FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Seymann, GB Southern, W Burger, A Brotman, DJ Chakraborti, C Harrison, R Parekh, V Sharpe, BA Pile, J Hunt, D Leykum, LK AF Seymann, Gregory B. Southern, William Burger, Alfred Brotman, Daniel J. Chakraborti, Chayan Harrison, Rebecca Parekh, Vikas Sharpe, Bradley A. Pile, James Hunt, Daniel Leykum, Luci K. TI Features of Successful Academic Hospitalist Programs: Insights from the SCHOLAR (SuCcessful HOspitaLists in Academics and Research) Project SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID MEDICINE; MENTORSHIP; CARE AB BACKGROUND: As clinical demands increase, understanding the features that allow academic hospital medicine programs (AHPs) to thrive has become increasingly important. OBJECTIVE: To develop and validate a quantifiable definition of academic success for AHPs. METHODS: A working group of academic hospitalists was formed. The group identified grant funding, academic promotion, and scholarship as key domains reflective of success, and specific metrics and approaches to assess these domains were developed. Self-reported data on funding and promotion were available from a preexisting survey of AHP leaders, including total funding/group, funding/fulltime equivalent (FTE), and number of faculty at each academic rank. Scholarship was defined in terms of research abstracts presented over a 2-year period. Lists of top performers in each of the 3 domains were constructed. Programs appearing on at least 1 list (the SCHOLAR cohort [SuCcessful HOspitaLists in Academics and Research]) were examined. We compared grant funding and proportion of promoted faculty within the SCHOLAR cohort to a sample of other AHPs identified in the preexisting survey. RESULTS: Seventeen SCHOLAR programs were identified, with a mean age of 13.2 years (range, 6-18 years) and mean size of 36 faculty (range, 18-95). The mean total grant funding/program was $4 million (range, $0-$15 million), with mean funding/FTE of $364,000 (range, $0-$1.4 million); both were significantly higher than the comparison sample. The majority of SCHOLAR faculty (82%) were junior, a lower percentage than the comparison sample. The mean number of research abstracts presented over 2 years was 10.8 (range, 9-23). DISCUSSION: Our approach effectively identified a subset of successful AHPs. Despite the relative maturity and large size of the programs in the SCHOLAR cohort, they were comprised of relatively few senior faculty members and varied widely in the quantity of funded research and scholarship. (C) 2016 Society of Hospital Medicine C1 [Seymann, Gregory B.] Univ Calif San Diego, Dept Med, Div Hosp Med, 200 W Arbor Dr, San Diego, CA 92103 USA. [Southern, William] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Burger, Alfred] Icahn Sch Med Mt Sinai, Mt Sinai Beth Israel, Dept Med, Div Hosp Med, New York, NY 10029 USA. [Brotman, Daniel J.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA. [Chakraborti, Chayan] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Harrison, Rebecca] Oregon Hlth & Sci Univ, Dept Hosp Med, Portland, OR 97201 USA. [Parekh, Vikas] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sharpe, Bradley A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Pile, James] Cleveland Clin, Inst Med, Dept Hosp Med, Cleveland, OH 44106 USA. [Hunt, Daniel] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Leykum, Luci K.] UT Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. RP Seymann, GB (reprint author), Univ Calif San Diego, 200 W Arbor Dr, San Diego, CA 92103 USA. EM gseymann@ucsd.edu FU Society of Hospital Medicine; Society of General Internal Medicine; SHM Academic Committee; SGIM Academic Hospitalist Task Force FX The authors thank all of the AHP leaders who participated in the SCHOLAR project. They also thank the Society of Hospital Medicine and Society of General Internal Medicine and the SHM Academic Committee and SGIM Academic Hospitalist Task Force for their support of this work. 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 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2016 VL 11 IS 10 BP 708 EP 713 DI 10.1002/jhm.2603 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EB0ZE UT WOS:000387074700007 PM 27189874 ER PT J AU Wang, J Lewis, RF AF Wang, Joanne Lewis, Richard F. TI Contribution of intravestibular sensory conflict to motion sickness and dizziness in migraine disorders SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE vestibular; migraine; motion sickness; vertigo; eye movements ID VESTIBULAR MIGRAINE; VESTIBULOOCULAR REFLEX; TILT; PERCEPTION AB Migraine is associated with enhanced motion sickness susceptibility and can cause episodic vertigo [vestibular migraine (VM)], but the mechanisms relating migraine to these vestibular symptoms remain uncertain. We tested the hypothesis that the central integration of rotational cues (from the semicircular canals) and gravitational cues (from the otolith organs) is abnormal in migraine patients. A postrotational tilt paradigm generated a conflict between canal cues (which indicate the head is rotating) and otolith cues (which indicate the head is tilted and stationary), and eye movements were measured to quantify two behaviors that are thought to minimize this conflict: suppression and reorientation of the central angular velocity signal, evidenced by attenuation ("dumping") of the vestibuloocular reflex and shifting of the rotational axis of the vestibuloocular reflex toward the earth vertical. We found that normal and migraine subjects, but not VM patients, displayed an inverse correlation between the extent of dumping and the size of the axis shift such that the net "conflict resolution" mediated through these two mechanisms approached an optimal value and that the residual sensory conflict in VM patients (but not migraine or normal subjects) correlated with motion sickness susceptibility. Our findings suggest that the brain normally controls the dynamic and spatial characteristics of central vestibular signals to minimize intravestibular sensory conflict and that this process is disrupted in VM, which may be responsible for the enhance motion intolerance and episodic vertigo that characterize this disorder. C1 [Wang, Joanne] Case Western Univ, Sch Med, Cleveland, OH USA. [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Lewis, Richard F.] Harvard Med Sch, Dept Neurol, Boston, MA USA. RP Lewis, RF (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Richard_lewis@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders [DC-012528] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grant DC-012528 (to R. F. Lewis). NR 29 TC 0 Z9 0 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2016 VL 116 IS 4 BP 1586 EP 1591 DI 10.1152/jn.00345.2016 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA EA7RC UT WOS:000386828400006 PM 27385797 ER PT J AU Whitney, K Chisholm, M Haag-Heitman, B Gale, S AF Whitney, Kevin Chisholm, Margery Haag-Heitman, Barbara Gale, Sharon TI Nursing Peer Review Perceptions and Practices A Survey of Chief Nurse Executives SO JOURNAL OF NURSING ADMINISTRATION LA English DT Review ID MODEL; SAFETY AB OBJECTIVE: This study sought to understand chief nurse executive perceptions of nursing peer review (NPR) and current NPR practices in their organizations to provide insights and recommendations for the path forward to a robust NPR approach nationally. BACKGROUND: Nursing peer review is a key component of professional nursing practice focused on self-regulation and improving quality and safety. Despite its known benefits, NPR is not broadly disseminated, and how it is currently used and perceived is not well understood. METHODS: A causal-comparison study design was used. A 25-question, Web-based survey was administered to collect data variables. RESULTS: Chief nurse executives perceived NPR as important in improving quality and safety; however, its prevalence was low. Chief nurse executives also reported NPR practices not aligned with the American Nurses Association (ANA) NPR guidelines. CONCLUSIONS: Results suggest that knowledge gaps exist regarding NPR's purpose, outcomes, and alignment with the ANA peer review guidelines. Interventions are needed to address these gaps to further advance NPR adoption nationally. C1 [Whitney, Kevin] Massachusetts Gen Hosp, Surg Orthopaed & Neurosci, Boston, MA 02114 USA. [Haag-Heitman, Barbara] Nursing Consulting Partners, Whitefish Bay, WI USA. [Chisholm, Margery] MGH Inst Hlth Profess, Charlestown, MA USA. [Gale, Sharon] Org Nurse Leaders MA RI & NH, Woburn, MA USA. RP Whitney, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND 347, Boston, MA 02114 USA. EM kbwhitney@mgh.harvard.edu NR 28 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2016 VL 46 IS 10 BP 541 EP 548 DI 10.1097/NNA.0000000000000399 PG 8 WC Nursing SC Nursing GA EB3EP UT WOS:000387246000011 PM 27681516 ER PT J AU Walling, AM Tisnado, D Ettner, SL Asch, SM Dy, SM Pantoja, P Lee, M Ahluwalia, SC Schreibeis-Baum, H Malin, JL Lorenz, KA AF Walling, Anne M. Tisnado, Diana Ettner, Susan L. Asch, Steven M. Dy, Sydney M. Pantoja, Philip Lee, Martin Ahluwalia, Sangeeta C. Schreibeis-Baum, Hannah Malin, Jennifer L. Lorenz, Karl A. TI Palliative Care Specialist Consultation Is Associated With Supportive Care Quality in Advanced Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Advanced cancer; quality; palliative care ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; OF-LIFE DISCUSSIONS; OLDER PATIENTS; HEALTH-CARE; INSTRUMENTAL VARIABLES; PRIVATE-SECTOR; END; OUTCOMES; PREDICTORS AB Context. Although recent randomized controlled trials support early palliative care for patients with advanced cancer, the specific processes of care associated with these findings and whether these improvements can be replicated in the broader health care system are uncertain. Objectives. The aim of this study was to evaluate the occurrence of palliative care consultation and its association with specific processes of supportive care in a national cohort of Veterans using the Cancer Quality ASSIST (Assessing Symptoms Side Effects and Indicators of Supportive Treatment) measures. Methods. We abstracted data from 719 patients' medical records diagnosed with advanced lung, colorectal, or pancreatic cancer in 2008 over a period of three years or until death who received care in the Veterans Affairs Health System to evaluate the association of palliative care specialty consultation with the quality of supportive care overall and by domain using a multivariate regression model. Results. All but 54 of 719 patients died within three years and 293 received at least one palliative care consult. Patients evaluated by a palliative care specialist at diagnosis scored seven percentage points higher overall (P < 0.001) and 11 percentage points higher (P < 0.001) within the information and care planning domain compared with those without a consult. Conclusion. Early palliative care specialist consultation is associated with better quality of supportive care in three advanced cancers, predominantly driven by improvements in information and care planning. This study supports the effectiveness of early palliative care consultation in three common advanced cancers within the Veterans Affairs Health System and provides a greater understanding of what care processes palliative care teams influence. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. C1 [Walling, Anne M.; Tisnado, Diana; Lee, Martin; Schreibeis-Baum, Hannah; Malin, Jennifer L.; Lorenz, Karl A.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.; Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Walling, Anne M.; Ahluwalia, Sangeeta C.] RAND Hlth, Santa Monica, CA USA. [Pantoja, Philip] RAND Populat & Labor, Santa Monica, CA USA. [Tisnado, Diana] Calif State Univ Fullerton, Dept Hlth Sci, Fullerton, CA 92634 USA. [Ettner, Susan L.; Ahluwalia, Sangeeta C.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Asch, Steven M.; Lorenz, Karl A.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Asch, Steven M.] Stanford Sch Med, Stanford, CA USA. [Dy, Sydney M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Walling, AM (reprint author), VA Greater Los Angeles Healthcare Syst, 911 Broxton Ave, Los Angeles, CA 90095 USA. EM awalling@mednet.ucla.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 09-097]; National Institutes of Health (NIH)/National Center for Advancing Translational Science UCLA CTSI grant [UL1TR000124]; NIH Loan Repayment Program FX This article is based on work supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (Project # IIR 09-097). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. Since July 2013, Dr. Walling has also been supported by the National Institutes of Health (NIH)/National Center for Advancing Translational Science UCLA CTSI grant (UL1TR000124) and the NIH Loan Repayment Program. The funding source had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. Drs Walling, Tisnado, Ettner, Asch, Dy, Lee, Ahluwalia, Schreibeis-Baum, and Pantoja do not have any relevant financial interests, activities, or relationships within the past three years to report. Dr. Malin is employed by and has stock ownership with Anthem. Dr. Lorenz is serving as a consultant to Otsuka Pharmaceuticals for data monitoring and safety in the evaluation of a Phase II trial of Sativex, a novel cannabinoid analgesic. 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2016 VL 52 IS 4 BP 507 EP 514 DI 10.1016/j.jpainsymman.2016.04.005 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA EA7RZ UT WOS:000386830900007 PM 27401515 ER PT J AU Ritchie, CS Kelley, AS Cenzer, IS Smith, AK Wallhagen, ML Covinsky, KE AF Ritchie, Christine S. Kelley, Amy S. Cenzer, Irena Stijacic Smith, Alexander K. Wallhagen, Margaret L. Covinsky, Kenneth E. TI High Levels of Geriatric Palliative Care Needs in Hip Fracture Patients Before the Hip Fracture SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Hip fracture; geriatric palliative care; multimorbidity ID OLDER-ADULTS; MORTALITY; VALIDATION; PATTERNS; INDEX AB Context. Most hip fracture care models are grounded in curative models where the goal is to return the patient to independent function. In many instances, however, hip fractures contribute to continued functional decline and mortality. Although the negative impact of hip fractures is appreciated once they have occurred, what is less understood is what proportion of older adults have high illness burden before experiencing hip fracture and might benefit from geriatric palliative care. Objectives. Using data from the Health and Retirement Study linked to Medicare claims (January 1992 through December 2010), we sought to understand the extent of premorbid illness burden before hip fracture. Methods. Characteristics were based on the interview before hip fracture. Features used to indicate need for geriatric palliative care included evidence of functional and medical vulnerability, pain, and depression. Results. Eight hundred fifty-six older adults who experienced a hip fracture were compared to 851 age-, gender-, and race-matched controls. Older adults with hip fractures had significantly more premorbid functional vulnerability (activities of daily living dependent 25.7% vs. 16.1% [P < 0.001]; dementia 16.2% vs. 7.3% (P < 0.001); use of helpers 41.2% vs. 28.7% [P < 0.001]). They also experienced more medical vulnerability (multimorbidity 43% vs. 29.8% [P < 0.001]; high health care utilization 30.0% vs. 20.9% [P < 0.001]; and poor prognosis 36.1% vs. 25.4% [P < 0.001] in controls). There was no difference in premorbid pain and depression between subsequent hip fracture patients and controls. Conclusions. A significant proportion of older adults have evidence of functional and medical vulnerability before hip fracture. For these individuals, integration of geriatric palliative care may be particularly important for optimizing quality of life and addressing the high morbidity experienced by this population. (C) 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Ritchie, Christine S.; Cenzer, Irena Stijacic; Smith, Alexander K.; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Cenzer, Irena Stijacic; Smith, Alexander K.; Covinsky, Kenneth E.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Kelley, Amy S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Kelley, Amy S.] James J Peters VA Med Ctr, Bronx, NY USA. [Wallhagen, Margaret L.] UCSF, Dept Physiol Nursing, San Francisco, CA USA. [Ritchie, Christine S.] Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. RP Ritchie, CS (reprint author), Univ Calif San Francisco, 3333 Calif St,Suite 380, San Francisco, CA 94143 USA. EM Christine.Ritchie@ucsf.edu FU National Institute for Nursing Research [R01 NR013347]; K07 Geriatric Academic Leadership Award from the National Institute on Aging [1K07AG31779-1A1]; K23 Beeson award from the National Institute on Aging [1K23AG040772, 1K23AG040774]; American Federation for Aging Research FX This project was funded by the National Institute for Nursing Research (R01 NR013347). Dr. Bitchier was funded by a K07 Geriatric Academic Leadership Award from the National Institute on Aging (1K07AG31779-1A1) and Dr. Smith was funded by a K23 Beeson award from the National Institute on Aging (1K23AG040772) and the American Federation for Aging Research. Dr. Kelley was funded by a K23 Beeson award from the National Institute on Aging (1K23AG040774) and the American Federation for Aging Research. NR 19 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2016 VL 52 IS 4 BP 533 EP 538 DI 10.1016/j.jpainsymman.2016.07.003 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA EA7RZ UT WOS:000386830900010 PM 27521282 ER PT J AU Kale, MS Ornstein, KA Smith, CB Kelley, AS AF Kale, Minal S. Ornstein, Katherine A. Smith, Cardinale B. Kelley, Amy S. TI End-of-Life Discussions with Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE end-of-life care preparation; Medicare; discussion ID ADVANCE DIRECTIVES; HEALTH-CARE; MULTIMORBIDITY; OUTCOMES; FRAILTY; IMPACT; RACE AB ObjectivesTo determine the prevalence of end-of-life (EOL) conversations with older adults. DesignNational Health and Aging Trends Study (NHATS), a prospective, longitudinal survey of Medicare beneficiaries. SettingNationally representative. ParticipantsA sample drawn from Wave 2 of the NHATS. MeasurementsThe main outcome was the report of an EOL planning discussion, based upon the participant's response to the question Have you talked to anyone about the types of medical treatment you would want or not want if you became seriously ill in the future? ResultsSixty-one percent of the sample (n = 1,993 individuals, weighted n = 11,123,910) responded that they had discussed EOL treatment preferences with someone. In multivariate regression, factors associated with reporting an EOL discussion included being younger (adjusted odds ratio (AOR) = 1.70, 95% confidence interval (CI) = 1.17-2.47), having more education (high school degree: AOR = 1.45, 95% CI = 1.02-2.07; some college: AOR = 2.03, 95% CI = 1.40-2.95), and having multiple chronic conditions (AOR = 1.25, 95% CI = 1.01-1.55). Black race was associated with lower odds of reporting a discussion (AOR = 0.46, 95% CI = 0.33-0.65). ConclusionForty percent of a nationally representative sample of Medicare beneficiaries had not discussed their preferences regarding EOL medical treatment. Promoting these conversations in clinical and nonclinical settings will be important to ensure that health care is delivered to individuals in a person-centered manner. C1 [Kale, Minal S.; Ornstein, Katherine A.] Icahn Sch Med Mt Sinai, Dept Med, Div Gen Internal Med, New York, NY 10029 USA. [Ornstein, Katherine A.; Smith, Cardinale B.; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Smith, Cardinale B.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Kale, MS (reprint author), Icahn Sch Med Mt Sinai, Div Gen Internal Med, One Gustave Levy Pl,Box 1087, New York, NY 10029 USA. EM minal.kale@mountsinai.org FU National Cancer Institute [K07 CA187071]; National Institute on Aging [K01AG047923]; K23 Beeson award from the National Institute on Aging [1K23AG040774]; American Federation for Aging Research FX Dr. Kale was supported with a grant from the National Cancer Institute (K07 CA187071) during the preparation of this manuscript. Dr. Ornstein was funded by a grant from the National Institute on Aging (K01AG047923). Dr. Kelley was funded by a K23 Beeson award from the National Institute on Aging (1K23AG040774) and the American Federation for Aging Research. NR 27 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 64 IS 10 BP 1962 EP 1967 DI 10.1111/jgs.14285 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FJ UT WOS:000387018500034 PM 27549494 ER PT J AU Smith, AK Currow, DC Abernethy, AP Johnson, MJ Miao, YH Boscardin, WJ Ritchie, CS AF Smith, Alexander K. Currow, David C. Abernethy, Amy P. Johnson, Miriam J. Miao, Yinghui Boscardin, W. John Ritchie, Christine S. TI Prevalence and Outcomes of Breathlessness in Older Adults: A National Population Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE breathlessness; older; decline ID OBSTRUCTIVE PULMONARY-DISEASE; DYSPNEA; MANAGEMENT; MECHANISMS; ILLNESS; CANCER; TRIAL AB ObjectivesTo determine the prevalence and outcomes of breathlessness in older Americans. SettingCommunity-dwelling older adults. ParticipantsIndividuals aged 70 and older in the nationally representative Health and Retirement Study (2008, follow-up through 2012) (N = 3,671; mean age 78). MeasurementsBreathlessness was assessed by asking the question, How often do you become short of breath while awake? Responses of often or sometimes were considered to represent a level of breathlessness sufficient to warrant clinical attention. The prevalence of breathlessness is described overall and in subpopulations, then rates of associated symptoms, well-being, and health services use of participants who were breathless are compared with rates of those who were not. The risk of decline in activities of daily living (ADLs) and death through 2012 was estimated by creating a multivariable Cox proportional hazards model, adjusting for age, sex, race and ethnicity, and education. ResultsTwenty-five percent of participants reported breathlessness. The prevalence of breathlessness was higher in certain subpopulations: chronic lung disease (63%), multimorbidity (2 chronic conditions) (45%), current smokers (38%), heart disease (36%), obesity (body mass index 30.0 kg/m(2)) (33%), and education less than high school (32%). Breathlessness was associated with higher rates of depression, anxiety, and severe fatigue; lower ratings of well-being; and higher rates of clinic and emergency department visits and hospitalizations (all P < .001). Breathlessness predicted ADL decline over 5 years (adjusted hazard ratio (aHR) = 1.43, 95% confidence interval (CI) = 1.22-1.68) and death (aHR 1.62, 95% CI = 1.32-2.02). ConclusionOne in four adults aged 70 and older in the United States experiences breathlessness, which is associated with lack of well-being, greater health services use, and a 40% greater risk of worsened function and 60% greater risk of death over the next 5 years. C1 [Smith, Alexander K.; Miao, Yinghui; Boscardin, W. John; Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Smith, Alexander K.; Boscardin, W. John] San Francisco VA Med Ctr, San Francisco, CA USA. [Currow, David C.; Miao, Yinghui] Flinders Univ S Australia, Discipline Support & Palliat Care, Bedford Pk, SA, Australia. [Abernethy, Amy P.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Abernethy, Amy P.] Duke Univ, Dept Med, Div Med Oncol, Durham, NC USA. [Johnson, Miriam J.] Univ Hull, Hull York Med Sch, Kingston Upon Hull, East Yorkshire, England. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. RP Smith, AK (reprint author), UCSF Div Geriatr, Med, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu OI Currow, David/0000-0003-1988-1250 FU National Institute on Aging [K23AG040772]; American Federation for Aging Research FX Dr. Smith was funded by a K23 Beeson award from the National Institute on Aging (K23AG040772) and the American Federation for Aging Research. NR 25 TC 0 Z9 0 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 OCT PY 2016 VL 64 IS 10 BP 2035 EP 2041 DI 10.1111/jgs.14313 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FJ UT WOS:000387018500044 PM 27603500 ER PT J AU King, BJ Steege, LM Winsor, K VanDenbergh, S Brown, CJ AF King, Barbara J. Steege, Linsey M. Winsor, Katie VanDenbergh, Shelly Brown, Cynthia J. TI Getting Patients Walking: A Pilot Study of Mobilizing Older Adult Patients via a Nurse-Driven Intervention SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospitalization; mobility; older adults; healthcare systems; qualitative evaluation ID ACUTE MEDICAL ILLNESS; PARTICIPATORY ERGONOMICS; HOSPITALIZATION; PROGRAM; CARE AB ObjectivesTo develop a system-based intervention including five components that target barriers to nurse-initiated patient ambulation. DesignPilot study of Mobilizing Older adult patients VIa a Nurse-driven intervention (MOVIN). SettingTwenty-six bed general medical unit. ParticipantsNursing staff (registered nurses and certified nursing assistants) were recruited to participate in focus groups. MeasurementsInformation on frequency and distance patients ambulated and nursing staff documentation of patient ambulation were retrieved from the electronic medical record. Regression discontinuity analysis was used to determine a difference between the preintervention and intervention periods in ambulation occurrence, ambulation distance, and percentage of numeric documentation of ambulation. Thematic analysis was used to analyze focus group interviews. ResultsA statistically significant increase in number of occurrences (t = 4.18, P = .001) and total distance (t = 2.75, P = .01) and a significantly higher positive slope in percentage of numeric documentation was found during the intervention than before the intervention. Thematic analysis identified three central categories (shifting ownership, feeling supported, making ambulation visible) that describe the effect of MOVIN on nursing staff behaviors and perceptions of the intervention. ConclusionDecreasing loss of independent ambulation in hospitalized older adults requires new and innovative approaches to addressing barriers that prevent nurse-initiated patient ambulation. MOVIN is a promising system-based intervention to promoting patient ambulation and improving outcomes for hospitalized older adults. C1 [King, Barbara J.; Steege, Linsey M.] Univ Wisconsin, Sch Nursing, 701 Highland Ave,Room 3179, Madison, WI 53705 USA. [Winsor, Katie; VanDenbergh, Shelly] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Brown, Cynthia J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Brown, Cynthia J.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. RP King, BJ (reprint author), Univ Wisconsin, Sch Nursing, 701 Highland Ave,Room 3179, Madison, WI 53705 USA. EM bjking2@wisc.edu RI Steege, Linsey/S-3070-2016; OI Steege, Linsey/0000-0002-8508-7787; King, Barbara/0000-0003-0577-9028 NR 32 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 64 IS 10 BP 2088 EP 2094 DI 10.1111/jgs.14364 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FJ UT WOS:000387018500051 PM 27548535 ER PT J AU Betz, ME Arias, SA Segal, DL Miller, I Camargo, CA Boudreaux, ED AF Betz, Marian E. Arias, Sarah A. Segal, Daniel L. Miller, Ivan Camargo, Carlos A., Jr. Boudreaux, Edwin D. TI Screening for Suicidal Thoughts and Behaviors in Older Adults in the Emergency Department SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE suicide; emergency department; depression; screening; older adult ID LATE-LIFE; RISK; MULTICENTER; DEPRESSION; POPULATION; PREVALENCE; VALIDATION; PREDICTORS; PREVENTION; PATTERNS AB ObjectivesTo estimate the prevalence of self-harm, suicidal ideation (SI), and suicide attempts (SA) in older adults in the emergency department (ED), including differences according to age, sex, and race and ethnicity. DesignQuasi-experimental, multiphase, eight-center study with prospective review of consecutive charts during enrollment shifts (November 2011-December 2014). SettingEight EDs in seven states, all with protocols for nurses to screen every patient for suicide risk (universal screening). ParticipantsAdults (18 years) registered in the ED. MeasurementsDemographic characteristics; documented screening for self-harm, SI, or SA; and positive self-harm, SI, or SA in those with screening performed. ResultsOf 142,534 visits, 23.3% were of individuals aged 60 and older. Documented screening for self-harm, SI, or SA declined with age, from approximately 81% in younger age groups to a low of 68% in those aged 85 and older. The prevalence of positive screens for self-harm, SI, or SA also declined with age, with peaks in young and middle-age (9.0%) and reaching the lowest point after the age of 75 (1.2%). ConclusionDocumented screening for suicide risk declined with age in this large sample of individuals in the ED. Although the reason for this finding is unclear, at least part of the decline may be related to increasing rates of altered mentation or other individual-level barriers to screening in the older population. These findings support the need for more-detailed examination of the best methods for identifyingand treatingsuicide risk in older adults. C1 [Betz, Marian E.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Arias, Sarah A.; Miller, Ivan] Brown Univ, Dept Psychiat & Human Behav, Butler Hosp, Providence, RI 02912 USA. [Segal, Daniel L.] Univ Colorado, Colorado Springs, CO 80907 USA. [Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Betz, ME (reprint author), Univ Colorado Denver, 12401 E 17th Ave B-215, Aurora, CO 80045 USA. EM marian.betz@ucdenver.edu FU National Institute of Mental Health [U01MH088278, R03MH107551]; Paul Beeson Career Development Award Program (National Institute on Aging, AFAR, John A. Hartford Foundation, Atlantic Philanthropies) [Betz-K23AG043123] FX This work was supported by Awards U01MH088278 and R03MH107551 from the National Institute of Mental Health and by the Paul Beeson Career Development Award Program (National Institute on Aging, AFAR, John A. Hartford Foundation, Atlantic Philanthropies; Betz-K23AG043123). NR 33 TC 0 Z9 0 U1 4 U2 4 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 OCT PY 2016 VL 64 IS 10 BP E72 EP E77 DI 10.1111/jgs.14529 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FJ UT WOS:000387018500003 PM 27596110 ER PT J AU Ko, MS Fung, KZ Shi, Y Espaldon, R Shergill, A Walter, LC AF Ko, Myung S. Fung, Kathy Z. Shi, Ying Espaldon, Roxanne Shergill, Amandeep Walter, Louise C. TI Barrett's Esophagus Commonly Diagnosed in Elderly Men with Limited Life Expectancy SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID MANAGEMENT C1 [Ko, Myung S.; Shi, Ying; Espaldon, Roxanne; Shergill, Amandeep; Walter, Louise C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Fung, Kathy Z.; Shi, Ying; Espaldon, Roxanne; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Fung, Kathy Z.; Shi, Ying; Espaldon, Roxanne; Walter, Louise C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shergill, Amandeep] San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. RP Ko, MS (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. FU National Institute on Aging, National Institutes of Health Award [K24AG041180] FX This work was supported by National Institute on Aging, National Institutes of Health Award K24AG041180 to Dr. Louise Walter. NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2016 VL 64 IS 10 BP E109 EP E111 DI 10.1111/jgs.14409 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA EB0FJ UT WOS:000387018500021 PM 27685424 ER PT J AU Kaufman, HL Russell, J Hamid, O Bhatia, S Terheyden, P D'Angelo, SP Shih, KC Lebbe, C Linette, GP Milella, M Brownell, I Lewis, KD Lorch, JH Chin, K Mahnke, L von Heydebreck, A Cuillerot, JM Nghiem, P AF Kaufman, Howard L. Russell, Jeffery Hamid, Omid Bhatia, Shailender Terheyden, Patrick D'Angelo, Sandra P. Shih, Kent C. Lebbe, Celeste Linette, Gerald P. Milella, Michele Brownell, Isaac Lewis, Karl D. Lorch, Jochen H. Chin, Kevin Mahnke, Lisa von Heydebreck, Anja Cuillerot, Jean-Marie Nghiem, Paul TI Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID PD-L1 EXPRESSION; PREDICTIVE BIOMARKER; UNITED-STATES; TUMOR-CELLS; POLYOMAVIRUS; IMMUNOTHERAPY; BLOCKADE; SURVIVAL; CANCER; METAANALYSIS AB Background Merkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy. Methods In this multicentre, international, prospective, single-group, open-label, phase 2 trial, patients with stage IV chemotherapy-refractory, histologically confirmed Merkel cell carcinoma (aged >= 18 years) were enrolled from 35 cancer treatment centres and academic hospitals in North America, Europe, Australia, and Asia. Key eligibility criteria were an ECOG performance status of 0 or 1, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, adequate haematological, hepatic, and renal function, and immune-competent status (patients with HIV, immunosuppression, haematological malignancies, and previous organ transplantation were excluded). Patient selection was not based on PD-L1 expression or Merkel cell polyomavirus status. Collection of biopsy material or use of archival tissue for these assessments was mandatory. Avelumab was given intravenously at a dose of 10 mg/kg every 2 weeks. The primary endpoint was confi rmed objective response (complete response or partial response) assessed according to RECIST version 1.1 by an independent review committee. Safety and clinical activity were assessed in all patients who received at least one dose of study drug (the modified intention-to-treat population). This trial is registered with ClinicalTrials.gov as NCT02155647. Findings Between July 25, 2014, and Sept 3, 2015, 88 patients were enrolled and received at least one dose of avelumab. Patients were followed up for a median of 10.4 months (IQR 8.6-13.1). The proportion of patients who achieved an objective response was 28 (31.8% [95.9% CI 21.9-43.1]) of 88 patients, including eight complete responses and 20 partial responses. Responses were ongoing in 23 (82%) of 28 patients at the time of analysis. Five grade 3 treatment-related adverse events occurred in four (5%) patients: lymphopenia in two patients, blood creatine phosphokinase increase in one patient, aminotransferase increase in one patient, and blood cholesterol increase in one patient; there were no treatment-related grade 4 adverse events or treatment-related deaths. Serious treatment-related adverse events were reported in five patients (6%): enterocolitis, infusion-related reaction, aminotransferases increased, chondrocalcinosis, synovitis, and interstitial nephritis (n=1 each). Interpretation Avelumab was associated with durable responses, most of which are still ongoing, and was well tolerated; hence, avelumab represents a new therapeutic option for advanced Merkel cell carcinoma. C1 [Kaufman, Howard L.] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. [Russell, Jeffery] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Bhatia, Shailender] Univ Washington, Med Ctr South Lake Union, Div Oncol, Seattle, WA 98195 USA. [Nghiem, Paul] Univ Washington, Med Ctr South Lake Union, Div Dermatol, Seattle, WA 98195 USA. [Terheyden, Patrick] Univ Lubeck, Dept Dermatol, Lubeck, Germany. [D'Angelo, Sandra P.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. [Shih, Kent C.] Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. [Lebbe, Celeste] Hop St Louis, AP HP, Fac Paris Diderot, Serv Dermatol,INSERM,U976, Paris, France. [Lebbe, Celeste] Hop St Louis, AP HP, Fac Paris Diderot, CIC,INSERM,U976, Paris, France. [Linette, Gerald P.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Milella, Michele] Regina Elena Inst Canc Res, Rome, Italy. [Brownell, Isaac] NCI, Bethesda, MD 20892 USA. [Lewis, Karl D.] Univ Colorado Denver, Sch Med, Div Med Oncol, Aurora, CO USA. [Lorch, Jochen H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chin, Kevin; Mahnke, Lisa; Cuillerot, Jean-Marie] EMD Serono, Billerica, MA USA. [von Heydebreck, Anja] Merck KGaA, Darmstadt, Germany. RP Kaufman, HL (reprint author), Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA. EM hk553@cinj.rutgers.edu FU Merck KGaA, Darmstadt, Germany FX Merck KGaA, Darmstadt, Germany NR 42 TC 9 Z9 9 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2016 VL 17 IS 10 BP 1374 EP 1385 DI 10.1016/S1470-2045(16)30364-3 PG 12 WC Oncology SC Oncology GA EB0SM UT WOS:000387055800039 PM 27592805 ER PT J AU Marina, NM Smeland, S Bielack, SS Bernstein, M Jovic, G Krailo, MD Hook, JM Arndt, C van den Berg, H Brennan, B Brichard, B Brown, KLB Butterfass-Bahloul, T Calaminus, G Daldrup-Link, HE Eriksson, M Gebhardt, MC Gelderblom, H Gerss, J Goldsby, R Goorin, A Gorlick, R Grier, HE Hale, JP Hall, KS Hardes, J Hawkins, DS Helmke, K Hogendoorn, PCW Isakoff, MS Janeway, KA Jurgens, H Kager, L Kuhne, T Lau, CC Leavey, PJ Lessnick, SL Mascarenhas, L Meyers, PA Mottl, H Nathrath, M Papai, Z Randall, RL Reichardt, P Renard, M Safwat, AA Schwartz, CL Stevens, MCG Strauss, SJ Teot, L Werner, M Sydes, MR Whelan, JS AF Marina, Neyssa M. Smeland, Sigbjorn Bielack, Stefan S. Bernstein, Mark Jovic, Gordana Krailo, Mark D. Hook, Jane M. Arndt, Carola van den Berg, Henk Brennan, Bernadette Brichard, Benedicte Brown, Ken L. B. Butterfass-Bahloul, Trude Calaminus, Gabriele Daldrup-Link, Heike E. Eriksson, Mikael Gebhardt, Mark C. Gelderblom, Hans Gerss, Joachim Goldsby, Robert Goorin, Allen Gorlick, Richard Grier, Holcombe E. Hale, Juliet P. Hall, Kirsten Sundby Hardes, Jendrik Hawkins, Douglas S. Helmke, Knut Hogendoorn, Pancras C. W. Isakoff, Michael S. Janeway, Katherine A. Juergens, Heribert Kager, Leo Kuhne, Thomas Lau, Ching C. Leavey, Patrick J. Lessnick, Stephen L. Mascarenhas, Leo Meyers, Paul A. Mottl, Hubert Nathrath, Michaela Papai, Zsuzsanna Randall, R. Lor Reichardt, Peter Renard, Marleen Safwat, Akmal Ahmed Schwartz, Cindy L. Stevens, Michael C. G. Strauss, Sandra J. Teot, Lisa Werner, Mathias Sydes, Matthew R. Whelan, Jeremy S. TI Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial SO LANCET ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; CHILDRENS-ONCOLOGY-GROUP; ADVANCED OSTEOGENIC-SARCOMA; ACUTE MYELOID-LEUKEMIA; STUDY-GROUP PROTOCOLS; MEAN SURVIVAL-TIME; PEDIATRIC-ONCOLOGY; NONMETASTATIC OSTEOSARCOMA; METASTATIC OSTEOSARCOMA; MURAMYL TRIPEPTIDE AB Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (>= 10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m(2), doxorubicin 37.5 mg/m(2) per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m(2) over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m(2)) at 2.8 g/m(2) per day with equidose mesna uroprotection, followed by etoposide 100 mg/m(2) per day over 1 h on days 1-5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials. gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62.1 months (IQR 46.6-76.6); 62.3 months (IQR 46.9-77.1) for the MAP group and 61.1 months (IQR 46.5-75.3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not diff er between treatment groups (hazard ratio [HR] 0.98 [95% CI 0.78-1.23]); hazards were non-proportional (p= 0.0003). The most common grade 3-4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was defi nitely related to their MAP treatment (specifi cally doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results defi ne standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifi que, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. C1 [Marina, Neyssa M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Marina, Neyssa M.; Daldrup-Link, Heike E.] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Smeland, Sigbjorn] Oslo Univ Hosp, Div Canc Med, Oslo, Norway. [Smeland, Sigbjorn] Univ Oslo, Scandinavian Sarcoma Grp, Oslo, Norway. [Smeland, Sigbjorn] Univ Oslo, Inst Clin Med, Oslo, Norway. [Bielack, Stefan S.] Klinikum Stuttgart, Olgahosp, Cooperat Osteosarcoma Study Grp COSS, Stuttgart, Germany. [Bernstein, Mark] Dalhousie Univ, IWK Hlth Ctr, Halifax, NS, Canada. [Jovic, Gordana; Hook, Jane M.; Sydes, Matthew R.] UCL, MRC, Clin Trials Unit, London WC2B 6NH, England. [Krailo, Mark D.] Univ Southern Calif, Keck Med Canter, Dept Prevent Med, Los Angeles, CA USA. [Krailo, Mark D.] Childrens Oncol Grp, Arcadia, CA USA. [Hook, Jane M.] Univ Leeds, Inst Clin Trials Res, Clin Trials Res Unit, Leeds, W Yorkshire, England. [Hook, Jane M.] St James Inst Oncol, Leeds, W Yorkshire, England. [Arndt, Carola] Mayo Clin, Div Pediat & Adolescent Med, Rochester, MN USA. [van den Berg, Henk] Emma Children Hosp, Acad Med Ctr, Amsterdam, Netherlands. [Brennan, Bernadette] Royal Manchester Childrens Hosp, Manchester, Lancs, England. [Brichard, Benedicte] Catholic Univ Louvain, Clin Univ St Luc, Dept Pediat Hematol Oncol, Brussels, Belgium. [Brown, Ken L. B.] Univ British Columbia, Dept Orthopaed, Vancouver, BC, Canada. [Butterfass-Bahloul, Trude] Univ Hosp Muenster, Ctr Clin Trials, Munster, Germany. [Calaminus, Gabriele] Univ Klinikum Bonn, Padiatr Hamatol & Onkol, Bonn, Germany. [Daldrup-Link, Heike E.] Stanford Univ, Dept Radiol, Palo Alto, CA 94304 USA. [Eriksson, Mikael] Skane Univ Hosp, Lund, Sweden. [Eriksson, Mikael] Lund Univ, Lund, Sweden. [Gebhardt, Mark C.] Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Goorin, Allen; Grier, Holcombe E.; Janeway, Katherine A.] Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA 02115 USA. [Gelderblom, Hans; Hogendoorn, Pancras C. W.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Gerss, Joachim] Univ Munster, Inst Biostat & Clin Res, Munster, Germany. [Hardes, Jendrik] Univ Munster, Klin Allgemeine Orthopadie & Tumororthopadie, Munster, Germany. [Juergens, Heribert] Univ Munster, Padiatr Hematol & Onkol, Munster, Germany. [Goldsby, Robert] UCSF Med Ctr Mission Bay, Pediat Oncol, San Francisco, CA USA. [Gorlick, Richard] Childrens Hosp Montefiore, Div Pediat Hematol Oncol, Bronx, NY USA. [Hale, Juliet P.] Newcastle Upon Tyne Hosp NHS Trust, Newcastle Upon Tyne, Tyne & Wear, England. [Hall, Kirsten Sundby] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Oncol, Scandinavian Sarcoma Grp, Oslo, Norway. [Hawkins, Douglas S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Helmke, Knut] AKK Altonaer Kinderkrankenhaus, Abt Padiatr Radiol, Hamburg, Germany. [Isakoff, Michael S.] Connecticut Childrens Med Ctr, Ctr Canc & Blood Disorders, Hartford, CT USA. [Kager, Leo] Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria. [Kuhne, Thomas] Univ Childrens Hosp Basel, Basel, Switzerland. [Lau, Ching C.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Leavey, Patrick J.] UT Southwestern, Dept Pediat, Dallas, TX USA. [Leavey, Patrick J.] Childrens Med Ctr, Dallas, TX 75235 USA. [Lessnick, Stephen L.] Nationwide Childrens Hosp, Ctr Childhood Canc & Blood Disorders, Columbus, OH USA. [Lessnick, Stephen L.] Ohio State Univ, Columbus, OH 43210 USA. [Mascarenhas, Leo] Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles,Dept Pediat, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA. [Meyers, Paul A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. [Mottl, Hubert] Univ Hosp Motol, Pediat Hematol Oncol, Prague, Czech Republic. [Nathrath, Michaela] Tech Univ Munich, Dept Pediat, Pediat Oncol Ctr, Clin Cooperat Grp Osteosarcoma, Munich, Germany. [Nathrath, Michaela] Klinikum Kassel, Dept Pediat Oncol, Kassel, Germany. [Papai, Zsuzsanna] Natl Med Ctr, Dept Oncol, Budapest, Hungary. [Randall, R. Lor] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA. [Reichardt, Peter] HELIOS Klinikum Berlin Buch, Klin Interdisziplinare Onkol, Berlin, Germany. [Renard, Marleen] Univ Hosp Leuven, Dept Pediat Hematooncol, Leuven, Belgium. [Safwat, Akmal Ahmed] Aarhus Univ Hosp, Aarhus C, Denmark. [Schwartz, Cindy L.] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. [Stevens, Michael C. G.] Bristol Royal Hosp Children, Bristol, Avon, England. [Strauss, Sandra J.; Whelan, Jeremy S.] Univ Coll Hosp, Dept Oncol, London, England. [Teot, Lisa] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Werner, Mathias] HELIOS Klinikum Emil von Behring GmbH, Orthopad Pathol, Berlin, Germany. RP Sydes, MR (reprint author), UCL, MRC, Clin Trials Unit, London WC2B 6NH, England. EM mrcctu.euramos@ucl.ac.uk RI GerSS, Joachim/B-5702-2013 FU National Cancer Institute, USA [U10CA180886, U10CA180899, U10CA098543, U10CA098413]; European Science Foundation under the EUROCORES Program European Clinical Trials [ERASCT-2003-980409, MM/NG/EMRC/0202]; St Anna Kinderkrebsforschung, Austria; Fonds National de la Recherche Scientifique, Belgium; Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Belgium; Parents Organization, Czech Republic; Danish Medical Research Council, Denmark; Academy of Finland, Finland; Deutsche Forschungsgemeinschaft, Germany (DFG) [GZ BI 1045/1-1, GZ BI 1045/1-2, JU 203/2-3]; Deutsche Krebshilfe (DKH) [50-2723-Bi2]; Federal Ministry of Education and Research, Germany [BMBF 01KN1105]; Semmelweis Foundation, Hungary; ZonMw (Council for Medical Research), Netherlands; Research Council of Norway, Norway; Scandinavian Sarcoma Group, Sweden; Swiss Paediatric Oncology Group, Switzerland; Cancer Research UK [CRUK/05/013]; Medical Research Council; National Institute for Health Research University College London Hospitals; Biomedical Research Centre, UK FX EURAMOS-1 is an academic clinical trial funded through multiple national and international government agencies and cancer charities: National Cancer Institute, USA (provides funding to the Children's Oncology Group in North America, Australasia, Switzerland; grant numbers U10CA180886, U10CA180899, U10CA098543, and U10CA098413); European Science Foundation under the EUROCORES Program European Clinical Trials (through contract number ERASCT-2003-980409 of the European Commission, DG Research, FP6, reference number MM/NG/EMRC/0202); St Anna Kinderkrebsforschung, Austria; Fonds National de la Recherche Scientifique, Belgium; Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Belgium; Parents Organization, Czech Republic; Danish Medical Research Council, Denmark; Academy of Finland, Finland; Deutsche Forschungsgemeinschaft, Germany (DFG reference number GZ BI 1045/1-1 & 1-2, JU 203/2-3; Deutsche Krebshilfe (DKH reference number 50-2723-Bi2) and Federal Ministry of Education and Research, Germany (BMBF 01KN1105); Semmelweis Foundation, Hungary; ZonMw (Council for Medical Research), Netherlands; Research Council of Norway, Norway; Scandinavian Sarcoma Group, Sweden; Swiss Paediatric Oncology Group, Switzerland; Cancer Research UK (CRUK/05/013); Medical Research Council; National Institute for Health Research University College London Hospitals; and Biomedical Research Centre, UK. NR 42 TC 7 Z9 7 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2016 VL 17 IS 10 BP 1396 EP 1408 DI 10.1016/S1470-2045(16)30214-5 PG 13 WC Oncology SC Oncology GA EB0SM UT WOS:000387055800041 PM 27569442 ER PT J AU O'Brien, S Jones, JA Coutre, SE Mato, AR Hillmen, P Tam, C Osterborg, A Siddiqi, T Thirman, MJ Furman, RR Ilhan, O Keating, MJ Call, TG Brown, JR Stevens-Brogan, M Li, YF Clow, F James, DF Chu, AD Hallek, M Stilgenbauer, S AF O'Brien, Susan Jones, Jeffrey A. Coutre, Steven E. Mato, Anthony R. Hillmen, Peter Tam, Constantine Osterborg, Anders Siddiqi, Tanya Thirman, Michael J. Furman, Richard R. Ilhan, Osman Keating, Michael J. Call, Timothy G. Brown, Jennifer R. Stevens-Brogan, Michelle Li, Yunfeng Clow, Fong James, Danelle F. Chu, Alvina D. Hallek, Michael Stilgenbauer, Stephan TI Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study SO LANCET ONCOLOGY LA English DT Article ID RITUXIMAB; THERAPY; TRIAL; ALEMTUZUMAB; METHYLPREDNISOLONE; CYCLOPHOSPHAMIDE; FLUDARABINE; GUIDELINES; MUTATIONS; DIAGNOSIS AB Background The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. Methods We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age >= 18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Findings Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11 . 5 months (IQR 11.1-13.8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall response according to investigator assessment. In an extended analysis with median follow-up of 27.6 months (IQR 14.6-27.7), the investigator-assessed overall response was reported in 120 patients (83%, 95% CI 76-89). 24-month progression-free survival was 63% (95% CI 54-70) and 24-month overall survival was 75% (67-81). Sustained haematological improvement was noted in 72 (79%) of 91 patients with any baseline cytopenia. No clinically relevant changes were noted from baseline to 6 months or 24 months in IgA (median 0.4 g/L at baseline, 0.6 g/L at 6 months, and 0.7 g/L at 24 months), IgG (5.0 g/L, 5.3 g/L, and 4.9 g/L), or IgM (0.3 g/L at each timepoint) concentrations. Common reasons for treatment discontinuation were progressive disease in 34 (24%) patients and adverse events, unacceptable toxicity, or death in 24 (17%) patients. Major bleeding occurred in 13 (9%) patients (11 [8%] grade 3-4). Grade 3 or worse infections occurred in 43 (30%) patients, including pneumonia in 19 (13%) patients. In the extended analysis, 38 patients died, 18 as a result of adverse events (four pneumonia, three chronic lymphocytic leukaemia, two Richter's syndrome, two sepsis, and one each of acute myocardial infarction, septic shock, encephalopathy, general deterioration in physical health, abnormal hepatic function, myocardial infarction, and renal infarction). Interpretation A high proportion of patients had an overall response to ibrutinib and the risk: benefi t profi le was favourable, providing further evidence for use of ibrutinib in the most diffi cult subset of patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma. Ibrutinib represents a clinical advance in the treatment of patients with del17p chronic lymphocytic leukaemia and has been incorporated into treatment algorithms as a primary treatment for these patients. Funding Pharmacyclics LLC, an AbbVie Company. C1 [O'Brien, Susan; Keating, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [O'Brien, Susan] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. [Jones, Jeffrey A.] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA. [Coutre, Steven E.] Stanford Univ, Sch Med, Div Hematol, Stanford Canc Ctr, Stanford, CA 94305 USA. [Mato, Anthony R.] Univ Penn, Ctr Chron Lymphocyt Leukemia, Philadelphia, PA 19104 USA. [Mato, Anthony R.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [Tam, Constantine] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia. [Osterborg, Anders] Karolinska Univ Hosp Solna, Dept Hematol, Stockholm, Sweden. [Siddiqi, Tanya] City Hope Natl Med Ctr, Dept Hematol Hematopoiet Cell Transplantat, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Thirman, Michael J.] Univ Chicago Med, Sect Hematol Oncol, Chicago, IL USA. [Furman, Richard R.] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY USA. [Ilhan, Osman] Ankara Univ, Sch Med, Dept Hematol, Ankara, Turkey. [Call, Timothy G.] Mayo Clin, Div Hematol, Rochester, MN USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F.; Chu, Alvina D.] Pharmacyclics LLC, Sunnyvale, CA USA. [Hallek, Michael] Univ Hosp Cologne, Dept Internal Med, Cologne, Germany. [Stilgenbauer, Stephan] Univ Ulm, Dept Internal Med 3, Ulm, Germany. RP O'Brien, S (reprint author), Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Sue & Ralph Stern Ctr Clin Trials & Res, Orange, CA 92868 USA.; O'Brien, S (reprint author), Univ Calif Irvine, Div Hematol Oncol, Orange, CA 92868 USA. EM obrien@uci.edu FU Pharmacyclics LLC, an AbbVie Company FX We thank the patients who participated in the study, their supporters, and the investigators and clinical research staff from the study centres. This manuscript was developed with editorial support from Luana Atherly-Henderson from Nexus Global Group Science LLC and funded by Pharmacyclics LLC, an AbbVie Company. NR 30 TC 6 Z9 6 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2016 VL 17 IS 10 BP 1409 EP 1418 DI 10.1016/S1470-2045(16)30212-1 PG 10 WC Oncology SC Oncology GA EB0SM UT WOS:000387055800042 PM 27637985 ER PT J AU Fontecha, CG Roca, I Barber, I Menendez, ME Collado, D Mascarenhas, VV Barrera-Ochoa, S Soldado, F AF Fontecha, Cesar G. Roca, Isabel Barber, Ignasi Menendez, Mariano E. Collado, Diego Mascarenhas, Vasco V. Barrera-Ochoa, Sergio Soldado, Francisco TI Femoral head bone viability after free vascularized fibular grafting for osteonecrosis: SPECT/CT study SO MICROSURGERY LA English DT Article ID SCINTIGRAPHY; NECROSIS; MRI; HIP AB PurposeTo evaluate femoral head bone viability following free vascularized fibular grafting (FVFG) for osteonecrosis using SPECT/CT imaging. MethodsTen hips (9 patients) with osteonecrosis of the femoral head (ONFH) undergoing FVFG were prospectively enrolled. Four cases showed ARCO stage II, while six showed ARCO stage III. The mean age at surgery was 15.7 years (range, 13-22 years). Hip Harris Score (HHS) was measured pre- and post-operative. Bone scintigraphy with SPECT/CT was performed at 2 weeks and 6 months following surgery. ResultsMean follow-up was 4.0 years (range, 2-5.9 years). Mean HHS increased from 37.2 to 92.3. SPECT/CT findings revealed a progressive increase of femoral head uptake in all cases, suggesting subchondral graft bone viability. No progressive deformation of the femoral head was evidenced in radiographic evaluation at final follow-up. ConclusionsThis study demonstrates FVFG's capacity for revitalizing femoral head subchondral bone grafting in patients with ONFH, surgically treated following Urbaniak's technique. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:573-577, 2016. C1 [Fontecha, Cesar G.] Hosp Univ Vall Dhebron, Pediat Orthopaed Unit, Barcelona, Spain. [Roca, Isabel] Hosp Univ Vall Dhebron, Dept Nucl Med, Barcelona, Spain. [Barber, Ignasi] Hosp Univ Vall Dhebron, Dept Pediat Radiol, Barcelona, Spain. [Menendez, Mariano E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Collado, Diego] Hosp Univ Vall Dhebron, Hip Surg Unit, Barcelona, Spain. [Mascarenhas, Vasco V.] Hosp Da Luz, Dept Radiol, UIME, Lisbon, Portugal. [Barrera-Ochoa, Sergio] Hosp Univ Vall Dhebron, Hand Surg, Barcelona, Spain. [Soldado, Francisco] Univ Barcelona, Pediat Hand Surg & Microsurg, Hosp St Joan De Deu, Barcelona, Spain. RP Soldado, F (reprint author), Hosp St Joan de Deu, Passeig St Joan de Deu 2, Barcelona 08950, Spain. EM drsoldado@cirugiamanoinfantil.com OI Mascarenhas, Vasco/0000-0002-5451-5021; Fontecha, Cesar G/0000-0002-6363-433X FU Fundacao Santa-Maria-Silva FX Grant sponsor: Fundacao Santa-Maria-Silva. NR 27 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0738-1085 EI 1098-2752 J9 MICROSURG JI Microsurgery PD OCT PY 2016 VL 36 IS 7 BP 573 EP 577 DI 10.1002/micr.22452 PG 5 WC Surgery SC Surgery GA EB2UD UT WOS:000387217200007 PM 26214835 ER PT J AU Didiot, MC Hall, LM Coles, AH Haraszti, RA Godinho, BMDC Chase, K Sapp, E Ly, S Alterman, JF Hassler, MR Echeverria, D Raj, L Morrissey, DV DiFiglia, M Aronin, N Khvorova, A AF Didiot, Marie-Cecile Hall, Lauren M. Coles, Andrew H. Haraszti, Reka A. Godinho, Bruno M. D. C. Chase, Kathryn Sapp, Ellen Ly, Socheata Alterman, Julia F. Hassler, Matthew R. Echeverria, Dimas Raj, Lakshmi Morrissey, David V. DiFiglia, Marian Aronin, Neil Khvorova, Anastasia TI Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing SO MOLECULAR THERAPY LA English DT Article ID EXTRACELLULAR VESICLES; IN-VITRO; CANCER-CELLS; DISEASE; PROTEIN; BRAIN; MICRORNAS; EFFICACY; MICE; COMMUNICATION AB Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for the treatment of neurological disorders, such as Huntington's disease. Small, endogenous vesicles known as exosomes have the potential to act as oligonucleotide delivery vehicles, but robust and scalable methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load into exosomes upon co-incubation, without altering vesicle size distribution or integrity. Exosomes loaded with hsiRNAs targeting Huntingtin mRNA were efficiently internalized by mouse primary cortical neurons and promoted dose-dependent silencing of Huntingtin mRNA and protein. Unilateral infusion of hsiRNA-loaded exosomes, but not hsiRNAs alone, into mouse striatum resulted in bilateral oligonucleotide distribution and statistically significant bilateral silencing of up to 35% of Huntingtin mRNA. The broad distribution and efficacy of hsiRNA-loaded exosomes delivered to brain is expected to advance the development of therapies for the treatment of Huntington's disease and other neurodegenerative disorders. C1 [Didiot, Marie-Cecile; Hall, Lauren M.; Coles, Andrew H.; Haraszti, Reka A.; Godinho, Bruno M. D. C.; Chase, Kathryn; Ly, Socheata; Alterman, Julia F.; Hassler, Matthew R.; Echeverria, Dimas; Aronin, Neil; Khvorova, Anastasia] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA USA. [Didiot, Marie-Cecile; Coles, Andrew H.; Haraszti, Reka A.; Godinho, Bruno M. D. C.; Ly, Socheata; Alterman, Julia F.; Hassler, Matthew R.; Echeverria, Dimas; Khvorova, Anastasia] Univ Massachusetts, Sch Med, Dept Mol Med, Worcester, MA USA. [Hall, Lauren M.; Chase, Kathryn; Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Sapp, Ellen; DiFiglia, Marian] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Charlestown, MA USA. [Raj, Lakshmi; Morrissey, David V.] Novartis Inst Biomed Res Inc, Cambridge, MA USA. RP Aronin, N; Khvorova, A (reprint author), Univ Massachusetts, Sch Med, 368 Plantat St, Worcester, MA 01605 USA. EM neil.aronin@umassmed.edu; anastasia.khvorova@umassmed.edu FU Novartis Institute of Biomedical Research; NIH [UH2-TR000888, UH3-4UH3TR000888-03, NS38194, S10 OD020012, R01 GM108803]; UMass CCTS [UL1 TR000161]; CHDI Foundation [A-6119] FX We thank the members of the Khvorova and Aronin Laboratories, NIH Extracellular RNA Consortium, and CHDI Foundation for helpful discussions. We thank the Sena Esteves and Mello laboratories for excellent technical assistance and guidance on microscopy. We thank Maire Osborn and Darryl Conte for editing the manuscript. M.-C.D. is supported by the Novartis Institute of Biomedical Research. This work is supported in part by grants from the NIH UH2-TR000888 and UH3-4UH3TR000888-03, NIH NS38194, NIH S10 OD020012, R01 GM108803, S10 OD020012, UMass CCTS UL1 TR000161 and CHDI Foundation (Research Agreement A-6119). The authors declare no conflict of interest. M.-C.D., N.A., and A.K. provided the conceptual framework for the study. M.-C.D., L.M.H., A.H.C., R.A.H., N.A., and A.K. designed experiments and discussed the results. M.-C.D. and A.K. wrote the manuscript. M.-C.D. contributed to experiments shown in Figures 1 to 5 and Figures S1 to S8; L.M.H. contributed to Figures 2 to 5 and Figures S4, S6 to S8; A.H.C., B.G. and K.C. contributed to Figures 3 to 5 and Figures S6 to S8; R.A.H. contributed to Figures 2 and 4 and Figures S1D and S2C; S.L. contributed to Figure 1; E.S. and M.D. performed EM for Figure 1 and Supplementary Figures S1 and S3 and Western blots for Figure 3 and Supplementary Figure S5; J.F.A., D.E., and M.R.H. contributed to synthesis and preparation of hsiRNAs. L.R. and D.V.M. contributed to result discussion. CHDI Foundation is a privately funded nonprofit biomedical research organization exclusively dedicated to developing Huntington's disease therapeutics and conducts research in a number of different ways. Research was conducted at the RNA Therapeutics Institute. NR 52 TC 2 Z9 2 U1 9 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD OCT PY 2016 VL 24 IS 10 BP 1836 EP 1847 DI 10.1038/mt.2016.126 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA EB3IF UT WOS:000387256700013 PM 27506293 ER PT J AU Kumar, DKV Eimer, WA Tanzi, RE Moir, RD AF Kumar, Deepak Kumar Vijaya Eimer, William A. Tanzi, Rudolph E. Moir, Robert D. TI Alzheimer's disease: the potential therapeutic role of the natural antibiotic amyloid-beta peptide SO NEURODEGENERATIVE DISEASE MANAGEMENT LA English DT Editorial Material DE Alzheimer's disease; amyloid-beta; infection ID ANTIMICROBIAL PEPTIDE; DEPENDENT MECHANISM; OLIGOMERS; PROTEIN; LL-37 C1 [Kumar, Deepak Kumar Vijaya; Eimer, William A.; Tanzi, Rudolph E.; Moir, Robert D.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. [Kumar, Deepak Kumar Vijaya; Eimer, William A.; Tanzi, Rudolph E.; Moir, Robert D.] Harvard Med Sch, Charlestown, MA 02129 USA. RP Moir, RD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA.; Moir, RD (reprint author), Harvard Med Sch, Charlestown, MA 02129 USA. EM moir@helix.mgh.harvard.edu NR 19 TC 1 Z9 1 U1 5 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2024 EI 1758-2032 J9 NEURODEGENER DIS MAN JI Neurodegener. Dis. Manag. PD OCT PY 2016 VL 6 IS 5 BP 345 EP 348 DI 10.2217/nmt-2016-0035 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA EB5ZM UT WOS:000387459800001 PM 27599536 ER PT J AU Gong, J Hutter, CM Newcomb, PA Ulrich, CM Bien, SA Campbell, PT Baron, JA Berndt, SI Bezieau, S Brenner, H Casey, G Chan, AT Chang-Claude, J Du, MM Duggan, D Figueiredo, JC Gallinger, S Giovannucci, EL Haile, RW Harrison, TA Hayes, RB Hoffmeister, M Hopper, JL Hudson, TJ Jeon, J Jenkins, MA Kocarnik, J Kury, S Le Marchand, L Lin, Y Lindor, NM Nishihara, R Ogino, S Potter, JD Rudolph, A Schoen, RE Schrotz-King, P Seminara, D Slattery, ML Thibodeau, SN Thornquist, M Toth, R Wallace, R White, E Jiao, S Lemire, M Hsu, L Peters, U AF Gong, Jian Hutter, Carolyn M. Newcomb, Polly A. Ulrich, Cornelia M. Bien, Stephanie A. Campbell, Peter T. Baron, John A. Berndt, Sonja I. Bezieau, Stephane Brenner, Hermann Casey, Graham Chan, Andrew T. Chang-Claude, Jenny Du, Mengmeng Duggan, David Figueiredo, Jane C. Gallinger, Steven Giovannucci, Edward L. Haile, Robert W. Harrison, Tabitha A. Hayes, Richard B. Hoffmeister, Michael Hopper, John L. Hudson, Thomas J. Jeon, Jihyoun Jenkins, Mark A. Kocarnik, Jonathan Kury, Sebastien Le Marchand, Loic Lin, Yi Lindor, Noralane M. Nishihara, Reiko Ogino, Shuji Potter, John D. Rudolph, Anja Schoen, Robert E. Schrotz-King, Petra Seminara, Daniela Slattery, Martha L. Thibodeau, Stephen N. Thornquist, Mark Toth, Reka Wallace, Robert White, Emily Jiao, Shuo Lemire, Mathieu Hsu, Li Peters, Ulrike CA CCFR GECCO TI Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer SO PLOS GENETICS LA English DT Article ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; ENVIRONMENT INTERACTION; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; POOLED ANALYSIS; COLON-CANCER; ASSOCIATION; METAANALYSIS; MTOR; POPULATION AB Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76x10(-8); permuted pvalue 3.51x10 -8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1x10(-4)) and TT genotypes (OR, 0.62 [95% CI, 0.51-0.75]; P = 1.3x10(-6)) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk. C1 [Gong, Jian; Newcomb, Polly A.; Ulrich, Cornelia M.; Bien, Stephanie A.; Du, Mengmeng; Harrison, Tabitha A.; Jeon, Jihyoun; Kocarnik, Jonathan; Lin, Yi; Potter, John D.; Thornquist, Mark; White, Emily; Jiao, Shuo; Hsu, Li; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Hutter, Carolyn M.] NHGRI, Div Genom Med, Bethesda, MD 20892 USA. [Ulrich, Cornelia M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kury, Sebastien] CHU Nantes, Serv Genet Med, Nantes, France. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Casey, Graham; Figueiredo, Jane C.; Haile, Robert W.] Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Med Sch, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Gallinger, Steven] Univ Hlth Network, Toronto Gen Hosp, Dept Surg, Toronto, ON, Canada. [Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia. [Hudson, Thomas J.; Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Nishihara, Reiko] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA USA. [Ogino, Shuji] Harvard Sch Publ Hlth, Dept Epidemiol, Harvard Med Sch, Boston, MA USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA. [Schrotz-King, Petra; Toth, Reka] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany. [Schrotz-King, Petra; Toth, Reka] German Canc Res Ctr, Heidelberg, Germany. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Genet, Rochester, MN USA. [Wallace, Robert] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM upeters@fhcrc.org RI Brenner, Hermann/B-4627-2017; OI Brenner, Hermann/0000-0002-6129-1572; Hayes, Richard/0000-0002-0918-661X; Bien, Stephanie/0000-0002-8713-4583; Hoffmeister, Michael/0000-0002-8307-3197 FU National Cancer Institute, National Institutes of Health, U.S. Department of Health, and Human Services [U01 CA137088, R01 CA059045, R01 CA120582]; Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); National Institutes of Health [R01 CA60987, UM1 CA167551, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, K07 CA190673, P50 CA 127003, R01 CA137178, P01 CA 087969, UM1 CA186107, R01 CA151993, R35 CA197735]; National Cancer Institute, National Institutes of Health [U01 CA122839, R01 CA143237]; German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; Ontario Research Fund; Canadian Institutes of Health Research; Ontario Institute for Cancer Research from the Ontario Ministry of Research and Innovation; Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]; NIH [U01 HG004446]; NIH GEI [U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; The National Institutes of Health [K07190673, R01 CA042182, R37 CA54281, P01 CA033619, R01 CA63464, U01 CA074783, R01 CA076366, K05 CA154337] FX GECCO is supported by National Cancer Institute, National Institutes of Health, U.S. Department of Health, and Human Services (U01 CA137088; R01 CA059045; R01 CA120582). ASTERISK is supported by a Hospital Clinical Research Program (PHRC), the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC). COLO2&3 is supported by National Institutes of Health (R01 CA60987). CCFR is supported by National Institutes of Health (UM1 CA167551) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome wide scan was supported by the National Cancer Institute, National Institutes of Health by U01 CA122839 and R01 CA143237 to Graham Casey. