, Environm Med Res Inst, Mil Performance Div, Natick, MA 01760 USA. [Krengel, Maxine H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Yee, MK (reprint author), VA Boston Healthcare Syst, Res Serv, 150 S Huntington Ave,D12-87, Boston, MA 02130 USA. EM meganyee@bu.edu OI Sullivan, Kimberly/0000-0001-7940-6123 NR 67 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2016 VL 31 IS 5 BP 320 EP 328 DI 10.1097/HTR.0000000000000173 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DX2ZY UT WOS:000384243600010 PM 26291628 ER PT J AU Alosco, ML Aslan, M Du, MT Ko, J Grande, L Proctor, SP Concato, J Vasterling, JJ AF Alosco, Michael L. Aslan, Mihaela Du, Mengtian Ko, John Grande, Laura Proctor, Susan P. Concato, John Vasterling, Jennifer J. TI Consistency of Recall for Deployment-Related Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE OIF; PTSD; recall consistency; TBI screening; traumatic brain injury ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-GUARD; MEMORY; VETERANS; IRAQ; STABILITY; VALIDITY; EVENTS; EXPOSURE; OUTCOMES AB Objective: To examine the temporal consistency of self-reported deployment-related traumatic brain injury (TBI) and its association with posttraumatic stress disorder (PTSD) symptom severity. Setting: In-person interviews at US Army installations (postdeployment); phone interviews (long-term follow-up). Participants: A total of 378 US Army soldiers and veterans deployed to Iraq; 14.3% (n = 54) reported TBI with loss of consciousness during an index deployment. Design: Participants were evaluated after returning from deployment and again 5 to 9 years later. Main Measures: Temporal consistency of TBI endorsement based on TBI screening interviews; PTSD Checklist, Civilian Version. Results: The concordance of deployment-related TBI endorsement from the postdeployment to long-term follow-up assessment was moderate (kappa = 0.53). Of the 54 participants reporting (predominantly mild) TBI occurring during an index deployment, 32 endorsed TBI inconsistently over time. More severe PTSD symptoms at postdeployment assessment were independently associated with discordant reporting (P =.0004); each 10-point increase in PCL scores increasing odds of discordance by 69% (odds ratio = 1.69; 95% confidence interval, 1.26-2.26). Conclusions: Deployment-related TBI may not be reported reliably over time, particularly among war-zone veterans with greater PTSD symptoms. Results of screening evaluations for TBI history should be viewed with caution in the context of PTSD symptom history. C1 [Alosco, Michael L.; Grande, Laura; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, 150 S Huntington Ave, Boston, MA 02130 USA. [Aslan, Mihaela; Ko, John; Concato, John] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. [Aslan, Mihaela; Ko, John; Concato, John] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Du, Mengtian] Yale Grad Sch Arts & Sci, Dept Publ Hlth, New Haven, CT USA. [Grande, Laura; Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Natick, MA USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. [Alosco, Michael L.] Boston Univ, Sch Med, Alzheimers Dis & CTE Ctr, Boston, MA 02118 USA. RP Vasterling, JJ (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM jennifer.vasterling@va.gov FU US Army Medical Research and Materiel Command [DAMD 17-03-0020]; Department of Veterans Affairs (VA) Clinical Sciences Research and Development; VA Cooperative Studies Program (VA CSP) [566] FX Funding for the collection of postdeployment data was provided by the US Army Medical Research and Materiel Command (DAMD 17-03-0020) and the Department of Veterans Affairs (VA) Clinical Sciences Research and Development. Funding for all other aspects of the work was provided by VA Cooperative Studies Program (VA CSP# 566). The authors are grateful to the soldiers and military veterans who comprise the Neurocognition Deployment Health Study cohort for their long-standing participation in the research and for their military service more generally. NR 33 TC 2 Z9 2 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2016 VL 31 IS 5 BP 360 EP 368 DI 10.1097/HTR.0000000000000201 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DX2ZY UT WOS:000384243600014 PM 26580696 ER PT J AU Myrga, JM Failla, MD Ricker, JH Dixon, CE Conley, YP Arenth, PM Wagner, AK AF Myrga, John M. Failla, Michelle D. Ricker, Joseph H. Dixon, C. Edward Conley, Yvette P. Arenth, Patricia M. Wagner, Amy K. TI A Dopamine Pathway Gene Risk Score for Cognitive Recovery Following Traumatic Brain Injury: Methodological Considerations, Preliminary Findings, and Interactions With Sex SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE cognition; dopamine; genetics; Rehabilomics; traumatic brain injury ID CATECHOL-O-METHYLTRANSFERASE; COMT VAL(158)MET POLYMORPHISM; PREFRONTAL CORTEX; MOLECULAR HETEROSIS; TRANSPORTER EXPRESSION; GENDER-DIFFERENCES; HEALTHY-ADULTS; WORKING-MEMORY; FEMALE RATS; RECEPTOR AB Objectives: With evidence of sexual dimorphism involving the dopamine (DA)-pathway, and the importance of DA pathways in traumatic brain injury (TBI) recovery, we hypothesized that sex x DA-gene interactions may influence cognition post-TBI. Participants: Adult survivors of severe TBI (n = 193) consecutively recruited from a level 1 trauma center. Design: Risk allele assignments were made for multiple DA pathway genes using a sex-specific stratified approach. Genetic risk alleles, and their impacts on cognition, were assessed at 6 and 12 months postinjury using unweighted, semiweighted, and weighted gene risk score (GRS) approaches. Main Measures: A cognitive composite score generated from 8 standardized neuropsychological tests targeting multiple cognitive domains. Results: A significant sex x gene interaction was observed at 6 and 12 months for ANKK1 rs1800497 (6M: P =.002, 12M: P =.001) and COMT rs4680 (6M: P =.048; 12M: P =.004); DRD2 rs6279 (P =.001) and VMAT rs363226 (P =.043) genotypes were independently associated with cognition at 6 months, with trends for a sex x gene interaction at 12 months. All GRS methods were significant predictors of cognitive performance in multivariable models. Weighted GRS multivariate models captured the greatest variance in cognition: R-2 = 0.344 (6 months); R-2 = 0.441 (12 months), significantly increasing the variance captured from the base prediction models. Conclusions: A sex-specific DA-pathway GRS may be a valuable tool when predicting cognitive recovery post-TBI. Future work should validate these findings and explore how DA-pathway genetics may guide therapeutic intervention. C1 [Myrga, John M.; Failla, Michelle D.; Dixon, C. Edward; Arenth, Patricia M.; Wagner, Amy K.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Failla, Michelle D.; Dixon, C. Edward; Wagner, Amy K.] Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA USA. [Ricker, Joseph H.] NYU, Sch Med, Dept Rehabil Med, New York, NY USA. [Dixon, C. Edward] Vet Affairs Pittsburgh Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, Pittsburgh, PA USA. [Conley, Yvette P.] Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. [Conley, Yvette P.] Univ Pittsburgh, Sch Nursing, Hlth Promot & Dev, Pittsburgh, PA 15261 USA. [Dixon, C. Edward; Conley, Yvette P.; Wagner, Amy K.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. RP Wagner, AK (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 Fifth Ave,Ste 202, Pittsburgh, PA 15213 USA. EM wagnerak@upmc.edu FU NIDILRR [H133A120087]; NIH [R01 HD048162, R01 NR013342]; DOD [W81XWH-071-0701] FX This research was supported by the following: NIDILRR: H133A120087; NIH: R01 HD048162; DOD: W81XWH-071-0701; NIH: R01 NR013342. NR 102 TC 2 Z9 2 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2016 VL 31 IS 5 BP E15 EP E29 DI 10.1097/HTR.0000000000000199 PG 15 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DX2ZY UT WOS:000384243600003 PM 26580694 ER PT J AU Leung, AM AF Leung, Angela M. TI Thyroid Emergencies SO JOURNAL OF INFUSION NURSING LA English DT Article DE hypothyroidism; hyperthyroidism; ICU; myxedema coma; thyroid emergencies; thyroid storm ID CLINICAL-FEATURES; EARLY-PREGNANCY; HORMONE ACTION; STORM; HYPOTHYROIDISM; THYROTOXICOSIS; ASSOCIATION; GUIDELINES; THYROXINE; CHILDREN AB Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states-which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively-is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting. C1 [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Med, Los Angeles, CA 90095 USA. [Leung, Angela M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Leung, AM (reprint author), VA Greater Los Angeles Healthcare Syst, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM AMLeung@mednet.ucla.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1533-1458 EI 1539-0667 J9 J INFUS MURS JI J. Infus.Nurs. PD SEP-OCT PY 2016 VL 39 IS 5 BP 281 EP 286 DI 10.1097/NAN.0000000000000186 PG 6 WC Nursing SC Nursing GA DX1GI UT WOS:000384114000004 PM 27598067 ER PT J AU Brand, SR Pickard, L Mack, JW Berry, LL AF Brand, Sarah R. Pickard, Lucy Mack, Jennifer W. Berry, Leonard L. TI What Adult Cancer Care Can Learn From Pediatrics SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID NEWLY-DIAGNOSED CANCER; SPECIAL-ISSUE; CHILDREN; PATIENT; HEALTH; COMMUNICATION; CAREGIVERS; SURVIVORS; FAMILIES; OUTCOMES C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Childrens Hosp, Boston, MA USA. Inst Healthcare Improvement, Cambridge, MA USA. Texas A&M Univ, Mays Business Sch, College Stn, TX USA. RP Berry, LL (reprint author), Mays Business Sch, Dept Mkt, 4112 TAMU, College Stn, TX 77843 USA. EM berryle@tamu.edu FU AHRQ HHS [T32 HS000063] NR 30 TC 0 Z9 0 U1 2 U2 2 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 SEP PY 2016 VL 12 IS 9 BP 765 EP 767 DI 10.1200/JOP.2016.015057 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DX3UO UT WOS:000384301100009 PM 27531379 ER PT J AU Bhatt, VR Steensma, DP AF Bhatt, Vijaya Raj Steensma, David P. TI Hematopoietic Cell Transplantation for Myelodysplastic Syndromes SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Review ID ACUTE MYELOID-LEUKEMIA; REDUCED-INTENSITY; HEMATOLOGIC MALIGNANCIES; MARROW-TRANSPLANTATION; CLONAL HEMATOPOIESIS; DECISION-ANALYSIS; SUICIDE GENE; OPEN-LABEL; LOW-RISK; SURVIVAL AB Allogeneic hematopoietic cell transplantation (HCT) offers the only potential cure for patients with myelodysplastic syndromes (MDS). However, with current approaches to HCT, many older patients with comorbidities are poor HCT candidates, and treatment-related morbidity and mortality may offset benefit for patients with lower-risk disease. Consequently, selection of patients with MDS for HCT should take into consideration disease risk category including mutational status, HCT comorbidity index, functional status, donor options, and available institutional resources. Formal geriatric assessment may further guide use of HCT and, if HCT is chosen, selection of conditioning intensity. Patients with higher-risk MDS should be considered for HCT at the time of diagnosis, whereas expectant nontransplant management is more appropriate for those with lower-risk disease. A high blast burden at the time of HCT increases the risk of subsequent relapse; however, the role of pretransplant cytoreductive therapy and the regimen of choice remain controversial. Patients with MDS younger than 65 years and with an HCT comorbidity index <= 4 may benefit from more intense conditioning regimens. The presence of complex or monosomal karyotype or mutations in TP53, DNMT3A, or other genes identify patients with poorer outcomes following HCT. Patients with TP53 mutations have particularly poor survival, and should be enrolled in clinical trials whenever possible. Several important HCT studies are ongoing and will better define the role of HCT inMDS as well as the value of pretransplant cytoreductive therapy or post-transplant relapse-prevention strategies. Given the apparent underuse ofHCT in eligible patients and lowenrollment inMDSHCT clinical trials to date, timely referral of patients with MDS to such trials and HCT programs is critical. C1 Univ Nebraska Med Ctr, Omaha, NE USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Bhatt, VR (reprint author), Univ Nebraska Med Ctr, Dept Internal Med, Div Hematol Oncol, 987680 Nebraska Med Ctr, Omaha, NE 68198 USA. EM vijaya.bhatt@unmc.edu NR 48 TC 0 Z9 0 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 SEP PY 2016 VL 12 IS 9 BP 786 EP 792 DI 10.1200/JOP.2016.015214 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DX3UO UT WOS:000384301100014 PM 27621329 ER PT J AU Bickel, KE McNiff, K Buss, MK Kamal, A Lupu, D Abernethy, AP Broder, MS Shapiro, CL Acheson, AK Malin, J Evans, T Krzyzanowska, MK AF Bickel, Kathleen E. McNiff, Kristen Buss, Mary K. Kamal, Arif Lupu, Dale Abernethy, Amy P. Broder, Michael S. Shapiro, Charles L. Acheson, Anupama Kurup Malin, Jennifer Evans, Tracey Krzyzanowska, Monika K. TI Defining High-Quality Palliative Care in Oncology Practice: An American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine Guidance Statement SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 [Bickel, Kathleen E.] White River Junct VA Med Ctr, 215 N Main St,Mail Code GEC 003, White River Jct, VT 05091 USA. Geisel Sch Med Dartmouth, White River Jct, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Durham, NC USA. Amer Acad Hosp & Palliat Med, Glenview, IL USA. Partnership Hlth Analyt Res, Beverly Hills, CA USA. Mt Sinai Ichan Sch Med, New York, NY USA. Providence Canc Ctr, Portland, OR USA. Anthem, Indianapolis, IN USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. RP Bickel, KE (reprint author), White River Junct VA Med Ctr, 215 N Main St,Mail Code GEC 003, White River Jct, VT 05091 USA. EM kathleen.bickel@outlook.com NR 0 TC 4 Z9 4 U1 3 U2 3 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 SEP PY 2016 VL 12 IS 9 BP 821 EP 822 DI 10.1200/JOP.2016.010686 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DX3UO UT WOS:000384301100001 PM 27531376 ER PT J AU Bickel, KE McNiff, K Buss, MK Kamal, A Lupu, D Abernethy, AP Broder, MS Shapiro, CL Acheson, AK Malin, J Evans, T Krzyzanowska, MK AF Bickel, Kathleen E. McNiff, Kristen Buss, Mary K. Kamal, Arif Lupu, Dale Abernethy, Amy P. Broder, Michael S. Shapiro, Charles L. Acheson, Anupama Kurup Malin, Jennifer Evans, Tracey Krzyzanowska, Monika K. TI Defining High-Quality Palliative Care in Oncology Practice: An American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine Guidance Statement SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article AB Purpose Integrated into routine oncology care, palliative care can improvesymptomburden, quality of life, and patient and caregiver satisfaction. However, not all oncology practices have access to specialist palliative medicine. This project endeavored to define what constitutes high-quality primary palliative care as delivered by medical oncology practices. Methods An expert steering committee outlined 966 palliative care service items, in nine domains, each describing a candidate element of primary palliative care delivery for patients with advanced cancer or high symptom burden. Using modified Delphi methodology, 31 multidisciplinary panelists rated each service item on three constructs: importance, feasibility, and scope within medical oncology practice. Results Panelistsendorsedthehighestproportionof palliative careserviceitems in thedomainsofEnd-ofLife Care (81%); Communication and SharedDecision Making (79%); andAdvance Care Planning (78%). The lowest proportions were in Spiritual and Cultural Assessment andManagement (35%) and Psychosocial Assessment and Management (39%). In the largest domain, Symptom Assessment and Management, there was consensus that all symptoms should be assessed and managed at a basic level, withmore comprehensive management for common symptoms such as nausea, vomiting, diarrhea, dyspnea, andpain. Within the AppropriatePalliative Care andHospice Referral domain, there was consensus that oncology practices should be able to describe the difference between palliative care and hospice to patients and refer patients appropriately. Conclusion This statement describes the elements comprising high-quality primary palliative care for patients with advanced cancer or high symptom burden, as delivered by oncology practices. Oncology providers wishing to enhance palliative care delivery may find this information useful to inform operational changes and quality improvement efforts. C1 [Bickel, Kathleen E.] White River Junct VA Med Ctr, 215 N Main St,Mail Code GEC 003, White River Jct, VT USA. Geisel Sch Med Dartmouth, White River Jct, VT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Durham, NC USA. Amer Acad Hosp & Palliat Med, Glenview, IL USA. Partnership Hlth Analyt Res, Beverly Hills, CA USA. Mt Sinai Ichan Sch Med, New York, NY USA. Providence Canc Ctr, Portland, OR USA. Anthem, Indianapolis, IN USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA. Princess Margaret Canc Ctr, Toronto, ON, Canada. RP Bickel, KE (reprint author), White River Junct VA Med Ctr, 215 N Main St,Mail Code GEC 003, White River Jct, VT USA. EM kathleen.bickel@outlook.com NR 4 TC 4 Z9 4 U1 3 U2 3 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 SEP PY 2016 VL 12 IS 9 BP E828 EP E837 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DX3UO UT WOS:000384301100002 PM 27531376 ER PT J AU Dyer, MA Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Dyer, Michael A. Chen, Ming-Hui Braccioforte, Michelle H. Moran, Brian J. D'Amico, Anthony V. TI Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable-risk prostate cancer SO JOURNAL OF RADIATION ONCOLOGY LA English DT Article DE Prostate cancer; Brachytherapy; Androgen deprivation therapy; Comorbidity ID RANDOMIZED-TRIAL; SUPPRESSION; RADIOTHERAPY AB Because survival may be shortened in prostate cancer (PC) patients with moderate/severe comorbidity receiving androgen deprivation therapy (ADT), we explored if comorbidity predicts ADT use in those with unfavorable-risk PC. Between 10/1997 and 5/2013, 3366 men with unfavorable-intermediate- (70.7 %) or high-risk (29.3 %) PC were treated at the Chicago Prostate Cancer Center using brachytherapy with/without neoadjuvant external-beam radiation therapy (EBRT) and/or ADT. Multivariable logistic regression analysis was performed to evaluate whether history of heart failure and/or myocardial infarction (CHF/MI) was associated with decreased odds of ADT use in men with unfavorable-intermediate- or high-risk PC, adjusting for age, PC prognostic factors, year of brachytherapy, and EBRT use. Among patients with unfavorable-intermediate-risk PC, 31.2 % received ADT. Among those with high-risk PC, 38.3, 12.3, and 4.8 % received > 0-6, > 6-18, and > 18 months of ADT, respectively. In men with unfavorable-intermediate-risk PC, history of CHF/MI was not significantly associated with decreased odds of ADT use (p = 0.49), but odds of ADT use decreased significantly over the study period, i.e., by year of brachytherapy (adjusted odds ratio [95 % confidence interval] (AOR [95%CI]) = 0.96 [0.94, 0.98], p = 0.0009). Similarly, in men with high-risk PC, history of CHF/MI was not significantly associated with odds of decreased ADT duration (all p values > 0.71), but odds of ADT use of various durations decreased over the years of the study period (AOR [95%CI] = 0.87 [0.83, 0.91], p < 0.0001; AOR [95%CI] = 0.93 [0.87, 0.99], p = 0.023; and AOR [95%CI] = 0.92 [0.83, 1.01], p = 0.089, for > 0-6; > 6-18; and > 18 months of ADT use, respectively, compared to no ADT). While neoadjuvant ADT use decreased over the study period in men with unfavorable-risk PC undergoing brachytherapy, ADT use was not less likely in those with a history of CHF/MI. C1 [Dyer, Michael A.] Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, 215 Glenbrook Rd U-4120, Storrs, CT 06269 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, 815 Pasquinelli Dr, Westmont, IL 60559 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. [D'Amico, Anthony V.] Harvard Med Sch, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. RP Dyer, MA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM mdyer2@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1948-7894 EI 1948-7908 J9 J RADIOL ONCOL JI J. RADIOL. ONCOL. PD SEP PY 2016 VL 5 IS 3 BP 293 EP 300 DI 10.1007/s13566-016-0253-8 PG 8 WC Oncology SC Oncology GA DX4BS UT WOS:000384324400009 ER PT J AU Warren, LEG Chen, MH Denham, JW Steigler, AB Renshaw, AA Loffredo, M Kantoff, PW D'Amico, AV AF Warren, Laura E. G. Chen, Ming-Hui Denham, James W. Steigler, Allison B. Renshaw, Andrew A. Loffredo, Marian Kantoff, Philip W. D'Amico, Anthony V. TI Gleason score and the risk of cause-specific and all-cause mortality following radiation with or without 6 months of androgen deprivation therapy for men with unfavorable-risk prostate cancer SO JOURNAL OF RADIATION ONCOLOGY LA English DT Article DE Androgen deprivation therapy; Co-morbidity; Gleason score; Prostate cancer; Radiation therapy ID PHASE-III TRIAL; CARDIOVASCULAR-DISEASE; RADICAL PROSTATECTOMY; RANDOMIZED-TRIAL; SHORT-TERM; SUPPRESSION; RADIOTHERAPY; ENZALUTAMIDE; CHEMOTHERAPY; COMORBIDITY AB We evaluated whether a differential impact of adding 6 months of androgen deprivation (ADT) to radiation therapy (RT) on all-cause (ACM), prostate cancer-specific (PCSM), and other-cause mortality (OCM) in men with unfavorable-risk prostate cancer (PC) exists within Gleason score (GS) subgroups. Individual patient data from 743 men with unfavorable-risk PC from two randomized ADT trials were utilized. Competing risks and Cox regression were used to determine whether adding 6 months of ADT to RT significantly impacted PCSM, OCM, and ACM within GS subgroups. Men with GS 9/10 versus aecurrency sign8 were significantly more likely to be over 75 (23.3 versus 12.7 %; p = 0.03). At a median follow-up of 11.93 and 11.81 years in the 683 and 60 patients with GS aecurrency sign8 and GS 9/10, 315 (46.1 %) and 44 (73.1 %) died, respectively. ADT in men with GS aecurrency sign8 was associated with significantly decreased ACM (adjusted hazard ratio (AHR) 0.66; 95 % confidence interval: 0.52-0.82; p < 0.001) and PCSM (0.43; 0.28-0.66; p < 0.001) but no significant difference in OCM (0.90; 0.68-1.17; p = 0.43) Among men with GS 9/10 PC ADT significantly reduced PCSM (0.33; 0.11-0.99; p = 0.048) but not ACM (0.79; 0.38-1.61; p = 0.51) and increased OCM (2.16; 0.81-5.79; p = 0.12), resulting in opposite effects of ADT on OCM by the GS subgroup such that the relative AHR of OCM in GS 9/10 versus aecurrency sign8 was nearly significantly increased (2.42 [0.87,6.71]; p = 0.09). While ADT reduced PCSM risk overall, survival was not prolonged in men with GS 9/10 due to ADT-driven increased OCM, which supports the hypothesis that older men with significant comorbidity may not experience prolonged survival when ADT is added to RT. C1 [Warren, Laura E. G.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Denham, James W.; Steigler, Allison B.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. [Loffredo, Marian; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Loffredo, Marian; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Warren, LEG (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM lewarren@partners.org NR 38 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1948-7894 EI 1948-7908 J9 J RADIOL ONCOL JI J. RADIOL. ONCOL. PD SEP PY 2016 VL 5 IS 3 BP 301 EP 308 DI 10.1007/s13566-016-0260-9 PG 8 WC Oncology SC Oncology GA DX4BS UT WOS:000384324400010 ER PT J AU Silverberg, ND Panenka, W Iverson, GL Brubacher, JR Shewchuk, JR Heran, MKS Oh, GCS Honer, WG Lange, RT AF Silverberg, Noah D. Panenka, William Iverson, Grant L. Brubacher, Jeffrey R. Shewchuk, Jason R. Heran, Manraj K. S. Oh, Gary C. S. Honer, William G. Lange, Rael T. TI Alcohol Consumption Does not Impede Recovery from Mild to Moderate Traumatic Brain Injury SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Craniocerebral trauma; Postconcussion symptoms; Neuropsychological tests; Magnetic resonance imaging; Diffusion tensor imaging; Alcohol drinking; Alcohol-related disorders ID NEUROPSYCHOLOGICAL ASSESSMENT BATTERY; WHITE-MATTER; SUBSTANCE-ABUSE; HEAD-INJURY; DRUG-USE; INTOXICATION; ANISOTROPY; DRINKING; LEVEL; TIME AB Objectives: To examine the effect of pre-injury alcohol use, acute alcohol intoxication, and post-injury alcohol use on outcome from mild to moderate traumatic brain injury (TBI). Methods: Prospective inception cohort of patients who presented to the Emergency Department with mild to moderate TBI and had a blood alcohol level (BAL) taken for clinical purposes. Those who completed the 1-year outcome assessment were eligible for this study (N=91). Outcomes of interest were the count of post-concussion symptoms (British Columbia Post-Concussion Symptom Inventory), low neuropsychological test scores (Neuropsychological Assessment Battery), and abnormal regions of interest on diffusion tensor imaging (low fractional anisotropy). The main predictors were pre-injury alcohol consumption (Cognitive Lifetime Drinking History interview), BAL, and post-injury alcohol use. Results: The alcohol use variables were moderately to strongly inter-correlated. None of the alcohol use variables (whether continuous or categorical) were related to 1-year TBI outcomes in generalized linear modeling. Participants in this cohort generally had a good clinical outcome, regardless of their pre-, peri-, and post-injury alcohol use. Conclusions: Alcohol may not significantly alter long-term outcome from mild to moderate TBI. C1 [Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Rehabil Res Program, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada. [Silverberg, Noah D.; Iverson, Grant L.] Harvard Med Sch, Dept Phys Med & Rehabil, Boston, MA USA. [Silverberg, Noah D.; Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Silverberg, Noah D.; Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Panenka, William] Univ British Columbia, British Columbia Neuropsychiat Program, Vancouver, BC, Canada. [Panenka, William; Iverson, Grant L.; Honer, William G.; Lange, Rael T.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Brubacher, Jeffrey R.] Univ British Columbia, Dept Emergency Med, Vancouver, BC, Canada. [Shewchuk, Jason R.; Heran, Manraj K. S.; Oh, Gary C. S.] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada. [Lange, Rael T.] Def & Vet Brain Injury Ctr, Bethesda, MD USA. [Lange, Rael T.] Natl Intrepid Ctr Excellence, Bethesda, MD USA. [Lange, Rael T.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. RP Silverberg, ND (reprint author), GF Strong Rehab Ctr, Rehabil Res Program, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada. EM noah.silverberg@vch.ca FU Canadian Institutes of Health Research [200903MOP-200377-BSB-CAAA-161276]; Vancouver Coastal Health Research Institute; INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium - Department of Defense Psychological Health/Traumatic Brain Injury Research Program [X81XWH-07-CC-CSDoD] FX Primary funding for this study was provided by the Canadian Institutes of Health Research (200903MOP-200377-BSB-CAAA-161276), to RTL as the Principal Applicant. NDS received salary support from the Vancouver Coastal Health Research Institute. GLI notes that he was supported in part by the INTRuST Posttraumatic Stress Disorder and Traumatic Brain Injury Clinical Consortium funded by the Department of Defense Psychological Health/Traumatic Brain Injury Research Program (X81XWH-07-CC-CSDoD). NR 77 TC 0 Z9 0 U1 5 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 2016 VL 22 IS 8 BP 816 EP 827 DI 10.1017/S1355617716000692 PG 12 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DX4BU UT WOS:000384324800003 PM 27534259 ER PT J AU Foster, S Talbot, S Woolf, C AF Foster, Simmie Talbot, Sebastien Woolf, Clifford TI Nociceptive Neurons Differentially Drive Type I and Type II Allergic Airway Inflammation SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Foster, Simmie] Harvard Univ, Dept Psychiat, Harvard Med Sch, Cambridge, MA 02138 USA. [Talbot, Sebastien; Woolf, Clifford] Harvard Univ, Dept Neurobiol, Harvard Med Sch, Cambridge, MA 02138 USA. [Foster, Simmie] Massachusetts Gen Hosp, Depress Clin Res Program, Boston, MA 02114 USA. [Talbot, Sebastien; Woolf, Clifford] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2016 VL 25 IS 9 MA P-13 BP 961 EP 962 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA DW9YP UT WOS:000384019000030 ER PT J AU Villasana, LE Peters, A Westbrook, GL Schnell, E AF Villasana, Laura E. Peters, Austin Westbrook, Gary L. Schnell, Eric TI Sex Differences in Post-Traumatic Hippocampal Neurogenesis SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Villasana, Laura E.; Peters, Austin; Schnell, Eric] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Peters, Austin] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Westbrook, Gary L.