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CFR. The following Colon CFR centers contributed data to this manuscript and were supported by National Institutes of Health: Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), and Seattle Colorectal Cancer Family Registry (U01/U24 CA074794). DACHS is supported by German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS is supported by National Institutes of Health (R01 CA48998 to MLS). HPFS is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, R35 CA197735, K07 CA190673, and P50 CA 127003), NHS by the National Institutes of Health (R01 CA137178, P01 CA 087969, UM1 CA186107, R01 CA151993, R35 CA197735, K07190673, and P50 CA 127003,) and PHS by the National Institutes of Health (R01 CA042182). MEC is supported by National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464). OFCCR is supported by National Institutes of Health through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783, see CCFR section above). Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research through generous support from the Ontario Ministry of Research and Innovation. PLCO is supported by Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager, M et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 2007 May;39(5):645-9), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir, L et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009 Sep;41(9):986-90, and Petersen, GM et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010 Mar;42(3):224-8), and the Lung Cancer and Smoking study (Landi MT, et al.; A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. Am J Hum Genet. 2009 Nov;85(5):679-91). The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http.//cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH is supported by National Institutes of Health (R01 CA076366 to P.A. Newcomb). VITAL is supported byNational Institutes of Health (K05 CA154337). WHI is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 90 TC 0 Z9 0 U1 5 U2 5 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 OCT PY 2016 VL 12 IS 10 AR e1006296 DI 10.1371/journal.pgen.1006296 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA EA5SM UT WOS:000386683300006 PM 27723779 ER PT J AU Johnson, EC Bjelland, DW Howrigan, DP Abdellaoui, A Breen, G Borglum, A Cichon, S Degenhardt, F Forstner, AJ Frank, J Genovese, G Heilmann-Heimbach, S Herms, S Hoffman, P Maier, W Mattheisen, M Morris, D Mowry, B Mueller-Mhysok, B Neale, B Nenadic, I Noethen, MM O'Dushlaine, C Rietschel, M Ruderfer, DM Rujescu, D Schulze, TG Simonson, MA Stahl, E Strohmaier, J Witt, SH Sullivan, PF Keller, MC AF Johnson, Emma C. Bjelland, Douglas W. Howrigan, Daniel P. Abdellaoui, Abdel Breen, Gerome Borglum, Anders Cichon, Sven Degenhardt, Franziska Forstner, Andreas J. Frank, Josef Genovese, Giulio Heilmann-Heimbach, Stefanie Herms, Stefan Hoffman, Per Maier, Wolfgang Mattheisen, Manuel Morris, Derek Mowry, Bryan Mueller-Mhysok, Betram Neale, Benjamin Nenadic, Igor Noethen, Markus M. O'Dushlaine, Colm Rietschel, Marcella Ruderfer, Douglas M. Rujescu, Dan Schulze, Thomas G. Simonson, Matthew A. Stahl, Eli Strohmaier, Jana Witt, Stephanie H. Sullivan, Patrick F. Keller, Matthew C. CA Psychiatric Genomics Consortium TI No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; EXTENDED TRACTS; CANDIDATE GENES; RISK; STRATIFICATION; POPULATIONS; DEPRESSION; DISORDER; LOCI AB It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (beta = 16.1, CI(beta) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (beta = 4.86, CI(beta) = [0.90,8.83], Z = 2.40, p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest. C1 [Johnson, Emma C.; Keller, Matthew C.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Johnson, Emma C.; Bjelland, Douglas W.; Keller, Matthew C.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Howrigan, Daniel P.; Neale, Benjamin] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Howrigan, Daniel P.; Genovese, Giulio; Neale, Benjamin; Stahl, Eli] Broad Inst, Cambridge, MA USA. [Howrigan, Daniel P.; Neale, Benjamin] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Abdellaoui, Abdel] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Breen, Gerome] Kings Coll London, Dept Social Genet & Dev Psychiat, London, England. [Borglum, Anders] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark. [Borglum, Anders] Aarhus Univ, iSEQ, Ctr Integrat Sequencing, Aarhus, Denmark. [Borglum, Anders] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Borglum, Anders] Aarhus Univ Hosp, Dept P, Risskov, Denmark. [Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffman, Per; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Cichon, Sven; Herms, Stefan; Hoffman, Per] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Cichon, Sven] Genom Imaging Res Ctr Juelich, Struct & Funct Org Brain, Inst Neurosci & Med INM 1, Julich, Germany. [Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffman, Per; Mattheisen, Manuel; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Frank, Josef; Rietschel, Marcella; Strohmaier, Jana; Witt, Stephanie H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany. [Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany. [Morris, Derek] St James Hosp, Trinity Ctr Hlth Sci, Sch Med, Dept Psychiat, Dublin, Ireland. [Morris, Derek] St James Hosp, Trinity Ctr Hlth Sci, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland. [Mowry, Bryan] Queensland Ctr Schizophrenia Mental Hlth Res, Ctr Mental Hlth, Wacol, Australia. [Mowry, Bryan] Univ Queensland, Dept Psychiat, Brisbane, Qld, Australia. [Mueller-Mhysok, Betram] Max Planck Inst Psychiat, Munich, Germany. [Mueller-Mhysok, Betram] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Mueller-Mhysok, Betram] Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England. [Nenadic, Igor] Jena Univ Hosp, Dept Psychiat & Psychotherapy, Jena, Germany. [O'Dushlaine, Colm] Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin, Ireland. [O'Dushlaine, Colm] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland. [Ruderfer, Douglas M.; Stahl, Eli] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [Rujescu, Dan] Univ Munich, Dept Psychiat, Mol & Clin Neurobiol, Munich, Germany. [Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, Halle, Germany. [Schulze, Thomas G.] Univ Munich, IPPG, Munich, Germany. [Simonson, Matthew A.] Mayo Clin, Dept Hlth Sci, Div Biomed Stat & Informat, Rochester, MN USA. [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Johnson, EC; Keller, MC (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.; Johnson, EC; Keller, MC (reprint author), Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. EM Emma.C.Johnson@colorado.edu; matthew.c.keller@gmail.com OI Johnson, Emma/0000-0003-0394-777X; murray, robin/0000-0003-0829-0519; Dinan, Timothy/0000-0002-2316-7220; McIntosh, Andrew/0000-0002-0198-4588 FU National Institutes of Health; National Institute of Mental Health [K01MH085812, R01MH100141, MH085520] FX This study was supported by grants from the National Institutes of Health and the National Institute of Mental Health (grants K01MH085812 and R01MH100141 to MCK and MH085520 to the Psychiatric Genomics Consortium). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 0 Z9 0 U1 5 U2 5 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 OCT PY 2016 VL 12 IS 10 AR e1006343 DI 10.1371/journal.pgen.1006343 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA EA5SM UT WOS:000386683300014 PM 27792727 ER PT J AU Kiando, SR Tucker, NR Castro-Vega, LJ Katz, A D'Escamard, V Treard, C Fraher, D Albuisson, J Kadian-Dodov, D Ye, Z Austin, E Yang, ML Hunker, K Barlassina, C Cusi, D Galan, P Empana, JP Jouven, X Gimenez-Roqueplo, AP Bruneval, P Kim, ESH Olin, JW Gornik, HL Azizi, M Plouin, PF Ellinor, PT Kullo, IJ Milan, DJ Ganesh, SK Boutouyrie, P Kovacic, JC Jeunemaitre, X Bouatia-Naji, N AF Kiando, Soto Romuald Tucker, Nathan R. Castro-Vega, Luis-Jaime Katz, Alexander D'Escamard, Valentina Treard, Cyrielle Fraher, Daniel Albuisson, Juliette Kadian-Dodov, Daniella Ye, Zi Austin, Erin Yang, Min-Lee Hunker, Kristina Barlassina, Cristina Cusi, Daniele Galan, Pilar Empana, Jean-Philippe Jouven, Xavier Gimenez-Roqueplo, Anne-Paule Bruneval, Patrick Kim, Esther Soo Hyun Olin, Jeffrey W. Gornik, Heather L. Azizi, Michel Plouin, Pierre-Francois Ellinor, Patrick T. Kullo, Iftikhar J. Milan, David J. Ganesh, Santhi K. Boutouyrie, Pierre Kovacic, Jason C. Jeunemaitre, Xavier Bouatia-Naji, Nabila TI PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance SO PLOS GENETICS LA English DT Article ID CORONARY-ARTERY DISSECTION; GENOME-WIDE ASSOCIATION; HUMAN ENDOTHELIAL-CELLS; RISK-FACTORS; METAANALYSIS; PREVALENCE; POPULATION; CANDIDATES; MIGRAINE; OUTCOMES AB Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (similar to 80%) but its pathophysiology is unclear. We analyzed similar to 26K common variants (MAF> 0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P< 10(-4)) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1).Three additional case control cohorts including 512 cases and 669 replicated this result and overall reached the genomic level of significance (OR = 1.39, P = 7.4x10(-10), 1,154 cases and 3,895 controls). The top variant, rs9349379, is intronic to PHACTR1, a risk locus for coronary artery disease, migraine, and cervical artery dissection. The analyses of geometrical parameters of carotids from similar to 2,500 healthy volunteers indicate higher intima media thickness (P = 1.97x10(-4)) and wall to lumen ratio (P = 0.002) in rs9349379-A carriers, suggesting indices of carotid hypertrophy previously described in carotids of FMD patients. Immunohistochemistry detected PHACTR1 in endothelium and smooth muscle cells of FMD and normal human carotids. The expression of PHACTR1 by genotypes in primary human fibroblasts showed higher expression in rs9349379-A carriers (N = 86, P = 0.003). Phactr1 knockdown in zebrafish resulted in dilated vessels indicating subtle impaired vascular development. We report the first susceptibility locus for FMD and provide evidence for a complex genetic pattern of inheritance and indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases. C1 [Kiando, Soto Romuald; Castro-Vega, Luis-Jaime; Treard, Cyrielle; Albuisson, Juliette; Empana, Jean-Philippe; Jouven, Xavier; Gimenez-Roqueplo, Anne-Paule; Bruneval, Patrick; Plouin, Pierre-Francois; Boutouyrie, Pierre; Jeunemaitre, Xavier; Bouatia-Naji, Nabila] UMR970 Paris Cardiovasc Res Ctr PARCC, INSERM, F-75015 Paris, France. [Kiando, Soto Romuald; Castro-Vega, Luis-Jaime; Treard, Cyrielle; Albuisson, Juliette; Empana, Jean-Philippe; Jouven, Xavier; Gimenez-Roqueplo, Anne-Paule; Bruneval, Patrick; Azizi, Michel; Plouin, Pierre-Francois; Boutouyrie, Pierre; Jeunemaitre, Xavier; Bouatia-Naji, Nabila] Paris Descartes Univ, Sorbonne Paris Cite, F-75006 Paris, France. [Tucker, Nathan R.; Fraher, Daniel; Ellinor, Patrick T.; Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Tucker, Nathan R.; Fraher, Daniel; Ellinor, Patrick T.; Milan, David J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Katz, Alexander; Yang, Min-Lee; Hunker, Kristina; Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Katz, Alexander; Yang, Min-Lee; Hunker, Kristina; Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [D'Escamard, Valentina; Kadian-Dodov, Daniella; Olin, Jeffrey W.; Kovacic, Jason C.] Marie Josee & Henry R Kravis Cardiovasc Hlth Ctr, Zena & Michael A Wiener Cardiovasc Inst, Icahn Sch Med, One Gustave L Levy Pl,Box 1030, New York, NY 10029 USA. [Albuisson, Juliette; Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, Referral Ctr Rare Vasc Dis, F-75015 Paris, France. [Albuisson, Juliette; Gimenez-Roqueplo, Anne-Paule; Jeunemaitre, Xavier] Hop Europeen Georges Pompidou, AP HP, Dept Genet, F-75015 Paris, France. [Ye, Zi; Austin, Erin; Kullo, Iftikhar J.] Mayo Clin, Dept Cardiovasc Dis, Rochester, MN 55905 USA. [Barlassina, Cristina] Dept Hlth Sci, Genom & Bioinformat Unit, Viale Ortles 22-4, I-20142 Milan, Italy. [Barlassina, Cristina] Univ Milan, Chair & Grad Sch Nephrol, Div Nephrol, San Paolo Hosp, I-20142 Milan, Italy. [Cusi, Daniele] Italian Natl Ctr Res, Inst Biomed Technol, Via Flli Cervi 93, I-20090 Segrate, Italy. [Galan, Pilar] UMR Univ Paris 13 Inserm U 557 INRA U 1125 CNAM, Sorbonne Paris Cite, Nutr Epidemiol Res Grp, F-93017 Bobigny, France. [Jouven, Xavier] Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, F-75015 Paris, France. [Kim, Esther Soo Hyun; Gornik, Heather L.] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44195 USA. [Azizi, Michel; Plouin, Pierre-Francois] Hop Europeen Georges Pompidou, AP HP, Dept Hypertens, F-75015 Paris, France. [Azizi, Michel] Hop Europeen Georges Pompidou, INSERM, Clin Invest Ctr CIC1418, F-75015 Paris, France. [Boutouyrie, Pierre] Hop Europeen Georges Pompidou, AP HP, Dept Pharmacol, F-75015 Paris, France. RP Bouatia-Naji, N (reprint author), UMR970 Paris Cardiovasc Res Ctr PARCC, INSERM, F-75015 Paris, France.; Bouatia-Naji, N (reprint author), Paris Descartes Univ, Sorbonne Paris Cite, F-75006 Paris, France. EM nabila.bouatia-naji@inserm.fr RI BOUATIA-NAJI, NABILA/D-5863-2013 FU GENET-FMD [ANR-13-JSV1-0002-01]; ANR GDPM2 [2010-BLANC-1129-02]; National French clinical grant (PHRC ARCADIA-PROFILE); Fondation pour la recherche Medicale (FRM MEDYA); Fondation pour la recherche Medicale [Equipe FRM 2015-2018 DEQ20150331716]; European funding FP7 HYPERGENES [FP7-HEALTH-F4-2007-201550]; National Institutes of Health [R01-HL127692, T32HL007824, 1RO1HL092577, R01HL128914, K24HL105780]; Doris Duke Charitable Foundation [2013104]; American Heart Association [13EIA14220013]; Fondation Leducq [14CVD01]; National Institutes of Health, National Center for Research Resources, CTSA, Cleveland, Ohio [1UL1RR024989] FX This study was supported by a Young Investigator funding GENET-FMD (ANR-13-JSV1-0002-01 to NBN), ANR GDPM2 (2010-BLANC-1129-02 to XJ), National French clinical grant (PHRC ARCADIA-PROFILE to PFP) and Fondation pour la recherche Medicale support (FRM MEDYA to MA and Equipe FRM 2015-2018 DEQ20150331716 to XJ and NBN), in part by a European funding FP7 HYPERGENES (FP7-HEALTH-F4-2007-201550 to XJ and DC), the National Institutes of Health (R01-HL127692 to DJM, and T32HL007824 to JK and VDE, and 1RO1HL092577, R01HL128914, K24HL105780 to PTE), the Doris Duke Charitable Foundation (Grant #:2013104 to SKG), an Established Investigator Award from the American Heart Association (13EIA14220013 to PTE) and by the Fondation Leducq (14CVD01 to PTE). Dr. Gomik and the Cleveland Clinic FMD Biorepository has been supported in part by the National Institutes of Health, National Center for Research Resources, CTSA 1UL1RR024989, Cleveland, Ohio. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 1 Z9 1 U1 3 U2 3 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 OCT PY 2016 VL 12 IS 10 AR e1006367 DI 10.1371/journal.pgen.1006367 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA EA5SM UT WOS:000386683300032 PM 27792790 ER PT J AU Nowak, C Salihovic, S Ganna, A Brandmaier, S Tukiainen, T Broeckling, CD Magnusson, PK Prenni, JE Wang-Sattler, R Peters, A Strauch, K Meitinger, T Giedraitis, V Auml;rnlov, J Berne, C Gieger, C Ripatti, S Lind, L Pedersen, NL Sundstrom, J Ingelsson, E Fall, T AF Nowak, Christoph Salihovic, Samira Ganna, Andrea Brandmaier, Stefan Tukiainen, Taru Broeckling, Corey D. Magnusson, Patrik K. Prenni, Jessica E. Wang-Sattler, Rui Peters, Annette Strauch, Konstantin Meitinger, Thomas Giedraitis, Vilmantas Arnlov, Johan Berne, Christian Gieger, Christian Ripatti, Samuli Lind, Lars Pedersen, Nancy L. Sundstrom, Johan Ingelsson, Erik Fall, Tove TI Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study SO PLOS GENETICS LA English DT Article ID STEAROYL-COA DESATURASE; HOMEOSTASIS MODEL ASSESSMENT; GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; GENE-EXPRESSION; OBESE MICE; RAT-LIVER; DYSFUNCTION; HEART AB Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development. C1 [Nowak, Christoph; Salihovic, Samira; Ingelsson, Erik; Fall, Tove] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Nowak, Christoph; Salihovic, Samira; Ingelsson, Erik; Fall, Tove] Uppsala Univ, Mol Epidemiol Unit, Sci Life Lab, Uppsala, Sweden. [Ganna, Andrea] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ganna, Andrea] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Ganna, Andrea] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ganna, Andrea; Magnusson, Patrik K.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden. [Brandmaier, Stefan; Wang-Sattler, Rui; Gieger, Christian] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany. [Brandmaier, Stefan; Wang-Sattler, Rui; Peters, Annette; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany. [Tukiainen, Taru; Ripatti, Samuli] Univ Helsinki, FIMM, Helsinki, Finland. [Broeckling, Corey D.; Prenni, Jessica E.] Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA. [Wang-Sattler, Rui; Peters, Annette; Gieger, Christian] German Ctr Diabet Res DZD, Munich, Germany. [Peters, Annette] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Strauch, Konstantin] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Giedraitis, Vilmantas] Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Uppsala, Sweden. [Arnlov, Johan] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden. [Arnlov, Johan; Lind, Lars; Sundstrom, Johan] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, Uppsala, Sweden. [Berne, Christian] Uppsala Univ, Dept Med Sci Clin Diabetol & Metab, Uppsala, Sweden. [Ripatti, Samuli] Univ Helsinki, Fac Med, Publ Hlth, Helsinki, Finland. [Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England. [Ingelsson, Erik] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Fall, T (reprint author), Uppsala Univ, Dept Med Sci, Uppsala, Sweden.; Fall, T (reprint author), Uppsala Univ, Mol Epidemiol Unit, Sci Life Lab, Uppsala, Sweden. EM tove.fall@medsci.uu.se RI Magnusson, Patrik/C-4458-2017; OI Salihovic, Samira/0000-0001-5752-4196; Fall, Tove/0000-0003-2071-5866; Wang-Sattler, Rui/0000-0002-8794-8229; Ganna, Andrea/0000-0002-8147-240X; Peters, Annette/0000-0001-6645-0985 FU Knut och Alice Wallenberg Foundation (Wallenberg Academy Fellow); Swedish Diabetes Foundation (Diabetesfonden) [DIA 2013-024]; Family Ernfors Foundation (Stiftelsen Familjen Ernfors fond); Lagermans donation; Borgstroms stiftelse; Goran Gustafssons stiftelse; Swedish Heart-Lung Foundation (Hjart-Lungfonden) [20120197, 20150429]; European Research Council [33595]; Swedish Research Council (Vetenskapsradet) [2012-1397, 2015-03477]; Karolinska Institutet; Swedish Research Council [M-2005-1112, 2016-00250]; GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254]; NIH [DK U01-066134]; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation [20070481]; Helmholtz Zentrum Munchen - German Research Center for Environmental Health; German Federal Ministry of Education and Research (BMBF); State of Bavaria; Munich Center of Health Sciences (MC-Health); Ludwig-Maximilians-Universitat, as part of LMUinnovativ; EU [HEALTH-2009-2.2.1-3/242114, HEALTH-2013-2.4.2-1/602936]; BMBF; Knut and Alice Wallenberg Foundation [2015.0327] FX This study was supported by grants from the Knut och Alice Wallenberg Foundation (Wallenberg Academy Fellow), the Swedish Diabetes Foundation (Diabetesfonden, grant no. DIA 2013-024), the Family Ernfors Foundation (Stiftelsen Familjen Ernfors fond), Lagermans donation, Borgstroms stiftelse, Goran Gustafssons stiftelse, the Swedish Heart-Lung Foundation (Hjart-Lungfonden, grants no. 20120197 and 20150429), the European Research Council (ERC-2013-StG, grant no. 33595) and the Swedish Research Council (Vetenskapsradet, grants no. 2012-1397 and 2015-03477). TwinGene is a sub study of The Swedish Twin Registry, which is financially supported by Karolinska Institutet. TwinGene have also received funding from the Swedish Research Council (grant no. M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Swedish Heart-Lung Foundation (grant no. 20070481). The KORA study was initiated and financed by the Helmholtz Zentrum Munchen - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ. Part of this project was supported by EU FP7 grants HEALTH-2009-2.2.1-3/242114 (Project OPTiMiSE) and HEALTH-2013-2.4.2-1/602936 (Project CarTarDis), and by a grant from the BMBF to the German Center for Diabetes Research (DZD e. V.). AG is supported by the Knut and Alice Wallenberg Foundation (grant no. 2015.0327) and the Swedish Research Council (grant no. 2016-00250). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 0 Z9 0 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 OCT PY 2016 VL 12 IS 10 AR e1006379 DI 10.1371/journal.pgen.1006379 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA EA5SM UT WOS:000386683300041 PM 27768686 ER PT J AU Mukherjee, K Chio, TI Ghosh, S Gu, H Lei, Z Grieco, SL Bane, S AF Mukherjee, Kamalika Chio, Tak Ian Ghosh, Saptarshi Gu, Han Lei, Zhen Grieco, Samantha L. Bane, Susan TI Rapid Bioorthogonal Protein Conjugation Reactions via ortho-Formylphenylboronic Acid-Based Coupling Chemistry SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 30th Anniversary Symposium of the Protein-Society CY JUL 16-19, 2016 CL Baltimore, MD SP Protein Soc C1 [Mukherjee, Kamalika] Harvard Med Sch, Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA USA. [Chio, Tak Ian; Ghosh, Saptarshi; Gu, Han; Lei, Zhen; Grieco, Samantha L.; Bane, Susan] SUNY Binghamton, Dept Chem, Binghamton, NY USA. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD OCT PY 2016 VL 25 SU S1 BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB1YJ UT WOS:000387152400046 ER PT J AU Chen, Y Seepersaud, R Bensing, BA Sullam, PM Rapoport, TA AF Chen, Yu Seepersaud, Ravin Bensing, Barbara A. Sullam, Paul M. Rapoport, Tom A. TI Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein SO PROTEIN SCIENCE LA English DT Meeting Abstract CT 30th Anniversary Symposium of the Protein-Society CY JUL 16-19, 2016 CL Baltimore, MD SP Protein Soc C1 [Chen, Yu; Rapoport, Tom A.] Harvard Med Sch, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA. [Chen, Yu; Rapoport, Tom A.] Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. [Seepersaud, Ravin; Bensing, Barbara A.; Sullam, Paul M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Seepersaud, Ravin; Bensing, Barbara A.; Sullam, Paul M.] Univ Calif San Francisco, San Francisco, CA 94121 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 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD OCT PY 2016 VL 25 SU S1 BP 90 EP 91 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EB1YJ UT WOS:000387152400146 ER PT J AU Hussain, SS Kumar, AP Ghosh, R AF Hussain, Suleman S. Kumar, Addanki P. Ghosh, Rita TI Food-based natural products for cancer management: Is the whole greater than the sum of the parts? SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Food-based extracts; Active compounds; Cancer prevention; Cancer therapy; Adjuvants ID HUMAN PROSTATE-CANCER; GRAPE SEED EXTRACT; CONTROLLED CLINICAL-TRIAL; ENDOTHELIAL GROWTH-FACTOR; PLACEBO-CONTROLLED TRIAL; HUMAN COLORECTAL-CANCER; GREEN TEA CATECHINS; CELLS IN-VITRO; PHASE-II; BLACK-RASPBERRIES AB The rise in cancer incidence and mortality in developing countries together with the human and financial cost of current cancer therapy mandates a closer look at alternative ways to overcome this burgeoning global healthcare problem. Epidemiological evidence for the association between cancer and diet and the long latency of most cancer progression have led to active exploration of whole and isolated natural chemicals from different naturally occurring substances in various preclinical and clinical settings. In general the lack of systemic toxicities of most 'whole' and 'isolated' natural compounds, their potential to reduce toxic doses and potential to delay the development of drug-resistance makes them promising candidates for cancer management. This review article examines the suggested molecular mechanisms affected by these substances focusing to a large extent on prostate cancer and deliberates on the disparate results obtained from cell culture, preclinical and clinical studies in an effort to highlight the use of whole extracts and isolated constituents for intervention. As such these studies underscore the importance of factors such as treatment duration, bioavailability, route of administration, selection criteria, standardized formulation and clinical end points in clinical trial design with both entities. Overall lack of parallel comparison studies between the whole natural products and their isolated compounds limits decisive conclusions regarding the superior utility of one over the other. We suggest the critical need for rigorous comparative research to identify which one of the two or both entities from nature would be best qualified to take on the mantle of cancer management. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Hussain, Suleman S.; Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. [Hussain, Suleman S.; Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Pharmacol, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Mol Med, San Antonio, TX 78229 USA. [Kumar, Addanki P.; Ghosh, Rita] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kumar, AP; Ghosh, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kumara3@uthscsa.edu; ghoshr@uthscsa.edu OI Hussain, Suleman/0000-0003-1342-143X FU CTRC at UT Health Science Center San Antonio (UTHSCSA) through NCI support grant [2P30 CA 054174-17]; [AT007448]; [CPRITRP150166]; [CA149516] FX Supported by funds from AT007448 and CPRITRP150166 (APK) CA149516 (RG) and by the CTRC at UT Health Science Center San Antonio (UTHSCSA) through NCI support grant #2P30 CA 054174-17. NR 139 TC 2 Z9 2 U1 13 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 2016 VL 40-41 BP 233 EP 246 DI 10.1016/j.semcancer.2016.06.002 PG 14 WC Oncology SC Oncology GA EA9UA UT WOS:000386989000014 PM 27397504 ER PT J AU Sargos, P Baumann, BC Eapen, LJ Bahl, A Murthy, V Roubaud, G Orre, M Efstathiou, JA Shariat, S Larre, S Richaud, P Christodouleas, JP AF Sargos, Paul Baumann, Brian C. Eapen, Libni J. Bahl, Amit Murthy, Vedang Roubaud, Guilhem Orre, Mathieu Efstathiou, Jason A. Shariat, Shahrokh Larre, Stephane Richaud, Pierre Christodouleas, John P. TI Adjuvant radiotherapy for pathological high-risk muscle invasive bladder cancer: time to reconsider? SO TRANSLATIONAL ANDROLOGY AND UROLOGY LA English DT Review DE Adjuvant radiotherapy; bladder neoplasm; cystectomy; loco-regional relapse ID TRANSITIONAL-CELL CARCINOMA; RADICAL CYSTECTOMY; RADIATION-THERAPY; UROTHELIAL CARCINOMA; BILHARZIAL BLADDER; NEOADJUVANT CHEMOTHERAPY; PREOPERATIVE IRRADIATION; LOCAL-CONTROL; POSTOPERATIVE RADIOTHERAPY; LOCOREGIONAL FAILURE AB Radical cystectomy with extended pelvic lymph-node dissection, associated with neo-adjuvant chemotherapy, remains the standard of care for advanced, non-metastatic muscle-invasive bladder cancer (MIBC). Loco-regional control is a key factor in the outcome of patients since it is related to overall survival (OS), disease-free survival (DFS) and cause-specific survival. The risk of loco-regional recurrence (LRR) is correlated to pathological factors as well as the extent of the lymphadenectomy. In addition, neither pre-nor post-operative chemotherapy have shown a clear impact on LRR-free survival. Several recent publications have led to the development of a nomogram predicting the risk of LRR, in order to identify patients most likely to benefit from adjuvant radiotherapy. Given the high risk of LRR for selected patients and improvements in radiation techniques that can reduce toxicity, there is a growing interest in adjuvant radiotherapy; international cooperative groups have come together to provide the rationale in favor of adjuvant radiotherapy. Clinical trials in order to reduce the risk of pelvic relapse are opened based on this optimizing patient selection. The aim of this critical literature review is to provide an overview of the rationale supporting the studies of adjuvant radiation for patients with pathologic high-risk MIBC. C1 [Sargos, Paul; Orre, Mathieu; Richaud, Pierre] Inst Bergonie, Dept Radiat Oncol, Bordeaux, France. [Baumann, Brian C.; Christodouleas, John P.] Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St, Philadelphia, PA 19104 USA. [Eapen, Libni J.] Ottawa Hosp, Dept Radiat Oncol, Ottawa, ON, Canada. [Bahl, Amit] Univ Hosp Bristol, Dept Radiat Oncol, Bristol, Avon, England. [Murthy, Vedang] Tata Mem Hosp, Dept Radiat Oncol, Bombay, Maharashtra, India. [Roubaud, Guilhem] Inst Bergonie, Dept Med Oncol, Bordeaux, France. [Efstathiou, Jason A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. [Shariat, Shahrokh] Med Univ Vienna, Vienna Gen Hosp, Dept Urol, Vienna, Austria. [Larre, Stephane] Reims Univ Hosp, Dept Urol, Reims, France. RP Sargos, P (reprint author), Inst Bergonie, Dept Radiotherapy, F-33076 Bordeaux, France. EM p.sargos@bordeaux.unicancer.fr NR 51 TC 0 Z9 0 U1 0 U2 0 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2223-4683 EI 2223-4691 J9 TRANSL ANDROL UROL JI Transl. Androl. Urol. PD OCT PY 2016 VL 5 IS 5 BP 702 EP 710 DI 10.21037/tau.2016.08.18 PG 9 WC Andrology SC Endocrinology & Metabolism GA EB1ID UT WOS:000387102200009 PM 27785427 ER PT J AU Buske, C Trotman, J Tedeschi, A Matous, JV Macdonald, D Tam, C Toumilhac, O Ma, S Oriol, A Heffner, LT Shustik, C Garcia-Sanz, R Cornell, RF de Larrea, CF Castillo, JJ Granell, M Kyrtsonis, MC Leblond, V Symeonidis, A Singh, P Li, J Graef, T Bilotti, E Treon, S Dimopoulos, MA AF Buske, C. Trotman, J. Tedeschi, A. Matous, J., V Macdonald, D. Tam, C. Toumilhac, O. Ma, S. Oriol, A. Heffner, L. T. Shustik, C. Garcia-Sanz, R. Cornell, R. F. Fernandez de Larrea, C. Castillo, J. J. Granell, M. Kyrtsonis, M-C Leblond, V Symeonidis, A. Singh, P. Li, J. Graef, T. Bilotti, E. Treon, S. Dimopoulos, M. A. CA INNOVATE Investigators TI Single-agent Ibrutinib is efficacious and well tolerated in Rituximab-refractory patients with Waldenstrom's Macroglobulinemia (WM): Initial results from an international, multicenter, open-label phase 3 substudy (INNOVATE (TM)) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Buske, C.] Univ Hosp Ulm, Inst Expt Canc Res, Comprehens Canc Ctr Ulm, Ulm, Germany. [Trotman, J.] Univ Sydney, Concord Hosp, Concord, Australia. [Tedeschi, A.] Osped Niguarda Ca Granda, Milan, Italy. [Matous, J., V] Colorado Blood Canc Inst, Denver, CO USA. [Macdonald, D.] Dalhousie Univ, Halifax, NS, Canada. [Tam, C.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tam, C.] St Vincents Hosp, Melbourne, Vic, Australia. [Toumilhac, O.] CHU Clermont Ferrand, Hematol Clin Adulte & Therapie Cellulaire, Clermont Ferrand, France. [Ma, S.] Northwestern Univ, Feinberg Sch Med, Robert H Luri Comprehens Canc Ctr, Chicago, IL 60611 USA. [Oriol, A.] Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Barcelona, Spain. [Heffner, L. T.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Shustik, C.] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Montreal, PQ, Canada. [Garcia-Sanz, R.] Hosp Univ Salamanca, Salamanca, Spain. [Cornell, R. F.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Fernandez de Larrea, C.] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain. [Castillo, J. J.; Treon, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Granell, M.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Kyrtsonis, M-C; Dimopoulos, M. A.] Univ Athens, Sch Med, Athens, Greece. [Leblond, V] UPMC, Hop Pitie Salpetriere, AP HP, Paris, France. [Symeonidis, A.] Univ Patras, Sch Med, Patras, Greece. [Singh, P.; Li, J.; Graef, T.; Bilotti, E.] Pharmacyclics LLC, Sunnyvale, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V391 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300287 ER PT J AU Kulkarni, A Natarajan, SK Chandrasekar, V Pandey, PR Sengupta, S AF Kulkarni, Ashish Natarajan, Siva Kumar Chandrasekar, Vineethkrishna Pandey, Prithvi Raj Sengupta, Shiladitya TI Combining Immune Checkpoint Inhibitors and Kinase-Inhibiting Supramolecular Therapeutics for Enhanced Anticancer Efficacy SO ACS NANO LA English DT Article DE cancer; supramolecular therapeutics; immune checkpoint inhibitors; targeted therapy ID CANCER-IMMUNOTHERAPY; ANTITUMOR EFFICACY; PD-L1 EXPRESSION; BREAST-CANCER; FORCE-FIELD; SEQUENTIAL APPLICATION; TARGETED THERAPY; BRAF INHIBITION; MEK INHIBITION; MELANOMA AB A major limitation of immune checkpoint inhibitors is that only a small subset of patients achieve durable clinical responses. This necessitates the development of combinatorial regimens with immunotherapy. However, some combinations, such as MEK- or PI3K-inhibitors with a PD1-PDL1 checkpoint inhibitor, are pharmacologically challenging to implement. We rationalized that such combinations can be enabled using nanoscale supramolecular targeted therapeutics, which spatially home into tumors and exert temporally sustained inhibition of the target. Here we describe two case studies where nanoscale MEK- and PI3K-targeting supramolecular therapeutics were engineered using a quantum mechanical all-atomistic simulation-based approach. The combinations of nanoscale MEK- and PI3K-targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively. Additionally, the temporal sequence of administration impacts the outcome. The combination of supramolecular therapeutics and immunotherapy could emerge as a paradigm shift in the treatment of cancer. C1 [Kulkarni, Ashish; Sengupta, Shiladitya] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Kulkarni, Ashish; Sengupta, Shiladitya] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kulkarni, Ashish; Natarajan, Siva Kumar; Chandrasekar, Vineethkrishna; Sengupta, Shiladitya] Brigham & Womens Hosp, Dept Med, Div Engn Med, 75 Francis St, Boston, MA 02115 USA. [Pandey, Prithvi Raj] India Innovat Res Ctr, New Delhi 110092, India. [Pandey, Prithvi Raj] 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 FU National Science Foundation under NSF [1541959]; DoD BCRP Collaborative Innovator Grant [W81XWH-09-1-0700]; NIH [RO1 (1R01CA135242-01A2)]; DoD [BC132168]; American Lung Association Innovation Award [LCD-259932-N]; Indo-US Joint Center Grant from IUSSTF FX The authors would like to thank the Dana Farber Cancer Institute Flow Cytometry Core Facility for their expertise, consulting, and assistance with flow cytometry experiments. 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. The authors would like to thank Dr. Sudip Roy (National Chemical Laboratory, Pune, India) for providing the support in computational analysis. This work was supported by a DoD BCRP Collaborative Innovator Grant (W81XWH-09-1-0700), a NIH RO1 (1R01CA135242-01A2), a DoD Breakthrough Award (BC132168), an American Lung Association Innovation Award (LCD-259932-N), and an Indo-US Joint Center Grant from IUSSTF to S.S. NR 52 TC 0 Z9 0 U1 8 U2 8 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 OCT PY 2016 VL 10 IS 10 BP 9227 EP 9242 DI 10.1021/acsnano.6b01600 PG 16 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA EA2LK UT WOS:000386423600023 ER PT J AU Tostanoski, LH Chiu, YC Andorko, JI Guo, M Zeng, XB Zhang, PP Royal, W Jewell, CM AF Tostanoski, Lisa H. Chiu, Yu-Chieh Andorko, James I. Guo, Ming Zeng, Xiangbin Zhang, Peipei Royal, Walter, III Jewell, Christopher M. TI Design of Polyelectrolyte Multilayers to Promote Immunological Tolerance SO ACS NANO LA English DT Article DE polyelectrolyte multilayers; immunology and vaccines; self-assembly; autoimmunity and tolerance; biomaterials; human patients and clinical data; nanotechnology ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; DNA VACCINATION; IMMUNE SIGNALS; ANTIGEN; CAPSULES; DELIVERY; MICROCAPSULES; ENCAPSULATION AB Recent studies demonstrate that excess signaling through inflammatory pathways (e.g., toll-like receptors, TLRs) contributes to the pathogenesis of human auto immune diseases, including lupus, diabetes, and multiple sclerosis (MS). We hypothesized that codelivery of a regulatory ligand of TLR9, GpG oligonucleotide, along with myelin the "self" molecule attacked in MS might restrain the pro-inflammatory signaling typically present during myelin presentation, redirecting T cell differentiation away from inflammatory populations and toward tolerogenic phenotypes such as regulatory T cells. Here we show that myelin peptide and GpG can be used as modular building blocks for co-assembly into immune polyelectrolyte multilayers (iPEMs). These nanostructured capsules mimic attractive features of biomaterials, including tunable cargo loading and codelivery, but eliminate all carriers and synthetic polymers, components that often exhibit intrinsic inflammatory properties that could exacerbate autoimmune disease. In vitro, iPEMs assembled from myelin and GpG oligonucleotide, but not myelin and a control oligonucleotide, restrain TLR9 signaling, reduce dendritic cell activation, and polarize myelin specific T cells toward tolerogenic phenotype and function. In mice, iPEMs blunt myelin-triggered inflammatory responses, expand regulatory T cells, and eliminate disease in a common model of MS. Finally, in samples from human MS patients, iPEMs bias myelin-triggered immune cell function toward tolerance. This work represents a unique opportunity to use PEMs to regulate immune function and promote tolerance, supporting iPEMs as a carrier-free platform to alter TLR function to reduce inflammation and combat autoimmunity. C1 [Tostanoski, Lisa H.; Chiu, Yu-Chieh; Andorko, James I.; Zeng, Xiangbin; Zhang, Peipei; Jewell, Christopher M.] Univ Maryland, Fischell Dept Bioengn, 8228 Paint Branch Dr, College Pk, MD 20742 USA. [Guo, Ming; Royal, Walter, III] Univ Maryland, Sch Med, Dept Neurol, 655 West Baltimore St, Baltimore, MD 21201 USA. [Royal, Walter, III] US Dept Vet Affairs, Multiple Sclerosis Ctr Excellence East, 655 West Baltimore St, Baltimore, MD 21201 USA. [Jewell, Christopher M.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, 685 West Baltimore St,HSF I Suite 380, Baltimore, MD 21201 USA. [Jewell, Christopher M.] US Dept Vet Affairs, 10 North Greene St, Baltimore, MD 21201 USA. [Jewell, Christopher M.] Marlene & Stewart Greenebaum Canc Ctr, 22 South Greene St, Baltimore, MD 21201 USA. RP Jewell, CM (reprint author), Univ Maryland, Fischell Dept Bioengn, 8228 Paint Branch Dr, College Pk, MD 20742 USA.; Jewell, CM (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 685 West Baltimore St,HSF I Suite 380, Baltimore, MD 21201 USA.; Jewell, CM (reprint author), US Dept Vet Affairs, 10 North Greene St, Baltimore, MD 21201 USA.; Jewell, CM (reprint author), Marlene & Stewart Greenebaum Canc Ctr, 22 South Greene St, Baltimore, MD 21201 USA. EM cmjewell@umd.edu FU National Multiple Sclerosis Society [RG-1501-02968, PP2103]; NSF [1351688, DGE1322106]; University of Maryland Venture Fund; Maryland Innovation Initiative; Veterans Affairs [I01BX007080, RX000293]; NIH [T32 CA154274, T32 AI089621]; Damon Runyon Foundation [DRR3415]; Young Investigator of the Alliance for Cancer Gene Therapy [15051543]; Melanoma Research Alliance [348963] FX The authors thank L. Hester at the University of Maryland Cytokine Core Laboratory for her assistance with analysis of human PBMC samples and K. Gaskell at the University of Maryland Department of Chemistry & Biochemistry for her assistance with atomic force microscopy analyses. The authors acknowledge the VALOMS Investigators. This work was supported by the National Multiple Sclerosis Society award nos. RG-1501-02968 and PP2103, NSF CAREER award no. 1351688, the University of Maryland Venture Fund, the Maryland Innovation Initiative, and Veterans Affairs nos. I01BX007080 and RX000293. L.H.T. is a NSF Graduate Fellow no. DGE1322106. Y.C. is a trainee on NIH Grant no. T32 CA154274. J.I.A. is a trainee on NIH Grant no. T32 AI089621 and a Graduate Fellow of the American Association of Pharmaceutical Scientists. C.M.J. is a Damon Runyon-Rachleff Innovator supported by the Damon Runyon Foundation (no. DRR3415) and a Young Investigator of the Alliance for Cancer Gene Therapy (no. 15051543) and the Melanoma Research Alliance (no. 348963). NR 45 TC 2 Z9 2 U1 13 U2 13 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 OCT PY 2016 VL 10 IS 10 BP 9334 EP 9345 DI 10.1021/acsnano.6b04001 PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA EA2LK UT WOS:000386423600033 ER PT J AU Fuehrlein, BS Mota, N Arias, AJ Trevisan, LA Kachadourian, LK Krystal, JH Southwick, SM Pietrzak, RH AF Fuehrlein, Brian S. Mota, Natalie Arias, Albert J. Trevisan, Louis A. Kachadourian, Lorig K. Krystal, John H. Southwick, Steven M. Pietrzak, Robert H. TI The burden of alcohol use disorders in US military veterans: results from the National Health and Resilience in Veterans Study SO ADDICTION LA English DT Article DE Alcohol use disorder; anxiety disorder; comorbidity; dual diagnosis; epidemiology; military; mood disorder; veterans ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDERS; AT-RISK DRINKING; EPIDEMIOLOGIC SURVEY; AUDIT-C; MENTAL-HEALTH; UNITED-STATES; DSM-IV; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION AB AimsTo analyze data from a large, contemporary, nationally representative sample of US veterans to evaluate: (1) the prevalence of life-time alcohol use disorder (AUD) and past-year AUD; (2) common psychiatric comorbidities associated with life-time AUD; and (3) correlates of life-time and past-year probable AUD. DesignData were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a web-based survey of a random probability sample of a contemporary, nationally representative sample of US military veterans. SettingUnited States. ParticipantsNationally representative sample of 3157 US veterans aged 21years and older. MeasurementsLife-time alcohol abuse and dependence were assessed according to DSM-IV diagnostic criteria using the Mini International Neuropsychiatric Interview, and combined into a single variable: AUD. Past-year probable AUD was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Correlates of AUD, including psychiatric comorbidities, suicidality and demographic characteristics, were also assessed. FindingsThe prevalence of life-time AUD and past-year probable AUD was 42.2% [95% confidence interval (CI)=40.5-43.9%)] and 14.8% (95% CI=13.6-16.0%), respectively. Compared with veterans without AUD, those with life-time AUD had substantially elevated rates of life-time and current mood and anxiety disorders [odds ratios (ORs)=2.6-4.1], drug use disorder (OR=10.7), life-time suicide attempt (OR=4.1) and current suicidal ideation (OR=2.1). Younger age, male sex, lower education, lower annual household income and greater number of life-time traumatic events were associated independently with life-time AUD. Younger age, male sex, unpartnered marital status and a life-time diagnosis of major depressive disorder were associated independently with past-year probable AUD. ConclusionsMore than 40% of US military veterans have a life-time history of alcohol use disorder. Veterans with a life-time history of alcohol use disorder have substantial comorbid psychiatric burden, including elevated rates of suicidal ideation and attempts. Certain socio-demographic (e.g. younger age, male sex, lower education) and clinical (e.g. trauma burden, history of depression) characteristics are associated with increased risk of AUD. C1 [Fuehrlein, Brian S.; Arias, Albert J.; Trevisan, Louis A.; Kachadourian, Lorig K.; Krystal, John H.; Southwick, Steven M.; Pietrzak, Robert H.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Fuehrlein, Brian S.; Mota, Natalie; Arias, Albert J.; Trevisan, Louis A.; Kachadourian, Lorig K.; Krystal, John H.; Southwick, Steven M.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krystal, John H.; Southwick, Steven M.; Pietrzak, Robert H.] Natl Ctr PTSD, Clin Neurosci Div, US Dept Vet Affairs, West Haven, CT USA. RP Fuehrlein, BS (reprint author), VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. EM fuehrlein@gmail.com NR 62 TC 2 Z9 2 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD OCT PY 2016 VL 111 IS 10 BP 1786 EP 1794 DI 10.1111/add.13423 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DW5UV UT WOS:000383713500021 PM 27061707 ER PT J AU Matteini, AM Tanaka, T Karasik, D Atzmon, G Chou, WC Eicher, JD Johnson, AD Arnold, AM Callisaya, ML Davies, G Evans, DS Holtfreter, B Lohman, K Lunetta, KL Mangino, M Smith, AV Smith, JA Teumer, A Yu, L Arking, DE Buchman, AS Chibinik, LB De Jager, PL Evans, DA Faul, JD Garcia, ME Gillham-Nasenya, I Gudnason, V Hofman, A Hsu, YH Ittermann, T Lahousse, L Liewald, DC Liu, YM Lopez, L Rivadeneira, F Rotter, JI Siggeirsdottir, K Starr, JM Thomson, R Tranah, GJ Uitterlinden, AG Volker, U Volzke, H Weir, DR Yaffe, K Zhao, W Zhuang, WV Zmuda, JM Bennett, DA Cummings, SR Deary, IJ Ferrucci, L Harris, TB Kardia, SLR Kocher, T Kritchevsky, SB Psaty, BM Seshadri, S Spector, TD Srikanth, VK Windham, BG Zillikens, MC Newman, AB Walston, JD Kiel, DP Murabito, JM AF Matteini, Amy M. Tanaka, Toshiko Karasik, David Atzmon, Gil Chou, Wen-Chi Eicher, John D. Johnson, Andrew D. Arnold, Alice M. Callisaya, Michele L. Davies, Gail Evans, Daniel S. Holtfreter, Birte Lohman, Kurt Lunetta, Kathryn L. Mangino, Massimo Smith, Albert V. Smith, Jennifer A. Teumer, Alexander Yu, Lei Arking, Dan E. Buchman, Aron S. Chibinik, Lori B. De Jager, Philip L. Evans, Denis A. Faul, Jessica D. Garcia, Melissa E. Gillham-Nasenya, Irina Gudnason, Vilmundur Hofman, Albert Hsu, Yi-Hsiang Ittermann, Till Lahousse, Lies Liewald, David C. Liu, Yongmei Lopez, Lorna Rivadeneira, Fernando Rotter, Jerome I. Siggeirsdottir, Kristin Starr, John M. Thomson, Russell Tranah, Gregory J. Uitterlinden, Andre G. Voelker, Uwe Voelzke, Henry Weir, David R. Yaffe, Kristine Zhao, Wei Zhuang, Wei Vivian Zmuda, Joseph M. Bennett, David A. Cummings, Steven R. Deary, Ian J. Ferrucci, Luigi Harris, Tamara B. Kardia, Sharon L. R. Kocher, Thomas Kritchevsky, Stephen B. Psaty, Bruce M. Seshadri, Sudha Spector, Timothy D. Srikanth, Velandai K. Windham, B. Gwen Zillikens, M. Carola Newman, Anne B. Walston, Jeremy D. Kiel, Douglas P. Murabito, Joanne M. TI GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium SO AGING CELL LA English DT Article DE aging; genomewide association; meta-analysis; muscle strength; older adults; SNP ID MUSCLE STRENGTH; C/EBP-BETA; OXIDATIVE STRESS; SKELETAL-MUSCLE; GENE-EXPRESSION; GRIP STRENGTH; ASSOCIATION; HEALTH; AGE; POLYMORPHISMS AB Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27581 individuals of European descent over 65years of age from 14 cohort studies. Genomewide association analysis was conducted on similar to 2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5x10(-8)) and 39 suggestive (P-value< 5x10(-5)) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (=0.47, SE=0.08, P-value=5.20x10(-10)). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein- (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength. C1 [Matteini, Amy M.; Walston, Jeremy D.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Karasik, David; Chou, Wen-Chi; Hsu, Yi-Hsiang; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Hebrew SeniorLife, Inst Aging Res, Boston, MA 02215 USA. [Karasik, David; Chou, Wen-Chi; Hsu, Yi-Hsiang; Ferrucci, Luigi; Kiel, Douglas P.] Harvard Med Sch, Boston, MA USA. [Karasik, David] Bar Ilan Univ, Fac Med Galilee, IL-13010 Safed, Israel. [Atzmon, Gil] Albert Einstein Coll Med, Inst Aging Res, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10467 USA. [Atzmon, Gil] Albert Einstein Coll Med, Inst Aging Res, Dept Genet, 1300 Morris Pk Ave, Bronx, NY 10467 USA. [Atzmon, Gil] Univ Haifa, Dept Human Biol, Haifa, Israel. [Eicher, John D.; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA. [Eicher, John D.; Johnson, Andrew D.; Lunetta, Kathryn L.; Seshadri, Sudha; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Callisaya, Michele L.; Srikanth, Velandai K.] Monash Univ, Stroke & Ageing Res Grp, Dept Med, Sch Clin Sci, Clayton, Vic, Australia. [Callisaya, Michele L.; Thomson, Russell; Srikanth, Velandai K.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Davies, Gail; Liewald, David C.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemol, Edinburgh, Midlothian, Scotland. [Davies, Gail; Lopez, Lorna] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Evans, Daniel S.; Tranah, Gregory J.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Holtfreter, Birte; Kocher, Thomas] Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodointol, Ctr Oral Hlth, Unit Periodontol, Greifswald, Germany. [Lohman, Kurt; Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mangino, Massimo; Gillham-Nasenya, Irina; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Mangino, Massimo] Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London, England. [Smith, Albert V.; Gudnason, Vilmundur; Siggeirsdottir, Kristin] Icelandic Heart Assoc, Kopavogur, Iceland. [Smith, Jennifer A.; Zhao, Wei; Kardia, Sharon L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Teumer, Alexander; Ittermann, Till; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Yu, Lei; Buchman, Aron S.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Buchman, Aron S.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Chibinik, Lori B.; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiatr Genom, 75 Francis St, Boston, MA 02115 USA. [Chibinik, Lori B.; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Evans, Denis A.] Rush Univ, Inst Hlth Aging, Med Ctr, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA. [Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA. [Garcia, Melissa E.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Hofman, Albert; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Hsu, Yi-Hsiang] Harvard Sch Publ Hlth, Dept Med Mol & Integrat Physiol Sci, Boston, MA USA. [Lahousse, Lies] Univ Ghent, Dept Resp Med, Ghent, Belgium. [Lahousse, Lies] Ghent Univ Hosp, Ghent, Belgium. [Rivadeneira, Fernando; Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] NCHA, NGI, Rotterdam, Netherlands. [Rotter, Jerome I.] Univ Calif Los Angeles, Dept Pediat, Div Genom Outcome, Los Angeles, CA 90024 USA. [Rotter, Jerome I.] Univ Calif Los Angeles, Dept Med, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst,Harbor UCLA Med Ctr, Los Angeles, CA 90024 USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Voelker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] German Ctr Cardiovasc Res DZHK, Greifswald, Germany. [Voelzke, Henry] German Ctr Diabet Res DZD, Greifswald, Germany. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Zhuang, Wei Vivian] Creighton Univ, Sch Med, Ctr Hlth Policy & Eth, Publ Hlth Program, Omaha, NE USA. [Zmuda, Joseph M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Windham, B. Gwen] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Matteini, AM (reprint author), Johns Hopkins Ctr Aging & Hlth, 2024 East Monument St,Suite 2-126, Baltimore, MD 21287 USA. EM amatteini@jhmi.edu RI Callisaya, Michele/I-2333-2013; Thomson, Russell/H-5653-2012; OI Callisaya, Michele/0000-0003-2122-1622; Thomson, Russell/0000-0003-4949-4120; Karasik, David/0000-0002-8826-0530; Smith, Jennifer/0000-0002-3575-5468; Lahousse, Lies/0000-0002-3494-4363 FU Johns Hopkins University Claude D. Pepper Older Americans Independence Center (NIA) [P30 AG021334]; Wellcome Trust [FP7/2007-2013]; National Institute for Health Research, National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; German Federal Ministry of Education and Research [01ZZ0103, 01ZZ0403, 01ZZ9603, 031S2061A, 03ZIK012]; National Institutes of Health [HHSN268200625226C, HHSN268200782096C, N01AG12 100, UL1RR025005]; Biotechnology and Biological Sciences Research Council; National Health and Medical Research Council [NHMRC 100089, NHMRC 1034483, NHMRC 1061457, NHMRC 403000, NHMRC491109, NHMRC606543]; National Institute on Aging [1R01AG032098-01A1, 263 MD 821336, 263 MD 9164, AG016495, AG033193, AG08122, N01AG62101, N01AG 62103, N01AG62106, P30AG10161]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01 AR41398, R01-AR051124, RC2ARO58973, U01 AR45580, U01 AR45 583, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654]; National Heart, Lung, and Blood Institute [HHSN268200800007C, HHSN268201100005C, HH5N268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HH5N268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C]; National Human Genome Research Institute [U01 HG004402]; Medical Research Council, Research Institute for Diseases in the Elderly [014-93-015, RIDE2]; Netherlands Organization for Scientific Research NWO Investments [050-060-810, 175.010.2005.011, 911-03-012]; National Center for Research Resources [UL1 RR024140, N02HL64278, N01-AG-1-2100, HHSN27120 120022C, HL105756, N01HC85083, N01HC85086, RC1 AG035835]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Research Foundation Flanders (FWO); UK Biotechnology and Biological Sciences Research Council; Royal Society; Chief Scientist Office of the Scottish Government, Age UK (The Disconnected Mind project), Lifelong Health and Wellbeing Initiative) [MR/K026992/1]; Medical Research Council; Netherlands Organization of Scientific Research NWO Investments [050-060-810, 175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; RIDE2; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; The National Institute on Aging [R01 AG005394, R01 AG005407, R01 AG0275747, R01 AG027576, R01 AR35582, R01 AR35583, R01AG 023629, R01AG040039, R01AG15819, R01AG17917, R01AG24480, R01AG29451, R01AG30146, R01AR35584, RC2 AG036495, U01 AG 18197, U01-AG027810, U01A0009740]; The National Heart, Lung, and Blood Institute [N01HC25195, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, R01HL086694, R01HL087641, R01HL103612, R01HL120393, R01HL59367, U01 HL080295] FX Johns Hopkins University Claude D. Pepper Older Americans Independence Center (NIA Grant/Award Number P30 AG021334), Wellcome Trust, (Grant/Award Number: 'FP7/2007-2013') National Institute for Health Research, National Institute of Diabetes and Digestive and Kidney Diseases, (Grant/Award Number: 'DK063491') German Federal Ministry of Education and Research, (Grant/Award Number: '01ZZ0103','01ZZ0403','01ZZ9603', '031S2061A','03ZIK012'), National Institutes of Health, (Grant/Award Number: 'HHSN268200625226C','HHSN268200782096C','N01AG12 100','UL1RR025005'), Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, (Grant/Award Number: 'NHMRC 100089','NHMRC 1034483','NHMRC 1061457','NHMRC 403000','NHMRC491109','NHMRC606543'), National Institute on Aging, (Grant/Award Number: '1R01AG032098-01A1','263 MD 821336'.'263 MD 9164 ','AG016495','AG033193,',AG08122','N01AG62101','N01AG 62103','N01AG62106','P30AG10161','R01 AG005394','R01 AG005407', 'R01 AG0275747','R01 AG027576','R01 AR35582','R01 AR35583','R01AG 023629','R01AG040039','R01AG15819','R01AG17917','R01AG24480', 'R01AG29451','R01AG30146','R01AR35584','RC2 AG036495','U01 AG 18197','U01-AG027810','U01A0009740'), National Institute of Arthritis and Musculoskeletal and Skin Diseases, (Grant/Award Number: 'R01 AR41398','R01-AR051124','RC2ARO58973','U01 AR45580','U01 AR45 583','U01 AR45614','U01 AR45632','U01 AR45647','U01 AR45654') National Heart, Lung, and Blood Institute, (Grant/Award Number: 'HHSN268200800007C','HHSN268201100005C','HH5N268201100006C','HHSN2682011 00007C','HHSN268201100008C','HHSN268201100009C','HH5N268201100010C','HHS N268201100011C','HHSN26820 1100012C','HHSN268201200036C','N01HC25195','N01HC55222','N01HC85079','N0 1HC85080','N01HC85081','N01HC85082','R01HL0866 94','R01HL087641','R01HL103612','R01HL120393','R01HL59367','U01 HL080295'), National Human Genome Research Institute, (Grant/Award Number: 'U01 HG004402') Medical Research Council, Research Institute for Diseases in the Elderly, (Grant/Award Number '014-93-015','RIDE2') Netherlands Organization for Scientific Research NWO Investments, (Grant/Award Number: '050-060-810','175.010.2005.011','911-03-012'), National Center for Research Resources, (Grant/Award Number: 'UL1 RR024140'). "N02HL64278", "N01-AG-1-2100", "HHSN27120 120022C", "HL105756", "N01HC85083", "N01HC85086", "RC1 AG035835", NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), the Althingi (the Icelandic Parliament), Research Foundation Flanders (FWO), UK Biotechnology and Biological Sciences Research Council, The Royal Society, The Chief Scientist Office of the Scottish Government, Age UK (The Disconnected Mind project), Lifelong Health and Wellbeing Initiative: "MR/K026992/1", Medical Research Council, Netherlands Organization of Scientific Research NWO Investments: "nr." 175.010.2005.011", "911-03-012", "050-060-810", Research Institute for Diseases in the Elderly: "014-93-015"; "RIDE2", Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA): "nr. 050-060-810." NR 32 TC 1 Z9 1 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2016 VL 15 IS 5 BP 792 EP 800 DI 10.1111/acel.12468 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DW5VN UT WOS:000383715600001 PM 27325353 ER PT J AU Teumer, A Qi, QB Nethander, M Aschard, H Bandinelli, S Beekman, M Berndt, SI Bidlingmaier, M Broer, L Cappola, A Ceda, GP Chanock, S Chen, MH Chen, TC Chen, YDI Chung, J Miglianico, FD Eriksson, J Ferrucci, L Friedrich, N Gnewuch, C Goodarzi, MO Grarup, N Guo, TW Hammer, E Hayes, RB Hicks, AA Hofman, A Houwing-Duistermaat, JJ Hu, F Hunter, DJ Husemoen, LL Isaacs, A Jacobs, KB Janssen, JAMJL Jansson, JO Jehmlich, N Johnson, S Juul, A Karlsson, M Kilpelainen, TO Kovacs, P Kraft, P Li, C Linneberg, A Liu, YM Loos, RJF Lorentzon, M Lu, YC Maggio, M Magi, R Meigs, J Mellstrom, D Nauck, M Newman, AB Pollak, MN Pramstaller, PP Prokopenko, I Psaty, BM Reincke, M Rimm, EB Rotter, JI Saint Pierre, A Schurmann, C Seshadri, S Sjogren, K Slagboom, PE Strickler, HD Stumvoll, M Suh, YS Sun, Q Zhang, CL Svensson, J Tanaka, T Tare, A Tonjes, A Uh, HW van Duijn, CM van Heemst, D Vandenput, L Vasan, RS Volker, U Willems, SM Ohlsson, C Wallaschofski, H Kaplan, RC AF Teumer, Alexander Qi, Qibin Nethander, Maria Aschard, Hugues Bandinelli, Stefania Beekman, Marian Berndt, Sonja I. Bidlingmaier, Martin Broer, Linda Cappola, Anne Ceda, Gian Paolo Chanock, Stephen Chen, Ming-Huei Chen, Tai C. Chen, Yii-Der Ida Chung, Jonathan Miglianico, Fabiola Del Greco Eriksson, Joel Ferrucci, Luigi Friedrich, Nele Gnewuch, Carsten Goodarzi, Mark O. Grarup, Niels Guo, Tingwei Hammer, Elke Hayes, Richard B. Hicks, Andrew A. Hofman, Albert Houwing-Duistermaat, Jeanine J. Hu, Frank Hunter, David J. Husemoen, Lise L. Isaacs, Aaron Jacobs, Kevin B. Janssen, Joop A. M. J. L. Jansson, John-Olov Jehmlich, Nico Johnson, Simon Juul, Anders Karlsson, Magnus Kilpelainen, Tuomas O. Kovacs, Peter Kraft, Peter Li, Chao Linneberg, Allan Liu, Yongmei Loos, Ruth J. F. Lorentzon, Mattias Lu, Yingchang Maggio, Marcello Magi, Reedik Meigs, James Mellstrom, Dan Nauck, Matthias Newman, Anne B. Pollak, Michael N. Pramstaller, Peter P. Prokopenko, Inga Psaty, Bruce M. Reincke, Martin Rimm, Eric B. Rotter, Jerome I. Saint Pierre, Aude Schurmann, Claudia Seshadri, Sudha Sjogren, Klara Slagboom, P. Eline Strickler, Howard D. Stumvoll, Michael Suh, Yousin Sun, Qi Zhang, Cuilin Svensson, Johan Tanaka, Toshiko Tare, Archana Toenjes, Anke Uh, Hae-Won van Duijn, Cornelia M. van Heemst, Diana Vandenput, Liesbeth Vasan, Ramachandran S. Voelker, Uwe Willems, Sara M. Ohlsson, Claes Wallaschofski, Henri Kaplan, Robert C. CA CHARGE Longevity Working Grp Body Composition Genetics Consorti TI Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits SO AGING CELL LA English DT Article DE aging; genomewide association study; growth hormone axis; IGF-I; IGFBP-3; longevity ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CIRCULATING LEVELS; GENETIC-VARIATION; FACTOR (IGF)-I; CANCER-RISK; INSULIN; DISEASE AB The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. C1 [Teumer, Alexander] Univ Med Greifswald, Inst Commun Med, D-17475 Greifswald, Germany. [Teumer, Alexander; Chanock, Stephen; Hammer, Elke; Jacobs, Kevin B.; Jehmlich, Nico; Voelker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany. [Qi, Qibin; Strickler, Howard D.; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Nethander, Maria] Univ Gothenburg, Salalgrenska Acad, Bioinformat Core Facil, S-40530 Gothenburg, Sweden. [Aschard, Hugues] Harvard Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Bandinelli, Stefania] Azienda Sanitaria Fimnze ASP, Geriatr Unit, Florence, Italy. [Beekman, Marian; Slagboom, P. Eline] Leiden Univ, Med Ctr, Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bidlingmaier, Martin; Reincke, Martin] Klinikum Univ Munchen, Med Klin & Poliklin 4, D-80336 Munich, Germany. [Broer, Linda] Erasmus MC, Dept Epidemiol, Subdiv Genet Epidemiol, Postbus 2040, NL-3000 CA Rotterdam, Netherlands. [Broer, Linda] Erasmus MC, Dept Internal Med, Postbus 2040, NL-3000 CA Rotterdam, Netherlands. [Cappola, Anne] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Endocrinol Diabet & Metab,Dept Med, Philadelphia, PA 19104 USA. [Ceda, Gian Paolo; Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Clin & Expt Med, Parma, Italy. [Ceda, Gian Paolo; Maggio, Marcello] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy. [Chen, Ming-Huei; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Chen, Ming-Huei; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Chen, Tai C.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Chen, Yii-Der Ida; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA. [Chung, Jonathan; Guo, Tingwei; Johnson, Simon; Li, Chao; Suh, Yousin; Tare, Archana] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Miglianico, Fabiola Del Greco; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy. [Miglianico, Fabiola Del Greco; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, D-23562 Lubeck, Germany. [Eriksson, Joel; Lorentzon, Mattias; Mellstrom, Dan; Sjogren, Klara; Svensson, Johan; Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Dept Internal Med & Clin Nutr, Inst Med, Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Ferrucci, Luigi; Tanaka, Toshiko] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA. [Friedrich, Nele; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Gnewuch, Carsten] Univ Regensburg, Med Ctr, Inst Clin Chem & Lab Med, D-93053 Regensburg, Germany. [Goodarzi, Mark O.] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Grarup, Niels; Kilpelainen, Tuomas O.] Univ Copenhagen, Ctr Basic Metab Res, Sect Metab Genet, Fac Hlth & Med Sci,Novo Nordisk Fdn, DK-2100 Copenhagen, Denmark. [Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY 10016 USA. [Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Houwing-Duistermaat, Jeanine J.; Isaacs, Aaron; Uh, Hae-Won] Leiden Univ, Med Ctr, Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands. [Hu, Frank; Hunter, David J.; Nauck, Matthias; Rimm, Eric B.; Sun, Qi] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank; Kraft, Peter; Rimm, Eric B.; Sun, Qi] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Hu, Frank; Kraft, Peter; Rimm, Eric B.; Sun, Qi] Harvard Med Sch, Boston, MA 02115 USA. [Hunter, David J.; Kraft, Peter; Nauck, Matthias] Harvard Sch Publ Hlth, Dept Epidemiol & Stat Genet, Boston, MA 02115 USA. [Husemoen, Lise L.; Linneberg, Allan] Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark. [Isaacs, Aaron; van Duijn, Cornelia M.; Willems, Sara M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands. [Isaacs, Aaron; van Duijn, Cornelia M.] Ctr Med Syst Biol, NL-2300 RC Leiden, Netherlands. [Janssen, Joop A. M. J. L.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Jansson, John-Olov] Uiaivers Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Physiol, S-41345 Gothenburg, Sweden. [Jehmlich, Nico] UFZ, Helmholtz Ctr Environm Res, Dept Prote, D-04318 Leipzig, Germany. [Juul, Anders] Univ Copenhagen, Dept Growth & Reprod, Rigshosp, DK-2100 Copenhagen, Denmark. [Karlsson, Magnus] Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, S-20502 Malmo, Sweden. [Kovacs, Peter; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany. [Kraft, Peter] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, DK-2600 Copenhagen, Denmark. [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Loos, Ruth J. F.; Lu, Yingchang] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Magi, Reedik] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. [Magi, Reedik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Meigs, James] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Meigs, James] Harvard Med Sch, Div Gen Med, Boston, MA 02115 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Pollak, Michael N.] McGill Univ, Dept Expt Med, Montreal, PQ H3A 0G4, Canada. [Pollak, Michael N.] McGill Univ, Dept Oncol, Montreal, PQ H3A 0G4, Canada. [Prokopenko, Inga] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Saint Pierre, Aude] INSERM, U1078, Brest, France. [Schurmann, Claudia] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Schurmann, Claudia] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Suh, Yousin] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Suh, Yousin] Guangdong Med Coll, Inst Aging Res, Dongguan, Peoples R China. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Executive Blvd, Rockville, MD 20852 USA. [Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany. [van Heemst, Diana] Leiden Univ, Med Ctr, Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands. [Vasan, Ramachandran S.] Boston Univ, Framingham, MA 01702 USA. [Vasan, Ramachandran S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA 01702 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Kaplan, RC (reprint author), Albert Einstein Coll Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM robert.kaplan@einstein.yu.edu RI Jehmlich, Nico/B-5403-2009; Slagboom, P. Eline/R-4790-2016; Grarup, Niels/K-2807-2015; Hicks, Andrew/E-9518-2017; OI Slagboom, P. Eline/0000-0002-2875-4723; Grarup, Niels/0000-0001-5526-1070; Hicks, Andrew/0000-0001-6320-0411; Ceda, Gian Paolo/0000-0002-9648-8295; Hayes, Richard/0000-0002-0918-661X; Vandenput, Liesbeth/0000-0002-1712-6131; Linneberg, Allan/0000-0002-0994-0184 FU NCATS NIH HHS [UL1 TR000124, UL1 TR001881]; NHLBI NIH HHS [HHSN268200800007C, HHSN268201200036C, N01HC85079, N01HC85081, N01HC85082, R01 HL075516]; NIA NIH HHS [P01 AG017242, P30 AG024827, R01 AG031890]; NIDDK NIH HHS [K24 DK080140, P30 DK020541, P30 DK063491, R01 DK078616, U01 DK078616] NR 58 TC 3 Z9 3 U1 7 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2016 VL 15 IS 5 BP 811 EP 824 DI 10.1111/acel.12490 PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DW5VN UT WOS:000383715600003 PM 27329260 ER PT J AU Strong, R Miller, RA Antebi, A Astle, CM Bogue, M Denzel, MS Fernandez, E Flurkey, K Hamilton, KL Lamming, DW Javors, MA de Magalhaes, JP Martinez, PA McCord, JM Miller, BF Muller, M Nelson, JF Ndukum, J Rainger, GE Richardson, A Sabatini, DM Salmon, AB Simpkins, JW Steegenga, WT Nadon, NL Harrison, DE AF Strong, Randy Miller, Richard A. Antebi, Adam Astle, Clinton M. Bogue, Molly Denzel, Martin S. Fernandez, Elizabeth Flurkey, Kevin Hamilton, Karyn L. Lamming, Dudley W. Javors, Martin A. de Magalhaes, Joao Pedro Martinez, Paul Anthony McCord, Joe M. Miller, Benjamin F. Muller, Michael Nelson, James F. Ndukum, Juliet Rainger, G. Ed Richardson, Arlan Sabatini, David M. Salmon, Adam B. Simpkins, James W. Steegenga, Wilma T. Nadon, Nancy L. Harrison, David E. TI Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an -glucosidase inhibitor or a Nrf2-inducer SO AGING CELL LA English DT Article DE acarbose; fish oil; metformin; NDGA; Protandim; rapamycin; UDCA; 17--estradiol ID GENETICALLY HETEROGENEOUS MICE; NORDIHYDROGUAIARETIC ACID; URSODEOXYCHOLIC ACID; DIETARY RESTRICTION; METFORMIN ACTION; FISH-OIL; IN-VIVO; RAPAMYCIN; MECHANISM; EXTENDS AB The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17--estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17--estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The -glucosidase inhibitor, acarbose, at a concentration previously tested (1000ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies. C1 [Strong, Randy; Fernandez, Elizabeth; Martinez, Paul Anthony] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Strong, Randy; Fernandez, Elizabeth; Martinez, Paul Anthony] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, South Texas Vet Hlth Care Syst, Dept Pharmacol, San Antonio, TX 78229 USA. [Strong, Randy; Fernandez, Elizabeth; Martinez, Paul Anthony; Nelson, James F.; Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78229 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Antebi, Adam; Denzel, Martin S.] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany. [Astle, Clinton M.; Bogue, Molly; Flurkey, Kevin; Ndukum, Juliet; Harrison, David E.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Hamilton, Karyn L.; Miller, Benjamin F.] Colorado State Univ, Ft Collins, CO 80523 USA. [Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [de Magalhaes, Joao Pedro] Univ Liverpool, Sch Biol Sci, Crown St, Liverpool L69 7ZB, Merseyside, England. [McCord, Joe M.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Muller, Michael] Univ East Anglia, Norwich Med Sch, Norwich, Norfolk, England. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Rainger, G. Ed] Univ Birmingham, Ctr Cardiovasc Sci, Sch Clin & Expt Med, Sch Med, Birmingham, W Midlands, England. [Richardson, Arlan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Oklahoma City, OK 73104 USA. [Richardson, Arlan] VA Med Ctr, Oklahoma City, OK 73104 USA. [Sabatini, David M.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. [Sabatini, David M.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Sabatini, David M.] Broad Inst Harvard & MIT, Seven Cambridge Ctr, Cambridge, MA 02142 USA. [Sabatini, David M.] MIT, David H Koch Inst Integrative Canc Res, Cambridge, MA 02139 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Simpkins, James W.] West Virginia Univ, Ctr Basic & Translat Stroke Res, Morgantown, WV 26506 USA. [Steegenga, Wilma T.] Univ Wageningen & Res Ctr, Div Human Nutr, Wageningen, Netherlands. [Nadon, Nancy L.] NIH, Div Aging Biol, Bethesda, MD 20892 USA. [de Magalhaes, Joao Pedro] Univ Liverpool, Inst Ageing & Chron Dis, Integrat Genom Ageing Grp, Liverpool L7 8TX, Merseyside, England. RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM strong@uthscsa.edu RI de Magalhaes, Joao Pedro/B-4741-2010 OI de Magalhaes, Joao Pedro/0000-0002-6363-2465 FU National Institute on Aging [AG013319, AG022303, AG022307, AG022308, AG024824, CA034196] FX National Institute on Aging, (Grant / Award Number: 'AG013319', 'AG022303', 'AG022307', 'AG022308', 'AG024824', 'CA034196'). NR 45 TC 0 Z9 0 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD OCT PY 2016 VL 15 IS 5 BP 872 EP 884 DI 10.1111/acel.12496 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DW5VN UT WOS:000383715600009 PM 27312235 ER PT J AU Calabrese, SK Mayer, KH Krakower, DS Magnus, M Underhill, K Earnshaw, VA Hansen, NB Kershaw, TS Betancourt, JR Dovidio, JF AF Calabrese, Sarah K. Mayer, Kenneth H. Krakower, Douglas S. Magnus, Manya Underhill, Kristen Earnshaw, Valerie A. Hansen, Nathan B. Kershaw, Trace S. Betancourt, Joseph R. Dovidio, John F. TI The Potential for Condom Ideology to Cloud Clinical Judgment around Prescribing HIV Pre-exposure Prophylaxis (PrEP) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Calabrese, Sarah K.; Kershaw, Trace S.] Yale Univ, Yale Sch Publ Hlth, New Haven, CT 06520 USA. [Calabrese, Sarah K.; Earnshaw, Valerie A.; Hansen, Nathan B.; Kershaw, Trace S.; Dovidio, John F.] Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Mayer, Kenneth H.; Krakower, Douglas S.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.; Krakower, Douglas S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Magnus, Manya] George Washington Univ, Milken Inst, Sch Publ Hlth, Washington, DC 20052 USA. [Underhill, Kristen] Yale Univ, Yale Law Sch, New Haven, CT 06520 USA. [Earnshaw, Valerie A.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, Athens, GA 30602 USA. [Betancourt, Joseph R.] Harvard Med Sch, Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA USA. [Dovidio, John F.] Yale Univ, Dept Psychol, New Haven, CT 06520 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA03.05 BP 44 EP 44 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600066 ER PT J AU Rodriguez-Garcia, M Shen, Z Kappes, J Ochsenbauer, C Wira, CR AF Rodriguez-Garcia, Marta Shen, Zheng Kappes, John Ochsenbauer, Christina Wira, Charles R. TI Characterization of Dendritic Cells with Rapid HIV Capture Potential from the Human Female Reproductive Tract SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Rodriguez-Garcia, Marta; Shen, Zheng; Wira, Charles R.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Kappes, John; Ochsenbauer, Christina] Univ Alabama Birmingham, Birmingham, AL USA. [Kappes, John] Birmingham Vet Affairs Med Ctr, Birmingham, AL 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA15.03 BP 79 EP 79 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600136 ER PT J AU Pyra, M Heffron, R Haberer, J Mugo, NR Celum, C Asiimwe, S Bukusi, E Katabira, E Baeten, JM AF Pyra, Maria Heffron, Renee Haberer, Jessica Mugo, Nelly R. Celum, Connie Asiimwe, Stephen Bukusi, Elizabeth Katabira, Elly Baeten, Jared M. CA Partners Demonstration Project TI PrEP Adherence among East African Women with HIV-infected Partners Participating in an Open-label Study SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Pyra, Maria; Heffron, Renee; Mugo, Nelly R.; Celum, Connie; Baeten, Jared M.] Univ Washington, Seattle, WA 98195 USA. [Haberer, Jessica] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haberer, Jessica] Harvard Med Sch, Boston, MA USA. [Haberer, Jessica; Asiimwe, Stephen] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Celum, Connie] Kabwohe Clin Res Ctr, Kabwohe, Uganda. [Katabira, Elly] Makerere Univ, Kampala, Uganda. 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA16.02 BP 81 EP 81 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600141 ER PT J AU Gosmann, C Anahtar, MN Handley, SA Farcasanu, M Abu-Ali, G Bowman, BA Padavattan, N Desai, C Droit, L Moodley, A Dong, M Ismail, N Ndung'u, T Ghebremichael, M Dong, KL Huttenhower, C Walker, BD Virgin, HW Kwon, DS AF Gosmann, Christina Anahtar, Melis N. Handley, Scott A. Farcasanu, Mara Abu-Ali, Galeb Bowman, Brittany A. Padavattan, Nikita Desai, Chandni Droit, Lindsay Moodley, Amber Dong, Mary Ismail, Nasreen Ndung'u, Thumbi Ghebremichael, Musie Dong, Krista L. Huttenhower, Curtis Walker, Bruce D. Virgin, Herbert W. Kwon, Douglas S. TI Cervicovaginal Bacterial Composition Impacts HIV Acquisition in Young African Women SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Gosmann, Christina; Anahtar, Melis N.; Farcasanu, Mara; Bowman, Brittany A.; Dong, Mary; Ndung'u, Thumbi; Ghebremichael, Musie; Dong, Krista L.; Walker, Bruce D.; Kwon, Douglas S.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Gosmann, Christina; Anahtar, Melis N.; Ghebremichael, Musie; Kwon, Douglas S.] Harvard Med Sch, Boston, MA USA. [Handley, Scott A.; Desai, Chandni; Droit, Lindsay; Virgin, Herbert W.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Abu-Ali, Galeb] Harvard Sch Publ Hlth, Boston, MA USA. [Padavattan, Nikita; Ismail, Nasreen; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa. [Moodley, Amber; Dong, Mary; Dong, Krista L.] Females Rising Educ Support & Hlth, Durban, South Africa. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Walker, Bruce D.; Kwon, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Virgin, Herbert W.] MIT, Cambridge, MA 02139 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD07.05LB BP 127 EP 127 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600225 ER PT J AU Madani, N Princiotto, A Easterhoff, D Bradley, T Luo, K Moody, MA Phad, G Bernat, NV Melillo, B Santra, S Ma, ZM Fritts, L Dutra, J Vrbanac, V Tager, A Smith, A Hedestam, GK Haynes, B Miller, C Sodroski, J AF Madani, Navid Princiotto, Amy Easterhoff, David Bradley, Todd Luo, Kan Moody, M. Anthony Phad, Ganesh Bernat, Nestor Vazquez Melillo, Bruno Santra, Sampa Ma, Zhong-Min Fritts, Linda Dutra, Joseph Vrbanac, Vladimir Tager, Andrew Smith, Amos Hedestam, Gunilla Karlsson Haynes, Barton Miller, Christopher Sodroski, Joseph TI Prevention of Vaginal Transmission of Simian-Human Immunodeficiency Virus (SHIV) in Rhesus Monkeys by Small-molecule CD4-mimetic Compounds SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Madani, Navid; Princiotto, Amy; Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. [Easterhoff, David; Bradley, Todd; Moody, M. Anthony; Haynes, Barton] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27706 USA. [Luo, Kan] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. [Phad, Ganesh; Bernat, Nestor Vazquez; Hedestam, Gunilla Karlsson] Karolinska Inst, S-10401 Stockholm, Sweden. [Melillo, Bruno; Smith, Amos] Univ Penn, Philadelphia, PA 19104 USA. [Santra, Sampa] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ma, Zhong-Min; Fritts, Linda; Dutra, Joseph; Miller, Christopher] Univ Calif Davis, Davis, CA 95616 USA. [Vrbanac, Vladimir; Tager, Andrew] 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD08.03LB BP 129 EP 129 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600228 ER PT J AU Richard, J Veillette, M Ding, S Zoubchenok, D Alsahafi, N Coutu, M Brassard, N Park, J Courter, JR Melillo, BN Smith, AB Shaw, GM Hahn, BH Sodroski, J Kaufmann, DE Finzi, A AF Richard, Jonathan Veillette, Maxime Ding, Shilei Zoubchenok, Daria Alsahafi, Nirmin Coutu, Mathieu Brassard, Nathalie Park, Jongwoo Courter, Joel R. Melillo, Bruno N. Smith, Amos B. Shaw, George M. Hahn, Beatrice H. Sodroski, Joseph Kaufmann, Daniel E. Finzi, Andres TI Role of Antibody-dependent Cell-mediated Cytotoxicity in HIV-1 Uninfected Bystander CD4+T Cell Killing SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Richard, Jonathan; Veillette, Maxime; Ding, Shilei; Zoubchenok, Daria; Kaufmann, Daniel E.; Finzi, Andres] Univ Montreal, CRCHUM, Montreal, PQ, Canada. [Alsahafi, Nirmin] CRCHUM McGill, Montreal, PQ, Canada. [Coutu, Mathieu; Brassard, Nathalie] CRCHUM, Montreal, PQ, Canada. [Park, Jongwoo; Courter, Joel R.; Melillo, Bruno N.; Smith, Amos B.; Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Philadelphia, PA 19104 USA. [Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.12 BP 137 EP 137 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600242 ER PT J AU Newman, RM Joshi, V Pack, M Batorsky, R Power, K Tully, DC Bazner, SB Rosenberg, ES Altfeld, M Allen, TM AF Newman, Ruchi M. Joshi, Vinita Pack, Melissa Batorsky, Rebecca Power, Karen Tully, Damien C. Bazner, Suzane B. Rosenberg, Eric S. Altfeld, Marcus Allen, Todd M. TI Characterizing Viral Evolution and bNAb Specificities in Two Subjects Infected with Closely Related Founder Strains of HIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Newman, Ruchi M.; Joshi, Vinita; Pack, Melissa; Batorsky, Rebecca; Power, Karen; Tully, Damien C.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Bazner, Suzane B.; Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Altfeld, Marcus] Heinrich Pette Inst, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P06.16LB BP 206 EP 206 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600376 ER PT J AU Tully, DC Bean, DJ Maldini, CR Vrbanac, VD Tager, AM Boutwell, CL Allen, TM AF Tully, Damien C. Bean, David J. Maldini, Colby R. Vrbanac, Vladimir D. Tager, Andrew M. Boutwell, Christian L. Allen, Todd M. TI BLT Humanized Mice Recapitulate the Preferential Transmission of Env N362 Observed During Heterosexual HIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Tully, Damien C.; Bean, David J.; Maldini, Colby R.; Boutwell, Christian L.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Vrbanac, Vladimir D.; Tager, Andrew M.] 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 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P12.08 BP 262 EP 262 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600482 ER PT J AU Jones, T Lockhart, JS Mendelsohn-Victor, KE Duquette, D Northouse, LL Duffy, SA Donley, R Merajver, SD Milliron, KJ Roberts, JS Katapodi, MC AF Jones, Tarsha Lockhart, Joan S. Mendelsohn-Victor, Kari E. Duquette, Debra Northouse, Laurel L. Duffy, Sonia A. Donley, Rosemary Merajver, Sofia D. Milliron, Kara J. Roberts, J. Scott Katapodi, Maria C. TI Use of Cancer Genetics Services in African-American Young Breast Cancer Survivors SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BLACK-WOMEN; HEREDITARY BREAST; OVARIAN-CANCER; CLINICAL CHARACTERISTICS; PLANNED BEHAVIOR; BRCA1/2; DISPARITIES; RISK; POPULATION; MUTATIONS AB Introduction: African-American women have higher rates of early-onset breast cancer compared with their Caucasian counterparts; yet, when diagnosed with breast cancer at a young age, they underuse genetic counseling and testing to manage their risk of developing future cancers. Methods: Self-reported baseline data were collected between September 2012 and January 2013 and analyzed in 2014 from a subpopulation of 340 African-American young breast cancer survivors (YBCSs) enrolled in an RCT. YBCSs were diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 20 and 45 years and were randomly selected from a statewide cancer registry. Logistic regression examined predictors of using cancer genetics services. Results: Overall, 28% of the sample reported having genetic counseling and 21% reported having genetic testing, which were significantly lower (p <= 0.005) compared with white/other YBCSs participating in the parent study. In a multivariate analysis, income was positively associated with counseling (B=0.254, p <= 0.01) and testing (B=0.297, p <= 0.01), whereas higher education levels (B=-0.328, p <= 0.05) and lack of access to healthcare services owing to cost (B=-1.10, p <= 0.03) were negatively associated with genetic counseling. Lower income and lack of care because of high out-of-pocket costs were commonly reported barriers. Conclusions: Despite national recommendations for genetic evaluation among women with early-onset breast cancer, few African-American YBCSs reported undergoing genetic counseling and testing. Most reported that their healthcare provider did not recommend these services. Interventions addressing patient, provider, and structural healthcare system barriers to using genetic counseling and testing in this population are needed. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Jones, Tarsha] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Jones, Tarsha; Lockhart, Joan S.; Donley, Rosemary] Duquesne Univ, Sch Nursing, Pittsburgh, PA 15219 USA. [Mendelsohn-Victor, Kari E.; Northouse, Laurel L.; Katapodi, Maria C.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Duquette, Debra] Michigan Dept Hlth & Human Serv, Canc Genom Program, Lansing, MI USA. [Duffy, Sonia A.] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Merajver, Sofia D.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Milliron, Kara J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Katapodi, Maria C.] Univ Basel, Inst Nursing Sci, Basel, Switzerland. RP Katapodi, MC (reprint author), Univ Basel, Nursing Sci, Fac Med, Bernoullistr 28,Room 113, CH-4056 Basel, Switzerland. EM maria.katapodi@unibas.ch OI Duffy, Sonia /0000-0002-8123-2692 FU CDC [RFA-DP-09-001, SIP 044, 5U48DP001901-03] FX The authors would like to acknowledge the contributions of Glenn Copeland, MBA, Director, Michigan Cancer Surveillance Program, for patient identification and recruitment; Beth Anderson, MPH, Michigan Department of Health and Human Services, Cancer Genomics Program, for patient identification and recruitment; Meghan Underhill, PhD, RN, AOCNS, Instructor, The Phyllis F. Cantor Center for Research in Nursing and Patient Care Services at Dana-Farber Cancer Institute, for editorial comments on the manuscript. The study was funded by CDC, RFA-DP-09-001, SIP 044, 5U48DP001901-03. Principal Investigator: Maria C. Katapodi. NR 46 TC 2 Z9 2 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 427 EP 436 DI 10.1016/j.amepre.2016.03.016 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200007 PM 27117712 ER PT J AU Cohen, JFW Gorski, MT Hoffman, JA Rosenfeld, L Chaffee, R Smith, L Catalano, PJ Rimm, EB AF Cohen, Juliana F. W. Gorski, Mary T. Hoffman, Jessica A. Rosenfeld, Lindsay Chaffee, Ruth Smith, Lauren Catalano, Paul J. Rimm, Eric B. TI Healthier Standards for School Meals and Snacks Impact on School Food Revenues and Lunch Participation Rates SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COMPETITIVE FOODS; CONSUMPTION; PROGRAM; WASTE AB Introduction: In 2012, the updated U.S. Department of Agriculture school meals standards and a competitive food law similar to the fully implemented version of the national Smart Snack standards went into effect in Massachusetts. This study evaluated the impact of these updated school meal standards and Massachusetts' comprehensive competitive food standards on school food revenues and school lunch participation. Methods: Revenue and participation data from 11 Massachusetts school districts were collected from 2011 to 2014 and analyzed in 2015 using multilevel modeling. The association between the change in compliance with the competitive food standards and revenues/participation was assessed using linear regression. Results: Schools experienced declines in school food revenues of $15.40/student in Year 1 from baseline (p = 0.05), due to competitive food revenue losses. In schools with 3 years of data, overall revenues rebounded by the second year post-implementation. Additionally, by Year 2, school lunch participation increased by 15% (p=0.0006) among children eligible for reduced-price meals. Better competitive food compliance was inversely associated with school food revenues in the first year only; an absolute change in compliance by 10% was associated with a $9.78/student decrease in food revenues over the entire school year (p=0.04). No association was seen between the change in compliance and school meal participation. Conclusions: Schools experienced initial revenue losses after implementation of the standards, yet longer-term school food revenues were not impacted and school meal participation increased among children eligible for reduced-price meals. Weakening the school meal or competitive food guidelines based on revenue concerns appears unwarranted. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Cohen, Juliana F. W.] Merrimack Coll, Dept Hlth Sci, 315 Turnpike St, N Andover, MA 01845 USA. [Cohen, Juliana F. W.; Rimm, Eric B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Gorski, Mary T.] Harvard Univ, Harvard Grad Sch Arts & Sci, Interfac Initiat Hlth Policy, Cambridge, MA USA. [Hoffman, Jessica A.; Chaffee, Ruth] Northeastern Univ, Bouve Coll Hlth Sci, Dept Appl Psychol, Boston, MA 02115 USA. [Rosenfeld, Lindsay] Brandeis Univ, Heller Sch Social Policy & Management, Inst Child Youth & Family Policy, Waltham, MA USA. [Smith, Lauren] FSG, Boston, MA USA. [Catalano, Paul J.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Rimm, Eric B.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Med Sch, Boston, MA USA. RP Cohen, JFW (reprint author), Merrimack Coll, Dept Hlth Sci, 315 Turnpike St, N Andover, MA 01845 USA. EM cohenj@merrimack.edu FU Nutritional Epidemiology of Cancer Education and Career Development Program [R25 CA 098566]; Agency for Healthcare Research and Quality [T32HS000055] FX The authors are grateful to MaryJo Culter, Thomas Land, Kathleen Millett, Christina Nordstrom, Julianna Valcour, and Laura York for their assistance throughout the study. Funding for the Nutrition Opportunities to Understand Reforms Involving Student Health study was provided by Harvard Catalyst and The Robert Wood Johnson Foundation. Juliana Cohen was supported by the Nutritional Epidemiology of Cancer Education and Career Development Program (grant no. R25 CA 098566). Mary Gorski is supported by the Agency for Healthcare Research and Quality (grant no. T32HS000055). NR 17 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 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 485 EP 492 DI 10.1016/j.amepre.2016.02.031 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200013 PM 27147133 ER PT J AU Ommerborn, MJ Blackshear, CT Hickson, DA Griswold, ME Kwatra, J Djousse, L Clark, CR AF Ommerborn, Mark J. Blackshear, Chad T. Hickson, DeMarc A. Griswold, Michael E. Kwatra, Japneet Djousse, Luc Clark, Cheryl R. TI Ideal Cardiovascular Health and Incident Cardiovascular Events The Jackson Heart Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; AFRICAN-AMERICANS; ATHEROSCLEROSIS RISK; DISEASE; STROKE; WOMEN; MEN; COMMUNITIES; INTERVENTIONS AB Introduction: The epidemiology of American Heart Association ideal cardiovascular health (CVH) metrics has not been fully examined in African Americans. This study examines the associations of CVH metrics with incident cardiovascular disease (CVD) in the Jackson Heart Study, a longitudinal cohort study of CVD in African Americans. Methods: Jackson Heart Study participants without CVD (n=4,702) were followed prospectively between 2000 and 2011. Incidence rates and Cox proportional hazard ratios estimated risks for incident CVD (myocardial infarction, stroke, cardiac procedures, and CVD mortality) associated with seven CVH metrics by sex. Analyses were performed in 2015. Results: Participants were followed for a median of 8.3 years; none had ideal health on all seven CVH metrics. The prevalence of ideal health was low for nutrition, physical activity, BMI, and blood pressure metrics. The age-adjusted CVD incidence rate (IR) per 1,000 person years was highest for individuals with the least ideal health metrics: zero to one (IR=12.5, 95% CI=9.7, 16.1), two (IR=8.2, 95% CI=6.5, 10.4), three (IR=5.7, 95% CI=4.2, 7.6), and four or more (IR=3.4, 95% CI=2.0, 5.9). Adjusting for covariates, individuals with four or more ideal CVH metrics had lower risks of incident CVD compared with those with zero or one ideal CVH metric (hazard ratio, 0.29; 95% CI=0.17, 0.52; p<0.001). Conclusions: African Americans with more ideal CVH metrics have lower risks of incident CVD. Comprehensive preventive behavioral and clinical supports should be intensified to improve CVD risk for African Americans with few ideal CVH metrics. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Ommerborn, Mark J.; Kwatra, Japneet; Clark, Cheryl R.] Brigham & Womens Hosp, Ctr Community Hlth & Hlth Equ, 1620 Tremont St, Boston, MA 02120 USA. [Blackshear, Chad T.; Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Hickson, DeMarc A.] My Bros Keeper Inc, Ctr Res Evaluat & Environm & Policy Change, Jackson, MS USA. [Hickson, DeMarc A.] Jackson State Univ, Dept Epidemiol & Biostat, Jackson, MS USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Djousse, Luc] Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Djousse, Luc; Clark, Cheryl R.] Harvard Med Sch, Boston, MA USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Clark, Cheryl R.] Brigham & Womens Faulkner Hosp Program, Div Gen Med & Primary Care, Boston, MA USA. RP Clark, CR (reprint author), Brigham & Womens Hosp, Ctr Community Hlth & Hlth Equ, 1620 Tremont St, Boston, MA 02120 USA. EM crclark@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Institutes of Aging [K08 AG 032357]; National Heart, Lung, and Blood Institute; National Center for Minority Health and Health Disparities [N01-HC-95170, N01-HC-95171, N01-HC-95172] FX This research was supported with funding from the National Institutes of Aging (K08 AG 032357). The Jackson Heart Study was supported by the National Heart, Lung, and Blood Institute and the National Center for Minority Health and Health Disparities (contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 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 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 502 EP 506 DI 10.1016/j.amepre.2016.07.003 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200015 PM 27539974 ER PT J AU McCarthy, AM Kim, JJ Beaber, EF Zheng, YY Burnett-Hartman, A Chubak, J Ghai, NR McLerran, D Breen, N Conant, EF Geller, BM Green, BB Klabunde, CN Inrig, S Skinner, CS Quinn, VP Haas, JS Schnall, M Rutter, CM Barlow, WE Corley, DA Armstrong, K Doubeni, CA AF McCarthy, Anne Marie Kim, Jane J. Beaber, Elisabeth F. Zheng, Yingye Burnett-Hartman, Andrea Chubak, Jessica Ghai, Nirupa R. McLerran, Dale Breen, Nancy Conant, Emily F. Geller, Berta M. Green, Beverly B. Klabunde, Carrie N. Inrig, Stephen Skinner, Celette Sugg Quinn, Virginia P. Haas, Jennifer S. Schnall, Mitchell Rutter, Carolyn M. Barlow, William E. Corley, Douglas A. Armstrong, Katrina Doubeni, Chyke A. CA PROSPR Consortium TI Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID OCCULT BLOOD-TEST; LOW-INCOME WOMEN; UNITED-STATES; CARE; MAMMOGRAPHY; DIAGNOSIS; QUALITY; PREDICTORS; TIME; IMPROVEMENT AB Introduction: Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group. Methods: Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy <= 3 months following positive FOBT/ FIT; additional imaging or biopsy <= 3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or <= 9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income. Results: Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21). Conclusions: Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, 50 Staniford St,940F, Boston, MA 02114 USA. [Kim, Jane J.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Beaber, Elisabeth F.; McLerran, Dale] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Zheng, Yingye] Fred Hutchinson Canc Res Ctr, Dept Biostat, 1124 Columbia St, Seattle, WA 98104 USA. [Burnett-Hartman, Andrea] Fred Hutchinson Canc Res Ctr, Div Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA. [Burnett-Hartman, Andrea] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Chubak, Jessica; Green, Beverly B.] Grp Hlth Res Inst, Seattle, WA USA. [Ghai, Nirupa R.; Quinn, Virginia P.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Breen, Nancy] NCI, Hlth Syst & Intervent Res Branch, Bethesda, MD 20892 USA. [Conant, Emily F.; Schnall, Mitchell] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Geller, Berta M.] Univ Vermont, Dept Family Med, Burlington, VT USA. [Klabunde, Carrie N.] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA. [Inrig, Stephen] Univ Texas Southwestern Med Ctr Dallas, Dept Hlth Policy & Hist Med, Dallas, TX 75390 USA. [Inrig, Stephen] Mt St Marys Univ, Dept Hlth Policy & Management, Los Angeles, CA USA. [Skinner, Celette Sugg] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Skinner, Celette Sugg] Univ Texas Southwestern Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA. [Barlow, William E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Corley, Douglas A.] Kaiser Permanente Northern Calif, Dept Gastroenterol, Oakland, CA USA. [Doubeni, Chyke A.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,940F, Boston, MA 02114 USA. EM amccarthy8@partners.org OI Inrig, Stephen/0000-0003-2091-5841 FU NIH/National Cancer Institute PROSPR program [U54CA163262, U54CA163261, U54CA163308, U54CA163313, U54CA163303, U54CA163307, U54CA164336, U01CA163304] FX This work was funded by the NIH/National Cancer Institute PROSPR program, grant numbers: Kaiser Foundation Research Institute U54CA163262, Group Health Research Institute U54CA163261, Parkland UT Southwestern U54CA163308, University of Pennsylvania U54CA163313, University of Vermont U54CA163303, Geisel School of Medicine at Dartmouth and Brigham and Women's Hospital U54CA163307, University of New Mexico U54CA164336, Fred Hutchinson Cancer Research Center U01CA163304. NR 32 TC 1 Z9 1 U1 8 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 507 EP 512 DI 10.1016/j.amepre.2016.03.017 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200016 PM 27132628 ER PT J AU Rigotti, NA Stoney, CM AF Rigotti, Nancy A. Stoney, Catherine M. TI CHARTing the Future Course of Tobacco-Cessation Interventions for Hospitalized Smokers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Med Sch, Boston, MA USA. [Stoney, Catherine M.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, 50 Staniford St,914, Boston, MA 02114 USA. EM nrigotti@partners.org FU NIH/National Heart, Lung, and Blood Institute [R01-HL11821] FX Dr. Rigotti was supported by NIH/National Heart, Lung, and Blood Institute grant number R01-HL11821, receives royalties from UpToDate, Inc., and has received travel expenses from Pfizer, Inc., to attend consultant meetings for which she received no honorarium. No other financial disclosures were reported by the authors of this paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or the U.S. Government. NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 549 EP 550 DI 10.1016/j.amepre.2016.07.012 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200024 PM 27647055 ER PT J AU Rigotti, NA Tindle, HA Regan, S Levy, DE Chang, YC Carpenter, KM Park, ER Kelley, JHK Streck, JM Reid, ZZ Ylioja, T Reyen, M Singer, DE AF Rigotti, Nancy A. Tindle, Hilary A. Regan, Susan Levy, Douglas E. Chang, Yuchiao Carpenter, Kelly M. Park, Elyse R. Kelley, Jennifer H. K. Streck, Joanna M. Reid, Zachary Z. Ylioja, Thomas Reyen, Michele Singer, Daniel E. TI A Post-Discharge Smoking-Cessation Intervention for Hospital Patients Helping Hand 2 Randomized Clinical Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SMOKERS; ADULTS; DISORDERS; ALCOHOL; WOMEN AB Introduction: Hospitalization provides an opportunity for smokers to quit, but tobacco-cessation interventions started in hospital must continue after discharge to be effective. This study aimed to improve the scalability of a proven effective post-discharge intervention by incorporating referral to a telephone quitline, a nationally available cessation resource. Study design: A three-site RCT compared Sustained Care, a post-discharge tobacco-cessation intervention, with Standard Care among hospitalized adult smokers who wanted to quit smoking and received in-hospital tobacco-cessation counseling. Setting/participants: A total of 1,357 daily smokers admitted to three hospitals were enrolled from December 2012 to July 2014. Intervention: Sustained Care started at discharge and included automated interactive voice response telephone calls and the patient's choice of cessation medication for 3 months. Each automated call advised cessation, supported medication adherence, and triaged smokers seeking additional counseling or medication support directly to a telephone quitline. Standard Care provided only medication and counseling recommendations at discharge. Main outcome measures: Biochemically confirmed past 7-day tobacco abstinence 6 months after discharge (primary outcome) and self-reported tobacco abstinence and tobacco-cessation treatment use at 1, 3, and 6 months and overall (0-6 months). Analyses were done in 2015-2016. Results: Smokers offered Sustained Care (n=680), versus those offered Standard Care (n=677), did not have greater biochemically confirmed abstinence at 6 months (17% vs 16%, p=0.58). However, the Sustained Care group reported more tobacco-cessation counseling and medication use at each follow-up and higher rates of self-reported past 7-day tobacco abstinence at 1 month (43% vs 32%, p<0.0001) and 3 months (37% vs 30%, p=0.008). At 6 months, the difference narrowed (31% vs 27%, p=0.09). Overall, the intervention increased self-reported 7-day abstinence over the 6-month follow-up (relative risk, 1.25; 95% CI=1.10, 1.40; p=0.0006). Conclusions: A 3-month post-discharge smoking-cessation intervention for hospitalized smokers who wanted to quit did not increase confirmed tobacco abstinence at 6 months but did increase self-reported abstinence during the treatment period (3months). Real-time linkage of interactive voice response calls to a quitline, done in this trial to increase scalability of a previously proven cessation intervention, demonstrated short-term promise but did not sustain long-term intervention effectiveness. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Rigotti, Nancy A.; Regan, Susan; Levy, Douglas E.; Park, Elyse R.; Kelley, Jennifer H. K.; Reid, Zachary Z.; Reyen, Michele] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,914, Boston, MA 02114 USA. [Rigotti, Nancy A.; Regan, Susan; Chang, Yuchiao; Reyen, Michele; Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Rigotti, Nancy A.; Levy, Douglas E.; Park, Elyse R.; Kelley, Jennifer H. K.; Reid, Zachary Z.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Rigotti, Nancy A.; Levy, Douglas E.; Park, Elyse R.; Kelley, Jennifer H. K.; Reid, Zachary Z.] Partners HealthCare, Boston, MA USA. [Rigotti, Nancy A.; Regan, Susan; Levy, Douglas E.; Chang, Yuchiao; Singer, Daniel E.] Harvard Med Sch, Dept Med, Boston, MA USA. [Tindle, Hilary A.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Carpenter, Kelly M.] Alere Wellbeing Inc, Seattle, WA USA. [Park, Elyse R.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Streck, Joanna M.] Univ Vermont, Dept Psychol Sci, Burlington, VT USA. [Ylioja, Thomas] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,914, Boston, MA 02114 USA. EM nrigotti@partners.org FU NIH/NHLBI [R01-HL11821] FX NIH/NHLBI grant #R01-HL11821. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr. Rigotti had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 21 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 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 597 EP 608 DI 10.1016/j.amepre.2016.04.005 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200029 PM 27647060 ER PT J AU Cruvinel, E Richter, KP Stoney, C Duffy, S Fellows, J Harrington, KF Rigotti, NA Sherman, S Tindle, HA Shireman, TI Shelley, D Waiwaiole, L Cummins, S AF Cruvinel, Erica Richter, Kimber P. Stoney, Catherine Duffy, Sonia Fellows, Jeffrey Harrington, Kathleen F. Rigotti, Nancy A. Sherman, Scott Tindle, Hilary A. Shireman, Theresa I. Shelley, Donna Waiwaiole, Lisa Cummins, Sharon TI CHARTing a Path to Pragmatic Tobacco Treatment Research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID TRIALS; PRECIS AB Introduction: It is important to consider the degree to which studies are explanatory versus pragmatic to understand the implications of their findings for patients, healthcare professionals, and policymakers. Pragmatic trials test the effectiveness of interventions in real-world conditions; explanatory trials test for efficacy under ideal conditions. The Consortium of Hospitals Advancing Research on Tobacco (CHART) is a network of seven NIH-funded trials designed to identify effective programs that can be widely implemented in routine clinical practice. Methods: A cross-sectional analysis of CHART trial study designs was conducted to place each study on the pragmatic-explanatory continuum. After reliability training, six raters independently scored each CHART study according to ten PRagmatic Explanatory Continuum Indicator Summary (PRECIS) dimensions, which covered participant eligibility criteria, intervention flexibility, practitioner expertise, follow-up procedures, participant compliance, practitioner adherence, and outcome analyses. Means and SDs were calculated for each dimension of each study, with lower scores representing more pragmatic elements. Results were plotted on "spoke and wheel" diagrams. The rating process and analyses were performed in October 2014 to September 2015. Results: All seven CHART trials tended toward the pragmatic end of the spectrum, although there was a range from 0.76 (SD = 0.23) to 1.85 (SD = 0.58). Most studies included some explanatory design elements. Conclusions: CHART findings should be relatively applicable to clinical practice. Funders and reviewers could integrate PRECIS criteria into their guidelines to better facilitate pragmatic research. CHART study protocols, coupled with scores reported here, may help readers improve the design of their own pragmatic trials. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Cruvinel, Erica] Univ Fed Juiz de Fora, Dept Psychol, Juiz De Fora, MG, Brazil. [Richter, Kimber P.] Univ Kansas, Med Ctr, Dept Prevent Med & Publ Hlth, Kansas City, KS 66103 USA. [Richter, Kimber P.] Univ Kansas, Med Ctr, Ctr Canc, Kansas City, KS 66103 USA. [Stoney, Catherine] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Duffy, Sonia] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Duffy, Sonia] Dept Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Fellows, Jeffrey; Waiwaiole, Lisa] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Harrington, Kathleen F.] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Rigotti, Nancy A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Rigotti, Nancy A.] Harvard Med Sch, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA USA. [Sherman, Scott] NYU, Sch Med, Dept Populat Hlth Med, New York, NY USA. [Sherman, Scott] NYU, Sch Med, Dept Med, New York, NY USA. [Sherman, Scott] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Tindle, Hilary A.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Shireman, Theresa I.] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Shelley, Donna] NYU, Sch Med, Dept Populat Med, New York, NY USA. [Cummins, Sharon] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. RP Cruvinel, E (reprint author), Univ Fed Juiz de Fora, Dept Psychol, Ctr Res Intervent & Evaluat Alcohol & Other Drugs, Juiz De Fora, MG, Brazil. EM ecruvinel@yahoo.com.br OI Sherman, Scott/0000-0003-1752-7303 FU Foundation for Research Support of Minas Gerais (FAPEMIG); National Council for Scientific and Technological Development (CNPq); Coordination for the Improvement of Higher Education Personnel (CAPES) of Brazil; National Heart, Lung, and Blood Institute [U01 HL105232-01] FX The authors thank Niaman Nazir, MBBS, MPH, for assistance with formatting the spoke and wheel diagrams. This work was supported by the National Heart, Lung, and Blood Institute (U01 HL105232-01) and the Foundation for Research Support of Minas Gerais (FAPEMIG), National Council for Scientific and Technological Development (CNPq), and Coordination for the Improvement of Higher Education Personnel (CAPES) of Brazil. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute; NIH; or the government of Brazil. The study sponsor had no role in study design; collection, analysis, or interpretation of data; writing the report; or the decision to submit the report for publication. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 630 EP 636 DI 10.1016/j.amepre.2016.05.025 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200032 PM 27647063 ER PT J AU Mei, ZB Duan, CY Li, CB Cui, L Ogino, S AF Mei, Z. B. Duan, C. Y. Li, C. B. Cui, L. Ogino, S. TI Prognostic role of tumor PIK3CA mutation in colorectal cancer: a systematic review and meta-analysis SO ANNALS OF ONCOLOGY LA English DT Review DE PIK3CA; mutation; colorectal cancer; prognosis ID III COLON-CANCER; PUBLICATION BIAS; PREDICTIVE-VALUE; POOR SURVIVAL; ASPIRIN USE; MICROSATELLITE INSTABILITY; ANTIBODY THERAPY; GENE-MUTATIONS; CELL-GROWTH; PTEN GENE AB This study has the largest sample size of over 12 000, and is also the most comprehensive assessment of the literature to date regarding prognostic role of tumor PIK3CA mutation in colorectal cancer (CRC). We find that in patients with CRC, PIK3CA mutation may not add prognostic information regarding overall survival or progression-free survival.Somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT pathway play a vital role in carcinogenesis. Approximately 15%-20% of colorectal cancers (CRCs) harbor activating mutations in PIK3CA, making it one of the most frequently mutated genes in CRC. We thus carried out a systematic review and meta-analysis investigating the prognostic significance of PIK3CA mutations in CRC. Electronic databases were searched from inception through May 2015. We extracted the study characteristics and prognostic data of each eligible study. The hazard ratio (HR) and 95% confidence interval (CI) were derived and pooled using the random-effects Mantel-Haenszel model. Twenty-eight studies enrolling 12 747 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 19 and 10 studies, respectively. Comparing PIK3CA-mutated CRC patients with PIK3CA-wild-type CRC patients, the summary HRs for OS and PFS were 0.96 (95% CI 0.83-1.12) and 1.20 (95% CI 0.98-1.46), respectively. The trim-and-fill, Copas model and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Five studies reported the CRC prognosis for PIK3CA mutations in exons 9 and 20 separately; neither exon 9 mutation nor exon 20 mutation in PIK3CA was significantly associated with patient survival. Our findings suggest that PIK3CA mutation has the neutral prognostic effects on CRC OS and PFS. Evidence was accumulating for the establishment of CRC survival between PIK3CA mutations and patient-specific clinical or molecular profiles. C1 [Mei, Z. B.] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Anorectal Surg, 528 Zhangheng Rd, Shanghai 201203, Peoples R China. [Duan, C. Y.] Third Mil Med Univ, Daping Hosp, State Key Lab Trauma Burns & Combined Injury, Dept Res 2,Inst Surg, Chongqing, Peoples R China. [Li, C. B.] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China. [Cui, L.] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Colorectal Surg, Shanghai, Peoples R China. [Ogino, S.] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA. [Ogino, S.] Harvard Med Sch, Boston, MA USA. [Ogino, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, S.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Mei, ZB (reprint author), Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Anorectal Surg, 528 Zhangheng Rd, Shanghai 201203, Peoples R China. EM herrmayor@126.com FU USA National Institute of Health [R01CA151993, R35CA197735]; Shanghai TCM promotion "3-year action plan" [ZY3-CCCX-3-3034, ZY3-CCCX-2-1003]; Science and Technology Commission of Shanghai Municipality [14401931000]; Shanghai Key Laboratory of Psychotic Disorders - Science and Technology Commission of Shanghai Municipality [13dz2260500] FX This research was supported by USA National Institute of Health (grant no. R01CA151993 and R35CA197735), Shanghai TCM promotion "3-year action plan" (grant no. ZY3-CCCX-3-3034 and ZY3-CCCX-2-1003), Science and Technology Commission of Shanghai Municipality (grant no. 14401931000). Shanghai Key Laboratory of Psychotic Disorders sponsored by the Science and Technology Commission of Shanghai Municipality (grant no. 13dz2260500). NR 60 TC 3 Z9 3 U1 0 U2 0 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 OCT PY 2016 VL 27 IS 10 BP 1836 EP 1848 DI 10.1093/annonc/mdw264 PG 13 WC Oncology SC Oncology GA DZ7BJ UT WOS:000386018200004 PM 27436848 ER PT J AU Bekendam, RH Flaumenhaft, R AF Bekendam, Roelof H. Flaumenhaft, Robert TI Inhibition of Protein Disulfide Isomerase in Thrombosis SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Scandinavian-Physiological-Society CY SEP 18-20, 2015 CL Aarhus, DENMARK SP Scandinavian Physiol Soc ID MEDIATES PLATELET-AGGREGATION; TISSUE FACTOR ACTIVATION; FORMATION IN-VIVO; SURFACE EXPRESSION; CHAPERONE FUNCTION; FIBRIN GENERATION; LINKED COMPLEXES; INTEGRIN; BINDING; DOMAIN AB This MiniReview addresses our current understanding of the mechanisms by which protein disulfide isomerase (PDI) mediates thrombus formation and discusses the potential of blocking thrombosis by targeting PDI. Thiol isomerases are ubiquitous oxidoreductases primarily localized to the endoplasmic reticulum (ER) where they serve a critical role in protein folding. PDI is the founding member of the thiol isomerase family. Although PDI is an essential intracellular enzyme, it can participate in pathological processes once released from cells. In particular, PDI serves a critical role in thrombus formation, the underlying cause of myocardial infarction and stroke. Both platelets and endothelial cells secrete PDI upon vascular injury. Secreted PDI appears to activate multiple extracellular substrates in the vasculature, enabling the initiation of thrombus formation. As an essential component of thrombus formation, extracellular PDI represents a new target for pharmacological inhibition of clinical thrombosis. Quercetin-3-rutinoside, a flavonol highly abundant in common foods, inhibits PDI and blocks thrombus formation both in vitro and in vivo. Such observations have prompted clinical trials targeting PDI in thrombotic diseases. C1 [Bekendam, Roelof H.; Flaumenhaft, Robert] Harvard Med Sch, BIDMC, Dept Med, Div Hemostasis & Thrombosis, Boston, MA USA. RP Flaumenhaft, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hemostasis & Thrombosis, 330 Brookline Ave, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu NR 57 TC 2 Z9 2 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-7835 EI 1742-7843 J9 BASIC CLIN PHARMACOL JI Basic Clin. Pharmacol. Toxicol. PD OCT PY 2016 VL 119 SU 3 BP 42 EP 48 DI 10.1111/bcpt.12573 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA EB0HO UT WOS:000387025100006 PM 26919268 ER PT J AU Singh, B Kulawiec, M Owens, KM Singh, A Singh, KK AF Singh, B. Kulawiec, M. Owens, K. M. Singh, A. Singh, K. K. TI Sustained early disruption of mitochondrial function contributes to arsenic-induced prostate tumorigenesis SO BIOCHEMISTRY-MOSCOW LA English DT Article DE arsenic; mitochondria; mtOXPHOS; genomic instability; tumorigenic transformation; prostate cancer ID INDUCED MALIGNANT-TRANSFORMATION; DRINKING-WATER; EPITHELIAL-CELLS; CANCER-MORTALITY; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; MAMMALIAN-CELLS; RISK-ASSESSMENT; LUNG-CANCER; WEST-BENGAL AB Arsenic is a well-known human carcinogen that affects millions of people worldwide, but the underlying mechanisms of carcinogenesis are unclear. Several epidemiological studies have suggested increased prostate cancer incidence and mortality due to exposure to arsenic. Due to lack of an animal model of arsenic-induced carcinogenesis, we used a prostate epithelial cell culture model to identify a role for mitochondria in arsenic-induced prostate cancer. Mitochondrial morphology and membrane potential was impacted within a few hours of arsenic exposure of non-neoplastic prostate epithelial cells. Chronic arsenic treatment induced mutations in mitochondrial genes and altered mitochondrial functions. Human non-neoplastic prostate epithelial cells continuously cultured for seven months in the presence of 5 A mu M arsenite showed tumorigenic properties in vitro and induced tumors in SCID mice, which indicated transformation of these cells. Protein and mRNA expression of subunits of mtOXPHOS complex I were decreased in arsenic-transformed cells. Alterations in complex I, a main site for reactive oxygen species (ROS) production as well as increased expression of ROS-producing NOX4 in arsenic-transformed cells suggested a role of oxidative stress in tumorigenic transformation of prostate epithelial cells. Whole genome cGH array analyses of arsenic-transformed prostate cells identified extensive genomic instability. Our study revealed mitochondrial dysfunction induced oxidative stress and decreased expression of p53 in arsenic-transformed cells as an underlying mechanism of the mitochondrial and nuclear genomic instability. These studies suggest that early changes in mitochondrial functions are sustained during prolong arsenic exposure. Overall, our study provides evidence that arsenic disruption of mitochondrial function is an early and key step in tumorigenic transformation of prostate epithelial cells. C1 [Singh, B.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. [Kulawiec, M.; Owens, K. M.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Singh, A.] SUNY Buffalo, Dept Pediat, Buffalo, NY 12246 USA. [Singh, K. K.] Univ Alabama Birmingham, Ctr Aging, Birmingham, AL 35294 USA. [Singh, K. K.] UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Genet, Birmingham, AL 35294 USA. [Singh, K. K.] UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Pathol, Birmingham, AL 35294 USA. [Singh, K. K.] UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Environm Hlth, Birmingham, AL 35294 USA. [Singh, K. K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Singh, KK (reprint author), Univ Alabama Birmingham, Ctr Aging, Birmingham, AL 35294 USA.; Singh, KK (reprint author), UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Genet, Birmingham, AL 35294 USA.; Singh, KK (reprint author), UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Pathol, Birmingham, AL 35294 USA.; Singh, KK (reprint author), UAB Comprehens Canc Ctr, Ctr Free Rad Biol, Dept Environm Hlth, Birmingham, AL 35294 USA.; Singh, KK (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. EM kksingh@uab.edu FU Veterans Administration [1I01BX001716] FX This study was supported by grant from Veterans Administration 1I01BX001716. NR 97 TC 0 Z9 0 U1 1 U2 1 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 EI 0320-9725 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD OCT PY 2016 VL 81 IS 10 BP 1089 EP 1100 DI 10.1134/S0006297916100072 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA4DF UT WOS:000386558100007 PM 27908234 ER PT J AU Lam, AD Zepeda, R Cole, AJ Cash, SS AF Lam, Alice D. Zepeda, Rodrigo Cole, Andrew J. Cash, Sydney S. TI Widespread changes in network activity allow non-invasive detection of mesial temporal lobe seizures SO BRAIN LA English DT Article DE temporal lobe epilepsy; temporal lobe; intracranial EEG; Alzheimer's disease; seizure detection ID ALZHEIMERS-DISEASE; EPILEPTIFORM ACTIVITY; EPILEPSY; DEMENTIA; PATTERNS; LOCALIZATION; IMPAIRMENTS; ELECTRODES; SUBTYPES; FOCI AB Focal seizures within the mesial temporal lobes often lack a scalp EEG ictal correlate, and intracranial recordings are typically required for their detection. Lam et al. develop a new approach to detect these seizures non-invasively and with high specificity on scalp EEG, using network connectivity measures and machine-learning techniques.Focal seizures within the mesial temporal lobes often lack a scalp EEG ictal correlate, and intracranial recordings are typically required for their detection. Lam et al. develop a new approach to detect these seizures non-invasively and with high specificity on scalp EEG, using network connectivity measures and machine-learning techniques.Decades of experience with intracranial recordings in patients with epilepsy have demonstrated that seizures can occur in deep cortical regions such as the mesial temporal lobes without showing any obvious signs of seizure activity on scalp electroencephalogram. Predicated on the idea that these seizures are purely focal, currently, the only way to detect these 'scalp-negative seizures' is with intracranial recordings. However, intracranial recordings are only rarely performed in patients with epilepsy, and are almost never performed outside of the context of epilepsy. As such, little is known about scalp-negative seizures and their role in the natural history of epilepsy, their effect on cognitive function, and their association with other neurological diseases. Here, we developed a novel approach to non-invasively identify scalp-negative seizures arising from the mesial temporal lobe based on scalp electroencephalogram network connectivity measures. We identified 25 scalp-negative mesial temporal lobe seizures in 10 patients and obtained control records from an additional 13 patients, all of whom underwent recordings with foramen ovale electrodes and scalp electroencephalogram. Scalp data from these records were used to train a scalp-negative seizure detector, which consisted of a pair of logistic regression classifiers that used scalp electroencephalogram coherence properties as input features. On cross-validation performance, this detector correctly identified scalp-negative seizures in 40% of patients, and correctly identified the side of seizure onset for each seizure detected. In comparison, routine clinical interpretation of these scalp electroencephalograms failed to identify any of the scalp-negative seizures. Among the patients in whom the detector raised seizure alarms, 80% had scalp-negative mesial temporal lobe seizures. The detector had a false alarm rate of only 0.31 per day and a positive predictive value of 75%. Of the 13 control patients, false seizure alarms were raised in only one patient. The fact that our detector specifically recognizes focal mesial temporal lobe seizures based on scalp electroencephalogram coherence features, lends weight to the hypothesis that even focal seizures are a network phenomenon that involve widespread neural connectivity. Our scalp-negative seizure detector has clear clinical utility in patients with temporal lobe epilepsy, and its potential easily translates to other neurological disorders, such as Alzheimer's disease, in which occult mesial temporal lobe seizures are suspected to play a significant role. Importantly, our work establishes a novel approach of using computational approaches to non-invasively detect deep seizure activity, without the need for invasive intracranial recordings. C1 [Lam, Alice D.; Zepeda, Rodrigo; Cole, Andrew J.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, WACC 735,55 Fruit St, Boston, MA 02114 USA. RP Lam, AD (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 735,55 Fruit St, Boston, MA 02114 USA. EM adlam@partners.org FU NIH-NINDS [R25-NS065743, R01-NS062092, K24-NS088568] FX A.D.L. was supported by NIH-NINDS R25-NS065743. S.S.C. was supported by NIH-NINDS R01-NS062092 and K24-NS088568. NR 30 TC 2 Z9 2 U1 7 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT PY 2016 VL 139 BP 2679 EP 2693 DI 10.1093/brain/aww198 PN 10 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DZ7CZ UT WOS:000386023000019 PM 27474219 ER PT J AU Biffi, A Rattani, A Anderson, CD Ayres, AM Gurol, EM Greenberg, SM Rosand, J Viswanathan, A AF Biffi, Alessandro Rattani, Abbas Anderson, Christopher D. Ayres, Alison M. Gurol, Edip M. Greenberg, Steven M. Rosand, Jonathan Viswanathan, Anand TI Delayed seizures after intracerebral haemorrhage SO BRAIN LA English DT Article DE intracerebral haemorrhage; seizure; epilepsy ID OCCULT CEREBROVASCULAR-DISEASE; MATTER HYPERINTENSITY VOLUME; CEREBRAL AMYLOID ANGIOPATHY; COGNITIVE STATUS TICS; LATE-ONSET EPILEPSY; TELEPHONE INTERVIEW; ISCHEMIC-STROKE; METAANALYSIS; DEMENTIA; VALIDITY AB The factors that predispose to delayed seizures after intracerebral haemorrhage are unclear. Biffi et al. demonstrate that delayed seizures are associated with different risk factors compared to early and recurring seizures. The former are also associated with poorer functional outcomes, but this is attributable to underlying cerebral small vessel disease.The factors that predispose to delayed seizures after intracerebral haemorrhage are unclear. Biffi et al. demonstrate that delayed seizures are associated with different risk factors compared to early and recurring seizures. The former are also associated with poorer functional outcomes, but this is attributable to underlying cerebral small vessel disease.Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants epsilon 2/epsilon 4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of a parts per thousand yen 1 APOE epsilon 4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted. C1 [Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Behav Neurol, 100 Cambridge St,20-2023, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Rattani, Abbas] Meharry Med Coll, Sch Med, Nashville, TN 37208 USA. [Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Gurol, Edip M.; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Div Stroke, Boston, MA 02114 USA. RP Biffi, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Behav Neurol, 100 Cambridge St,20-2023, Boston, MA 02114 USA. EM abiffi@mgh.harvard.edu FU National Institute of Health [R25 NS065743, R01 NS063925, R01 NS059727, K23 NS086873, P50 NS051343, R01 AG26484] FX The authors' work on this study was supported by funding from the National Institute of Health (R25 NS065743, R01 NS063925, R01 NS059727, K23 NS086873, P50 NS051343 and R01 AG26484). All funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the report and in the decision to submit the paper for publication. NR 34 TC 1 Z9 1 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT PY 2016 VL 139 BP 2694 EP 2705 DI 10.1093/brain/aww199 PN 10 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DZ7CZ UT WOS:000386023000020 PM 27497491 ER PT J AU Lim, YY Hassenstab, J Cruchaga, C Goate, A Fagan, AM Benzinger, TLS Maruff, P Snyder, PJ Masters, CL Allegri, R Chhatwal, J Farlow, MR Graff-Radford, NR Laske, C Levin, J McDade, E Ringman, JM Rossor, M Salloway, S Schofield, PR Holtzman, DM Morris, JC Bateman, RJ AF Lim, Yen Ying Hassenstab, Jason Cruchaga, Carlos Goate, Alison Fagan, Anne M. Benzinger, Tammie L. S. Maruff, Paul Snyder, Peter J. Masters, Colin L. Allegri, Ricardo Chhatwal, Jasmeer Farlow, Martin R. Graff-Radford, Neill R. Laske, Christoph Levin, Johannes McDade, Eric Ringman, John M. Rossor, Martin Salloway, Stephen Schofield, Peter R. Holtzman, David M. Morris, John C. Bateman, Randall J. CA Dominantly Inherited Alzheimer TI BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease SO BRAIN LA English DT Article DE Alzheimer's disease; amyloid-beta; tau; dementia; genetics ID A-BETA ACCUMULATION; NEUROTROPHIC FACTOR; COGNITIVE DECLINE; DOWN-REGULATION; AMYLOID LOAD; OLDER-ADULTS; BRAIN; POLYMORPHISM; EXPRESSION; APOE AB The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism modulates A beta+ related memory decline in sporadic Alzheimer's disease. Yen Ying Lim et al. report that this polymorphism also affects outcomes in autosomal dominant Alzheimer's disease. Met66 carriers show greater dysfunction in cognition, glucose metabolism and tau, with implications for clinical trial design.See Rogaeva and Schmitt-Ulms (doi:related-article ext-link-type="doi" id="RA3" related-article-type="companion" xlink:href="10.1093/brain/aww201"10.1093/aww201related-article) for a scientific commentary on this article. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism modulates A beta+ related memory decline in sporadic Alzheimer's disease. Yen Ying Lim et al. report that this polymorphism also affects outcomes in autosomal dominant Alzheimer's disease. Met66 carriers show greater dysfunction in cognition, glucose metabolism and tau, with implications for clinical trial design.The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-beta-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-beta in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) epsilon 4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val(66) homozygotes, 48 Met(66) carriers). Among preclinical mutation carriers, Met(66) carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val(66) homozygotes. Cortical amyloid-beta and cerebrospinal fluid amyloid-beta(42) levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val(66) homozygotes and Met(66) carriers. There was an effect of APOE on amyloid-beta levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-beta on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met(66) carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-beta in autosomal dominant Alzheimer's disease. C1 [Lim, Yen Ying; Maruff, Paul; Masters, Colin L.] Univ Melbourne, Florey Inst, Parkville, Vic, Australia. [Hassenstab, Jason; Fagan, Anne M.; McDade, Eric; Holtzman, David M.; Morris, John C.; Bateman, Randall J.] Washington Univ, Dept Neurol, St Louis, MO USA. [Cruchaga, Carlos] Washington Univ, Dept Psychiat, St Louis, MO USA. [Goate, Alison] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Benzinger, Tammie L. S.] Washington Univ, Dept Radiol, St Louis, MO USA. [Maruff, Paul] Cogstate Ltd, Melbourne, Vic, Australia. [Snyder, Peter J.; Salloway, Stephen] Brown Univ, Warren Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Allegri, Ricardo] Inst Invest Neurol Raul Carrea FLENI, Ageing & Memory Ctr, Buenos Aires, DF, Argentina. [Chhatwal, Jasmeer] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Chhatwal, Jasmeer] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA USA. [Farlow, Martin R.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Laske, Christoph] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany. [Laske, Christoph] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, Sect Dementia Res, Tubingen, Germany. [Laske, Christoph] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany. [Levin, Johannes] Univ Munich, Dept Neurol, Munich, Germany. [Ringman, John M.] Univ Southern Calif, Keck Sch Med, Memory & Aging Ctr, Los Angeles, CA USA. [Rossor, Martin] UCL Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat Dis, London, England. [Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW, Australia. [Schofield, Peter R.] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia. RP Lim, YY (reprint author), 155 Oak St, Parkville, Vic 3052, Australia. EM yen.lim@florey.edu.au RI Levin, Johannes/E-4052-2010 OI Levin, Johannes/0000-0001-5092-4306 FU Dominantly Inherited Alzheimer's Network (DIAN) - National Institute on Aging (NIA) [U19AG032438]; German Center for Neurodegenerative Diseases (DZNE); NIHR Queen Square Dementia Biomedical Research Unit; MRC Dementias Platform UK [MR/L023784/1, MR/009076/1]; NCI Cancer Center Support Grant [P30 CA91842]; ICTS/CTSA from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1TR000448]; NIH Roadmap for Medical Research; Alzheimer's Australia Dementia Research Fellowship; Yulgilbar Alzheimer's Research Program; NHMRC-ARC Dementia Research Development Fellowship; [K23-AG049087] FX Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer's Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA) and the German Center for Neurodegenerative Diseases (DZNE). This work was also supported by the NIHR Queen Square Dementia Biomedical Research Unit and the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant#UL1TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Data and/or tissue generated from DIAN fibroblasts (or IPSCs) and/or exome chip sequencing was supported by the DIAN-TU Pharma Consortium, (the DIAN-TU Pharma Consortium, http://dian-tu.wustl.edu/en/pharma-consortium-members/). This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. JP Chhatwal is supported by K23-AG049087. YY Lim is supported by the Alzheimer's Australia Dementia Research Fellowship, the Yulgilbar Alzheimer's Research Program, and the NHMRC-ARC Dementia Research Development Fellowship. NR 48 TC 3 Z9 3 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT PY 2016 VL 139 BP 2766 EP 2777 DI 10.1093/brain/aww200 PN 10 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DZ7CZ UT WOS:000386023000025 PM 27521573 ER PT J AU Mauldin, IS Wages, NA Stowman, AM Wang, E Olson, WC Deacon, DH Smith, KT Galeassi, N Teague, JE Smolkin, ME Chianese-Bullock, KA Clark, RA Petroni, GR Marincola, FM Mullins, DW Slingluff, CL AF Mauldin, Ileana S. Wages, Nolan A. Stowman, Anne M. Wang, Ena Olson, Walter C. Deacon, Donna H. Smith, Kelly T. Galeassi, Nadedja Teague, Jessica E. Smolkin, Mark E. Chianese-Bullock, Kimberly A. Clark, Rachael A. Petroni, Gina R. Marincola, Francesco M. Mullins, David W. Slingluff, Craig L., Jr. TI Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Immunotherapy; Human; Cytotoxic T lymphocytes; Melanoma; Tumor vaccines; TLR agonists ID RESPONSE MODIFIER IMIQUIMOD; MALIGNANT-MELANOMA; T-CELLS; HUMAN MONOCYTES; M EXPRESSION; IRAK-M; TRIAL; ADJUVANT; CARCINOMAS; APOPTOSIS AB Infiltration of cancers by T cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T cell infiltration of tumors are not known. This study was designed to assess whether topical treatment of melanoma metastases with the TLR7 agonist imiquimod plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to metastatic tumors daily. Adverse events were recorded, and effects on the tumor microenvironment were evaluated from sequential tumor biopsies. T cell responses were assessed by IFN gamma ELIspot assay and T cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Four eligible patients were enrolled, and administration of imiquimod and vaccination were well tolerated. Circulating T cell responses to the vaccine was detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. C1 [Mauldin, Ileana S.; Stowman, Anne M.; Olson, Walter C.; Deacon, Donna H.; Smith, Kelly T.; Galeassi, Nadedja; Chianese-Bullock, Kimberly A.; Slingluff, Craig L., Jr.] Univ Virginia, Ctr Canc, Human Immune Therapy Ctr, Div Surg Oncol,Dept Surg, 1352 Jordan Hall,POB 801457, Charlottesville, VA 22908 USA. [Wages, Nolan A.; Smolkin, Mark E.; Petroni, Gina R.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. [Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar. [Teague, Jessica E.; Clark, Rachael A.] Harvard Med Sch, Dept Dermatol, Brigham & Womens Hosp, Boston, MA USA. [Teague, Jessica E.; Clark, Rachael A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Mullins, David W.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Norris Cotton Canc Ctr, Lebanon, NH USA. RP Slingluff, CL (reprint author), Univ Virginia, Ctr Canc, Human Immune Therapy Ctr, Div Surg Oncol,Dept Surg, 1352 Jordan Hall,POB 801457, Charlottesville, VA 22908 USA. EM cls8h@virginia.edu FU University of Virginia Cancer Center Support Grant (NIH/National Cancer Institute) [P30 CA44579]; Commonwealth Foundation for Cancer Research; Rebecca Clary Harris Fellowship; University of Virginia Cancer Training [T32 CA009109]; Melanoma Research Alliance Young Investigator Award; United States Public Health Service [R01 CA134799]; NIH/National Cancer Institute [K25 CA181638] FX Support for this work was provided by the University of Virginia Cancer Center Support Grant (NIH/National Cancer Institute P30 CA44579: Clinical Trials Office, Biorepository and Tissue Research Facility, Flow Cytometry Core, Biomolecular Core Facility, Biostatistics Shared Resource and pilot projects funding). Additional philanthropic support was provided by George and Linda Suddock and by Alice and Bill Goodwin and the Commonwealth Foundation for Cancer Research. Support was also provided by the Rebecca Clary Harris Fellowship (Ileana S Mauldin) and the University of Virginia Cancer Training Grant T32 CA009109 (Ileana S Mauldin), a Melanoma Research Alliance Young Investigator Award (David Mullins) and United States Public Health Service R01 CA134799 (David Mullins), and NIH/National Cancer Institute grant K25 CA181638 (Nolan A Wages). NR 37 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 2016 VL 65 IS 10 BP 1201 EP 1212 DI 10.1007/s00262-016-1880-z PG 12 WC Oncology; Immunology SC Oncology; Immunology GA EA3PE UT WOS:000386515000006 PM 27522582 ER PT J AU Joehanes, R Just, AC Marioni, RE Pilling, LC Reynolds, LM Mandaviya, PR Guan, WH Xu, T Elks, CE Aslibekyan, S Moreno-Macias, H Smith, JA Brody, JA Dhingra, R Yousefi, P Pankow, JS Kunze, S Shah, SH McRae, AF Lohman, K Sha, J Absher, DM Ferrucci, L Zhao, W Demerath, EW Bressler, J Grove, ML Huan, TX Liu, CY Mendelson, MM Yao, C Kiel, DP Peters, A Wang-Sattler, R Visscher, PM Wray, NR Starr, JM Ding, JZ Rodriguez, CJ Wareham, NJ Irvin, MR Zhi, DG Barrdahl, M Vineis, P Ambatipudi, S Uitterlinden, AG Hofman, A Schwartz, J Colicino, E Hou, LF Vokonas, PS Hernandez, DG Singleton, AB Bandinelli, S Turner, ST Ware, EB Smith, AK Klengel, T Binder, EB Psaty, BM Taylor, KD Gharib, SA Swenson, BR Liang, LM DeMeo, DL O'Connor, GT Herceg, Z Ressler, KJ Conneely, KN Sotoodehnia, N Kardia, SLR Melzer, D Baccarelli, AA van Meurs, JBJ Romieu, I Arnett, DK Ong, KK Liu, YM Waldenberger, M Deary, IJ Fornage, M Levy, D London, SJ AF Joehanes, Roby Just, Allan C. Marioni, Riccardo E. Pilling, Luke C. Reynolds, Lindsay M. Mandaviya, Pooja R. Guan, Weihua Xu, Tao Elks, Cathy E. Aslibekyan, Stella Moreno-Macias, Hortensia Smith, Jennifer A. Brody, Jennifer A. Dhingra, Radhika Yousefi, Paul Pankow, James S. Kunze, Sonja Shah, Sonia H. McRae, Allan F. Lohman, Kurt Sha, Jin Absher, Devin M. Ferrucci, Luigi Zhao, Wei Demerath, Ellen W. Bressler, Jan Grove, Megan L. Huan, Tianxiao Liu, Chunyu Mendelson, Michael M. Yao, Chen Kiel, Douglas P. Peters, Annette Wang-Sattler, Rui Visscher, Peter M. Wray, Naomi R. Starr, John M. Ding, Jingzhong Rodriguez, Carlos J. Wareham, Nicholas J. Irvin, Marguerite R. Zhi, Degui Barrdahl, Myrto Vineis, Paolo Ambatipudi, Srikant Uitterlinden, Andre G. Hofman, Albert Schwartz, Joel Colicino, Elena Hou, Lifang Vokonas, Pantel S. Hernandez, Dena G. Singleton, Andrew B. Bandinelli, Stefania Turner, Stephen T. Ware, Erin B. Smith, Alicia K. Klengel, Torsten Binder, Elisabeth B. Psaty, Bruce M. Taylor, Kent D. Gharib, Sina A. Swenson, Brenton R. Liang, Liming DeMeo, Dawn L. O'Connor, George T. Herceg, Zdenko Ressler, Kerry J. Conneely, Karen N. Sotoodehnia, Nona Kardia, Sharon L. R. Melzer, David Baccarelli, Andrea A. van Meurs, Joyce B. J. Romieu, Isabelle Arnett, Donna K. Ong, Ken K. Liu, Yongmei Waldenberger, Melanie Deary, Ian J. Fornage, Myriam Levy, Daniel London, Stephanie J. TI Epigenetic Signatures of Cigarette Smoking SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE biomarkers; genome-wide association study; meta-analysis; methylation; smoking ID DIFFERENTIAL DNA METHYLATION; EPIGENOME-WIDE ASSOCIATION; F2RL3 METHYLATION; HUMAN GENOME; METAANALYSIS; NUTRITION; EXPRESSION; BIOMARKERS; DISCOVERY; EXPOSURE AB Background DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1x10(-7) (18760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1x10(-7) (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke. C1 [Joehanes, Roby; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Joehanes, Roby; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [DeMeo, Dawn L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ressler, Kerry J.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Joehanes, Roby; Huan, Tianxiao; Liu, Chunyu; Mendelson, Michael M.; Yao, Chen; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Joehanes, Roby; Huan, Tianxiao; Liu, Chunyu; Mendelson, Michael M.; Yao, Chen; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Just, Allan C.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Marioni, Riccardo E.; Visscher, Peter M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.; Shah, Sonia H.; McRae, Allan F.; Visscher, Peter M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [McRae, Allan F.; Visscher, Peter M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia. [Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. [Reynolds, Lindsay M.; Rodriguez, Carlos J.; Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Lohman, Kurt] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Mandaviya, Pooja R.; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Mandaviya, Pooja R.] Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. [Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Guan, Weihua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Xu, Tao; Kunze, Sonja; Peters, Annette; Wang-Sattler, Rui; Waldenberger, Melanie] Helmhotz Zentrum Muenchen, Inst Epidemiol 2, Res Unit Mol Epidemiol, Munich, Germany. [Elks, Cathy E.; Wareham, Nicholas J.; Ong, Ken K.] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Aslibekyan, Stella; Sha, Jin; Irvin, Marguerite R.; Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Moreno-Macias, Hortensia] Autonomous Metropolitan Univ Iztapalapa, Mexico City, DF, Mexico. [Moreno-Macias, Hortensia; Ambatipudi, Srikant; Herceg, Zdenko; Romieu, Isabelle] Int Agcy Res Canc, Lyon, France. [Smith, Jennifer A.; Zhao, Wei; Ware, Erin B.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Ware, Erin B.] Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI USA. [Brody, Jennifer A.; Psaty, Bruce M.; Swenson, Brenton R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Gharib, Sina A.] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA USA. [Sotoodehnia, Nona] Univ Washington, Dept Epidemiol, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Dhingra, Radhika] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. [Yousefi, Paul; Demerath, Ellen W.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Absher, Devin M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Bressler, Jan; Grove, Megan L.; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Zhi, Degui] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA. [Mendelson, Michael M.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Barrdahl, Myrto] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Vineis, Paolo] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. [Vineis, Paolo] HuGeF Fdn, Turin, Italy. [Sha, Jin; Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Vokonas, Pantel S.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Smith, Alicia K.; Binder, Elisabeth B.; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Conneely, Karen N.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Klengel, Torsten; Binder, Elisabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany. [Klengel, Torsten; Ressler, Kerry J.] McLean Hosp, Div Depress & Anxiety Disorders, 115 Mill St, Belmont, MA 02178 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Taylor, Kent D.] Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Taylor, Kent D.] Harbor UCLA Med Ctr, Div Genom Outcomes, Dept Pediat, Torrance, CA 90509 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Liang, Liming] Harvard Sch Publ Hlth, Boston, MA USA. [O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [London, Stephanie J.] NIEHS, Epidemiol Branch, US Dept HHS, NIH, POB 12233,Room A306, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, US Dept HHS, NIH, POB 12233,Room A306, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Shah, Sonia/N-7547-2013; OI Shah, Sonia/0000-0001-5860-4526; Colicino, Elena/0000-0002-1875-8448; Smith, Jennifer/0000-0002-3575-5468; Just, Allan/0000-0003-4312-5957; Pankow, James/0000-0001-7076-483X; AMBATIPUDI, SRIKANT/0000-0003-3102-3603; Mendelson, Michael/0000-0001-7590-3958; London, Stephanie/0000-0003-4911-5290 FU National Heart, Lung, and Blood Institute [R01HL105756]; NIH; National Institute of Environmental Health Sciences; National Heart Lung and Blood Institute FX Infrastructure for the CHARGE consortium is provided by the National Heart, Lung, and Blood Institute grant R01HL105756. This work was supported in part by the Intramural Research Program of the NIH; National Institute of Environmental Health Sciences; and the National Heart Lung and Blood Institute. Additional funding sources for each cohort can be found in the Data Supplement. NR 43 TC 6 Z9 6 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2016 VL 9 IS 5 BP 436 EP 447 DI 10.1161/CIRCGENETICS.116.001506 PG 12 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA EA4OY UT WOS:000386593700007 PM 27651444 ER PT J AU Meester, RGS Zauber, AG Doubeni, CA Jensen, CD Quinn, VP Helfand, M Dominitz, JA Levin, TR Corley, DA Lansdorp-Vogelaar, I AF Meester, Reinier G. S. Zauber, Ann G. Doubeni, Chyke A. Jensen, Christopher D. Quinn, Virginia P. Helfand, Mark Dominitz, Jason A. Levin, Theodore R. Corley, Douglas A. Lansdorp-Vogelaar, Iris TI Consequences of Increasing Time to Colonoscopy Examination After Positive Result From Fecal Colorectal Cancer Screening Test SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Colorectal Neoplasms; Screening and Early Detection; Occult Blood; Time Factors ID OCCULT-BLOOD-TEST; COST-EFFECTIVENESS ANALYSIS; ADENOMA DETECTION RATE; SOCIETY TASK-FORCE; MEDICARE POPULATION; LARGE-INTESTINE; LARGE-BOWEL; ASYMPTOMATIC ADULTS; AMERICAN-COLLEGE; POLYPECTOMY RATE AB BACKGROUND & AIMS: Delays in diagnostic testing after a positive result from a screening test can undermine the benefits of colorectal cancer (CRC) screening, but there are few empirical data on the effects of such delays. We used microsimulation modeling to estimate the consequences of time to colonoscopy after a positive result from a fecal immunochemical test (FIT). METHODS: We used an established microsimulation model to simulate an average-risk United States population cohort that underwent annual FIT screening (from ages 50 to 75 years), with follow-up colonoscopy examinations for individuals with positive results (cutoff, 20 mu g/g) at different time points in the following 12 months. Main evaluated outcomes were CRC incidence and mortality; additional outcomes were total life-years lost and net costs of screening. RESULTS: For individuals who underwent diagnostic colonoscopy within 2 weeks of a positive result from an FIT, the estimated lifetime risk of CRC incidence was 35.5/1000 persons, and mortality was 7.8/1000 persons. Every month added until colonoscopy was associated with a 0.1/1000 person increase in cancer incidence risk (an increase of 0.3%/month, compared with individuals who received colonoscopies within 2 weeks) and mortality risk (increase of 1.4%/month). Among individuals who received colonoscopy examinations 12 months after a positive result from an FIT, the incidence of CRC was 27.0/1000 persons (increase of 4%, compared with 2 weeks), and mortality was 9.1/1000 persons (increase of 16%). Total years of life gained for the entire screening cohort decreased from an estimated 93.7/1000 persons with an almost immediate follow-up colonoscopy (cost savings of $ 208 per patient, compared with no colonoscopy) to 84.8/1000 persons with follow-up colonoscopies at 12 months (decrease of 9%; cost savings of $ 100/patient, compared with no colonoscopy). CONCLUSIONS: By using a microsimulation model of an average-risk United States screening cohort, we estimated that delays of up to 12 months after a positive result from an FIT can produce proportional losses of up to nearly 10% in overall screening benefits. These findings indicate the importance of timely follow-up colonoscopy examinations of patients with positive results from FITs. C1 [Meester, Reinier G. S.; Lansdorp-Vogelaar, Iris] Erasmus MC, Univ Med Ctr, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Doubeni, Chyke A.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Doubeni, Chyke A.] Univ Penn, Perelman Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USA. [Doubeni, Chyke A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Doubeni, Chyke A.] Univ Penn, Ctr Publ Hlth Initiat, Philadelphia, PA 19104 USA. [Jensen, Christopher D.; Levin, Theodore R.; Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Quinn, Virginia P.] Kaiser Permanente Southern Calif, Res & Evaluat, Pasadena, CA 91101 USA. [Helfand, Mark] Vet Affairs Portland Healthcare Syst, Portland, OR USA. [Dominitz, Jason A.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Meester, RGS (reprint author), Erasmus MC, Univ Med Ctr, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM r.meester@erasmusmc.nl FU National Cancer Institute at the United States National Institutes of Health [U54 CA163262, U01 CA152959, U01 CA151736, U24 CA171524, P30 CA008748]; VA Puget Sound Health Care System FX Supported by grants from the National Cancer Institute at the United States National Institutes of Health (#U54 CA163262 and also U01 CA152959, U01 CA151736, U24 CA171524, and P30 CA008748). This material is the result of work supported in part by resources from the VA Puget Sound Health Care System. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Cancer Institute or of the Department of Veterans Affairs. NR 61 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2016 VL 14 IS 10 BP 1445 EP + DI 10.1016/j.cgh.2016.05.017 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA6SO UT WOS:000386759500016 PM 27211498 ER PT J AU Maura, D Ballok, AE Rahme, LG AF Maura, Damien Ballok, Alicia E. Rahme, Laurence G. TI Considerations and caveats in anti-virulence drug development SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID QUORUM-SENSING INHIBITORS; PSEUDOMONAS-AERUGINOSA VIRULENCE; STAPHYLOCOCCUS-AUREUS VIRULENCE; SMALL-MOLECULE INHIBITORS; BIOFILM FORMATION; BACTERIAL VIRULENCE; ACINETOBACTER-BAUMANNII; SECRETION SYSTEM; RISK-FACTORS; INFECTIONS AB As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials. Development of a defined pipeline for anti-virulence agents, which differs in important ways from conventional antibiotics, is imperative for the future success of these critically needed drugs. C1 [Maura, Damien; Ballok, Alicia E.; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Maura, Damien; Ballok, Alicia E.; Rahme, Laurence G.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Maura, Damien; Ballok, Alicia E.; Rahme, Laurence G.] Shriners Hosp Children Boston, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.; Rahme, LG (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Rahme, LG (reprint author), Shriners Hosp Children Boston, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu FU Shriners Hospital Postdoctoral Fellowship [84206]; Cystic Fibrosis Foundation fellowship [BALLOK15F0]; Shriners [8770]; Cystic Fibrosis Foundation [11P0]; NIAID [R33AI105902, R56AI063433] FX We would like to acknowledge all our colleagues who contributed to the antivirulence research over the years, and apologize if we did not refer to all anti-virulence published work due to space limitations. This work was supported by Shriners Hospital Postdoctoral Fellowship #84206 to DM, Cystic Fibrosis Foundation fellowship #BALLOK15F0 to AB and by the research grants, Shriners #8770, Cystic Fibrosis Foundation #11P0, NIAID R33AI105902 and R56AI063433 to L.G.R. NR 67 TC 1 Z9 1 U1 11 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 2016 VL 33 BP 41 EP 46 DI 10.1016/j.mib.2016.06.001 PG 6 WC Microbiology SC Microbiology GA EA9SS UT WOS:000386985600009 PM 27318551 ER PT J AU Hamblin, MR AF Hamblin, Michael R. TI Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID IN-VIVO; CATIONIC BACTERIOCHLORINS; WOUND INFECTIONS; DRUG DISCOVERY; THERAPY; PHOTOSENSITIZERS; BACTERIA; PHOTOINACTIVATION; FULLERENES; OXYGEN AB Photodynamic therapy (PDT) uses photosensitizers (non-toxic dyes) that are activated by absorption of visible light to form reactive oxygen species (including singlet oxygen) that can oxidize biomolecules and destroy cells. Antimicrobial photodynamic inactivation (aPDI) can treat localized infections. aPDI neither causes any resistance to develop in microbes, nor is affected by existing drug resistance status. We discuss some recent developments in aPDI. New photosensitizers including polycationic conjugates, stable synthetic bacteriochlorins and functionalized fullerenes are described. The microbial killing by aPDI can be synergistically potentiated (several logs) by harmless inorganic salts via photochemistry. Genetically engineered bioluminescent microbial cells allow PDT to treat infections in animal models. Photoantimicrobials have a promising future in the face of the unrelenting increase in antibiotic resistance. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875] FX Michael R Hamblin was supported by US NIH grant R01AI050875. NR 49 TC 2 Z9 2 U1 28 U2 28 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 2016 VL 33 BP 67 EP 73 DI 10.1016/j.mib.2016.06.008 PG 7 WC Microbiology SC Microbiology GA EA9SS UT WOS:000386985600012 PM 27421070 ER PT J AU Zhu, J Kahn, P Knudsen, J Mehta, SN Gabbay, RA AF Zhu, Jia Kahn, Peter Knudsen, Janine Mehta, Sanjeev N. Gabbay, Robert A. TI Predictive Model for Estimating the Cost of Incident Diabetes Complications SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID ACCOUNTABLE CARE ORGANIZATIONS; DIRECT MEDICAL COSTS; UNITED-STATES; RISK-FACTORS; MELLITUS; DISEASE; BURDEN; EYE AB Background: The cost of diabetes care accounts for a significant proportion of healthcare expenditures. Cost models based on updated incident complication rates and associated costs are needed to improve financial planning and quality assessment across the U.S. healthcare system. We developed a cost model using published data to estimate the direct medical costs of incident diabetes-related complications in a U.S. population of adults. Materials and Methods: A systematic literature review of MEDLINE, EMBASE, and TRIP databases was conducted on studies reporting the incidence and/or cost of diabetes-related complications (cardiovascular disease, neuropathy, nephropathy, ophthalmological disease, and acute metabolic events). A total of 54 studies met eligibility criteria. A baseline model was constructed for a U.S. population with type 1 and 2 diabetes mellitus and used to determine the expected costs of managing such a population over 1-, 3-, and 5-year time horizons. Results: The most costly incident complications in a population of 10,000 adults with diabetes were (1) congestive heart failure (CHF): annual expected cost of $7,320,287, 5-year expected cost of $50,697,865; (2) end-stage renal disease (ESRD): annual expected cost of $4,225,384, 5-year expected cost of $13,211,204; and (3) gangrene: annual expected cost of $2,844,381, 5-year expected cost of $17,200,417. Conclusions: This cost model estimates the direct healthcare costs of incident diabetes-related complications in a U.S. adult population with diabetes and provides a benchmark for evaluating the cost-effectiveness and potential leakage within a care delivery network. C1 [Zhu, Jia; Kahn, Peter; Knudsen, Janine; Mehta, Sanjeev N.; Gabbay, Robert A.] Joslin Diabet Ctr, One Joslin Pl,2nd Floor, Boston, MA 02215 USA. [Zhu, Jia] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Kahn, Peter] Albert Einstein Coll Med, New York, NY USA. [Knudsen, Janine] NYU Langone Med Ctr, Dept Med, New York, NY USA. RP Gabbay, RA (reprint author), Joslin Diabet Ctr, One Joslin Pl,2nd Floor, Boston, MA 02215 USA. EM robert.gabbay@joslin.harvard.edu NR 26 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD OCT PY 2016 VL 18 IS 10 BP 625 EP 634 DI 10.1089/dia.2016.0132 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA3BM UT WOS:000386473000005 PM 27583583 ER PT J AU Williams, JS Walker, RJ Smalls, BL Hill, R Egede, LE AF Williams, Joni S. Walker, Rebekah J. Smalls, Brittany L. Hill, Rachel Egede, Leonard E. TI Patient-Centered Care, Glycemic Control, Diabetes Self-Care, and Quality of Life in Adults with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID HEALTH; INTERVENTION; VALIDITY; IMPACT AB Background: The Affordable Care Act places a newfound emphasis on patient-centered medical home and patient-centered care (PCC). The purpose of this study was to evaluate the relationship between PCC, diabetes self-care, glycemic control, and quality of life (QOL) in a sample of adults with type 2 diabetes. Methods: Six hundred fifteen patients were recruited from two adult primary care clinics in the southeastern United States. Primary outcome variables were self-care behaviors (medication adherence, diet, exercise, blood sugar testing, and foot care), glycemic control, and QOL (physical component summary [PCS] score and mental component summary [MCS] score of SF12). PCC was assessed using a modified 7-item Picker Patient Experience Questionnaire. Regression modeling was used to assess independent associations while adjusting for relevant covariates. Results: In adjusted analyses, PCC was significantly associated with PCS QOL (=-0.03, 95% confidence interval [CI] -0.05 to -0.01), MCS QOL (=0.09, 95% CI 0.04-0.14), medication adherence (=0.12, 95% CI 0.08-0.17), general diet (=0.12, 95% CI 0.07-0.17), specific diet (=0.05, 95% CI 0.01-0.08), blood sugar testing (=0.09, 95% CI 0.04-0.15), and foot care (=0.12, 95% CI 0.07-0.18). Conclusion: PCC is associated with diabetes self-management and QOL, but was not significantly associated with glycemic control in patients with diabetes. PCC may be an important factor in self-care behaviors, but the process of focusing care around the patient may need to expand throughout the healthcare system before changes in outcomes such as glycemic control are noted. C1 [Williams, Joni S.; Walker, Rebekah J.; Hill, Rachel; Egede, Leonard E.] Med Univ South Carolina, Dept Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. [Williams, Joni S.; Walker, Rebekah J.; Hill, Rachel; Egede, Leonard E.] Med Univ South Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr HEROIC, Charleston, SC USA. [Smalls, Brittany L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. RP Egede, LE (reprint author), Med Univ South Carolina, Dept Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: L.E.E.). NR 33 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD OCT PY 2016 VL 18 IS 10 BP 644 EP 649 DI 10.1089/dia.2016.0079 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA3BM UT WOS:000386473000007 PM 27541872 ER PT J AU Zheng, J Zhang, Q Mul, JD Yu, M Xu, JP Qi, CJ Wang, T Xiao, XH AF Zheng, Jia Zhang, Qian Mul, Joram D. Yu, Miao Xu, Jianping Qi, Cuijuan Wang, Tong Xiao, Xinhua TI Maternal high-calorie diet is associated with altered hepatic microRNA expression and impaired metabolic health in offspring at weaning age SO ENDOCRINE LA English DT Article DE Maternal high-calorie diet; Glucose homeostasis; Liver inflammation; miRNA; Offspring; Mice ID HIGH-FAT DIET; INSULIN-RESISTANCE; CHRONIC INFLAMMATION; GLUCOSE-METABOLISM; FETAL SHEEP; OBESITY; MOUSE; LIVER; LIFE; UNDERNUTRITION AB High-calorie diet (HCD) feeding in mice predisposes offspring for impaired glucose homeostasis and obesity. However, the mechanisms underlying these detrimental effects of maternal nutrition, especially during early life of offspring, are incompletely understood. MicroRNAs (miRNAs) are small non-coding RNAs that can regulate target gene expression. Here we hypothesized that impaired metabolic health in offspring from HCD-fed dams at weaning is associated with dysregulated expression of hepatic miRNAs. Dams were fed a chow diet (CD; 11.4 % kcal fat, 62.8 % from carbohydrate, 25.8 % from protein) or HCD (58 % kcal from fat; 25.6 % from carbohydrate, 16.4 % from protein) during gestation and lactation, and metabolic health was assessed in male offspring at weaning. Hepatic levels of miRNAs and target genes were investigated in offspring from CD- or HCD-fed dams using gene and protein expression. Maternal HCD feeding impaired metabolic health in offspring compared to offspring from CD-fed dams. Microarray analysis indicated that expressions of miR-615-5p, miR-3079-5p, miR-124*, and miR-101b* were downregulated, whereas miR-143* was upregulated, in livers from offspring from HCD-fed dams. Our functional enrichment analysis indicated that the target genes of these differentially expressed miRNAs, including tumor necrosis factor-alpha (TNF-alpha) and mitogen-activated protein kinase 1 (MAPK1), were mapped to inflammatory pathways. Finally, we verified that both mRNA and protein levels of the pro-inflammatory modulators TNF-alpha and MAPK1 were significantly increased in livers of offspring from HCD-fed dams at weaning. Maternal HCD feeding predisposes offspring to a higher body weight and impaired glucose metabolism at weaning. To the best of knowledge, our study is the first to show that maternal HCD consumption impairs metabolic health, modulates hepatic miRNA expression, and increases markers of hepatic inflammation in offspring as early as at weaning age. C1 [Zheng, Jia; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong; Xiao, Xinhua] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Diabet Res Ctr, Dept Endocrinol,Key Lab Endocrinol,Minist Hlth, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China. [Zheng, Jia; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong; Xiao, Xinhua] Peking Union Med Coll, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China. [Mul, Joram D.] Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA USA. RP Xiao, XH (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Diabet Res Ctr, Dept Endocrinol,Key Lab Endocrinol,Minist Hlth, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China.; Xiao, XH (reprint author), Peking Union Med Coll, 1 Shuaifuyuan,Wangfujing St, Beijing 100730, Peoples R China. EM xiaoxinhua@medmail.com.cn FU National Natural Science Foundation of China [81570715, 81170736]; National Natural Science Foundation for Young Scholars of China [81300649]; National Key Program of Clinical Science and Peking Union Medical College Hospital FX This project was supported by the National Natural Science Foundation of China (No. 81570715 and No. 81170736) and the National Natural Science Foundation for Young Scholars of China (No. 81300649), the National Key Program of Clinical Science and Peking Union Medical College Hospital. NR 51 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD OCT PY 2016 VL 54 IS 1 BP 70 EP 80 DI 10.1007/s12020-016-0959-9 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA4WL UT WOS:000386616300010 PM 27106801 ER PT J AU Elder, JS AF Elder, Jack S. TI Surgical Management of the Undescended Testis: Recent Advances and Controversies SO EUROPEAN JOURNAL OF PEDIATRIC SURGERY LA English DT Review DE orchiopexy; undescended testis; abdominal testis; retractile testis; Fowler-Stephens orchiopexy ID FOWLER-STEPHENS ORCHIOPEXY; INTRAABDOMINAL TESTIS; NONPALPABLE TESTIS; CRYPTORCHID TESTIS; ORCHIDOPEXY; BOYS; FERTILITY; GROWTH; AGE; PREVALENCE AB Undescended testis (UDT) is the most common disorder of sexual development in boys and affects 3.5% of male newborns. Although approximately half of newborn UDTs descend spontaneously, some boys develop an ascending testis later in childhood. Recent guideline recommendations advocate orchiopexy by 18 months of age to maximize potential for fertility and perhaps reduce the risk for testicular carcinoma in the future. For palpable testes, a standard inguinal approach is appropriate. However, the prescrotal approach is often effective for low inguinal testes and reduces surgical time and patient discomfort with an equivalent success rate in boys with an ascending testis. Some advocate monitoring until adolescence to determine whether the testis will spontaneously descend into the scrotum, but data do not support this approach. Instead, prompt orchiopexy is recommended. In boys with a nonpalpable testis, approximately 50% are abdominal or high in the inguinal canal and 50% are atrophic, typically in the scrotum. Routine inguinal/scrotal ultrasound is not recommended, although in an older boy who is overweight, it is appropriate. If the patient has contralateral testicular hypertrophy, scrotal exploration is appropriate, and removal of the testicular remnant and contralateral scrotal orchiopexy to prevent future contralateral testicular torsion is recommended. In most cases, diagnostic laparoscopy is advised to determine whether the testis is abdominal. For the abdominal testis, there are numerous treatment options. If the testis is mobile or a peeping testis just distal to the internal inguinal ring, standard one-stage laparoscopic or open orchiopexy should be attempted using the Prentiss maneuver. If the testicular vessels are short or the testis is not mobile, a two-stage Fowler-Stephens orchiopexy is appropriate. The second stage can be performed laparoscopically or open. Another option is microvascular testicular autotransplantation, which is a technically demanding procedure. Surgical results of abdominal orchiopexy are highly variable, short term, and highly subjective. Prospective clinical trials with follow-up into adolescence and adulthood are necessary to assess the success of various surgical approaches. C1 [Elder, Jack S.] Massachusetts Gen Hosp, Div Pediat Urol, 55 Fruit St,WRN 11, Boston, MA 02114 USA. RP Elder, JS (reprint author), Massachusetts Gen Hosp, Div Pediat Urol, 55 Fruit St,WRN 11, Boston, MA 02114 USA. EM jselder@mgh.harvard.edu NR 55 TC 0 Z9 0 U1 2 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0939-7248 EI 1439-359X J9 EUR J PEDIATR SURG JI Eur. J. Pediatr. Surg. PD OCT PY 2016 VL 26 IS 5 BP 418 EP 426 DI 10.1055/s-0036-1592197 PG 9 WC Pediatrics; Surgery SC Pediatrics; Surgery GA DZ8LS UT WOS:000386122500005 PM 27631723 ER PT J AU Petrozza, JC AF Petrozza, John C. TI Mayer-Rokitansky-Kuster-Hauser syndrome and associated malformations: are they as common as we think? SO FERTILITY AND STERILITY LA English DT Editorial Material C1 [Petrozza, John C.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Reprod Med & IVF, Boston, MA 02114 USA. RP Petrozza, JC (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Reprod Med & IVF, Boston, MA 02114 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 OCT PY 2016 VL 106 IS 5 BP 1047 EP 1048 DI 10.1016/j.fertnstert.2016.06.033 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA7RG UT WOS:000386828800014 PM 27430204 ER PT J AU Hamdane, N Juhling, F Bandiera, S Thumann, C El Saghire, H Davidson, I Pessaux, P Bardeesy, N Hoshida, Y Zeisel, MB Baumert, TF AF Hamdane, Nourdine Juehling, Frank Bandiera, Simonetta Thumann, Christine El Saghire, Hussein Davidson, Irwin Pessaux, Patrick Bardeesy, Nabeel Hoshida, Yujin Zeisel, Mirjam B. Baumert, Thomas F. TI Hepatitis C virus-induced epigenetic reprogramming as driver of hepatocarcinogenesis and target for cancer chemoprevention SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Hamdane, Nourdine; Juehling, Frank; Bandiera, Simonetta; Thumann, Christine; El Saghire, Hussein; Pessaux, Patrick; Zeisel, Mirjam B.; Baumert, Thomas F.] Univ Strasbourg, Inst Viral & Liver Dis, INSERM, U1110, Strasbourg, France. [Hamdane, Nourdine; Juehling, Frank; Bandiera, Simonetta; Thumann, Christine; El Saghire, Hussein; Zeisel, Mirjam B.; Baumert, Thomas F.] Univ Strasbourg, Strasbourg, France. [Davidson, Irwin] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. [Pessaux, Patrick] Nouvel Hop Civil, Inst Hosp Univ, Pole Hepatodigestif, Strasbourg, France. [Bardeesy, Nabeel] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Hoshida, Yujin] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Med, Div Liver Dis,Liver Canc Program, New York, NY 10029 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 7 BP 4A EP 4A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800008 ER PT J AU Ioannou, GN Beste, LA Chang, M Green, P Lowy, E Tsui, J Su, F Berry, K AF Ioannou, George N. Beste, Lauren A. Chang, Michael Green, Pamela Lowy, Elliott Tsui, Judith Su, Feng Berry, Kristin TI Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir and Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir-Based Antiviral Regimens for Hepatitis C in 17,847 patients in the Veterans Affairs National Healthcare System SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.; Tsui, Judith; Su, Feng] Univ Washington, Seattle, WA 98195 USA. [Ioannou, George N.; Beste, Lauren A.; Green, Pamela; Lowy, Elliott; Berry, Kristin] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Chang, Michael] Vet Affairs Portland Healthcare Syst, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 21 BP 11A EP 11A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800022 ER PT J AU Corey, KE Yates, KP Abdelmalek, MF Sanyal, AJ Tetri, BA Kowdley, KV Cummings, O Tonascia, J Chalasani, NP AF Corey, Kathleen E. Yates, Katherine P. Abdelmalek, Manal F. Sanyal, Arun J. Tetri, Brent A. Kowdley, Kris V. Cummings, Oscar Tonascia, James Chalasani, Naga P. TI Longitudinal relationship between changes in liver histology and renal function in adults with NASH: The NASH Clinical Research Network Experience SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Corey, Kathleen E.] Massachusetts Gen Hosp, Gastroenterol, Cambridge, MA USA. [Cummings, Oscar; Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Yates, Katherine P.; Tonascia, James] JHU, Baltimore, MD USA. [Abdelmalek, Manal F.] Duke Univ, Durham, NC USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA. [Kowdley, Kris V.] Swedish Med Ctr, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 39 BP 20A EP 20A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800040 ER PT J AU Shah, JA Patel, MS Elias, N Alvarez, NN Hertl, M Cosimi, AB Markmann, JF Sachs, D Vagefi, PA AF Shah, Jigesh A. Patel, Madhukar S. Elias, Nahel Alvarez, Nalu Navarro Hertl, Martin Cosimi, A. Benedict Markmann, James F. Sachs, David Vagefi, Parsia A. TI Markedly Improved Survival Following Pig-to-Baboon Hepatic Xenotransplantation: Progress Towards Clinical Application as a Bridge to Allotransplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shah, Jigesh A.; Patel, Madhukar S.; Elias, Nahel; Alvarez, Nalu Navarro; Hertl, Martin; Cosimi, A. Benedict; Markmann, James F.; Sachs, David; Vagefi, Parsia A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 92 BP 51A EP 51A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800093 ER PT J AU Chhatwal, J Samur, S Klebanoff, M Corey, KE Banken, R Chapman, RH Ollendorf, DA Hur, C AF Chhatwal, Jagpreet Samur, Sumeyye Klebanoff, Matthew Corey, Kathleen E. Banken, Reiner Chapman, Richard H. Ollendorf, Daniel A. Hur, Chin TI Long-term Clinical Outcomes and Cost-Effectiveness of Obeticholic Acid for Treatment of Nonalcoholic Steatohepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chhatwal, Jagpreet; Samur, Sumeyye; Klebanoff, Matthew; Corey, Kathleen E.; Hur, Chin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Banken, Reiner; Chapman, Richard H.; Ollendorf, Daniel A.] Inst Clin & Econ Review, Boston, MA USA. [Chhatwal, Jagpreet; Samur, Sumeyye; Corey, Kathleen E.; Hur, Chin] Harvard Med Sch, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 98 BP 53A EP 54A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800099 ER PT J AU Samur, S Hur, C Klebanoff, M Pratt, DS Banken, R Chapman, RH Ollendorf, DA Chhatwal, J AF Samur, Sumeyye Hur, Chin Klebanoff, Matthew Pratt, Daniel S. Banken, Reiner Chapman, Richard H. Ollendorf, Daniel A. Chhatwal, Jagpreet TI Long-term Clinical Outcomes and Cost-Effectiveness of Obeticholic Acid for Treatment of Primary Biliary Cholangitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Samur, Sumeyye; Hur, Chin; Klebanoff, Matthew; Pratt, Daniel S.; Chhatwal, Jagpreet] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Banken, Reiner; Chapman, Richard H.; Ollendorf, Daniel A.] Inst Clin & Econ Review, Boston, MA USA. [Samur, Sumeyye; Hur, Chin; Chhatwal, Jagpreet] Harvard Med Sch, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 99 BP 54A EP 54A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800100 ER PT J AU Chaturantabut, S Cox, AG North, TE Goessling, W AF Chaturantabut, Saireudee Cox, Andrew G. North, Trista E. Goessling, Wolfram TI Estrogen sensing in the liver by the G protein-coupled receptor GPER1 regulates PI3K/Akt and mTOR activity and controls gender dimorphisms in cell proliferation and metabolism SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chaturantabut, Saireudee; Cox, Andrew G.; Goessling, Wolfram] Brigham & Womens Hosp, Genet, 75 Francis St, Boston, MA 02115 USA. [Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [North, Trista E.] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 148 BP 80A EP 80A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800149 ER PT J AU Coombes, JD Manka, PP Swiderska-Syn, M Reid, D Riva, A Claridge, LC Dolle, L Younis, R Briones, MA Kitamura, N Mehta, K Mi, ZY Kuo, PC Williams, R Diehl, AM van Grunsven, LA Chokshi, S Canbay, A Flamant, F Gauthier, K Eksteen, B Syn, WK AF Coombes, Jason D. Manka, Paul P. Swiderska-Syn, Marzena Reid, Danielle Riva, Antonio Claridge, Lee C. Dolle, Laurent Younis, Rasha Briones, Marco A. Kitamura, Naoto Mehta, Kosha Mi, Zhiyong Kuo, Paul C. Williams, Roger Diehl, Anna Mae van Grunsven, Leo A. Chokshi, Shilpa Canbay, Ali Flamant, Frederic Gauthier, Karine Eksteen, Bertus Syn, Wing-Kin TI Cholangiocyte chemokine secretion and macrophage accumulation is mediated by osteopontin in murine liver models SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Coombes, Jason D.; Manka, Paul P.; Younis, Rasha; Briones, Marco A.; Kitamura, Naoto; Mehta, Kosha; Williams, Roger; Syn, Wing-Kin] Kings Coll London, Inst Hepatol, Regenerat & Repair, London, England. [Manka, Paul P.; Canbay, Ali] Univ Hosp Essen, Gastroenterol & Hepatol, Essen, Germany. [Swiderska-Syn, Marzena; Diehl, Anna Mae] Duke Univ, Med & Gastroenterol, Durham, NC USA. [Reid, Danielle; Eksteen, Bertus] Univ Calgary, Snyder Inst Chron Dis, Calgary, AB, Canada. [Riva, Antonio; Williams, Roger; Chokshi, Shilpa] Kings Coll London, Inst Hepatol, Viral Hepatitis & Alcohol Res Grp, London, England. [Claridge, Lee C.] Leeds Teaching Hosp NHS Trust, Dept Hepatol, Leeds, W Yorkshire, England. [Dolle, Laurent; van Grunsven, Leo A.] Vrije Univ Brussels, Liver Cell Biol, Brussels, Belgium. [Mi, Zhiyong; Kuo, Paul C.] Loyola Univ, Dept Surg, Chicago, IL 60611 USA. [Flamant, Frederic; Gauthier, Karine] Ecole Normale Super Lyon, Inst Genom Fonct Lyon, Lyon, France. [Syn, Wing-Kin] Med Univ South Carolina, Div Gastroenterol & Hepatol, Charleston, SC USA. [Syn, Wing-Kin] Ralph H Johnson Vet Affairs Med Ctr, Gastroenterol Sect, Charleston, SC 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 168 BP 89A EP 90A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800169 ER PT J AU Beste, LA Green, P Berry, K Ioannou, GN AF Beste, Lauren A. Green, Pamela Berry, Kristin Ioannou, George N. TI Effectiveness of direct antiviral agents for hepatitis C virus in 624 patients with hepatocellular carcinoma in the Veterans Affairs Healthcare System SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Beste, Lauren A.; Green, Pamela; Berry, Kristin] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 169 BP 90A EP 90A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800170 ER PT J AU Moon, AM Green, P Berry, K Ioannou, GN AF Moon, Andrew M. Green, Pamela Berry, Kristin Ioannou, George N. TI Towards eradication of hepatitis C virus infection in the Veterans Affairs national healthcare system: a study of 107,079 antiviral treatment regimens administered from 1999-2015 SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Moon, Andrew M.; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Green, Pamela; Berry, Kristin] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 227 BP 120A EP 120A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800228 ER PT J AU Chhatwal, J Samur, S Kues, B Ayer, T Roberts, MS Kanwal, F Hur, C Donnell, DM Chung, RT AF Chhatwal, Jagpreet Samur, Sumeyye Kues, Brian Ayer, Turgay Roberts, Mark S. Kanwal, Fasiha Hur, Chin Donnell, Drew M. Chung, Raymond T. TI Optimal Timing of Hepatitis C Treatment for Patients on the Liver Transplant Waiting List SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chhatwal, Jagpreet; Samur, Sumeyye; Hur, Chin; Chung, Raymond T.] Harvard Med Sch, Boston, MA USA. [Kues, Brian; Ayer, Turgay] Georgia Inst Technol, Atlanta, GA 30332 USA. [Roberts, Mark S.; Donnell, Drew M.] Univ Pittsburgh, Pittsburgh, PA USA. [Kanwal, Fasiha] Baylor Coll Med, Houston, TX 77030 USA. [Kanwal, Fasiha] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Chhatwal, Jagpreet; Samur, Sumeyye; Hur, Chin; Chung, Raymond T.] Massachusetts Gen Hosp, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 254 BP 133A EP 134A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800255 ER PT J AU Tsai, MC Lee, YM Zhang, DY Kim, RS Bian, CB Goossens, N Fuchs, BC Bhattacharya, D Chou, HI Hoshida, Y Friedman, SL AF Tsai, Ming-Chao Lee, Young-Min Zhang, David Y. Kim, Rosa S. Bian, C. Billie Goossens, Nicolas Fuchs, Bryan C. Bhattacharya, Dipankar Chou, Hsin I. Hoshida, Yujin Friedman, Scott L. TI A Protocadherin, PCDH7, Regulates a Distinct Program in Hepatic Stellate Cells that Promotes Proliferation and Migration but not Fibrogenesis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tsai, Ming-Chao; Lee, Young-Min; Zhang, David Y.; Kim, Rosa S.; Bian, C. Billie; Bhattacharya, Dipankar; Chou, Hsin I.; Hoshida, Yujin; Friedman, Scott L.] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA. [Tsai, Ming-Chao] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Hepatogastroenterol, Kaohsiung, Taiwan. [Tsai, Ming-Chao] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Fuchs, Bryan C.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Goossens, Nicolas; Hoshida, Yujin; Friedman, Scott L.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Liver Canc Program, New York, NY 10029 USA. [Goossens, Nicolas; Hoshida, Yujin; Friedman, Scott L.] Univ Hosp Geneva, Div Gastroenterol & Hepatol, Geneva, Switzerland. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 321 BP 165A EP 165A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801063 ER PT J AU Chen, JY Ren, YJ Chung, RT Butt, AA AF Chen, Jennifer Y. Ren, Yanjie Chung, Raymond T. Butt, Adeel A. TI Tricyclic Antidepressant Use and the Risk of Fibrosis Progression and Hepatocellular Carcinoma in Hepatitis C-Infected Persons: Results from ERCHIVES SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chen, Jennifer Y.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastroenterol Hepatol, Boston, MA 02114 USA. [Butt, Adeel A.] Weill Cornell Med Coll, New York, NY USA. [Ren, Yanjie] Univ Pittsburgh, Pittsburgh, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 408 BP 208A EP 209A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801150 ER PT J AU Roberts, LR Farshidfar, F Zheng, SY Gingras, MC Newton, Y Shih, J Robertson, AG Hinoue, T Hoadley, KA Gibbs, R Roszik, J Covington, K Wu, CC Shinbrot, E Stransky, N Hegde, AM Yang, JD Reznik, E Sadeghi, S Pedamallu, CS Ojesina, AI Hess, J Auman, JT Rhie, SK Bowlby, R Borad, MJ Stuart, J Sander, C Akbani, R Cherniack, AD Laird, PW Deshpande, V Mounajjed, T Foo, WC Torbenson, M Kleiner, DE Wheeler, DA Mcree, AJ Bathe, OF Andersen, JB Bardeesy, N Kwong, LN AF Roberts, Lewis R. Farshidfar, Farshad Zheng, Siyuan Gingras, Marie-Claude Newton, Yulia Shih, Juliann Robertson, A. Gordon Hinoue, Toshinori Hoadley, Katherine A. Gibbs, Richard Roszik, Jason Covington, Kyle Wu, Chia-Chin Shinbrot, Eve Stransky, Nicolas Hegde, Apurva M. Yang, Ju Dong Reznik, Ed Sadeghi, Sara Pedamallu, Chandra Sekhar Ojesina, Akinyemi I. Hess, Julian Auman, J. Todd Rhie, Suhn K. Bowlby, Reanne Borad, Mitesh J. Stuart, Josh Sander, Chris Akbani, Rehan Cherniack, Andrew D. Laird, Peter W. Deshpande, Vikram Mounajjed, Taofic Foo, Wai Chin Torbenson, Michael Kleiner, David E. Wheeler, David A. Mcree, Autumn J. Bathe, Oliver F. Andersen, Jesper B. Bardeesy, Nabeel Kwong, Lawrence N. TI Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Roberts, Lewis R.; Yang, Ju Dong; Mounajjed, Taofic; Torbenson, Michael] Mayo Clin, Coll Med, Rochester, MN USA. [Farshidfar, Farshad] Univ Calgary, Calgary, AB, Canada. [Zheng, Siyuan; Roszik, Jason; Wu, Chia-Chin; Hegde, Apurva M.; Akbani, Rehan; Foo, Wai Chin; Kwong, Lawrence N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gingras, Marie-Claude; Gibbs, Richard; Covington, Kyle; Shinbrot, Eve; Wheeler, David A.] Baylor Coll Med, Houston, TX 77030 USA. [Newton, Yulia; Stuart, Josh] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Shih, Juliann; Cherniack, Andrew D.] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA USA. [Robertson, A. Gordon; Sadeghi, Sara; Bowlby, Reanne] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Hinoue, Toshinori; Laird, Peter W.] Van Andel Res Inst, Grand Rapids, MI USA. [Hoadley, Katherine A.; Auman, J. Todd; Mcree, Autumn J.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Stransky, Nicolas] Blueprint Med, Cambridge, MA USA. [Reznik, Ed] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Pedamallu, Chandra Sekhar; Sander, Chris] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ojesina, Akinyemi I.] Univ Alabama Birmingham, Birmingham, AL USA. [Rhie, Suhn K.] Univ Southern Calif, Los Angeles, CA USA. [Borad, Mitesh J.] Mayo Clin, Scottsdale, AZ USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Bathe, Oliver F.] Tom Baker Canc Clin, Calgary, AB, Canada. [Andersen, Jesper B.] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Bardeesy, Nabeel] Harvard Med Sch, Ctr Canc, Gen Hosp 1Massachusetts, Boston, MA USA. [Hess, Julian] Broad Inst, Cambridge, MA USA. [Deshpande, Vikram] Massachusetts Gen Hosp, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 447 BP 227A EP 227A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801189 ER PT J AU Briones, MA Coombes, JD Mellone, M Rispoli, R Tolosa, E Manka, PP Kitamura, N Quaglia, A Canbay, A Alpini, G Glaser, SS Williams, R Papa, S Fernandez-Zapico, ME Syn, WK AF Briones, Marco A. Coombes, Jason D. Mellone, Massimiliano Rispoli, R. Tolosa, Ezequiel Manka, Paul P. Kitamura, Naoto Quaglia, Alberto Canbay, Ali Alpini, Gianfranco Glaser, Shannon S. Williams, Roger Papa, Salvatore Fernandez-Zapico, Martin E. Syn, Wing-Kin TI The role of osteopontin isoforms in cholangiocarcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Syn, Wing-Kin] Med Univ South Carolina, Med, Charleston, SC USA. [Briones, Marco A.; Coombes, Jason D.; Manka, Paul P.; Kitamura, Naoto; Williams, Roger; Papa, Salvatore] Kings Coll London, Inst Hepatol, Fac Life Sci & Med, Div Transplantat Immunol & Mucosal Biol, London, England. [Syn, Wing-Kin] Ralph H Johnson VAMC, Gastroenterol, Charleston, SC USA. [Mellone, Massimiliano] Univ Southampton, Canc Sci Unit, London, England. [Rispoli, R.] John Radcliffe Hosp Oxford, Weatherall Inst Mol Med, Oxford, England. [Tolosa, Ezequiel; Fernandez-Zapico, Martin E.] Mayo Clin, Oncol, Rochester, MN USA. [Manka, Paul P.; Canbay, Ali] Univ Hosp Essen, Gastroenterol & Hepatol, Essen, Germany. [Alpini, Gianfranco; Glaser, Shannon S.] Cent Texas Vet Hlth Care Syst, Med, Temple, TX USA. [Alpini, Gianfranco; Glaser, Shannon S.] Texas A&M Hlth Sci Ctr, Med, Temple, TX USA. [Quaglia, Alberto] Kings Coll London, Liver Pathol, London, England. [Papa, Salvatore] Univ Leeds, Inst Canc & Pathol, Leeds, W Yorkshire, England. [Fernandez-Zapico, Martin E.] Mayo Clin, Gastroenterol, Rochester, MN 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 463 BP 235A EP 235A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801205 ER PT J AU He, L Zheng, DD Lin, WY Jin, QM Hu, LJ Zhou, YC Yang, GX Fusco, D Chung, RT Hong, J AF He, Lu Zheng, Dandan Lin, Wenyu Jin, Qimeng Hu, Lijuan Zhou, Yuchen Yang, Guoxiong Fusco, Dahlene Chung, Raymond T. Hong, Jian TI MSI2 expression is associated with HCC invasion in activated hepatic stellate cells SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [He, Lu] Guangzhou Med Univ, Affiliated Tumour Hosp, Dept Radiat Oncol, Guangzhou, Guangdong, Peoples R China. [Zheng, Dandan; Jin, Qimeng; Zhou, Yuchen; Yang, Guoxiong; Hong, Jian] Southern Med Univ, Ctr Canc, Dept Abdominal Surg, Guangzhou, Guangdong, Peoples R China. [Lin, Wenyu; Fusco, Dahlene; Chung, Raymond T.; Hong, Jian] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA USA. [Hu, Lijuan] Guangzhou Med Univ, Affiliated Tumour Hosp, Dept Med Oncol, Guangzhou, Guangdong, Peoples R China. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 488 BP 247A EP 247A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801230 ER PT J AU Tu, Z Yuan, L Hu, Y Hu, JL Duan, XQ Liu, X Holmes, JA Huang, AL Lin, WY Chung, RT AF Tu, Zeng Yuan, Lin Hu, Yuan Hu, Jieli Duan, Xiaoqiong Liu, Xiao Holmes, Jacinta A. Huang, Ailong Lin, Wenyu Chung, Raymond T. TI ADAR1 modulates HBV replication SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tu, Zeng; Duan, Xiaoqiong; Liu, Xiao; Holmes, Jacinta A.; Lin, Wenyu; Chung, Raymond T.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Tu, Zeng; Yuan, Lin] Chongqing Med Univ, Coll Basic Med Sci, Dept Pathogen Biol, Chongqing, Peoples R China. [Tu, Zeng; Yuan, Lin; Hu, Yuan; Hu, Jieli; Huang, Ailong] Chongqing Med Univ, Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 578 BP 288A EP 288A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801318 ER PT J AU Ajmera, VH Huang, HL Daly, M Lee, WM Chung, RT AF Ajmera, Veeral H. Huang, Hailiang Daly, Mark Lee, William M. Chung, Raymond T. TI A CXCL16 polymorphism is associated with Hepatitis B Virus-related Acute Liver Failure in Caucasians and African Americans SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ajmera, Veeral H.] UCSF, Gastroenterol, San Francisco, CA USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. [Huang, Hailiang; Daly, Mark] Broad Inst, Boston, MA USA. [Lee, William M.] UT Southwestern, Gastroenterol, Dallas, TX 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 583 BP 290A EP 290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801323 ER PT J AU Lin, WY Duan, XQ Cai, DC Tu, Z Liu, X Holmes, JA Hong, J Zhu, CL Schaefer, EAA Salloum, S Brisac, C Chung, RT AF Lin, Wenyu Duan, Xiaoqiong Cai, Dachuan Tu, Zeng Liu, Xiao Holmes, Jacinta A. Hong, Jian Zhu, Chuanlong Schaefer, Esper-Ance A. Salloum, Shadi Brisac, Cynthia Chung, Raymond T. TI MX1 variants regulate both HBV and HCV replication SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Duan, Xiaoqiong; Cai, Dachuan; Tu, Zeng; Liu, Xiao; Holmes, Jacinta A.; Hong, Jian; Zhu, Chuanlong; Schaefer, Esper-Ance A.; Salloum, Shadi; Brisac, Cynthia; Chung, Raymond T.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Duan, Xiaoqiong] Chinese Acad Med Sci, Inst Blood Transfus, Chengdu, Peoples R China. [Duan, Xiaoqiong] Peking Union Med Coll, Chengdu, Peoples R China. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 626 BP 312A EP 312A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801366 ER PT J AU Zhu, B Wei, L Day, H Rietz, T Farrar, CT Lauwers, GY Tanabe, KK Rosen, B Fuchs, BC Caravan, P AF Zhu, Bo Wei, Lan Day, Helen Rietz, Tyson Farrar, Christian T. Lauwers, Gregory Y. Tanabe, Kenneth K. Rosen, Bruce Fuchs, Bryan C. Caravan, Peter TI Combined MR elastography and collagen molecular MR imaging accurately stage liver fibrosis in a rat model SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Zhu, Bo; Day, Helen; Rietz, Tyson; Farrar, Christian T.; Rosen, Bruce; Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA USA. [Zhu, Bo] Harvard Univ, Phys, Cambridge, MA 02138 USA. [Wei, Lan; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Surg Oncol, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 649 BP 322A EP 323A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801389 ER PT J AU Farrar, CT Wei, L Choi, JK Huang, S Ferriera, DDS Ghoshal, S Masia, R Li, Y Chau, MD Tanabe, KK Or, YS Caravan, P Jiang, L Fuchs, BC AF Farrar, Christian T. Wei, Lan Choi, Ji-Kyung Huang, Shuning Ferriera, Diego Dos Santos Ghoshal, Sarani Masia, Ricard Li, Yang Chau, Mary D. Tanabe, Kenneth K. Or, Yat Sun Caravan, Peter Jiang, Lijuan Fuchs, Bryan C. TI The Novel Farnesoid X Receptor (FXR) agonist, EDP-305, Reduces Fibrosis Progression in Bile Duct Ligated Rats SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wei, Lan; Ghoshal, Sarani; Tanabe, Kenneth K.; Fuchs, Bryan C.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Farrar, Christian T.; Choi, Ji-Kyung; Huang, Shuning; Ferriera, Diego Dos Santos; Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Masia, Ricard] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Li, Yang; Chau, Mary D.; Or, Yat Sun; Jiang, Lijuan] Enanta Pharmaceut, Watertown, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 650 BP 323A EP 323A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801390 ER PT J AU Ebel, N Hsu, E Berry, K Horslen, S Ioannou, GN AF Ebel, Noelle Hsu, Evelyn Berry, Kristin Horslen, Simon Ioannou, George N. TI Waitlist and post-transplantation outcomes in liver transplant registrants and recipients ages 18-24 years old: analysis of the UNOS database SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ebel, Noelle; Hsu, Evelyn; Horslen, Simon] Seattle Childrens Hosp, Seattle, WA USA. [Ebel, Noelle; Hsu, Evelyn; Horslen, Simon] Univ Washington, Sch Med, Pediat, Seattle, WA USA. [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 668 BP 332A EP 332A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801408 ER PT J AU Mehta, K Briones, MA Manka, PP Coombes, JD Williams, R Patel, VB Syn, WK AF Mehta, Kosha Briones, Marco A. Manka, Paul P. Coombes, Jason D. Williams, Roger Patel, Vinood B. Syn, Wing-Kin TI Iron enhances hepatic fibrogenesis through TGF-beta activation SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Syn, Wing-Kin] Med Univ South Carolina, Gastroenterol & Hepatol, Charleston, SC USA. [Syn, Wing-Kin] Ralph H Johnson VAMC, Gastroenterol, Charleston, SC USA. [Mehta, Kosha; Briones, Marco A.; Manka, Paul P.; Coombes, Jason D.; Williams, Roger] Kings Coll London, Fac Life Sci, Inst Hepatol, Div Transplantat Immunol & Mucosal Biol, London, England. [Mehta, Kosha; Patel, Vinood B.] Univ Westminster, Biomed Sci, London, England. [Manka, Paul P.] Univ Hosp Essen, Gastroenterol & Hepatol, Essen, Germany. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 727 BP 360A EP 360A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801467 ER PT J AU Butt, AA Ren, Y AF Butt, Adeel A. Ren, Yanjie TI Comparing Child-Pugh, MELD and FIB-4 Scores to Predict Mortality, Hepatic Decompensation and Hepatocellular Carcinoma in HCV Infected Persons: ERCHIVES Study SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Butt, Adeel A.] Weill Cornell Med Coll, Div Infect Dis, Mars, PA USA. [Ren, Yanjie] VA Pittsburgh Healthcare Syst, Pittsburgh, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 742 BP 367A EP 367A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802013 ER PT J AU Wurcel, AG Burke, DJ Engle, B Noonan, K Knox, TA Kim, AY Linas, BP AF Wurcel, Alysse G. Burke, Deirdre J. Engle, Brian Noonan, Kathryn Knox, Tamsin A. Kim, Arthur Y. Linas, Benjamin P. TI HCV is an independent predictor of hospital readmission in inmates SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wurcel, Alysse G.; Burke, Deirdre J.] Tufts Med Ctr, Geog Med & Infect Dis, Boston, MA USA. [Wurcel, Alysse G.; Burke, Deirdre J.; Engle, Brian; Knox, Tamsin A.] Tufts Univ, Sch Med, Publ Hlth & Community Med, Boston, MA USA. [Linas, Benjamin P.] Boston Med Ctr, Infect Dis, Boston, MA USA. [Noonan, Kathryn] Lemuel Shattuck Hosp, Boston, MA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Infect Dis, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 774 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802044 ER PT J AU Jain, V Otero, D Gavrancic, T Liu, Q Marcus, S Brau, N AF Jain, Varun Otero, Diana Gavrancic, Tatjana Liu, Qing Marcus, Sonja Brau, Norbert TI Spontaneous Clearance of Chronic HCV Infection is More Frequent in HIV/HCV Coinfection and in HCV Genotype 2 and 3 SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jain, Varun; Otero, Diana; Gavrancic, Tatjana; Liu, Qing; Brau, Norbert] James J Peters VA Med Ctr, Program Med, Bronx, NY USA. [Jain, Varun; Otero, Diana; Gavrancic, Tatjana; Liu, Qing; Brau, Norbert] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Marcus, Sonja] James J Peters VA Med Ctr, Res Program, Bronx, NY 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 779 BP 384A EP 384A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802049 ER PT J AU Benhammou, J Yu, CY Kawamoto, JK Dixit, V Pimstone, N Sheinbaum, AJ Pisegna, JR AF Benhammou, Jihane Yu, Christine Y. Kawamoto, Jenna K. Dixit, Vivek Pimstone, Neville Sheinbaum, Alan J. Pisegna, Joseph R. TI Hepatitis C SVR is not affected by the metabolic syndrome or diabetes in patients treated at a single VA hospital clinic SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Benhammou, Jihane; Yu, Christine Y.] Univ Calif Los Angeles, Santa Monica, CA USA. [Kawamoto, Jenna K.; Dixit, Vivek; Pimstone, Neville; Sheinbaum, Alan J.; Pisegna, Joseph R.] VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 787 BP 387A EP 388A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802056 ER PT J AU Chan, J Gogela, N Zheng, H Lammert, S Ajayi, T Fricker, Z Kim, AY Robbins, GK Chung, RT AF Chan, Justin Gogela, Neliswa Zheng, Hui Lammert, Sara Ajayi, Tokunbo Fricker, Zachary Kim, Arthur Y. Robbins, Gregory K. Chung, Raymond T. TI Direct Acting Anti-Viral (DAA) Therapy for Chronic Hepatitis C Virus (HCV) Infection Is Associated with Regression of Liver Fibrosis, Assessed by Serial Transient Elastography (Fibroscan) SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chan, Justin; Lammert, Sara; Kim, Arthur Y.; Robbins, Gregory K.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Chan, Justin; Zheng, Hui; Lammert, Sara; Ajayi, Tokunbo; Fricker, Zachary; Kim, Arthur Y.; Robbins, Gregory K.; Chung, Raymond T.] Harvard Med Sch, Boston, MA USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Ajayi, Tokunbo; Fricker, Zachary; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gogela, Neliswa] Univ Cape Town, Div Hepatol, Cape Town, South Africa. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 803 BP 395A EP 396A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802072 ER PT J AU Chhatwal, J Chen, Q Ayer, T Kanwal, F Kowdley, KV Wang, XJ Roberts, MS Gordon, SC AF Chhatwal, Jagpreet Chen, Qiushi Ayer, Turgay Kanwal, Fasiha Kowdley, Kris V. Wang, Xiaojie Roberts, Mark S. Gordon, Stuart C. TI Patients who Fail Treatment in the era of DAAs: Projections from HEP-SIM Model SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chhatwal, Jagpreet] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. [Kowdley, Kris V.] Swedish Med Ctr, Seattle, WA USA. [Gordon, Stuart C.] Henry Ford Hosp, Detroit, MI 48202 USA. [Chen, Qiushi; Ayer, Turgay; Wang, Xiaojie] Georgia Inst Technol, Atlanta, GA 30332 USA. [Kanwal, Fasiha] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kanwal, Fasiha] Baylor Coll Med, Houston, TX 77030 USA. [Roberts, Mark S.] Univ Pittsburgh, Pittsburgh, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 839 BP 412A EP 412A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802107 ER PT J AU Tran, TT Feld, JJ Foster, GR Naik, S Eggleton, ES Zhang, J Natha, M Llewellyn, J Kreter, B Brainard, DM Wyles, DL Sulkowski, MS Rogal, SS AF Tran, Tram T. Feld, Jordan J. Foster, Graham R. Naik, Sarjita Eggleton, Edward S. Zhang, Jie Natha, Macky Llewellyn, Joseph Kreter, Bruce Brainard, Diana M. Wyles, David L. Sulkowski, Mark S. Rogal, Shari S. TI Gender Differences in Patients Treated for HCV: Efficacy and Safety of Sofosbuvir/Velpatasvir in Women SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tran, Tram T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Feld, Jordan J.] Univ Toronto, Toronto, ON, Canada. [Foster, Graham R.] Queen Marys Univ London, London, England. [Naik, Sarjita; Eggleton, Edward S.; Zhang, Jie; Natha, Macky; Llewellyn, Joseph; Kreter, Bruce; Brainard, Diana M.] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA. [Wyles, David L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Baltimore, MD USA. [Rogal, Shari S.] VA Pittsburgh Healthcare Syst, Pittsburgh, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 857 BP 422A EP 422A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802125 ER PT J AU Butt, AA Ren, Y Marks, KM Shaikh, OS Sherman, KE AF Butt, Adeel A. Ren, Yanjie Marks, Kristen M. Shaikh, Obaid S. Sherman, Kenneth E. TI Does Paritaprevir/ritonavir, Ombitasvir, Dasabuvir Combination Increase the Risk of Hepatic Decompensation and Renal Insufficiency in Patients with Cirrhosis? SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Butt, Adeel A.; Marks, Kristen M.] Weill Cornell Med Coll, Div Infect Dis, Mars, PA USA. [Ren, Yanjie; Shaikh, Obaid S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sherman, Kenneth E.] Univ Cincinnatti, Cincinnati, OH 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 902 BP 451A EP 451A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802169 ER PT J AU Tsui, J Williams, E Green, P Berry, K Su, F Ioannou, GN AF Tsui, Judith Williams, Emily Green, Pamela Berry, Kristin Su, Feng Ioannou, George N. TI Alcohol use and hepatitis C virus treatment outcomes among 15,151 patients receiving direct antiviral agents SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tsui, Judith; Su, Feng; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Williams, Emily; Green, Pamela; Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 911 BP 457A EP 458A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802178 ER PT J AU Butt, AA Yan, P Marks, KM Shaikh, OS Sherman, KE AF Butt, Adeel A. Yan, Peng Marks, Kristen M. Shaikh, Obaid S. Sherman, Kenneth E. TI Real-world SVR Rates for Paretaprevir/ritonavir, Ombitasvir, Dasabuvir vs. Sofosbuvir/ledipasvir Regimens With and Without Ribavirin SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Butt, Adeel A.; Marks, Kristen M.] Weill Cornell Med Coll, Div Infect Dis, Mars, PA USA. [Yan, Peng; Shaikh, Obaid S.] VA Pittsburgh Healtcare Syst, Pittsburgh, PA USA. [Sherman, Kenneth E.] Univ Cincinnati, Cincinnati, OH 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 930 BP 468A EP 468A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802197 ER PT J AU Fuchs, M Morgan, TR Charafeddine, M Brau, N Schmidt, WN Kozal, M Naggie, S Cheung, R Pilot-Matias, T Yu, Y Richards, K Mullally, V Cohen, DE Monto, A Toro, DH AF Fuchs, Michael Morgan, Timothy R. Charafeddine, Mariem Brau, Norbert Schmidt, Warren N. Kozal, Michael Naggie, Susanna Cheung, Ramsey Pilot-Matias, Tami Yu, Yao Richards, Kristine Mullally, Victoria Cohen, Daniel E. Monto, Alexander Toro, Doris H. TI An Open-Label, Multicenter Study of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with or without Ribavirin in US Veterans with Genotype 1 Chronic Hepatitis C Infection: Efficacy and Safety Results of TOPAZ-VA SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fuchs, Michael] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Charafeddine, Mariem; Pilot-Matias, Tami; Yu, Yao; Richards, Kristine; Mullally, Victoria; Cohen, Daniel E.] AbbVie Inc, N Chicago, IL USA. [Brau, Norbert] James J Peters VA Med Ctr, Bronx, NY USA. [Schmidt, Warren N.] Iowa City VA Healthcare Syst, Iowa City, IA 5 USA. [Kozal, Michael] VA Connecticut Healthcare Syst, New Haven, CT USA. [Kozal, Michael] Yale Univ, Sch Med, New Haven, CT USA. [Naggie, Susanna] Durham VA Med Ctr, Durham, NC USA. [Cheung, Ramsey] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Monto, Alexander] San Francisco VA Med Ctr, San Francisco, CA USA. [Toro, Doris H.] VA Caribbean Healthcare Syst, San Juan, PR 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 963 BP 488A EP 488A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802230 ER PT J AU Golden-Mason, LM Giugliano, S Campbell, EL Cheng, LL Collins, CA Rosen, HR AF Golden-Mason, Lucy M. Giugliano, Silvia Campbell, Eric L. Cheng, Linling Collins, Christine A. Rosen, Hugo R. TI Advanced Nonalcoholic Steatohepatitis (NASH) Associated with Activated, Proinflammatory Phenotypes of Circulating Neutrophils SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Golden-Mason, Lucy M.; Giugliano, Silvia; Campbell, Eric L.; Cheng, Linling; Collins, Christine A.; Rosen, Hugo R.] Univ Colorado, GI Hepatol, Aurora, CO USA. [Golden-Mason, Lucy M.; Collins, Christine A.; Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1158 BP 583A EP 583A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802425 ER PT J AU Giugliano, S Kriss, M Golden-Mason, LM Wilson, C Rosen, HR AF Giugliano, Silvia Kriss, Michael Golden-Mason, Lucy M. Wilson, Cara Rosen, Hugo R. TI Alcohol Exposure Differentially Regulates Immune Responses of Liver Endothelial Cells and Hepatic Stellate Cells to E. coli Infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Giugliano, Silvia; Kriss, Michael; Golden-Mason, Lucy M.; Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Anschutz Med Campus, Aurora, CO USA. [Wilson, Cara] Univ Colorado, Div Infect Dis, Anschutz Med Campus, Aurora, CO USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1225 BP 615A EP 615A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803032 ER PT J AU Goossens, N Singal, AG King, LY Andersson, KL Fuchs, BC Besa, C Taouli, B Chung, RT Hoshida, Y AF Goossens, Nicolas Singal, Amit G. King, Lindsay Y. Andersson, Karin L. Fuchs, Bryan C. Besa, Cecilia Taouli, Bachir Chung, Raymond T. Hoshida, Yujin TI Cost-effectiveness of a risk-stratified hepatocellular carcinoma surveillance strategy in patients with cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Goossens, Nicolas; Hoshida, Yujin] Icahn Sch Med Mt Sinai, Liver Dis, New York, NY 10029 USA. [Goossens, Nicolas] Univ Hosp Geneva, Gastroenterol & Hepatol, Geneva, Switzerland. [Andersson, Karin L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Liver Ctr, Boston, MA 02114 USA. [Fuchs, Bryan C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Besa, Cecilia; Taouli, Bachir] Icahn Sch Med Mt Sinai, Dept Radiol, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Singal, Amit G.] UT Southwestern Med Ctr, Dept Internal Med, Dallase, TX USA. [Singal, Amit G.] UT Southwestern Med Ctr, Harold C Simmons Canc Ctr, Dallase, TX USA. [King, Lindsay Y.] Duke Univ Hlth Syst, Durham, NC 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1254 BP 630A EP 630A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803061 ER PT J AU Jay, CL Washburn, K Halff, GA Abrahamian, G Pugh, J AF Jay, Colleen L. Washburn, Kenneth Halff, Glenn A. Abrahamian, Greg Pugh, Jacqueline TI Graft quality matters: KDPI is more predictive of survival than SLK compared with liver transplant alone in a propensity score matched cohort SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jay, Colleen L.; Halff, Glenn A.; Abrahamian, Greg] Univ Texas Hlth Sci Ctr San Antonio, Transplant Ctr, San Antonio, TX 78229 USA. [Washburn, Kenneth] Ohio State Univ, Med Ctr, Comprehens Transplant Ctr, Columbus, TX USA. [Pugh, Jacqueline] South Texas Vet Hlth Care Syst, San Antonio, TX 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1381 BP 691A EP 691A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803188 ER PT J AU Tonnerre, P Aljabban, J Tully, D Bean, D Brown, JA Wolski, D Torres-Cornejo, A Robidoux, M Kvistad, D Gustafson, J Aneja, J Allen, T Chung, RT Kim, AY Lauer, GM AF Tonnerre, Pierre Aljabban, Jihad Tully, Damien Bean, David Brown, Joelle A. Wolski, David Torres-Cornejo, Almudena Robidoux, Maxwell Kvistad, Daniel Gustafson, Jenna Aneja, Jasneet Allen, Todd Chung, Raymond T. Kim, Arthur Y. Lauer, Georg M. TI Reversal of HCV-specific CD8+T cell exhaustion after removal of cognate antigen SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tonnerre, Pierre; Aljabban, Jihad; Brown, Joelle A.; Wolski, David; Torres-Cornejo, Almudena; Robidoux, Maxwell; Kvistad, Daniel; Gustafson, Jenna; Aneja, Jasneet; Chung, Raymond T.; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Tonnerre, Pierre; Aljabban, Jihad; Brown, Joelle A.; Wolski, David; Torres-Cornejo, Almudena; Robidoux, Maxwell; Kvistad, Daniel; Gustafson, Jenna; Aneja, Jasneet; Chung, Raymond T.; Lauer, Georg M.] Harvard Med Sch, Boston, MA USA. [Tully, Damien; Bean, David; Allen, Todd] Ragon Inst Massachusetts Gen Hosp Massachusettset, Cambridge, MA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Arthur Y.] Harvard Med Sch, Boston, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1464 BP 731A EP 732A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803271 ER PT J AU Duan, XQ Li, SL Li, YJ Jiao, BH Tut, Z Liu, X Holmes, JA Chen, LM Line, WY Chung, RT AF Duan, Xiaoqiong Li, Shilin Li, Yujia Jiao, Baihai Tu, Zeng Liu, Xiao Holmes, Jacinto A. Chen, Limin Lin, Wenyu Chung, Raymond T. TI MicroRNA-130a regulates HCV and HBV replication through a central metabolic pathway SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Duan, Xiaoqiong; Li, Shilin; Li, Yujia; Jiao, Baihai; Chen, Limin] Chinese Acad Med Sci, Inst Blood Transfus, Chengdu, Peoples R China. [Duan, Xiaoqiong; Li, Shilin; Li, Yujia; Jiao, Baihai; Chen, Limin] Peking Union Med Coll, Chengdu, Peoples R China. [Duan, Xiaoqiong; Tu, Zeng; Liu, Xiao; Holmes, Jacinto A.; Lin, Wenyu; Chung, Raymond T.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1469 BP 734A EP 734A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803276 ER PT J AU Liu, X Hong, J Coi, DC Duan, XQ Tu, Z Salloum, S Holmes, JA Lidofsky, A Xu, ZW Lin, WY Chung, RT AF Liu, Xiao Hong, Jian Coi, Dachuan Duan, Xiaoqiong Tu, Zeng Salloum, Shadi Holmes, Jacinto A. Lidofsky, Anna Xu, Zhiwen Lin, Wenyu Chung, Raymond T. TI The mechanism of lncRNA IFI6 regulation of HCV infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Liu, Xiao; Hong, Jian; Coi, Dachuan; Duan, Xiaoqiong; Tu, Zeng; Salloum, Shadi; Holmes, Jacinto A.; Lidofsky, Anna; Lin, Wenyu; Chung, Raymond T.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. [Liu, Xiao; Xu, Zhiwen] Sichuan Agr Univ, Coll Vet Med, Anim Biotechnol Ctr, Yaan, Peoples R China. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1479 BP 739A EP 740A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803286 ER PT J AU McMahan, R Porsche, C McGettigan, B Rosen, HR AF McMahan, Rachel Porsche, Cara McGettigan, Brett Rosen, Hugo R. TI Oxidized low-density lipoprotein (oxLDL) induces a pro-inflammatory/pro-fibrotic response from liver sinusoidal endothelial cells that is attenuated by activation of the nuclear bile acid receptor FXR SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [McMahan, Rachel; Porsche, Cara; McGettigan, Brett; Rosen, Hugo R.] Univ Colorado Denver, Gastroenterol & Hepatol, Aurora, CO USA. [Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1500 BP 749A EP 749A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803307 ER PT J AU Golden-Mason, LM McMahan, R Cheng, LL Rosen, HR AF Golden-Mason, Lucy M. McMahan, Rachel Cheng, Linling Rosen, Hugo R. TI Group 2 Innate Lymphoid Cells (ILC2s) are Altered in Fatty Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Golden-Mason, Lucy M.; McMahan, Rachel; Cheng, Linling; Rosen, Hugo R.] Univ Colorado, GI Hepatol, Aurora, CO USA. [Golden-Mason, Lucy M.; Rosen, Hugo R.] Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1506 BP 751A EP 752A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803313 ER PT J AU Masia, R McCarly, WJ Lahmann, C Luther, J Chung, RT Yarmush, ML Yellen, G AF Masia, Ricard McCarly, William J. Lahmann, Carolina Luther, Jay Chung, Raymond T. Yarmush, Martin L. Yellen, Gary TI Live cell imaging of hepatocyte cytosolic NADH/NAD(+) ratio in mouse liver slices SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Masia, Ricard] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [McCarly, William J.; Yarmush, Martin L.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Masia, Ricard; Lahmann, Carolina; Yellen, Gary] Harvard Med Sch, Neurobiol, Boston, MA USA. [Luther, Jay; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1509 BP 753A EP 753A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803316 ER PT J AU Fuchs, BC Waghorn, PA Atanasova, I Wei, L Masia, R Chen, I Rotile, N Jones, C Tanabe, KK Caravan, P AF Fuchs, Bryan C. Waghorn, Philip A. Atanasova, Iliyana Wei, Lan Masia, Ricard Chen, Iris Rotile, Nicholas Jones, Chloe Tanabe, Kenneth K. Caravan, Peter TI Quantitative molecular magnetic resonance imaging of fibrogenesis and fat content in the liver during non-alcoholic steatohepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fuchs, Bryan C.; Wei, Lan; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Waghorn, Philip A.; Atanasova, Iliyana; Chen, Iris; Rotile, Nicholas; Jones, Chloe; Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Masia, Ricard] Massachusetts Gen Hosp, Pathol, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1512 BP 754A EP 755A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803319 ER PT J AU Chen, HQ Li, Y Sherban, A Nocon, A Luo, T Wang, H Bin Gao, Zang, MW AF Chen, Hanqing Li, Yu Sherban, Alex Nocon, Allison Luo, Ting Wang, Hua Bin Gao Zang, Mengwei TI Pharmacological and Molecular inhibition of mTORC1 Activation Reduces Ethanol-Induced ER Stress and Ameliorates Alcoholic Liver Injury in Mice SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chen, Hanqing; Li, Yu; Sherban, Alex; Nocon, Allison; Luo, Ting] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wang, Hua; Bin Gao] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. [Chen, Hanqing; Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Ctr Hlth Aging, San Antonio, TX 78229 USA. [Chen, Hanqing; Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Zang, Mengwei] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1515 BP 756A EP 756A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803322 ER PT J AU Luther, J Gala, M King, KR Garber, J Masial, R Adams, D Yarmush, ML Chung, RT Patel, SJ AF Luther, Jay Gala, Manish King, Kevin R. Garber, John Masial, Ricard Adams, Daniel Yarmush, Martin L. Chung, Raymond T. Patel, Suraj J. TI Connexin 32 is a critical gatekeeper at the nexus between inflammation and steatosis in ALD and NAFLD SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Luther, Jay; Gala, Manish; Garber, John; Masial, Ricard; Chung, Raymond T.; Patel, Suraj J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [King, Kevin R.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA. [Adams, Daniel] HeproTech, Camebridge, MA USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, CCM, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1517 BP 756A EP 757A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803324 ER PT J AU Kruger, AJ Fuchs, BC Vig, P Lefebvre, E Holmes, JA Masia, R Wei, L Alatrakchi, N Salloum, S Brisac, C Chung, RT AF Kruger, Annie J. Fuchs, Bryan C. Vig, Pamela Lefebvre, Eric Holmes, Jacinto A. Masia, Ricard Wei, Lan Alatrakchi, Nadia Salloum, Shadi Brisac, Cynthia Chung, Raymond T. TI Cenicriviroc (CVC), a dual inhibitor of chemokine receptors (CCR) 2 and 5, decreases hepatic inflammation by altering inflammatory macrophage populations in a mouse model of NASH SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kruger, Annie J.; Holmes, Jacinto A.; Alatrakchi, Nadia; Salloum, Shadi; Brisac, Cynthia; Chung, Raymond T.] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA. [Vig, Pamela; Lefebvre, Eric] Tobira Therapeut, San Francisco, CA USA. [Fuchs, Bryan C.; Wei, Lan] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Masia, Ricard] Massachusetts Gen Hosp, Pathol, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1564 BP 777A EP 777A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803371 ER PT J AU Ikenagal, N Yue, P Vaid, K Mikels-Vigdal, A Smith, V Popov, Y AF Ikenagal, Naoki Yue, Peng Vaid, Kahini Mikels-Vigdal, Amanda Smith, Victoria Popov, Yury TI RNA-seq analysis identifies early gene signature associated with antifibrotic efficacy of dual combination therapy directed against lysyl oxidase-like 2 (LOXL2) and apoptosis signal-regulating kinase 1 (ASK1) in BALBc. Mdr2-/-mice SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ikenagal, Naoki; Vaid, Kahini; Popov, Yury] Beth Israel Deaconness Med Ctr, Gastroenterol, Boston, MA USA. [Yue, Peng; Mikels-Vigdal, Amanda; Smith, Victoria] Gilead Sci Inc, Foster City, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1664 BP 823A EP 823A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804026 ER PT J AU Feldbrugge, L Csizmadia, E Mitsuhashi, S Yee, EU Vaid, K Popov, Y Robson, SC Jiang, ZG AF Feldbrugge, Linda Csizmadia, Eva Mitsuhashi, Shuji Yee, Eric U. Vaid, Kahini Popov, Yury Robson, Simon C. Jiang, Z. Gordon TI Mice with genetic deletion of ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) are protected from development of both biliary and parenchymal-type liver fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Feldbrugge, Linda; Csizmadia, Eva; Mitsuhashi, Shuji; Vaid, Kahini; Popov, Yury; Robson, Simon C.; Jiang, Z. Gordon] BIDMC, Gastroenterol, Boston, MA USA. [Yee, Eric U.] BIDMC, Pathol, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1681 BP 831A EP 832A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804043 ER PT J AU Chhatwal, J Li, K He, TH Roberts, MS Ayer, T Samur, S Grefenstette, J Spaulding, AC AF Chhatwal, Jaapreet Li, Kan He, Tianhua Roberts, Mark S. Ayer, Turgay Samur, Sumeyye Grefenstette, John Spaulding, Anne C. TI Hepatitis C Treatment in United States Prisons Prevents Transmission and is Cost-Saving for the Society SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chhatwal, Jaapreet; Samur, Sumeyye] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chhatwal, Jaapreet; Samur, Sumeyye] Harvard Med Sch, Boston, MA USA. [Li, Kan] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [He, Tianhua] Tsinghua Univ, Sch Med, Beijing, Peoples R China. [Roberts, Mark S.; Grefenstette, John] Univ Pittsburgh, Pittsburgh, PA USA. [Ayer, Turgay] Georgia Inst Technol, Atlanta, GA 30332 USA. [Spaulding, Anne C.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1723 BP 851A EP 852A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804085 ER PT J AU Rubin, J Dave, S Aulakh, H Bacchus, A Earnest, GE Gager, K Tubbs, R Zejnullahu, K Dulay, M AF Rubin, Jessica Dave, Shravan Aulakh, Hardeep Bacchus, Alicia Earnest, Gillian E. Gager, Krista Tubbs, Ruth Zejnullahu, Kreshnik Dulay, Maya TI Improving Age-Based Hepatitis C Screening at a Veterans Affairs Primary Care Clinic SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Rubin, Jessica; Dave, Shravan; Aulakh, Hardeep; Bacchus, Alicia; Zejnullahu, Kreshnik] UCSF, San Francisco, CA USA. [Earnest, Gillian E.; Gager, Krista; Tubbs, Ruth; Dulay, Maya] San Francisco VA Med Ctr, San Francisco, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1745 BP 862A EP 862A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804107 ER PT J AU Rogal, SS Andrea, R Calgaro, L Daley, MB McCarthy, R Jonassaint, NL Zickmund, S AF Rogal, Shari S. Andrea, Reid Calgaro, Linda Daley, Molly B. McCarthy, Rory Jonassaint, Naudia L. Zickmund, Susan TI Primary Care and Hepatology Provider Attitudes Towards Hepatitis C Treatment Candidacy and Adherence SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Rogal, Shari S.; Calgaro, Linda; Daley, Molly B.; McCarthy, Rory; Zickmund, Susan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rogal, Shari S.; Jonassaint, Naudia L.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Rogal, Shari S.; Jonassaint, Naudia L.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Andrea, Reid] Washington DC VA Healthcare Syst, Div Gastroenterol Hepatol & Nutr, Washington, DC USA. [Zickmund, Susan] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1755 BP 866A EP 867A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804117 ER PT J AU Goldberg, DS Taddei, TH Serper, M Mehta, R Dieperink, E Aytaman, A Baytarian, M Fox, RK Hunt, KK Pedrosa, M Pocha, C Valderama, A Kaplan, DE AF Goldberg, David S. Taddei, Tamar H. Serper, Marina Mehta, Rajni Dieperink, Eric Aytaman, Ayse Baytarian, Michelle Fox, Rena K. Hunt, Kristel K. Pedrosa, Marcos Pocha, Christine Valderama, Adriana Kaplan, David E. TI Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Goldberg, David S.; Serper, Marina] Hosp Univ Penn, Div Gastroenterol, 3400 Spruce St, Philadelphia, PA 19104 USA. [Taddei, Tamar H.; Mehta, Rajni] VA Connecticut Healthcare Syst, New Haven, CT USA. [Dieperink, Eric] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Aytaman, Ayse] VA New York Harbor Hlth Care Syst, Brooklyn, NY USA. [Baytarian, Michelle; Pedrosa, Marcos] Boston VA Healthcare Syst, Boston, MA USA. [Fox, Rena K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hunt, Kristel K.] James J Peters VA Med Ctr, Bronx, NY USA. [Pocha, Christine] Univ Bern, Bern, Switzerland. [Valderama, Adriana] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Kaplan, David E.] Corporal Michael J Crescenz VA Med Ctr, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1768 BP 873A EP 873A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804130 ER PT J AU Su, F Green, P Berry, K Ioannou, GN AF Su, Feng Green, Pamela Berry, Kristin Ioannou, George N. TI The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Su, Feng; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Green, Pamela; Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1913 BP 946A EP 947A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804273 ER PT J AU Belperio, PS Bhattacharya, D Shahoumian, TA Loomis, TP Goetz, MB Mole, LA Backus, LI AF Belperio, Pamela S. Bhattacharya, Debika Shahoumian, Troy A. Loomis, Timothy P. Goetz, Matthew B. Mole, Larry A. Backus, Lisa I. TI Effectiveness of Ledipasvir/Sofosbuvir +/- Ribavirin and Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir +/- Ribavirin in 996 Genotype 1 HIV/HCV Coinfected Patients Treated in Routine Practice SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Belperio, Pamela S.; Shahoumian, Troy A.; Loomis, Timothy P.; Mole, Larry A.; Backus, Lisa I.] Vet Affairs Palo Alto Hlth Care Syst, Populat Hlth Serv, Palo Alto, CA USA. [Bhattacharya, Debika; Goetz, Matthew B.] Vet Affairs Greater Los Angeles Hlth Care Syst, Med, Los Angeles, CA USA. [Bhattacharya, Debika; Goetz, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Backus, Lisa I.] Palo Alto Hlth Care Syst, Dept Vet Affairs, Med, Palo Alto, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1935 BP 957A EP 958A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804295 ER PT J AU Su, F Greene, P Berry, K Ioannou, GN AF Su, Feng Greene, Pamela Berry, Kristin Ioannou, George N. TI High Effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection in Elderly Patients in a National Healthcare System SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Su, Feng; Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA. [Greene, Pamela; Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1940 BP 960A EP 960A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804300 ER PT J AU Sise, ME Alkhouri, N Borg, BB Carp, M De-Oertel, S Fuchs, M Gilles, H Llewellyn, J McQuaid, T Natha, M Reau, N Brainard, DM AF Sise, Meghan E. Alkhouri, Naim Borg, Brian B. Carp, Marc De-Oertel, Shampa Fuchs, Michael Gilles, HoChong Llewellyn, Joseph McQuaid, Thomas Natha, Macky Reau, Nancy Brainard, Diana M. TI Use of Ledipasvir/Sofosbuvir (LDV/SOF) in Patients with Advanced Chronic Kidney Disease (eGFR <= 30ml/min): A Case Series SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Llewellyn, Joseph; McQuaid, Thomas; Natha, Macky] Gilead Sci, Med Affairs, Norwalk, CT USA. [Sise, Meghan E.] Massachusetts Gen Hosp, Nephrol, Boston, MA 02114 USA. [Alkhouri, Naim] Cleveland Clin, Cleveland, OH 44106 USA. [Borg, Brian B.] Univ Mississippi, Med Ctr, Gastroenterol, Jackson, MS 39216 USA. [Carp, Marc] Gastro Hlth, Miami, FL USA. [Fuchs, Michael; Gilles, HoChong] Vet Affairs Med Ctr, Gastroenterol, Richmond, VA USA. [Reau, Nancy] Rush Univ, Med Ctr, Hepatol, Chicago, IL 60612 USA. [Brainard, Diana M.] Gilead Sci, Clin Res, Foster City, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1951 BP 967A EP 967A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804311 ER PT J AU Lim, K Palsson, R Siedlecki, A AF Lim, Kenneth Palsson, Ragnar Siedlecki, Andrew TI Dialysis Initiation During the Hospital Stay SO HOSPITAL MEDICINE CLINICS LA English DT Article DE Dialysis; Renal replacement therapy (RRT); Ultrafiltration; Uremia; Acute kidney injury (AKI) ID RENAL REPLACEMENT THERAPY; ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; LOW-EFFICIENCY DIALYSIS; INTENSIVE-CARE-UNIT; PERITONEAL-DIALYSIS; VASCULAR ACCESS; CLINICAL-OUTCOMES; HEMODIALYSIS; FAILURE AB The decision to commence renal replacement therapy is a pivotal milestone in the management of patients with acute kidney injury and advanced chronic kidney disease. There is currently a paucity of evidence to help guide clinicians on the optimal timing of renal replacement therapy initiation and no consensus currently exists to help guide decision-making strategy. As a result, considerable variation exists in practice among physicians and centers. This review discusses important issues that should be considered in the evaluation of hospitalized patients for the commencement of dialysis. C1 [Lim, Kenneth; Palsson, Ragnar] Harvard Med Sch, Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St, Boston, MA 02114 USA. [Palsson, Ragnar; Siedlecki, Andrew] Harvard Med Sch, Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. RP Siedlecki, A (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02115 USA. EM asiedlecki@bwh.harvard.edu NR 37 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-5943 J9 HOSP MED CLIN JI Hosp. Med. Clin. PD OCT PY 2016 VL 5 IS 4 BP 467 EP + DI 10.1016/j.ehmc.2016.05.008 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA EA8HQ UT WOS:000386876300002 ER PT J AU Crotty, GF Bhattacharyya, S AF Crotty, Grace F. Bhattacharyya, Shamik TI Toxic-Metabolic Encephalopathy SO HOSPITAL MEDICINE CLINICS LA English DT Article DE Encephalopathy; Delirium; Toxic-metabolic; Confusion; Altered mental status ID HOSPITALIZED OLDER PATIENTS; HEPATIC-ENCEPHALOPATHY; WERNICKES ENCEPHALOPATHY; UREMIC ENCEPHALOPATHY; SURGERY PATIENTS; DELIRIUM; PEOPLE; RISK; HALOPERIDOL; ASSOCIATION AB Toxic-metabolic encephalopathy, synonymous with delirium or altered mental status, is commonly seen in hospital settings. It is an acute confusional state that can occur in a vulnerable person from a variety of insults. The presence of delirium is associated with increased mortality, cognitive impairment, and institutionalization. Primary prevention and treatment of underlying medical disorder are imperative to reducing cases of delirium. In this article, the authors review the underlying pathophysiology, outline key features in diagnosis, and discuss prevention and management. C1 [Crotty, Grace F.; Bhattacharyya, Shamik] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Crotty, Grace F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. RP Crotty, GF (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM gcrotty@partners.org NR 49 TC 0 Z9 0 U1 11 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-5943 J9 HOSP MED CLIN JI Hosp. Med. Clin. PD OCT PY 2016 VL 5 IS 4 BP 555 EP + DI 10.1016/j.ehmc.2016.05.001 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA EA8HQ UT WOS:000386876300009 ER PT J AU DiNapoli, EA Cinna, C Whiteman, KL Fox, L Appelt, CJ Kasckow, J AF DiNapoli, Elizabeth A. Cinna, Christopher Whiteman, Karen L. Fox, Lauren Appelt, Cathleen J. Kasckow, John TI Mental health treatment preferences and challenges of living with multimorbidity from the veteran perspective SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE multimorbidity; veteran; self-management; mental health; treatment preferences ID CARDIOVASCULAR-DISEASE RISK; RANDOMIZED CONTROLLED-TRIAL; BIPOLAR DISORDER; PRIMARY-CARE; COLLABORATIVE CARE; DEPRESSION; ILLNESS; SERVICES; OUTCOMES; SYSTEM AB Objective: To explore middle-aged and older veterans' current disease-management practices, mental health treatment preferences, and challenges of living with multiple chronic health conditions (i.e., multimorbidity). Methods: Semi-structured qualitative interviews and self-report measures were collected from 28 middle-aged and older (50 years of age or older) veterans with multimorbidity. Results: Our sample of veterans with multimorbidity was, on average, mildly depressed and anxious with elevated stress and disability. Veterans acknowledged the interaction of physical and emotional symptoms, which caused greater difficulty with health care management and daily functioning. Veterans had many concerns regarding their physical and emotional health conditions, such as continued disease progression and the addition of other emotional and physical health complications. Veterans also identified specific self-care approaches for disease management (e.g., medication, healthy lifestyle practices, and psychological stress management techniques), as well as barriers to engaging in care (e.g., money, transportation, and stigma). Participants preferred a combination of medication, psychotherapy, and healthy lifestyle practices for mental health treatment. The majority of participants (88.5%) agreed that these mental health treatments would be beneficial to integrate into disease management for older veterans with multimorbidity. Lastly, veterans provided an array of recommendations for improving Veteran's Administration services and reducing mental health stigma. Conclusions: These findings provide support for patient-centered approaches and integrated mental and physical health self-management in the Veteran's Administration for middle-aged and older veterans with multiple chronic conditions. Copyright (C) 2016 John Wiley & Sons, Ltd. C1 [DiNapoli, Elizabeth A.; Cinna, Christopher; Fox, Lauren; Appelt, Cathleen J.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15261 USA. [DiNapoli, Elizabeth A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Cinna, Christopher; Appelt, Cathleen J.] Duquesne Univ, Grad Ctr Social & Publ Policy, Pittsburgh, PA 15219 USA. [Whiteman, Karen L.] Dartmouth Ctr Hlth & Aging, Lebanon, NH USA. [Whiteman, Karen L.] CDC Hlth Promot Res Ctr Dartmouth, Lebanon, NH USA. [Whiteman, Karen L.] Geisel Sch Med Dartmouth, Dept Psychiat, Pittsburgh, PA USA. [Appelt, Cathleen J.] Duquesne Univ, Dept Sociol, Pittsburgh, PA 15219 USA. [Kasckow, John] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Kasckow, John] VA Pittsburgh Healthcare Syst, MIRECC, Pittsburgh, PA USA. [Kasckow, John] VA Pittsburgh Healthcare Syst, Behav Hlth, Pittsburgh, PA USA. [Kasckow, John] VA Pittsburgh Ctr Hlth & Equ Promot, Pittsburgh, PA USA. RP DiNapoli, EA (reprint author), VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA 15261 USA.; DiNapoli, EA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. EM Elizabeth.Dinapoli2@va.gov FU VISN 4 MIRECC Pilot Project FX This project was funded by VISN 4 MIRECC Pilot Project (PI: DiNapoli). The attitudes expressed are those of the authors and do not necessarily reflect those of the Pittsburgh VA Healthcare System, Department of Veterans Affairs, or US government. NR 29 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 2016 VL 31 IS 10 BP 1097 EP 1104 DI 10.1002/gps.4550 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA EB0KY UT WOS:000387033900002 PM 27442187 ER PT J AU Cao, Y Chan, AT AF Cao, Yin Chan, Andrew T. TI Aspirin and Cancer Risk Reply SO JAMA ONCOLOGY LA English DT Letter ID COLORECTAL-CANCER C1 [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, GRJ 825C, Boston, MA 02114 USA. [Cao, Yin; Chan, Andrew T.] Harvard Med Sch, GRJ 825C, Boston, MA 02114 USA. [Cao, Yin; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, GRJ 825C, Boston, MA 02114 USA. [Cao, Yin] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Chan, Andrew T.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, GRJ 825C, Boston, MA 02114 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, GRJ 825C, Boston, MA 02114 USA.; Chan, AT (reprint author), Harvard Med Sch, GRJ 825C, Boston, MA 02114 USA. EM achan@mgh.harvard.edu NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD OCT 1 PY 2016 VL 2 IS 10 BP 1372 EP 1373 DI 10.1001/jamaoncol.2016.2295 PG 2 WC Oncology SC Oncology GA EA3GB UT WOS:000386488600029 PM 27532272 ER PT J AU Patel, MS Chaikof, EL AF Patel, Madhukar S. Chaikof, Elliot L. TI Disclosing Industry Relationships-A Patient-Centered Approach SO JAMA SURGERY LA English DT Editorial Material ID PHYSICIANS C1 [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Patel, Madhukar S.; Chaikof, Elliot L.] Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. [Chaikof, Elliot L.] Harvard Med Sch, Boston, MA USA. RP Chaikof, EL (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, 110 Francis St,Ste 9F, Boston, MA 02115 USA. EM echaikof@bidmc.harvard.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 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD OCT PY 2016 VL 151 IS 10 BP 895 EP 896 DI 10.1001/jamasurg.2016.1063 PG 2 WC Surgery SC Surgery GA EA5WS UT WOS:000386696200001 PM 27366991 ER PT J AU Glass, LRD Elliott, AT AF Glass, Lora R. Dagi Elliott, Alexandra T. TI Large upper eyelid coloboma repair: a one-stage, one-site technique SO JOURNAL OF AAPOS LA English DT Article ID RECONSTRUCTION AB Current techniques for repairing large eyelid colobomas require preparation of other tissue sites and occasionally more than one procedure. We present a technique that requires only one procedure and is limited to the colobomatous eyelid; in addition, it is specifically designed to help avoid postoperative astigmatic and obstructive amblyopia. Outcomes are demonstrated in 3 cases of hemifacial microsomia. Large colobomas on the upper eyelid can be successfully and aesthetically repaired with only one procedure, incising only the congenitally abnormal eyelid. C1 [Glass, Lora R. Dagi] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Plast Surg Serv, Boston, MA 02114 USA. [Elliott, Alexandra T.] Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. [Elliott, Alexandra T.] Harvard Med Sch, Boston, MA USA. RP Elliott, AT (reprint author), Boston Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM alexandra.elliott@childrens.harvard.edu NR 10 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD OCT PY 2016 VL 20 IS 5 BP 459 EP 461 DI 10.1016/j.jaapos.2016.05.018 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA EA5FL UT WOS:000386644700022 ER PT J AU Schneeweiss, S Carver, PL Datta, K Galar, A Johnson, MD Johnson, MG Marty, FM Nagel, J Najdzinowicz, M Saul, M Shoham, S Silveira, FP Varughese, CA Wilck, M Weatherby, L Auton, T Walker, AM AF Schneeweiss, Sebastian Carver, Peggy L. Datta, Kausik Galar, Alicia Johnson, Melissa D. Johnson, Matthew G. Marty, Francisco M. Nagel, Jerod Najdzinowicz, Maryann Saul, Melissa Shoham, Shmuel Silveira, Fernanda P. Varughese, Christy A. Wilck, Marissa Weatherby, Lisa Auton, Tim Walker, Alexander M. TI Short-term risk of liver and renal injury in hospitalized patients using micafungin: a multicentre cohort study SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; TRANSPLANT RECIPIENTS; CELL TRANSPLANTATION; AMPHOTERICIN-B; DOUBLE-BLIND; HEPATOTOXICITY; CANDIDIASIS; SAFETY; TRIAL; VORICONAZOLE AB Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR=0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR=0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. C1 [Schneeweiss, Sebastian; Weatherby, Lisa; Walker, Alexander M.] WHISCON, Newton, MA 02466 USA. [Schneeweiss, Sebastian] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, 1 Brigham Circle,Suite 3030, Boston, MA 02120 USA. [Schneeweiss, Sebastian; Galar, Alicia; Varughese, Christy A.] Harvard Med Sch, Boston, MA 02115 USA. [Carver, Peggy L.; Nagel, Jerod] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Datta, Kausik; Marty, Francisco M.; Shoham, Shmuel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Galar, Alicia] Brigham & Womens Hosp, Dept Med, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Johnson, Melissa D.; Johnson, Matthew G.] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC USA. [Najdzinowicz, Maryann; Wilck, Marissa] Univ Penn, Perelman Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Saul, Melissa; Silveira, Fernanda P.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA. [Varughese, Christy A.] Massachusetts Gen Hosp, Dept Pharm, Div Infect Dis, Boston, MA 02114 USA. [Auton, Tim] Astellas Pharma Europe, Leiden, Netherlands. RP Schneeweiss, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, 1 Brigham Circle,Suite 3030, Boston, MA 02120 USA.; Schneeweiss, S (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM schneeweiss@post.harvard.edu FU Astellas Pharma Europe FX This study was sponsored by Astellas Pharma Europe through a research contract with WHISCON, LLC. Astellas is the manufacturer of micafungin, one of the study drugs. NR 31 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD OCT PY 2016 VL 71 IS 10 BP 2938 EP 2944 DI 10.1093/jac/dkw225 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA EA2VO UT WOS:000386453900031 PM 27407049 ER PT J AU Kaiser, AP Proctor, SP Vasterling, JJ AF Kaiser, Anica Pless Proctor, Susan P. Vasterling, Jennifer J. TI Consistency of Reporting for Stressful Life Events Among Nondeployed Soldiers SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE assessment; posttraumatic stress disorder; stressful life events; inconsistent reporting; veterans ID NEUROCOGNITION DEPLOYMENT HEALTH; POTENTIALLY TRAUMATIC EVENTS; POSTTRAUMATIC-STRESS; MEMORY; VETERANS; EXPOSURE; RECALL; STABILITY; SYMPTOMS; PTSD AB ObjectivesMeasurement of stress exposure is central to understanding military mental health outcomes. Although temporal stability of combat event reporting has been examined, less is known about the stability of reporting for noncombat events in military samples. Objectives are to examine consistency in reporting stressful life events in nondeployed U.S. Army soldiers and its association with posttraumatic stress disorder (PTSD) symptomatology. MethodExamined reporting consistency over approximately 8 months among 466 soldiers. Regression models examined factors associated with decreased, increased, and stable reporting. ResultsStability of the number of events endorsed over time was high. However, item-level agreement was slight to moderate (kappas: .13-.54), with inconsistencies due primarily to decreased reporting. After adjusting for covariates and initial PTSD, second assessment PTSD was associated with increased and stable reporting. ConclusionsInconsistent reporting extends beyond combat events to other stressful life events in military personnel and is associated with PTSD. C1 [Kaiser, Anica Pless; Vasterling, Jennifer J.] VA Boston Healthcare Syst, Behav Sci Div, VA Natl Ctr PTSD, Boston, MA USA. [Kaiser, Anica Pless; Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Proctor, Susan P.] US Army, Environm Med Res Inst, Mil Performance Div, Natick, MA USA. [Proctor, Susan P.] VA Boston Healthcare Syst, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Kaiser, AP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,116B-2, Boston, MA 02130 USA. EM Anica.PlessKaiser@va.gov FU U.S. Army Medical Research and Material Command [DAMD 17-03-0020]; Department of Veterans Affairs, Clinical Science Research and Development FX Support for this study was provided by the U.S. Army Medical Research and Material Command (DAMD 17-03-0020) and the Department of Veterans Affairs, Clinical Science Research and Development. The manuscript underwent scientific and administrative review at the U.S. Army Research Institute of Environmental Medicine. The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army or Department of Veterans Affairs. NR 31 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 2016 VL 72 IS 10 BP 1088 EP 1098 DI 10.1002/jclp.22311 PG 11 WC Psychology, Clinical SC Psychology GA DW5TO UT WOS:000383710000008 ER PT J AU Goodson, JT Haeffel, GJ Raush, DA Hershenberg, R AF Goodson, Jason T. Haeffel, Gerald J. Raush, David A. Hershenberg, Rachel TI The Safety Behavior Assessment Form: Development and Validation SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE safety behaviors; anxiety; scale construction; Veterans ID PANIC DISORDER; SOCIAL PHOBIA; PSYCHOMETRIC PROPERTIES; ANXIETY DISORDERS; MAINTENANCE; EXPOSURE; THERAPY; SEEKING; SCALE; AGORAPHOBIA AB ObjectiveTo develop and validate an easy to administer measure of safety behaviors called the Safety Behavior Assessment Form (SBAF). MethodWe provide reliability and validity evidence from four studies. The first study used a cross-sectional design with a sample consisting of both clinical (U.S. military Veterans; n = 42) and nonclinical participants (undergraduates; n = 198). Study 2 used a cross-sectional design with a sample of U.S. military Veterans (n = 215). Study 3 used a pre-post treatment design with a sample of U.S. military Veterans (n = 42). Study 4 used a 2-time-point longitudinal design with a sample of undergraduates (n = 77). ResultsThe SBAF demonstrated strong levels of internal consistency and test-retest reliability in all four studies. The SBAF also demonstrated predictive and discriminant validity. In Study 3, the SBAF predicted anxious, but not depressive, treatment outcomes in a sample of Veterans. In Study 4, the SBAF predicted prospective changes in anxiety over a 2-week interval in a sample of undergraduates even after controlling for a competing measure of safety behaviors. ConclusionResults of these four studies indicate that the SBAF is a reliable and valid measure of safety behaviors that can be used in both clinical and nonclinical settings. C1 [Goodson, Jason T.; Raush, David A.; Hershenberg, Rachel] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Goodson, Jason T.; Raush, David A.; Hershenberg, Rachel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Haeffel, Gerald J.] Univ Notre Dame, Notre Dame, IN 46556 USA. RP Goodson, JT (reprint author), Philadelphia VA Med Ctr, Behav Hlth 116, 3900 Woodland & Univ Ave, Philadelphia, PA 19104 USA. EM Jason.Goodson@va.gov NR 41 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 2016 VL 72 IS 10 BP 1099 EP 1111 DI 10.1002/jclp.22325 PG 13 WC Psychology, Clinical SC Psychology GA DW5TO UT WOS:000383710000009 PM 27228035 ER PT J AU Sharma, G Lian, CG Lin, WM Amin-Mansour, A Jane-Valbuena, J Garraway, L Bao, W Yoon, CH Ibrahim, N AF Sharma, Gaurav Lian, Christine G. Lin, William M. Amin-Mansour, Ali Jane-Valbuena, Judit Garraway, Levi Bao, Wendi Yoon, Charles H. Ibrahim, Nageatte TI Distinct genetic profiles of extracranial and intracranial acral melanoma metastases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE acral melanoma; brain metastases; cutaneous metastases; mismatch repair genes; NRAS ID BRAIN METASTASES; LENTIGINOUS MELANOMA; GENOMIC CHARACTERIZATION; MUTATIONS; CANCER; EXPRESSION; PATHWAY; SAMPLES; NRAS AB Background: There is limited knowledge of the genetic alterations in acral melanoma metastases at different anatomic sites. Here, we characterized the genetic abnormalities of metastases in a 51-year-old man with stage IIIC heel melanoma who developed concomitant brain and cutaneous metastases in spite of multiple treatment modalities. Methods: Melanoma cells were isolated following palliative resection of the patient's cortical tumor and biopsy of cutaneous thigh metastasis. Mutational analysis using polymerase chain reaction amplification and BLAST, as well as exome sequencing (160Mb coverage) was performed on the tumors, cell lines generated thereof and normal lymph nodes. Results: All specimens had neuroblastoma RAS viral oncogene homolog Q61K mutations. There was a 40-fold higher somatic mutation frequency in the brain metastasis compared to the cutaneous metastasis. The former showed truncations of DNA mismatch repair genes (MLH1 and MSH2), and non-canonical BRAF (v-raf murine sarcoma viral oncogene homolog B1), PIK3CA and NF-1 mutations not observed in the extracranial lesion. Genomic profiling of each cell line was concordant with the respective original tumor tissue. Conclusions: We present the mutational differences between brain and cutaneous acral melanoma metastases in a patient with concomitant lesions. Further genetic and functional studies are needed to understand the biology of metastatic disease appearing at different sites. C1 [Sharma, Gaurav; Bao, Wendi; Yoon, Charles H.; Ibrahim, Nageatte] Harvard Med Sch, Dana Farber Brigham & Womens Canc Ctr, Dept Surg, Div Surg Oncol, Boston, MA USA. [Lian, Christine G.; Lin, William M.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol, Boston, MA USA. [Amin-Mansour, Ali; Jane-Valbuena, Judit; Garraway, Levi] Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA USA. [Ibrahim, Nageatte] Merck Res Labs, Oncol, 351 North Sumneytown Pike, N Wales, PA 19454 USA. RP Yoon, CH (reprint author), Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM chyoon@partners.org NR 33 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2016 VL 43 IS 10 BP 884 EP 891 DI 10.1111/cup.12746 PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA EA6ZT UT WOS:000386778500012 PM 27251777 ER PT J AU Ostrom, QT Gittleman, H Kruchko, C Louis, DN Brat, DJ Gilbert, MR Petkov, VI Barnholtz-Sloan, JS AF Ostrom, Quinn T. Gittleman, Haley Kruchko, Carol Louis, David N. Brat, Daniel J. Gilbert, Mark R. Petkov, Valentina I. Barnholtz-Sloan, Jill S. TI Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004-2012, varying) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE WHO grade; Brain tumors; Cancer registration; MGMT methylation; 1p/19q codeletion ID MGMT PROMOTER METHYLATION; CENTRAL-NERVOUS-SYSTEM; DNA-REPAIR GENE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ANAPLASTIC OLIGODENDROGLIOMAS; GRADE GLIOMAS; TEMOZOLOMIDE; MUTATIONS; CLASSIFICATION; TRIAL AB Cancer registries are an important source of population-level information on brain tumor incidence and survival. Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status. We assessed 'completeness', defined as having valid values over the time periods that they have been collected, overall, by year, histology, and registry. Data were obtained through a SEER custom data request for four factors related to brain tumors for the years 2004-2012 (3/4 factors were collected only from 2010 to 2012). SEER*Stat was used to generate frequencies of 'completeness' for each factor overall, and by year, histology and registry. The four factors varied in completeness, but increased over time. WHO grade has been collected the longest, and showed significant increases in completeness. Completeness of MGMT and 1p/19q codeletion was highest for glioma subtypes for which testing is recommended by clinical practice guidelines. Completeness of all factors varied by histology and cancer registry. Overall, several of the factors had high completeness, and all increased in completeness over time. With increasing focus on 'precision medicine' and the incorporation of molecular parameters into the 2016 WHO CNS tumor classification, it is critical that the data are complete, and factors collected at the population level are fully integrated into cancer reporting. It is critical that cancer registries continue to collect established and emerging prognostic and predictive factors. C1 [Ostrom, Quinn T.; Gittleman, Haley; Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 11100 Euclid Ave,Wearn 152, Cleveland, OH 44106 USA. [Ostrom, Quinn T.; Gittleman, Haley; Kruchko, Carol; Barnholtz-Sloan, Jill S.] CBTRUS, Hinsdale, IL 60521 USA. [Louis, David N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Brat, Daniel J.] Emory Univ, Dept Pathol & Lab Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Gilbert, Mark R.] NIH, Neurooncol Branch, Bldg 10, Bethesda, MD 20892 USA. [Petkov, Valentina I.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Barnholtz-Sloan, JS (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 11100 Euclid Ave,Wearn 152, Cleveland, OH 44106 USA.; Barnholtz-Sloan, JS (reprint author), CBTRUS, Hinsdale, IL 60521 USA. EM jsb42@case.edu FU National Cancer Institute Case Comprehensive Cancer Center [P30CA043703]; CBTRUS database: the Centers for Disease Control and Prevention (CDC) [5U58DP00383]; Sontag Foundation, Genentech, Novocure, Inc; Celldex Therapeutics, Inc; AbbVie, Inc; Musella Foundation; Voices Against Brain Cancer, Elekta FX QTO, HG, and JSB-S were supported by the National Cancer Institute Case Comprehensive Cancer Center Support Grant (P30CA043703). CBTRUS is honored to be included among the research grant recipients of the following organizations, which have contributed to the maintenance of the CBTRUS database: the Centers for Disease Control and Prevention (CDC) under Agreement 5U58DP00383, the Sontag Foundation, Genentech, Novocure, Inc., Celldex Therapeutics, Inc., AbbVie, Inc., along with the Musella Foundation, Voices Against Brain Cancer, Elekta, the Zelda Dorin Memorial Fund, as well as private and in kind donations. NR 42 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 130 IS 1 BP 31 EP 42 DI 10.1007/s11060-016-2217-7 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EA4FH UT WOS:000386565200004 PM 27418206 ER PT J AU Sacks, GD Ulloa, JG Shew, SB AF Sacks, Greg D. Ulloa, Jesus G. Shew, Stephen B. TI Is there a relationship between hospital volume and patient outcomes in gastroschisis repair? SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Volume outcome; Gastroschisis; Newborn surgery; Regionalization ID MORTALITY; SURGERY; ESOPHAGECTOMY; OPERATIONS; IMPACT; CARE AB Purpose: Given the well-established relationship between surgical volume and outcomes for many surgical procedures, we examined whether the same relationship exists for gastroschisis closure. Methods: We conducted a retrospective analysis of infants who underwent gastroschisis closure between 1999 and 2007 using a California birth-linked cohort. Hospitals were divided into terciles based on the number of gastroschisis closures performed annually. Using regression techniques, we examined the effects of hospital volume on patient mortality and length of stay while controlling for patient and hospital confounders. Results: We identified 1537 infants who underwent gastroschisis repair at 55 hospitals, 4 of which were high-volume and 42 of which were low-volume. The overall in-hospital mortality rate was 4.8% and the median length of stay was 46.5 days. After controlling for other factors, patients treated at high-volume hospitals had significantly lower odds of inpatient mortality (OR 0.40; 95% CI 0.21, 0.76). There was a near-significant trend towards shorter hospital length of stay at highvolume hospitals (p=0.066). Conclusions: Patients who undergo gastroschisis closure at high-volume hospitals in California experience lower odds of in-hospital mortality compared to those treated at low-volume hospitals. These findings offer initial evidence to support policies that limit the number of hospitals providing complex newborn surgical care. (C) 2016 Elsevier Inc. All rights reserved. C1 [Sacks, Greg D.; Shew, Stephen B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. [Sacks, Greg D.; Ulloa, Jesus G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ulloa, Jesus G.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu FU Robert Wood Johnson Foundation (RWJF)/Veterans Affairs Clinical Scholars program at the University of California, Los Angeles FX GDS and JGU were supported by the Robert Wood Johnson Foundation (RWJF)/Veterans Affairs Clinical Scholars program at the University of California, Los Angeles. RWJF had no role in the preparation, review, or approval of the manuscript. NR 28 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 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD OCT PY 2016 VL 51 IS 10 BP 1650 EP 1654 DI 10.1016/j.jpedsurg.2016.04.009 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA EA4MT UT WOS:000386587500014 PM 27139881 ER PT J AU Seward, C Skolny, M Brunelle, C Asdourian, M Salama, L Taghian, AG AF Seward, Cara Skolny, Melissa Brunelle, Cheryl Asdourian, Maria Salama, Laura Taghian, Alphonse G. TI A Comprehensive Review of Bioimpedance Spectroscopy as a Diagnostic Tool for the Detection and Measurement of Breast Cancer-Related Lymphedema SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE bioimpedance spectroscopy; breast cancer-related lymphedema (BCRL); early detection; perometry; L-Dex; multiple frequency bioimpedance analysis (MFBIA) ID BIOELECTRICAL-IMPEDANCE SPECTROSCOPY; ARM LYMPHEDEMA; PEROMETRY; VOLUME; QUANTIFICATION; RELIABILITY; PREVALENCE; SURGERY AB As treatment for breast cancer improves and the threat of life-long chronic lymphedema becomes more prevalent, the need for effective screening tools emerges as crucial. This review was conducted using literature beginning in 1992 to analyze primary research testing the accuracy of bioimpedance spectroscopy as a diagnostic and early detection tool for breast cancer-related lymphedema. We concluded bioimpedance is an accurate diagnostic tool for pre-existent lymphedema, however, it has not been validated for early detection. (C) 2016 Wiley Periodicals, Inc. C1 [Seward, Cara; Skolny, Melissa; Asdourian, Maria; Salama, Laura; Taghian, Alphonse G.] Harvard Med Sch, Massachusetts Gen Hosp, Lymphedema Studies Program, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. [Brunelle, Cheryl] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Lymphedema Studies Program, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118]; Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema [P50CA089393] FX Grant sponsor: National Cancer Institute; Grant number: R01CA139118; Grant sponsor: The Adele McKinnon Research Fund for Breast Cancer-Related Lymphedema; Grant number: P50CA089393. NR 30 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT 1 PY 2016 VL 114 IS 5 BP 537 EP 542 DI 10.1002/jso.24365 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA EB0JY UT WOS:000387031300002 PM 27393376 ER PT J AU Bernstein, KD Delaney, T AF Bernstein, Karen De Amorim Delaney, Thomas TI Chordomas and Chondrosarcomas-The Role of Radiation Therapy SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE proton therapy; rare tumors; base of skull/spine ID CARBON ION RADIOTHERAPY; SOFT-TISSUE SARCOMAS; DOSE PHOTON/PROTON RADIOTHERAPY; TERM-FOLLOW-UP; SKULL BASE; PROGNOSTIC-FACTORS; MOBILE SPINE; SACRAL CHORDOMAS; CLINICOPATHOLOGICAL ANALYSIS; PROTON THERAPY AB Achieving negative surgical margins can be challenging for skull base and spinal/paraspinal sarcomas. Data shows that pre-or post-operative radiation therapy improves local control. Delivery of sufficient dose of radiation can be difficult because of the proximity to normal organs/tissues that are sensitive to radiation therapy and therefore dose-limiting. A comprehensive literature search was conducted using PubMed search engine. The scarcity of prospective, randomized data limits the ability to generate definitive treatment recommendations. (C) 2016 Wiley Periodicals, Inc. C1 [Bernstein, Karen De Amorim; Delaney, Thomas] Harvard Med Sch, Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. RP Bernstein, KD (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. EM kbernstein@mgh.harvard.edu 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 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT 1 PY 2016 VL 114 IS 5 BP 564 EP 569 DI 10.1002/jso.24368 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA EB0JY UT WOS:000387031300006 ER PT J AU Marchegiani, G Andrianello, S Massignani, M Malleo, G Maggino, L Paiella, S Ferrone, CR Luchini, C Scarpa, A Capelli, P Mino-Kenudson, M Lillemoe, KD Bassi, C Fernandez-Del Castillo, C Salvia, R AF Marchegiani, Giovanni Andrianello, Stefano Massignani, Marta Malleo, Giuseppe Maggino, Laura Paiella, Salvatore Ferrone, Cristina R. Luchini, Claudio Scarpa, Aldo Capelli, Paola Mino-Kenudson, Mari Lillemoe, Keith D. Bassi, Claudio Fernandez-Del Castillo, Carlos Salvia, Roberto TI Solid Pseudopapillary Tumors of the Pancreas: Specific Pathological Features Predict the Likelihood of Postoperative Recurrence SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE solid pseudopapillary tumors; solid pseudopapillary neoplasms; SPT; SPN; cystic pancreatic neoplasm; pancreas ID INTERNATIONAL STUDY-GROUP; OF-THE-LITERATURE; HEPATIC METASTASIS; SURGERY ISGPS; NEOPLASMS; DEFINITION; MALIGNANCY; EXPERIENCE; MANAGEMENT; BEHAVIOR AB Background: Since their introduction in the WHO classification, the incidence of solid pseudopapillary tumors (SPTs) of the pancreas has progressively increased, mainly because of the widespread use of cross-sectional imaging. Few recent studies have analyzed the biological behavior of SPTs, but reliable data on long-term follow-up are needed. Methods: Retrospective analysis of two Institutions with high caseload, The Department of General Surgery-Pancreas Institute, University of Verona Hospital Trust and the Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, was carried out. Data from 131 consecutive resections for SPT performed during the last three decades were collected and analyzed. Results: The majority of patients were female (86.3%) with a median age of 33 (7-68) years. The prevalent location was the pancreatic tail (33.5%). Applying the WHO criteria, 16 (12.2%) SPTs were considered malignant due to the presence of at least pancreatic parenchyma (9.9%), perineural (4.6%), and/or angiovascular invasion (2.3%). After a median of 62 months after surgery, only two patients had a recurrence (1.5%). Both of them fulfilled the WHO criteria for malignant SPT (vs. 10.7% of those who did not recur, P = 0.01), had an infiltrative growth pattern (vs. 10.8%, P = 0.01), pancreatic parenchyma invasion (vs. 9.7%, P = 0.01) and capsular invasion (vs. 4.9%, P = 0.004). Conclusion: Overall, SPTs are associated with excellent survival results after surgical resection. Disease recurrence is extremely rare, and might occur if the primary tumor presents with either pancreatic parenchyma or capsule invasion. (C) 2016 Wiley Periodicals, Inc. C1 [Marchegiani, Giovanni; Andrianello, Stefano; Massignani, Marta; Malleo, Giuseppe; Maggino, Laura; Paiella, Salvatore; Bassi, Claudio; Salvia, Roberto] Univ Verona Hosp Trust, Pancreas Inst, Dept Gen & Pancreat Surg, Ple Scuro 10, I-37134 Verona, Italy. [Ferrone, Cristina R.; Lillemoe, Keith D.; Fernandez-Del Castillo, Carlos] Harvard Med Sch, Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA USA. [Luchini, Claudio; Scarpa, Aldo; Capelli, Paola] Univ Verona Hosp Trust, ARC Net Res Ctr, Dept Diagnost & Publ Hlth, Verona, Italy. [Mino-Kenudson, Mari] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Salvia, R (reprint author), Univ Verona Hosp Trust, Pancreas Inst, Dept Gen & Pancreat Surg, Ple Scuro 10, I-37134 Verona, Italy. EM roberto.salvia@univr.it OI Luchini, Claudio/0000-0003-4901-4908 FU Associazione Italiana Ricerca Cancro [12182, 17132]; Fondazione Italiana per lo Studio delle Malattie del Pancreas [FIMP-CUP_J33G13000210001]; FP7 European Community Grant Cam-Pac [602783] FX Grant sponsor: Associazione Italiana Ricerca Cancro; Grant numbers: n. 12182, n. 17132; Grant sponsor: Fondazione Italiana per lo Studio delle Malattie del Pancreas; Grant number: FIMP-CUP_J33G13000210001; Grant sponsor: FP7 European Community Grant Cam-Pac; Grant number: n. 602783. NR 30 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT 1 PY 2016 VL 114 IS 5 BP 597 EP 601 DI 10.1002/jso.24380 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA EB0JY UT WOS:000387031300011 PM 27471041 ER PT J AU Chen, ST Li, T Han, JL Qureshi, AA Cho, E AF Chen, Steven T. Li, Tricia Han, Jiali Qureshi, Abrar A. Cho, Eunyoung TI Type 2 diabetes mellitus and risk of cutaneous squamous cell carcinoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID WOMEN C1 [Chen, Steven T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Chen, Steven T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Internal Med, Boston, MA USA. [Li, Tricia; Qureshi, Abrar A.; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Li, Tricia; Qureshi, Abrar A.; Cho, Eunyoung] Harvard Med Sch, Boston, MA USA. [Han, Jiali] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA. [Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Han, Jiali] Indiana Univ, Sch Med, Dept Dermatol, Indianapolis, IN USA. [Qureshi, Abrar A.; Cho, Eunyoung] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Qureshi, Abrar A.; Cho, Eunyoung] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, 593 Eddy St,Apc 10, Providence, RI 02903 USA. RP Cho, E (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, 593 Eddy St,Apc 10, Providence, RI 02903 USA. EM eunyoung_cho@brown.edu FU NCATS NIH HHS [UL1 TR001108]; NCI NIH HHS [UM1 CA167552, R21 CA198216, R01 CA137365, UM1 CA176726, UM1 CA186107] NR 5 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2016 VL 75 IS 4 BP 831 EP 834 DI 10.1016/j.jaad.2016.05.013 PG 5 WC Dermatology SC Dermatology GA EA6VI UT WOS:000386766700047 PM 27646740 ER PT J AU Soura, E Stratigos, AJ Tsao, H AF Soura, Efthymia Stratigos, Alexander J. Tsao, Hensin TI Reply to: "The absence of multiple atypical nevi in germline CDKN2A mutations'' SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID HEREDITARY MELANOMA UPDATE C1 [Soura, Efthymia; Stratigos, Alexander J.] Univ Athens, Andreas Sygros Hosp, Sch Med, Dept Dermatol 1,Univ Clin, Athens, Greece. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Melanoma Genet Program, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Edwards 211,50 Blossom St, Boston, MA 02114 USA.; Tsao, H (reprint author), Harvard Med Sch, Wellman Ctr Photomed, Edwards 211,50 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 4 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2016 VL 75 IS 4 BP E159 EP E159 DI 10.1016/j.jaad.2016.05.002 PG 1 WC Dermatology SC Dermatology GA EA6VI UT WOS:000386766700015 PM 27646764 ER PT J AU Donigan, JM Snowden, C Carter, JB Kimball, AB AF Donigan, J. M. Snowden, C. Carter, J. B. Kimball, A. B. TI The temporal association between cutaneous T-cell lymphoma and psoriasis: implications for common biologic processes SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter ID FINNISH PATIENTS; UNITED-KINGDOM; COHORT; CANCER; RISK C1 [Donigan, J. M.] Mass Gen Hosp, Clin Unit Res Trials & Outcomes Skin, Dept Dermatol, Boston, MA USA. [Snowden, C.] Princeton Univ, Boston, MA USA. [Carter, J. B.] Mass Gen Hosp, Comprehens Cutaneous Lymphoma Program, Canc Ctr, Boston, MA USA. [Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, A. B.] Harvard Med Sch, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.; Kimball, AB (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0926-9959 EI 1468-3083 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD OCT PY 2016 VL 30 IS 10 BP E31 EP E32 DI 10.1111/jdv.13281 PG 2 WC Dermatology SC Dermatology GA EA5UD UT WOS:000386688300002 PM 26337297 ER PT J AU Li, CR Brooks, YS Jia, WX Wang, DG Xiao, XM Li, Q Li, M Mao, QX Wang, B AF Li, C. -R. Brooks, Y. S. Jia, W. -X. Wang, D. -G. Xiao, X. -M. Li, Q. Li, M. Mao, Q. -X. Wang, B. TI Pathogenicity of POFUT1 mutations in two Chinese families with Dowling-Degos disease SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Letter ID O-FUCOSYL-TRANSFERASE; RETICULATE ACROPIGMENTATION; KITAMURA; SPECTRUM C1 [Li, C. -R.; Jia, W. -X.; Xiao, X. -M.; Li, Q.; Mao, Q. -X.; Wang, B.] Chinese Acad Med Sci, Inst Dermatol, Dept Dermatol, Nanjing, Jiangsu, Peoples R China. [Li, C. -R.; Jia, W. -X.; Xiao, X. -M.; Li, Q.; Mao, Q. -X.; Wang, B.] Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China. [Brooks, Y. S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA USA. [Wang, D. -G.] Nanjing Med Univ, Affiliated Hosp 1, Dept Dermatol, Nanjing, Jiangsu, Peoples R China. [Li, M.] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Dermatol, Shanghai, Peoples R China. [Wang, B.] Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China. RP Li, CR; Wang, B (reprint author), Chinese Acad Med Sci, Inst Dermatol, Dept Dermatol, Nanjing, Jiangsu, Peoples R China.; Li, CR; Wang, B (reprint author), Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.; Wang, B (reprint author), Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China. EM nylcr72@163.com; wangbx@ncstdlc.org NR 10 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0926-9959 EI 1468-3083 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD OCT PY 2016 VL 30 IS 10 BP E79 EP E81 DI 10.1111/jdv.13323 PG 3 WC Dermatology SC Dermatology GA EA5UD UT WOS:000386688300032 PM 26486618 ER PT J AU Qu, JZ Alston, TA AF Qu, Jason Z. Alston, Theodore A. TI When the nerve block is blocked by local resistance SO MINERVA ANESTESIOLOGICA LA English DT Editorial Material ID SODIUM-CHANNEL; PAIN; ANESTHETICS; INHIBITION; MECHANISMS; MUTATIONS; NA(V)1.7 C1 [Qu, Jason Z.; Alston, Theodore A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Alston, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM talston@mgh.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD OCT PY 2016 VL 82 IS 10 BP 1029 EP 1031 PG 3 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA EA8NL UT WOS:000386892300003 PM 27579628 ER PT J AU Lerin, C Goldfine, AB Boes, T Liu, M Kasif, S Dreyfuss, JM De Sousa-Coelho, AL Daher, G Manoli, I Sysol, JR Isganaitis, E Jessen, N Goodyear, LJ Beebe, K Gall, W Venditti, CP Patti, ME AF Lerin, Carles Goldfine, Allison B. Boes, Tanner Liu, Manway Kasif, Simon Dreyfuss, Jonathan M. De Sousa-Coelho, Ana Luisa Daher, Grace Manoli, Irini Sysol, Justin R. Isganaitis, Elvira Jessen, Niels Goodyear, Laurie J. Beebe, Kirk Gall, Walt Venditti, Charles P. Patti, Mary-Elizabeth TI Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism SO MOLECULAR METABOLISM LA English DT Article DE Insulin sensitivity; BCAA; Fatty acid oxidation; TCA cycle ID TYPE-2 DIABETES-MELLITUS; VISCERAL ADIPOSE-TISSUE; CIRCULATING BCAA LEVELS; INSULIN-RESISTANCE; SKELETAL-MUSCLE; METHYLMALONIC ACIDEMIA; GENE-EXPRESSION; ENZYME-ACTIVITY; WEIGHT-LOSS; OBESITY AB Objective: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. (C) 2016 The Authors. Published by Elsevier GmbH. C1 [Lerin, Carles; Goldfine, Allison B.; Boes, Tanner; Dreyfuss, Jonathan M.; De Sousa-Coelho, Ana Luisa; Daher, Grace; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J.; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Res Div, Boston, MA 02215 USA. [Lerin, Carles; Goldfine, Allison B.; De Sousa-Coelho, Ana Luisa; Isganaitis, Elvira; Patti, Mary-Elizabeth] Harvard Med Sch, Boston, MA 02215 USA. [Lerin, Carles] Hosp St Joan Deu, Inst Recerca Pediat, Endocrinol Dept, Barcelona 08950, Spain. [Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Manoli, Irini; Sysol, Justin R.; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Beebe, Kirk; Gall, Walt] Metabolon Inc, Durham, NC 27723 USA. [Gall, Walt] Saffron Technol, Cary, NC 27513 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA.; Lerin, C (reprint author), Hosp St Joan Deu, Inst Recerca Pediat, Barcelona 08950, Spain. EM clerin@fsjd.org; mary.elizabeth.patti@joslin.harvard.edu OI Jessen, Niels/0000-0001-5613-7274 FU NICHD NIH HHS [K99 HD064793]; NIDDK NIH HHS [K23 DK002795, P30 DK036836, R01 DK101043]; NLM NIH HHS [U54 LM008748] NR 64 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD OCT PY 2016 VL 5 IS 10 BP 926 EP 936 DI 10.1016/j.molmet.2016.08.001 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA8KC UT WOS:000386882700012 PM 27689005 ER PT J AU Reddy, HM Hamed, SA Lek, M Mitsuhashi, S Estrella, E Jones, MD Mahoney, LJ Duncan, AR Cho, KA Macarthur, DG Kunkel, LM Kang, PB AF Reddy, Hemakumar M. Hamed, Sherifa A. Lek, Monkol Mitsuhashi, Satomi Estrella, Elicia Jones, Michael D. Mahoney, Lane J. Duncan, Anna R. Cho, Kyung-Ah Macarthur, Daniel G. Kunkel, Louis M. Kang, Peter B. TI HOMOZYGOUS NONSENSE MUTATION IN SGCA IS A COMMON CAUSE OF LIMB-GIRDLE MUSCULAR DYSTROPHY IN ASSIUT, EGYPT SO MUSCLE & NERVE LA English DT Article DE founder effect; homozygosity mapping; limb-girdle muscular dystrophy; sarcoglycanopathy; whole exome sequencing ID ALPHA-SARCOGLYCAN GENE; GAMMA-SARCOGLYCAN; DUCHENNE; POPULATION; DIAGNOSIS; SIBLINGS; COMPLEX; LGMD2I; FAMILY; 2D AB Introduction: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. Methods: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. Results: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. Conclusions: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. C1 [Reddy, Hemakumar M.; Jones, Michael D.; Cho, Kyung-Ah; Kang, Peter B.] Univ Florida, Div Pediat Neurol, Coll Med, POB 100296, Gainesville, FL 32610 USA. [Hamed, Sherifa A.] Assiut Univ Hosp, Dept Neurol & Psychiat, Assiut, Egypt. [Lek, Monkol; Macarthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Lek, Monkol; Mitsuhashi, Satomi; Estrella, Elicia; Mahoney, Lane J.; Duncan, Anna R.; Macarthur, Daniel G.; Kunkel, Louis M.] Harvard Med Sch, Boston, MA USA. [Lek, Monkol; Macarthur, Daniel G.