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. [Schnell, Eric] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2016 VL 25 IS 9 MA P-49 BP 974 EP 974 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA DW9YP UT WOS:000384019000066 ER PT J AU Jacobs, EG Weiss, B Whitfield-Gabrieli, S Klibanski, A Goldstein, JM AF Jacobs, Emily G. Weiss, Blair Whitfield-Gabrieli, Sue Klibanski, Anne Goldstein, Jill M. TI Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Jacobs, Emily G.; Weiss, Blair; Goldstein, Jill M.] Harvard Univ, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Jacobs, Emily G.; Klibanski, Anne; Goldstein, Jill M.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02138 USA. [Whitfield-Gabrieli, Sue] MIT, Cambridge, MA 02139 USA. [Klibanski, Anne] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2016 VL 25 IS 9 MA O-2 BP 977 EP 977 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA DW9YP UT WOS:000384019000073 ER PT J AU Don, PK Evans, JL Chiaromonte, F Kowaleski, AM AF Don, Prabhani Kuruppumullage Evans, Jenni L. Chiaromonte, Francesca Kowaleski, Alex M. TI Mixture-Based Path Clustering for Synthesis of ECMWF Ensemble Forecasts of Tropical Cyclone Evolution SO MONTHLY WEATHER REVIEW LA English DT Article ID MULTIVARIATE FUNCTIONAL DATA; EXTRATROPICAL TRANSITION; SINGULAR VECTORS; LIFE-CYCLE; UNCERTAINTY; TRACKS; DEPTH AB In this article, three tropical cyclones and their 120-h, 50-member ECMWF Integrated Forecasting System (IFS) ensemble track forecasts at 10 initialization times are considered. The IFS forecast tracks are clustered with a regression mixture model, and two traditional diagnostics (the Bayesian information criterion and a measure of strength of cluster assignment) are used to determine the optimal polynomial order and number of clusters to use in the model. In addition, cross-validation versions of the two diagnostics are formulated and computed to further aid in model selection. Both traditional and cross-validation diagnostics suggest that third-order polynomials and five clusters are effective options although the evidence is less conclusive for the number of clusters than for the polynomial order, and the cross-validation diagnostics favor a smaller number of clusters than the traditional ones. Path clustering of IFS tropical cyclone track forecasts with this third-order polynomial, five-cluster regression mixture model produces interpretable partitions by direction and speed of motion for each of the storms and initialization times considered. Thus, this approach effectively synthesizes the forecast spreads within the IFS into a small number of representative trajectories. Based on how forecasts distribute across clusters, this approach also provides information on the likelihood of each such representative trajectory. If used operationally, this information has the potential to aid forecasters in parsing and quantifying the uncertainty in tropical cyclone track forecasts. C1 [Don, Prabhani Kuruppumullage] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Don, Prabhani Kuruppumullage] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Evans, Jenni L.; Kowaleski, Alex M.] Penn State Univ, Dept Meteorol, 503 Walker Bldg, University Pk, PA 16802 USA. [Chiaromonte, Francesca] Penn State Univ, Dept Stat, University Pk, PA 16802 USA. RP Evans, JL (reprint author), Penn State Univ, Dept Meteorol, 503 Walker Bldg, University Pk, PA 16802 USA. EM jle7@psu.edu OI Evans, Jenni/0000-0003-3425-0932 FU National Science Foundation [ATM-1322532] FX We are grateful to Mr. Casey Webster, Dr. Julia Keller, and Dr. Sarah Jones for many helpful conversations. We thank Dr. Chuck Pavloski and Mr. Chad Bahrmann for their excellent programming assistance and database management. The comments of three anonymous reviewers led to substantial improvements in the manuscript. The ECMWF ensemble forecasts were obtained via the TIGGE database. This research was supported by the National Science Foundation under Grant ATM-1322532. NR 32 TC 1 Z9 1 U1 2 U2 2 PU AMER METEOROLOGICAL SOC PI BOSTON PA 45 BEACON ST, BOSTON, MA 02108-3693 USA SN 0027-0644 EI 1520-0493 J9 MON WEATHER REV JI Mon. Weather Rev. PD SEP PY 2016 VL 144 IS 9 BP 3301 EP 3320 DI 10.1175/MWR-D-15-0214.1 PG 20 WC Meteorology & Atmospheric Sciences SC Meteorology & Atmospheric Sciences GA DW8RN UT WOS:000383923300013 ER PT J AU Collins, CDE Ivry, B Bowen, JD Cheng, EM Dobson, R Goodin, DS Lechner-Scott, J Kappos, L Galea, I AF Collins, Christian D. E. Ivry, Ben Bowen, James D. Cheng, Eric M. Dobson, Ruth Goodin, Douglas S. Lechner-Scott, Jeannette Kappos, Ludwig Galea, Ian TI A comparative analysis of Patient-Reported Expanded Disability Status Scale tools SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Expanded disability status scale; Kurtzke scale; Neurostatus; multiple sclerosis; Patient-reported Expanded Disability Status Scale; patient reported; self administered ID RATING NEUROLOGIC IMPAIRMENT; MULTIPLE-SCLEROSIS; FUNCTIONAL-SYSTEMS; SELF-ASSESSMENT; AGREEMENT; EDSS; INTERRATER; VALIDATION; SCORES AB Background: Patient-Reported Expanded Disability Status Scale (PREDSS) tools are an attractive alternative to the Expanded Disability Status Scale (EDSS) during long term or geographically challenging studies, or in pressured clinical service environments. Objectives: Because the studies reporting these tools have used different metrics to compare the PREDSS and EDSS, we undertook an individual patient data level analysis of all available tools. Methods: Spearman's rho and the Bland-Altman method were used to assess correlation and agreement respectively. Results: A systematic search for validated PREDSS tools covering the full EDSS range identified eight such tools. Individual patient data were available for five PREDSS tools. Excellent correlation was observed between EDSS and PREDSS with all tools. A higher level of agreement was observed with increasing levels of disability. In all tools, the 95% limits of agreement were greater than the minimum EDSS difference considered to be clinically significant. However, the intra-class coefficient was greater than that reported for EDSS raters of mixed seniority. The visual functional system was identified as the most significant predictor of the PREDSS-EDSS difference. Conclusion: This analysis will (1) enable researchers and service providers to make an informed choice of PREDSS tool, depending on their individual requirements, and (2) facilitate improvement of current PREDSS tools. C1 [Collins, Christian D. E.; Ivry, Ben; Galea, Ian] Univ Southampton, Southampton Gen Hosp, Clin Neurosci Clin & Expt Sci, Fac Med, Mailpoint 806,Level D, Southampton SO16 6YD, Hants, England. [Bowen, James D.] Swedish Neurosci Inst, Multiple Sclerosis Ctr, Seattle, WA USA. [Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Dobson, Ruth] Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London, England. [Goodin, Douglas S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lechner-Scott, Jeannette] Univ Newcastle, Hunter Med Res Inst, Callaghan, NSW 2308, Australia. [Lechner-Scott, Jeannette] John Hunter Hosp, Dept Neurol, Newcastle, NSW, Australia. [Kappos, Ludwig] Univ Basel Hosp, Dept Med, Basel, Switzerland. [Kappos, Ludwig] Univ Basel Hosp, Dept Clin Res, Basel, Switzerland. [Kappos, Ludwig] Univ Basel Hosp, Dept Biomed, Basel, Switzerland. [Kappos, Ludwig] Univ Basel Hosp, Dept Biomed Engn, Basel, Switzerland. [Galea, Ian] Univ Hosp Southampton NHS Fdn Trust, Wessex Neurosci Ctr, Southampton, Hants, England. RP Galea, I (reprint author), Univ Southampton, Southampton Gen Hosp, Clin Neurosci Clin & Expt Sci, Fac Med, Mailpoint 806,Level D, Southampton SO16 6YD, Hants, England. EM I.Galea@soton.ac.uk RI Galea, Ian/B-7997-2011 OI Galea, Ian/0000-0002-1268-5102 FU University of Southampton; National Institute of Health Research (NIHR) FX This study was funded by the University of Southampton and National Institute of Health Research (NIHR). NR 27 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD SEP PY 2016 VL 22 IS 10 BP 1349 EP 1358 DI 10.1177/1352458515616205 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV5KP UT WOS:000382966300014 PM 26564998 ER PT J AU Gilmartin, HM Sousa, KH Battaglia, C AF Gilmartin, Heather M. Sousa, Karen H. Battaglia, Catherine TI Capturing the Central Line Bundle Infection Prevention Interventions: Comparison of Reflective and Composite Modeling Methods SO NURSING RESEARCH LA English DT Article DE critical care; epidemiology; factor analysis; iatrogenic infection; statistical models ID BLOOD-STREAM INFECTIONS; FORMATIVE MEASUREMENT; ORGANIZATIONAL RESEARCH; HEALTH; INDICATORS; REDUCTION; COHORT AB Background The central line (CL) bundle interventions are important for preventing central line-associated bloodstream infections (CLABSIs), but a modeling method for testing the CL bundle interventions within a health systems framework is lacking. Objectives Guided by the Quality Health Outcomes Model (QHOM), this study tested the CL bundle interventions in reflective and composite, latent, variable measurement models to assess the impact of the modeling approaches on an investigation of the relationships between adherence to the CL bundle interventions, organizational context, and CLABSIs. Methods A secondary data analysis study was conducted using data from 614 U.S. hospitals that participated in the Prevention of Nosocomial Infection and Cost-Effectiveness Refined study. The sample was randomly split into exploration and validation subsets. Results The two CL bundle modeling approaches resulted in adequate fitting structural models (RMSEA = .04; CFI = .94) and supported similar relationships within the QHOM. Adherence to the CL bundle had a direct effect on organizational context (reflective = .23; composite = .20; p = .01) and CLABSIs (reflective = -.28; composite = -.25; p = .01). The relationship between context and CLABSIs was not significant. Both modeling methods resulted in partial support of the QHOM. Discussion There were little statistical, but large, conceptual differences between the reflective and composite modeling approaches. The empirical impact of the modeling approaches was inconclusive, for both models resulted in a good fit to the data. Lessons learned are presented. The comparison of modeling approaches is recommended when initially modeling variables that have never been modeled or with directional ambiguity to increase transparency and bring confidence to study findings. C1 [Gilmartin, Heather M.; Battaglia, Catherine] Denver VA Med Ctr, Denver Seattle Ctr Innovat, Dept Vet Affairs, 1055 Clermont St, Denver, CO 80220 USA. [Sousa, Karen H.] Univ Colorado, Coll Nursing, Res & Extramural Affairs, Anschutz Med Campus, Aurora, CO USA. RP Gilmartin, HM (reprint author), Denver VA Med Ctr, Denver Seattle Ctr Innovat, Dept Vet Affairs, 1055 Clermont St, Denver, CO 80220 USA. EM Heather.gilmartin@va.gov FU National Institute of Nursing Research [R01NR010107] FX The authors acknowledge that funding for the PNICER study was provided by the National Institute of Nursing Research (R01NR010107). NR 43 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 0029-6562 EI 1538-9847 J9 NURS RES JI Nurs. Res. PD SEP-OCT PY 2016 VL 65 IS 5 BP 397 EP 407 DI 10.1097/NNR.0000000000000168 PG 11 WC Nursing SC Nursing GA DX4BX UT WOS:000384325100008 PM 27579507 ER PT J AU Bateman, BT Patorno, E Desai, RJ Seely, EW Mogun, H Maeda, A Fischer, MA Hernandez-Diaz, S Huybrechts, KF AF Bateman, Brian T. Patorno, Elisabetta Desai, Rishi J. Seely, Ellen W. Mogun, Helen Maeda, Ayumi Fischer, Michael A. Hernandez-Diaz, Sonia Huybrechts, Krista F. TI Late Pregnancy beta Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia SO PEDIATRICS LA English DT Article ID POSTPARTUM HEMORRHAGE; ANTIDEPRESSANT USE; UNITED-STATES; TIGHT CONTROL; LESS-TIGHT; COHORT; HYPERTENSION; POPULATION; PATTERNS; OUTCOMES AB BACKGROUND AND OBJECTIVES: beta blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to beta blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries. METHODS: We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to beta blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications. RESULTS: There were 10 585 (0.5%) pregnancies exposed to beta blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the beta blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively). CONCLUSION Our findings suggest that neonates born to mothers exposed to beta blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia. C1 [Bateman, Brian T.; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Fischer, Michael A.; Huybrechts, Krista F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. [Seely, Ellen W.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA USA. [Bateman, Brian T.; Maeda, Ayumi] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM bbateman@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) [K08HD075831]; National Heart Lung and Blood Institute at the National Institutes of Health [K24HL096141]; National Institute of Mental Health [K01MH099141]; Agency for Healthcare Research and Quality grant [R01HS018533]; National Institutes of Health (NIH) FX Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (Bethesda, Maryland) under award K08HD075831 (Dr Bateman), the National Heart Lung and Blood Institute at the National Institutes of Health under grant K24HL096141 (Dr Seely), and the National Institute of Mental Health under grant K01MH099141(Dr Huybrechts). The Medicaid Analytic eXtract pregnancy cohort was supported by Agency for Healthcare Research and Quality grant R01HS018533. The content is soley the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH). NR 28 TC 1 Z9 1 U1 2 U2 2 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 SEP PY 2016 VL 138 IS 3 AR e20160731 DI 10.1542/peds.2016-0731 PG 8 WC Pediatrics SC Pediatrics GA DW9SE UT WOS:000384002100033 ER PT J AU Murphy, JM Bergmann, P Chiang, C Sturner, R Howard, B Abel, MR Jellinek, M AF Murphy, J. Michael Bergmann, Paul Chiang, Cindy Sturner, Raymond Howard, Barbara Abel, Madelaine R. Jellinek, Michael TI The PSC-17: Subscale Scores, Reliability, and Factor Structure in a New National Sample SO PEDIATRICS LA English DT Article ID PEDIATRIC SYMPTOM CHECKLIST; PARENT-REPORT MEASURE; PRIMARY-CARE; PSYCHOSOCIAL PROBLEMS; BEHAVIORAL-PROBLEMS; TRACK OUTCOMES; CHILDREN; DISORDERS; IDENTIFICATION; POPULATIONS AB BACKGROUND: The Pediatric Symptom Checklist-17 (PSC-17) is a widely used, briefer version of the PSC-35, a parent-completed measure of children's psychosocial functioning. Despite the extensive use of the PSC-17 over the past 15 years there has not been a large-scale replication of the original derivation study. OBJECTIVE: To examine the prevalence of positive screens, reliability, and factor structure of PSC-17 scores in a new national sample and compare them with the derivation sample. METHODS: Data were collected on 80 680 pediatric outpatients, ages 4 to 15 years, whose parents filled out the PSC-17 from 2006 to 2015 via the Child Health and Development Interactive System, an electronic system that presents and scores clinical measures. RESULTS: The rates of positive screening on the overall PSC-17 (11.6%) and on the internalizing (10.4%) and attention (9.1%) subscales were comparable to rates found in the original sample, although the rate of externalizing problems (10.2%) was lower than in the derivation study. Reliability was high (internal consistency 0.89; test-retest 0.85), and a confirmatory factor analysis provided support for the original 3-factor model. CONCLUSIONS: Fifteen years after the PSC-17 was derived in a large nationally representative outpatient pediatric sample, a new and larger national sample found rates of positive screening, reliability, and factor structure that were comparable. Findings from this study support the continued use of the PSC-17 clinically as a screening tool in pediatric settings and in research. C1 [Murphy, J. Michael; Chiang, Cindy; Abel, Madelaine R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bergmann, Paul] PrairieCare Inst, Minneapolis, MN USA. [Bergmann, Paul] Foresight Log Inc, St Paul, MN USA. [Sturner, Raymond] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sturner, Raymond] Johns Hopkins Univ, Ctr Promot Child Dev Primary Care, Baltimore, MD USA. [Howard, Barbara] Johns Hopkins Univ, Sch Med & Total Child Hlth, Baltimore, MD USA. [Murphy, J. Michael; Jellinek, Michael] Harvard Med Sch, Boston, MA USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Yawkey 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org FU National Institutes of Mental Health of the National Institutes of Health [R44MH086302]; National Institutes of Health (NIH) FX Funding for the data analysis and writing of this article was provided by the Fuss Family Fund. Research data collection reported in this publication was supported by National Institutes of Mental Health of the National Institutes of Health under award number R44MH086302. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH). NR 49 TC 0 Z9 0 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD SEP PY 2016 VL 138 IS 3 AR e20160038 DI 10.1542/peds.2016-0038 PG 8 WC Pediatrics SC Pediatrics GA DW9SE UT WOS:000384002100019 ER PT J AU Schrager, SM Arthur, KC Nelson, J Edwards, AR Murphy, JM Mangione-Smith, R Chen, AY AF Schrager, Sheree M. Arthur, Kimberly C. Nelson, Justine Edwards, Anne R. Murphy, J. Michael Mangione-Smith, Rita Chen, Alex Y. TI Development and Validation of a Method to Identify Children With Social Complexity Risk Factors SO PEDIATRICS LA English DT Article ID HEALTH; CARE AB OBJECTIVES: We sought to develop and validate a method to identify social complexity risk abstract factors (eg, limited English proficiency) using Minnesota state administrative data. A secondary objective was to examine the relationship between social complexity and caregiver-reported need for care coordination. METHODS: A total of 460 caregivers of children with noncomplex chronic conditions enrolled in a Minnesota public health care program were surveyed and administrative data on these caregivers and children were obtained. We validated the administrative measures by examining their concordance with caregiver-reported indicators of social complexity risk factors using tetrachoric correlations. Logistic regression analyses subsequently assessed the association between social complexity risk factors identified using Minnesota's state administrative data and caregiver-reported need for care coordination, adjusting for child demographics. RESULTS: Concordance between administrative and caregiver-reported data was moderate to high (correlation range 0.31-0.94, all P values <.01), with only current homelessness (r = -0.01, P = .95) failing to align significantly between the data sources. The presence of any social complexity risk factor was significantly associated with need for care coordination before (unadjusted odds ratio = 1.65; 95% confidence interval, 1.07-2.53) but not after adjusting for child demographic factors (adjusted odds ratio = 1.53; 95% confidence interval, 0.98-2.37). CONCLUSIONS: Social complexity risk factors may be accurately obtained from state administrative data. The presence of these risk factors may heighten a family's need for care coordination and/or other services for children with chronic illness, even those not considered medically complex. C1 [Schrager, Sheree M.] Childrens Hosp Los Angeles, Div Hosp Med, 4650 Sunset Blvd,MS 94, Los Angeles, CA 90027 USA. [Arthur, Kimberly C.; Mangione-Smith, Rita] Seattle Childrens Hosp, Seattle, WA USA. [Arthur, Kimberly C.; Mangione-Smith, Rita] Seattle Childrens Res Inst, Seattle, WA USA. [Nelson, Justine] Minnesota Dept Human Serv, St Paul, MN USA. [Edwards, Anne R.] Park Nicollet Hlth Serv, Minneapolis, MN USA. [Murphy, J. Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Murphy, J. Michael] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Mangione-Smith, Rita] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Chen, Alex Y.] Univ Southern Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA USA. RP Schrager, SM (reprint author), Childrens Hosp Los Angeles, Div Hosp Med, 4650 Sunset Blvd,MS 94, Los Angeles, CA 90027 USA. EM sschrager@chla.usc.edu FU Agency for Healthcare Research and Quality; Centers for Medicare and Medicaid Services [U18HS020506] FX This study was funded by a cooperative agreement with the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services, grant #U18HS020506, part of the Children's Health Insurance Program Reauthorization Act Pediatric Quality Measures Program. NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD SEP PY 2016 VL 138 IS 3 AR e20153787 DI 10.1542/peds.2015-3787 PG 8 WC Pediatrics SC Pediatrics GA DW9SE UT WOS:000384002100006 ER PT J AU Sisk, BA Bluebond-Langner, M Wiener, L Mack, J Wolfe, J AF Sisk, Bryan A. Bluebond-Langner, Myra Wiener, Lori Mack, Jennifer Wolfe, Joanne TI Prognostic Disclosures to Children: A Historical Perspective SO PEDIATRICS LA English DT Article ID OF-LIFE CARE; FATALLY ILL CHILDREN; CANCER-PATIENTS; DYING CHILD; PEDIATRIC ONCOLOGISTS; INFORMED-CONSENT; COMMUNICATION; PARENTS; DEATH; ILLNESS AB Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Before 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a "protective" approach to disclosure, where children were shielded from the harms of bad news. We identified 4 main arguments in the literature at this time supporting this "protective" approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more "open" approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this "open" approach. Then, by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from "never tell" to "always tell." In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple "black-and-white" recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight 4 categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. C1 [Sisk, Bryan A.] St Louis Childrens Hosp, Dept Pediat, St Louis, MO USA. [Bluebond-Langner, Myra] UCL, Inst Child Hlth, Louis Dundas Ctr Childrens Palliat Care, London, England. [Wiener, Lori] NCI, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Mack, Jennifer] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mack, Jennifer] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Mack, Jennifer] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA. [Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. RP Sisk, BA (reprint author), St Louis Childrens Hosp, 1 Childrens Pl,3S34, St Louis, MO 63110 USA. EM sisk_b@kids.wustl.edu FU True Colours Trust, London, England; Intramural Research Programs of the Center for Cancer Research, National Institutes of Health; National Institutes of Health (NIH) FX This work was supported in part by the True Colours Trust, London, England, and by the Intramural Research Programs of the Center for Cancer Research, National Institutes of Health. Funded by the National Institutes of Health (NIH). NR 101 TC 0 Z9 0 U1 6 U2 6 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 SEP PY 2016 VL 138 IS 3 AR e20161278 DI 10.1542/peds.2016-1278 PG 10 WC Pediatrics SC Pediatrics GA DW9SE UT WOS:000384002100050 ER PT J AU Koch, J Flemming, J Zeffiro, T Rufer, M Orr, SP Mueller-Pfeiffer, C AF Koch, Jennifer Flemming, Jan Zeffiro, Thomas Rufer, Michael Orr, Scott P. Mueller-Pfeiffer, Christoph TI Effects of Posture and Stimulus Spectral Composition on Peripheral Physiological Responses to Loud Sounds SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; STARTLING TONES; VIETNAM VETERANS; TRAUMA SURVIVORS; HEART-RATE; INTENSITY; REACTIVITY; AMPLITUDE; DURATION; WOMEN AB In the "loud-tone" procedure, a series of brief, loud, pure-tone stimuli are presented in a task-free situation. It is an established paradigm for measuring autonomic sensitization in posttraumatic stress disorder (PTSD). Successful use of this procedure during fMRI requires elicitation of brain responses that have sufficient signal-noise ratios when recorded in a supine, rather than sitting, position. We investigated the modulating effects of posture and stimulus spectral composition on peripheral psychophysiological responses to loud sounds. Healthy subjects (N = 24) weekly engaged in a loud-tone-like procedure that presented 500 msec, 95 dB sound pressure level, pure-tone or white-noise stimuli, either while sitting or supine and while peripheral physiological responses were recorded. Heart rate, skin conductance, and eye blink electromyographic responses were larger to white-noise than pure-tone stimuli (p's < 0.001, generalized eta squared 0.073-0.076). Psychophysiological responses to the stimuli were similar in the sitting and supine position (p's >= 0.082). Presenting white noise, rather than pure-tone, stimuli may improve the detection sensitivity of the neural concomitants of heightened autonomic responses by generating larger responses. Recording in the supine position appears to have little or no impact on psychophysiological response magnitudes to the auditory stimuli. C1 [Koch, Jennifer; Flemming, Jan; Rufer, Michael; Mueller-Pfeiffer, Christoph] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Zurich, Switzerland. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Orr, Scott P.] Harvard Med Sch, Boston, MA USA. RP Mueller-Pfeiffer, C (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Zurich, Switzerland. EM christoph.mueller-pfeiffer@access.uzh.ch RI Dey, Kamalesh/E-6568-2017 NR 37 TC 0 Z9 0 U1 6 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 1 PY 2016 VL 11 IS 9 AR e0161237 DI 10.1371/journal.pone.0161237 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DV3WN UT WOS:000382855600017 PM 27583659 ER PT J AU Yaffe, K Nasrallah, I Hoang, TD Lauderdale, DS Knutson, KL Carnethon, MR Launer, LJ Lewis, CE Sidney, S AF Yaffe, Kristine Nasrallah, Ilya Hoang, Tina D. Lauderdale, Diane S. Knutson, Kristen L. Carnethon, Mercedes R. Launer, Lenore J. Lewis, Cora E. Sidney, Stephen TI Sleep Duration and White Matter Quality in Middle-Aged Adults SO SLEEP LA English DT Article DE sleep duration; white matter integrity; white matter hyperintensities; midlife ID COGNITIVE DECLINE; OLDER-ADULTS; MEMORY IMPAIRMENT; TEST-PERFORMANCE; HEALTH; WOMEN; RISK; METAANALYSIS; INTEGRITY; DISEASE AB Study Objectives: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. Methods: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to <= 8 h) and short sleep duration (<= 6 h) at baseline (2005-2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. Results: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). Conclusions: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke. C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Nasrallah, Ilya] Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA. [Lauderdale, Diane S.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Knutson, Kristen L.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Carnethon, Mercedes R.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Launer, Lenore J.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Sidney, Stephen] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kristine.yaffe@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA [AG0005, K24 AG031155]; NHLBI [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300029C, AG0005, HL122658] FX This was not an industry supported study. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C & HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). The CARDIA Cognitive Function Ancillary Study is supported by NHLBI HL122658. Dr. Yaffe is also supported by NIA K24 AG031155. This manuscript has been reviewed by CARDIA for scientific content. Drs. Yaffe, Carnethon, Lewis, and Sidney report grant support for the CARDIA study NHLBI HL122658, HHSN268201300027C, HHSN268201300025C & HHSN268201300026C, HHSN268201300029C. The other authors have indicated no financial conflicts of interest. NR 47 TC 0 Z9 0 U1 4 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD SEP 1 PY 2016 VL 39 IS 9 BP 1743 EP 1747 DI 10.5665/sleep.6104 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX4EG UT WOS:000384333400014 PM 27397561 ER PT J AU Herschkopf, MD Peteet, JR AF Herschkopf, Marta D. Peteet, John R. TI Ethical Considerations Regarding Religion/Spirituality in Consultation Psychiatry SO SPIRITUALITY IN CLINICAL PRACTICE LA English DT Article DE ethics; spirituality; religion; consultation-liaison psychiatry; capacity AB Psychiatrists who practice in medical settings often receive requests for consultation regarding value-laden issues such as coping and capacity. When patients' values are intertwined with their religious faith, such requests can raise ethical concerns about the psychiatrist's scope of practice, as illustrated here by 2 case examples. Furthermore, clinicians' own religious or spiritual values may cause them to experience ethical conflict when they are expected to provide care in cases involving issues such as abortion or assisted suicide. C1 [Herschkopf, Marta D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peteet, John R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Herschkopf, MD (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Rabb 2, Boston, MA 02215 USA. EM mherschk@bidmc.harvard.edu NR 5 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 2326-4500 EI 2326-4519 J9 SPIRITUAL CLIN PRACT JI Spiritual. Clin. Pract. PD SEP PY 2016 VL 3 IS 3 BP 155 EP 158 DI 10.1037/scp0000113 PG 4 WC Psychology, Clinical SC Psychology GA DX4BV UT WOS:000384324900002 ER PT J AU Capron, AM Delmonico, FL Dominguez-Gil, B Martin, DE Danovitch, GM Chapman, J AF Capron, Alexander Morgan Delmonico, Francis L. Dominguez-Gil, Beatriz Martin, Dominique Elizabeth Danovitch, Gabriel M. Chapman, Jeremy TI Statement of the Declaration of Istanbul Custodian Group Regarding Payments to Families of Deceased Organ Donors SO TRANSPLANTATION LA English DT Article ID DONATION AB Governmental and private programs that pay next of kin who give permission for the removal of their deceased relative's organs for transplantation exist in a number of countries. Such payments, which may be given to the relatives or paid directly for funeral expenses or hospital bills unrelated to being a donor, aim to increase the rate of donation. The Declaration of Istanbul Custodian Groupin alignment with the World Health Organization Guiding Principles and the Council of Europe Convention Against Trafficking in Human Organshas adopted a new policy statement opposing such practices. Payment programs are unwise because they produce a lower rate of donations than in countries with voluntary, unpaid programs; associate deceased donation with being poor and marginal in society; undermine public trust in the determination of death; and raise doubts about fair allocation of organs. Most important, allowing families to receive money for donation from a deceased person, who is at no risk of harm, will make it impossible to sustain prohibitions on paying living donors, who are at risk. Payment programs are also unethical. Tying coverage for funeral expenses or healthcare costs to a family allowing organs to be procured is exploitative, not charitable. Using payment to overcome reluctance to donate based on cultural or religious beliefs especially offends principles of liberty and dignity. Finally, while it is appropriate to make donation financially neutralby reimbursing the added medical costs of evaluating and maintaining a patient as a potential donorsuch reimbursement may never be conditioned on a family agreeing to donate. C1 [Capron, Alexander Morgan] Univ Southern Calif, Pacific Ctr Hlth Policy & Eth, Los Angeles, CA USA. [Delmonico, Francis L.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Delmonico, Francis L.] New England Organ Bank Inc, Boston, MA USA. [Dominguez-Gil, Beatriz] ONT, Madrid, Spain. [Martin, Dominique Elizabeth] Deakin Univ, Sch Med, Fac Hlth, Hlth Eth & Professionalism, Geelong, Vic, Australia. [Danovitch, Gabriel M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Kidney & Pancreas Transplant Program, Los Angeles, CA 90095 USA. [Chapman, Jeremy] Westmead Hosp, Div Med & Canc, Sydney, NSW, Australia. RP Capron, AM (reprint author), Univ Southern Calif, Gould Sch Law, 699 Exposit Blvd, Los Angeles, CA 90089 USA. EM acapron@law.usc.edu NR 12 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2016 VL 100 IS 9 BP 2006 EP 2009 DI 10.1097/TP.0000000000001198 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DW8NG UT WOS:000383912100040 PM 27355820 ER PT J AU Clements, KM Mitra, M Zhang, JY Iezzoni, LI AF Clements, Karen M. Mitra, Monika Zhang, Jianying Iezzoni, Lisa I. TI Pregnancy Characteristics and Outcomes among Women at Risk for Disability from Health Conditions Identified in Medical Claims SO WOMENS HEALTH ISSUES LA English DT Article ID PHYSICAL-DISABILITIES; BIRTH; LIFE; CARE AB Background: Women with disabilities are at risk for poor birth outcomes. Little is known about specific potentially disabling health conditions and their effects on pregnancies. Using hospital claims, we identified women at risk for disability and evaluated the relationship between disability risk and demographic characteristics, pregnancy risks, and infant and maternal outcomes. Methods: The 2006 through 2009 Massachusetts Pregnancy to Early Life Longitudinal data system linked birth certificate and hospital claims one year pre-pregnancy through delivery. Access Risk Classification System categorized International Classification of Diseases, Ninth Revision, Clinical Modification/Current Procedural Terminology codes into disability risk groups (no/limited vs. medium/high). Generalized estimating equations evaluated the association between disability risk and infant and maternal outcomes. Results: Of 221,867 women, 14,701 (6.6%) were at medium or high risk of disability. Health conditions were classified as circulatory (23%), musculoskeletal (10%), nervous system/sensory (13%), other physical (19%), two or more physical (5%), mental illness (24%), and comorbid mental/physical (6%). Women at risk of disability were more likely than others to have socioeconomic and pregnancy risks, and adverse infant and maternal outcomes. Socioeconomic and risk profile varied by health condition category. Adjusted risk ratios for preterm birth ranged from 1.2 (95% confidence interval [CI], 1.1-1.4) for women with nervous system/sensory diagnoses to 1.6 (95% CI, 1.4-1.9) for women with two or more physical diagnoses; risk ratios for maternal delivery hospitalization for more than 5 days ranged from 1.5 (95% CI, 1.2-1.9) for women with musculoskeletal diagnoses to 3.0 (95% CI, 2.5-3.6) for women with comorbid mental/physical diagnoses. Conclusions: Disability risk identified through claims is associated with poor infant and maternal outcomes. Risk profiles vary by underlying health condition. (C) 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Clements, Karen M.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, 333 South St, Shrewsbury, MA 01545 USA. [Clements, Karen M.; Zhang, Jianying] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Mitra, Monika] Brandeis Univ, Heller Sch Social Policy & Management, Lurie Inst Disabil Policy, Waltham, MA USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Clements, KM (reprint author), Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, 333 South St, Shrewsbury, MA 01545 USA. EM Karen.clements@umassmed.edu FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD 074581] FX This research is funded by a grant from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Award Number: R01HD 074581. NR 18 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 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2016 VL 26 IS 5 BP 504 EP 510 DI 10.1016/j.whi.2016.06.001 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DX1TT UT WOS:000384150600005 PM 27477954 ER PT J AU Gilmore, AK Brignone, E Painter, JM Lehavot, K Fargo, J Suo, Y Simpson, T Carter, ME Blais, RK Gundlapalli, AV AF Gilmore, Amanda K. Brignone, Emily Painter, Janelle M. Lehavot, Keren Fargo, Jamison Suo, Ying Simpson, Tracy Carter, Marjorie E. Blais, Rebecca K. Gundlapalli, Adi V. TI Military Sexual Trauma and Co-occurring Posttraumatic Stress Disorder, Depressive Disorders, and Substance Use Disorders among Returning Afghanistan and Iraq Veterans SO WOMENS HEALTH ISSUES LA English DT Article ID MENTAL-HEALTH DIAGNOSES; RANDOMIZED CONTROLLED-TRIAL; WOMEN VETERANS; GENDER-DIFFERENCES; RISK-FACTORS; ALCOHOL MISUSE; CARE; FEMALE; PTSD; PREFERENCES AB Purpose: Posttraumatic stress disorder (PTSD), depressive disorders (DD), and substance use disorders (SUD) are prevalent among veterans. A positive military sexual trauma (MST) screen is associated with higher likelihood of each of these disorders. The current study examined the associations between MST, gender, and co-occurring PTSD, DD, and SUD among veterans receiving services at the Department of Veterans Affairs to inform assessment and treatment. We were specifically interested in the interactions between MST and gender on co-occurring disorders. Methods: The sample included 494,822 Department of Veterans Affairs service-seeking veterans (12.5% women) deployed to Iraq and Afghanistan who recently separated from the military and were screened for MST between 2004 and 2013. Main Findings: Veterans with positive MST screens had higher odds than those with negative screens of individual and co-occurring PTSD, DD, and SUD. The association between positive MST screens and diagnostic outcomes, including PTSD, was stronger for women than for men, and the association between positive MST screens and some diagnostic outcomes, including DD, was stronger for men than for women. Conclusions: These results highlight the importance of assessing for and recognizing the potential MST and gender interactions in the clinical context among veterans with co-occurring PTSD, DD, and/or SUD. (C) 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Gilmore, Amanda K.] Med Univ South Carolina, Dept Psychiat, Natl Crime Victims Res & Treatment Ctr, Charleston, SC USA. [Gilmore, Amanda K.; Painter, Janelle M.; Lehavot, Keren; Simpson, Tracy] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Brignone, Emily; Fargo, Jamison; Blais, Rebecca K.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Brignone, Emily; Fargo, Jamison; Suo, Ying; Carter, Marjorie E.; Gundlapalli, Adi V.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Suo, Ying; Gundlapalli, Adi V.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. RP Gilmore, AK (reprint author), Natl Crime Victims & Treatment Ctr, Dept Psychiat, 67 President St,MSC 861, Charleston, SC 29425 USA. EM gilmoram@musc.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Projects [HIR 10-002, IIR 12-084]; Career Development Award from CSRD [IK2 CX000867]; NIMH [T32] FX Funding for this project was provided by grants from the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Projects # HIR 10-002 and # IIR 12-084 (PI: AVG). Resources and administrative support were provided by the VA Salt Lake City Health Care System (IDEAS Center). Dr. Lehavot was supported by a Career Development Award from CSR&D (IK2 CX000867). Dr. Gilmore was supported by an NIMH-funded T32 (PIs: Kilpatrick & Danielson). NR 41 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 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD SEP-OCT PY 2016 VL 26 IS 5 BP 546 EP 554 DI 10.1016/j.whi.2016.07.001 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DX1TT UT WOS:000384150600011 PM 27528358 ER PT J AU Weiner, SG Raja, AS Bittner, JC Curtis, KM Weimersheimer, P Hasegawa, K Espinola, JA Camargo, CA AF Weiner, Scott G. Raja, Ali S. Bittner, Jane C. Curtis, Kevin M. Weimersheimer, Peter Hasegawa, Kohei Espinola, Janice A. Camargo, Carlos A., Jr. TI Opioid-related Policies in New England Emergency Departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID PRESCRIPTION; OVERDOSES AB Objectives: The opioid abuse and overdose epidemic in the United States has led to the need for new practice policies to guide clinicians. We describe implementation of opioid-related policies in emergency departments (EDs) in New England to gauge progress and determine where further work is needed. Methods: This study analyzed data from the 2015 National Emergency Department Inventory-New England survey. The survey queried directors of every ED (n = 195) in the six New England states to determine the implementation of five specific policies related to opioid management. ED characteristics (e.g., annual visits, location, and admission rates) were also obtained and a multivariable analysis was conducted to identify ED characteristics independently associated with the number of opioid-related policies implemented. Results: Overall, 169 EDs (87%) responded, with a >80% response rate in each state. Implementation of opioid-related policies varied as follows: 1) use of a screening tool for patients with suspected prescription opioid abuse potential (n = 30, 18%), 2) access state prescription drug monitoring program (PDMP) before prescribing opioids (n = 132, 78%), 3) notify the primary opioid prescriber when prescribing opioids for ED patients with chronic pain (n = 69, 41%), 4) refer patients with opioid abuse to recovery resources (n = 117, 70%), and 5) prescribe naloxone to patients at risk of opioid overdose after ED discharge (n = 19, 12%). EDs located in metropolitan areas and with at least one attending physician on duty 24/7 were less likely to implement opioid policies (incident rate ratio [IRR] = 0.65, 95% confidence interval [CI] = 0.48-0.89; and IRR = 0.78, 95% CI = 0.6-1.0, respectively) while EDs with = 15% hospitalization rate that used electronic computerized medication ordering and those in Rhode Island were more likely to implement opioid policies (IRR = 1.23, 95% CI = 1.03-1.48; IRR = 1.95, 95% CI = 1.19-3.22; and IRR = 1.30, 95% CI = 1.08-1.56, respectively). Conclusions: The implementation of opioid-related policies varies among New England EDs. The presence of policies recommending use of screening tools and prescribing naloxone for at-risk patients was low, whereas those regarding utilization of the PDMP and referral of patients with opioid abuse to recovery resources were more common. These data provide important benchmarks for future evaluations and recommendations. (C) 2016 by the Society for Academic Emergency Medicine C1 [Weiner, Scott G.] Harvard Med Sch, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Raja, Ali S.; Bittner, Jane C.; Hasegawa, Kohei; Espinola, Janice A.; Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Curtis, Kevin M.] Geisel Sch Med Dartmouth, Dartmouth Hitchcock Med Ctr, Sect Emergency Med, Lebanon, NH USA. [Weimersheimer, Peter] Univ Vermont, Dept Surg, Med Ctr, Div Emergency Med,Coll Med, Burlington, VT 05405 USA. RP Weiner, SG (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. EM sweiner@massmed.org NR 10 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2016 VL 23 IS 9 BP 1086 EP 1090 DI 10.1111/acem.12992 PG 5 WC Emergency Medicine SC Emergency Medicine GA DW1CE UT WOS:000383379600016 PM 27098615 ER PT J AU Owens, EA Henary, M El Fakhri, G Choi, HS AF Owens, Eric A. Henary, Maged El Fakhri, Georges Choi, Hak Soo TI Tissue-Specific Near-Infrared Fluorescence Imaging SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID QUANTUM DOTS; PHOTODYNAMIC THERAPY; FLUOROPHORES; CANCER; AGENTS; PROBE; DYES; NANOPARTICLES; BONE AB Near-infrared (NIR) fluorescence light has been widely utilized in clinical imaging by providing surgeons highly specific images of target tissue. The NIR window from 650 to 900 nm is especially useful due to several special features such as minimal autofluorescence and absorption of biomolecules in tissue, as well as low light scattering. Compared with visible wavelengths, NIR fluorescence light is invisible, thus allowing highly sensitivity real-time image guidance in human surgery without changing the surgical field. The benefit of using NIR fluorescence light as a clinical imaging technology can be attributed to its molecular fluorescence as an exogenous contrast agent. Indeed, whole body preoperative imaging of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) remains important in diagnostic utility, but they lack the efficacy of innocuous and targeted NIR fluorophores to simultaneously facilitate the real-time delineation of diseased tissue while preserving vital tissues. Admittedly, NIR imaging technology has been slow to enter clinical use mostly due to the late-coming development of truly breakthrough contrast agents for use with current imaging systems. Therefore, clearly defining the physical margins of tumorous tissue remains of paramount importance in bioimaging and targeted therapy. An equally noteworthy yet less researched goal is the ability to outline healthy vital tissues that should be carefully navigated without transection during the intraoperative surgery. Both of these paths require optimizing a gauntlet of design considerations to obtain not only an effective imaging agent in the NIR window but also high molecular brightness, water solubility, biocompatibility, and tissue-specific targetability. The imaging community recognizes three strategic approaches which include (1) passive targeting via the EPR effect, (2) active targeting using the innate overall biodistribution of known molecules, and (3) activatable targeting through an internal stimulus, which turns on fluorescence from an off state. Recent advances in nanomedicine and bioimaging offer much needed promise toward fulfilling these stringent requirements as we develop a successful catalog of targeted contrast agents for illuminating both tumors and vital tissues in the same surgical space by employing spectrally distinct fluorophores in real time. These tissue-specific contrast agents can be versatile arsenals to physicians for real-time intraoperative navigation as well as image-guided targeted therapy. There is a versatile library of tissue-specific fluorophores available in the literature, with many discussed herein, which offers clinicians an array of possibilities that will undoubtedly improve intraoperative success and long-term postoperation prognosis. C1 [Owens, Eric A.; Henary, Maged] Georgia State Univ, Dept Chem, Ctr Diagnost & Therapeut, Atlanta, GA 30303 USA. [El Fakhri, Georges; Choi, Hak Soo] Massachusetts Gen Hosp, Dept Radiol, Gordon Ctr Med Imaging, Boston, MA 02114 USA. [El Fakhri, Georges; Choi, Hak Soo] Harvard Med Sch, Boston, MA 02114 USA. RP Henary, M (reprint author), 100 Piedmont Ave 315, Atlanta, GA 30303 USA.; Choi, HS (reprint author), 55 Fruit St,White 427, Boston, MA 02114 USA. EM mhenary1@gsu.edu; hchoi12@mgh.harvard.edu FU Georgia State University; NIH/NIBIB [R01-EB-011523, R01-EB-017699]; Center for Diagnostics and Therapeutics FX This study was supported by a Georgia State University dissertation grant (E.A.O.) and the NIH/NIBIB Grant Nos. R01-EB-011523 (H.S.C.) and R01-EB-017699 (H.S.C.). E.A.O. was supported through a predoctoral fellowship from the Center for Diagnostics and Therapeutics. NR 35 TC 2 Z9 2 U1 67 U2 67 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD SEP PY 2016 VL 49 IS 9 BP 1731 EP 1740 DI 10.1021/acs.accounts.6b00239 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA DX0GA UT WOS:000384038600015 PM 27564418 ER PT J AU Pasquale, LR Borras, T Fingert, JH Wiggs, JL Ritch, R AF Pasquale, Louis R. Borras, Terete Fingert, John H. Wiggs, Janey L. Ritch, Robert TI Exfoliation syndrome: assembling the puzzle pieces SO ACTA OPHTHALMOLOGICA LA English DT Article DE animal models; CACNA1A; exfoliation syndrome; homocysteine; LOXL1 ID SENSORINEURAL HEARING-LOSS; PRIMARY OPEN-ANGLE; SYNTHASE GENE VARIANTS; PSEUDOEXFOLIATION SYNDROME; METHYLENETETRAHYDROFOLATE REDUCTASE; OCULAR PSEUDOEXFOLIATION; GLAUCOMA INTERACTIONS; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; ABDOMINAL-AORTA AB PurposeTo summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. MethodsThe highlights of three categories of talks on cutting edge research in the field were summarized. ResultsExfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. ConclusionMeeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and exvivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to upstream solutions' to reduce the ocular morbidity produced by XFS. C1 [Pasquale, Louis R.; Wiggs, Janey L.] Harvard Med Sch, Dept Ophthalmol, Mass Eye & Ear Infirm, Boston, MA USA. [Pasquale, Louis R.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Borras, Terete] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. [Fingert, John H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Ritch, Robert] New York Eye & Ear Infirm Mt Sinai, Einhorn Clin Res Ctr, New York, NY USA. RP Ritch, R (reprint author), New York Eye & Ear Infirm Mt Sinai, 310 East 14th St,304, New York, NY 10003 USA. EM ritchmd@earthlink.net NR 78 TC 0 Z9 0 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD SEP PY 2016 VL 94 IS 6 BP E505 EP E512 DI 10.1111/aos.12918 PG 8 WC Ophthalmology SC Ophthalmology GA DW3CX UT WOS:000383520800019 PM 26648185 ER PT J AU Allegretti, AS Ortiz, G Cui, J Wenger, J Bhan, I Chung, RT Thadhani, RI Irani, Z AF Allegretti, Andrew S. Ortiz, Guillermo Cui, Jie Wenger, Julia Bhan, Ishir Chung, Raymond T. Thadhani, Ravi I. Irani, Zubin TI Changes in Kidney Function After Transjugular Intrahepatic Portosystemic Shunts Versus Large-Volume Paracentesis in Cirrhosis: A Matched Cohort Analysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Transjugular intrahepatic portosystemic shunt (TIPS); TIPS placement; large-volume paracentesis (LVP); cirrhosis; refractory ascites; estimated glomerular filtration rate (eGFR); renal function; mortality; portal hypertension; liver; kidney ID REFRACTORY ASCITES; HEPATORENAL-SYNDROME; STENT-SHUNT; RENAL-FAILURE; LIVER-TRANSPLANTATION; ALCOHOLIC CIRRHOSIS; PLUS ALBUMIN; SHORT-TERM; HEMODYNAMICS; INJURY AB Background: Patients with cirrhosis and refractory ascites have physiologic and hormonal dysregulation that contributes to decreased kidney function. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) can reverse these changes and potentially improve kidney function. We sought to evaluate change in estimated glomerular filtration rate (eGFR) following TIPS placement. Study Design: Retrospective, matched cohort analysis. Settings & Participants: Patients who underwent first-time TIPS placement for refractory ascites in 1995 to 2014. Frequency matching was used to generate a comparator group of patients with cirrhosis and ascites treated with serial large-volume paracentesis (LVP) in a 1: 1 fashion. Predictor: TIPS placement compared to serial LVP. Outcome: Change in eGFR over 90 days' follow-up. Measurements: Multivariable regression stratified by baseline eGFR, 60 versus >= 60 mL/min/1.73 m(2); analysis of effect modification between TIPS placement and baseline eGFR. Results: 276 participants (TIPS, n 5 138; serial LVP, n 5 138) were analyzed. After 90 days, eGFRs increased significantly after TIPS placement in participants with baseline eGFRs, 60 mL/min/1.73 m(2) compared to treatment with serial LVP (21 [95% CI, 13-29] mL/min/1.73 m(2); P<0.001) and was no different in those with eGFRs >= 60 mL/min/1.73 m(2) (1 [95% CI, 29 to 12] mL/min/1.73 m(2); P < 0.8). There was significant effect modification between TIPS status and baseline eGFR (P < 0.001) in a model that included all participants. Limitations: Outcomes restricted by clinically recorded data; clinically important differences may still exist between the TIPS and LVP cohorts despite good statistical matching. Conclusions: TIPS placement was associated with significant improvement in kidney function. This was most prominent in participants with baseline eGFRs, 60 mL/min/1.73 m(2). Prospective studies of TIPS use in populations with eGFRs, 60 mL/min/1.73 m(2) are needed to evaluate these findings. (C) 2016 by the National Kidney Foundation, Inc. C1 [Allegretti, Andrew S.; Ortiz, Guillermo; Cui, Jie; Wenger, Julia; Bhan, Ishir; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Ctr Liver, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Div, Dept Med, Boston, MA 02114 USA. [Irani, Zubin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Allegretti, AS (reprint author), 55 Fruit St,GRB 1008, Boston, MA 02114 USA. EM aallegretti@partners.org FU National Institutes of Health (NIH) [5T32DK007540-30]; NIH [K24 DK078772, R01 DK094486, K24 DK094872] FX Funding for this study was from departmental funds. No external sources influenced study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. Dr Allegretti is supported by National Institutes of Health (NIH) grant 5T32DK007540-30; Dr Chung, by NIH grant K24 DK078772; and Dr Thadhani, by NIH grants R01 DK094486 and K24 DK094872. NR 51 TC 2 Z9 2 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2016 VL 68 IS 3 BP 381 EP 391 DI 10.1053/j.ajkd.2016.02.041 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA DW8FU UT WOS:000383891000009 PM 26994685 ER PT J AU Dauvilliers, Y Benes, H Partinen, M Rauta, V Rifkin, D Dohin, E Goldammer, N Schollmayer, E Schroder, H Winkelman, JW AF Dauvilliers, Yves Benes, Heike Partinen, Markku Rauta, Virpi Rifkin, Daniel Dohin, Elisabeth Goldammer, Nadine Schollmayer, Erwin Schroeder, Hanna Winkelman, John W. TI Rotigotine in Hemodialysis-Associated Restless Legs Syndrome: A Randomized Controlled Trial SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease (CKD); dopamine agonist; rotigotine; restless legs syndrome (RLS); periodic limb movements (PLM); periodic limb movement index (PLMI); hemodialysis; end-stage renal disease (ESRD); randomized controlled trial (RCT) ID STAGE RENAL-DISEASE; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; TRANSDERMAL ROTIGOTINE; CROSSOVER TRIAL; SLEEP; MOVEMENTS; MORTALITY; MULTICENTER; FAILURE AB Background: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. Study Design: Double-blind placebo-controlled study. Setting & Participants: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] >= 15) and Periodic Limb Movement Index (PLMI) >= 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. Intervention: Following randomization and titration (<= 21 + 3 days) to optimal-dose rotigotine (1-3 mg/24h) or placebo, patients entered a 2-week maintenance period. Polysomnography was performed at baseline and the end of maintenance. Outcomes & Measurements: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. Results: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7 +/- 0.4 for rotigotine and 1.3 +/- 0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P = 0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P = 0.05] and -0.81 [95% CI, -1.94 to 0.33; P = 0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (>= 50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (>= 2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). Limitations: Small sample size and short duration. Conclusions: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients. (C) 2016 by the National Kidney Foundation, Inc. C1 [Dauvilliers, Yves] CHU Montpellier, Guide Chauliac Hosp, Sleep Disorders Ctr, INSERM U1061,Dept Nephrol, Montpellier, France. [Benes, Heike] Somni Bene Inst Med Forsch & Schlafmed, Schwerin, Germany. [Benes, Heike] Univ Rostock, Med Ctr, Rostock, Germany. [Partinen, Markku] Helsinki Sleep Clin, Vitalmed Res Ctr, Helsinki, Finland. [Rauta, Virpi] Helsinki Univ Cent Hosp, Helsinki, Finland. [Rifkin, Daniel] Sleep Med Ctr Western New York, West Seneca, NY USA. [Dohin, Elisabeth] UCB Pharma, Brussels, Belgium. [Goldammer, Nadine; Schollmayer, Erwin; Schroeder, Hanna] UCB Pharma, Monheim, Germany. [Winkelman, John W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Sleep Disorders Clin Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA. EM jwwinkelman@partners.org FU UCB Pharma, Monheim am Rhein, Germany; UCB Pharma; Jazz; Bioprojet; Sanofi-Aventis; Fresenius Medical Care; Baxter; B. Braun; AbbVie; Roche; Merck; NeuroMetrix; Purdue FX Support: This study was supported by UCB Pharma, Monheim am Rhein, Germany. All costs associated with manuscript development and publication were met by the sponsor. The sponsor was involved in the design of the study, analysis and interpretation of the data, writing the report, and the decision to submit the manuscript for publication. Writing and editorial assistance was provided by Hannah Carney, PhD, and Beth Sesler, PhD ( Evidence Scientific Solutions, Horsham, United Kingdom) and contracted by UCB Pharma, Brussels, Belgium. Publication coordination was provided by Cedric Laloyaux (Global Publications Manager CNS, UCB Pharma, Brussels, Belgium).; Financial Disclosure: Dr Dauvilliers has received personal compensation from UCB Pharma for consulting services and financial support for research activities from UCB Pharma, Jazz, and Bioprojet. Dr Benes has received personal compensation for serving on advisory boards from UCB Pharma and Mundipharma. Dr Partinen has received speaker honoraria and consulting compensation from GSK, Boehringer Ingelheim, Sanofi-Aventis, Orion Pharma, and UCB Pharma and financial support for research activities from Sanofi-Aventis and UCB Pharma. Dr Rauta has received speaking fees from Fresenius Medical Care, Baxter, B. Braun, AbbVie, and Roche. Dr Rifkin has received financial support for research activities from UCB Pharma, Merck, and Sanofi-Aventis. Dr Dohin is an employee of UCB Pharma and receives stock options. Dr Goldammer, Dr Schollmayer, and Ms Schrder are employees of UCB Pharma. Dr Winkelman has received personal compensation for consulting from UCB Pharma, personal compensation and stock options for consulting from FlexPharma, personal compensation for serving on scientific advisory boards from Merck and Insys, and personal compensation for writing from UpToDate; he has also received financial support for research activities from UCB Pharma, NeuroMetrix, and Purdue. NR 36 TC 5 Z9 5 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2016 VL 68 IS 3 BP 434 EP 443 DI 10.1053/j.ajkd.2015.12.027 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA DW8FU UT WOS:000383891000014 PM 26851201 ER PT J AU Hundemer, GL Rosales, IA Chen, YB Colvin, RB Tolkoff-Rubin, NE AF Hundemer, Gregory L. Rosales, Ivy A. Chen, Yi-Bin Colvin, Robert B. Tolkoff-Rubin, Nina E. TI Hydroxyurea for Treatment of Nephrotic Syndrome Associated With Polycythemia Vera SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Hydroxyurea; polycythemia vera; myeloproliferative disorder; nephrotic syndrome; proteinuria; focal segmental glomerulosclerosis (FSGS); kidney biopsy; renal function; case report ID GROWTH-FACTOR; DISEASE; GLOMERULOSCLEROSIS; RUXOLITINIB; EXPRESSION; SCLEROSIS; PDGF AB Myeloproliferative disorders are a rare cause of focal segmental glomerulosclerosis (FSGS), although the mechanism is unclear. Hydroxyurea is commonly used in these disorders for its cytoreductive properties; however, the effect of this treatment on proteinuria or kidney function remains unclear in cases of myeloproliferative disorder-associated FSGS. We describe the clinical course of a patient with polycythemia vera and nephrotic-range proteinuria, demonstrated to have FSGS on biopsy. The patient had a distant history of granulomatosis with polyangiitis (Wegener's), for which he routinely had his kidney function and proteinuria measured, allowing for early detection of nephrotic syndrome soon after being diagnosed with polycythemia vera. Treatment with hydroxyurea resulted in rapid improvement in proteinuria that correlated with a decrease in hematocrit. This response was replicated 2 additional times when the patient was taken off and then restarted on hydroxyurea therapy. He now maintains a steady dose of hydroxyurea with favorable kidney measures (proteinuria with <1 g/d of protein excretion and serum creatinine of 1.27 mg/dL [corresponding to estimated glomerular filtration rate of 56 mL/min/1.73 m(2)]). This case suggests that early screening and treatment for myeloproliferative disorder-associated FSGS may lead to improved long-standing kidney function. (C) 2016 by the National Kidney Foundation, Inc. C1 [Hundemer, Gregory L.; Tolkoff-Rubin, Nina E.] Massachusetts Gen Hosp, Div Nephrol, Ste 1008,Gray Bigelow 10,55 Fruit St, Boston, MA 02114 USA. [Rosales, Ivy A.