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Mitsuhashi, Satomi; Estrella, Elicia; Mahoney, Lane J.; Duncan, Anna R.; Kunkel, Louis M.] Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Kang, Peter B.] Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. [Kang, Peter B.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA. RP Kang, PB (reprint author), Univ Florida, Div Pediat Neurol, Coll Med, POB 100296, Gainesville, FL 32610 USA.; Kang, PB (reprint author), Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA.; Kang, PB (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32611 USA. EM pbkang@ufl.edu FU NIH [R01 NS080929, R01 GM104371]; Muscular Dystrophy Association [186796]; Bernard F. and Alva B. Gimbel Foundation; Department of Pediatrics at the University of Florida College of Medicine; National Human Genome Research Institute [U54HG003067] FX This project was funded by NIH R01 NS080929 (H.M.R. and P.B.K.), R01 GM104371 (D.G.M.), Muscular Dystrophy Association Grant 186796 (P.B.K.), the Bernard F. and Alva B. Gimbel Foundation (L.M.K.), and the Department of Pediatrics at the University of Florida College of Medicine (H.M.R., M.D.J., K.A.C., and P.B.K.). Sanger DNA sequencing was performed at the IDDRC Molecular Genetics Core Facility at Boston Children's Hospital and the Interdisciplinary Center for Biotechnology Research (ICBR) Sanger Sequencing Core at the University of Florida. Exome sequencing was supported by Medical Sequencing Program Grant U54HG003067 from the National Human Genome Research Institute. NR 42 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2016 VL 54 IS 4 BP 690 EP 695 DI 10.1002/mus.25094 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EA5XF UT WOS:000386697800006 PM 26934379 ER PT J AU Kulkarni, AA Vijaykumar, VE Natarajan, SK Sengupta, S Sabbisetti, VS AF Kulkarni, Ashish A. Vijaykumar, Vijay Elakkya Natarajan, Siva Kumar Sengupta, Shiladitya Sabbisetti, Venkata S. TI Sustained inhibition of cMET-VEGFR2 signaling using liposome-mediated delivery increases efficacy and reduces toxicity in kidney cancer SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Renal cell carcinoma; Liposomes; c-Met inhibitor; Kinase inhibitor delivery ID RENAL-CELL CARCINOMA; POTENTIAL THERAPEUTIC TARGET; ANTIANGIOGENIC THERAPY; CABOZANTINIB XL184; MET PROTOONCOGENE; DRUG-DELIVERY; TUMOR-GROWTH; C-MET; RESISTANCE; ANGIOGENESIS AB c-Met pathway is implicated in the resistance to anti-VEGF therapy in renal cell carcinoma ( RCC). However, clinical translation of therapies targeting these pathways has been limited due to dose-limiting toxicities, feedback signaling, and low intratumoral drug accumulation. Here, we developed liposomes encapsulating a multi-receptor tyrosine kinase inhibitor ( XL184) to explore the possibility of improving intratumoral concentration, enhancing antitumor efficacy and reducing toxicities. The liposomes showed increased cytotoxicity than XL184, and resulted in a sustained inhibition of phosphorylation of Met, AKT and MAPK pathways in RCC cells. In a RCC tumor xenograft model, the liposomes induced sustained inhibition of tumor growth as compared to XL184, consistent with higher inhibition of kinase signaling pathways. Biodistribution studies revealed higher accumulation of the liposomes in tumor, which translated into lower toxicities. This study shows the use of liposomes for effective inhibition of multi-kinase pathways, which can potentially emerge as a new treatment for RCC. (C) 2016 Elsevier Inc. All rights reserved. C1 [Kulkarni, Ashish A.; Natarajan, Siva Kumar; Sengupta, Shiladitya] Harvard Med Sch, Brigham & Womens Hosp, Div Biomed Engn, Boston, MA 02115 USA. [Vijaykumar, Vijay Elakkya; Sabbisetti, Venkata S.] Harvard Med Sch, Brigham & Womens Hosp, Renal Div, Boston, MA USA. [Kulkarni, Ashish A.; Vijaykumar, Vijay Elakkya; Natarajan, Siva Kumar; Sengupta, Shiladitya; Sabbisetti, Venkata S.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sengupta, Shiladitya] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Sengupta, Shiladitya] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kulkarni, AA (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Biomed Engn, Boston, MA 02115 USA.; Kulkarni, AA (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.; Sabbisetti, VS (reprint author), Harvard Inst Med, Boston, MA 02115 USA. EM akulkarni@research.bwh.harvard.edu; vsabbisetti@partners.org OI Natarajan, Siva Kumar /0000-0002-9663-079X FU NCI NIH HHS [R21 CA186009, R01 CA135242] NR 40 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD OCT PY 2016 VL 12 IS 7 BP 1853 EP 1861 DI 10.1016/j.nano.2016.04.002 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA EA1JJ UT WOS:000386348000012 PM 27084552 ER PT J AU Ahmad, R Jacobson, A Hornicek, F Haynes, AB Choy, E Cote, G Nielsen, GP Chen, YL DeLaney, TF Mullen, JT AF Ahmad, Rima Jacobson, Aalex Hornicek, Francis Haynes, Alex B. Choy, Edwin Cote, Gregory Nielsen, G. Petur Chen, Yen-Lin DeLaney, Thomas F. Mullen, John T. TI The Width of the Surgical Margin Does Not Influence Outcomes in Extremity and Truncal Soft Tissue Sarcoma Treated With Radiotherapy SO ONCOLOGIST LA English DT Article DE Soft tissue sarcoma; Extremity; Margin width; Radiation therapy; Outcome ID PROGNOSTIC-SIGNIFICANCE; ADJUVANT RADIATION; LOCAL RECURRENCE; SURVIVAL; THERAPY; GRADE; WALL AB Background and Objectives. It is unclear whether the quantitative width of the surgical margin influences outcomes in patients with extremity and truncal soft tissue sarcoma (STS) treated with radiotherapy (RT). Methods. We performed a retrospective review of 382 patients with localized extremity or truncal STS who underwent limb-sparing surgery and RT from 1983 to 2010, and we analyzed the significance of resection margin status and quantitative margin width on outcomes. Results. Surgical margins were positive in 68 (18%) patients and negative in 314 (82%) patients. For those patients with a reported quantitative margin width (n = 235), the width of the negative margin was <= 1 mm (n = 128), > 1 mm and <= 5 mm(n = 79), and > 5 mm (n = 28). At a median follow-up of 82 months, the local recurrence rates were 5.4% and 11.8% for margin-negative and margin-positive patients, respectively. There were no differences in the rates of local or distant recurrence nor of any survival outcome based on the quantitative width of the surgical margin, provided that it was negative. Conclusions. In patients undergoing RT and limb-sparing surgery for STS, achieving a negative margin is essential for optimizing both local control and survival. However, the absolute quantitative width of the negative margin does not significantly influence outcome, and so attempts at wide margins of resection appear to be unnecessary. Importantly, the conclusions drawn from this study must not be applied to those patients undergoing surgery alone as the local treatment of their STS, in which case wider margins of resection may be necessary. C1 [Ahmad, Rima; Haynes, Alex B.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. [Jacobson, Aalex; Chen, Yen-Lin; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hornicek, Francis] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Choy, Edwin; Cote, Gregory] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org OI Cote, Gregory/0000-0003-0181-886X NR 26 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD OCT PY 2016 VL 21 IS 10 BP 1269 EP 1276 DI 10.1634/theoncologist.2015-0534 PG 8 WC Oncology SC Oncology GA EA3ES UT WOS:000386483400015 PM 27440063 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Thoughts About Greg Curt In Memoriam SO ONCOLOGIST LA English DT Biographical-Item C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bchabner@partners.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD OCT PY 2016 VL 21 IS 10 BP 1277 EP 1277 DI 10.1634/theoncologist.2016-0338 PG 1 WC Oncology SC Oncology GA EA3ES UT WOS:000386483400016 ER PT J AU Kuhn, MWM Song, E Feng, Z Sinha, A Chen, CW Deshpande, AJ Cusan, M Farnoud, NR Koche, RP Bradner, JE De Stanchina, E Vassiliou, GS Hoshii, T Armstrong, SA AF Kuehn, M. W. M. Song, E. Feng, Z. Sinha, A. Chen, C-W Deshpande, A. J. Cusan, M. Farnoud, N. R. Koche, R. P. Bradner, J. E. De Stanchina, E. Vassiliou, G. S. Hoshii, T. Armstrong, S. A. TI Synergistic inhibition of chromatin modifiers reverses a leukemogenic gene expression program in NPM1 mutant leukemia SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Kuehn, M. W. M.] Univ Med Johannes Gutenberg Univ Mainz, Med Klin 3, Mainz, Germany. [Kuehn, M. W. M.; Song, E.; Feng, Z.; Sinha, A.; Chen, C-W; Deshpande, A. J.; Cusan, M.; Farnoud, N. R.; Koche, R. P.; Hoshii, T.; Armstrong, S. A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. [Bradner, J. E.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [De Stanchina, E.] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Facil, 1275 York Ave, New York, NY 10021 USA. [Vassiliou, G. S.] Wellcome Trust Sanger Inst, Cambridge, England. [Armstrong, S. A.] Harvard Med Sch, Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V349 BP 108 EP 108 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300260 ER PT J AU Bashari, MH Malvestiti, S Fan, F Vallet, S Sattler, M Cardone, MH Opferman, JT Jager, D Podar, K AF Bashari, M. H. Malvestiti, S. Fan, F. Vallet, S. Sattler, M. Cardone, M. H. Opferman, J. T. Jaeger, D. Podar, K. TI Mcl-1 inhibition as a novel approach for personalized breast cancer therapy SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Bashari, M. H.; Malvestiti, S.; Fan, F.; Vallet, S.; Jaeger, D.; Podar, K.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Med Oncol, Heidelberg, Germany. [Bashari, M. H.] Padjadjaran State Univ, Dept Pharmacol & Therapy, Fac Med, Bandung, Indonesia. [Sattler, M.] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA USA. [Cardone, M. H.] Eutrop Pharmaceut Inc, Cambridge, MA USA. [Opferman, J. T.] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V387 BP 117 EP 117 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300283 ER PT J AU Goldschmidt, H Vij, R Kuter, D Cella, D Zyczynski, T Davis, C Popov, S Cook, G AF Goldschmidt, H. Vij, R. Kuter, D. Cella, D. Zyczynski, T. Davis, C. Popov, S. Cook, G. TI Healthcare resource utilization (HCRU) in relapsed/refractory multiple myeloma (RRMM): results from PREAMBLE SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Goldschmidt, H.] Univ Klinikum Heidelberg, Med Klin 5, Heidelberg, Germany. [Vij, R.] Washington Univ, Sch Med, St Louis, MO USA. [Kuter, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cella, D.] Northwestern Univ, Evanston, IL USA. [Zyczynski, T.; Davis, C.] Bristol Myers Squibb, Princeton, NJ USA. [Popov, S.] Parexel, St Petersburg, Russia. [Cook, G.] Univ Leeds, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA P544 BP 162 EP 162 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300398 ER PT J AU Karthaus, M Van Cutsem, E Mayer, RJ Ohtsu, A AF Karthaus, M. Van Cutsem, E. Mayer, R. J. Ohtsu, A. CA RECOURSE Study Grp TI TAS-102 versus placebo plus best supportive care in patients with metastatic colorectal cancer refractory to standard therapies: Final survival results of the phase III RECOURSE trial SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Karthaus, M.] Klinikum Neuperlach, Hamatol & Onkol, Munich, Germany. [Van Cutsem, E.] Univ Hosp Leuven, Leuven, Belgium. [Mayer, R. J.] Dana Farber Canc Ctr, Boston, MA USA. [Ohtsu, A.] Natl Canc Ctr Hosp East, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V645 BP 197 EP 198 PG 2 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300489 ER PT J AU Stelljes, M Kreuzer, KA Deangelo, DJ Advani, AS Gokbuget, N Liedtke, M Stock, W Martinelli, G O'Brien, S Wang, K Wang, T Paccagnella, ML Sleight, B Vandendries, E Jabbour, EJ Kantarjian, HM AF Stelljes, M. Kreuzer, K. -A Deangelo, D. J. Advani, A. S. Goekbuget, N. Liedtke, M. Stock, W. Martinelli, G. O'Brien, S. Wang, K. Wang, T. Paccagnella, M. L. Sleight, B. Vandendries, E. Jabbour, E. J. Kantarjian, H. M. TI Inotuzumab ozogamicin (InO) for relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) in the global phase 3 randomized controlled ino-vate trial: efficacy and safety by age and prior therapy SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Stelljes, M.] Univ Klinikum Munster, Munster, Germany. [Kreuzer, K. -A] Univ Cologne, Cologne, Germany. [Deangelo, D. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Advani, A. S.] Cleveland Clin, Cleveland, OH 44106 USA. [Goekbuget, N.] Goethe Univ Frankfurt, Frankfurt, Germany. [Liedtke, M.] Stanford Canc Inst, Stanford, CA USA. [Stock, W.] Univ Chicago, Chicago, IL 60637 USA. [Martinelli, G.] Univ Bologna, Inst Seragnoli, DIMES, Bologna, Italy. [O'Brien, S.] Univ Calif Irvine, Orange, CA USA. [Wang, K.] Pfizer Inc, Pearl River, NY USA. [Wang, T.; Paccagnella, M. L.; Sleight, B.] Pfizer Inc, Groton, CT 06340 USA. [Vandendries, E.] Pfizer Inc, Cambridge, MA USA. [Jabbour, E. J.; Kantarjian, H. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V658 BP 201 EP 202 PG 2 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300498 ER PT J AU Weisel, K Dimopoulos, MA Palumbo, A Richardson, P Mateos, MV Moreau, P Gupta, M Sheng, J Passey, C Sy, O Katz, J Lonial, S AF Weisel, K. Dimopoulos, M. A. Palumbo, A. Richardson, P. Mateos, M. -, V Moreau, P. Gupta, M. Sheng, J. Passey, C. Sy, O. Katz, J. Lonial, S. TI Elotuzumab plus lenalidomide and dexamethasone (ELd) in relapsed/refractory multiple myeloma (RRMM): ELOQUENT-2 post-hoc analysis of progression-free survival (PFS), tumor regrowth by time from diagnosis and prior lines of therapy, and median duration of response (DOR) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Weisel, K.] Univ Tubingen, Tubingen, Germany. [Dimopoulos, M. A.] Univ Athens, Alexandra Hosp, Athens, Greece. [Palumbo, A.] AOU San Giovanni Battista Torino, Osped Molinette, Turin, Italy. [Richardson, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mateos, M. -, V] Complejo Asistencial Univ Salamanca IBSAL, Salamanca, Spain. [Moreau, P.] Univ Hosp, Nantes, France. [Gupta, M.; Sheng, J.; Passey, C.; Sy, O.; Katz, J.] Bristol Myers Squibb, Princeton, NJ USA. [Lonial, S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RI richard, chrystelle/K-8595-2015 NR 1 TC 0 Z9 0 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V730 BP 223 EP 223 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300549 ER PT J AU Lorenzen, S Thuss-Patience, P Hofheinz, RD Bruck, P Emig, M Hozak, RR Ferry, D Melemed, S Ouyang, H Fuchst, CS Wilke, HJ AF Lorenzen, S. Thuss-Patience, P. Hofheinz, R. -D Brueck, P. Emig, M. Hozak, R. R. Ferry, D. Melemed, S. Ouyang, H. Fuchst, C. S. Wilke, H. -J TI Summary of biomarker data from 2 randomized, double-blind placebo-controlled phase 3 trials (RAINBOW and REGARD) of second-line Ramucirumab for advanced gastric or gastro-esophageal junction carcinoma SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Lorenzen, S.] Klinikum Rechts Der Isar, Med Klin 3, Munich, Germany. [Thuss-Patience, P.] Charite, Med Klin mS Hamatol Onkol & Tumorimmunol, Berlin, Germany. [Hofheinz, R. -D] Univ Med Mannheim, TagesTherapieZentrum, Interdisziplinares Tumorzentrum, Mannheim, Germany. [Brueck, P.; Emig, M.] Lilly Deutschland GmbH, Med Abt Onkol, Bad Homburg, Germany. [Hozak, R. R.] Eli Lilly & Co, Global Stat, Indianapolis, IN 46285 USA. [Ferry, D.] Eli Lilly & Co, Oncol, Bridgewater, MA USA. [Melemed, S.; Ouyang, H.] Eli Lilly & Co, Oncol, Indianapolis, IN 46285 USA. [Fuchst, C. S.] Harvard Med Sch, Dept Med Oncol, Dana Farber Inst, Boston, MA USA. [Wilke, H. -J] Klinikum Essen Mitte, Med Onkol Hamatol, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA P875 BP 263 EP 264 PG 2 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300658 ER PT J AU Grunwald, V Motzer, RJ Sharma, P Escudier, B McDermott, DF George, S Srinivas, S Tykodi, SS Sosman, JA Plimack, ER Nathan, P Tomita, Y Zhao, H Waxman, IM Hammers, HJ AF Gruenwald, V Motzer, R. J. Sharma, P. Escudier, B. McDermott, D. F. George, S. Srinivas, S. Tykodi, S. S. Sosman, J. A. Plimack, E. R. Nathan, P. Tomita, Y. Zhao, H. Waxman, I. M. Hammers, H. J. TI Correlation of response with overall survival (OS) for nivolumab vs everolimus in advanced renal cell carcinoma (aRCC): Results from the phase III CheckMate 025 study SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Gruenwald, V] Hannover Med Sch, Hannover, Germany. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Escudier, B.] Inst Gustave Roussy, Villejuif, France. [McDermott, D. F.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [George, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Srinivas, S.] Stanford Canc Inst, Stanford, CA USA. [Tykodi, S. S.] Univ Washington, Seattle, WA 98195 USA. [Tykodi, S. S.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Sosman, J. A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Plimack, E. R.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Nathan, P.] Mt Vernon Canc Ctr, Northwood, Middx, England. [Tomita, Y.] Niigata Univ, Niigata, Japan. [Zhao, H.] Bristol Myers Squibb, Pennington, NJ USA. [Waxman, I. M.] Bristol Myers Squibb, Lawrenceville, NJ USA. [Hammers, H. J.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA P878 BP 264 EP 265 PG 2 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300661 ER PT J AU Jaeger, D Sharma, P Bono, P Kim, J Spiliopoulou, P Calvo, E Pillai, RN Ott, PA de Braud, F Morse, M Le, D Chan, E Harbison, C Lin, CS Tschaika, M Azrilevich, A Rosenberg, J AF Jaeger, D. Sharma, P. Bono, P. Kim, J. Spiliopoulou, P. Calvo, E. Pillai, R. N. Ott, P. A. de Braud, F. Morse, M. Le, D. Chan, E. Harbison, C. Lin, C. -S Tschaika, M. Azrilevich, A. Rosenberg, J. TI Nivolumab monotherapy in metastatic urothelial cancer (mUC): efficacy (by PD-L1 expression) and safety results from the CheckMate 032 study SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Jaeger, D.] Univ Heidelberg Hosp, Heidelberg, Germany. [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bono, P.] Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Kim, J.] Yale Canc Ctr, New Haven, CT USA. [Spiliopoulou, P.] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Calvo, E.] START Madrid, Ctr Integral Oncol Clara Campal, Madrid, Spain. [Pillai, R. N.] Emory Winship Canc Inst, Atlanta, GA USA. [Ott, P. A.] Dana Farber Canc Ctr, Boston, MA USA. [de Braud, F.] Ist Nazl Tumori, Milan, Italy. [Morse, M.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Le, D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Chan, E.] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Harbison, C.; Lin, C. -S; Tschaika, M.; Azrilevich, A.] Bristol Myers Squibb, Princeton, NJ USA. [Rosenberg, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA P888 BP 269 EP 269 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300671 ER PT J AU Chawla, S Schoffski, P Grignani, G Blay, JY Maki, RG D'Adamo, DR Guo, M Demetri, GD AF Chawla, S. Schoeffski, P. Grignani, G. Blay, J. -Y Maki, R. G. D'Adamo, D. R. Guo, M. Demetri, G. D. TI Subtype-specific activity in Liposarcoma (LPS) patients (pts) from a phase 3, open-label, randomized study of eribulin (ERI) versus dacarbazine (DTIC) in pts with advanced LPS and leiomyosarcoma (LMS) SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Chawla, S.] Sarcoma Oncol Ctr, Santa Monica, CA USA. [Schoeffski, P.] Univ Hosp Leuven, Leuven, Belgium. [Grignani, G.] Fdn Piemonte Oncol IRCC, Candiolo, Italy. [Blay, J. -Y] Univ Lyon 1, Lyon, France. [Blay, J. -Y] Ctr Leon Berard, Lyon, France. [Maki, R. G.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA. [D'Adamo, D. R.; Guo, M.] Eisai Inc, Woodcliff Lake, NJ USA. [Demetri, G. D.] Dana Farber Canc Inst, Sarcoma Ctr, Boston, MA 02115 USA. [Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, G. D.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V990 BP 306 EP 306 PG 1 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300768 ER PT J AU Bethel, M Weaver, FM Bailey, L Miskevics, S Svircev, JN Burns, SP Hoenig, H Lyles, K Carbone, LD AF Bethel, M. Weaver, F. M. Bailey, L. Miskevics, S. Svircev, J. N. Burns, S. P. Hoenig, H. Lyles, K. Carbone, L. D. TI Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Clinical; Comorbidities; Fractures; SCI-related; Spinal cord injury ID BONE-MINERAL DENSITY; LOWER-EXTREMITY FRACTURES; POPULATION-BASED-COHORT; POSTMENOPAUSAL WOMEN; HIP FRACTURE; LUMBAR SPINE; OPIOID USE; MEN; ASSOCIATION; METAANALYSIS AB Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture. Few studies to date have comprehensively addressed clinical risk factors for fracture in persons with spinal cord injury (SCI). The purpose of this study was to identify risk factors for incident osteoporotic fractures in persons with a SCI that can be easily determined at the point of care. The Veteran's Affairs Spinal Cord Dysfunction Registry, a national database of persons with a SCI, was used to examine clinical and SCI-related risk factors for fracture. Incident fractures were identified in a cohort of persons with chronic SCI, defined as SCI present for at least 2 years. Cox regression models were used to estimate the risk of incident fractures. There were 22,516 persons with chronic SCI included in the cohort with 3365 incident fractures. The mean observational follow-up time for the overall sample was 6.2 years (median 6.0, IQR 2.9-11.0). The mean observational follow-up time for the fracture group was 3.9 years (median 3.3, IQR 1.4-6.1) and 6.7 years (median 6.7, IQR 3.1-11.0) for the nonfracture group. By the end of the study, which included predominantly older Veterans with a SCI observed for a relatively short period of time, the absolute (i.e., cumulative hazard) for incident fractures was 0.17 (95%CI 0.14-0.21). In multivariable analysis, factors associated with an increased risk of fracture included White race, traumatic etiology of SCI, paraplegia, complete extent of SCI, longer duration of SCI, use of anticonvulsants and opioids, prevalent fractures, and higher Charlson Comorbidity Indices. Women aged 50 and older were also at higher risk of sustaining an incident fracture at any time during the 11-year follow-up period. There are multiple clinical and SCI-related risk factors which can be used to predict fracture in persons with a SCI. Clinicians should be particularly concerned about incident fracture risk in persons with a SCI who have had a previous fracture. C1 [Bethel, M.; Carbone, L. D.] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA 30904 USA. [Bethel, M.; Carbone, L. D.] Augusta Univ, Dept Med, Med Coll Georgia, 1120 15th St, Augusta, GA 30912 USA. [Weaver, F. M.; Bailey, L.; Miskevics, S.] Edward J Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Weaver, F. M.] Loyola Univ, Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. [Bailey, L.] Univ Illinois, Sch Publ Hlth, Dept Epidemiol & Biostat, Chicago, IL USA. [Svircev, J. N.; Burns, S. P.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Svircev, J. N.; Burns, S. P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hoenig, H.] Durham VA Med Ctr, Durham, NC USA. [Lyles, K.] Duke Univ, Dept Med, Durham, NC USA. [Lyles, K.] VAMC, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP Bethel, M (reprint author), Charlie Norwood Vet Affairs Med Ctr, Augusta, GA 30904 USA.; Bethel, M (reprint author), Augusta Univ, Dept Med, Med Coll Georgia, 1120 15th St, Augusta, GA 30912 USA. EM mbethel@gru.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [IIR 11-103-3] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development IIR 11-103-3. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 65 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD OCT PY 2016 VL 27 IS 10 BP 3011 EP 3021 DI 10.1007/s00198-016-3627-2 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ2LM UT WOS:000385673300011 PM 27230522 ER PT J AU Honda, JR Hasan, NA Davidson, RM Williams, MD Epperson, LE Reynolds, PR Smith, T Iakhiaeva, E Bankowski, MJ Wallace, RJ Chan, ED Falkinham, JO Strong, M AF Honda, Jennifer R. Hasan, Nabeeh A. Davidson, Rebecca M. Williams, Myra D. Epperson, L. Elaine Reynolds, Paul R. Smith, Terry Iakhiaeva, Elena Bankowski, Matthew J. Wallace, Richard J., Jr. Chan, Edward D. Falkinham, Joseph O., III Strong, Michael TI Environmental Nontuberculous Mycobacteria in the Hawaiian Islands SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID AVIUM COMPLEX; LUNG-DISEASE; UNITED-STATES; EPIDEMIOLOGY; INFECTIONS; WATER; INTRACELLULARE; ABSCESSUS; PATHOGENS; CHELONAE AB Lung disease caused by nontuberculous mycobacteria (NTM) is an emerging infectious disease of global significance. Epidemiologic studies have shown the Hawaiian Islands have the highest prevalence of NTM lung infections in the United States. However, potential environmental reservoirs and species diversity have not been characterized. In this cross-sectional study, we describe molecular and phylogenetic comparisons of NTM isolated from 172 household plumbing biofilms and soil samples from 62 non-patient households and 15 respiratory specimens. Although non-uniform geographic sampling and availability of patient information were limitations, Mycobacterium chimaera was found to be the dominant species in both environmental and respiratory specimens. In contrast to previous studies from the continental U.S., no Mycobacterium avium was identified. Mycobacterium intracellulare was found only in respiratory specimens and a soil sample. We conclude that Hawai'i's household water sources contain a unique composition of Mycobacterium avium complex (MAC), increasing our appreciation of NTM organisms of pulmonary importance in tropical environments. C1 [Honda, Jennifer R.; Chan, Edward D.; Strong, Michael] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Anschutz Med Campus, Aurora, CO 80045 USA. [Honda, Jennifer R.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [Honda, Jennifer R.; Hasan, Nabeeh A.; Davidson, Rebecca M.; Epperson, L. Elaine; Reynolds, Paul R.; Chan, Edward D.; Strong, Michael] Natl Jewish Hlth, Denver, CO 80206 USA. [Williams, Myra D.; Smith, Terry; Iakhiaeva, Elena; Falkinham, Joseph O., III] Virginia Tech, Blacksburg, VA USA. [Bankowski, Matthew J.] Diagnost Lab Serv Inc, Aiea, HI USA. [Bankowski, Matthew J.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Pathol & Trop Med, Honolulu, HI 96822 USA. [Bankowski, Matthew J.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Med Microbiol, Honolulu, HI 96822 USA. [Bankowski, Matthew J.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Pharmacol, Honolulu, HI 96822 USA. [Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr, Tyler, TX USA. RP Honda, JR (reprint author), Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Anschutz Med Campus, Aurora, CO 80045 USA.; Honda, JR (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.; Honda, JR (reprint author), Natl Jewish Hlth, Denver, CO 80206 USA. EM Jennifer.Honda@ucdenver.edu FU NIH Biomedical Informatics training grant [2T15LM009451-06]; Amon G. Carter Foundation FX JRH acknowledges the University of Colorado AMC Division of Pulmonary Medicine and the Shoot for the Cure Foundation. NAH acknowledges the NIH Biomedical Informatics training grant 2T15LM009451-06. MS acknowledges the Boettcher Webb-Waring Foundation and the Potts Memorial Foundation. Finally, the University of Texas Health Science Center and National Jewish Health would like to acknowledge support from the Amon G. Carter Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 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 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2016 VL 10 IS 10 AR e0005068 DI 10.1371/journal.pntd.0005068 PG 17 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA EA5QH UT WOS:000386676200048 PM 27780201 ER PT J AU Pereira, TA Syn, WK Amancio, FF Cunha, PHD Caporali, JFM Trindade, GVD Santos, ET Souza, MM Andrade, ZA Witek, RP Secor, WE Pereira, FEL Lambertucci, JR Diehl, AM AF Pereira, Thiago Almeida Syn, Wing-Kin Amancio, Frederico Figueiredo Diniz Cunha, Pedro Henrique Morais Caporali, Julia Fonseca de Melo Trindade, Guilherme Vaz Santos, Elisangela Trindade Souza, Marcia Maria Andrade, Zilton Araujo Witek, Rafal P. Secor, William Evan Lima Pereira, Fausto Edmundo Lambertucci, Jose Roberto Diehl, Anna Mae TI Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID GRANULOMA-FORMATION; LIVER; INFLAMMATION; INFECTION; RESPONSES; FIBROSIS; INJURY; CELLS AB Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necroticexudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a noninvasive biomarker of this form of disease. C1 [Pereira, Thiago Almeida; Diehl, Anna Mae] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. [Pereira, Thiago Almeida; Amancio, Frederico Figueiredo; Diniz Cunha, Pedro Henrique; Morais Caporali, Julia Fonseca; de Melo Trindade, Guilherme Vaz; Lambertucci, Jose Roberto] Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Lab Doencas Infecciosas & Parasitarias, Belo Horizonte, MG, Brazil. [Pereira, Thiago Almeida; Santos, Elisangela Trindade; Souza, Marcia Maria; Andrade, Zilton Araujo] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Lab Patol Expt, Salvador, BA, Brazil. [Pereira, Thiago Almeida] NIAID, Immunopathogesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Syn, Wing-Kin] Ralph H Johnson Vet Affairs Med Ctr, Gastroenterol Sect, Charleston, SC USA. [Syn, Wing-Kin] Med Univ South Carolina, Div Gastroenterol & Hepatol, Charleston, SC USA. [Syn, Wing-Kin] Fdn Liver Res, Inst Hepatol, Liver Regenerat & Repair Res Grp, London, England. [de Melo Trindade, Guilherme Vaz] Natl Univ Ireland, Sch Med, Dept Physiol, Galway, Ireland. [Witek, Rafal P.] Thermo Fisher Sci, Frederick, MD USA. [Secor, William Evan] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lima Pereira, Fausto Edmundo] Univ Fed Espirito Santo, Nucleo Doencas Infecciosas, Vitoria, ES, Brazil. RP Diehl, AM (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA.; Lambertucci, JR (reprint author), Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Lab Doencas Infecciosas & Parasitarias, Belo Horizonte, MG, Brazil. EM jrlambertu@gmail.com; annamae.diehl@duke.edu FU National Institutes of Health [R01-DK-077794]; National Institutes of Health (Division of Intramural Research, NIAID, NIH); Duke University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Ministry of Science, Technology and Innovation of Brazil (CNPq); Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) FX This work was supported by National Institutes of Health (grant number R01-DK-077794 (to AMD); Division of Intramural Research, NIAID, NIH (to TAP)); the Duke University Endowment (the Florence McAlister Professorship) (to AMD), the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Ministry of Science, Technology and Innovation of Brazil (CNPq) (to TAP, FELP, JRL and ZAA); and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) (to JRL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 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 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD OCT PY 2016 VL 10 IS 10 AR e0005057 DI 10.1371/journal.pntd.0005057 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA EA5QH UT WOS:000386676200038 PM 27755536 ER PT J AU Perez, GK Mutchler, J Yang, MS Tree-Mcgrath, CF Park, ER AF Perez, Giselle K. Mutchler, Jan Yang, Mai See Tree-Mcgrath, Cheyenne Fox Park, Elyse R. TI Promoting quality care in patients with cancer with limited English proficiency: perspectives of medical interpreters SO PSYCHO-ONCOLOGY LA English DT Letter DE cancer; oncology; interpreters; limited English fluency; quality care ID SERVICES; ROLES C1 [Perez, Giselle K.; Park, Elyse R.] Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Mutchler, Jan; Yang, Mai See; Tree-Mcgrath, Cheyenne Fox] Univ Massachusetts, Boston, MA 02125 USA. RP Perez, GK (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM gperez@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 2 U2 2 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 OCT PY 2016 VL 25 IS 10 SI SI BP 1241 EP 1245 DI 10.1002/pon.4176 PG 5 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ3CA UT WOS:000385720300016 PM 27198473 ER PT J AU Oh, JY Hamm, J Xu, X Genschmer, K Zhong, M Lebensburger, J Marques, MB Kerby, JD Pittet, JF Gaggar, A Patel, RP AF Oh, Joo-Yeun Hamm, Jennifer Xu, Xin Genschmer, Kristopher Zhong, Ming Lebensburger, Jeffrey Marques, Marisa B. Kerby, Jeffrey D. Pittet, Jean-Francois Gaggar, Amit Patel, Rakesh P. TI Absorbance and redox based approaches for measuring free heme and free hemoglobin in biological matrices SO REDOX BIOLOGY LA English DT Article DE Exosomes; Microparticles; Hemin ID SICKLE-CELL-DISEASE; NITRIC-OXIDE BIOAVAILABILITY; ACUTE CHEST SYNDROME; STORAGE LESION; MOUSE MODELS; FERRYL IRON; HEMOPEXIN; ASSOCIATION; HAPTOGLOBIN; HEMOLYSIS AB Cell-free heme (CFH) and hemoglobin (Hb) have emerged as distinct mediators of acute injury characterized by inflammation and microcirculatory dysfunction in hemolytic conditions and critical illness. Several reports have shown changes in Hb and CFH in specific pathophysiological settings. Using PBS, plasma from patients with sickle cell disease, acute respiratory distress syndrome (ARDS) patients and supernatants from red cells units, we found that commonly used assays and commercially available kits do not distinguish between CFH and Hb. Furthermore, they suffer from a variety of false-positive interferences and limitations (including from bilirubin) that lead to either over-or underestimation of CFH and/or Hb. Moreover, commonly used protocols to separate CFH and Hb based on molecular weight (MWt) are inefficient due to CFH hydrophobicity. In this study, we developed and validated a new approach based on absorbance spectrum deconvolution with least square fitting analyses that overcomes these limitations and simultaneously measures CFH and Hb in simple aqueous buffers, plasma or when associated with red cell derived microvesicles. We show how incorporating other plasma factors that absorb light over the visible wavelength range (specifically bilirubin), coupled with truncating the wavelength range analyzed, or addition of mild detergent significantly improves fits allowing measurement of oxyHb, CFH and metHb with >90% accuracy. When this approach was applied to samples from SCD patients, we observed that CFH levels are higher than previously reported and of similar magnitude to Hb. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license C1 [Marques, Marisa B.; Patel, Rakesh P.] Univ Alabama Birmingham, Dept Pathol, BMR 2,Room 532,901 19th St South, Birmingham, AL 35294 USA. [Hamm, Jennifer; Lebensburger, Jeffrey] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL 35294 USA. [Xu, Xin; Genschmer, Kristopher; Zhong, Ming; Gaggar, Amit] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kerby, Jeffrey D.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Pittet, Jean-Francois] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL 35294 USA. [Pittet, Jean-Francois] Univ Alabama Birmingham, Dept Perioperat Med, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, Birmingham, AL 35294 USA. [Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Kerby, Jeffrey D.; Gaggar, Amit] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Zhong, Ming] Shandong Univ, Qili Hosp, Dept Cardiol, Jinan, Shandong, Peoples R China. RP Patel, RP (reprint author), Univ Alabama Birmingham, Dept Pathol, BMR 2,Room 532,901 19th St South, Birmingham, AL 35294 USA. EM rakeshpatel@uabmc.edu OI Marques, Marisa/0000-0002-6689-7856 NR 39 TC 1 Z9 1 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD OCT PY 2016 VL 9 BP 167 EP 177 DI 10.1016/j.redox.2016.08.003 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA6RQ UT WOS:000386757000019 PM 27566280 ER PT J AU Byon, CH Heath, JM Chen, YB AF Byon, Chang Hyun Heath, Jack M. Chen, Yabing TI Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells SO REDOX BIOLOGY LA English DT Review DE Oxidative stress; Hydrogen peroxide; Vascular smooth muscle cells; Calcification; Runx2 ID LOW-DENSITY-LIPOPROTEIN; GLYCATION END-PRODUCTS; MITOCHONDRIAL RESPIRATORY-CHAIN; OXIDATIVE DNA-DAMAGE; PROTEIN-KINASE-C; E-DEFICIENT MICE; REACTIVE OXYGEN; ENDOTHELIAL-CELLS; GROWTH-FACTOR; SUPEROXIDE-PRODUCTION AB Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS), which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2) exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC) undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC. (C) 2016. Published by Elsevier B.V. C1 [Byon, Chang Hyun; Heath, Jack M.; Chen, Yabing] Dept Pathol, Birmingham, AL 35294 USA. [Chen, Yabing] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Chen, Yabing] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Chen, YB (reprint author), Univ Alabama Birmingham, Dept Pathol, 614 Shelby Biomed Res Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM ybchen@uab.edu FU National Institutes of Health [HL092215, DK100847]; Veterans Administration [BX000369, BX001591] FX Due to the scope and limitation, we apologize for not being able to include all the important work in the field. The authors thank Jay M McDonald, MD and Victor Darley-Usmar, PhD (University of Alabama at Birmingham, UAB) for critical review. The original research programs of the authors are supported by grants from the National Institutes of Health, HL092215, DK100847 and Veterans Administration BX000369 and BX001591 (project 2) to YC. NR 159 TC 1 Z9 1 U1 5 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD OCT PY 2016 VL 9 BP 244 EP 253 DI 10.1016/j.redox.2016.08.015 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA6RQ UT WOS:000386757000026 PM 27591403 ER PT J AU Han, JY Weisbrod, RM Shao, D Watanabe, Y Yin, XY Bachschmid, MM Seta, F Janssen-Heininger, YMW Matsui, R Zang, MW Hamburg, NM Cohen, RA AF Han, Jingyan Weisbrod, Robert M. Shao, Di Watanabe, Yosuke Yin, Xiaoyan Bachschmid, Markus M. Seta, Francesca Janssen-Heininger, Yvonne M. W. Matsui, Reiko Zang, Mengwei Hamburg, Naomi M. Cohen, Richard A. TI The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells SO REDOX BIOLOGY LA English DT Article DE Protein S-glutathionylation; Glutaredoxin-1; Actin cytoskeleton; Small Rho GTPase Rac1; Endothelial barrier function; ApoE-deficient mice ID REVERSIBLE S-GLUTATHIONYLATION; NITRIC-OXIDE SYNTHASE; FREE FATTY-ACIDS; INSULIN-RESISTANCE; OXIDATIVE STRESS; DIABETES-MELLITUS; THIOL-OXIDATION; UP-REGULATION; IN-VIVO; KINASE AB Background: Oxidative stress is implicated in increased vascular permeability associated with metabolic disorders, but the underlying redox mechanism is poorly defined. S-glutathionylation, a stable adduct of glutathione with protein sulfhydryl, is a reversible oxidative modification of protein and is emerging as an important redox signaling paradigm in cardiovascular physiopathology. The present study determines the role of protein S-glutathionylation in metabolic stress-induced endothelial cell permeability. Methods and results: In endothelial cells isolated from patients with type-2 diabetes mellitus, protein S-glutathionylation level was increased. This change was also observed in aortic endothelium in ApoE deficient (ApoE(-I-)) mice fed on Western diet. Metabolic stress-induced protein S-glutathionylation in human aortic endothelial cells (HAEC) was positively correlated with elevated endothelial cell permeability, as reflected by disassembly of cell-cell adherens junctions and cortical actin structures. These impairments were reversed by adenoviral overexpression of a specific de-glutathionylation enzyme, glutaredoxin-1 in cultured HAECs. Consistently, transgenic overexpression of human Glrx-1 in ApoE(-/-)mice fed the Western diet attenuated endothelial protein S-glutathionylation, actin cytoskeletal disorganization, and vascular permeability in the aorta. Mechanistically, glutathionylation and inactivation of Rac1, a small RhoGPase, were associated with endothelial hyperpermeability caused by metabolic stress. Glutathionylation of Rac1 on cysteine 81 and 157 located adjacent to guanine nucleotide binding site was required for the metabolic stress to inhibit Racl activity and promote endothelial hyperpermeability. Conclusions: Glutathionylation and inactivation of Racl in endothelial cells represent a novel redox mechanism of vascular barrier dysfunction associated with metabolic disorders. (C) 2016 The Authors. Published by Elsevier B.V. C1 [Han, Jingyan; Shao, Di; Watanabe, Yosuke; Bachschmid, Markus M.; Seta, Francesca; Matsui, Reiko; Cohen, Richard A.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect,Evans Dept Med, Boston, MA 02118 USA. [Weisbrod, Robert M.; Hamburg, Naomi M.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Weisbrod, Robert M.; Hamburg, Naomi M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Yin, Xiaoyan] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA. [Janssen-Heininger, Yvonne M. W.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Mol Med, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. RP Han, JY (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Vasc Biol Sect,Evans Dept Med, Boston, MA 02118 USA. EM jingyanh@bu.edu OI Seta, Francesca/0000-0001-7985-5615; Bachschmid, Markus Michael/0000-0002-0748-5528 FU AHA [SDG20140036, 1UL1TR001430, T32 HL07224, R37 HL104017] FX This study is supported by AHA SDG20140036 (J.H.), 1UL1TR001430 (BU CTSI), T32 HL07224, and R37 HL104017 (R.A.C.). NR 63 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD OCT PY 2016 VL 9 BP 306 EP 319 DI 10.1016/j.redox.2016.09.003 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA6RQ UT WOS:000386757000032 PM 27693992 ER PT J AU Gaskins, AJ Williams, PL Keller, MG Souter, I Hauser, R Chavarro, JE AF Gaskins, Audrey J. Williams, Paige L. Keller, Myra G. Souter, Irene Hauser, Russ Chavarro, Jorge E. CA EARTH Study Team TI Maternal physical and sedentary activities in relation to reproductive outcomes following IVF SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE assisted reproductive technology; in vitro fertilization; physical activity; sedentary activity ID IN-VITRO FERTILIZATION; BODY-MASS INDEX; WOMEN; PREGNANCY; EXERCISE; INFERTILITY; OVULATION; STRESS; COHORT; HEALTH AB Physical activity could benefit reproductive function through its ability to regulate energy balance and improve insulin sensitivity, but its association with IVF outcomes remains unclear. The aim of this study was to evaluate whether pre-treatment physical and sedentary activity is associated with outcomes of IVF. The Environment and Reproductive Health Study is an ongoing prospective cohort study that enrols subfertile couples at Massachusetts General Hospital Fertility Center. Time spent in physical and sedentary activities in the year before IVF treatment is self-reported using a validated questionnaire. This analysis included 273 women who underwent 427 IVF cycles. Women engaged in a median of 2.8 h per week of moderate-to-vigorous activities. Time spent in moderate-to-vigorous physical activities and total metabolic equivalent task hours before IVF were not associated with probability of implantation, clinical pregnancy or live birth. Of the specific physical activities, only greater time spent in aerobics, rowing, and on the ski or stair machine was associated with higher probability of live birth. Time spent in total and specific sedentary activities were not associated with clinical outcomes of IVF. Physical activity is unlikely to have a deleterious effect on IVF success and certain forms of vigorous activity may be beneficial. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. [Gaskins, Audrey J.; Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 655 Huntington Ave, Boston, MA 02115 USA. [Williams, Paige L.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. [Keller, Myra G.; Souter, Irene; Hauser, Russ] Massachusetts Gen Hosp, Fertil Ctr, 32 Fruit St,Suite 10A, Boston, MA 02114 USA. [Keller, Myra G.; Souter, Irene; Hauser, Russ] Harvard Med Sch, 32 Fruit St,Suite 10A, Boston, MA 02114 USA. [Keller, Myra G.; Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 655 Huntington Ave, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. RP Gaskins, AJ (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.; Gaskins, AJ (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 655 Huntington Ave, Boston, MA 02115 USA. EM ajg219@mail.harvard.edu FU NIH [R01-ES009718, R01-ES022955, P30-DK046200, T32-DK007703-16, L50-HD085359] FX The authors are supported by NIH grants R01-ES009718, R01-ES022955, P30-DK046200, T32-DK007703-16, and L50-HD085359. NR 23 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1472-6483 EI 1472-6491 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD OCT PY 2016 VL 33 IS 4 BP 513 EP 521 DI 10.1016/j.rbmo.2016.07.002 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA4OA UT WOS:000386590900009 PM 27474489 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Risk of infection with preoperative epidural injections SO SPINE JOURNAL LA English DT Letter ID SPINAL PAIN C1 [Manchikanti, Laxmaiah] Univ Louisville, Sch Med, 2301 South 23rd St, Louisville, KY 40292 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, Sch Med, 2301 South 23rd St, Louisville, KY 40292 USA.; Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD OCT PY 2016 VL 16 IS 10 BP 1282 EP 1282 DI 10.1016/j.spinee.2016.04.024 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA EA8TA UT WOS:000386910400049 PM 27745627 ER PT J AU Itchaki, G Brown, JR AF Itchaki, Gilad Brown, Jennifer R. TI The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia SO THERAPEUTIC ADVANCES IN HEMATOLOGY LA English DT Review DE ABT-199; B-cell chronic lymphocytic leukemia; venetoclax ID EFFICIENTLY INDUCES APOPTOSIS; MEDIATED TREATMENT RESISTANCE; KINASE INHIBITOR IBRUTINIB; B-CELL MALIGNANCIES; LYMPHOID MALIGNANCIES; ANTITUMOR-ACTIVITY; BH3 MIMETICS; BCL-2 INHIBITION; MCL-1 EXPRESSION; TARGETING BCL2 AB Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL), it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN. We further strive to contextualize VEN in the current CLL treatment landscape and discuss potential mechanisms of resistance. C1 [Brown, Jennifer R.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Itchaki, Gilad] Beilinson Med Ctr, Rabin Med Ctr, Petah Tiqwa, Israel. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_brown@dfci.harvard.edu NR 94 TC 1 Z9 1 U1 8 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2040-6207 EI 2040-6215 J9 THER ADV HEMATOL JI Ther. Adv. Hematol. PD OCT PY 2016 VL 7 IS 5 BP 270 EP 287 DI 10.1177/2040620716655350 PG 18 WC Hematology SC Hematology GA EA8YV UT WOS:000386927100003 PM 27695617 ER PT J AU Kumar, V Boucher, Y Liu, H Ferreira, D Hooker, J Catana, C Hoover, AJ Ritter, T Jain, RK Guimaraes, AR AF Kumar, Vidhya Boucher, Yves Liu, Hao Ferreira, Diego Hooker, Jacob Catana, Ciprian Hoover, Andrew J. Ritter, Tobias Jain, Rakesh K. Guimaraes, Alexander R. TI Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma SO TRANSLATIONAL ONCOLOGY LA English DT Article ID CONTRAST-ENHANCED MRI; RECEPTOR TYROSINE KINASES; TUMOR ANGIOGENESIS; CLINICAL-TRIALS; STEADY-STATE; GROWTH; INHIBITION; CANCER; SIZE; CHEMOTHERAPY AB PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC) models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI) of magnetic iron oxide nanoparticles (MNPs) and micro-positron emission tomography (PET) measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan. METHOD AND MATERIALS: All experiments were approved by the local Institutional Animal Care and Use Committee. FVB mice with orthotopic PDAC were treated daily with an i.p. injection of losartan (70 mg/kg) or saline (control vehicle) for 5 days. In order to calculate the fractional blood volume, vessel size index, and vessel density index, MRI was performed at 4.7 T following the injection of 3 mg/kg iron ferumoxytol (i.v.). Dynamic PET images were also acquired for 60 minutes using an F-18-5FU tracer dose of 200 mu Ci and analyzed for time activity curves normalized to muscle. Statistical analyses compared both cohorts using an unpaired two-tailed t test. RESULTS: In comparison to the control treatment, the losartan administration significantly increased the fractional blood volume (mean +/- SEM) [12.1 +/- 1.7 (n = 19) vs 6.7 +/- 1.1 (n = 20); P < .02] and vessel size index (128.2 +/- 35.6 vs 57.5 +/- 18; P < .05). Losartan also induced a significant increase in the intratumoral uptake of F-18-5FU by 53% (P < .0001). CONCLUSION: MRI using FDA-approved MNPs provides a noninvasive, translatablemeans of assaying microvascular parameters induced by losartan in pancreatic cancer. PET measurements demonstrated that losartan significantly increased the uptake of F-18-5FU. C1 [Kumar, Vidhya; Ferreira, Diego; Hooker, Jacob; Catana, Ciprian; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Boucher, Yves; Liu, Hao; Jain, Rakesh K.] Harvard Med Sch, EL Steele Labs Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. [Boucher, Yves; Liu, Hao; Jain, Rakesh K.] Massachusetts Gen Hosp, 100 Blossom St,Cox 7, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Div Body Imaging, Dept Diagnost Radiol, Portland, OR USA. [Hoover, Andrew J.; Ritter, Tobias] Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. [Ritter, Tobias] Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany. RP Guimaraes, AR (reprint author), Oregon Hlth & Sci Univ, Radiol, Dept Diagnost Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code L340, Portland, OR 97239 USA.; Guimaraes, AR (reprint author), Oregon Hlth & Sci Univ, Body Imaging, Dept Diagnost Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code L340, Portland, OR 97239 USA.; Boucher, Y (reprint author), Massachusetts Gen Hosp, Steele Lab Tumor Biol, Dept Radiat Oncol, 149 13th St, Charlestown, MA 02129 USA. EM guimaraa@ohsu.edu FU National Institutes of Health [K08 EB 012859-04, P01-CA080124, R01-CA098706, R21CA173518]; Lustgarten Foundation FX A.R.G. acknowledges the National Institutes of Health grant K08 EB 012859-04, and Y.B. and R.K.J. acknowledge the National Institutes of Health grants P01-CA080124 (R. K. J.), R01-CA098706 (Y. B.), and R21CA173518 (Y. B.) and a grant from the Lustgarten Foundation. NR 37 TC 0 Z9 0 U1 9 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-5233 J9 TRANSL ONCOL JI Transl. Oncol. PD OCT PY 2016 VL 9 IS 5 BP 431 EP 437 DI 10.1016/j.tranon.2016.07.004 PG 7 WC Oncology SC Oncology GA EA6XQ UT WOS:000386772900007 PM 27751347 ER PT J AU Perlis, RH AF Perlis, Roy H. TI Abandoning personalization to get to precision in the pharmacotherapy of depression SO WORLD PSYCHIATRY LA English DT Article DE Antidepressants; major depression; precision medicine; risk stratification; personalized medicine; biomarkers; treatment matching ID ELECTRONIC HEALTH RECORDS; BIPOLAR I DISORDER; STAR-ASTERISK-D; MAJOR DEPRESSION; ANTIDEPRESSANT RESPONSE; CONTROLLED-TRIAL; VARIANT GADL1; DOUBLE-BLIND; LITHIUM; RISK AB Effectiveness studies and analyses of naturalistic cohorts demonstrate that many patients with major depressive disorder do not experience symptomatic remission with antidepressant treatments. In an effort to better match patients with effective treatments, numerous investigations of predictors or moderators of treatment response have been reported over the past five decades, including clinical features as well as biological measures. However, none of these have entered routine clinical practice; instead, clinicians typically personalize treatment on the basis of patient preferences as well as their own. Here, we review the reasons why it has been challenging to identify and deploy treatment-specific predictors of response, and suggest strategies that may be required to achieve true precision in the pharmacotherapy of depression. We emphasize the need for changes in how depression care is delivered, measured, and used to inform future practice. C1 [Perlis, Roy H.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02115 USA. [Perlis, Roy H.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02115 USA.; Perlis, RH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA. NR 52 TC 6 Z9 6 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2016 VL 15 IS 3 BP 228 EP 235 DI 10.1002/wps.20345 PG 8 WC Psychiatry SC Psychiatry GA DZ8RY UT WOS:000386140200008 PM 27717262 ER PT J AU Yeo, S Rosen, B Bosch, P van den Noort, M Lim, S AF Yeo, Sujung Rosen, Bruce Bosch, Peggy van den Noort, Maurits Lim, Sabina TI Gender differences in the neural response to acupuncture: clinical implications SO ACUPUNCTURE IN MEDICINE LA English DT Article DE ACUPUNCTURE ID BRAINS DEFAULT MODE; PAIN; STIMULATION; FMRI; SEX; NETWORK; ELECTROACUPUNCTURE; OSTEOARTHRITIS; CORTEX; KNEE AB Objective To examine gender differences and similarities in the psychophysical and brain responses to acupuncture at GB34, a point that is frequently used to treat motor function issues in Traditional Chinese Medicine. Methods Functional MRI (fMRI) was used to measure brain activation in response to acupuncture at GB34 (on the right) in 19 healthy participants (9 male, 10 female). De qi sensations were rated to measure their psychophysical responses. Results Overall de qi scores did not differ by gender, although females reported greater intensity of aching (p=0.04). Acupuncture activated the hippocampus, thalamus, globus pallidus, caudate body, claustrum, cingulate gyrus, and culmen in males, and the middle and inferior frontal gyrus, precuneus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, caudate body, insula, fusiform gyrus, cingulate gyrus, amygdala, and parahippocampal gyrus in females. The middle/medial frontal gyrus, middle temporal gyrus, thalamus, globus pallidus, caudate body, uvula, and cerebellar tonsil were activated when data from all subjects were combined. Relative to males, females exhibited greater brain activation in the right-sided postcentral gyrus, precentral gyrus, precuneus, postcentral gyrus, inferior parietal lobule, declive, middle occipital gyrus and parahippocampal gyrus. Conclusions The neural effects of GB34 acupuncture might differ between males and females because different brain structures were modulated in response to acupuncture. This potential gender effect should be taken into account in future clinical research. We also revealed that the caudate body was activated by GB34 acupuncture in both males and females and may represent a major target of GB34 acupuncture. Trial registration number KMC IRB 0861-06. C1 [Rosen, Bruce; van den Noort, Maurits; Lim, Sabina] Kyung Hee Univ, WHO Collaborating Ctr Tradit Med, East West Med Res Inst, Coll Korean Med,Dept Meridian & Acupoint, 47 Gyeonghuidae Gil, Seoul 130701, South Korea. [Rosen, Bruce] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bosch, Peggy] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [van den Noort, Maurits; Lim, Sabina] Kyung Hee Univ, Res Grp Pain & Neurosci, Seoul, South Korea. RP Yeo, S (reprint author), Sang Ji Univ, Dept Meridian & Acupoint, Coll Korean Med, 83 Sangjidae Gil, Wonju 220702, Gangwon Do, South Korea.; Yeo, S (reprint author), Sang Ji Univ, Coll Korean Med, Wonju, Gangwon Do, South Korea.; Lim, S (reprint author), Kyung Hee Univ, WHO Collaborating Ctr Tradit Med, East West Med Res Inst, Coll Korean Med,Dept Meridian & Acupoint, 47 Gyeonghuidae Gil, Seoul 130701, South Korea. EM pinkteeth@hanmail.net; lims@khu.ac.kr FU National Research Foundation of Korea (NRF) - Korean government [2014R1A2A1A11052795, 2014R1A1A1004100] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (no. 2014R1A2A1A11052795, 2014R1A1A1004100). NR 38 TC 0 Z9 0 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-5284 EI 1759-9873 J9 ACUPUNCT MED JI Acupunct. Med. PD OCT PY 2016 VL 34 IS 5 BP 364 EP 372 DI 10.1136/acupmed-2015-011025 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA EA2WE UT WOS:000386455700005 PM 27193838 ER PT J AU Yetisen, AK Butt, H Mikulchyk, T Ahmed, R Montelongo, Y Humar, M Jiang, N Martin, S Naydenova, I Yun, SH AF Yetisen, Ali K. Butt, Haider Mikulchyk, Tatsiana Ahmed, Rajib Montelongo, Yunuen Humar, Matjaz Jiang, Nan Martin, Suzanne Naydenova, Izabela Yun, Seok Hyun TI Color-Selective 2.5D Holograms on Large-Area Flexible Substrates for Sensing and Multilevel Security SO ADVANCED OPTICAL MATERIALS LA English DT Article ID 3-DIMENSIONAL PHOTONIC CRYSTALS; BANDGAP; LIGHT; NANOSTRUCTURES; LITHOGRAPHY; DIFFRACTION; FABRICATION; ELEMENTS; SENSORS; ARRAYS AB 2.5D photonic nanostructures with narrow-band diffraction characteristics have a vast range of potential applications in information storage, tunable lasers, optical filters, and biosensors. However, fabrication of 2.5D photonic devices over large areas remains expertise-dependent, inaccurate, and high-cost, limiting their widespread use in practical applications and consumer products. Here, large area printing of quasi 2.5D holograms is demonstrated in the visible spectrum. These holographic surface-relief gratings are hexagonally packed lateral microscale honeycomb pyramids consisting of vertical nanoscale steps. The consecutive steps act as Bragg gratings producing constructive interference of selective visible wavelengths. The 2.5D nanostepped pyramids exhibit coloration due to the narrow-band Bragg diffraction that is tuned in the visible spectrum and a wide angular range. Roll-to-roll processing allows for rapid nanoimprinting the 2.5D nanostepped pyramid arrays over large areas of acrylate polymer film on poly(ethylene terephthalate) substrate. The utilities of the 2.5D holograms are demonstrated by creating colorimetric refractive index and relative humidity sensors, quick response codes, fingerprints, signatures, and encrypted labels. It is envisioned that 2.5D holograms can be integrated with desktop dot-matrix printers for application in sensing, data storage, and security. C1 [Yetisen, Ali K.; Humar, Matjaz; Yun, Seok Hyun] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Humar, Matjaz; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Humar, Matjaz; Jiang, Nan; Yun, Seok Hyun] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Butt, Haider; Ahmed, Rajib] Univ Birmingham, Sch Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Mikulchyk, Tatsiana; Martin, Suzanne; Naydenova, Izabela] Dublin Inst Technol, Sch Phys, Coll Sci & Hlth, Ctr Ind & Engn Opt, Kevin St, Dublin 8, Ireland. [Montelongo, Yunuen] Imperial Coll London, Dept Chem, South Kensington Campus, London SW7 2AZ, England. [Humar, Matjaz] J Stefan Inst, Condensed Matter Dept, Jamova 39, SI-1000 Ljubljana, Slovenia. RP Yetisen, AK; Yun, SH (reprint author), Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK; Yun, SH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK; Yun, SH (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM ayetisen@mgh.harvard.edu; syun@mgh.harvard.edu OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust [RF-2016-039]; Wellcome Trust [201929/Z/16/Z] FX This work was supported by the Leverhulme Trust (RF-2016-039) and the Wellcome Trust (201929/Z/16/Z). The authors acknowledge James J. Cowan and W. Dennis Slafer for fabricating the gratings used in this study and discussions on fabrication. The authors thank Jeff Blyth for discussions. The authors also thank Grant England, Elijah Shirman, Ida Pavlichenko, Joanna Aizenberg, B. V. Lotsch, and Viola D. for angular measurements, SEM and AFM imaging. Author Contributions: A.K.Y. designed the project and wrote the article. A.K.Y., T.M., and M.H. performed the experiments. H.B., R.A., and Y.M. carried out the simulations. A.Y., H.B., R.A., I.N, and S.M. analyzed the data and revised the article. The authors declare no competing financial interests. NR 43 TC 5 Z9 5 U1 23 U2 23 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 2195-1071 J9 ADV OPT MATER JI Adv. Opt. Mater. PD OCT PY 2016 VL 4 IS 10 BP 1589 EP 1600 DI 10.1002/adom.201600162 PG 12 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA EA1MR UT WOS:000386356900019 ER PT J AU Drucker, AM Li, WQ Cho, E Li, T Sun, Q Camargo, CA Qureshi, AA AF Drucker, A. M. Li, W. -Q. Cho, E. Li, T. Sun, Q. Camargo, C. A., Jr. Qureshi, A. A. TI Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women SO ALLERGY LA English DT Article DE atopic dermatitis; cardiovascular disease; comorbidity; myocardial infarction; stroke ID CARDIOVASCULAR-DISEASE; ISCHEMIC-STROKE; POPULATION; ADULT; RISK; ECZEMA; PREVALENCE; PSORIASIS; COHORT; HEALTH AB We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age-and multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age-or multivariate-adjusted analyses. AD was significantly associated with stroke in the age-adjusted analysis (OR 1.38, 95% CI 1.03-1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98-1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86-1.58). AD was not independently associated with nonfatal MI or stroke in this study. C1 [Drucker, A. M.; Li, W. -Q.; Cho, E.; Qureshi, A. A.] Warren Alpert Med Sch, Dept Dermatol, 593 Eddy St,APC-10, Providence, RI 02903 USA. [Drucker, A. M.; Qureshi, A. A.] Rhode Isl Hosp, Dept Dermatol, Providence, RI USA. [Drucker, A. M.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA. [Li, W. -Q.; Cho, E.; Qureshi, A. A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Cho, E.; Li, T.; Sun, Q.; Camargo, C. A., Jr.; Qureshi, A. A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Cho, E.; Li, T.; Sun, Q.; Camargo, C. A., Jr.; Qureshi, A. A.] Harvard Med Sch, Boston, MA USA. [Sun, Q.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Camargo, C. A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, C. A., Jr.