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Hundemer, GL (reprint author), Massachusetts Gen Hosp, Div Nephrol, Ste 1008,Gray Bigelow 10,55 Fruit St, Boston, MA 02114 USA. EM ghundemer@partners.org NR 14 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2016 VL 68 IS 3 BP 465 EP 468 DI 10.1053/j.ajkd.2016.02.056 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DW8FU UT WOS:000383891000017 PM 27133437 ER PT J AU Hundemer, GL Fenves, AZ Phillips, KM Emmett, M AF Hundemer, Gregory L. Fenves, Andrew Z. Phillips, Kristy M. Emmett, Michael TI Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Letter ID CALCIFIC UREMIC ARTERIOLOPATHY; THERAPY; CALCIPHYLAXIS C1 [Hundemer, Gregory L.; Fenves, Andrew Z.; Phillips, Kristy M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Emmett, Michael] Baylor Univ, Med Ctr, Dallas, TX USA. [Emmett, Michael] Texas A&M Coll Med, Dallas, TX USA. RP Hundemer, GL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ghundemer@partners.org NR 10 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2016 VL 68 IS 3 BP 499 EP 500 DI 10.1053/j.ajkd.2016.02.040 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA DW8FU UT WOS:000383891000022 PM 26992479 ER PT J AU Vachha, BA Ginat, DT Mallur, P Cunnane, M Moonis, G AF Vachha, B. A. Ginat, D. T. Mallur, P. Cunnane, M. Moonis, G. TI "Finding a Voice": Imaging Features after Phonosurgical Procedures for Vocal Fold Paralysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID CROSS-LINKED HYALURONAN; INJECTION LARYNGOPLASTY; GLOTTAL INSUFFICIENCY; THYROPLASTY; AUGMENTATION; COMPLICATIONS; IMMOBILITY; IMPLANT; DERMIS AB Altered communication (hoarseness, dysphonia, and breathy voice) that can result from vocal fold paralysis, secondary to numerous etiologies, may be amenable to surgical restoration. In this article, both traditional and cutting-edge phonosurgical procedures targeting the symptoms resulting from vocal fold paralysis are reviewed, with emphasis on the characteristic imaging appearances of various injectable materials, implants, and augmentation procedures used in the treatment of vocal fold paralysis. In addition, complications of injection laryngoplasty and medialization laryngoplasty are illustrated. Familiarity with the expected imaging changes following treatment of vocal fold paralysis may prevent the misinterpretation of posttreatment changes as pathology. Identifying common complications related to injection laryngoplasty and localization of displaced implants is crucial in determining specific management in patients who have undergone phonosurgical procedures for the management of vocal fold paralysis. C1 [Vachha, B. A.] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA. [Vachha, B. A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Ginat, D. T.] Univ Chicago, Dept Radiol, Chicago, IL USA. [Mallur, P.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Otol & Laryngol, Boston, MA USA. [Cunnane, M.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA USA. [Moonis, G.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA. RP Vachha, BA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA. EM vachhab@mskcc.org NR 28 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2016 VL 37 IS 9 BP 1574 EP 1580 DI 10.3174/ajnr.A4781 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DV7JR UT WOS:000383112700001 PM 27173367 ER PT J AU MacMahon, PJ Huang, AJ Palmer, WE AF MacMahon, Peter J. Huang, Ambrose J. Palmer, William E. TI Spine Injectables: What Is the Safest Cocktail? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE corticosteroids; crystals; epidural; infarction; injection; local anesthetic; safety ID EPIDURAL STEROID INJECTIONS; LOW-BACK-PAIN; CONTAMINATED METHYLPREDNISOLONE INJECTIONS; CERVICAL TRANSFORAMINAL INJECTIONS; DORSAL-ROOT GANGLION; OF-THE-LITERATURE; CELLS IN-VITRO; NERVE ROOT; RADICULAR PAIN; NONPARTICULATE CORTICOSTEROIDS AB OBJECTIVE. Spinal injections are common pain management procedures using corticosteroids and local anesthetics. Most corticosteroid preparations are particulate suspensions, such as methylprednisolone acetate and triamcinolone acetonide. In the cervical spine, particulate corticosteroids have been linked to catastrophic complications, including blindness, paralysis, and death. Serious neurologic injuries have also been reported at the thoracic, lumbar, and sacral levels. CONCLUSION. Nonparticulate preparations, such as dexamethasone, are safer but have shorter-lived antiinflammatory effects. Local anesthetics are often mixed with corticosteroids in pain management procedures. Although everyday risks are minimal, injection techniques should take into account neural and cardiac toxicities. In this article, we discuss the potential for serious adverse events associated with injected medications. We review the current literature to make conclusions on medication combinations that balance safety and efficacy. C1 [MacMahon, Peter J.] Mater Misericordiae Univ Hosp, Dept Radiol, Whitty Bldg,North Circular Rd, Dublin 7, Ireland. [Huang, Ambrose J.; Palmer, William E.] Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP MacMahon, PJ (reprint author), Mater Misericordiae Univ Hosp, Dept Radiol, Whitty Bldg,North Circular Rd, Dublin 7, Ireland. EM pmacmahon@mater.ie NR 112 TC 1 Z9 1 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 SEP PY 2016 VL 207 IS 3 BP 526 EP 533 DI 10.2214/AJR.16.16379 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DW9LF UT WOS:000383980200014 PM 27341350 ER PT J AU Zwang, NA Zhang, R Germana, S Fan, MY Hastings, WD Cao, A Turka, LA AF Zwang, N. A. Zhang, R. Germana, S. Fan, M. Y. Hastings, W. D. Cao, A. Turka, L. A. TI Selective Sparing of Human Tregs by Pharmacologic Inhibitors of the Phosphatidylinositol 3-Kinase and MEK Pathways SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE translational research; science; immunosuppression; immune modulation; signaling; signaling pathways: PI-3 kinase; Akt pathway; T cell biology ID REGULATORY T-CELLS; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAY; REG-CELLS; IN-VITRO; SUPPRESSIVE FUNCTION; CATALYTIC ISOFORMS; GENE-EXPRESSION; MAPK PATHWAY; CROSS-TALK AB Phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated (MEK) signaling are central to the survival and proliferation of many cell types. Multiple lines of investigation in murine models have shown that control of the PI3K pathway is particularly important for regulatory T cell (Treg) stability and function. PI3K and MEK inhibitors are being introduced into the clinic, and we hypothesized that pharmacologic inhibition of PI3K, and possibly MEK, in mixed cultures of human mononuclear cells would preferentially affect CD4(+) and CD8(+) lymphocytes compared with Tregs. We tested this hypothesis using four readouts: proliferation, activation, functional suppression, and signaling. Results showed that Tregs were less susceptible to inhibition by both and isoform-specific PI3K inhibitors and by an MEK inhibitor compared with their conventional CD4(+) and CD8(+) counterparts. These studies suggest less functional reliance on PI3K and MEK signaling in Tregs compared with conventional CD4(+) and CD8(+) lymphocytes. Therefore, the PI3K and MEK pathways are attractive pharmacologic targets for transplantation and treatment of autoimmunity. In vitro agents that block the PI-3 kinase and/or MEK pathways preferentially block nonregulatory T cells, relatively sparing regulatory T cells, suggesting that these pathways may be attractive targets in transplantation. C1 [Zwang, N. A.; Zhang, R.; Germana, S.; Fan, M. Y.; Turka, L. A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Zwang, N. A.] Massachusetts Gen Hosp Brigham & Womens Hosp Neph, Boston, MA USA. [Hastings, W. D.; Cao, A.] Novartis Pharmaceut, Cambridge, MA USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. EM lturka@partners.org FU Massachusetts General Hospital/Brigham; Women's Hospital Nephrology Joint Fellowship Program; American Society of Nephrology Donald E. Wesson Research Fellowship FX We thank Christopher M. Borges for assistance with flow cytometry, and the Massachusetts General Hospital/Brigham and Women's Hospital Nephrology Joint Fellowship Program for its support. N.Z. was supported by the American Society of Nephrology Donald E. Wesson Research Fellowship. NR 65 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2016 VL 16 IS 9 BP 2624 EP 2638 DI 10.1111/ajt.13805 PG 15 WC Surgery; Transplantation SC Surgery; Transplantation GA DW6PZ UT WOS:000383774700016 PM 27017850 ER PT J AU Peacock, WF Diercks, D Birkhahn, R Singer, AJ Hollander, JE Nowak, R Safdar, B Miller, CD Peberdy, M Counselman, F Chandra, A Kosowsky, J Neuenschwander, J Schrock, J Lee-Lewandrowski, E Arnold, W Nagurney, J AF Peacock, W. Frank Diercks, Deborah Birkhahn, Robert Singer, Adam J. Hollander, Judd E. Nowak, Richard Safdar, Basmah Miller, Chadwick D. Peberdy, Mary Counselman, Francis Chandra, Abhinav Kosowsky, Joshua Neuenschwander, James Schrock, Jon Lee-Lewandrowski, Elizabeth Arnold, William Nagurney, John TI Can a Point-of-Care Troponin I Assay be as Good as a Central Laboratory Assay? A MIDAS Investigation SO ANNALS OF LABORATORY MEDICINE LA English DT Article DE Troponin; Point-of-care; Emergency medicine; Diagnostic accuracy ID CHEST-PAIN; MYOCARDIAL-INFARCTION; ASSOCIATION; POPULATION; MORTALITY AB Background: We aimed to compare the diagnostic accuracy of the Alere Triage Cardio3 Tropinin I (TnI) assay (Alere, Inc., USA) and the PathFast cTnI-II (Mitsubishi Chemical Medience Corporation, Japan) against the central laboratory assay Singulex Erenna TnI assay (Singulex, USA). Methods: Using the Markers in the Diagnosis of Acute Coronary Syndromes (MIDAS) study population, we evaluated the ability of three different assays to identify patients with acute myocardial infarction (AMI). The MIDAS dataset, described elsewhere, is a prospective multicenter dataset of emergency department (ED) patients with suspected acute coronary syndrome (ACS) and a planned objective myocardial perfusion evaluation. Myocardial infarction (MI) was diagnosed by central adjudication. Results: The C-statistic with 95% confidence intervals (CI) for diagnosing MI by using a common population (n=241) was 0.95 (0.91-0.99), 0.95 (0.91-0.99), and 0.93 (0.89-0.97) for the Triage, Singulex, and PathFast assays, respectively. Of samples with detectable troponin, the absolute values had high Pearson (R-P) and Spearman (R-S) correlations and were R-P=0.94 and R-S=0.94 for Triage vs Singulex, R-P=0.93 and R-S=0.85 for Triage vs PathFast, and R-P=0.89 and R-S=0.73 for PathFast vs Singulex. Conclusions: In a single comparative population of ED patients with suspected ACS, the Triage Cardio3 TnI, PathFast, and Singulex TnI assays provided similar diagnostic performance for MI. C1 [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Diercks, Deborah] Univ Texas Southwestern, Dallas, TX USA. [Birkhahn, Robert] New York Methodist Hosp, Brooklyn, NY USA. [Singer, Adam J.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Hollander, Judd E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Nowak, Richard] Henry Ford Hosp, Detroit, MI 48202 USA. [Safdar, Basmah] Yale Univ, New Haven, CT USA. [Miller, Chadwick D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Peberdy, Mary] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Counselman, Francis] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Chandra, Abhinav] Duke Univ, Durham, NC USA. [Kosowsky, Joshua; Lee-Lewandrowski, Elizabeth; Nagurney, John] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neuenschwander, James] Genesis Healthcare Syst, Zanesville, OH USA. [Schrock, Jon] Metrohlth Med Ctr, Cleveland, OH USA. [Arnold, William] Alere Inc, San Diego, CA USA. RP Peacock, WF (reprint author), Baylor Coll Med, Emergency Med, Ben Taub Gen Hosp, 1504 Taub Loop, Houston, TX 77030 USA. EM Frankpeacock@gmail.com NR 15 TC 0 Z9 0 U1 1 U2 1 PU KOREAN SOC LABORATORY MEDICINE PI SEOUL PA A505-ASTERIUM SEOUL, 372 HANGANG-DAERO, YONGSAN-GU, SEOUL, 04323, SOUTH KOREA SN 2234-3806 EI 2234-3814 J9 ANN LAB MED JI Ann. Lab. Med. PD SEP PY 2016 VL 36 IS 5 BP 405 EP 412 DI 10.3343/alm.2016.36.5.405 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA DW2KL UT WOS:000383471200002 PM 27374704 ER PT J AU Messacar, K Schreiner, TL Van Haren, K Yang, M Glaser, CA Tyler, KL Dominguez, SR AF Messacar, Kevin Schreiner, Teri L. Van Haren, Keith Yang, Michele Glaser, Carol A. Tyler, Kenneth L. Dominguez, Samuel R. TI Acute flaccid myelitis: A clinical review of US cases 2012-2015 SO ANNALS OF NEUROLOGY LA English DT Review ID POLIOMYELITIS-LIKE ILLNESS; ACUTE NEUROLOGICAL ILLNESS; ENTEROVIRUS 71 INFECTION; UPPER RESPIRATORY-TRACT; UNITED-STATES; MRI FINDINGS; CHILDREN; D68; PARALYSIS; OUTBREAK AB This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States. Ann Neurol 2016;80:326-338 C1 [Messacar, Kevin] Childrens Hosp Colorado, Dept Pediat, Sect Hosp Med, Aurora, CO USA. [Messacar, Kevin; Dominguez, Samuel R.] Childrens Hosp Colorado, Dept Pediat, Sect Pediat Infect Dis, Aurora, CO USA. [Schreiner, Teri L.; Yang, Michele] Childrens Hosp Colorado, Dept Pediat, Neurol Sect, Aurora, CO USA. Univ Colorado, Sch Med, Aurora, CO USA. [Van Haren, Keith] Stanford Univ, Dept Neurol, Sch Med, Stanford, CA 94305 USA. [Glaser, Carol A.] Kaiser Permanente Med Ctr, Oakland, CA USA. [Glaser, Carol A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Med, Denver, CO USA. [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Immunol Microbiol, Denver, CO USA. [Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Messacar, K (reprint author), Childrens Hosp Colorado, Dept Hosp Med, B055,13123 East 16th Ave, Aurora, CO 80045 USA.; Messacar, K (reprint author), Childrens Hosp Colorado, Dept Infect Dis, B055,13123 East 16th Ave, Aurora, CO 80045 USA.; Messacar, K (reprint author), Univ Colorado, Sch Med, B055,13123 East 16th Ave, Aurora, CO 80045 USA. EM Kevin.messacar@childrenscolorado.org FU NIAID NIH HHS [T32 AI052066] NR 56 TC 3 Z9 4 U1 5 U2 5 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 SEP PY 2016 VL 80 IS 3 BP 326 EP 338 DI 10.1002/ana.24730 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW9YH UT WOS:000384018200003 PM 27422805 ER PT J AU Byblow, W Schlaug, G Wittenberg, G AF Byblow, Winston Schlaug, Gottfried Wittenberg, George TI What's the perfect dose for practice to make perfect? SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID CHRONIC STROKE PATIENTS; MOTOR RECOVERY; THERAPY; STIMULATION; INTEGRITY; DEPENDS; MUSIC; BRAIN C1 [Byblow, Winston] Univ Auckland, Dept Exercise Sci, Auckland, New Zealand. [Byblow, Winston] Univ Auckland, Ctr Brain Res, Auckland, New Zealand. [Schlaug, Gottfried] Beth Israel Deaconess Med Ctr, Dept Neurol, Div Stroke Recovery & Neurorestorat, Neuroimaging & Stroke Recovery Lab, Boston, MA 02215 USA. [Schlaug, Gottfried] Harvard Med Sch, Boston, MA USA. [Wittenberg, George] US Dept Vet Affairs, Maryland Exercise & Robot Ctr Excellence, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Wittenberg, George] Univ Maryland, Lab Res Arm Funct & Therapy, Older Amer Independence Ctr, Dept Neurol,Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA. [Wittenberg, George] Univ Maryland, Lab Res Arm Funct & Therapy, Older Amer Independence Ctr, Div Gerontol & Geriatr Med,Dept Phys Therapy & Re, Baltimore, MD 21201 USA. [Wittenberg, George] Univ Maryland, Lab Res Arm Funct & Therapy, Older Amer Independence Ctr, Div Gerontol & Geriatr Med,Dept Med, Baltimore, MD 21201 USA. RP Byblow, W (reprint author), Univ Auckland, Dept Exercise Sci, Auckland, New Zealand.; Byblow, W (reprint author), Univ Auckland, Ctr Brain Res, Auckland, New Zealand. OI Wittenberg, George/0000-0001-5603-1197 NR 18 TC 0 Z9 0 U1 1 U2 1 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 SEP PY 2016 VL 80 IS 3 BP 339 EP 341 DI 10.1002/ana.24735 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW9YH UT WOS:000384018200004 PM 27447540 ER PT J AU Takeda, S Commins, C DeVos, SL Nobuhara, CK Wegmann, S Roe, AD Costantino, I Fan, ZY Nicholls, SB Sherman, AE Lipsanopoulos, ATT Scherzer, CR Carlson, GA Pitstick, R Peskind, ER Raskind, MA Li, G Montine, TJ Frosch, MP Hyman, BT AF Takeda, Shuko Commins, Caitlin DeVos, Sarah L. Nobuhara, Chloe K. Wegmann, Susanne Roe, Allyson D. Costantino, Isabel Fan, Zhanyun Nicholls, Samantha B. Sherman, Alexis E. Lipsanopoulos, Ana T. Trisini Scherzer, Clemens R. Carlson, George A. Pitstick, Rose Peskind, Elaine R. Raskind, Murray A. Li, Ge Montine, Thomas J. Frosch, Matthew P. Hyman, Bradley T. TI Seed-competent high-molecular-weight tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients SO ANNALS OF NEUROLOGY LA English DT Article ID CSF BIOMARKERS; IN-VIVO; PROPAGATION; PATHOLOGY; BRAIN; TAUOPATHY; MICE; AGE AB ObjectiveCerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or, in fact, a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in the postmortem AD brain and can be taken up by neurons and seed aggregates. MethodsWe have examined seeding and uptake properties of brain extracellular tau from various sources, including interstitial fluid (ISF) and CSF from an AD transgenic mouse model and postmortem ventricular and antemortem lumbar CSF from AD patients. ResultsWe found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients, and its levels were significantly elevated compared to control subjects. HMW tau derived from CSF of AD patients was seed competent in vitro. InterpretationThese findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species, giving new insights into the role of CSF tau and biomarker development for AD. Ann Neurol 2016;80:355-367 C1 [Takeda, Shuko] Osaka Univ, Dept Clin Gene Therapy, Ctr Med Innovat & Transnatl Res, Sch Med, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan. [Takeda, Shuko; Commins, Caitlin; DeVos, Sarah L.; Nobuhara, Chloe K.; Wegmann, Susanne; Roe, Allyson D.; Costantino, Isabel; Fan, Zhanyun; Nicholls, Samantha B.; Sherman, Alexis E.; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Med Sch, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Alzheimers Dis Res Lab,Dept Neurol, Charlestown, MA USA. [Lipsanopoulos, Ana T. Trisini] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. [Scherzer, Clemens R.] Harvard Med Sch, Neurogen Lab, Cambridge, MA USA. [Scherzer, Clemens R.] Harvard Med Sch, Parkinson Personalized Med Program, Cambridge, MA USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA USA. [Carlson, George A.; Pitstick, Rose] McLaughlin Res Inst, Great Falls, MT USA. [Peskind, Elaine R.; Raskind, Murray A.; Li, Ge] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Peskind, Elaine R.; Raskind, Murray A.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Li, Ge] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Takeda, S (reprint author), Osaka Univ, Dept Clin Gene Therapy, Ctr Med Innovat & Transnatl Res, Sch Med, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan. EM takeda@cgt.med.osaka-u.ac.jp FU NIH [AG026249, PDBP U01 NS082157]; Massachusetts ADRC [P50AG05134]; University of Washington ADRC [P50AG05136]; Massachusetts Life Sciences Foundation; JPB foundation; Japan Society for the Promotion of Science (JSPS); German Research Foundation; M.E.M.O. Hoffman Foundation; U.S. Department of Defense FX This research is supported by NIH grant AG026249, Massachusetts ADRC (P50AG05134), the University of Washington ADRC (P50AG05136), the Massachusetts Life Sciences Foundation, The JPB foundation (to B.T.H.), and an anonymous foundation. The Harvard Biomarkers Study is, in part, supported by a gift from Rick and Nancy Moskovitz. S.T. is supported by the fellowship from the Japan Society for the Promotion of Science (JSPS). S.L.D. is supported by the NIH T32 training grant "Training in the Molecular Biology of Neurodegeneration". S.W. is supported by a fellowship from the German Research Foundation. C.R.S's work is supported by NIH grant PDBP U01 NS082157, the M.E.M.O. Hoffman Foundation, and the U.S. Department of Defense. NR 28 TC 4 Z9 4 U1 6 U2 6 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 SEP PY 2016 VL 80 IS 3 BP 355 EP 367 DI 10.1002/ana.24716 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DW9YH UT WOS:000384018200006 PM 27351289 ER PT J AU Jimenez, X Psutka, SP Stone, JH Carruthers, MN AF Jimenez, Xavier Psutka, Sarah P. Stone, John H. Carruthers, Mollie N. TI A 53-Year-Old Man With Dysuria, Pyuria, and Genital Ulcers SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; WEGENERS-GRANULOMATOSIS; POLYARTERITIS-NODOSA; MICROSCOPIC POLYANGIITIS; NECROTIZING VASCULITIS; LOCALIZED AMYLOIDOSIS; PERIARTERITIS-NODOSA; BLADDER INVOLVEMENT; BEHCETS-SYNDROME; URINARY-BLADDER C1 [Jimenez, Xavier] Univ Penn, Penn Hosp, Philadelphia, PA 19104 USA. [Psutka, Sarah P.] Mayo Clin, Rochester, MN USA. [Stone, John H.; Carruthers, Mollie N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stone, John H.; Carruthers, Mollie N.] Harvard Med Sch, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU Genentech; Roche FX Dr. Stone has received consulting fees, speaking fees, and/or honoraria from Genentech and Roche (less than $10,000 each). NR 41 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2016 VL 68 IS 9 BP 1371 EP 1377 DI 10.1002/acr.22617 PG 7 WC Rheumatology SC Rheumatology GA DW2WL UT WOS:000383502400018 PM 25989159 ER PT J AU Honigberg, MC Wallace, ZS Castelino, FV AF Honigberg, Michael C. Wallace, Zachary S. Castelino, Flavia V. TI A 30-Year-Old Woman With Chest Pain and Coronary Artery Aneurysms SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EHLERS-DANLOS-SYNDROME; LONG-TERM MANAGEMENT; KAWASAKI-DISEASE; FOLLOW-UP; EOSINOPHILIC GRANULOMATOSIS; ANTIPHOSPHOLIPID SYNDROME; MYOCARDIAL-INFARCTION; POLYARTERITIS-NODOSA; OSTIAL STENOSIS C1 [Honigberg, Michael C.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Honigberg, Michael C.; Wallace, Zachary S.; Castelino, Flavia V.] Harvard Med Sch, Boston, MA USA. [Wallace, Zachary S.; Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Castelino, FV (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM fcastelino@mgh.harvard.edu NR 50 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2016 VL 68 IS 9 BP 1378 EP 1384 DI 10.1002/acr.22476 PG 7 WC Rheumatology SC Rheumatology GA DW2WL UT WOS:000383502400019 PM 25220598 ER PT J AU Wallace, ZS Wallace, CJ Lu, N Choi, HK Stone, JH AF Wallace, Zachary S. Wallace, Carly J. Lu, Na Choi, Hyon K. Stone, John H. TI Association of IgG4-Related Disease With History of Malignancy SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID AUTOIMMUNE PANCREATITIS; CANCER; RISK; DERMATOMYOSITIS; POLYMYOSITIS; COHORT AB Objective. IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4-RD patients who have a history of malignancy preceding the clinical onset of IgG4-RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis. Methods. We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression. Results. The meanSD age at IgG4-RD onset was 50.3 +/- 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1-3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6-6.2). Conclusion. Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment. C1 [Wallace, Zachary S.; Lu, Na; Choi, Hyon K.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wallace, Carly J.] Boston Univ, Boston, MA 02215 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Rheumatol Clin, Yawkey Ctr 2, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu FU National Institute of Allergy and Infectious Diseases, NIH [AI-110495] FX Supported by the National Institute of Allergy and Infectious Diseases, NIH (grant AI-110495). NR 25 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2016 VL 68 IS 9 BP 2283 EP 2289 DI 10.1002/art.39773 PG 7 WC Rheumatology SC Rheumatology GA DW2VB UT WOS:000383498800028 PM 27273903 ER PT J AU Graf, SA Vaughn, JE Chauncey, TR Storer, BE Gopal, AK Holmberg, LA McCune, JS Bensinger, WI Maloney, DG Press, OW Storb, R Sorror, ML AF Graf, Solomon A. Vaughn, Jennifer E. Chauncey, Thomas R. Storer, Barry E. Gopal, Ajay K. Holmberg, Leona A. McCune, Jeannine S. Bensinger, William I. Maloney, David G. Press, Oliver W. Storb, Rainer Sorror, Mohamed L. TI Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after Autologous Hematopoietic Cell Transplantation for Lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Lymphoma; Autologous; Transplant; HCT-CI; Alcohol ID BONE-MARROW-TRANSPLANTATION; NON-HODGKIN-LYMPHOMA; HIGH-DOSE THERAPY; ELDERLY-PATIENTS; PSYCHOSOCIAL FACTORS; RESPONSE CRITERIA; REDUCED-INTENSITY; MULTIPLE-MYELOMA; SCREENING SCORES; INDEX AB Autologous hematopoietic cell transplantation (HCT) is a treatment option for many patients diagnosed with lymphoma. The effects of patient-specific factors on outcomes after autologous HCT are not well characterized. Here, we studied a sequential cohort of 754 patients with lymphoma treated with autologous HCT between 2000 and 2010. In multivariate analysis, patient-specific factors that were statistically significantly associated with nonrelapse mortality (NRM) included HCT-specific comorbidity index (HCT-CI) scores >= 3 (HR, 1.94; P = .05), a history of alcohol use disorder (AUD) (HR, 2.17; P = .004), and older age stratified by decade (HR, 1.29; P = .02). HCT-CI >= 3, a history of AUD, and age > 50 were combined into a composite risk model: NRM and overall mortality rates at 5 years increased from 6% to 30% and 32% to 58%, respectively, in patients with 0 versus all 3 risk factors. The HCT-CI is a valid tool in predicting mortality risks after autologous HCT for lymphoma. AUD and older age exert independent prognostic impact on outcomes. Whether AUD indicates additional organ dysfunction or sociobehavioral abnormality warrants further investigation. The composite model may improve risk stratification before autologous HCT. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation. C1 [Graf, Solomon A.; Vaughn, Jennifer E.; Chauncey, Thomas R.; Storer, Barry E.; Gopal, Ajay K.; Holmberg, Leona A.; McCune, Jeannine S.; Bensinger, William I.; Maloney, David G.; Press, Oliver W.; Storb, Rainer; Sorror, Mohamed L.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Graf, Solomon A.; Vaughn, Jennifer E.; Chauncey, Thomas R.; Gopal, Ajay K.; Holmberg, Leona A.; Bensinger, William I.; Maloney, David G.; Press, Oliver W.; Storb, Rainer; Sorror, Mohamed L.] Univ Washington, Dept Med, Seattle, WA USA. [Graf, Solomon A.; Chauncey, Thomas R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Vaughn, Jennifer E.] Virginia Tech Carilion Sch Med, Dept Med, Blue Ridge Canc Care, Roanoke, VA USA. [Storer, Barry E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McCune, Jeannine S.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. RP Sorror, ML (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,Mail Stop D5-280, Seattle, WA 98109 USA. EM msorror@fredhutch.org FU National Institutes of Health [CA018029, HL088021, T32 HL007093-38, K24 CA184039]; American Cancer Society [RSG-13-084-01-CPHPS]; Patient-Centered Outcomes Research Institute [CE-1304-7451] FX Financial disclosure: This study was supported by the National Institutes of Health (grant numbers CA018029 and HL088021 to M.L.S., T32 HL007093-38 to S.A.G., T32 HL007093-38 to J.E.V., K24 CA184039 to A.K.G), the American Cancer Society (Research Scholar grant no. RSG-13-084-01-CPHPS to M.L.S.), and the Patient-Centered Outcomes Research Institute [contract no. CE-1304-7451 to M.L.S.). NR 35 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2016 VL 22 IS 9 BP 1582 EP 1587 DI 10.1016/j.bbmt.2016.06.007 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DT8YK UT WOS:000381781400007 PM 27311969 ER PT J AU Ballen, K Ahn, KW Chen, M Abdel-Azim, H Ahmed, I Aljurf, M Antin, J Bhatt, AS Boeckh, M Chen, G Dandoy, C George, B Laughlin, MJ Lazarus, HM MacMillan, ML Margolis, DA Marks, DI Norkin, M Rosenthal, J Saad, A Savani, B Schouten, HC Storek, J Szabolcs, P Ustun, C Verneris, MR Waller, EK Weisdorf, DJ Williams, KM Wingard, JR Wirk, B Wolfs, T Young, JAH Auletta, J Komanduri, KV Lindemans, C Riches, ML AF Ballen, Karen Ahn, Kwang Woo Chen, Min Abdel-Azim, Hisham Ahmed, Ibrahim Aljurf, Mahmoud Antin, Joseph Bhatt, Ami S. Boeckh, Michael Chen, George Dandoy, Christopher George, Biju Laughlin, Mary J. Lazarus, Hillard M. MacMillan, Margaret L. Margolis, David A. Marks, David I. Norkin, Maxim Rosenthal, Joseph Saad, Ayman Savani, Bipin Schouten, Harry C. Storek, Jan Szabolcs, Paul Ustun, Celalettin Verneris, Michael R. Waller, Edmund K. Weisdorf, Daniel J. Williams, Kirsten M. Wingard, John R. Wirk, Baldeep Wolfs, Tom Young, Jo-Anne H. Auletta, Jeffrey Komanduri, Krishna V. Lindemans, Caroline Riches, Marcie L. TI Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Umbilical cord blood; Leukemia; Infection ID UMBILICAL-CORD BLOOD; INVASIVE FUNGAL DISEASE; ACUTE MYELOID-LEUKEMIA; UNRELATED DONORS; BONE-MARROW; HEMATOLOGIC MALIGNANCIES; PERIPHERAL-BLOOD; IMMUNE RECONSTITUTION; CONDITIONING REGIMEN; INTERNATIONAL BLOOD AB Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n = 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and < .0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) >= 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Ballen, Karen] Massachusetts Gen Hosp, Div Hematol Oncol, Suite 118, Boston, MA 02115 USA. [Ahn, Kwang Woo; Chen, Min] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Abdel-Azim, Hisham] Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA. [Ahmed, Ibrahim] Childrens Mercy Hosp & Clin, Dept Hematol Oncol & Bone Marrow Transplantat, Kansas City, MO USA. [Aljurf, Mahmoud] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia. [Antin, Joseph] Dana Farber Canc Inst, Dept Med Oncol, Ctr Hematol Oncol, Boston, MA 02115 USA. [Bhatt, Ami S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Boeckh, Michael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA. [Chen, George] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Dandoy, Christopher] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [George, Biju] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Laughlin, Mary J.] Cleveland Cord Blood Ctr, Cleveland, OH USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [MacMillan, Margaret L.; Verneris, Michael R.; Young, Jo-Anne H.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Margolis, David A.] Med Coll Wisconsin, Dept Pediat, Sect Hematol Oncol & BMT, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. [Marks, David I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Norkin, Maxim; Wingard, John R.] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA. [Rosenthal, Joseph] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Saad, Ayman] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Savani, Bipin] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Schouten, Harry C.] Acad Ziekenhuis, Dept Hematol, Maastricht, Netherlands. [Storek, Jan] Univ Calgary, Dept Med, Calgary, AB, Canada. [Szabolcs, Paul] Childrens Natl Hlth Syst, Div Blood & Marrow Transplantat, Washington, DC USA. [Ustun, Celalettin; Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. [Waller, Edmund K.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Williams, Kirsten M.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Wirk, Baldeep] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA. [Wolfs, Tom] Wilhelmina Childrens Hosp, Div Pediat, Utrecht, Netherlands. [Auletta, Jeffrey] Nationwide Childrens Hosp, Host Def Program, Div Hematol, Columbus, OH USA. [Auletta, Jeffrey] Nationwide Childrens Hosp, Host Def Program, Div Oncol, Columbus, OH USA. [Auletta, Jeffrey] Nationwide Childrens Hosp, Host Def Program, Div Bone Marrow Transplant, Columbus, OH USA. [Auletta, Jeffrey] Nationwide Childrens Hosp, Host Def Program, Div Infect Dis, Columbus, OH USA. [Komanduri, Krishna V.] Univ Miami, Adult Stem Cell Transplantat Program, Miami, FL USA. [Lindemans, Caroline] Univ Med Ctr Utrecht, Pediat Blood & Marrow Transplantat Program, Utrecht, Netherlands. [Riches, Marcie L.] Univ North Carolina Chapel Hill, Div Hematol Oncol, Chapel Hill, NC USA. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Suite 118, Boston, MA 02115 USA. EM kballen@partners.org OI Saad, Ayman /0000-0003-0003-0130 FU National Cancer Institute, the National Heart, Lung and Blood Institute [5U24-CA076518]; National Institute of Allergy and Infectious Diseases; NCI [5U10HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Alexion; Amgen, Inc.; NHLBI FX The CIBMTR is supported by public health service grant/cooperative agreement 5U24-CA076518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; a grant/cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from Alexion; daggerAmgen, Inc.; an anonymous donation to the Medical College of Wisconsin; Be the Match Foundation; daggerBristol Myers Squibb Oncology; daggerCelgene Corporation; daggerChimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; daggerGilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; daggerJazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; daggerMillennium: The Takeda Oncology Co.; daggerMiltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. - Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; daggerSanofi US; Seattle Genetics; Sigma Tau Pharmaceuticals; daggerSpectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; daggerSunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, -Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; and daggerWellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government. daggerIndicates corporate members. NR 40 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2016 VL 22 IS 9 BP 1636 EP 1645 DI 10.1016/j.bbmt.2016.06.012 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DT8YK UT WOS:000381781400015 PM 27343716 ER PT J AU Li, SL Gray, RJ AF Li, Shuli Gray, Robert J. TI Estimating Treatment Effect in a Proportional Hazards Model in Randomized Clinical Trials with All-or-Nothing Compliance SO BIOMETRICS LA English DT Article DE All-or-nothing compliance; EM algorithm; Proportional hazards model; Randomized clinical trial; Weighted partial likelihood ID NEGATIVE BREAST-CANCER; NONCOMPLIANCE; CHEMOTHERAPY; LIKELIHOOD; REGRESSION AB We consider methods for estimating the treatment effect and/or the covariate by treatment interaction effect in a randomized clinical trial under noncompliance with time-to-event outcome. As in Cuzick et al. (2007), assuming that the patient population consists of three (possibly latent) subgroups based on treatment preference: the ambivalent group, the insisters, and the refusers, we estimate the effects among the ambivalent group. The parameters have causal interpretations under standard assumptions. The article contains two main contributions. First, we propose a weighted per-protocol (Wtd PP) estimator through incorporating time-varying weights in a proportional hazards model. In the second part of the article, under the model considered in Cuzick et al. (2007), we propose an EM algorithm to maximize a full likelihood (FL) as well as the pseudo likelihood (PL) considered in Cuzick et al. (2007). The E step of the algorithm involves computing the conditional expectation of a linear function of the latent membership, and the main advantage of the EM algorithm is that the risk parameters can be updated by fitting a weighted Cox model using standard software and the baseline hazard can be updated using closed-form solutions. Simulations show that the EM algorithm is computationally much more efficient than directly maximizing the observed likelihood. The main advantage of the Wtd PP approach is that it is more robust to model misspecifications among the insisters and refusers since the outcome model does not impose distributional assumptions among these two groups. C1 [Li, Shuli; Gray, Robert J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Li, SL (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM shuli@jimmy.harvard.edu; gray@jimmy.harvard.edu FU National Institutes of Health [T32CA009337] FX Support for Shuli Li's research was provided by National Institutes of Health doctoral training grant T32CA009337. The authors thank ECOG-ACRIN for permission to use the data. NR 18 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2016 VL 72 IS 3 BP 742 EP 750 DI 10.1111/biom.12472 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA DW0YJ UT WOS:000383369000008 PM 26799700 ER PT J AU Ramchandani, R Schoenfeld, DA Finkelstein, DM AF Ramchandani, Ritesh Schoenfeld, David A. Finkelstein, Dianne M. TI Global Rank Tests for Multiple, Possibly Censored, Outcomes SO BIOMETRICS LA English DT Article DE ALS; Global test; Multiple endpoints; Nonparametric; Rank-sum; U-statistic ID AMYOTROPHIC-LATERAL-SCLEROSIS; ACUTE HEART-FAILURE; CLINICAL-TRIALS; END-POINTS; COMPARING SAMPLES; MORTALITY AB Clinical trials often collect multiple outcomes on each patient, as the treatment may be expected to affect the patient on many dimensions. For example, a treatment for a neurological disease such as ALS is intended to impact several dimensions of neurological function as well as survival. The assessment of treatment on the basis of multiple outcomes is challenging, both in terms of selecting a test and interpreting the results. Several global tests have been proposed, and we provide a general approach to selecting and executing a global test. The tests require minimal parametric assumptions, are flexible about weighting of the various outcomes, and are appropriate even when some or all of the outcomes are censored. The test we propose is based on a simple scoring mechanism applied to each pair of subjects for each endpoint. The pairwise scores are then reduced to a summary score, and a rank-sum test is applied to the summary scores. This can be seen as a generalization of previously proposed nonparametric global tests (e.g., O'Brien, 1984). We discuss the choice of optimal weighting schemes based on power and relative importance of the outcomes. As the optimal weights are generally unknown in practice, we also propose an adaptive weighting scheme and evaluate its performance in simulations. We apply the methods to analyze the impact of a treatment on neurological function and death in an ALS trial. C1 [Ramchandani, Ritesh; Schoenfeld, David A.; Finkelstein, Dianne M.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. [Schoenfeld, David A.; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Dept Biostat, 50 Staniford St, Boston, MA 02114 USA. RP Ramchandani, R (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. EM ritesh@mail.harvard.edu FU NIH [T32NS048005] FX We would like to thank committee member Rebecca Betensky for her input and discussion on this project. Thanks to the referees and the Associate Editor for their thoughtful suggestions, which have helped improve this article. This work was supported by NIH grant T32NS048005. NR 27 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2016 VL 72 IS 3 BP 926 EP 935 DI 10.1111/biom.12475 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA DW0YJ UT WOS:000383369000026 PM 26812695 ER PT J AU Levin, N Spencer, A Harrison, SJ Chauhan, D Burrows, FJ Anderson, KC Reich, SD Richardson, PG Trikha, M AF Levin, Nancy Spencer, Andrew Harrison, Simon J. Chauhan, Dharminder Burrows, Francis J. Anderson, Kenneth C. Reich, Steven D. Richardson, Paul G. Trikha, Mohit TI Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE marizomib; proteasome hyperactivation; pan-proteasome inhibitor ID CASPASE-LIKE SITES; TRYPSIN-LIKE SITES; PHASE-I; BORTEZOMIB; CARFILZOMIB; CELLS; RESISTANCE; NPI-0052; THERAPY; MALIGNANCIES AB Proteasome inhibitors (PIs) are highly active in multiple myeloma (MM) but resistance is commonly observed. All clinical stage PIs effectively inhibit chymotrypsin-like (CT-L) activity; one possible mechanism of resistance is compensatory hyperactivation of caspase-like (C-L) and trypsin-like (T-L) subunits, in response to CT-L blockade. Marizomib (MRZ), an irreversible PI that potently inhibits all three 20S proteasome subunits with a specificity distinct from other PIs, is currently in development for treatment of MM and malignant glioma. The pan-proteasome pharmacodynamic activity in packed whole blood and peripheral blood mononuclear cells was measured in two studies in patients with advanced solid tumours and haematological malignancies. Functional inhibition of all proteasome subunits was achieved with once- or twice-weekly MRZ dosing; 100% inhibition of CT-L was frequently achieved within one cycle at therapeutic doses. Concomitantly, C-L and T-L activities were either unaffected or increased, suggesting compensatory hyperactivation of these subunits. Importantly, this response was overcome by continued administration of MRZ, with robust inhibition of T-L and C-L (up to 80% and 50%, respectively) by the end of Cycle 2 and maintained thereafter. This enhanced proteasome inhibition was independent of tumour type and may underlie the clinical activity of MRZ in patients resistant to other PIs. C1 [Levin, Nancy; Burrows, Francis J.; Reich, Steven D.; Trikha, Mohit] Triphase Accelerator, 3210 Merryfield Row, San Diego, CA 92121 USA. [Spencer, Andrew] Monash Univ, Alfred Hlth, Melbourne, Vic, Australia. [Harrison, Simon J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Chauhan, Dharminder; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Trikha, M (reprint author), Triphase Accelerator, 3210 Merryfield Row, San Diego, CA 92121 USA. EM mohit.trikha@triphaseco.com OI Harrison, Simon/0000-0003-4555-6582 FU Trikha: Employee of Triphase Accelerator Corp. FX Levin: Employee of Triphase Accelerator Corp. Spencer: Celgene Corporation, Honoraria and Research Funding. Harrison: No disclosures. Chauhan: Consultant for Triphase Accelerator Corp. Burrows: Consultant for Triphase Accelerator Corp. Anderson: Bristol-Myers Squibb Pharmaceuticals, Celgene Corporation, Gilead Pharmaceuticals, Millenium (The Takeda Oncology Company): Advisor Board. Acetylon Pharmaceutcials, OncoPep, Inc: Scientific Founder. Reich: Consultant for Triphase Accelerator Corp. Richardson: Celgene and Millenium (The Takeda Oncology Company); Service on Advisory Committees, Research Funding. Trikha: Employee of Triphase Accelerator Corp. NR 48 TC 2 Z9 2 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2016 VL 174 IS 5 BP 711 EP 720 DI 10.1111/bjh.14113 PG 10 WC Hematology SC Hematology GA DW6QE UT WOS:000383775200008 PM 27161872 ER PT J AU Agranat, JS Kitos, NR Jacobs, DS AF Agranat, Joshua S. Kitos, Nicole R. Jacobs, Deborah S. TI Prosthetic replacement of the ocular surface ecosystem: impact at 5years SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Cornea; Vision; Ocular surface; Prosthesis; Contact lens ID SCLERAL CONTACT-LENS; VERSUS-HOST-DISEASE; QUALITY-OF-LIFE; CORNEAL ECTASIA; VISUAL FUNCTION; TRANSPLANTATION; KERATOPLASTY; THERAPY; DEVICE; EYE AB Background/aims To determine the impact of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment at 5years. Methods Retrospective review of clinical, manufacturing and quality databases at the Boston Foundation for Sight. Results 121 patients who completed treatment and had 5-year follow-up data were identified from a cohort of patients (n=199) seen in consultation for PROSE treatment from January 2008 to June 2008. Mean age was 52years, M:F=56:65. The primary indication for treatment was ocular surface disease (OSD) in 64 patients and distorted corneal surface in 57 patients. At 5years, continued device wear was confirmed in 89/121 (73.6%) patients. Discontinuation of wear was confirmed in 32/121 (26.4%). There was an increased likelihood of continued device wear at 5years in patients with distorted cornea (84%) compared with those with OSD (64%), (p=0.0121, (2)). National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score increased for patients wearing PROSE devices at 6months (=+23 points, mean=82, p<0.001, two-tailed t test) with no significant decline among those still wearing a device at 5years (=-4 points, mean=78, p=0.22, two-tailed t test). At 5years, those wearing (mean=78) had a higher NEI VFQ-25 than those not wearing (mean=70, p=0.029, two-tailed t test). Conclusions PROSE treatment offers continued benefit, as defined by improved visual function and continued device wear at 5years, in patients with complex corneal disease. Patients with distorted cornea have a higher rate of continued wear at 5years than patients with OSD, although this is not true among all subgroups within OSD. C1 [Agranat, Joshua S.; Jacobs, Deborah S.] Boston Fdn Sight, 464 Hillside Ave 205, Needham, MA 02494 USA. [Agranat, Joshua S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kitos, Nicole R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Agranat, JS (reprint author), Boston Fdn Sight, 464 Hillside Ave 205, Needham, MA 02494 USA. EM Jagranat@bu.edu NR 19 TC 0 Z9 0 U1 5 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2016 VL 100 IS 9 BP 1171 EP 1175 DI 10.1136/bjophthalmol-2015-307483 PG 5 WC Ophthalmology SC Ophthalmology GA DV9VK UT WOS:000383290100003 PM 26644423 ER PT J AU Shi, Y Wang, HZ Yin, J Li, M Zhang, XF Xin, C Chen, XY Wang, NL AF Shi, Yan Wang, Huaizhou Yin, Jia Li, Meng Zhang, Xifang Xin, Chen Chen, Xiaoya Wang, Ningli TI Microcatheter-assisted trabeculotomy versus rigid probe trabeculotomy in childhood glaucoma SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Glaucoma; Child health (paediatrics) ID 360-DEGREES SUTURE TRABECULOTOMY; PRIMARY CONGENITAL GLAUCOMA; ILLUMINATED MICROCATHETER; DEVELOPMENTAL GLAUCOMA; CIRCUMFERENTIAL TRABECULOTOMY; GONIOTOMY; OUTCOMES; SURGERY AB Purpose To compare microcatheter-assisted trabeculotomy with standard rigid probe trabeculotomy for the treatment of childhood glaucoma. Methods The early postoperative (12months) results of microcatheter-assisted trabeculotomy (group 1) performed by single surgeon were retrospectively compared with those of rigid probe trabeculotomy (group 2) performed by the same surgeon in patients treated for childhood glaucoma. Success was defined as an intraocular pressure (IOP) <21mmHg with at least a 30% reduction from preoperative IOP with (qualified success) or without (complete success) the use of anti-glaucoma medication. Results A total of 43 eyes of 36 patients were included. Mean IOP in group 1 was significantly lower than that in group 2 at 6months (17.05.1 vs 22.59.8; p=0.042), 9months (16.3 +/- 5.0 vs 21.6 +/- 9.6; p=0.009) and 12months (14.8 +/- 2.5 vs 19.0 +/- 7.1; p=0.049) postoperatively. The mean percentage reduction in IOP from preoperative to the last postoperative follow-up was greater in group 1 (47.3 +/- 17.7%) than in group 2 (34.2 +/- 21.9%) (p=0.036). group 1 demonstrated an 81.0% complete and 86.4% qualified success rate, exceeding the 51.6% complete (p=0.060) and 61.9% qualified (p=0.037) success rate of group 2. There were no long-term complications in either group, but choroidal detachment occurred in one eye in group 2. Conclusion Microcatheter-assisted circumferential trabeculotomy is a more effective treatment and is as safe as traditional trabeculotomy with a rigid probe for primary congenital glaucoma in the early postoperative course. Trial registration number ChiCTR-OCC-15005789, Results. C1 [Shi, Yan; Wang, Huaizhou; Li, Meng; Zhang, Xifang; Wang, Ningli] Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China. [Yin, Jia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Xin, Chen] Beijing Anzhen Hosp, Dept Ophthalmol, Beijing, Peoples R China. [Chen, Xiaoya] First Peoples Hosp Xuzhou, Dept Ophthalmol, Xuzhou, Peoples R China. RP Wang, NL (reprint author), Beijing Tongren Hosp, 1 Dongjiaominxiang St, Beijing 100730, Peoples R China. EM wningli@vip.163.com NR 26 TC 2 Z9 2 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD SEP PY 2016 VL 100 IS 9 BP 1257 EP 1262 DI 10.1136/bjophthalmol-2015-307880 PG 6 WC Ophthalmology SC Ophthalmology GA DV9VK UT WOS:000383290100019 PM 26674778 ER PT J AU Kirch, R Reaman, G Feudtner, C Wiener, L Schwartz, LA Sung, L Wolfe, J AF Kirch, Rebecca Reaman, Gregory Feudtner, Chris Wiener, Lori Schwartz, Lisa A. Sung, Lillian Wolfe, Joanne TI Advancing a comprehensive cancer care agenda for children and their families: Institute of Medicine Workshop highlights and next steps SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article DE end of life; oncology; palliative care; patient-reported outcomes; pediatric; psychosocial care; quality of life; supportive care; survivorship ID PEDIATRIC PALLIATIVE CARE; PSYCHOSOCIAL ASSESSMENT-TOOL; PATIENT-REPORTED OUTCOMES; CHRONIC HEALTH CONDITIONS; CHILDHOOD-CANCER; FOLLOW-UP; ADULT SURVIVORS; HIGH-RISK; ONCOLOGY; LIFE AB This article highlights key findings from the Comprehensive Cancer Care for Children and Their Families March 2015 joint workshop by the Institute of Medicine (IOM) and the American Cancer Society. This initiative convened more than 100 family members, clinician investigators, advocates, and members of the public to discuss emerging evidence and care models and to determine the next steps for optimizing quality-of-life outcomes and well-being for children and families during pediatric cancer treatment, after treatment completion, and across the life spectrum. Participants affirmed the triple aim of pediatric oncology that strives for every child with cancer to be cured; provides high-quality palliative and psychosocial supportive, restorative, and rehabilitative care to children and families throughout the illness course and survivorship; and assures receipt of high-quality end-of-life care for patients with advancing disease. Workshop outcomes emphasized the need for new pediatric cancer drug development and identified critical opportunities to prioritize palliative care and psychosocial support as an integral part of pediatric cancer research and treatment, including the necessity for adequately resourcing these supportive services to minimize suffering and distress, effectively address quality-of-life needs for children and families at all stages of illness, and mitigate the long-term health risks associated with childhood cancer and its treatment. Next steps include dismantling existing silos and enhancing collaboration between clinical investigators, disease-directed specialists, and supportive care services; expanding the use of patient-reported and parent-reported outcomes; effectively integrating palliative and psychosocial care; and clinical communication skills development. CA Cancer J Clin 2016;66:398-407. (c) 2016 American Cancer Society. C1 [Kirch, Rebecca] Ctr Adv Palliat Care, New York, NY USA. [Kirch, Rebecca] Cameron & Hayden Lord Fdn, New York, NY USA. [Reaman, Gregory] USDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Feudtner, Chris] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Feudtner, Chris] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Wiener, Lori] NCI, Behav Hlth Core, Bethesda, MD 20892 USA. [Wiener, Lori] NCI, Psychosocial Support & Res Program, Bethesda, MD 20892 USA. [Schwartz, Lisa A.] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Schwartz, Lisa A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sung, Lillian] Hosp Sick Children, Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Wolfe, Joanne] Dana Farber Canc Inst, Pediat Palliat Care Serv, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02115 USA. [Wolfe, Joanne] Boston Childrens Hosp, Pediat Palliat Care, Boston, MA USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Pediat Palliat Care Serv, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02115 USA. EM joanne_wolfe@dfci.harvard.edu NR 83 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 2016 VL 66 IS 5 BP 398 EP 407 DI 10.3322/caac.21347 PG 10 WC Oncology SC Oncology GA DX0CQ UT WOS:000384029500007 PM 27145249 ER PT J AU Shantakumar, S Nordstrom, BL Djousse, L Hall, SA Gagnon, DR Fraeman, KH van Herk-Sukel, M Chagin, K Nelson, J AF Shantakumar, Sumitra Nordstrom, Beth L. Djousse, Luc Hall, Susan A. Gagnon, David R. Fraeman, Kathy H. van Herk-Sukel, Myrthe Chagin, Karen Nelson, Jeanenne TI Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Hepatotoxicity; Liver chemistry; Renal cell carcinoma; Pazopanib; Anti-VEGF ID CANCER-PATIENTS; HYS LAW; ANGIOGENESIS AB To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients. A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, Department of Veterans Affairs (VA) and an oncology practice network (Altos), and the PHARMO Database Network in The Netherlands. A common protocol was used to collect liver chemistry (LC) data from anti-VEGF initiation through 4 years of follow-up. In the VA population, suspected drug-induced liver injury (DILI) outcomes were investigated via chart review, with adjudication by hepatologists. In Altos and VA, respectively, the total RCC patients were: pazopanib (156, 243), bevacizumab (122, 99), sorafenib (82, 249) and sunitinib (285, 751). PHARMO contained too few patients to be included. Few cases of alanine aminotransferase (ALT) aeyen8x the upper limit of normal were seen across the anti-VEGF cohorts; incidence rates (per 100 person-years) ranged from 0 (sunitinib) to 8.2 (pazopanib) in Altos and from 0 (bevacizumab and sorafenib) to 2.1 (pazopanib) among VA patients. No cases of Hy's law identified by combination LC elevations were seen in patients treated with pazopanib or bevacizumab; one case was observed in those treated with sorafenib, and two cases were found among sunitinib users. One case of adjudicated DILI was observed in a sunitinib-treated patient; none were found among patients treated with pazopanib, bevacizumab or sorafenib. Severe liver injury occurred infrequently during exposure to pazopanib and other anti-VEGF therapies in a population-based setting. C1 [Shantakumar, Sumitra] GlaxoSmithKline, Worldwide Epidemiol, R&D, 150 Beach Rd,26-00 Gateway West, Singapore 189720, Singapore. [Nelson, Jeanenne] GlaxoSmithKline, Worldwide Epidemiol Dept, R&D, Res Triangle Pk, NC USA. [Nordstrom, Beth L.; Fraeman, Kathy H.] Evidera, Ctr Excellence Epidemiol, Lexington, MA USA. [Djousse, Luc; Gagnon, David R.] Boston VA Healthcare Syst, Dept Vet Affairs, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Hall, Susan A.] New England Res Inst Inc, Watertown, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [van Herk-Sukel, Myrthe] PHARMO Inst Drug Outcomes Res, Utrecht, Netherlands. [Chagin, Karen] GlaxoSmithKline, Global Clin Safety & Pharmacovigilance, Collegeville, PA USA. RP Shantakumar, S (reprint author), GlaxoSmithKline, Worldwide Epidemiol, R&D, 150 Beach Rd,26-00 Gateway West, Singapore 189720, Singapore. EM sumitra.y.shantakumar@gsk.com RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU GlaxoSmithKline (GSK) FX This study was funded by GlaxoSmithKline (GSK). NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2016 VL 78 IS 3 BP 559 EP 566 DI 10.1007/s00280-016-3112-9 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA DV6YN UT WOS:000383083100013 PM 27438066 ER PT J AU Rutherford, JD Braunwald, E AF Rutherford, John D. Braunwald, Eugene TI Limitation of Infarct Size and the Open Artery Hypothesis A Conversation With Eugene Braunwald, MD SO CIRCULATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; TISSUE-PLASMINOGEN ACTIVATOR; ST-SEGMENT-ELEVATION; LEFT-VENTRICULAR DYSFUNCTION; OXYGEN-CONSUMPTION; HEMODYNAMIC DETERMINANTS; CONSERVATIVE STRATEGIES; THROMBOLYTIC THERAPY; BETA-BLOCKADE AB Eugene Braunwald received an MD from the New York University School of Medicine. He completed an internal medicine residency at Johns Hopkins Hospital and cardiology fellowships at Mount Sinai Hospital, Columbia University, and the National Heart Institute. He served as chief of cardiology and subsequently clinical director of the institute. From 1968 to 1972, he was the founding chair of medicine at the University of California, San Diego. From 1972 to 1996, he served as chair of medicine at the Brigham and Women's Hospital. In 1975, he was elected to the National Academy of Sciences. He is now the Distinguished Hersey Professor of Medicine at Harvard Medical School and a senior investigator of the TIMI Study Group, which he founded in 1984. C1 [Braunwald, Eugene] Mt Sinai Hosp, New York, NY 10029 USA. [Braunwald, Eugene] Columbia Univ, New York, NY 10027 USA. [Braunwald, Eugene] Natl Heart Inst, Delhi, India. [Braunwald, Eugene] Univ Calif San Diego, Med, La Jolla, CA 92093 USA. [Braunwald, Eugene] Brigham & Womens Hosp, Med, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Med Sch, Boston, MA 02115 USA. [Braunwald, Eugene] TIMI Study Grp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Mt Sinai Hosp, New York, NY 10029 USA.; Braunwald, E (reprint author), Columbia Univ, New York, NY 10027 USA.; Braunwald, E (reprint author), Natl Heart Inst, Delhi, India.; Braunwald, E (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Braunwald, E (reprint author), TIMI Study Grp, Boston, MA 02115 USA. NR 52 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP PY 2016 VL 134 IS 12 BP 839 EP 846 DI 10.1161/CIRCULATIONAHA.116.024714 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX0NI UT WOS:000384059400006 ER PT J AU Bonaca, MP Goto, S Bhatt, DL Steg, PG Storey, RF Cohen, M Goodrich, E Mauri, L Ophuis, TO Ruda, M Spinar, J Seung, KB Hu, D Dalby, AJ Jensen, E Held, P Morrow, DA Braunwald, E Sabatine, MS AF Bonaca, Marc P. Goto, Shinya Bhatt, Deepak L. Steg, P. Gabriel Storey, Robert F. Cohen, Marc Goodrich, Erica Mauri, Laura Ophuis, Ton Oude Ruda, Mikhail Spinar, Jindrich Seung, Ki-Bae Hu, Dayi Dalby, Anthony J. Jensen, Eva Held, Peter Morrow, David A. Braunwald, Eugene Sabatine, Marc S. TI Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) SO CIRCULATION LA English DT Article DE hemorrhagic stroke; ischemic stroke; platelet aggregation inhibitors; secondary prevention; stroke; thrombosis; ticagrelor ID DUAL ANTIPLATELET THERAPY; TRANSIENT ISCHEMIC ATTACK; RECENT LACUNAR STROKE; SECONDARY PREVENTION; ATRIAL-FIBRILLATION; CONTROLLED-TRIAL; CLOPIDOGREL; RISK; ATHEROTHROMBOSIS; OUTPATIENTS AB BACKGROUND: In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. METHODS: Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. RESULTS: Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). CONCLUSIONS: High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. C1 [Bonaca, Marc P.; Bhatt, Deepak L.; Goodrich, Erica; Morrow, David A.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Med Sch, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Goto, Shinya] Tokai Univ, Sch Med, Isehara, Kanagawa, Japan. [Goto, Shinya] Inst Med Sci, Isehara, Kanagawa, Japan. [Steg, P. Gabriel] INSERM, U1148, AP HP, FACT,DHU FIRE, Paris, France. [Steg, P. Gabriel] Univ Paris Diderot, Paris, France. [Steg, P. Gabriel] Royal Brompton Hosp, NHLI Imperial Coll, London, England. [Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England. [Cohen, Marc] Rutgers New Jersey Med Sch, Newark Beth Israel Med Ctr, Div Cardiol, Newark, DE 08901 USA. [Mauri, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mauri, Laura] Harvard Med Sch, Harvard Clin Res Inst, Boston, MA 02115 USA. [Ophuis, Ton Oude] CWZ Hosp, Nijmegen, Netherlands. [Ruda, Mikhail] Cardiol Res & Prod Complex MH RF, Moscow, Russia. [Spinar, Jindrich] Univ Hosp & Med Fac, Internal Cardiol Dept, Brno, Czech Republic. [Seung, Ki-Bae] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Seoul, South Korea. [Hu, Dayi] Peking Univ, People Hosp, Heart Inst Intervent Ctr, Beijing, Peoples R China. [Dalby, Anthony J.] Life Fourways Hosp, Randburg, South Africa. [Jensen, Eva; Held, Peter] AstraZeneca, Molndal, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org NR 21 TC 0 Z9 0 U1 20 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP PY 2016 VL 134 IS 12 BP 861 EP + DI 10.1161/CIRCULATIONAHA.116.024637 PG 21 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX0NI UT WOS:000384059400009 PM 27576775 ER PT J AU Lu, MT Onuma, OK Massaro, JM D'Agostino, RB O'Donnell, CJ Hoffmann, U AF Lu, Michael T. Onuma, Oyere K. Massaro, Joseph M. D'Agostino, Ralph B. O'Donnell, Christopher J. Hoffmann, Udo TI Lung Cancer Screening Eligibility in the Community Cardiovascular Risk Factors, Coronary Artery Calcification, and Cardiovascular Events SO CIRCULATION LA English DT Letter DE cardiac computed tomography; coronary artery calcium; prevention; screening smoking ID TRIAL C1 [Lu, Michael T.; Hoffmann, Udo] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. [Onuma, Oyere K.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Onuma, Oyere K.; Massaro, Joseph M.; D'Agostino, Ralph B.; O'Donnell, Christopher J.; Hoffmann, Udo] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Onuma, Oyere K.; Massaro, Joseph M.; D'Agostino, Ralph B.; O'Donnell, Christopher J.; Hoffmann, Udo] Boston Univ, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Med Sch, Boston Vet Adm Healthcare Syst, Dept Med, Cardiol Sect, Boston, MA 02114 USA. RP Lu, MT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM mlu@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL071039, R01 HL077447, N01HC25195, N01 HC025195, R01 HL060040, T32 HL076136, R01 HL107385, R01 HL080124, R01 HL076784, R01 HL070100, K24 HL113128]; NIA NIH HHS [R01 AG028321] 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 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP PY 2016 VL 134 IS 12 BP 897 EP 899 DI 10.1161/CIRCULATIONAHA.116.023957 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX0NI UT WOS:000384059400013 PM 27647299 ER PT J AU Graw, JA Mayeur, C Rosales, I Liu, YM Sabbisetti, VS Riley, FE Rechester, O Malhotra, R Warren, HS Colvin, RB Bonventre, JV Bloch, DB Zapol, WM AF Graw, Jan A. Mayeur, Claire Rosales, Ivy Liu, Yumin Sabbisetti, Venkata S. Riley, Frank E. Rechester, Osher Malhotra, Rajeev Warren, H. Shaw Colvin, Robert B. Bonventre, Joseph V. Bloch, Donald B. Zapol, Warren M. TI Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells SO CIRCULATION LA English DT Article DE blood; critical care; haptoglobin; hemoglobin; hemorrhage ID ACUTE KIDNEY INJURY; INHALED NITRIC-OXIDE; ACUTE-RENAL-FAILURE; BLOOD-CELLS; CARDIAC-SURGERY; STORED-BLOOD; HEMORRHAGIC-SHOCK; FREE HEMOGLOBIN; ENDOTHELIAL DYSFUNCTION; EXCHANGE-TRANSFUSION AB BACKGROUND: Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs. METHODS: To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin. RESULTS: Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects. CONCLUSIONS: In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension. C1 [Graw, Jan A.; Mayeur, Claire; Bloch, Donald B.; Zapol, Warren M.] Harvard Med Sch, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Rosales, Ivy; Colvin, Robert B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Riley, Frank E.; Rechester, Osher; Warren, H. Shaw] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA. [Malhotra, Rajeev] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Malhotra, Rajeev] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA USA. [Bloch, Donald B.] Harvard Med Sch, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA USA. [Liu, Yumin; Sabbisetti, Venkata S.; Warren, H. Shaw] Harvard Med Sch, Brigham & Womens Hosp, Div Renal, Boston, MA USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Thier 503, Boston, MA 02114 USA.; Zapol, WM (reprint author), Harvard Med Sch, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@mgh.harvard.edu FU NHLBI NIH HHS [K08 HL111210]; NIAID NIH HHS [R01 AI059010]; NIDDK NIH HHS [R01 DK072381, R01 DK082971] NR 55 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP PY 2016 VL 134 IS 13 BP 945 EP + DI 10.1161/CIRCULATIONAHA.115.019955 PG 32 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX0NS UT WOS:000384060400013 PM 27515135 ER PT J AU Stone, MT Weed, V Kulich, RJ AF Stone, Melissa T. Weed, Valerie Kulich, Ronald J. TI Opioid Treatment of Migraine: Risk Factors and Behavioral Issues SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Opioids; Risk; Screening; Addiction; Headache; Migraine ID CHRONIC NONCANCER PAIN; QUALITY-OF-LIFE; LOW-BACK-PAIN; EPISODIC MIGRAINE; CONTROLLED-TRIAL; SELF-EFFICACY; UNITED-STATES; HEADACHE; DISABILITY; THERAPY AB Migraine can impact every aspect of a person's functioning. Psychological comorbidities, cognitive constructs, and behavioral responses to pain greatly impact the perception of migraine pain, treatment efficacy and outcome, and overall quality of life and functioning. Current considerations for migraine treatment emphasize the utility of the biopsychosocial model in understanding and treating migraine, noting both the importance of addressing psychological factors such as cognitive beliefs as well as psychiatric comorbidities. The guidelines for migraine treatment implicate opioid therapy as a second or third tier treatment. Guidelines and recommendations for the safe use of opioid medications among patients with chronic pain emphasize the importance of screening prior to prescribing opioid medications. Chronic opioid therapy has been shown to further levels of disability, decrease quality of life, and correlate to psychiatric comorbidities, concerns that are already present in migraine patients. While opioid treatment provides an alternative for persons with contraindications for alternative migraine treatments, it is critical that opioids be used sparingly and exclusively in conjunction with comprehensive assessment and integration of psychological treatment. C1 [Stone, Melissa T.] Integrated Behav Associates, 169 Libbey Pkwy, Weymouth, MA 02189 USA. [Stone, Melissa T.] South Shore Med Ctr, 143 Longwater Dr, Norwell, MA 02061 USA. [Weed, Valerie] Boston PainCare Ctr, Waltham, MA USA. [Weed, Valerie] Tufts Sch Med, Waltham, MA USA. [Weed, Valerie] Shriners Hosp Children Boston, 85 First Ave, Waltham, MA 02145 USA. [Kulich, Ronald J.] Tufts Univ, Sch Dent Med, Dept Diagnost Sci, Craniofacial Pain & Headache Ctr, Boston, MA 02111 USA. [Kulich, Ronald J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Anesthesia Crit Care & Pain Med, 1 Kneeland St, Boston, MA 02111 USA. RP Stone, MT (reprint author), Integrated Behav Associates, 169 Libbey Pkwy, Weymouth, MA 02189 USA.; Stone, MT (reprint author), South Shore Med Ctr, 143 Longwater Dr, Norwell, MA 02061 USA. EM mstone@cfpsych.org; vweed@bostonpaincare.com; rkulich@mgh.harvard.edu NR 57 TC 0 Z9 0 U1 7 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD SEP PY 2016 VL 20 IS 9 AR 51 DI 10.1007/s11916-016-0581-9 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DV1NX UT WOS:000382689000005 PM 27474093 ER PT J AU Shankar, SS Vella, A Raymond, RH Staten, MA Calle, RA Bergman, RN Cao, C Chen, D Cobelli, C Man, CD Deeg, M Dong, JQ Lee, DS Polidori, D Robertson, RP Ruetten, H Stefanovski, D Vassileva, MT Weir, GC Fryburg, DA AF Shankar, Sudha S. Vella, Adrian Raymond, Ralph H. Staten, Myrlene A. Calle, Roberto A. Bergman, Richard N. Cao, Charlie Chen, Danny Cobelli, Claudio Man, Chiara Dalla Deeg, Mark Dong, Jennifer Q. Lee, Douglas S. Polidori, David Robertson, R. Paul Ruetten, Hartmut Stefanovski, Darko Vassileva, Maria T. Weir, Gordon C. Fryburg, David A. CA Fdn Natl Inst Hlth B-Cell TI Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of beta-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; MINIMAL-MODEL; ORAL GLUCOSE; PLUS METFORMIN; TYPE-2; SECRETION; RESISTANCE; INDEXES AB OBJECTIVE Standardized, reproducible, and feasible quantification of beta-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was > 86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (similar to 50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from similar to 0.3 to similar to 0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. C1 [Shankar, Sudha S.; Deeg, Mark] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Vella, Adrian] Mayo Clin, Coll Med, Div Endocrinol Diabet & Metab, Rochester, MN USA. [Raymond, Ralph H.] R Squared Solut, Skillman, NJ USA. [Staten, Myrlene A.] NIDDK, Kelly Govt Solut, Rockville, MD USA. [Calle, Roberto A.; Chen, Danny; Dong, Jennifer Q.; Lee, Douglas S.] Pfizer, Cambridge, MA USA. [Calle, Roberto A.; Chen, Danny; Dong, Jennifer Q.; Lee, Douglas S.] Pfizer, Groton, CT USA. [Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA. [Cao, Charlie] Takeda Dev Ctr Amer, Deerfield, IL USA. [Cobelli, Claudio; Man, Chiara Dalla] Univ Padua, Dept Informat Engn, Padua, Italy. [Polidori, David] Janssen Res & Dev, San Diego, CA USA. [Robertson, R. Paul] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Robertson, R. Paul] Univ Washington, Dept Med, Div Endocrinol, Seattle, WA USA. [Robertson, R. Paul] Univ Washington, Dept Pharmacol, Div Endocrinol, Seattle, WA 98195 USA. [Ruetten, Hartmut] Sanofi, Paris, France. [Stefanovski, Darko] Univ Penn, Philadelphia, PA 19104 USA. [Vassileva, Maria T.] Fdn Natl Inst Hlth, Bethesda, MD USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Fryburg, David A.] ROI Biopharma Consulting, East Lyme, CT 06333 USA. RP Fryburg, DA (reprint author), ROI Biopharma Consulting, East Lyme, CT 06333 USA. EM dfryburg@roibiopharma.com FU FNIH Biomarkers Consortium; FNIH; NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); FDA; AstraZeneca; Janssen; Eli Lilly and Company; Merck; Novartis; Novo Nordisk; Pfizer; Sanofi; Takeda; American Diabetes Association; JDRF FX The methodological study described in this report was designed and implemented under the auspices of the FNIH Biomarkers Consortium. The Biomarkers Consortium is a public private partnership that develops and validates biological markers, which speed up the development of therapies for the detection, prevention, diagnosis, and treatment of disease and are ultimately aimed at improving patient care. For this study, the Consortium brought together diabetes experts from leading academic institutions, the U.S. Food and Drug Administration (FDA), the National Institutes of Health (NIH), the nonprofit sector, and the pharmaceutical industry to develop the project. The results of the partnership, discussed in this study, are important because they address a critical unmet medical need and involve key stakeholders in the diabetes treatment field. FNIH has acted as a neutral convener for the partners and provided the project management expertise needed for the execution of the overall project. In the future, this type of partnership can be used as a model for establishing common standards for testing in other therapeutic areas as well. Under the auspices of the FNIH, this project was jointly funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the FDA and the following participating pharmaceutical companies: Amylin (now AstraZeneca), Janssen, Eli Lilly and Company, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda. An in-kind donation of P800 tubes was made by Becton Dickinson (D. Craft). Additional support was also received from the American Diabetes Association and JDRF. NR 44 TC 2 Z9 2 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 SEP PY 2016 VL 39 IS 9 BP 1602 EP 1613 DI 10.2337/dc15-0931 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW5DT UT WOS:000383663000030 PM 27407117 ER PT J AU Braffett, BH Bebu, I Lachin, JM Dagogo-Jack, S Larkin, M Sivitz, W Kolterman, O Genuth, S AF Braffett, Barbara H. Bebu, Ionut Lachin, John M. Dagogo-Jack, Samuel Larkin, Mary Sivitz, William Kolterman, Orville Genuth, Saul CA Writing Grp DCCT EDIC Res Grp TI Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study SO DIABETES CARE LA English DT Article ID COMPLICATIONS-TRIAL/EPIDEMIOLOGY; PULSE PRESSURE; BLOOD-PRESSURE; INTERVENTIONS; MORTALITY; DISEASE; DYSLIPIDEMIA; HYPERTENSION; PATTERNS; MELLITUS AB OBJECTIVE The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the beneficial effect of intensive therapy on atherosclerosis and clinical cardiovascular outcomes, while identifying hyperglycemia as a dominant risk factor for type 1 diabetes. The current analyses evaluate the extent to which glycemic exposure influences long-term changes in established risk factors for cardiovascular disease (CVD) among patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The DCCT study randomized 1,441 participants to receive intensive or conventional diabetes therapy; and after an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study for an additional 20 years of follow-up. Annual visits included a detailed medical history and physical examination. Blood and urine samples were collected and assayed centrally. Longitudinal models for repeated measurements were used. RESULTS Higher HbA(1c) level was a significant correlate of the longitudinal changes in all of the traditional CVD risk factors over the 30-year follow-up. The strongest longitudinal associations were among the lipid measurements and concurrent glycemia. CONCLUSIONS A better understanding of the interrelationships between diabetes-related risk factors and traditional CVD risk factors may assist with the development of targeted treatment regimens for persons with type 1 diabetes who are at risk for CVD. C1 [Braffett, Barbara H.; Bebu, Ionut; Lachin, John M.] George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA. [Dagogo-Jack, Samuel] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN USA. [Larkin, Mary] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Diabet, Boston, MA USA. [Sivitz, William] Univ Iowa, Dept Internal Med, Div Endocrinol & Metab, Iowa City, IA 52242 USA. [Kolterman, Orville] Univ Calif San Diego, La Jolla, CA 92093 USA. [Genuth, Saul] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Braffett, BH (reprint author), George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA. EM braffett@bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841 FU Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK-094176, U01-DK-094157]; National Eye Institute; National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical Translational Science Center Program, Bethesda, MD FX The DCCT/EDIC study has been supported by cooperative agreement grants (1982-1993, 2012-2017) and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (current grant numbers U01-DK-094176 and U01-DK-094157) and through support by the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006 to present), Bethesda, MD. Industry contributors have had no role in the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants' adherence to the study, as follows: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North American Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet Corporation (Bedford, MA), LifeScan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi (Bridgewater, NJ). NR 24 TC 0 Z9 0 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2016 VL 39 IS 9 BP 1621 EP 1630 DI 10.2337/dc16-0502 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW5DT UT WOS:000383663000032 ER PT J AU Bell, KJ Toschi, E Steil, GM Wolpert, HA AF Bell, Kirstine J. Toschi, Elena Steil, Garry M. Wolpert, Howard A. TI Optimized Mealtime Insulin Dosing for Fat and Protein in Type 1 Diabetes: Application of a Model-Based Approach to Derive Insulin Doses for Open-Loop Diabetes Management SO DIABETES CARE LA English DT Article ID POSTPRANDIAL GLUCOSE EXCURSIONS; BOLUS; CHILDREN; INDEX; SENSITIVITY; IMPACT; LEVEL; PUMP AB OBJECTIVE To determine insulin dose adjustments required for coverage of high-fat, high-protein (HFHP) meals in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Ten adults with T1D received low-fat, low-protein (LFLP) and HFHP meals with identical carbohydrate content, covered with identical insulin doses. On subsequent occasions, subjects repeated the HFHP meal with an adaptive model-predictive insulin bolus until target postprandial glycemic control was achieved. RESULTS With the same insulin dose, the HFHP increased the glucose incremental area under the curve over twofold (13,320 6 2,960 vs. 27,092 6 1,709 mg/dL . min; P = 0.0013). To achieve target glucose control following the HFHP, 65% more insulin was required (range 17%-124%) with a 30%/70% split over 2.4 h. CONCLUSIONS This study demonstrates that insulin dose calculations need to consider meal composition in addition to carbohydrate content and provides the foundation for new insulin-dosing algorithms to cover meals of varying macronutrient composition. C1 [Bell, Kirstine J.] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia. [Bell, Kirstine J.] Univ Sydney, Sch Mol Biosci, Sydney, NSW, Australia. [Bell, Kirstine J.; Toschi, Elena; Wolpert, Howard A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Toschi, Elena; Steil, Garry M.; Wolpert, Howard A.] Harvard Med Sch, Boston, MA USA. [Steil, Garry M.] Boston Childrens Hosp, Boston, MA USA. RP Wolpert, HA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.; Wolpert, HA (reprint author), Harvard Med Sch, Boston, MA USA. EM howard.wolpert@joslin.harvard.edu FU JDRF FX This project was supported by a grant from JDRF (to H.A.W.). NR 19 TC 3 Z9 3 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2016 VL 39 IS 9 BP 1631 EP 1634 DI 10.2337/dc15-2855 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW5DT UT WOS:000383663000033 PM 27388474 ER PT J AU Shirakawa, J Kulkarni, RN AF Shirakawa, J. Kulkarni, R. N. TI Novel factors modulating human beta-cell proliferation SO DIABETES OBESITY & METABOLISM LA English DT Review DE GNF4877; harmine; human beta-cell proliferation; osteoprotegrin; SerpinB1; WS6 ID GLYCOGEN-SYNTHASE KINASE-3-BETA; GESTATIONAL DIABETES-MELLITUS; INSULIN-RESISTANT STATES; STRESS-INDUCED APOPTOSIS; HUMAN ISLETS; ROAD MAP; DYRK1A; MICE; MASS; INHIBITION AB beta-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of beta-cells, and an understanding of the cellular mechanism(s) that regulate beta-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human beta-cell proliferation is one potential approach to restore beta-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance beta-cell replication in animal models or cell lines, promoting effective human beta-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human beta-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3 beta and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. C1 [Shirakawa, J.; Kulkarni, R. N.] Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Rm 410,One Joslin Pl, Boston, MA 02215 USA. [Shirakawa, J.; Kulkarni, R. N.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Kulkarni, R. N.] Harvard Med Sch, Harvard Stem Cell Inst, Boston, MA USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Rm 410,One Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu FU NIH [RO1 DK67536, RO1 DK103215, UC4 104167]; Japan Society for the Promotion of Science (JSPS) FX This work was supported by NIH RO1 DK67536, RO1 DK103215 and UC4 104167 (to R.N.K.). J.S. is supported by a Post-doctoral Fellowship for Research Abroad, the Japan Society for the Promotion of Science (JSPS). NR 78 TC 1 Z9 1 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2016 VL 18 SU 1 BP 71 EP 77 DI 10.1111/dom.12731 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW1CL UT WOS:000383380300009 PM 27615134 ER PT J AU Mashamba-Thompson, TP Sartorius, B Drain, PK AF Mashamba-Thompson, Tivani P. Sartorius, Benn Drain, Paul K. TI Point-of-Care Diagnostics for Improving Maternal Health in South Africa SO DIAGNOSTICS LA English DT Review DE HIV; maternal health; point-of-care diagnostics; resource-limited settings ID RESOURCE-LIMITED SETTINGS; CHILD HIV TRANSMISSION; PREGNANCY TEST KITS; NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; ANTENATAL CARE; RURAL HEALTH; TESTS; WOMEN; INITIATION AB Improving maternal health is a global priority, particularly in high HIV-endemic, resource-limited settings. Failure to use health care facilities due to poor access is one of the main causes of maternal deaths in South Africa. "Point-of-care" (POC) diagnostics are an innovative healthcare approach to improve healthcare access and health outcomes in remote and resource-limited settings. In this review, POC testing is defined as a diagnostic test that is carried out near patients and leads to rapid clinical decisions. We review the current and emerging POC diagnostics for maternal health, with a specific focus on the World Health Organization (WHO) quality-ASSURED (Affordability, Sensitivity, Specificity, User friendly, Rapid and robust, Equipment free and Delivered) criteria for an ideal point-of-care test in resource-limited settings. The performance of POC diagnostics, barriers and challenges related to implementing POC diagnostics for maternal health in rural and resource-limited settings are reviewed. Innovative strategies for overcoming these barriers are recommended to achieve substantial progress on improving maternal health outcomes in these settings. C1 [Mashamba-Thompson, Tivani P.; Sartorius, Benn] Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth, ZA-4001 Durban, South Africa. [Drain, Paul K.] Univ Washington, Dept Global Hlth, Int Clin Res Ctr, Seattle, WA 98195 USA. [Drain, Paul K.] Univ Washington, Div Infect Dis, Dept Med, Seattle, WA 98195 USA. [Drain, Paul K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Drain, Paul K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Mashamba-Thompson, TP (reprint author), Univ KwaZulu Natal, Sch Nursing & Publ Hlth, Discipline Publ Hlth, ZA-4001 Durban, South Africa. EM Mashamba-Thompson@ukzn.ac.za; Sartorius@ukzn.ac.za; pkdrain@uw.edu NR 91 TC 0 Z9 0 U1 4 U2 4 PU MDPI AG PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 2075-4418 J9 DIAGNOSTICS JI Diagnostics PD SEP PY 2016 VL 6 IS 3 AR 31 DI 10.3390/diagnostics6030031 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA DW7MD UT WOS:000383833900005 ER PT J AU Barrett, LF Gendron, M AF Barrett, Lisa Feldman Gendron, Maria TI The Importance of Context: Three Corrections to Cordaro, Keltner, Tshering, Wangchuk, and Flynn (2016) SO EMOTION LA English DT Editorial Material DE emotion perception; basic emotion theory; emotion recognition; culture ID FACIAL EXPRESSIONS; EMOTION PERCEPTION; VOCALIZATIONS; RECOGNITION; CULTURES AB In their recently published article, "The Voice Conveys Emotion in Ten Globalized Cultures and One Remote Village in Bhutan," Cordaro, Keltner, Tshering, Wangchuk, and Flynn conclude that certain emotion categories are universally recognized by people around the world, barring illness and measurement error. The impact of Cordaro et al.'s article, like that of all empirical studies, is determined not only by its research findings but also by how the research findings are situated. Accuracy in characterizing the scientific context of new findings is as important as maintaining the highest standards for other aspects of the scientific method. In this regard, we point out three areas of concern in Cordaro et al.'s discussion of past research on remote samples, the use of more discovery-oriented (and less confirmatory) experimental methods in past research, and the use of manipulation checks in past research. Ultimately, a study's contribution to scientific progress is limited when ambiguities and oversights obscure the real value of its findings. C1 [Barrett, Lisa Feldman; Gendron, Maria] Northeastern Univ, Dept Psychol, 125 Nightingale Hall,360 Huntington Ave, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Barrett, Lisa Feldman] Harvard Med Sch, Boston, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale Hall,360 Huntington Ave, Boston, MA 02115 USA. EM l.barrett@neu.edu FU U.S. Army Research Institute for the Behavioral and Social Sciences [W911NF-15-1-0647]; National Institute of Mental Health Ruth L. Kirschstein National Research Service FX Preparation of this article was supported by a contract from the U.S. Army Research Institute for the Behavioral and Social Sciences (W911NF-15-1-0647), as well as a National Institute of Mental Health Ruth L. Kirschstein National Research Service Award to Maria Gendron. The views, opinions, and findings contained in this article are those of the authors and should not be construed as an official position, policy, or decision of the U.S. National Institutes of Health or Department of the Army unless so designated by other documents. NR 32 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD SEP PY 2016 VL 16 IS 6 BP 803 EP 806 DI 10.1037/emo0000217 PG 4 WC Psychology, Experimental SC Psychology GA DW8OG UT WOS:000383914800004 PM 27584725 ER PT J AU Castillo, JJ AF Castillo, Jorge J. TI Risk factors for progression from smoldering into active myeloma: additional insights from a population-based study SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Editorial Material ID MULTIPLE-MYELOMA; SUPPRESSION; SURVIVAL; PAIR C1 [Castillo, Jorge J.] Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave,Mayer 221, Boston, MA 02215 USA. RP Castillo, JJ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave,Mayer 221, Boston, MA 02215 USA. EM Jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 EI 1600-0609 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD SEP PY 2016 VL 97 IS 3 BP 217 EP 218 DI 10.1111/ejh.12750 PG 2 WC Hematology SC Hematology GA DW2KB UT WOS:000383470200003 PM 26918423 ER PT J AU Moghimi, MH Leonard, DA Cho, CH Schoenfeld, AJ Phan, P Harris, MB Bono, CM AF Moghimi, Michael H. Leonard, Dana A. Cho, Charles H. Schoenfeld, Andrew J. Phan, Philippe Harris, Mitchel B. Bono, Christopher M. TI Answer to the Letter to the Editor of M. D. Sewell et al. concerning "Virtually bloodless posterior midline exposure of the lumbar spine using the 'para-midline' fatty plane" by Moghimi MH, Leonard DA, Cho CH, Schoenfeld AJ, Phan P, Harris MB, Bono CM: Eur Spine J (2016) 25;956-962 SO EUROPEAN SPINE JOURNAL LA English DT Letter C1 [Moghimi, Michael H.] Harvard Med Sch, Brigham & Womens Hosp, Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. [Leonard, Dana A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Cho, Charles H.; Schoenfeld, Andrew J.; Harris, Mitchel B.; Bono, Christopher M.] Harvard Med Sch, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Phan, Philippe] Univ Ottawa, Ottawa Hosp, Civic Campus,1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. RP Leonard, DA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dleonard7@partners.org NR 2 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD SEP PY 2016 VL 25 IS 9 BP 3012 EP 3013 DI 10.1007/s00586-016-4575-4 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA DW2IG UT WOS:000383465500042 PM 27160825 ER PT J AU Pourriahi, M Gurman, P Daich, J Cynamon, P Richler, A Elman, N Rosen, Y AF Pourriahi, Mahyar Gurman, Pablo Daich, Jonathan Cynamon, Philip Richler, Aaron Elman, Noel Rosen, Yitzhak TI The use of micro-electro mechanical systems in vascular monitoring: implications for clinical use SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE Micro-electro-mechanical systems; vascular monitoring; heart failure; piezoresistive pressure sensors; capacitive pressure sensors; catheter-tip-sensor; wireless implantable sensors ID INTRASAC PRESSURE MEASUREMENTS; SYSTOLIC HEART-FAILURE; TERM-FOLLOW-UP; ENDOVASCULAR REPAIR; MICROELECTROMECHANICAL SYSTEMS; AORTIC-ANEURYSMS; BIOMEMS; DISEASE; TRIAL; HOSPITALIZATIONS AB Introduction: BioMEMS relates to the implementation of Micro-Electro-Mechanical Systems (MEMS), in the biological and medical sphere. BioMEMS sensors are being utilized for many clinical applications, including a wireless urinary pressure system, right heart pressure sensor, and measurements on shearing force on the vascular system An important application of BioMEMS is on Heart failure (HF), a common disease, with a prevalence of 10% or more in persons 70 years of age or older, associated with high morbidity and mortality. HF affects over 5 million people and contributes to over 200,000 deaths a year in the United States alone.Areas covered: The purpose of this paper is to provide a short overview on the successful implementation of BioMEMS sensors in heart failure and vascular medicine.Expert commentary: BioMEMS devices have overcome current limitations in pharmacotherapies for resistant hypertension by electrical modulation of the baroreceeptors. This represents a step towards the development of biomedical micro-devices for those conditions in which pharmacotherapies result poorly effective or elicit unacceptable toxicity. C1 [Pourriahi, Mahyar; Daich, Jonathan; Cynamon, Philip; Richler, Aaron; Rosen, Yitzhak] Super Nano Biosyst LLC, 65 Donaldson St, Highland Pk, NJ 08904 USA. [Gurman, Pablo] Univ Texas Dallas, Dept Mat Sci & Engn, Richardson, TX 75083 USA. [Elman, Noel] Charles Stark Draper Labs, Bio Grp, Div Mat, Cambridge, MA USA. [Elman, Noel] Massachusetts Gen Hosp, Ctr Innovat Care Delivery, Boston, MA 02114 USA. RP Rosen, Y (reprint author), Super Nano Biosyst LLC, 65 Donaldson St, Highland Pk, NJ 08904 USA. EM yitzhakrosen@gmail.com NR 46 TC 0 Z9 0 U1 13 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1743-4440 EI 1745-2422 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD SEP PY 2016 VL 13 IS 9 BP 831 EP 837 DI 10.1080/17434440.2016.1207520 PG 7 WC Engineering, Biomedical SC Engineering GA DW8NT UT WOS:000383913500007 PM 27487249 ER PT J AU Cronholm, PF Klusaritz, H Nguyen, GT Kellom, K Kearney, M Miller-Day, M Gabbay, R AF Cronholm, Peter F. Klusaritz, Heather Nguyen, Giang T. Kellom, Katherine Kearney, Matthew Miller-Day, Michelle Gabbay, Robert TI Resident Engagement in the Patient-Centered Medical Home SO FAMILY MEDICINE LA English DT Article ID FAMILY MEDICINE; CARE; PCMH; COST; IMPLEMENTATION; TRANSFORMATION; CURRICULUM; REDESIGN; PROGRAMS AB BACKGROUND AND OBJECTIVES: This study's objectives were to assess resident understanding and engagement with the patient-centered medical home (PCMH) model and to assess the impact of participation in a PCMH transformation collaborative on residents' experiences and perceptions related to their training environment. METHODS: Residents from practices participating in the largest state-wide PCMH learning collaborative were asked to complete surveys describing their experiences with the collaborative and the PCMH transformation process. Residents from four representative participating residencies were recruited to participate in focus groups designed to provide qualitative data to augment our understanding of the quantitative survey results. RESULTS: We had a reasonable average response rate (39%) with a total of 100 completed resident surveys. Quantitative data illustrated high levels of residents' endorsement of PCMH awareness, engagement, and PCMH-related skills acquisition. The analyses suggested higher levels of PCMH engagement, understanding, and sense of adequacy of preparation among residents who attended learning collaborative sessions compared to those who did not. While qualitative data validated many of the quantitative findings, they also illustrated a somewhat detached and peripheral description of resident experiences with the transformation process. CONCLUSIONS: The presented data describe the complexities of preparing the next generation of providers for practice. Our mixed methods study illustrated the strengths of participating in the learning collaborative but also areas of focus necessary for improving the experience and educational benefits of PCMH-related curricula involving residents. C1 [Cronholm, Peter F.] Univ Penn, Mixed Methods Res Lab, Philadelphia, PA 19104 USA. [Cronholm, Peter F.; Klusaritz, Heather; Nguyen, Giang T.] Univ Penn, Dept Family Med & Community Hlth, 142-A Anat & Chem Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. [Cronholm, Peter F.; Klusaritz, Heather; Nguyen, Giang T.; Kearney, Matthew] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Cronholm, Peter F.; Nguyen, Giang T.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Kellom, Katherine] Childrens Hosp Philadelphia, PolicyLab, Philadelphia, PA 19104 USA. [Miller-Day, Michelle] Chapman Univ, Dept Hlth & Strateg Commun, Orange, CA USA. [Gabbay, Robert] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. RP Cronholm, PF (reprint author), Univ Penn, Dept Family Med & Community Hlth, 142-A Anat & Chem Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM peter.cronholm@uphs.upenn.edu OI Nguyen, Giang/0000-0003-2031-9943 FU Agency for Healthcare Research and Quality [R18HW019150]; Aetna Foundation FX This project was supported by grant number R18HW019150 from the Agency for Healthcare Research and Quality and by a grant from the Aetna Foundation. 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 38 TC 0 Z9 0 U1 1 U2 1 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 EI 1938-3800 J9 FAM MED JI Fam. Med. PD SEP PY 2016 VL 48 IS 8 BP 603 EP 612 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA DW6BD UT WOS:000383730500003 PM 27655192 ER PT J AU Cuevas, AG O'Brien, K Saha, S AF Cuevas, Adolfo G. O'Brien, Kerth Saha, Somnath TI African American Experiences in Healthcare: "I Always Feel Like I'm Getting Skipped Over" SO HEALTH PSYCHOLOGY LA English DT Article DE communication; medical mistrust; patient-provider relationships; perceived discrimination; race concordance ID PATIENT-PROVIDER COMMUNICATION; QUALITY-OF-CARE; MEDICATION ADHERENCE; RACIAL-DISCRIMINATION; DECISION-MAKING; RACIAL/ETHNIC DISCRIMINATION; PERCEIVED DISCRIMINATION; PHYSICIAN COMMUNICATION; DISPARITIES RESEARCH; BLACK PATIENTS AB Objective: Although African Americans perceive discrimination in health care settings, experience higher levels of medical mistrust compared with European Americans, and experience poorer communication with health care providers, little is known as to how these barriers to quality patient-provider relationships arise and manifest themselves. This study examined experiences of African American community members regarding these barriers and additionally explored participants' perspectives on race in the patient-provider relationship. Methods: Focus groups were conducted as part of a study exploring participants' experiences and relationships in health care settings. Sixty African American adults were recruited through community settings and activities to participate in 1 of 9 focus groups segmented by gender. Transcripts were reviewed for content related to perceived discrimination, mistrust, poor communication, and race discordance. Themes providing insight into participants' subjective experience of these potential relationship barriers were derived through qualitative coding (using NVivo 10) and iterative discussion. Results: Perceived discrimination arose when African American patients, particularly women, felt their symptoms or problems were discredited. Medical mistrust occurred when clinicians did not convey respect to patients, leaving patients to wonder whether their clinician's treatment was discriminatory or not. Poor communication arose when clinicians did not acknowledge patients' perspectives during interactions. Patients often viewed these actions as discriminatory. Conclusions: African Americans experience poor communication with their health care providers, medical mistrust, and perceived discrimination when accessing health care in numerous and sometimes interrelated ways. The investigators recommend ways to reduce the experience of such barriers and to improve patient-provider relationships for African Americans in health care. C1 [Cuevas, Adolfo G.; O'Brien, Kerth] Portland State Univ, Dept Psychol, Portland, OR 97207 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Cuevas, AG (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Kresge Bldg,Rm 604a,677 Huntington Ave, Boston, MA 02115 USA. EM acuevas@hsph.harvard.edu OI Cuevas, Adolfo/0000-0001-9875-3825; O'Brien, Kerth/0000-0002-1566-7364 FU Robert Wood Johnson Foundation FX Project EQUALED was funded by a grant from the Robert Wood Johnson Foundation. The authors thank Cameron T. McCabe for his feedback on the manuscript, and Thomas Kindermann and Yves Labissiere for their feedback and critique on early iterations of this work. In addition we thank the community leaders and organizations involved in Project EQUALED, whose expertise and collaboration helped to create this project and make it a success. NR 52 TC 1 Z9 1 U1 9 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2016 VL 35 IS 9 BP 987 EP 995 DI 10.1037/hea0000368 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA DW6XB UT WOS:000383793600007 PM 27175576 ER PT J AU Liberman, LD Liberman, MC AF Liberman, Leslie D. Liberman, M. Charles TI Postnatal maturation of auditory-nerve heterogeneity, as seen in spatial gradients of synapse morphology in the inner hair cell area SO HEARING RESEARCH LA English DT Article DE Auditory nerve; Inner ear; Synaptic ribbon; Glutamate receptor ID SPIRAL GANGLION NEURONS; AFFERENT SYNAPSES; CAT COCHLEA; RIBBON SIZE; FIBERS; INNERVATION; RETRACTION; CHANNELS; ORGAN; CORTI AB Auditory nerve fibers in the adult ear are divided into functional subgroups according to spontaneous rate (SR) and threshold sensitivity. The high-threshold, low-SR fibers are morphologically and spatially distinct from the low-threshold high-SR fibers at their synaptic contacts with inner hair cells. This distinction between SR groups in the adult ear is visible in confocal microscopy as complementary size gradients of presynaptic ribbons and post-synaptic glutamate receptor patches across the modiolar-pillar and habenular-cuticular axes in the inner hair cell area. The aim of the present study was to track the post-natal development of this morphological gradient, in mouse, to determine the earliest age at which this important aspect of cochlear organization is fully mature. Here we show, using morphometric analysis of the organ of Corti immunostained for pre- and post-synaptic markers of efferent and afferent innervation, that this SR-based morphological gradient is not fully established until postnatal day 28, well after other features, such as synaptic counts and efferent innervation density in both the inner and outer hair cell areas, appear fully mature. (C) 2016 Elsevier B.V. All rights reserved. C1 [Liberman, M. Charles] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Liberman, Leslie D.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU NIDCD [R01 DC 0188, P30 DC 05209] FX Research supported by grants from the NIDCD: R01 DC 0188 and P30 DC 05209. NR 43 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD SEP PY 2016 VL 339 BP 12 EP 22 DI 10.1016/j.heares.2016.06.002 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DW8ZP UT WOS:000383944300002 PM 27288592 ER PT J AU Kamakura, T Nadol, JB AF Kamakura, Takefumi Nadol, Joseph B., Jr. TI Correlation between word recognition score and intracochlear new bone and fibrous tissue after cochlear implantation in the human SO HEARING RESEARCH LA English DT Article DE Cochlear implant; Fibrous tissue; New bone; Insertional trauma; Word recognition score; Human inner ear ID INNER-EAR; HISTOPATHOLOGY; ELECTRODES; RECONSTRUCTION; STIMULATION; INSERTION; HEARING AB Cochlear implantation is an effective, established procedure for patients with profound deafness. Although implant electrodes have been considered as biocompatible prostheses, surgical insertion of the electrode induces various changes within the cochlea. Immediate changes include insertional trauma to the cochlea. Delayed changes include a tissue response consisting of inflammation, fibrosis and neo-osteogenesis induced by trauma and an immunologic reaction to a foreign body. The goal of this study was to evaluate the effect of these delayed changes on the word recognition scores achieved post-operatively. Seventeen temporal bones from patients who in life had undergone cochlear implantation were prepared for light microscopy. We digitally calculated the volume of fibrous tissue and new bone within the cochlea using Amira (R) three-dimensional reconstruction software and assessed the correlations of various clinical and histologic factors. The postoperative CNC word score was positively correlated with total spiral ganglion cell count. Fibrous tissue and new bone were found within the cochlea of all seventeen specimens. The postoperative CNC word score was negatively correlated with the % volume of new bone within the scala tympani, scala media/vestibuli and the cochlea, but not with the % volume of fibrous tissue. The % volume of new bone in the scala media/vestibuli was positively correlated with the degree of intracochlear insertional trauma, especially trauma to the basilar membrane. Our results revealed that the % volume of new bone as well as residual total spiral ganglion cell count are important factors influencing post-implant hearing performance. New bone formation may be reduced by limiting insertional trauma and increasing the biocompatibility of the electrodes. (C) 2016 Elsevier B.V. All rights reserved. C1 [Kamakura, Takefumi; Nadol, Joseph B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Human Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. [Kamakura, Takefumi; Nadol, Joseph B., Jr.] Harvard Med Sch, Dept Otolaryngol, Boston, MA USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Human Otopathol Lab, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD) [R01-DC000152] FX This work was supported. by grant R01-DC000152 from the National Institute on Deafness and Other Communication Disorders (NIDCD). NR 26 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD SEP PY 2016 VL 339 BP 132 EP 141 DI 10.1016/j.heares.2016.06.015 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DW8ZP UT WOS:000383944300014 PM 27371868 ER PT J AU Shen, Z Feng, Y Muthupalani, S Sheh, A Cheaney, LE Kaufman, CA Gong, G Paster, BJ Fox, JG AF Shen, Z. Feng, Y. Muthupalani, S. Sheh, A. Cheaney, L. E. Kaufman, C. A. Gong, G. Paster, B. J. Fox, J. G. TI Novel Helicobacter Species H. japonicum Isolated from Laboratory Mice from Japan Induces Typhlocolitis and Lower Bowel Carcinoma in C57BL/129 IL10(-/-) Mice SO HELICOBACTER LA English DT Meeting Abstract CT 29th International Workshop on Helicobacter and Microbiota in Inflammation and Cancer CY SEP 15-17, 2016 CL Magdeburg, GERMANY C1 [Shen, Z.; Feng, Y.; Muthupalani, S.; Sheh, A.; Cheaney, L. E.; Kaufman, C. A.; Gong, G.; Fox, J. G.] MIT, Cambridge, MA 02139 USA. [Paster, B. J.] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1083-4389 EI 1523-5378 J9 HELICOBACTER JI Helicobacter PD SEP PY 2016 VL 21 SU 1 SI SI MA W6.2 BP 90 EP 90 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA DW3BR UT WOS:000383517600056 ER PT J AU Walesky, C Goessling, W AF Walesky, Chad Goessling, Wolfram TI Nature and nurture: Environmental toxins and biliary atresia SO HEPATOLOGY LA English DT Editorial Material ID METABOLISM C1 [Walesky, Chad; Goessling, Wolfram] Harvard Med Sch, Brigham & Womens Hosp, Genet Div, Boston, MA USA. [Goessling, Wolfram] Harvard Med Sch, Brigham & Womens Hosp, Gastroenterol Div, Boston, MA USA. [Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Goessling, Wolfram] Broad Inst MIT & Harvard, Cambridge, MA USA. [Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA USA. RP Goessling, W (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Genet Div,Gastrointestinal Canc Ctr, NRB 458,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM wgoessling@partners.org NR 9 TC 0 Z9 0 U1 4 U2 4 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 SEP PY 2016 VL 64 IS 3 BP 717 EP 719 DI 10.1002/hep.28701 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DV9TU UT WOS:000383285900005 PM 27349921 ER PT J AU Turner, TH Renfroe, JB Morella, K Marriott, BP AF Turner, Travis H. Renfroe, Jenna B. Morella, Kristen Marriott, Bernadette P. CA BRAVO Working Grp TI Evaluating cognitive effort in a randomized controlled trial SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE clinical trials; malingering; effort; neurocognition; suicide ID PREDICTS SUICIDAL-BEHAVIOR; TRAUMATIC BRAIN-INJURY; PERFORMANCE TEST-II AB Many randomized controlled trials (RCTs) of neuropsychiatric conditions involve cognitive outcome measures; however, validity of cognitive data relies on adequate effort during testing, and such screening is seldom performed. Given well-established rates of 10 to 30% poor effort in clinical settings, this is not a trivial concern. This preliminary study evaluated effort during cognitive testing in an RCT of omega-3 supplementation to reduce suicidality in a high-risk psychiatric population. An interim analysis of sustained attentions measures from the Connors Performance Test (CPT-2) at baseline for the first 60 participants was conducted. Previously validated cut points to detect insufficient effort on the CPT-2 were applied. At baseline, 12% (7) were identified as giving poor effort. Follow-up analyses indicated less psychiatric distress and suicidality among those who gave poor effort. Results suggest comparable likelihood of a poor effort on cognitive testing in clinical and RCT participation. Reduced psychiatric distress in the poor effort group raises concern regarding interpretation of other measures. The importance of screening cognitive data for effort in RCTs is highlighted. Future studies will examine effort at follow-up visits, and explore relationships to attrition, adherence, and response to treatment. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Turner, Travis H.] Ralph H Johnson VAMC, Mental Hlth Serv, Charleston, SC USA. [Turner, Travis H.; Marriott, Bernadette P.] Dept Psychiat & Behav Sci, Charleston, SC USA. [Turner, Travis H.; Renfroe, Jenna B.] Med Univ South Carolina, Dept Neurol Neurosci, Movement Disorders Program, Charleston, SC USA. [Morella, Kristen] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Marriott, Bernadette P.] Med Univ South Carolina, Div Gastroenterol & Hepatol, Nutr Sect, Dept Med, Charleston, SC USA. RP Turner, TH (reprint author), VAMC MH 116, RHJ, 109 Bee St, Charleston, SC 29401 USA. EM turnertr@musc.edu FU Department of Defense (DoD) [W81XWH-13-2-0015]; US Army Medical Research and Materiel Command (USAMRMC); Congressionally Directed Medical Research Programs (CDMRP) through the US Army Medical Research Acquisition Authority (USAMRAA); intramural program of the National Institute on Alcohol Abuse and Alcoholism FX The BRAVO study is sponsored by award # W81XWH-13-2-0015 from the Department of Defense (DoD), US Army Medical Research and Materiel Command (USAMRMC), Congressionally Directed Medical Research Programs (CDMRP) through the US Army Medical Research Acquisition Authority (USAMRAA). The intramural program of the National Institute on Alcohol Abuse and Alcoholism also provides support for this study. The BRAVO study team wishes to acknowledge the excellent support of Samantha Wise in all aspects of the study. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1049-8931 EI 1557-0657 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD SEP PY 2016 VL 25 IS 3 BP 199 EP 204 DI 10.1002/mpr.1505 PG 6 WC Psychiatry SC Psychiatry GA DW6HE UT WOS:000383750200005 PM 27074873 ER PT J AU Alfaris, N Kyle, TK Nadai, J Stanford, FC AF Alfaris, N. Kyle, T. K. Nadai, J. Stanford, F. C. TI A new era of addiction treatment amplifies the stigma of disease and treatment for individuals with obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Editorial Material ID GENERAL-PRACTITIONERS; RELEASE NALTREXONE; DRUG-USERS; HEALTH; ATTITUDES; CARE; DISCRIMINATION; MANAGEMENT; OVERWEIGHT; WEIGHT C1 [Alfaris, N.; Nadai, J.; Stanford, F. C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, MGH Weight Ctr, Boston, MA 02114 USA. [Alfaris, N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Alfaris, N.; Nadai, J.; Stanford, F. C.] Harvard Med Sch Boston, Dept Med, Boston, MA 02115 USA. [Kyle, T. K.] ConscienHealth, Pittsburgh, PA USA. [Kyle, T. K.] Obes Act Coalit, Tampa, FL USA. [Stanford, F. C.] Massachusetts Gen Hosp, Dept Pediat Endocrinol, Boston, MA 02114 USA. RP Alfaris, N (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, MGH Weight Ctr, Boston, MA 02114 USA.; Alfaris, N (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Obes Metab & Nutr Inst, Boston, MA 02114 USA.; Alfaris, N (reprint author), Harvard Med Sch Boston, Dept Med, Boston, MA 02115 USA. EM nalfaris@mgh.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X NR 25 TC 0 Z9 0 U1 6 U2 6 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 SEP PY 2016 VL 40 IS 9 BP 1335 EP 1336 DI 10.1038/ijo.2016.101 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DW6SI UT WOS:000383781100001 PM 27323868 ER PT J AU May, FP Whitman, CB Varlyguina, K Bromley, EG Spiegel, BMR AF May, Folasade P. Whitman, Cynthia B. Varlyguina, Ksenia Bromley, Erica G. Spiegel, Brennan M. R. TI Addressing Low Colorectal Cancer Screening in African Americans: Using Focus Groups to Inform the Development of Effective Interventions SO JOURNAL OF CANCER EDUCATION LA English DT Article DE African American; Colorectal cancer; Screening; Disparities; Qualitative ID CARE; KNOWLEDGE AB African Americans have the highest burden of colorectal cancer (CRC) in the United States of America (USA) yet lower CRC screening rates than whites. Although poor screening has prompted efforts to increase screening uptake, there is a persistent need to develop public health interventions in partnership with the African American community. The aim of this study was to conduct focus groups with African Americans to determine preferences for the content and mode of dissemination of culturally tailored CRC screening interventions. In June 2013, 45-75-year-old African Americans were recruited through online advertisements and from an urban Veterans Affairs system to create four focus groups. A semi-structured interview script employing open-ended elicitation was used, and transcripts were analyzed using ATLAS.ti software to code and group data into a concept network. A total of 38 participants (mean age = 54) were enrolled, and 59 ATLAS.ti codes were generated. Commonly reported barriers to screening included perceived invasiveness of colonoscopy, fear of pain, and financial concerns. Facilitators included poor diet/health and desire to prevent CRC. Common sources of health information included media and medical providers. CRC screening information was commonly obtained from medical personnel or media. Participants suggested dissemination of CRC screening education through commercials, billboards, influential African American public figures, Internet, and radio. Participants suggested future interventions include culturally specific information, including details about increased risk, accessing care, and dispelling of myths. Public health interventions to improve CRC screening among African Americans should employ media outlets, emphasize increased risk among African Americans, and address race-specific barriers. Specific recommendations are presented for developing future interventions. C1 [May, Folasade P.; Spiegel, Brennan M. R.] VA Greater Angeles Healthcare Syst, Div Gastroenterol, Dept Med, Los Angeles, CA USA. [May, Folasade P.; Bromley, Erica G.