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Qureshi, AA (reprint author), Warren Alpert Med Sch, Dept Dermatol, 593 Eddy St,APC-10, Providence, RI 02903 USA. EM abrar_qureshi@brown.edu FU Department of Dermatology, Warren Alpert Medical School of Brown University; Nurses' Health Study II grant [NIH UM1 CA176726] FX The study was supported in part by Department of Dermatology, Warren Alpert Medical School of Brown University, and Nurses' Health Study II grant (NIH UM1 CA176726). The funders had no role in the design and conduct of the study, collection, management, analysis and interpretation of data, preparation, review or approval of the manuscript, or the decision to submit the manuscript for publication. NR 19 TC 2 Z9 2 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 OCT PY 2016 VL 71 IS 10 BP 1496 EP 1500 DI 10.1111/all.12957 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA DZ7YX UT WOS:000386085800015 PM 27291834 ER PT J AU Lin, AE Michot, C Cormier-Daire, V L'Ecuyer, TJ Matherne, GP Barnes, BH Humberson, JB Edmondson, AC Zackai, E O'Connor, MJ Kaplan, JD Ebeid, MR Krier, J Krieg, E Ghoshhajra, B Lindsay, ME AF Lin, Angela E. Michot, Caroline Cormier-Daire, Valerie L'Ecuyer, Thomas J. Matherne, G. Paul Barnes, Barrett H. Humberson, Jennifer B. Edmondson, Andrew C. Zackai, Elaine O'Connor, Matthew J. Kaplan, Julie D. Ebeid, Makram R. Krier, Joel Krieg, Elizabeth Ghoshhajra, Brian Lindsay, Mark E. TI Gain-of-function mutations in SMAD4 cause a distinctive repertoire of cardiovascular phenotypes in patients with Myhre syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE cardiovascular malformation; coarctation; congenital heart defect; pericarditis; pericardial effusion; restrictive cardiomyopathy; SMAD4 mutations; TGF- signaling ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; RESTRICTIVE CARDIOMYOPATHY; MULIBREY NANISM; CLINICAL-FEATURES; GELEOPHYSIC DYSPLASIA; SHORT STATURE; LAPS SYNDROME; STENOSIS; FEMALE; COMPLICATIONS AB Myhre syndrome is a rare, distinctive syndrome due to specific gain-of-function mutations in SMAD4. The characteristic phenotype includes short stature, dysmorphic facial features, hearing loss, laryngotracheal anomalies, arthropathy, radiographic defects, intellectual disability, and a more recently appreciated spectrum of cardiovascular defects with a striking fibroproliferative response to surgical intervention. We report four newly described patients with typical features of Myhre syndrome who had (i) a mildly narrow descending aorta and restrictive cardiomyopathy; (ii) recurrent pericardial and pleural effusions; (iii) a large persistent ductus arteriosus with juxtaductal aortic coarctation; and (iv) restrictive pericardial disease requiring pericardiectomy. Additional information is provided about a fifth previously reported patient with fatal pericardial disease. A literature review of the cardiovascular features of Myhre syndrome was performed on 54 total patients, all with a SMAD4 mutation. Seventy percent had a cardiovascular abnormality including congenital heart defects (63%), pericardial disease (17%), restrictive cardiomyopathy (9%), and systemic hypertension (15%). Pericarditis and restrictive cardiomyopathy are associated with high mortality (three patients each among 10 deaths); one patient with restrictive cardiomyopathy also had epicarditis. Cardiomyopathy and pericardial abnormalities distinguish Myhre syndrome from other disorders caused by mutations in the TGF- signaling cascade (Marfan, Loeys-Dietz, or Shprintzen-Goldberg syndromes). We hypothesize that the expanded spectrum of cardiovascular abnormalities relates to the ability of the SMAD4 protein to integrate diverse signaling pathways, including canonical TGF-, BMP, and Activin signaling. The co-occurrence of congenital and acquired phenotypes demonstrates that the gene product of SMAD4 is required for both developmental and postnatal cardiovascular homeostasis. (c) 2016 Wiley Periodicals, Inc. C1 [Lin, Angela E.] Harvard Med Sch, MassGen Hosp Children, Massachusetts Gen Hosp, Genet Unit, Boston, MA USA. [Michot, Caroline; Cormier-Daire, Valerie] Paris Descartes Univ Sorbonne Paris Cite, Necker Enfants Malad Hosp, Inst Imagine, INSERM Unit UMR1163,Dept Genet, Paris, France. [L'Ecuyer, Thomas J.; Matherne, G. Paul] Univ Virginia, Dept Pediat, Childrens Hosp, Div Cardiol, Charlottesville, VA USA. [Barnes, Barrett H.] Univ Virginia, Dept Pediat, Childrens Hosp, Div Gastroenterol, Charlottesville, VA USA. [Humberson, Jennifer B.] Univ Virginia, Dept Pediat, Childrens Hosp, Div Genet, Charlottesville, VA USA. [Edmondson, Andrew C.; Zackai, Elaine] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [O'Connor, Matthew J.] Childrens Hosp Philadelphia, Div Cardiol, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA. [Kaplan, Julie D.] Univ Mississippi, Med Ctr, Dept Pediat, Div Med Genet, Jackson, MS 39216 USA. [Ebeid, Makram R.] Univ Mississippi, Med Ctr, Dept Pediat, Div Cardiol, Jackson, MS 39216 USA. [Krier, Joel; Krieg, Elizabeth] Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Boston, MA USA. [Ghoshhajra, Brian; Lindsay, Mark E.] Harvard Med Sch, Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA USA. [Ghoshhajra, Brian] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Lindsay, Mark E.] Harvard Med Sch, Massachusetts Gen Hosp, MassGen Hosp Children, Div Pediat Cardiol,Dept Pediat, Boston, MA USA. [Lindsay, Mark E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. [Lindsay, Mark E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, 185 Cambridge St,CPZN-2222, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu NR 61 TC 0 Z9 0 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 OCT PY 2016 VL 170 IS 10 SI SI BP 2617 EP 2631 DI 10.1002/ajmg.a.37739 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA DW4KQ UT WOS:000383612200019 PM 27302097 ER PT J AU Renda, G Zimarino, M Ricci, F Piccini, JP Ezekowitz, MD Patel, MR Cappato, R Giugliano, RP De Caterina, R AF Renda, Giulia Zimarino, Marco Ricci, Fabrizio Piccini, Jonathan P. Ezekowitz, Michael D. Patel, Manesh R. Cappato, Riccardo Giugliano, Robert P. De Caterina, Raffaele TI Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants After Cardioversion for Nonvalvular Atrial Fibrillation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Atrial fibrillation; Cardioversion; Major bleeding; Non-vitamin K antagonist oral anticoagulants; Stroke; Vitamin K antagonists ID PUBLIC-HEALTH; WARFARIN; METAANALYSIS; OUTCOMES; RIVAROXABAN; THROMBOSIS; APIXABAN AB BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are proven alternatives to vitamin K antagonists (VKAs) for the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. However, there are few data on the efficacy and safety of NOAC therapy after cardioversion, where the risk of thromboembolic events is heightened. METHODS: We performed a random-effects meta-analysis of patients who underwent both electrical and pharmacologic cardioversion for atrial fibrillation in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, and X-VeRT trials. We assessed Mantel-Haenszel pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs) for stroke/systemic embolism and major bleeding at <= 42 days of follow-up. RESULTS: The analysis pooled 3949 patients in whom a total of 4900 cardioversions for atrial fibrillation were performed. Compared with VKAs, NOAC therapy was associated with a similar risk of stroke/systemic embolism (RR 0.84; 95% CI, 0.34-2.04) and major bleeding (RR 1.12; 95% CI, 0.52-2.42); no significant statistical heterogeneity was found among studies (Cochrane Q P = .59, I-2 = 0% for stroke/systemic embolism; P = .47; I-2 = 0% for major bleeding). CONCLUSIONS: The short-term incidences of thromboembolic and major hemorrhagic events after cardioversion on NOACs were low and comparable to those observed on dose-adjusted VKA therapy. Non-vitamin K oral anticoagulants are a reasonable alternative to VKAs in patients undergoing cardioversion. (C) 2016 Elsevier Inc. All rights reserved. C1 [Renda, Giulia; Zimarino, Marco; Ricci, Fabrizio; De Caterina, Raffaele] Univ G DAnnunzio, Inst Cardiol, Chieti, Italy. [Renda, Giulia; Zimarino, Marco; Ricci, Fabrizio; De Caterina, Raffaele] Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy. [Piccini, Jonathan P.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Ezekowitz, Michael D.] Thomas Jefferson Med Coll, Philadelphia, PA USA. [Cappato, Riccardo] Ist Clin Humanitas, Milan, Italy. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. RP De Caterina, R (reprint author), Univ G DAnnunzio, Inst Cardiol, Osped SS Annunziata, Via Vestini, I-66013 Chieti, Italy. EM rdecater@unich.it NR 27 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD OCT PY 2016 VL 129 IS 10 BP 1117 EP + DI 10.1016/j.amjmed.2016.05.007 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA EA1EA UT WOS:000386334100040 PM 27262782 ER PT J AU Wakeman, SE AF Wakeman, Sarah E. TI Science Alone Is Not Enough Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Wakeman, Sarah E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wakeman, Sarah E.] Harvard Med Sch, Boston, MA 02115 USA. RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.; Wakeman, SE (reprint author), Harvard Med Sch, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD OCT PY 2016 VL 129 IS 10 BP E251 EP E251 DI 10.1016/j.amjmed.2016.05.022 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA EA1EA UT WOS:000386334100013 PM 27671852 ER PT J AU Fagenholz, PJ Peev, MP Thabet, A Michailidou, M Chang, YC Mueller, PR Hahn, PF Velmahos, GC AF Fagenholz, Peter J. Peev, Miroslav P. Thabet, Ashraf Michailidou, Maria Chang, Yuchiao Mueller, Peter R. Hahn, Peter F. Velmahos, George C. TI Abscess due to perforated appendicitis: factors associated with successful percutaneous drainage SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Appendicitis; Abscess; Radiology; Interventional ID MANAGEMENT; APPENDECTOMY; CHILDREN AB BACKGROUND: Percutaneous drainage is the standard treatment for perforated appendicitis with abscess. We studied factors associated with complete resolution (CR) with percutaneous drainage alone. METHODS: Ninety-eight patients underwent percutaneous drainage for acute appendicitis complicated by abscess (October 1990 to September 2010). CR was defined as clinical recovery, resolution of the abscess on imaging, and drain removal without recurrence. Patients achieving CR were compared with patients not achieving CR. RESULTS: The rate of CR was 78.6% (n = 5 77). Abscess grade was the only radiological factor associated with CR (P = .007). The CR rate was higher with transgluteal drainage (90.9% vs 79.2%) than with other anatomic approaches (P = .018) and higher with computed tomography-guided drainage than with ultrasound-guided drainage (82.7% vs 64.3%, P = .046). CONCLUSION: CR was more likely to be achieved in patients with lower abscess grade, computed tomography-guided drainage, and a transgluteal approach. (C) 2015 Elsevier Inc. All rights reserved. C1 [Fagenholz, Peter J.; Peev, Miroslav P.; Michailidou, Maria; Chang, Yuchiao; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, 165 Cambridge St, Boston, MA 02114 USA. [Thabet, Ashraf; Mueller, Peter R.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Peev, Miroslav P.] Tufts Univ, Med Ctr, Dept Surg, Residency Off, 800 Washington St, Boston, MA 02111 USA. [Michailidou, Maria] Univ Arizona, Coll Med, Dept Surg, Residency Off, 1501 N Campbell Ave,POB 245058, Tucson, AZ 85724 USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, 165 Cambridge St, Boston, MA 02114 USA. EM pfagenholz@mgh.harvard.edu NR 15 TC 0 Z9 0 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2016 VL 212 IS 4 BP 794 EP 798 DI 10.1016/j.amjsurg.2015.07.017 PG 5 WC Surgery SC Surgery GA DZ5UB UT WOS:000385925900034 PM 26499054 ER PT J AU Tukey, MH Clark, JA Bolton, R Kelley, MJ Slatore, CG Au, DH Wiener, RS AF Tukey, Melissa H. Clark, Jack A. Bolton, Rendelle Kelley, Michael J. Slatore, Christopher G. Au, David H. Wiener, Renda Soylemez TI Readiness for Implementation of Lung Cancer Screening A National Survey of Veterans Affairs Pulmonologists SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: To mitigate the potential harms of screening, professional societies recommend that lung cancer screening be conducted in multidisciplinary programs with the capacity to provide comprehensive care, from screening through pulmonary nodule evaluation to treatment of screen-detected cancers. The degree to which this standard can be met at the national level is unknown. Objectives: To assess the readiness of clinical facilities in a national healthcare system for implementation of comprehensive lung cancer screening programs, as compared with the ideal described in policy recommendations. Methods: This was a cross-sectional, self-administered survey of staff pulmonologists in pulmonary outpatient clinics in Veterans Health Administration facilities. Measurements and Main Results: The facility-level response rate was 84.1% (106 of 126 facilities with pulmonary clinics); 88.7% of facilities showed favorable provider perceptions of the evidence for lung cancer screening, and 73.6% of facilities had a favorable provider-perceived local context for screening implementation. All elements of the policy recommended infrastructure for comprehensive screening programs were present in 36 of 106 facilities (34.0%); the most common deficiencies were the lack of on-site positron emission tomography scanners or radiation oncology services. Overall, 26.5% of Veterans Health Administration facilities were ideally prepared for lung cancer screening implementation (44.1% if the policy recommendations for on-site positron emission tomography scanners and radiation oncology services were waived). Conclusions: Many facilities may be less than ideally positioned for the implementation of comprehensive lung cancer screening programs. To ensure safe, effective screening, hospitals may need to invest resources or coordinate care with facilities that can offer comprehensive care for screening through downstream evaluation and treatment of screen-detected cancers. C1 [Tukey, Melissa H.] Brown Univ, Alpert Med Sch, Div Pulm Crit Care & Sleep, Providence, RI 02912 USA. [Clark, Jack A.; Bolton, Rendelle; Wiener, Renda Soylemez] Edith Nourse Rogers Mem Vet Affairs Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA. [Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Kelley, Michael J.] Durham Vet Affairs Med Ctr, Med Serv, Durham, NC USA. [Kelley, Michael J.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Kelley, Michael J.] Duke Univ, Med Ctr, Dept Med, Durham, NC USA. [Slatore, Christopher G.] Vet Affairs Portland Hlth Care Syst, Ctr Improve Veteran Involvement Care, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Au, David H.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Innovat Veteran Ctr & Value Driven Care, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm Crit Care Med, Seattle, WA 98195 USA. [Wiener, Renda Soylemez] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. RP Wiener, RS (reprint author), Edith Nourse Rogers Mem Vet Affairs Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135 FU Veterans Health Administration (VA) QUERI [RRP 12-533]; Edith Nourse Rogers Memorial Veterans Affairs Hospital, Bedford, Massachusetts; Veterans Affairs Portland Health Care System, Portland, Oregon; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX Supported by Veterans Health Administration (VA) QUERI RRP 12-533; the study was also supported with resources from the Edith Nourse Rogers Memorial Veterans Affairs Hospital, Bedford, Massachusetts, the Veterans Affairs Portland Health Care System, Portland, Oregon, and Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD OCT PY 2016 VL 13 IS 10 BP 1794 EP 1801 DI 10.1513/AnnalsATS.201604-294OC PG 8 WC Respiratory System SC Respiratory System GA DZ8KG UT WOS:000386118700021 PM 27409524 ER PT J AU Levy, SD Oren-Grinberg, A McSparron, JI AF Levy, Sean D. Oren-Grinberg, Achikam McSparron, Jakob I. TI Paradoxical Air Embolus after Removal of a Central Venous Catheter SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Editorial Material C1 [Levy, Sean D.; McSparron, Jakob I.] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA. [Levy, Sean D.] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Oren-Grinberg, Achikam] Massachusetts Gen Hosp, Div Pulm Crit Care & Sleep Med, Boston, MA 02114 USA. RP Levy, SD (reprint author), Massachusetts Gen Hosp, 55 Fruit St,BUL 148, Boston, MA 02114 USA. EM sdlevy@mgh.harvard.edu 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 OCT PY 2016 VL 13 IS 10 BP 1856 EP 1857 DI 10.1513/AnnalsATS.201604-228CC PG 2 WC Respiratory System SC Respiratory System GA DZ8KG UT WOS:000386118700029 PM 27726443 ER PT J AU Lewis, NA Towey, C Bruinvels, G Howatson, G Pedlar, CR AF Lewis, Nathan A. Towey, Colin Bruinvels, Georgie Howatson, Glyn Pedlar, Charles R. TI Effects of exercise on alterations in redox homeostasis in elite male and female endurance athletes using a clinical point-of-care test SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM LA English DT Article DE oxidative stress; monitoring; biomarkers; antioxidant; fatigue ID OXIDATIVE STRESS BIOMARKERS; WELL-TRAINED ROWERS; SKELETAL-MUSCLE; VITAMIN-C; ANTIOXIDANT CAPACITY; AEROBIC EXERCISE; BLOOD; PROTEIN; MEN; SUPPLEMENTATION AB Exercise causes alterations in redox homeostasis (ARH). Measuring ARH in elite athletes may aid in the identification of training tolerance, fatigued states, and underperformance. To the best of our knowledge, no studies have examined ARH in elite male and female distance runners at sea level. The monitoring of ARH in athletes is hindered by a lack of reliable and repeatable in-the-field testing tools and by the rapid turnaround of results. We examined the effects of various exercise intensities on ARH in healthy (non-over-reached) elite male and female endurance athletes using clinical point-of-care (POC) redox tests, referred to as the free oxygen radical test (FORT) (pro-oxidant) and the free oxygen radical defence (FORD) (antioxidant). Elite male and female endurance athletes (n = 22) completed a discontinuous incremental treadmill protocol at submaximal running speeds and a test to exhaustion. Redox measures were analyzed via blood sampling at rest, warm-up, submaximal exercise, exhaustion, and recovery. FORD was elevated above rest after submaximal and maximal exercise, and recovery (p < 0.05, d = 0.87-1.55), with only maximal exercise and recovery increasing FORT (p < 0.05, d = 0.23-0.32). Overall, a decrease in oxidative stress in response to submaximal and maximal exercise was evident (p < 0.05, d = 0.46). There were no gender differences for ARH (p > 0.05). The velocity at lactate threshold (vLT) correlated with the FORD response at rest, maximal exercise, and recovery (p < 0.05). Using the clinical POC redox test, an absence of oxidative stress after exhaustive exercise is evident in the nonfatigued elite endurance athlete. The blood antioxidant response (FORD) to exercise appears to be related to a key marker of aerobic fitness: vLT. C1 [Lewis, Nathan A.; Towey, Colin; Bruinvels, Georgie; Pedlar, Charles R.] St Marys Univ, Sch Sport Hlth & Appl Sci, London TW1 4SX, England. [Lewis, Nathan A.; Bruinvels, Georgie; Pedlar, Charles R.] Natl Univ Ireland Galway, Business Innovat Ctr, ORRECO, Unit 103, Galway H91 RW53, Ireland. [Lewis, Nathan A.] Univ Bath, English Inst Sport, Bath BA2 7AY, Avon, England. [Bruinvels, Georgie] UCL, Div Surg & Intervent Sci, London WC1E 6BT, England. [Howatson, Glyn] Northumbria Univ, Dept Sport Exercise & Rehabil, Newcastle NE7 7XA, England. [Howatson, Glyn] Northwest Univ, Water Res Grp, Sch Environm Sci & Dev, ZA-2531 Potchefstroom, South Africa. [Pedlar, Charles R.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP Lewis, NA (reprint author), St Marys Univ, Sch Sport Hlth & Appl Sci, London TW1 4SX, England.; Lewis, NA (reprint author), Natl Univ Ireland Galway, Business Innovat Ctr, ORRECO, Unit 103, Galway H91 RW53, Ireland.; Lewis, NA (reprint author), Univ Bath, English Inst Sport, Bath BA2 7AY, Avon, England. EM nathan.lewis@eis2win.co.uk FU research support fund in the School of Sport, Health and Applied Science at St. Mary's University, Twickenham, London, UK FX We thank all the participants for willingly taking part in this study. This study was supported financially by the research support fund in the School of Sport, Health and Applied Science at St. Mary's University, Twickenham, London, UK. NR 50 TC 0 Z9 0 U1 9 U2 9 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 1715-5312 EI 1715-5320 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD OCT PY 2016 VL 41 IS 10 BP 1026 EP 1032 DI 10.1139/apnm-2016-0208 PG 7 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA DZ8NZ UT WOS:000386128400003 PM 27625070 ER PT J AU Tromberg, BJ Zhang, Z Leproux, A O'Sullivan, TD Cerussi, AE Carpenter, PM Mehta, RS Roblyer, D Yang, W Paulsen, KD Pogue, BW Jiang, SD Kaufman, PA Yodh, AG Chung, SH Schnall, M Snyder, BS Hylton, N Boas, DA Carp, SA Isakoff, SJ Mankoff, D AF Tromberg, Bruce J. Zhang, Zheng Leproux, Anais O'Sullivan, Thomas D. Cerussi, Albert E. Carpenter, Philip M. Mehta, Rita S. Roblyer, Darren Yang, Wei Paulsen, Keith D. Pogue, Brian W. Jiang, Shudong Kaufman, Peter A. Yodh, Arjun G. Chung, So Hyun Schnall, Mitchell Snyder, Bradley S. Hylton, Nola Boas, David A. Carp, Stefan A. Isakoff, Steven J. Mankoff, David CA ACRIN 6691 Investigators TI Predicting Responses to Neoadjuvant Chemotherapy in Breast Cancer: ACRIN 6691 Trial of Diffuse Optical Spectroscopic Imaging SO CANCER RESEARCH LA English DT Article ID PATHOLOGICAL COMPLETE RESPONSE; MENSTRUAL-CYCLE; TUMOR RESPONSE; FDG-PET; MAMMOGRAPHY; TOMOGRAPHY; WOMEN; THERAPY; TISSUE; STATE AB The prospective multicenter ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a diffuse optical spectroscopic imaging (DOSI)-derived imaging endpoint, the tissue optical index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine (Irvine, CA), and delivered to six institutions where 60 subjects with newly diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO(2)), water (ctH(2)O), lipid, and TOI (ctHHb x ctH(2)O/lipid) were acquired on both breasts up to four times during NAC treatment: baseline, 1-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 +/- 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor-to-normal TOI ratio (% TOITN) from baseline to midtherapy ranged from -82% to 321%, with a median of -36%. Using pCR as the reference standard and ROC curve methodology, % TOITN AUC was 0.60 (95% CI, 0.39-0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (% StO(2)) greater than the 77% population median, % TOITN AUC improved to 0.83 (95% CI, 0.63-1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction. (C) 2016 AACR. C1 [Tromberg, Bruce J.; Leproux, Anais; O'Sullivan, Thomas D.; Cerussi, Albert E.] Univ Calif Irvine, Beckman Laser Inst & Med Clin, 1002 Hlth Sci Rd, Irvine, CA 92612 USA. [Zhang, Zheng] Brown Univ, Sch Publ Hlth, Dept Biostat, Providence, RI 02912 USA. [Zhang, Zheng; Snyder, Bradley S.] Brown Univ, Sch Publ Hlth, Ctr Stat Sci, Providence, RI 02912 USA. [Carpenter, Philip M.] Univ Southern Calif, Dept Pathol, Los Angeles, CA USA. [Mehta, Rita S.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Roblyer, Darren] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Yang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [Paulsen, Keith D.; Pogue, Brian W.; Jiang, Shudong] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Kaufman, Peter A.] Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Sect Hematol & Oncol, Lebanon, NH USA. [Yodh, Arjun G.; Chung, So Hyun] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. [Schnall, Mitchell; Mankoff, David] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Hylton, Nola] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Boas, David A.; Carp, Stefan A.] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. [Isakoff, Steven J.] Harvard Med Sch, Massachusetts Gen Hosp, Hematol Oncol, Boston, MA USA. RP Tromberg, BJ (reprint author), Univ Calif Irvine, Beckman Laser Inst & Med Clin, 1002 Hlth Sci Rd, Irvine, CA 92612 USA. EM bjtrombe@uci.edu FU NCATS NIH HHS [UL1 TR001414]; NCI NIH HHS [R01 CA142989, P30 CA016520, P30 CA062203, R01 CA176086, U01 CA079778, U01 CA080098, U10 CA079778, U54 CA136400]; NIBIB NIH HHS [P41 EB015890, P41 EB015893] NR 57 TC 0 Z9 0 U1 5 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 20 BP 5933 EP 5944 DI 10.1158/0008-5472.CAN-16-0346 PG 12 WC Oncology SC Oncology GA DZ1UW UT WOS:000385627600005 PM 27527559 ER PT J AU Campbell, PT Newton, CC Freedman, ND Koshiol, J Alavanja, MC Freeman, LEB Buring, JE Chan, AT Chong, DQ Datta, M Gaudet, MM Gaziano, JM Giovannucci, EL Graubard, BI Hollenbeck, AR King, L Lee, IM Linet, MS Palmer, JR Petrick, JL Poynter, JN Purdue, MP Robien, K Rosenberg, L Sahasrabuddhe, VV Schairer, C Sesso, HD Sigurdson, AJ Stevens, VL Wactawski-Wende, J Zeleniuch-Jacquotte, A Renehan, AG McGlynn, KA AF Campbell, Peter T. Newton, Christina C. Freedman, Neal D. Koshiol, Jill Alavanja, Michael C. Freeman, Laura E. Beane Buring, Julie E. Chan, Andrew T. Chong, Dawn Q. Datta, Mridul Gaudet, Mia M. Gaziano, J. Michael Giovannucci, Edward L. Graubard, Barry I. Hollenbeck, Albert R. King, Lindsey Lee, I-Min Linet, Martha S. Palmer, Julie R. Petrick, Jessica L. Poynter, Jenny N. Purdue, Mark P. Robien, Kim Rosenberg, Lynn Sahasrabuddhe, Vikrant V. Schairer, Catherine Sesso, Howard D. Sigurdson, Alice J. Stevens, Victoria L. Wactawski-Wende, Jean Zeleniuch-Jacquotte, Anne Renehan, Andrew G. McGlynn, Katherine A. TI Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for US Adults SO CANCER RESEARCH LA English DT Article ID EPIC-OXFORD PARTICIPANTS; BILIARY-TRACT CANCER; HEPATOCELLULAR-CARCINOMA; EUROPEAN COHORT; UNITED-STATES; MELLITUS; OBESITY; METAANALYSIS; ASSOCIATION; WEIGHT AB Incidence rates for liver cancer have increased 3-fold since the mid-1970s in the United States in parallel with increasing trends for obesity and type II diabetes mellitus. Weconducted an analysis of baseline body mass index (BMI), waist circumference (WC), and type II diabetes mellitus with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated HRs and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and type II diabetes mellitus). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n = 220) and controls (n = 547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m(2), was associated with higher risks of liver cancer, more so for men (HR = 1.38; 95% CI, 1.30-1.46) than women (HR = 1.25; 95% CI, 1.17-1.35; P-interaction = 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR = 1.08; 95% CI, 1.04-1.13). Type II diabetes mellitus was associated with higher risk of liver cancer (HR = 2.61; 95% CI, 2.34-2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and type II diabetes mellitus are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. (C) 2016 AACR. C1 [Campbell, Peter T.; Newton, Christina C.; Gaudet, Mia M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Freedman, Neal D.; Koshiol, Jill; Alavanja, Michael C.; Freeman, Laura E. Beane; Graubard, Barry I.; Linet, Martha S.; Petrick, Jessica L.; Purdue, Mark P.; Sahasrabuddhe, Vikrant V.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Buring, Julie E.; Chan, Andrew T.; Gaziano, J. Michael; King, Lindsey; Lee, I-Min; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Buring, Julie E.; Giovannucci, Edward L.; Lee, I-Min; Sesso, Howard D.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Chan, Andrew T.; King, Lindsey] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsey] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsey] Harvard Med Sch, Boston, MA USA. [Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore. [Datta, Mridul] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Palmer, Julie R.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Poynter, Jenny N.] Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. [Poynter, Jenny N.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Robien, Kim] George Washington Univ, Milken Inst, Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Renehan, Andrew G.] Univ Manchester, Fac Inst Canc Sci, Manchester, Lancs, England. RP Campbell, PT (reprint author), Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA. EM peter.campbell@cancer.org RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU Intramural NIH HHS [Z01 CP010119-12, Z01 ES049030-11]; NCI NIH HHS [UM1 CA186107, P01 CA055075, P01 CA087969, P30 CA016087, R01 CA034944, R01 CA034944-03, R01 CA039742, R01 CA040360, R01 CA047988, R01 CA049449, R01 CA058420, R01 CA097193, R01 CA098661, UM1 CA164974, UM1 CA167552]; NHLBI NIH HHS [R01 HL026490, R01 HL026490-03, R01 HL034595, R01 HL034595-07, R01 HL043851, R01 HL080467]; NIEHS NIH HHS [P30 ES000260, Z01 ES049030] NR 37 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 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 20 BP 6076 EP 6083 DI 10.1158/0008-5472.CAN-16-0787 PG 8 WC Oncology SC Oncology GA DZ1UW UT WOS:000385627600018 PM 27742674 ER PT J AU Langs, G Wang, DH Golland, P Mueller, S Pan, RQ Sabuncu, MR Sun, W Li, KC Liu, HS AF Langs, Georg Wang, Danhong Golland, Polina Mueller, Sophia Pan, Ruiqi Sabuncu, Mert R. Sun, Wei Li, Kuncheng Liu, Hesheng TI Identifying Shared Brain Networks in Individuals by Decoupling Functional and Anatomical Variability SO CEREBRAL CORTEX LA English DT Article DE functional parcellation; individual differences; resting-state fMRI ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HEMISPHERIC ASYMMETRIES; LANGUAGE LATERALIZATION; ASSOCIATION NETWORKS; PREFRONTAL CORTEX; COORDINATE SYSTEM; DIFFUSION MAPS; CONNECTIVITY; SCHIZOPHRENIA AB The connectivity architecture of the human brain varies across individuals. Mapping functional anatomy at the individual level is challenging, but critical for basic neuroscience research and clinical intervention. Using resting-state functional connectivity, we parcellated functional systems in an "embedding space" based on functional characteristics common across the population, while simultaneously accounting for individual variability in the cortical distribution of functional units. The functional connectivity patterns observed in resting-state data were mapped in the embedding space and the maps were aligned across individuals. A clustering algorithm was performed on the aligned embedding maps and the resulting clusters were transformed back to the unique anatomical space of each individual. This novel approach identified functional systems that were reproducible within subjects, but were distributed across different anatomical locations in different subjects. Using this approach for intersubject alignment improved the predictability of individual differences in language laterality when compared with anatomical alignment alone. Our results further revealed that the strength of association between function and macroanatomy varied across the cortex, which was strong in unimodal sensorimotor networks, but weak in association networks. C1 [Langs, Georg] Med Univ Vienna, Computat Imaging Res Lab, Dept Biomed Imaging & Image guided Therapy, Vienna, Austria. [Langs, Georg; Golland, Polina; Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Wang, Danhong; Mueller, Sophia; Pan, Ruiqi; Sabuncu, Mert R.; Liu, Hesheng] Harvard Med Sch, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA 02115 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, Munich, Germany. [Pan, Ruiqi; Li, Kuncheng] Capital Med Univ, Dept Radiol, Beijing, Peoples R China. [Sun, Wei] Capital Med Univ, Dept Neurol, Xuanwu Hosp, Beijing, Peoples R China. RP Liu, HS (reprint author), Harvard Med Sch, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA 02115 USA. EM hesheng@nmr.mgh.harvard.edu FU NIH [K25NS069805, R01NS091604, P50MH106435]; NIH NICHD [R01HD067312]; NIH NIBIB NAC [P41EB015902]; OeNB [14812, 15929]; EU [2012-PIEF-GA-33003]; NIH NIBIB [1K25EB013649-01]; BrightFocus Alzheimer's disease pilot research grant [AHAF A2012333]; Medical Imaging Cluster at Medical University of Vienna FX This work is supported by NIH grants K25NS069805 (H.L.), R01NS091604 (H.L.), and P50MH106435 (H.L.). NIH NICHD R01HD067312 (P.G., G.L.) and NIH NIBIB NAC P41EB015902 (P.G., G.L.), OeNB 14812 and 15929 (G.L.), and EU FP7 2012-PIEF-GA-33003 (G.L.). M.R.S. is supported by NIH NIBIB 1K25EB013649-01 and a BrightFocus Alzheimer's disease pilot research grant (AHAF A2012333). This research was partly supported by the Medical Imaging Cluster at Medical University of Vienna (G.L.). NR 49 TC 3 Z9 3 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2016 VL 26 IS 10 BP 4004 EP 4014 DI 10.1093/cercor/bhv189 PG 11 WC Neurosciences SC Neurosciences & Neurology GA DZ7IT UT WOS:000386039000012 PM 26334050 ER PT J AU Narayanan, S Lam, A Vaishampayan, U Harshman, L Fan, A Pachynski, R Poushnejad, S Haas, D Li, SF Srinivas, S AF Narayanan, Sujata Lam, Anthony Vaishampayan, Ulka Harshman, Lauren Fan, Alice Pachynski, Russell Poushnejad, Shermeen Haas, Denise Li, Shufeng Srinivas, Sandy TI Phase II Study of Pazopanib and Paclitaxel in Patients With Refractory Urothelial Cancer SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Angiogenesis inhibitor; Chemotherapy; Combination; Second line; Targeted therapy ID TRANSITIONAL-CELL CARCINOMA; PLATINUM-CONTAINING REGIMEN; COOPERATIVE-ONCOLOGY-GROUP; 2ND-LINE TREATMENT; BLADDER-CANCER; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; SOLID TUMORS; SINGLE GROUP; OPEN-LABEL AB The present phase II study of paclitaxel with an antiangiogenic agent for refractory urothelial cancer resulted in a high objective response rate with limited toxicity. Introduction: Currently, no standard treatments are available for relapsed or refractory urothelial carcinoma (UC). Paclitaxel has demonstrated efficacy in the treatment of UC when used alone or combined with other cytotoxic therapies. We designed a phase II trial combining paclitaxel with pazopanib, a commonly used antiangiogenic agent with significant antitumor activity in various solid tumors. Patients and Methods: We enrolled 32 patients with refractory UC who had demonstrated disease progression after 2 previous chemotherapeutic regimens. The patients received paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle and oral pazopanib 800 mg daily. The primary endpoint was the overall response rate (ORR). The secondary endpoints included progression-free survival, overall survival, and a safety assessment of the combination. Results: Of the 28 evaluable patients, a complete response was observed in 3 patients and a partial response in 12, with an ORR of 54% (95% confidence interval, 33.9-72.5). The median progression-free and overall survival was 6.2 and 10 months, respectively. The most frequent side effects noted (all grades) were fatigue (63%), diarrhea (44%), and nausea and vomiting (41%). Hematologic toxicities were common and included (all grades) anemia (69%), neutropenia (38%), and thrombocytopenia (47%). Growth factor support was required for 44% of the patients. Conclusion: The combination of paclitaxel and pazopanib resulted in a promising ORR of 54% in patients with advanced pretreated UC. This represents a greater response rate and median survival than found with other existing second-line regimens for UC and is worthy of further study. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lam, Anthony] Skyline Urol, Torrance, CA USA. [Harshman, Lauren] Dana Farber Canc Inst, Boston, MA 02115 USA. [Harshman, Lauren] Harvard Med Sch, Boston, MA USA. [Pachynski, Russell] Washington Univ, Sch Med, St Louis, MO USA. [Narayanan, Sujata; Lam, Anthony; Harshman, Lauren; Fan, Alice; Pachynski, Russell; Poushnejad, Shermeen; Haas, Denise; Li, Shufeng; Srinivas, Sandy] Stanford Canc Ctr, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. [Vaishampayan, Ulka] Karmanos Canc Inst, Detroit, MI USA. RP Srinivas, S (reprint author), Stanford Canc Ctr, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM sandysri@stanford.edu FU GlaxoSmith Kline FX Funding for the present study was provided by GlaxoSmith Kline. The sponsor had no involvement in manuscript preparation. NR 38 TC 0 Z9 0 U1 1 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD OCT PY 2016 VL 14 IS 5 BP 432 EP 437 DI 10.1016/j.clgc.2016.03.011 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA EA0YS UT WOS:000386316100011 PM 27068017 ER PT J AU Kadri, SS Rhee, C Magda, G Strich, JR Cai, RM Sun, JF Decker, BK O'Grady, NP AF Kadri, Sameer S. Rhee, Chanu Magda, Gabriela Strich, Jeffrey R. Cai, Rongman Sun, Junfeng Decker, Brooke K. O'Grady, Naomi P. TI Synergy, Salary, and Satisfaction: Benefits of Training in Critical Care Medicine and Infectious Diseases Gleaned From a National Pilot Survey of Dually Trained Physicians SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE critical care; infectious diseases; survey ID UNITED-STATES; EMERGENCY PHYSICIANS; MORTALITY; CONSULTATIONS; SUBSPECIALTY; CHALLENGES; PREVENTION; PULMONARY; EDUCATION; THERAPY AB A survey of physicians trained in critical care medicine (CCM) and infectious diseases (ID) suggested this combination is synergistic and satisfying. However, most respondents had to train in individual specialties at separate institutions. Avenues for CCM-ID training should be considered.Methods.aEuro integral All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. Results.aEuro integral Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. Conclusions.aEuro integral CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. C1 [Kadri, Sameer S.; Cai, Rongman; Sun, Junfeng; O'Grady, Naomi P.] NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,B10 2C-145, Bethesda, MD 20892 USA. [Rhee, Chanu] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Rhee, Chanu] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Rhee, Chanu] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Magda, Gabriela] Georgetown Univ Hosp, Medstar, Dept Med, Washington, DC 20007 USA. [Strich, Jeffrey R.] NIAID, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Decker, Brooke K.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA USA. RP Kadri, SS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,B10 2C-145, Bethesda, MD 20892 USA. EM sameer.kadri@nih.gov FU National Institutes of Health FX This work was supported by intramural funds from the National Institutes of Health. NR 34 TC 3 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2016 VL 63 IS 7 BP 868 EP 875 DI 10.1093/cid/ciw441 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ7JL UT WOS:000386041100009 PM 27358351 ER PT J AU Blumenthal, KG Shenoy, ES AF Blumenthal, Kimberly G. Shenoy, Erica S. TI Fortune Favors the Bold: Give a Beta-Lactam! SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE hypersensitivity; allergy; quality; adverse reaction ID PENICILLIN ALLERGY; ANTIMICROBIAL STEWARDSHIP; HOSPITALIZED-PATIENTS; ANTIBIOTICS; PREVALENCE; GUIDELINES; THERAPY; HISTORY; IMPACT C1 [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Shenoy, Erica S.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Dept Med, Boston, MA 02114 USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Edward P Lawrence Ctr Qual & Safety, Boston, MA 02114 USA. [Shenoy, Erica S.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Shenoy, Erica S.] Harvard Med Sch, Boston, MA USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Flr, Boston, MA 02114 USA. EM kblumenthal1@partners.org NR 27 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 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2016 VL 63 IS 7 BP 911 EP 913 DI 10.1093/cid/ciw467 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ7JL UT WOS:000386041100016 PM 27402818 ER PT J AU Lipsett, SC Branda, JA McAdam, AJ Vernacchio, L Gordon, CD Gordon, CR Nigrovic, LE AF Lipsett, Susan C. Branda, John A. McAdam, Alexander J. Vernacchio, Louis Gordon, Caroline D. Gordon, Catherine R. Nigrovic, Lise E. TI Evaluation of the C6 Lyme Enzyme Immunoassay for the Diagnosis of Lyme Disease in Children and Adolescents SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Lyme disease; Lyme disease diagnostics; C6; pediatrics ID UNITED-STATES; BORRELIA-BURGDORFERI; IGM IMMUNOBLOTS; MENINGITIS; PREDICTION; COMPLICATIONS; SERODIAGNOSIS; LABORATORIES; PERFORMANCE; VALIDATION AB In children and adolescents undergoing evaluation for Lyme disease, the C6 enzyme immunoassay had similar sensitivity but lower specificity than standard 2-tiered testing. This assay could be used to guide initial management decisions, but supplemental immunoblot should still be performed.Methods.aEuro integral We collected discarded serum samples from children and adolescents (aged a parts per thousand currency sign21 years) undergoing conventional 2-tiered testing for Lyme disease at a single hospital-based clinical laboratory located in an area endemic for Lyme disease. We performed a C6 EIA on all collected specimens, followed by a supplemental immunoblot if the C6 EIA result was positive but the whole-cell sonicate EIA result was negative. We defined a case of Lyme disease as either a clinician-diagnosed erythema migrans lesion or a positive standard 2-tiered serologic result in a patient with symptoms compatible with Lyme disease. We then compared the performance of the C6 EIA alone and as a first-tier test followed by immunoblot, with that of standard 2-tiered serology for the diagnosis of Lyme disease. Results.aEuro integral Of the 944 specimens collected, 114 (12%) were from patients with Lyme disease. The C6 EIA alone had sensitivity similar to that of standard 2-tiered testing (79.8% vs 81.6% for standard 2-tiered testing; P = .71) with slightly lower specificity (94.2% vs 98.8% 2; P < .002). Addition of a supplemental immunoblot improved the specificity of the C6 EIA to 98.6%. Conclusions.aEuro integral For children and adolescents undergoing evaluation for Lyme disease, the C6 EIA could guide initial clinical decision making, although a supplemental immunoblot should still be performed. C1 [Lipsett, Susan C.; Gordon, Caroline D.; Gordon, Catherine R.; Nigrovic, Lise E.] Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. [Vernacchio, Louis] Boston Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [McAdam, Alexander J.] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Vernacchio, Louis] Pediat Phys Org Childrens, Brookline, MA USA. RP Lipsett, SC (reprint author), Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM susan.lipsett@childrens.harvard.edu OI Lipsett, Susan/0000-0002-4758-6905 FU Boston Children's Hospital; Harvard Medical School FX This work was supported by Boston Children's Hospital (House Officers research grant and Michael Shannon research grant to S. C. L. and Research Faculty Council pilot grant to L. E. N.) and Harvard Medical School (Harvard Catalyst Early Clinical Data grant to L. E. N.). NR 25 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2016 VL 63 IS 7 BP 922 EP 928 DI 10.1093/cid/ciw427 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ7JL UT WOS:000386041100018 PM 27358358 ER PT J AU D'Elia, JA Bayliss, G Gleason, RE Weinrauch, LA AF D'Elia, John A. Bayliss, George Gleason, Ray E. Weinrauch, Larry A. TI Cardiovascular-renal complications and the possible role of plasminogen activator inhibitor: a review SO CLINICAL KIDNEY JOURNAL LA English DT Review DE cardiovascular; end-stage renal disease; renin-angiotensin system; thrombosis; type 2 diabetes ID TYPE-2 DIABETES-MELLITUS; HUMAN ADIPOSE-TISSUE; SMOOTH-MUSCLE CELLS; RISK-FACTORS; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; NEOINTIMA FORMATION; ENDOTHELIAL-CELLS; CYNOMOLGUS MONKEY; CARDIAC FIBROSIS AB Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin-angiotensin-aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction. While the renin-angiotensin-aldosterone system and growth factors, such as transforming growth factor-beta (TGF-beta), are almost always part of the process, there are rare experimental observations of PAI-1 expression without their interaction. Here we review the literature on PAI-1 and its role in vascular, fibrotic and oxidative injury as well as work suggesting potential areas of intervention in the pathogenesis of multiple disorders. C1 [D'Elia, John A.; Gleason, Ray E.; Weinrauch, Larry A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [D'Elia, John A.; Gleason, Ray E.; Weinrauch, Larry A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [D'Elia, John A.; Weinrauch, Larry A.] Harvard Med Sch, Boston, MA USA. [Bayliss, George] Rhode Isl Hosp, Div Kidney Dis & Hypertens, 593 Eddy St, Providence, RI 02903 USA. [Bayliss, George] Miriam Hosp, Providence, RI 02906 USA. [Bayliss, George] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Gleason, Ray E.; Weinrauch, Larry A.] EP Joslin Res Lab, Boston, MA USA. [Gleason, Ray E.; Weinrauch, Larry A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Bayliss, G (reprint author), Rhode Isl Hosp, Div Kidney Dis & Hypertens, 593 Eddy St, Providence, RI 02903 USA.; Bayliss, G (reprint author), Miriam Hosp, Providence, RI 02906 USA.; Bayliss, G (reprint author), Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. EM gbayliss@lifespan.org NR 87 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1753-0784 EI 1753-0792 J9 CLIN KIDNEY J JI Clin. Kidney J. PD OCT PY 2016 VL 9 IS 5 BP 705 EP 712 DI 10.1093/ckj/sfw080 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DZ8OX UT WOS:000386131400009 PM 27679717 ER PT J AU Canali, S Vecchi, C Garuti, C Montosi, G Babitt, JL Pietrangelo, A AF Canali, Susanna Vecchi, Chiara Garuti, Cinzia Montosi, Giuliana Babitt, Jodie L. Pietrangelo, Antonello TI The SMAD Pathway Is Required for Hepcidin Response During Endoplasmic Reticulum Stress SO ENDOCRINOLOGY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ELEMENT-BINDING PROTEIN; IRON-METABOLISM; TRANSCRIPTION FACTOR; PEPTIDE HEPCIDIN; ACTIVIN B; ER STRESS; IN-VIVO; EXPRESSION; INFLAMMATION AB Hepcidin, the iron hormone, is regulated by a number of stimulatory and inhibitory signals. The cAMP responsive element binding protein 3-like 3 (CREB3L3) mediates hepcidin response to endoplasmic reticulum (ER) stress. In this study we asked whether hepcidin response to ER stress also requires the small mother against decapentaplegic (SMAD)-1/5/8 pathway, which has a major role in hepcidin regulation in response to iron and other stimuli. We analyzed hepcidin mRNA expression and promoter activity in response to ER stressors in HepG2 cells in the presence of the bone morphogenetic protein (BMP) type I receptor inhibitor LDN-193189, mutated hepcidin promoter or small interfering RNA against different SMAD proteins. We then used a similar approach in vivo in wild-type, Smad1/5, or Creb3l3(-/-) animals undergoing ER stress. In vitro, LDN-193189 prevented hepcidin mRNA induction by different ER stressors. Seemingly, mutation of a BMP-responsive element in the hepcidin promoter prevented ER stress-mediated up-regulation. Moreover, in vitro silencing of SMAD proteins by small interfering RNA, in particular SMAD5, blunted hepcidin response to ER stress. On the contrary, hepcidin induction by ER stress was maintained when using antibodies against canonical BMP receptor ligands. In vivo, hepcidin was induced by ER stress and prevented by LDN-193189. In addition, in Smad1/5 knockout mice, ER stress was unable to induce hepcidin expression. Finally, in Creb3l3 knockout mice, in response to ER stress, SMAD1/5 were correctly phosphorylated and hepcidin induction was still appreciable, although to a lesser extent as compared with the control mice. In conclusion, our study indicates that hepcidin induction by ER stress involves the central regulatory SMAD1/5 pathway. C1 [Canali, Susanna; Vecchi, Chiara; Garuti, Cinzia; Montosi, Giuliana; Pietrangelo, Antonello] Univ Modena & Reggio Emilia, Univ Hosp Modena, Ctr Hemochromatosis, I-41100 Modena, Italy. [Canali, Susanna; Babitt, Jodie L.] Harvard Med Sch, Massachusetts Gen Hosp, Program Anemia Signaling Res, Div Nephrol,Program Membrane Biol,Ctr Syst Biol, Boston, MA 02114 USA. RP Pietrangelo, A (reprint author), Univ Hosp Modena, Div Internal Med 2, Via Pozzo 71, I-41100 Modena, Italy.; Pietrangelo, A (reprint author), Univ Hosp Modena, Ctr Hemochromatosis, Dept Med & Surg Sci Children & Adults, Via Pozzo 71, I-41100 Modena, Italy. EM antonello.pietrangelo@unimore.it RI Pietrangelo, Antonello/K-1517-2016; Vecchi, Chiara/C-1552-2014 OI Pietrangelo, Antonello/0000-0002-7411-935X; FU Telethon Grant [GGP14285]; National Institutes of Health [R01-DK087727] FX This work was supported by the Telethon Grant GGP14285 (to A.P.) and by National Institutes of Health Grant R01-DK087727 (to J.L.B.). NR 45 TC 1 Z9 1 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 OCT PY 2016 VL 157 IS 10 BP 3935 EP 3945 DI 10.1210/en.2016-1258 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ7QT UT WOS:000386061800025 PM 27483343 ER PT J AU Song, L Papaioannou, G Zhao, H Luderer, HF Miller, C Dall'Osso, C Nazarian, RM Wagers, AJ Demay, MB AF Song, Lige Papaioannou, Garyfallia Zhao, Hengguang Luderer, Hilary F. Miller, Christine Dall'Osso, Claudia Nazarian, Rosalynn M. Wagers, Amy J. Demay, Marie B. TI The Vitamin D Receptor Regulates Tissue Resident Macrophage Response to Injury SO ENDOCRINOLOGY LA English DT Article ID DENDRITIC CELLS; KNOCKOUT MICE; SELF-RENEWAL; ADULT LIFE; NULL MICE; ACTIVATION; DIFFERENTIATION; ALOPECIA; REPAIR; STATE AB Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status. Wound cytokine analyses demonstrated a decrease in macrophage colony-stimulating factor (M-CSF) protein levels in VDR KO mice. Consistent with this, induction of M-CSF gene expression by TGF beta and 1,25-dihydroxyvitamin D was impaired in dermal fibroblasts isolated from VDRKO mice. Because M-CSF is important for macrophage self-renewal, studies were performed to evaluate the response of tissue resident macrophages to this cytokine. A decrease in M-CSF induced proliferation and cyclin D1 expression was observed in peritoneal resident macrophages isolated from VDR KO mice, suggesting an intrinsic macrophage abnormality. Consistent with this, wound-healing assays in mice with macrophage-specific VDR ablation demonstrate that a normal wound microenvironment cannot compensate for the absence of the VDR in macrophages and thus confirm a critical role for the macrophage VDR in the inflammatory response to injury. C1 [Song, Lige; Papaioannou, Garyfallia; Zhao, Hengguang; Luderer, Hilary F.; Demay, Marie B.] Harvard Med Sch, Massachusetts Gen Hosp, Endocrine Unit, Thier 11,50 Blossom St, Boston, MA 02114 USA. [Nazarian, Rosalynn M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Miller, Christine; Dall'Osso, Claudia; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Demay, MB (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Endocrine Unit, Thier 11,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR066261]; National Institutes of Health [R01DK46974, UO1 HL100402]; Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases P30 Core facility (Grant AR066261) and by grants from the National Institutes of Health (Grant R01DK46974) (to M.B.D.) and (Grant UO1 HL100402) (to A.J.W.). H.Z. was supported by a Research Fellowship from the Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University. A.J.W. is an Early Career Scientist of Howard Hughes Medical Institute. NR 56 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 OCT PY 2016 VL 157 IS 10 BP 4066 EP 4075 DI 10.1210/en.2016-1474 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ7QT UT WOS:000386061800037 PM 27526034 ER PT J AU Razzak, A Smith, D Zahid, M Papachristou, G Khalid, A AF Razzak, Anthony Smith, Dineen Zahid, Maliha Papachristou, Georgios Khalid, Asif TI Effect of quality metric monitoring and colonoscopy performance SO ENDOSCOPY INTERNATIONAL OPEN LA English DT Article ID INCREASED ADENOMA DETECTION; SCREENING COLONOSCOPY; WITHDRAWAL TIMES; DETECTION RATES; FOLLOW-UP; CANCER; PROGRAM; INDICATORS; MORTALITY; IMPACT AB Background and aims: Adenoma detection rate (ADR) and cecal withdrawal time (CWT) have been identified as measures of colonoscopy quality. This study evaluates the impact of monitoring these measures on provider performance. Methods: Six blinded gastroenterologists practicing at a Veterans Affairs Medical Center were prospectively monitored over 9 months. Data for screening, adenoma surveillance, and fecal occult blood test positive (FOBT+) indicated colonoscopies were obtained, including exam preparation quality, cecal intubation rate, CWT, ADR, adenomas per colonoscopy (APC), and adverse events. Metrics were continuously monitored after a period of informed CWT monitoring and informed CWT+ADR monitoring. The primary outcome was impact on ADR and APC. Results: A total of 1671 colonoscopies were performed during the study period with 540 before informed monitoring, 528 during informed CWT monitoring, and 603 during informed CWT+ADR monitoring. No statistically significant impact on ADR was noted across each study phase. Multivariate regression revealed a trend towards fewer adenomas removed during the CWT monitoring phase (OR=0.79; 95%CI 0.62-1.02, P=0.065) and a trend towards more adenomas removed during the CWT+ADR monitoring phase when compared to baseline (OR=1.26; 95%CI 0.99-1.61, P=0.062). Indication for examination and provider were significant predictors for higher APC. Provider-specific data demonstrated a direct relationship between high ADR performers and increased CWT. Conclusions: Monitoring quality metrics did not significantly alter colonoscopy performance across a small heterogeneous group of providers. Non-significant trends towards higher APC were noted with CWT+ADR monitoring. Providers with a longer CWT had a higher ADR. Further studies are needed to determine the impact of monitoring on colonoscopy performance. C1 [Razzak, Anthony; Papachristou, Georgios; Khalid, Asif] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Smith, Dineen] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Zahid, Maliha] Univ Pittsburgh, Pittsburgh, PA USA. RP Khalid, A (reprint author), M2,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 19 TC 0 Z9 0 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 2364-3722 EI 2196-9736 J9 ENDOSC INT OPEN JI Endosc. Int. Open PD OCT PY 2016 VL 4 IS 10 BP E1023 EP E1027 DI 10.1055/s-0042-110787 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA0XQ UT WOS:000386313200001 PM 27747273 ER PT J AU Richard, MLL Brandon, D Lou, N Sato, S Caldwell, T Nowling, TK Gilkeson, G Zhang, XK AF Richard, Mara L. Lennard Brandon, Danielle Lou, Ning Sato, Shuzo Caldwell, Tomika Nowling, Tamara K. Gilkeson, Gary Zhang, Xian K. TI Acetylation impacts Fli-1-driven regulation of granulocyte colony stimulating factor SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Cytokines; G-CSF; Fli-1; Gene regulation; Inflammation; Transcriptional factors ID FLI-1 TRANSCRIPTION FACTOR; DNA-BINDING; G-CSF; ETS FAMILY; NEUTROPHIL MOBILIZATION; RHEUMATOID-ARTHRITIS; DECREASED EXPRESSION; PROGENITOR CELLS; LUPUS NEPHRITIS; MRL/LPR MICE AB Fli-1 has emerged as a critical regulator of inflammatory mediators, including MCP-1, CCL5, and IL-6. The cytokine, granulocyte colony stimulating factor (G-CSF) regulates neutrophil precursor maturation and survival, and activates mature neutrophils. Previously, a significant decrease in neutrophil infiltration into the kidneys of Fli-1(+/-) lupusprone mice was observed. In this study, a significant decrease in G-CSF protein expression was detected in stimulated murine and human endothelial cells when expression of Fli-1 was inhibited. The murine G-CSF promoter contains numerous putative Fli-1 binding sites and several regions within the proximal promoter are significantly enriched for Fli-1 binding. Transient transfection assays indicate that Fli-1 drives transcription from the G-CSF promoter and mutation of the Fli-1 DNA binding domain resulted in a 94% loss of transcriptional activation. Mutation of a known acetylation site, led to a significant increase in G-CSF promoter activation. The histone acetyltransferases p300/CBP and p300/CBP associated factor (PCAF) significantly decrease Fli-1 specific activation of the G-CSF promoter. Thus, acetylation appears to be an important mechanism behind Fli-1 driven activation of the G-CSF promoter. These results further support the theory that Fli-1 plays a major role in the regulation of several inflammatory mediators, ultimately affecting inflammatory disease pathogenesis. C1 [Richard, Mara L. Lennard; Brandon, Danielle; Lou, Ning; Sato, Shuzo; Caldwell, Tomika; Nowling, Tamara K.; Gilkeson, Gary; Zhang, Xian K.] Med Univ South Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA. [Gilkeson, Gary; Zhang, Xian K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29464 USA. [Lou, Ning] Shandong Univ, Jinan Cent Hosp, Jinan, Shangdong, Peoples R China. RP Zhang, XK (reprint author), Med Univ South Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA.; Zhang, XK (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29464 USA. EM zhangjo@musc.edu FU National Institute of Health (NIAMS) [AR056670]; MUSC Multidisciplinary Clinical Research Center; American Association of Immunologists (AAI) FX The authors would like to thank Mercedes Zapata-Garcia for her technical support and Dr. Maria Trojanowska (Boston University, School of Medicine Arthritis Center, Boston, MA) who provided several expression vectors. This research study was supported by the National Institute of Health grant (NIAMS, AR056670 to X.K.Z.). This study was supported in part by a pilot project program from MUSC Multidisciplinary Clinical Research Center (X.K.Z.). M.L.R is a recipient of the Careers in Immunology Fellowship from the American Association of Immunologists (AAI) in 2015. Author contributions - M.L.R. and X.K.Z. conceived the study, designed the experiments, and prepared the manuscript, M.L.R. designed all of the primers, obtained or cloned the constructs used, and performed all of the transfection experiments, the LPS stimulated ChIP assay, and mRNA analysis, D.B. and N.L. performed the siRNA experiments and ELISA, S.S. and T.C. performed the ChIP assay, T.K.N. and G.G. contributed supplies, made suggestions regarding the experimental design and assisted in editing the final manuscript. NR 53 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2016 VL 46 IS 10 BP 2322 EP 2332 DI 10.1002/eji.201646315 PG 11 WC Immunology SC Immunology GA DZ9VV UT WOS:000386229600006 ER PT J AU Kousoulis, A Mylonas, K Economopoulos, K AF Kousoulis, Antonis A. Mylonas, Konstantinos S. Economopoulos, Konstantinos P. TI Violent death and trauma in Norse mythology: a systematic reading of the Prose Edda SO EUROPEAN SURGERY-ACTA CHIRURGICA AUSTRIACA LA English DT Article DE Trauma; Death; Prose Edda; Medical history; Medical education & training ID HOMERS ILIAD; INJURIES AB Background This paper attempts to assess surgical knowledge presented in Norse mythology. The Prose Edda constitutes the most comprehensive source of Norse mythology. Literature and myth offer unique educational insights into life practices of previous eras, provided approached with a cautious and unbiased perspective. Methods English translations of Gylfaginning and Skaldskaparmal, texts from the Prose Edda, were systematically reviewed. International Statistical Classification of Diseases and Related Health Problems, 10th edition (ICD-10) definitions for trauma and violent death were utilized. A basic tabulation was followed for the recording of extracted data, including the chapter, characters involved and the text extract. Recorded cases were categorized by applying three distinct classifications and assessed by body part affected, cause of morbidity/mortality and character involved. Results A total of 52 cases of trauma were identified (19 cases in Gylfaginning and 33 in Skaldskaparsmal). In 27 cases of injury the afflicted body region was unspecified, but in the majority of specified cases it concerned a craniofacial trauma. 37 events were an outcome of personal assault, whereas 11 occurred during warfare. Moreover, three cases were suicides and one an accident. Critical assessment of the texts indicates that the predominant theme of Gylfaginning is the struggles of Norse Gods, whilst Skaldskaparmal tales revolve mostly around humans. Notably, a lack of allusion to medical knowledge and surgical practice is observed. Conclusion The systematic reading of the Prose Edda highlights the common theme of violence in Norse Mythology and distinguishes beheading in battle. The absence of documentation on medical practice is in accordance with the fact that Scandinavian mythological texts rarely elaborate on disease. C1 [Kousoulis, Antonis A.; Mylonas, Konstantinos S.; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Kousoulis, Antonis A.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London, England. [Mylonas, Konstantinos S.] Aristotle Univ Thessaloniki, Sch Med, Fac Hlth Sci, Thessaloniki, Greece. [Economopoulos, Konstantinos P.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Mylonas, K (reprint author), Aristotle Univ Thessaloniki, Sch Med, Fac Hlth Sci, Thessaloniki, Greece. EM ksmylonas@gmail.com OI Mylonas, Konstantinos/0000-0002-2356-6694 NR 14 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1682-8631 EI 1682-4016 J9 EUR SURG JI Eur. Surg. PD OCT PY 2016 VL 48 IS 5 BP 304 EP 310 DI 10.1007/s10353-016-0438-9 PG 7 WC Surgery SC Surgery GA EA1WH UT WOS:000386382300009 ER PT J AU Sarosiek, KA Letai, A AF Sarosiek, Kristopher A. Letai, Anthony TI Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise SO FEBS JOURNAL LA English DT Review DE apoptosis; BCL-2 family; chemotherapy; mitochondria; targeted therapy; therapeutics ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BCL-2 FAMILY PROTEINS; ACUTE LYMPHOBLASTIC-LEUKEMIA; SELECTIVE SMALL-MOLECULE; INDUCE APOPTOSIS; MEMBRANE PERMEABILIZATION; ANTISENSE THERAPY; ABT-199 GDC-0199; PI3K INHIBITORS AB Apoptosis within cancer cells is controlled by the BCL-2 family of proteins, making them powerful arbiters of cell fate in response to stress induced by neoplastic transformation as well as exposure to anti-cancer therapies. Many cancers evade pro-apoptotic stress signals by up-regulating anti-apoptotic proteins such as BCL-2, BCL-X-L or MCL-1 to maintain their survival. However, this may come at a cost, as these cancers may also become dependent on these anti-apoptotic proteins for survival. The development and deployment of BCL-2 family inhibitors (drugs that mimic the activity of pro-apoptotic BH3-only proteins or BH3 mimetics') is based on this paradigm, and the first potent and specific molecules are now being evaluated in clinical trials. We review the recent successes in this field, the challenges currently being faced, and the promising future ahead. C1 [Sarosiek, Kristopher A.; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer 430, Boston, MA 02115 USA. [Sarosiek, Kristopher A.; Letai, Anthony] Harvard Med Sch, Boston, MA USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer 430, Boston, MA 02115 USA. EM Anthony_Letai@dfci.harvard.edu FU American Cancer Society [121360-PF-11-256-01-TBG]; Alex's Lemonade Stand Foundation for Childhood Cancers Young Investigator Award; US National Institutes of Health [K99CA188679, RO1CA129974]; AbbVie FX We are grateful to the many researchers who contributed to our understanding of apoptosis as well as cancer biology and therapeutics, and apologize that we could not cite all of the relevant research due to space restrictions. We would like to acknowledge funding from the American Cancer Society Postdoctoral Fellowship 121360-PF-11-256-01-TBG (to K.A.S.) and an Alex's Lemonade Stand Foundation for Childhood Cancers Young Investigator Award (to K.A.S.), as well as grants K99CA188679 and RO1CA129974 from the US National Institutes of Health to K.A.S. and A.L., respectively. A.L. was a Leukemia and Lymphoma Society scholar. A.L. has received payment for consulting and his laboratory has received research sponsorship from AbbVie. NR 92 TC 5 Z9 5 U1 11 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD OCT PY 2016 VL 283 IS 19 BP 3523 EP 3533 DI 10.1111/febs.13714 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DZ7GU UT WOS:000386033700002 PM 26996748 ER PT J AU Schure, MB Goins, RT AF Schure, Marc B. Goins, R. Turner TI An Examination of the Disablement Process Among Older American Indians: The Native Elder Care Study SO GERONTOLOGIST LA English DT Article DE Disablement process; American Indians; Structural equation modeling ID CHRONIC PAIN; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; DISABILITY; ADULTS; HEALTH; PREDICTORS; IMPACT; RACE; INTERVENTIONS AB Purpose of the Study: Older American Indians disproportionately suffer from poorer physical and mental health and have greater disability compared to their racial and ethnic counterparts. The purpose of this study was to examine the disablement process among older American Indians. Design and Methods: Data analyzed were from the Native Elder Care Study, which included in-person interviews with 505 community-dwelling American Indians aged >= 55 years. We used structural equation modeling to examine the contributive direct and indirect effects of health, demographic, and psychosocial risk factors on disability. Results: Pathology had direct and indirect effects through social support and depressive symptoms on chronic pain intensity. Pathology also had direct and indirect effects on disability. Chronic pain intensity was a significant mediator between pathology and functional limitations. With contributive effects of older age and female sex, greater functional limitations were associated with increased disability. Implications: Our results support the theorized main pathway of the Disablement Process Model with our sample of older American Indians. Our findings support the importance of taking into account intra and extraindividual factors in assessing the prevalence and incidence of disability for older American Indians. C1 [Schure, Marc B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Goins, R. Turner] Western Carolina Univ, Coll Hlth & Human Sci, Dept Social Work, Cullowhee, NC 28723 USA. RP Schure, MB (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. EM Mark.Schure@va.gov NR 48 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2016 VL 56 IS 5 BP 948 EP 955 DI 10.1093/geront/gnv001 PG 8 WC Gerontology SC Geriatrics & Gerontology GA DZ7XI UT WOS:000386081600018 PM 26035880 ER PT J AU Razavi, P Ravicz, ME Dobrev, I Cheng, JT Furlong, C Rosowski, JJ AF Razavi, Payam Ravicz, Michael E. Dobrev, Ivo Cheng, Jeffrey Tao Furlong, Cosme Rosowski, John J. TI Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 7th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO) CY JUL 01-05, 2015 CL Aalborg, DENMARK DE Tympanic membrane; Transient response; Click response; Mechanical impulse; Impulse response; Human ID TIME-AVERAGED HOLOGRAPHY; MIDDLE-EAR TRANSMISSION; STROBOSCOPIC HOLOGRAPHY; MOTION; VIBRATIONS; SURFACE; EARDRUM AB The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 mu s for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. (C) 2016 Elsevier B.V. All rights reserved. C1 [Razavi, Payam; Dobrev, Ivo; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA. [Ravicz, Michael E.; Cheng, Jeffrey Tao; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Ravicz, Michael E.; Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Ravicz, ME (reprint author), Mass Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mike_ravicz@meei.harvard.edu FU NIDCD NIH HHS [R01 DC008642] NR 32 TC 2 Z9 2 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 OCT PY 2016 VL 340 BP 15 EP 24 DI 10.1016/j.heares.2016.01.019 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA EA2JF UT WOS:000386417900003 PM 26880098 ER PT J AU Chhan, D Bowers, P McKinnon, ML Rosowski, JJ AF Chhan, David Bowers, Peter McKinnon, Melissa L. Rosowski, John J. TI Middle-ear and inner-ear contribution to bone conduction in chinchilla: The development of Carhart's notch SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 7th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO) CY JUL 01-05, 2015 CL Aalborg, DENMARK DE Bone conduction; Chinchilla; Intracochlear sound pressures; Carhart's notch ID PRESSURE MEASUREMENTS; COCHLEAR AQUEDUCT; INPUT IMPEDANCE; ROUND-WINDOW; GUINEA-PIGS; AIR; SOUND; STIMULATION; ADMITTANCE; HEARING AB While the cochlea is considered the primary site of the auditory response to bone conduction (BC) stimulation, the paths by which vibratory energy applied to the skull (or other structures) reaches the inner ear are a matter of continued investigation. We present acoustical measurements of sound in the inner ear that separate out the components of BC stimulation that excite the inner ear via ossicular motion (compression of the walls of the ear canal or ossicular inertia) from the components that act directly on the cochlea (cochlear compression or inertia, and extra-cochlear 'third-window' pathways). The results are consistent with our earlier suggestion that the inner-ear mechanisms play a large role in bone-conduction stimulation in the chinchilla at all frequencies. However, the data also suggest the pathways that conduct vibration to the inner ear via ossicular-motion make a significant contribution to the response to BC stimulation in the 1-3 kHz range, such that interruption of these path leads to a 5 dB reduction in total stimulation in that frequency range. The mid-frequency reduction produced by ossicular manipulations is similar to the 'Carhart's notch' phenomenon observed in otology and audiology clinics in cases of human ossicular disorders. We also present data consistent with much of the ossicular-conducted sound in chinchilla depending on occlusion of the ear canal. (C) 2016 Elsevier B.V. All rights reserved. C1 [Chhan, David; Bowers, Peter; McKinnon, Melissa L.; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab, 243 Charles St, Boston, MA 02476 USA. [Bowers, Peter; Rosowski, John J.] Harvard Med Sch, Div Med Sci, Speech & Hearing Biosci & Technol Program, Boston, MA 02115 USA. [Rosowski, John J.