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [May, Folasade P.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [May, Folasade P.; Whitman, Cynthia B.; Varlyguina, Ksenia; Spiegel, Brennan M. R.] Cedars Sinai Med Ctr, Dept Med, CS CORE, Los Angeles, CA 90048 USA. RP May, FP (reprint author), VA Greater Angeles Healthcare Syst, Div Gastroenterol, Dept Med, Los Angeles, CA USA.; May, FP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA.; May, FP (reprint author), Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA.; May, FP (reprint author), Cedars Sinai Med Ctr, Dept Med, CS CORE, Los Angeles, CA 90048 USA. EM fmay@mednet.ucla.edu FU NIH Training grant [T32DK07180-40] FX This research was supported by the NIH Training grant (T32DK07180-40) for Dr. May. There was no sponsor for this research or publication. NR 25 TC 2 Z9 2 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD SEP PY 2016 VL 31 IS 3 BP 567 EP 574 DI 10.1007/s13187-015-0842-z PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA DU1UA UT WOS:000381993900023 PM 25963898 ER PT J AU Vaduganathan, M Kornowski, R Vaknin-Assa, H Greenberg, G Bental, T Lev, EI Assali, AR AF Vaduganathan, Muthiah Kornowski, Ran Vaknin-Assa, Hana Greenberg, Gabriel Bental, Tamir Lev, Eli I. Assali, Abid R. TI Coronary stenting approaches in the treatment of chronic total occlusion: contemporary registry-based experience SO JOURNAL OF CARDIOVASCULAR MEDICINE LA English DT Article DE bare metal stents; chronic total occlusion; drug-eluting stents; stenting; target vessel revascularization ID DRUG-ELUTING STENTS; SINGLE-CENTER EXPERIENCE; TERM CLINICAL-OUTCOMES; BARE-METAL STENTS; PERCUTANEOUS RECANALIZATION; DIABETES-MELLITUS; ELDERLY-PATIENTS; FOLLOW-UP; INTERVENTION; IMPLANTATION AB Aims This 'real-world' investigation attempted to determine the long-term prognoses of patients who have undergone successful revascularization of chronic total occlusion (CTO) lesions. Methods All consecutive unselected patients from January 2006 to June 2011, undergoing stenting for CTO (n=272), were retrospectively identified through an institutional registry. Procedural failure was defined as final diameter stenosis greater than 30% or postdilatation thrombolysis in myocardial infarction flow less than 3. Outcomes were assessed based on stenting type [ bare metal stent (BMS), drug-eluting stent (DES), or mixed] in the successful procedural cohort. Multiple logistic regression analyses were used to account for known baseline cardiovascular risk imbalances. The primary endpoint was 2-year target vessel revascularization. Results Overall procedural failure occurred in 55 (20.2%) patients presenting with CTO lesions. Failed revascularization was independently associated with multivessel disease, lesion lengths greater than 15 mm, tortuous segments, and presence of calcifications. Major complications included coronary dissection (10%) and perforation (2%). Of the successful procedures, 141 (64%) underwent pure DES, 46 (21%) pure BMS, and 34 (15%) mixed stenting. At 2-year follow-up, fewer patients in the DES group required repeat revascularization compared to the mixed stenting group (6 vs. 26%; P=0.002). Mixed stenting was an independent predictor of long-term target vessel revascularization (adjusted odds ratio 2.1, 95% confidence interval 1.1-4.1, P=0.02) compared to DES. Conclusions Failed revascularization of CTO lesions occurs in a fifth of patients and appears to be associated with complex vessel anatomy. Our data suggest that DES use in this setting are associated with improved 2-year clinical endpoints compared with pure BMS or mixed stenting approaches. C1 [Vaduganathan, Muthiah] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. [Kornowski, Ran; Vaknin-Assa, Hana; Greenberg, Gabriel; Bental, Tamir; Lev, Eli I.; Assali, Abid R.] Tel Aviv Univ, Dept Cardiol, Rabin Med Ctr, Tel Aviv, Israel. RP Vaduganathan, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM muthu@md.northwestern.edu NR 24 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1558-2027 EI 1558-2035 J9 J CARDIOVASC MED JI J. Cardiovasc. Med. PD SEP PY 2016 VL 17 IS 9 BP 673 EP 679 DI 10.2459/JCM.0000000000000231 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW9DC UT WOS:000383954500006 PM 25806471 ER PT J AU Sahlem, GL Short, EB Kerns, S Snipes, J DeVries, W Fox, JB Burns, C Schmidt, M Nahas, ZH George, MS Sackeim, HA AF Sahlem, Gregory L. Short, E. Baron Kerns, Suzanne Snipes, Jon DeVries, William Fox, James B. Burns, Carol Schmidt, Matthew Nahas, Ziad H. George, Mark S. Sackeim, Harold A. TI Expanded Safety and Efficacy Data for a New Method of Performing Electroconvulsive Therapy: Focal Electrically Administered Seizure Therapy SO JOURNAL OF ECT LA English DT Article DE electroconvulsive therapy; ECT; depression; FEAST; efficacy; cognitive adverse effects ID RANDOMIZED CONTROLLED-TRIAL; MAGNETIC COIL STIMULATION; ELECTRODE PLACEMENT; MAJOR DEPRESSION; PERIPHERAL-NERVE; DOUBLE-BLIND; UNIDIRECTIONAL CURRENTS; ANATOMICAL VARIABILITY; CONVULSIVE THERAPY; MOTOR CORTEX AB Objective Electroconvulsive therapy (ECT) is the most rapid and effective antidepressant treatment but with concerns about cognitive adverse effects. A new form of ECT, focal electrically administered seizure therapy (FEAST), was designed to increase the focality of stimulation and better match stimulus parameters with neurophysiology. We recently reported on the safety and feasibility of FEAST in a cohort (n = 17) of depressed patients. We now report on the safety, feasibility, preliminary efficacy, and cognitive effects of FEAST in a new cohort. Methods Open-label FEAST was administered to 20 depressed adults (6 men; 3 with bipolar disorder; age 49.1 10.6 years). Clinical and cognitive assessments were obtained at baseline and end of course. Time to orientation recovery was assessed at each treatment. Nonresponders switched to conventional ECT. Results Participants tolerated the treatment well with no dropouts. Five patients (25%) transitioned from FEAST to conventional ECT due to inadequate response. After FEAST (mean, 9.3 +/- 3.5 sessions; range, 4-14), there was a 58.1% +/- 36.0% improvement in Hamilton Rating Scale for Depression scores compared with that in the baseline (P < 0.0001); 13 (65%) of 20 patients met response criteria, and 11 (55%) of 20 met remission criteria. Patients achieved reorientation (4 of 5 items) in 4.4 +/- 3.0 minutes (median, 4.5 minutes), timed from eyes opening. There was no deterioration in neuropsychological measures. Conclusions These findings provide further support for the safety and efficacy of FEAST. The remission and response rates were in the range found using conventional ECT, and the time to reorientation may be quicker. However, without a randomized comparison group, conclusions are tentative. C1 [Sahlem, Gregory L.; Short, E. Baron; Kerns, Suzanne; Snipes, Jon; DeVries, William; Fox, James B.; Burns, Carol; Schmidt, Matthew; Nahas, Ziad H.; George, Mark S.] Med Univ South Carolina, Dept Psychiat, Brain Stimulat Div, 67 President St,502 N, Charleston, SC 29425 USA. [Schmidt, Matthew; Sackeim, Harold A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Schmidt, Matthew; Sackeim, Harold A.] Columbia Univ, Dept Radiol, New York, NY USA. [Nahas, Ziad H.] Amer Univ Beirut, Med Ctr, Dept Psychiat, Beirut, Lebanon. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Sahlem, GL (reprint author), Med Univ South Carolina, Dept Psychiat, Brain Stimulat Div, 67 President St,502 N, Charleston, SC 29425 USA. EM sahlem@musc.edu FU MECTA Corporation FX This study was supported in part by an unrestricted educational grant from the MECTA Corporation. The MECTA Corporation also provided a custom-modified MECTA spECTrum 5000Q device. Dr Sackeim is the inventor on a patent for FEAST (US8712532 B2) and serves as a consultant to the MECTA Corporation and Neuronetics, Inc. All other authors have no conflicts of interest or financial disclosures to report. NR 65 TC 3 Z9 3 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1095-0680 EI 1533-4112 J9 J ECT JI J. ECT PD SEP PY 2016 VL 32 IS 3 BP 197 EP 203 DI 10.1097/YCT.0000000000000328 PG 7 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA DW8OB UT WOS:000383914300027 PM 27379790 ER PT J AU Bajrami, B Zhu, HY Kwak, HJ Mondal, S Hou, QM Geng, GF Karatepe, K Zhang, YC Nombela-Arrieta, C Park, SY Loison, F Sakai, J Xu, YF Silberstein, LE Luo, HR AF Bajrami, Besnik Zhu, Haiyan Kwak, Hyun-Jeong Mondal, Subhanjan Hou, Qingming Geng, Guangfeng Karatepe, Kutay Zhang, Yu C. Nombela-Arrieta, Cesar Park, Shin-Young Loison, Fabien Sakai, Jiro Xu, Yuanfu Silberstein, Leslie E. Luo, Hongbo R. TI G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; STEM-CELL MOBILIZATION; ESCHERICHIA-COLI PNEUMONIA; TUMOR-SUPPRESSOR PTEN; RECRUITMENT IN-VIVO; BONE-MARROW; HEMATOPOIETIC STEM; ANTAGONIST PLERIXAFOR; PROGENITOR CELLS; WHIM SYNDROME AB Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. C1 [Bajrami, Besnik; Kwak, Hyun-Jeong; Mondal, Subhanjan; Hou, Qingming; Karatepe, Kutay; Zhang, Yu C.; Nombela-Arrieta, Cesar; Park, Shin-Young; Loison, Fabien; Sakai, Jiro; Silberstein, Leslie E.; Luo, Hongbo R.] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. [Bajrami, Besnik; Kwak, Hyun-Jeong; Mondal, Subhanjan; Hou, Qingming; Karatepe, Kutay; Zhang, Yu C.; Nombela-Arrieta, Cesar; Park, Shin-Young; Loison, Fabien; Sakai, Jiro; Silberstein, Leslie E.; Luo, Hongbo R.] Childrens Hosp Boston, Joint Program Transfus Med, Stem Cell Program, Dept Lab Med, Boston, MA 02115 USA. [Bajrami, Besnik; Kwak, Hyun-Jeong; Mondal, Subhanjan; Hou, Qingming; Karatepe, Kutay; Zhang, Yu C.; Nombela-Arrieta, Cesar; Park, Shin-Young; Loison, Fabien; Sakai, Jiro; Silberstein, Leslie E.; Luo, Hongbo R.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Zhu, Haiyan; Geng, Guangfeng; Xu, Yuanfu] Chinese Acad Med Sci, Ctr Stem Cell Med, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China. [Zhu, Haiyan; Geng, Guangfeng; Xu, Yuanfu] Chinese Acad Med Sci, Ctr Stem Cell Med, Blood Dis Hosp, Tianjin 300020, Peoples R China. [Zhu, Haiyan; Geng, Guangfeng; Xu, Yuanfu] Peking Union Med Coll, Tianjin 300020, Peoples R China. [Nombela-Arrieta, Cesar] Univ Zurich Hosp, Dept Expt Hematol, CH-8091 Zurich, Switzerland. [Loison, Fabien] Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand. RP Luo, HR (reprint author), Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA.; Luo, HR (reprint author), Childrens Hosp Boston, Joint Program Transfus Med, Stem Cell Program, Dept Lab Med, Boston, MA 02115 USA.; Luo, HR (reprint author), Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. EM Hongbo.Luo@childrens.harvard.edu FU National Basic Research Program of China [2015CB964903, 2012CB966403]; National Natural Sciences Foundation of China [31271484, 31471116]; Natural Science Foundation of Tianjin City [12JCZDJC24600]; National Institutes of Health [R01AI103142, R01HL092020, P01 HL095489]; FAMRI [CIA 123008] FX Y.Xu is supported by the grants from National Basic Research Program of China (2015CB964903 and 2012CB966403), National Natural Sciences Foundation of China (31271484 and 31471116), and Natural Science Foundation of Tianjin City (12JCZDJC24600). H. Luo is supported by National Institutes of Health grants (R01AI103142, R01HL092020, and P01 HL095489) and a grant from FAMRI (CIA 123008). NR 78 TC 1 Z9 1 U1 2 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD SEP PY 2016 VL 213 IS 10 BP 1999 EP 2018 DI 10.1084/jem.20160393 PG 20 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA DX1ED UT WOS:000384107700006 PM 27551153 ER PT J AU Im, HY Bedard, P Song, JH AF Im, Hee Yeon Bedard, Patrick Song, Joo-Hyun TI Long Lasting Attentional-Context Dependent Visuomotor Memory SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article DE visuomotor learning; attentional-context; memory retrieval ID DIVIDED ATTENTION; MOTOR ADAPTATION; TASK; SET; EXPERIENCE; RETRIEVAL; MOVEMENTS; OBJECTS AB Using a dual-task paradigm, we recently reported that visuomotor adaptation acquired under distraction of a secondary attention-demanding discrimination task could be remembered only when a similar distraction was present. In contrast, when tested without the distracting task, performance reverted to untrained levels (Song & Bcdard, 2015). Here, we demonstrated that this newfound paradoxical benefit of consistent dual-task context lasts over 1 day, such that visuomotor memory retrieval is enhanced under conditions where it is more difficult to engage in attentional selection of the motor task. Furthermore, this long-term effect was evident even when the task type or sensory modality of the secondary task differed between initial adaptation and the delayed recall on the next day. We conclude that attentional diversion by performing a dual-task forms a long-term vital context for visuomotor memory independent of external contexts without taxing capacity limited attention. C1 [Im, Hee Yeon; Song, Joo-Hyun] Brown Univ, Dept Cognit Linguist & Psychol Sci, Box 1821, Providence, RI 02912 USA. [Bedard, Patrick] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Bedard, Patrick; Song, Joo-Hyun] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Im, Hee Yeon] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Song, JH (reprint author), Brown Univ, Dept Cognit Linguist & Psychol Sci, Box 1821, Providence, RI 02912 USA. EM joo-hyun_song@brown.edu FU NIGMS-NIH IDeA [P20GM103645]; Rhode Island Foundation; Center for Vision Research at Brown University FX This project was supported by NIGMS-NIH IDeA P20GM103645 and the Rhode Island Foundation to Joo-Hyun Song. Hee Yeon Im was partially supported by the postdoc fellowship from the Center for Vision Research at Brown University. NR 30 TC 2 Z9 2 U1 6 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-1523 EI 1939-1277 J9 J EXP PSYCHOL HUMAN JI J. Exp. Psychol.-Hum. Percept. Perform. PD SEP PY 2016 VL 42 IS 9 BP 1269 EP 1274 DI 10.1037/xhp0000271 PG 6 WC Psychology; Psychology, Experimental SC Psychology GA DW8CC UT WOS:000383879900001 PM 27454139 ER PT J AU Romain, F Courtwright, A AF Romain, Frederic Courtwright, Andrew TI Can I trust them to do everything? The role of distrust in ethics committee consultations for conflict over life-sustaining treatment among Afro-Caribbean patients SO JOURNAL OF MEDICAL ETHICS LA English DT Article DE End of Life Care; Ethics Committees; Consultation; Health Care for Specific Diseases; Groups; Minorities ID INTENSIVE-CARE UNITS; HEALTH-CARE; END; RACISM; PHYSICIAN; PROVIDERS; MISTRUST; POLICY; AIDS; RACE AB Background Distrust in the American healthcare system is common among Afro-Caribbeans but the role of this distrust in conflict over life-sustaining treatment is not well described. Objective To identify the ways that distrust manifests in ethics committee consultation for conflict over life-sustaining treatment among Afro-Caribbean patients. Methods This was a retrospective cohort study at a large academic hospital of all ethics committee consultations for life-sustaining treatment among Afro-Caribbean patients and their surrogates. We reviewed medical records and identified cases in which ethics consultants described distrust as playing a role in the conflict over life-sustaining treatment. Results Of the 169 ethics committee consultation cases for conflict over life-sustaining treatment, 11 (6.5%) involved patients who self-identified as Afro-Caribbean. Distrust played a role in several of these cases, with surrogates of three patients, in particular, illustrating the way that perceived heath disparities, past labelling and concerns about continued maltreatment generated distrust leading to conflict over life-sustaining treatment. Conclusions Exploring issues of distrust may help ethics consultants identify the source of conflict over life-sustaining treatment among Afro-Caribbean patients. C1 [Romain, Frederic] Mass Gen Hosp, Resp Care, 55 Fruit St,Ells 4, Boston, MA 02114 USA. [Courtwright, Andrew] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Courtwright, Andrew] Brigham & Womens Hosp, Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP Romain, F (reprint author), Mass Gen Hosp, Resp Care, 55 Fruit St,Ells 4, Boston, MA 02114 USA. EM jromain@mgh.harvard.edu FU National Institutes of Health [5T32HL007633-30] FX National Institutes of Health (5T32HL007633-30). NR 24 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 0306-6800 EI 1473-4257 J9 J MED ETHICS JI J. Med. Ethics PD SEP PY 2016 VL 42 IS 9 BP 582 EP 585 DI 10.1136/medethics-2015-103137 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DW2LA UT WOS:000383472700008 PM 27178534 ER PT J AU Davies, EC Jakobiec, FA Stagner, AM Rizzo, JF AF Davies, Emma C. Jakobiec, Frederick A. Stagner, Anna M. Rizzo, Joseph F., III TI An Atypical Case of Lymphocytic Panhypophysitis in a Pregnant Woman SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID HYPOPHYSITIS AB We describe a case of lymphocytic panhypophysitis (LPH) in a 30-year-old woman presenting with throbbing headaches and vision changes during her third trimester. LPH is the rarest subclassification of lymphocytic hypophysitis; it is typically found in males and has not previously been associated with pregnancy. Anterior and posterior pituitary deficits together with headaches should raise a high degree of suspicion regarding the possibility of LPH. The atypical magnetic resonance imaging finding of a heterogeneous pituitary mass additionally raised concern about pituitary apoplexy. Tissue from a transsphenoidal biopsy permitted diagnosis of lymphocytic hypophysitis. There was infiltration of the pituitary gland by small B and T lymphocytes. Resolution of the visual symptoms occurred after the biopsy and treatment with intravenous steroids. C1 [Davies, Emma C.; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Neuroophthalmol Serv, Boston, MA 02114 USA. [Davies, Emma C.; Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Davies, Emma C.; Jakobiec, Frederick A.; Stagner, Anna M.; Rizzo, Joseph F., III] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu 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 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2016 VL 36 IS 3 BP 313 EP 316 DI 10.1097/WNO.0000000000000362 PG 4 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA DV9PZ UT WOS:000383274600021 PM 27008424 ER PT J AU Cestari, DM Arnold, A AF Cestari, Dean M. Arnold, Anthony TI Does Nocturnal Hypotension Play a Causal Role in Nonarteritic Anterior Ischemic Optic Neuropathy? SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID ARTERIAL-HYPOTENSION; DECOMPRESSION TRIAL; NERVE HEAD; PRESSURE; PATHOGENESIS; DISORDERS; GLAUCOMA C1 [Cestari, Dean M.] Harvard Med Sch, Mass Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. [Arnold, Anthony] Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. RP Cestari, DM (reprint author), Harvard Med Sch, Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Dean_Cestari@MEEI.HARVARD.EDU NR 25 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2016 VL 36 IS 3 BP 329 EP 333 DI 10.1097/WNO.0000000000000397 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA DV9PZ UT WOS:000383274600024 PM 27380214 ER PT J AU Rizzo, JF AF Rizzo, Joseph F. TI Simmons Lessell, MD (1931-2016) In Memoriam SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Biographical-Item C1 [Rizzo, Joseph F.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Rizzo, JF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM joseph_rizzo@meei.harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2016 VL 36 IS 3 BP 341 EP 342 DI 10.1097/WNO.0000000000000434 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA DV9PZ UT WOS:000383274600036 ER PT J AU Swetz, KM AF Swetz, Keith M. TI Response to Legalized Physician-Assisted Death: Check Yourself Before You Wreck Yourself SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter C1 [Swetz, Keith M.] Univ Alabama Birmingham, Ctr Palliat & Support Care, 1720 2nd Ave South,BDB 650, Birmingham, AL 35294 USA. [Swetz, Keith M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Swetz, KM (reprint author), Univ Alabama Birmingham, Ctr Palliat & Support Care, 1720 2nd Ave South,BDB 650, Birmingham, AL 35294 USA. EM kswetz@uabmc.edu NR 4 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2016 VL 19 IS 9 BP 902 EP 903 DI 10.1089/jpm.2016.0162 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DU5HF UT WOS:000382242100002 PM 27135596 ER PT J AU Gidwani, R Joyce, N Kinosian, B Faricy-Anderson, K Levy, C Miller, SC Ersek, M Wagner, T Mor, V AF Gidwani, Risha Joyce, Nina Kinosian, Bruce Faricy-Anderson, Katherine Levy, Cari Miller, Susan C. Ersek, Mary Wagner, Todd Mor, Vincent TI Gap between Recommendations and Practice of Palliative Care and Hospice in Cancer Patients SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; VETERANS AFFAIRS; END; OUTCOMES; SYSTEM AB Background: Specialty societies recommend patients with advanced cancer receive early exposure to palliative care and exposure to hospice care. Objective: We sought to understand real-world practice of care, specifically, the timing of palliative care, and how timing and duration of hospice care varied across Medicare, VA, and VA-Purchased care. Design: We conducted a retrospective analysis of administrative data for veterans aged 65 years or older who died with cancer in 2012. Multilevel logistic regression was used to evaluate the likelihood of receiving palliative care, receiving hospice care, and receiving hospice care for at least three days. Setting: Medicare, VA, and VA-Purchased care environments. Measurements: The receipt and timing of palliative care within VA and the receipt and timing of hospice care across three healthcare environments. Results: Most veterans received hospice care (71%), whereas fewer received palliative care (52%). Among all cancer decedents, 59% received hospice care for their last three days of life. Patients who received hospice care did so a median of 20 days before death (interquartile range [IQR]: 7-46). Patients who received palliative care did so a median of 38 days before death (IQR: 13-94). Adjusted analyses revealed significant differences in receipt of palliative care across cancer type, and significant differences in receipt of hospice care across cancer type. After adjusting for age and cancer type, patients who received VA hospice care were significantly less likely to receive it for at least three days compared with patients who received VA-Purchased or Medicare hospice care. Conclusions: There remains a gap between recommended timing of supportive services and real-world practice of care. Results suggest that difficulties in prognosticating death are not fully responsible for underexposure to hospice. C1 [Gidwani, Risha; Wagner, Todd] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, HERC, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. [Gidwani, Risha] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Joyce, Nina; Miller, Susan C.; Mor, Vincent] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Kinosian, Bruce; Ersek, Mary] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kinosian, Bruce] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. [Faricy-Anderson, Katherine] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Faricy-Anderson, Katherine; Miller, Susan C.; Mor, Vincent] Providence VA Med Ctr, Providence, RI USA. [Levy, Cari] Eastern Colorado VA Healthcare Syst, Denver, CO USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Wagner, Todd] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Gidwani, R (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat Ci2i, HERC, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM risha.gidwani@va.gov FU VA Health Services Research and Development [IIR 12-121]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development; VA Information Resource Center [SDR 02-237, 98-004]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR 12-121] FX Funding support was provided by VA Health Services Research and Development (IIR 12-121). This work was presented at the American Society of Clinical Oncology's Palliative Care Symposium in October 2015. Support for VA/CMS data is provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, and VA Information Resource Center (Project Nos. SDR 02-237 and 98-004). Support for this research study is also provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (Project No. IIR 12-121). NR 23 TC 1 Z9 1 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2016 VL 19 IS 9 BP 957 EP 963 DI 10.1089/jpm.2015.0514 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DU5HF UT WOS:000382242100012 PM 27228478 ER PT J AU Singer, AE Goebel, JR Kim, YS Dy, SM Ahluwalia, SC Clifford, M Dzeng, E O'Hanlon, CE Motala, A Walling, AM Goldberg, J Meeker, D Ochotorena, C Shanman, R Cui, MK Lorenz, KA AF Singer, Adam E. Goebel, Joy R. Kim, Yan S. Dy, Sydney M. Ahluwalia, Sangeeta C. Clifford, Megan Dzeng, Elizabeth O'Hanlon, Claire E. Motala, Aneesa Walling, Anne M. Goldberg, Jaime Meeker, Daniella Ochotorena, Claudia Shanman, Roberta Cui, Mike Lorenz, Karl A. TI Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CANCER PAIN MANAGEMENT; EVIDENCE-BASED RECOMMENDATIONS; CELL LUNG-CANCER; OBSTRUCTIVE PULMONARY-DISEASE; HEART-FAILURE MANAGEMENT; COPING STRATEGY PROGRAM; TERMINALLY-ILL PATIENTS; PATIENT-HELD RECORDS; FRAIL OLDER-PEOPLE AB Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness'' and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence Review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited. C1 [Singer, Adam E.; Walling, Anne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Singer, Adam E.; Ahluwalia, Sangeeta C.; Clifford, Megan; O'Hanlon, Claire E.; Motala, Aneesa; Walling, Anne M.; Shanman, Roberta; Lorenz, Karl A.] RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90840 USA. [Kim, Yan S.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Dy, Sydney M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Dzeng, Elizabeth] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [O'Hanlon, Claire E.] RAND Corp, Pardee RAND Grad Sch, Santa Monica, CA USA. [Walling, Anne M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goldberg, Jaime] Cedars Sinai Med Ctr, Support Care Med, Los Angeles, CA 90048 USA. [Meeker, Daniella] Univ Southern Calif, Dept Prevent Med, Los Angeles, CA USA. [Ochotorena, Claudia] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Cui, Mike] RAND Corp, Pittsburgh, PA USA. [Lorenz, Karl A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Singer, AE (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA. EM asinger@rand.org FU National Institute of Nursing Research [R01 NR013372]; Cambia Health Foundation; California HealthCare Foundation; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI [UL1 TR000124]; NIH; [T32 GM008042] FX This work was supported by grant R01 NR013372 from the National Institute of Nursing Research, a Cambia Health Foundation Sojourns Award, and the California HealthCare Foundation. Dr. Singer received support from grant T32 GM008042 as a member of the Medical Scientist Training Program at the University of California, Los Angeles. Dr. Walling received support from the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI grant UL1 TR000124 and the NIH loan repayment program. NR 146 TC 4 Z9 4 U1 30 U2 30 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 SEP PY 2016 VL 19 IS 9 BP 995 EP 1008 DI 10.1089/jpm.2015.0367 PG 14 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DU5HF UT WOS:000382242100019 PM 27533892 ER PT J AU Zehm, A Mullin, J Zhang, HP AF Zehm, April Mullin, Jonathan Zhang, Haipeng TI Thirst in Palliative Care #313 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID RANDOMIZED-CLINICAL-TRIAL; QUALITY-OF-LIFE; HEART-FAILURE; UNIT PATIENTS; CANCER-PATIENTS; WEIGHT-GAIN; DRY MOUTH; FLUID; HEMODIALYSIS; DEHYDRATION C1 [Zehm, April] Massachusetts Gen Hosp, Div Palliat Care, 55 Fruit St,Founders 600, Boston, MA 02114 USA. RP Zehm, A (reprint author), Massachusetts Gen Hosp, Div Palliat Care, 55 Fruit St,Founders 600, Boston, MA 02114 USA. EM azehm@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2016 VL 19 IS 9 BP 1009 EP 1010 DI 10.1089/jpm.2016.0205 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DU5HF UT WOS:000382242100020 PM 27258019 ER EF