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02476 USA. EM John_Rosowski@meei.harvard.edu FU NIDCD NIH HHS [T32 DC000038, R01 DC000194] NR 32 TC 2 Z9 2 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 OCT PY 2016 VL 340 BP 144 EP 152 DI 10.1016/j.heares.2016.02.015 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA EA2JF UT WOS:000386417900018 PM 26923425 ER PT J AU Kozin, ED Black, NL Cheng, JT Cotler, MJ McKenna, MJ Lee, DJ Lewis, JA Rosowski, JJ Remenschneider, AK AF Kozin, Elliott D. Black, Nicole L. Cheng, Jeffrey T. Cotler, Max J. McKenna, Michael J. Lee, Daniel J. Lewis, Jennifer A. Rosowski, John J. Remenschneider, Aaron K. TI Design, fabrication, and in vitro testing of novel three-dimensionally printed tympanic membrane grafts. SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 7th International Symposium on Middle Ear Mechanics in Research and Otology (MEMRO) CY JUL 01-05, 2015 CL Aalborg, DENMARK DE Tympanic membrane; 3D printing; Holography; Tympanoplasty; Biomimetic; Tissue engineering ID TIME-AVERAGED HOLOGRAPHY; CHRONIC EAR SURGERY; STROBOSCOPIC HOLOGRAPHY; BIOMEDICAL APPLICATIONS; THICKNESS DISTRIBUTION; HYDROGEL SCAFFOLDS; SOUND-TRANSMISSION; FIBER ARRANGEMENT; DRUG-DELIVERY; CARTILAGE AB The tympanic membrane (TM) is an exquisite structure that captures and transmits sound from the environment to the ossicular chain of the middle ear. The creation of TM grafts by multi-material three-dimensional (3D) printing may overcome limitations of current graft materials, e.g. temporalis muscle fascia, used for surgical reconstruction of the TM. TM graft scaffolds with either 8 or 16 circumferential and radial filament arrangements were fabricated by 3D printing of polydimethylsiloxane (PDMS), flexpolyactic acid (PIA) and polycaprolactone (PCL) materials followed by uniform infilling with a fibrin collagen composite hydrogel. Digital opto-electronic holography (DOEH) and laser Doppler vibrometry (LDV) were used to measure acoustic properties including surface motions and velocity of TM grafts in response to sound. Mechanical properties were determined using dynamic mechanical analysis (DMA). Results were compared to fresh cadaveric human TMs and cadaveric temporalis fascia. Similar to the human TM, TM grafts exhibit simple surface motion patterns at lower frequencies (400 Hz), with a limited number of displacement maxima. At higher frequencies (>1000 Hz), their displacement patterns are highly organized with multiple areas of maximal displacement separated by regions of minimal displacement. By contrast, temporalis fascia exhibited asymmetric and less regular holographic patterns. Velocity across frequency sweeps (0.2-10 kHz) measured by LDV demonstrated consistent results for 3D printed grafts, while velocity for human fascia varied greatly between specimens. TM composite grafts of different scaffold print materials and varied filament count (8 or 16) displayed minimal, but measurable differences in DOEH and LDV at tested frequencies. TM graft mechanical load increased with higher filament count and is resilient over time, which differs from temporalis fascia, which loses over 70% of its load bearing properties during mechanical testing. This study demonstrates the design, fabrication and preliminary in vitro acoustic and mechanical evaluation of 3D printed TM grafts. Data illustrate the feasibility of creating TM grafts with acoustic properties that reflect sound induced motion patterns of the human TM; furthermore, 3D printed grafts have mechanical properties that demonstrate increased resistance to deformation compared to temporalis fascia. (C) 2016 Elsevier B.V. All rights reserved. C1 [Kozin, Elliott D.; Cheng, Jeffrey T.; McKenna, Michael J.; Lee, Daniel J.; Rosowski, John J.; Remenschneider, Aaron K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02118 USA. [Kozin, Elliott D.; Cheng, Jeffrey T.; McKenna, Michael J.; Lee, Daniel J.; Rosowski, John J.; Remenschneider, Aaron K.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02118 USA. [Kozin, Elliott D.; Cheng, Jeffrey T.; McKenna, Michael J.; Lee, Daniel J.; Rosowski, John J.; Remenschneider, Aaron K.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Black, Nicole L.; Cotler, Max J.; Lewis, Jennifer A.] Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Black, Nicole L.; Cotler, Max J.; Lewis, Jennifer A.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. RP Remenschneider, AK (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02118 USA. EM Aaron_Remenschneider@meei.harvard.edu OI Gaihede, Michael/0000-0001-6998-2506 NR 69 TC 1 Z9 1 U1 17 U2 17 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 OCT PY 2016 VL 340 BP 191 EP 203 DI 10.1016/j.heares.2016.03.005 PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA EA2JF UT WOS:000386417900024 PM 26994661 ER PT J AU Dubin, RF Guajardo, I Ayer, A Mills, C Donovan, C Beussink, L Scherzer, R Ganz, P Shah, SJ AF Dubin, Ruth F. Guajardo, Isabella Ayer, Amrita Mills, Claire Donovan, Catherine Beussink, Lauren Scherzer, Rebecca Ganz, Peter Shah, Sanjiv J. TI Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease SO HYPERTENSION LA English DT Article DE cardiovascular disease; echocardiography; heart failure ID PRESERVED EJECTION FRACTION; FLOW-MEDIATED VASODILATATION; HEART-FAILURE; HEMODIALYSIS-PATIENTS; ASYMMETRIC DIMETHYLARGININE; DEPENDENT VASODILATION; CARDIOVASCULAR-DISEASE; DIETARY PHOSPHORUS; SYSTOLIC FUNCTION; MASS AB Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. To evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle-tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral of hyperemic blood flow after cuff deflation. Impaired flow-mediated dilation was associated with higher left ventricular mass, independently of age and blood pressure: per 2-fold lower flow-mediated dilation, left ventricular mass was 4.1% higher (95% confidence interval, 0.49-7.7; P=0.03). After adjustment for demographics, blood pressure, comorbidities, and medications, a 2-fold lower velocity time integral was associated with 9.5% higher E/e ratio (95% confidence interval, 1.0-16; P=0.03) and 6.7% lower absolute right ventricular longitudinal strain (95% confidence interval, 2.0-12; P=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. C1 [Dubin, Ruth F.; Guajardo, Isabella; Ayer, Amrita; Scherzer, Rebecca] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Mills, Claire; Donovan, Catherine; Ganz, Peter] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Vasc Excellence, Div Cardiol, San Francisco, CA USA. [Beussink, Lauren; Shah, Sanjiv J.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. RP Dubin, RF (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM ruth.dubin@ucsf.edu FU National Institutes of Health [K23 DK092354, R03 DK104013]; University of California, San Francisco (UCSF); National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 TR000004]; [R01 HL107577]; [R01 HL127028] FX National Institutes of Health (K23 DK092354 and R03 DK104013 [to R.F.D.]; University of California, San Francisco (UCSF) Resource Allocation Program Pilot Grant for Junior Investigators [to R.F.D.]; and R01 HL107577 and R01 HL127028 [to S.J.S.]). This project was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004. NR 42 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD OCT PY 2016 VL 68 IS 4 BP 913 EP 920 DI 10.1161/HYPERTENSIONAHA.116.07489 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX1LB UT WOS:000384127800018 PM 27550915 ER PT J AU Le, M Delingette, H Kalpathy-Cramer, J Gerstner, ER Batchelor, T Unkelbach, J Ayache, N AF Le, Matthieu Delingette, Herve Kalpathy-Cramer, Jayashree Gerstner, Elizabeth R. Batchelor, Tracy Unkelbach, Jan Ayache, Nicholas TI MRI Based Bayesian Personalization of a Tumor Growth Model SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bayesian; glioblastoma; LBM; monte carlo; personalization; reaction-diffusion; tumor growth ID CARDIAC ELECTROPHYSIOLOGY; MATHEMATICAL-MODEL; GLIOMA GROWTH; BRAIN-TUMORS; SEGMENTATION; ANGIOGENESIS; RADIOTHERAPY; DIFFUSION; IMAGES; REGISTRATION AB The mathematical modeling of brain tumor growth has been the topic of numerous research studies. Most of this work focuses on the reaction-diffusion model, which suggests that the diffusion coefficient and the proliferation rate can be related to clinically relevant information. However, estimating the parameters of the reaction-diffusion model is difficult because of the lack of identifiability of the parameters, the uncertainty in the tumor segmentations, and the model approximation, which cannot perfectly capture the complex dynamics of the tumor evolution. Our approach aims at analyzing the uncertainty in the patient specific parameters of a tumor growth model, by sampling from the posterior probability of the parameters knowing the magnetic resonance images of a given patient. The estimation of the posterior probability is based on: 1) a highly parallelized implementation of the reaction-diffusion equation using the Lattice Boltzmann Method (LBM), and 2) a high acceptance rate Monte Carlo technique called Gaussian Process Hamiltonian Monte Carlo (GPHMC). We compare this personalization approach with two commonly used methods based on the spherical asymptotic analysis of the reaction-diffusion model, and on a derivative-free optimization algorithm. We demonstrate the performance of the method on synthetic data, and on seven patients with a glioblastoma, the most aggressive primary brain tumor. This Bayesian personalization produces more informative results. In particular, it provides samples from the regions of interest and highlights the presence of several modes for some patients. In contrast, previous approaches based on optimization strategies fail to reveal the presence of different modes, and correlation between parameters. C1 [Le, Matthieu; Delingette, Herve; Ayache, Nicholas] Inria Sophia Antipolis, Asclepios Project, F-06902 Sophia Antipolis, France. [Kalpathy-Cramer, Jayashree] Harvard Mit Div Hlth Sci & Technol, Martinos Ctr Biomed Imaging, Charlestown, MA 02139 USA. [Gerstner, Elizabeth R.; Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan] Harvard Med Sch, Boston, MA 02114 USA. RP Le, M (reprint author), Inria Sophia Antipolis, Asclepios Project, F-06902 Sophia Antipolis, France. EM matthieu.le@inria.fr FU European Research Council through the ERC Advanced Grant MedYMA [2011-291080] FX Part of this work was funded by the European Research Council through the ERC Advanced Grant MedYMA 2011-291080. Asterisk indicates corresponding author. NR 49 TC 0 Z9 0 U1 9 U2 9 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 OCT PY 2016 VL 35 IS 10 BP 2329 EP 2339 DI 10.1109/TMI.2016.2561098 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 DZ6PU UT WOS:000385985200012 PM 27164582 ER PT J AU Thomas, JJ Murray, HB AF Thomas, Jennifer J. Murray, Helen B. TI Cognitive-behavioral treatment of adult rumination behavior in the setting of disordered eating: A single case experimental design SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE rumination disorder; binge eating; DSM-5; single case experimental design; diaphragmatic breathing ID BULIMIA NERVOSA; PICA AB The integration of feeding and eating disorders into a single DSM-5 chapter introduces an opportunity to explore common mechanisms and transdiagnostic treatment approaches. In contrast to a robust literature on the evidence-based treatment of eating disorders, very few data guide the treatment of rumination disorder (RD). In a single case experimental design, we describe the treatment of a 27-year-old woman who presented to an eating-disorder clinic with a 15-year history of untreated rumination and intermittent binge eating. According to time series analysis, she reduced rumination frequency at trend-level during the initial baseline phase (self-monitoring only), and exhibited significant reductions during the active intervention phase (self-monitoring+cognitive-behavioral techniques including diaphragmatic breathing and behavioral experimentation). She maintained these gains at 23 weeks post-intervention. Although more rigorous systematic investigation is needed, these data suggest that selected cognitive and behavioral techniques already familiar to eating-disorder clinicians may have heuristic value for RD treatment. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:967-972) C1 [Thomas, Jennifer J.; Murray, Helen B.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Thomas, Jennifer J.] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. [Murray, Helen B.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA.; Thomas, JJ (reprint author), Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. EM jjthomas@mgh.harvard.edu NR 16 TC 1 Z9 1 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD OCT PY 2016 VL 49 IS 10 BP 967 EP 972 DI 10.1002/eat.22566 PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA DZ9VG UT WOS:000386227700009 PM 27302894 ER PT J AU Irvine, HJ Battey, TWK Ostwaldt, AC Campbell, BCV Davis, SM Donnan, GA Sheth, KN Kimberly, WT AF Irvine, Hannah J. Battey, Thomas W. K. Ostwaldt, Ann-Christin Campbell, Bruce C. V. Davis, Stephen M. Donnan, Geoffrey A. Sheth, Kevin N. Kimberly, W. Taylor TI Early neurological stability predicts adverse outcome after acute ischemic stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE Outcome; secondary neurological injury; ischemic stroke; magnetic resonance image; edema; deterioration ID INTRAVENOUS THROMBOLYSIS; TRANSCRANIAL DOPPLER; CLINICAL DETERIORATION; RISK-FACTORS; RECANALIZATION; REPERFUSION; THERAPY; RECOVERY; TRIAL; MULTICENTER AB Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (NIHSS4), early neurological recovery (NIHSS-4) or early neurological stability (NIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale=0-2) at 3 months compared to those with early neurological recovery (P<0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery (P=0.03; P<0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion (P<0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors. C1 [Irvine, Hannah J.; Battey, Thomas W. K.; Ostwaldt, Ann-Christin; Kimberly, W. Taylor] Massachusetts Gen Hosp, Ctr Human Genet Res, 55 Fruit St,Lunder 644, Boston, MA 02114 USA. [Irvine, Hannah J.; Battey, Thomas W. K.; Ostwaldt, Ann-Christin; Kimberly, W. Taylor] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, 55 Fruit St,Lunder 644, Boston, MA 02114 USA. [Campbell, Bruce C. V.; Davis, Stephen M.] Univ Melbourne, Dept Med & Neurol, Parkville, Vic, Australia. [Campbell, Bruce C. V.; Donnan, Geoffrey A.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. [Sheth, Kevin N.] Yale New Haven Med Ctr, Div Neurocrit Care & Emergency Neurol, 20 York St, New Haven, CT 06504 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. RP Kimberly, WT (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 55 Fruit St,Lunder 644, Boston, MA 02114 USA.; Kimberly, WT (reprint author), Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, 55 Fruit St,Lunder 644, Boston, MA 02114 USA. EM wtkimberly@mgh.harvard.edu FU NINDS NIH HHS [K23 NS076597] NR 32 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 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD OCT PY 2016 VL 11 IS 8 SI SI BP 882 EP 889 DI 10.1177/1747493016654484 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DZ6YI UT WOS:000386008400012 PM 27334760 ER PT J AU Schlunk, F Chang, YC Ayres, A Battey, T Vashkevich, A Raffeld, M Rost, N Viswanathan, A Gurol, ME Schwab, K Greenberg, SM Rosand, J Goldstein, JN AF Schlunk, Frieder Chang, Yuchiao Ayres, Alison Battey, Thomas Vashkevich, Anastasia Raffeld, Miriam Rost, Natalia Viswanathan, Anand Gurol, M. Edip Schwab, Kristin Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Blood pressure burden and outcome in warfarin-related intracerebral hemorrhage SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE Stroke; warfarin; intracerebral hemorrhage; blood pressure; stroke subtype ID STROKE ACUTE MANAGEMENT; RISK-FACTOR ASSESSMENT; HEMATOMA EXPANSION; ANTIHYPERTENSIVE-TREATMENT; CLINICAL-OUTCOMES; ARTERIAL-PRESSURE; REDUCTION; TRIAL; ANTICOAGULATION; VARIABILITY AB Background and purpose Blood pressure reduction is a promising intervention for acute intracerebral hemorrhage, but clinical trials of this treatment often exclude those with anticoagulant-associated intracerebral hemorrhage, leaving it unclear whether this population might benefit. We examined whether persistently elevated blood pressure values (blood pressure burden) over the first 24h are associated with hematoma expansion and mortality in anticoagulant-associated intracerebral hemorrhage. Methods We retrospectively identified consecutive patients with primary anticoagulant-associated intracerebral hemorrhage (warfarin anticoagulation) who presented within 6h after symptom onset and a matched set of non-anticoagulant-associated intracerebral hemorrhage patients. Associations between 24h blood pressure burden, hematoma expansion, and mortality were evaluated using univariable and multivariable logistic regression. Results Sixty-nine anticoagulant-associated intracerebral hemorrhage and 69 matched non-anticoagulant-associated intracerebral hemorrhage patients were included. Hematoma expansion occurred in 25 anticoagulant-associated intracerebral hemorrhage patients (36%) and 15 control patients (22 %; p=0.091). Twenty-four-hour blood pressure burden was in fact lower in anticoagulant-associated intracerebral hemorrhage than in non-anticoagulant-associated intracerebral hemorrhage patients (p=0.033). No association was found in anticoagulant-associated intracerebral hemorrhage and non-anticoagulant-associated intracerebral hemorrhage between BP burden, hematoma expansion, and 30-day mortality. Conclusion We found no evidence that higher 24h blood pressure burden is associated with hematoma expansion or mortality in anticoagulant-associated intracerebral hemorrhage. C1 [Schlunk, Frieder; Ayres, Alison; Battey, Thomas; Vashkevich, Anastasia; Raffeld, Miriam; Rost, Natalia; Viswanathan, Anand; Gurol, M. Edip; Schwab, Kristin; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM JGOLDSTEIN@mgh.harvard.edu NR 30 TC 0 Z9 0 U1 2 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD OCT PY 2016 VL 11 IS 8 SI SI BP 898 EP 909 DI 10.1177/1747493016658300 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DZ6YI UT WOS:000386008400014 PM 27462095 ER PT J AU Cole, AJ AF Cole, Andrew J. TI Status Epilepticus and Brain Atrophy Shrinkage Is a Growing Problem SO JAMA NEUROLOGY LA English DT Editorial Material ID RISK C1 [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Cole, Andrew J.] Harvard Med Sch, Dept Neurol, Boston, MA USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Div Clin Neurophysiol, WACC, Ste 739-L Fruit St, Boston, MA 02114 USA. EM cole.andrew@mgh.harvard.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 OCT 1 PY 2016 VL 73 IS 10 BP 1182 EP 1183 DI 10.1001/jamaneurol.2016.2639 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DZ8LO UT WOS:000386122100005 PM 27532774 ER PT J AU Quinn, JF AF Quinn, Joseph F. TI Do omega-3 Fatty Acids Regulate Cerebral beta Amyloid? SO JAMA NEUROLOGY LA English DT Editorial Material ID DOCOSAHEXAENOIC ACID; ALZHEIMER-DISEASE; MOUSE MODEL; TRIAL; PATHOLOGY C1 [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. RP Quinn, JF (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM quinnj@ohsu.edu NR 13 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 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT 1 PY 2016 VL 73 IS 10 BP 1183 EP 1184 DI 10.1001/jamaneurol.2016.2534 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DZ8LO UT WOS:000386122100006 PM 27533600 ER PT J AU Mormino, EC Papp, KV Rentz, DM Schultz, AP LaPoint, M Amariglio, R Hanseeuw, B Marshall, GA Hedden, T Johnson, KA Sperling, RA AF Mormino, Elizabeth C. Papp, Kathryn V. Rentz, Dorene M. Schultz, Aaron P. LaPoint, Molly Amariglio, Rebecca Hanseeuw, Bernard Marshall, Gad A. Hedden, Trey Johnson, Keith A. Sperling, Reisa A. TI Heterogeneity in Suspected Non-Alzheimer Disease Pathophysiology Among Clinically Normal Older Individuals SO JAMA NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA; PART; DEMENTIA; DECLINE; NEURODEGENERATION; TAUOPATHY; PATHOLOGY; AD AB IMPORTANCE A substantial proportion of clinically normal (CN) older individuals are classified as having suspected non-Alzheimer disease pathophysiology (SNAP), defined as biomarker negative for beta-amyloid (A beta-) but positive for neurodegeneration (ND+). The etiology of SNAP in this population remains unclear. OBJECTIVE To determine whether CN individuals with SNAP show evidence of early Alzheimer disease (AD) processes (ie, elevated tau levels and/or increased risk for cognitive decline). DESIGN, SETTING, AND PARTICIPANTS This longitudinal observational study performed in an academic medical center included 247 CN participants from the Harvard Aging Brain Study. Participants were classified into preclinical AD stages using measures of A beta (Pittsburgh Compound B [PIB]-labeled positron emission tomography) and ND (hippocampal volume or cortical glucose metabolism from AD-vulnerable regions). Classifications included stages 0 (A beta-/ND-), 1 (A beta+/ND-), and 2 (A beta+/ND+) and SNAP (A beta-/ND+). Continuous levels of PiB and ND, tau levels in the medial and inferior temporal lobes, and longitudinal cognition were examined. Data collection began in 2010 and is ongoing. Data were analyzed from 2015 to 2016. MAIN OUTCOMES AND MEASURES Evidence of amyloid-independent tau deposition and/or cognitive decline. RESULTS Of the 247 participants (142 women [57.5%]; 105 men [42.5%]; mean age, 74 [range, 63-90] years), 64 (25.9%) were classified as having SNAP. Compared with the stage 0 group, the SNAP group was not more likely to have subthreshold PiB values (higher values within the A beta-range), suggesting that misclassification due to the PiB cutoff was not a prominent contributor to this group (mean [SD] distribution volume ratio, 1.08 [0.05] for the SNAP group; 1.09 [0.05] for the stage 1 group). Tau levels in the medial and inferior temporal lobes were indistinguishable between the SNAP and stage 0 groups (entorhinal cortex, beta = -0.005 [SE, 0.036]; parahippocampal gyrus, beta = -0.001 [SE, 0.027]; and inferior temporal lobe, beta = -0.004 [SE, 0.027]; P >= .88) and were lower in the SNAP group compared with the stage 2 group (entorhinal cortex, beta = -0.125 [SE, 0.041]; parahippocampal gyrus, beta = -0.074 [SE, 0.030]; and inferior temporal lobe, beta = -0.083 [SE, 0.031]; P <= .02). The stage 2 group demonstrated greater cognitive decline compared with all other groups (stage 0, beta = -0.239 [SE, 0.042]; stage 1, beta = -0.242 [SE, 0.051]; and SNAP, beta = -0.157 [SE, 0.044]; P <= .001), whereas the SNAP group showed a diminished practice effect over time compared with the stage 0 group (beta = -0.082 [SE, 0.037]; P = .03). CONCLUSIONS AND RELEVANCE In this study, clinically normal adults with SNAP did not exhibit evidence of elevated tau levels, which suggests that this biomarker construct does not represent amyloid-independent tauopathy. At the group level, individuals with SNAP did not show cognitive decline but did show a diminished practice effect. SNAP is likely heterogeneous, with a subset of this group at elevated risk for short-term decline. Future refinement of biomarkers will be necessary to subclassify this group and determine the biological correlates of ND markers among A beta-CN individuals. C1 [Mormino, Elizabeth C.; Papp, Kathryn V.; Rentz, Dorene M.; Schultz, Aaron P.; LaPoint, Molly; Amariglio, Rebecca; Hanseeuw, Bernard; Marshall, Gad A.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Papp, Kathryn V.; Rentz, Dorene M.; Amariglio, Rebecca; Marshall, Gad A.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Med Sch, Ctr Alzheimer Res & Treatment, Dept Neurol, Brigham & Womens Hosp, Boston, MA USA. [Schultz, Aaron P.; Hedden, Trey] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Schultz, Aaron P.; Hedden, Trey; Johnson, Keith A.; Sperling, Reisa A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Johnson, Keith A.] Harvard Med Sch, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA USA. RP Mormino, EC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM bmormino@nmr.mgh.harvard.edu FU NIH [P01 AG036694, R01 AG046396]; National Institute on Aging [F32AG044054, K24AG035007] FX The study was supported grants P01 AG036694 and R01 AG046396 from the NIH and grants F32AG044054 and K24AG035007 from the National Institute on Aging. NR 37 TC 2 Z9 2 U1 3 U2 3 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 OCT 1 PY 2016 VL 73 IS 10 BP 1185 EP 1191 DI 10.1001/jamaneurol.2016.2237 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DZ8LO UT WOS:000386122100007 PM 27548655 ER PT J AU Davis, MY Johnson, CO Leverenz, JB Weintraub, D Trojanowski, JQ Chen-Plotkin, A Van Deerlin, VM Quinn, JF Chung, KA Peterson-Hiller, AL Rosenthal, LS Dawson, T Albert, MS Goldman, JG Stebbins, GT Bernard, B Wszolek, ZK Ross, OA Dickson, DW Eidelberg, D Mattis, PJ Niethammer, M Yearout, D Hu, SC Cholerton, BA Smith, M Mata, IF Montine, TJ Edwards, KL Zabetian, CP AF Davis, Marie Y. Johnson, Catherine O. Leverenz, James B. Weintraub, Daniel Trojanowski, John Q. Chen-Plotkin, Alice Van Deerlin, Vivianna M. Quinn, Joseph F. Chung, Kathryn A. Peterson-Hiller, Amie L. Rosenthal, Liana S. Dawson, Tedm. Albert, Marilyn S. Goldman, Jennifer G. Stebbins, Glenn T. Bernard, Bryan Wszolek, Zbigniew K. Ross, Owen A. Dickson, Dennis W. Eidelberg, David Mattis, Paul J. Niethammer, Martin Yearout, Dora Hu, Shu-Ching Cholerton, Brenna A. Smith, Megan Mata, Ignacio F. Montine, Thomas J. Edwards, Karen L. Zabetian, Cyrus P. TI Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease SO JAMA NEUROLOGY LA English DT Article ID GLUCOCEREBROSIDASE MUTATIONS; GAUCHER-DISEASE; RATING-SCALE; IMPAIRMENT; COHORT AB IMPORTANCE Parkinson disease (PD) is heterogeneous in symptom manifestation and rate of progression. Identifying factors that influence disease progression could provide mechanistic insight, improve prognostic accuracy, and elucidate novel therapeutic targets. OBJECTIVE To determine whether GBA mutations and the E326K polymorphism modify PD symptom progression. DESIGN, SETTING, AND PARTICIPANTS The entire GBA coding region was screened for mutations and E326K in 740 patients with PD enrolled at 7 sites from the PD Cognitive Genetics Consortium. Detailed longitudinal motor and cognitive assessments were performed with patients in the on state. MAIN OUTCOMES AND MEASURES Linear regression was used to test for an association between GBA genotype and motor progression, with the Movement Disorder Society-sponsored version of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) score at the last assessment as the outcome and GBA genotype as the independent variable, with adjustment for levodopa equivalent dose, sex, age, disease duration, MDS-UPDRS III score at the first assessment, duration of follow-up, and site. Similar methods were used to examine the association between genotype and tremor and postural instability and gait difficulty (PIGD) scores. To examine the effect of GBA genotype on cognitive progression, patients were classified into those with conversion to mild cognitive impairment or dementia during the study (progression) and those without progression. The association between GBA genotype and progression status was then tested using logistic regression, adjusting for sex, age, disease duration, duration of follow-up, years of education, and site. RESULTS Of the total sample of 733 patients who underwent successful genotyping, 226 (30.8%) were women and 507 (69.2%) were men (mean [SD] age, 68.1 [8.8] years). The mean (SD) duration of follow-up was 3.0 (1.7) years. GBA mutations (beta = 4.65; 95% CI, 1.72-7.58; P = .002), E326K (beta = 3.42; 95% CI, 0.66-6.17; P = .02), and GBA variants combined as a single group (beta = 4.01; 95% CI, 1.95-6.07; P = 1.5 x 10(-4)) were associated with a more rapid decline in MDS-UPDRS III score. Combined GBA variants (beta = 0.38; 95% CI, 0.23-0.53; P = .01) and E326K (beta = 0.64; 95% CI, 0.43-0.86; P = .002) were associated with faster progression in PIGD scores, but not in tremor scores. A significantly higher proportion of E326K carriers (10 of 21 [47.6%]; P = .01) and GBA variant carriers (15 of 39 [38.5%]; P = .04) progressed to mild cognitive impairment or dementia. CONCLUSIONS AND RELEVANCE GBA variants predict a more rapid progression of cognitive dysfunction and motor symptoms in patients with PD, with a greater effect on PIGD than tremor. Thus, GBA variants influence the heterogeneity in symptom progression observed in PD. C1 [Davis, Marie Y.; Hu, Shu-Ching; Cholerton, Brenna A.; Mata, Ignacio F.; Zabetian, Cyrus P.] Puget Sound Hlth Care Syst, 1660 S Columbian Way,GRECC S-182, Seattle, WA 98108 USA. [Davis, Marie Y.; Johnson, Catherine O.; Yearout, Dora; Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.] Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Neurol Inst, Cleveland, OH 44106 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Chen-Plotkin, Alice] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson-Hiller, Amie L.] Portland VA Med Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson-Hiller, Amie L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Rosenthal, Liana S.; Dawson, Tedm.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neurodegenerat & Stem Cell Programs, Baltimore, MD USA. [Rosenthal, Liana S.; Dawson, Tedm.; Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Dawson, Tedm.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA. [Dawson, Tedm.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD USA. [Goldman, Jennifer G.; Stebbins, Glenn T.; Bernard, Bryan] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Ross, Owen A.; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Eidelberg, David; Mattis, Paul J.; Niethammer, Martin] Feinstein Inst Med Res, Ctr Neurosci, Manhasset, NY USA. [Eidelberg, David; Mattis, Paul J.] Northwell Hlth, Dept Neurol, Manhasset, NY USA. [Cholerton, Brenna A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA USA. [Smith, Megan; Edwards, Karen L.] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA. RP Zabetian, CP (reprint author), Puget Sound Hlth Care Syst, 1660 S Columbian Way,GRECC S-182, Seattle, WA 98108 USA. EM zabetian@u.washington.edu FU Department of Veterans Affairs [1I01BX000531]; Michael J. Fox Foundation; NIH [K23 NS060949, P50 NS038377, P50 NS053488, P50 NS062684, P50 NS071675, P50 NS072187, R01 NS035069, R01 NS065070]; Dolsen Foundation; Jane and Lee Seidman Fund FX This study was supported by grant 1I01BX000531 from the Department of Veterans Affairs, the Michael J. Fox Foundation, grants K23 NS060949, P50 NS038377, P50 NS053488, P50 NS062684, P50 NS071675, P50 NS072187, R01 NS035069, and R01 NS065070 from the NIH, the Dolsen Foundation, and the Jane and Lee Seidman Fund. NR 36 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT 1 PY 2016 VL 73 IS 10 BP 1217 EP 1224 DI 10.1001/jamaneurol.2016.2245 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DZ8LO UT WOS:000386122100011 PM 27571329 ER PT J AU Charidimou, A AF Charidimou, Andreas TI The Dark Matter of Cerebral Microbleeds: Implications for Thrombolysis and Other Clinical Scenarios SO JAMA NEUROLOGY LA English DT Letter ID INTRACEREBRAL HEMORRHAGE; METAANALYSIS; RISK C1 [Charidimou, Andreas] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Charidimou, Andreas] Harvard Med Sch, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. RP Charidimou, A (reprint author), Harvard Med Sch, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM andreas.charidimou.09@ucl.ac.uk 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 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD OCT 1 PY 2016 VL 73 IS 10 BP 1255 EP 1256 DI 10.1001/jamaneurol.2016.2948 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA DZ8LO UT WOS:000386122100023 PM 27533002 ER PT J AU Kaczkurkin, AN Asnaani, A Hall-Clark, B Peterson, AL Yarvis, JS Foa, EB AF Kaczkurkin, Antonia N. Asnaani, Anu Hall-Clark, Brittany Peterson, Alan L. Yarvis, Jeffrey S. Foa, Edna B. CA STRONG STAR Consortium TI Ethnic and racial differences in clinically relevant symptoms in active duty military personnel with posttraumatic stress disorder SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Race; Ethnicity; PTSD; Depression; Alcohol; Anger ID IDENTIFICATION TEST AUDIT; PSYCHOMETRIC PROPERTIES; AFRICAN-AMERICAN; ALCOHOL-USE; RACIAL/ETHNIC DIFFERENCES; SERVICE MEMBERS; COMBAT VETERANS; UNITED-STATES; WAR VETERANS; IRAQ WAR AB Previous research has shown racial/ethnic differences in Vietnam veterans on symptoms related to post traumatic stress disorder (PTSD). The current study explored racial/ethnic differences in PTSD symptoms and clinically relevant symptoms. Resilience and social support were tested as potential moderators of racial/ethnic differences in symptoms. The sample included 303 active duty male service members seeking treatment for PTSD. After controlling for age, education, military grade, and combat exposure, Hispanic/Latino and African American service members reported greater PTSD symptoms compared to non-Hispanic White service members. Higher alcohol consumption was endorsed by Hispanic/Latino service members compared to non-Hispanic White or African American service members, even after controlling for PTSD symptom severity. No racial/ethnic differences were found with regard to other variables. These results suggest that care should be made to thoroughly assess PTSD patients, especially those belonging to minority groups, for concurrent substance use problems that may impede treatment utilization or adherence. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Kaczkurkin, Antonia N.; Asnaani, Anu; Foa, Edna B.] Univ Penn, Dept Psychiat, 3535 Market St, Philadelphia, PA 19104 USA. [Hall-Clark, Brittany; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, 7400 Merton Minter, San Antonio, TX 78229 USA. [Peterson, Alan L.] Univ Texas San Antonio, 1 UTSA Circle, San Antonio, TX 78249 USA. [Yarvis, Jeffrey S.] Carl R Darnall Army Med Ctr, 36000 Darnall Loop, Ft Hood, TX 76544 USA. RP Kaczkurkin, AN (reprint author), Ctr Treatment & Study Anxiety, Dept Psychiat, 3535 Market St,Suite 600 North, Philadelphia, PA 19104 USA. EM antoniak@mail.med.upenn.edu; aasnaani@mail.med.upenn.edu; hallclark@uthscsa.edu; petersona3@uthscsa.edu; jeffrey.s.yarvis.mil@mail.mil; foa@mail.med.upenn.edu FU U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program [W81XWH-08-02-0111, W81XWH-08-02-109, W81XWH-08-02-0114] FX This study was conducted with support from the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program awards W81XWH-08-02-0111 (Edna B. Foa), W81XWH-08-02-109 (Alan L. Peterson), and W81XWH-08-02-0114 (Brett T. Litz). The views expressed in this article are solely those of the authors and do not reflect an endorsement by or the official policy of the U.S. Army, the Department of Defense, the Department of Veterans Affairs, or the U.S. Government. NR 59 TC 0 Z9 0 U1 9 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD OCT PY 2016 VL 43 BP 90 EP 98 DI 10.1016/j.janxdis.2016.09.004 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DZ8FQ UT WOS:000386106700011 PM 27639110 ER PT J AU Reisner, SL Hughto, JMW Gamarel, KE Keuroghlian, AS Mizock, L Pachankis, JE AF Reisner, Sari L. Hughto, Jaclyn M. White Gamarel, Kristi E. Keuroghlian, Alex S. Mizock, Lauren Pachankis, John E. TI Discriminatory Experiences Associated With Posttraumatic Stress Disorder Symptoms Among Transgender Adults SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE PTSD; discrimination; stigma; transgender ID FULLY CONDITIONAL SPECIFICATION; INTIMATE PARTNER VIOLENCE; NEW-YORK-CITY; COMMUNITY-HEALTH-CENTER; SCREEN PC-PTSD; 3 US CITIES; MENTAL-HEALTH; SUBSTANCE USE; YOUNG-ADULTS; PERCEIVED DISCRIMINATION AB Discrimination has been shown to disproportionately burden transgender people; however, there has been a lack of clinical attention to the mental health sequelae of discrimination, including posttraumatic stress disorder (PTSD) symptoms. Additionally, few studies contextualize discrimination alongside other traumatic stressors in predicting PTSD symptomatology. The current study sought to fill these gaps. A community-based sample of 412 transgender adults (mean age 33, SD = 13; 63% female-to-male spectrum; 19% people of color; 88% sampled online) completed a cross-sectional self-report survey of everyday discrimination experiences and PTSD symptoms. Multivariable linear regression models examined the association between self-reported everyday discrimination experiences, number of attributed domains of discrimination, and PTSD symptoms, adjusting for prior trauma, sociodemographics, and psychosocial comorbidity. The mean number of discrimination attributions endorsed was 4.8 (SD = 2.4) and the 5 most frequently reported reasons for discrimination were: gender identity and/or expression (83%), masculine and feminine appearance (79%), sexual orientation (68%), sex (57%), and age (44%). Higher everyday discrimination scores (beta = 0.25; 95% CL [0.21, 0.30]) and greater number of attributed reasons for discrimination experiences (beta = 0.05; 95% CL [0.01, 0.10]) were independently associated with PTSD symptoms, even after adjusting for prior trauma experiences. Everyday discrimination experiences from multiple sources necessitate clinical consideration in treatment for PTSD symptoms in transgender people. C1 [Reisner, Sari L.] Harvard Med Sch, Boston Childrens Hosp, Div Gen Pediat, Boston, MA USA. [Reisner, Sari L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Reisner, Sari L.; Hughto, Jaclyn M. White; Keuroghlian, Alex S.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Hughto, Jaclyn M. White; Pachankis, John E.] Yale Sch Publ Hlth, Chron Dis Epidemiol, New Haven, CT USA. [Gamarel, Kristi E.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Keuroghlian, Alex S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Mizock, Lauren] Worcester State Univ, Dept Psychol, Worcester, MA USA. RP Reisner, SL (reprint author), 300 Longwood Ave,Mailstop BCH 320, Boston, MA 02115 USA. EM sari.reisner@childrens.harvard.edu FU Miller Foundation; Fenway; NIMH [T32MH020031, P30MH062294, T32MH078788]; [NIMH R01MH094323] FX This project was partly supported with funding from the Miller Foundation and Fenway. Dr. Reisner is partly supported by Grant NIMH R01MH094323; Ms. White Hughto by NIMH T32MH020031 and P30MH062294; Dr. Gamarel by NIMH T32MH078788; Dr. Keu-roghlian by the Kraft Family National Center for Leadership & Training in Community Health. Funding sources had no role in study design, collection, data analysis and interpretation, article writing, or decision to submit for publication. The authors do not have any conflicts of interest. We thank our participants, outreach consultants (Lorelei Erisis, Maria Roman), and community partners: Massachusetts Transgender Political Coalition (MTPC); Jesse Begenyi, Mason Dunn, Gunner Scott, Devyn Shea); Boston Medical Center Health Care for the Homeless (Pam Klein, Rebecca Thal); Network/La Red (Tre'Andre Valentine); AIDS Project Worcester (Jesse Pack); Boston Glass (Tharyn Grant); Fenway staff (Emilia Dunham, Julia Coffey-Esquivel, Amaya Perez-Brumer, Angela Robertson, Nelisa Rash, Layla Stamper, Dana Pardee, Justice Williams, Anum Awan). NR 113 TC 4 Z9 4 U1 9 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 EI 1939-2168 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD OCT PY 2016 VL 63 IS 5 BP 509 EP 519 DI 10.1037/cou0000143 PG 11 WC Psychology, Educational; Psychology, Applied SC Psychology GA DZ7QR UT WOS:000386061500002 PM 26866637 ER PT J AU Sivak, WN Bourne, DA Miller, MP Manders, EK AF Sivak, Wesley N. Bourne, Debra A. Miller, Matthew P. Manders, Ernest K. TI Simplified Calvarial Reconstruction: Coverage of Bare Skull With GammaGraft Promotes Granulation and Facilitates Skin Grafting SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Allograft skin; calvarial defect; scalp reconstruction; skin graft ID SCALP DEFECTS; DERMIS AB Repair of scalp defects with exposed calvaria remains a difficult clinical problem. Herein, we present a simple alternative method of scalp reconstruction. Coverage of bare skull with GammaGraft (Promethean LifeSciences, Inc, Pittsburgh, PA) promotes the evolution of granulation tissue and permits subsequent skin grafting without need for burring, drilling, or other manipulation of the outer table of the calvaria. A retrospective review of patients undergoing scalp reconstruction utilizing GammaGraft and subsequent skin grafting was performed at our institution. From our cohort, 5 patients treated with GammaGraft and subsequent skin grafting had both immediate and long-term follow-up available. Indications for scalp reconstruction included erosions of prior skin grafts and direct excision of full-thickness scalp and pericranium. Average time to definitive skin grafting was 3 weeks; repeat application of GammaGraft was required in some patients with reapplication to subsequent smaller wounds as healing occurred. Complications were minor and consisted of ongoing wound drainage. Alternative flap reconstruction was not required in any patient due to treatment failures. No major complications, wound infections, or early reoperations occurred in any of the patients; 1 patient to date has required repeat reconstruction due to recurrent disease. Coverage of bare skull with GammaGraft and subsequent skin grafting provides a simple and elegant solution to an often too difficult clinical problem. Confirmed by results in out limited series, the utilization of GammaGraft in calvarial reconstruction represents an alternative method in surgical care of complex scalp defects with exposed bone. C1 [Sivak, Wesley N.; Bourne, Debra A.; Miller, Matthew P.; Manders, Ernest K.] Univ Pittsburgh, Dept Plast Surg, 3550 Terrace St,Scaife Hall,Suite 6B, Pittsburgh, PA 15261 USA. [Manders, Ernest K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Manders, Ernest K.] McGowan Inst Regenerat Med, Pittsburgh, PA USA. RP Manders, EK (reprint author), Univ Pittsburgh, Dept Plast Surg, 3550 Terrace St,Scaife Hall,Suite 6B, Pittsburgh, PA 15261 USA. EM mandersek@upmc.edu NR 10 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 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD OCT PY 2016 VL 27 IS 7 BP 1808 EP 1809 DI 10.1097/SCS.0000000000003037 PG 2 WC Surgery SC Surgery GA EA1KW UT WOS:000386352100103 PM 27557466 ER PT J AU Ananthakrishnan, AN Shi, HY Tang, W Law, CCY Sung, JJY Chan, FKL Ng, SC AF Ananthakrishnan, Ashwin N. Shi, Hai Yun Tang, Whitney Law, Cindy C. Y. Sung, Joseph J. Y. Chan, Francis K. L. Ng, Siew C. TI Systematic Review and Meta-analysis: Phenotype and Clinical Outcomes of Older-onset Inflammatory Bowel Disease SO JOURNAL OF CROHNS & COLITIS LA English DT Article DE Older-onset IBD; phenotype; natural history; outcomes ID ANTI-TNF THERAPY; CROHNS-DISEASE; ULCERATIVE-COLITIS; ELDERLY-PATIENTS; FOLLOW-UP; AGE-GROUP; DIAGNOSIS; FEATURES; COHORT; COMPLICATIONS AB Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects. A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age a parts per thousand yen 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated. We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57]. Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA. [Shi, Hai Yun; Tang, Whitney; Sung, Joseph J. Y.; Chan, Francis K. L.; Ng, Siew C.] Chinese Univ Hong Kong, Inst Digest Dis, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Law, Cindy C. Y.] Univ Ottawa, Sch Med, Ottawa, ON, Canada. RP Ng, SC (reprint author), Chinese Univ Hong Kong, LKS Inst Hlth Sci, State Key Lab Digest Dis, Dept Med & Therapeut,Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China. EM siewchienng@cuhk.edu.hk RI Ng, Siew Chien/N-4733-2015; Chan, Francis K. L./F-4851-2010 OI Ng, Siew Chien/0000-0002-6850-4454; Chan, Francis K. L./0000-0001-7388-2436 FU US National Institutes of Health [K23 DK097142] FX AA is supported by funding from the US National Institutes of Health [K23 DK097142]. NR 74 TC 4 Z9 4 U1 7 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD OCT PY 2016 VL 10 IS 10 BP 1224 EP 1236 DI 10.1093/ecco-jcc/jjw054 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DZ7MP UT WOS:000386050300013 PM 26928965 ER PT J AU Neuman, HB Rathouz, PJ Winslow, E Weiss, JM LoConte, NK Lin, CP Wurm, M Smith, MA Schrag, D Greenberg, CC AF Neuman, Heather B. Rathouz, Paul J. Winslow, Emily Weiss, Jennifer M. LoConte, Noelle K. Lin, Chee Paul Wurm, Mike Smith, Maureen A. Schrag, Deborah Greenberg, Caprice C. TI Use of a novel statistical technique to examine the delivery of breast cancer follow-up care by different types of oncology providers SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE breast cancer; care coordination; coefficient of variation; health care delivery; surveillance; survivorship ID MEDICARE CLAIMS; SURVIVORS; SPECIALISTS AB Rationale, aims and objectivesFrequent follow-up is recommended for the more than 3 million breast cancer survivors living in the USA. Given the multidisciplinary nature of breast cancer treatment, follow-up may be provided by medical oncologists, radiation oncologists, surgeons and primary care providers. This creates the potential for significant redundancy as well as gaps in care. The objective was to examine patterns of breast cancer follow-up provided by different types of oncologists and develop a statistical means of quantifying visit distribution over time. MethodsWe identified stage I-III breast cancer patients who underwent breast conservation from 2000 to 2006 (n = 12 139) within the SEER-Medicare linked database. Provider type was defined using Medicare specialty provider codes and AMA Masterfile. The coefficient of variation (CV) for time between oncologist follow-up visits was calculated. Ordinal logistic regression assessed factors associated with CV. ResultsSubstantial variation in CV was observed. Sixty-seven per cent of patients with low CV (high visit regularity) received follow-up from a single oncologist type, versus 8% with high CV (low visit regularity). The number of oncologist types participating in follow-up had the greatest association with high CV (odds ratio 7.4 [6.7-8.3] and 15.4 [13.6-17.6] for two and three oncologist types). ConclusionsUsing a novel means of quantifying follow-up visit regularity, we determined that breast cancer patients with dispersed follow-up with more than one oncologist have more disordered care. The CV could be used in electronic medical records to identify cancer survivors with more disordered. C1 [Neuman, Heather B.] UW Madison Sch Med & Publ Hlth, Dept Surg, Wisconsin Surg Outcomes Res Program, CSC H4-726,600 Highland Ave, Madison, WI 53792 USA. [Winslow, Emily; Greenberg, Caprice C.] UW Madison Sch Med & Publ Hlth, Dept Surg, Wisconsin Surg Outcomes Res Program, Surg, Madison, WI 53792 USA. [Neuman, Heather B.; Greenberg, Caprice C.] Univ Wisconsin, Carbone Canc Ctr, UW Madison Sch Med & Publ Hlth, Surg, Madison, WI USA. [Weiss, Jennifer M.; LoConte, Noelle K.] Univ Wisconsin, Carbone Canc Ctr, UW Madison Sch Med & Publ Hlth, Med, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Carbone Canc Ctr, UW Madison Sch Med & Publ Hlth, Populat Hlth Sci, Madison, WI USA. [Rathouz, Paul J.] UW Madison Sch Med & Publ Hlth, Dept Biostat & Med Informat, Biostat & Med Informat, Madison, WI 53792 USA. [Wurm, Mike] UW Madison Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Weiss, Jennifer M.] UW Madison Sch Med & Publ Hlth, Dept Med, Div Gastroenterol & Hepatol, Med, Madison, WI 53792 USA. [Lin, Chee Paul] Univ Alabama Birmingham, Sch Med, Ctr Clin & Translat Sci, Birmingham, AL USA. [Smith, Maureen A.] UW Madison Sch Med & Publ Hlth, Populat Hlth Sci, Dept Populat Hlth Sci, Madison, WI USA. [LoConte, Noelle K.] UW Madison Sch Med & Publ Hlth, Div Hematol & Oncol, Dept Med, Med, Madison, WI USA. [Smith, Maureen A.] UW Madison Sch Med & Publ Hlth, Dept Family Med, Populat Hlth Sci, Madison, WI USA. [Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Med, Boston, MA 02115 USA. RP Neuman, HB (reprint author), UW Madison Sch Med & Publ Hlth, Dept Surg, Wisconsin Surg Outcomes Res Program, CSC H4-726,600 Highland Ave, Madison, WI 53792 USA. EM neuman@surgery.wisc.edu FU University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC) Academic Oncologist Training Program [NIH 5K12CA087718]; Building Interdisciplinary Research Careers in Women's Health Scholar Program [NIH K12 HD055894]; Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) programme [HHSA290201000006I]; SEER-Medicare group from the National Cancer Institute [P30 CA014520]; Health Innovation Program; Community-Academic Partnerships and Biostatistics cores of the University of Wisconsin Institute for Clinical and Translational Research from the Clinical and Translational Science Award program of the National Center for Research Resources [UL1TR0000427]; NIH National Center for Advancing Translational Sciences [NCATS]); UW School of Medicine and Public Health from The Wisconsin Partnership Program FX This project was funded through the University of Wisconsin Carbone Comprehensive Cancer Center (UWCCC) Academic Oncologist Training Program (NIH 5K12CA087718) and the Building Interdisciplinary Research Careers in Women's Health Scholar Program (NIH K12 HD055894). Further funding came from contract no. HHSA290201000006I from the Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) programme. Finally, funding support for the SEER-Medicare group came from grant number P30 CA014520 from the National Cancer Institute, the Health Innovation Program, the Community-Academic Partnerships and Biostatistics cores of the University of Wisconsin Institute for Clinical and Translational Research (grant number UL1TR0000427 from the Clinical and Translational Science Award program of the National Center for Research Resources, NIH National Center for Advancing Translational Sciences [NCATS]) and the UW School of Medicine and Public Health from The Wisconsin Partnership Program. NR 20 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 EI 1365-2753 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD OCT PY 2016 VL 22 IS 5 BP 737 EP 744 DI 10.1111/jep.12529 PG 8 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA DW3ZG UT WOS:000383581000015 PM 26991311 ER PT J AU Huffman, JC Millstein, RA Mastromauro, CA Moore, SV Celano, CM Bedoya, CA Suarez, L Boehm, JK Januzzi, JL AF Huffman, Jeff C. Millstein, Rachel A. Mastromauro, Carol A. Moore, Shannon V. Celano, Christopher M. Bedoya, C. Andres Suarez, Laura Boehm, Julia K. Januzzi, James L. TI A Positive Psychology Intervention for Patients with an Acute Coronary Syndrome: Treatment Development and Proof-of-Concept Trial SO JOURNAL OF HAPPINESS STUDIES LA English DT Article DE Myocardial infarction; Unstable angina; Positive affect; Optimism; Mental health; Intervention ID RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; BYPASS GRAFT-SURGERY; CARDIOVASCULAR-DISEASE; RISK-FACTOR; DISPOSITIONAL OPTIMISM; MYOCARDIAL-INFARCTION; MEDICATION ADHERENCE; PHYSICAL-ACTIVITY; MAJOR DEPRESSION AB Positive psychological constructs are associated with superior outcomes in cardiac patients, but there has been minimal study of positive psychology (PP) interventions in this population. Our objective was to describe the intervention development and pilot testing of an 8-week phone-based PP intervention for patients following an acute coronary syndrome (ACS). Initial intervention development and single-arm proof-of-concept trial, plus comparison of the PP intervention to a subsequently-recruited treatment as usual (TAU) cohort. PP development utilized existing literature, expert input, and qualitative interview data in ACS patients. In the proof-of-concept trial, the primary outcomes were feasibility and acceptability, measured by rates of exercise completion and participant ratings of exercise ease/utility. Secondary outcomes were pre-post changes in psychological outcomes and TAU comparisons, measured using effect sizes (Cohen's d). The PP intervention and treatment manual were successfully created. In the proof-of-concept trial, 17/23 PP participants (74 %) completed at least 5 of 8 exercises. Participants rated the ease (M = 7.4/10; SD = 2.1) and utility (M = 8.1/10, SD = 1.6) of PP exercises highly. There were moderate pre-post improvements (ds = .46-.69) in positive affect, anxiety, and depression, but minimal effects on dispositional optimism (d = .08). Compared to TAU participants (n = 22), PP participants demonstrated greater improvements in positive affect, anxiety, and depression (ds = . 47-.71), but not optimism. A PP intervention was feasible, well-accepted, and associated with improvements in most psychological measures among cardiac patients. These results provide support for a larger trial focusing on behavioral outcomes. C1 [Huffman, Jeff C.; Millstein, Rachel A.; Mastromauro, Carol A.; Moore, Shannon V.; Celano, Christopher M.; Bedoya, C. Andres; Suarez, Laura; Januzzi, James L.] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Blake 11, Boston, MA 02114 USA. [Huffman, Jeff C.; Millstein, Rachel A.; Mastromauro, Carol A.; Moore, Shannon V.; Celano, Christopher M.; Bedoya, C. Andres; Suarez, Laura] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. [Boehm, Julia K.] Chapman Univ, Dept Psychol, Orange, CA USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Blake 11, Boston, MA 02114 USA.; Huffman, JC (reprint author), Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. EM jhuffman@partners.org FU National Institutes of Health (NIH) [R01HL113272] FX This work was supported by the National Institutes of Health (NIH) Grant R01HL113272. NR 72 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-4978 EI 1573-7780 J9 J HAPPINESS STUD JI J. Happiness Stud. PD OCT PY 2016 VL 17 IS 5 BP 1985 EP 2006 DI 10.1007/s10902-015-9681-1 PG 22 WC Psychology, Multidisciplinary; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA EA1TI UT WOS:000386374400012 PM 28082831 ER PT J AU Hunt, PW Lee, SA Siedner, MJ AF Hunt, Peter W. Lee, Sulggi A. Siedner, Mark J. TI Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE immune activation; inflammation; biomarkers; morbidity; mortality; HIV-1 infection; antiretroviral therapy ID T-CELL-ACTIVATION; INITIATING ANTIRETROVIRAL THERAPY; IMMUNE ACTIVATION; PREDICT MORTALITY; MICROBIAL TRANSLOCATION; TRYPTOPHAN CATABOLISM; SYSTEMIC INFLAMMATION; MONOCYTE ACTIVATION; KYNURENINE PATHWAY; SOLUBLE CD14 AB Despite marked improvements in the modern treatment era, human immunodeficiency virus (HIV)-infected individuals, particularly those who initiated antiretroviral therapy (ART) at advanced disease stages, continue to have increased age-related morbidity and mortality, compared with the general population. Immune activation and inflammation persist despite suppressive ART and predict many of these morbidities. The goal of this review is to examine the evidence suggesting a link between the persistent inflammatory state and morbidity and mortality in this setting, to describe the impact of early ART initiation on these factors, and to highlight important unanswered questions for the field. We also advance a hypothesis to explain why some morbidities-and their root inflammatory drivers-may be prevented more than others by early ART initiation. C1 [Hunt, Peter W.; Lee, Sulggi A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Siedner, Mark J.] Harvard Med Sch, Boston, MA USA. RP Hunt, PW (reprint author), 1001 Potrero Ave,SFGH Bldg 3,6th Flr, San Francisco, CA 94110 USA. EM peter.hunt@ucsf.edu FU National Institutes of Health [R01AI110271, K23MH099916] FX This work was supported by the National Institutes of Health (grants R01AI110271 and K23MH099916). NR 50 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 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2016 VL 214 SU 2 BP S44 EP S50 DI 10.1093/infdis/jiw275 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ8UP UT WOS:000386147600002 PM 27625430 ER PT J AU Andolfi, C Jalilvand, A Plana, A Fisichella, PM AF Andolfi, Ciro Jalilvand, Anahita Plana, Alejandro Fisichella, P. Marco TI Surgical Treatment of Paraesophageal Hernias: A Review SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Review DE paraesophageal hernias; laparoscopic approach; esophageal function testing ID GASTROESOPHAGEAL-REFLUX DISEASE; LARGE HIATAL-HERNIA; RANDOMIZED-CONTROLLED-TRIAL; IRON-DEFICIENCY ANEMIA; LAPAROSCOPIC REPAIR; FOLLOW-UP; SLEEVE GASTRECTOMY; OBESE-PATIENTS; MANAGEMENT; FUNDOPLICATION AB The management of paraesophageal hernia (PEH) can be challenging due to the lack of consensus regarding indications and principles of operative treatment. In addition, data about the pathophysiology of the hernias are scant. Therefore, the goal of this review is to shed light and describe the classification, pathophysiology, clinical presentation, and indications for treatment of PEHs, and provide an overview of the surgical management and a description of the technical principles of the repair. C1 [Andolfi, Ciro; Plana, Alejandro] Univ Chicago, Dept Surg, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Jalilvand, Anahita] Ohio State, Dept Surg, Columbus, OH USA. [Fisichella, P. Marco] Harvard Med Sch, Boston VA Healthcare Syst, Boston, MA USA. RP Fisichella, PM (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 84 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 OCT PY 2016 VL 26 IS 10 BP 778 EP 783 DI 10.1089/lap.2016.0332 PG 6 WC Surgery SC Surgery GA DZ8MI UT WOS:000386124100007 PM 27398823 ER PT J AU Orthopoulos, G Oriel, BS Siegert, CJ Lebenthal, A Gooey, J Fisichella, PM AF Orthopoulos, George Oriel, Brad S. Siegert, C. Jeff Lebenthal, Abraham Gooey, John Fisichella, P. Marco TI Results of a Tailored Approach to Zenker's Diverticulum: A Single VA Experience SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES LA English DT Article DE Zenker's diverticulum; esophageal diverticulum; endoscopic management; transcervical approach AB The transoral division of the esophageal-diverticula septum with a linear stapler, with CO2 laser, or with harmonic scalpel under rigid endoscopy has revolutionized the surgical management of Zenker's diverticula. Nevertheless, the open approach still plays a role in select cases. Our goals are to illustrate the techniques and the results of our tailored approach to the surgical management of Zenker's diverticula in U.S. veterans. C1 [Orthopoulos, George] St Elizabeth Hosp, Brighton, MA USA. [Oriel, Brad S.; Siegert, C. Jeff] Boston VA Hlth Care Syst, Boston, MA USA. [Lebenthal, Abraham] Boston VA Hlth Care Syst, Brigham & Womens Hosp, Div Thorac Surg, Boston, MA USA. [Gooey, John] Boston VA Hlth Care Syst, Div Otolayngol, Boston, MA USA. [Fisichella, P. Marco] Boston VA Hlth Care Syst, Brigham & Womens Hosp, Dept Surg, Boston, MA USA. RP Fisichella, PM (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Boston VA Healthcare Syst, Dept Surg, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 6 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 OCT PY 2016 VL 26 IS 10 BP 806 EP 807 DI 10.1089/lap.2016.0331 PG 2 WC Surgery SC Surgery GA DZ8MI UT WOS:000386124100011 PM 27611880 ER PT J AU Chao, LL AF Chao, Linda L. TI Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in Theater and Visuospatial Function in Gulf War Veterans SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SPATIAL MENTAL-IMAGERY; SURFACE-BASED ANALYSIS; LONG-DISTANCE TRANSIT; SUBWAY SARIN ATTACK; PESTICIDE APPLICATORS; ALZHEIMER-DISEASE; WEAPONS FALLOUT; NERVOUS-SYSTEM; RISK-FACTORS; EXPOSURE AB Objective:The aim of this study was to examine the relationship between the self-reported frequencies of hearing chemical alarms during deployment and visuospatial function in Gulf War (GW) veterans.Methods:The relationship between the self-reported frequency of hearing chemical alarms, neurobehavioral, and volumetric brain imaging data was examined with correlational, regression, and mediation analyses.Results:The self-reported frequency of hearing chemical alarms was inversely associated with and significantly predicted performance on a visuospatial task (ie, Block Design) over and above potentially confounding variables, including concurrent, correlated GW-related exposures. This effect was partially mediated by the relationship between hearing chemical alarms and lateral occipital cortex volume.Conclusions:Exposure to substances that triggered chemical alarms during GW deployment likely had adverse effects on veterans' brain structure and function, warranting further investigation of whether these GW veterans are at an increased risk for dementia. C1 San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Chao, LL (reprint author), 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU VA grant [CX000798] FX This study supported by VA grant no. CX000798 entitled "Longitudinal Assessment of Gulf War Veterans with Suspected Sarin Exposure." NR 47 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 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 2016 VL 58 IS 10 BP 1014 EP 1020 DI 10.1097/JOM.0000000000000851 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA1HQ UT WOS:000386343500008 PM 27513172 ER PT J AU Karagozian, R Bhardwaj, G Wakefield, DB Baffy, G AF Karagozian, Raffi Bhardwaj, Gaurav Wakefield, Dorothy B. Baffy, Gyorgy TI Obesity paradox in advanced liver disease: obesity is associated with lower mortality in hospitalized patients with cirrhosis SO LIVER INTERNATIONAL LA English DT Article DE cirrhosis; hospital charges; ICD-9; leptin; National Inpatient Sample ID BODY-MASS INDEX; CHRONIC HEPATITIS; LEPTIN LEVELS; RISK-FACTOR; METAANALYSIS; OUTCOMES; IMPACT; PREVALENCE; WEIGHT; ADULTS AB Background & AimsTo investigate how obesity impacts inpatient mortality, length of stay (LOS) and costs in patients with cirrhosis. Obesity is a growing epidemic associated with multiple co-morbidities, increased morbidity, and a significant economic burden on healthcare. Despite the overall harmful impact of obesity, the obesity paradox' has been described as decreased mortality among obese vs non-obese patients in various chronic medical conditions. MethodsAnalysis of the Nationwide Inpatient Sample (NIS) for 2012, which contains data from 44 states and 4378 hospitals. Data from all cases with primary, secondary or tertiary discharge diagnosis of cirrhosis identified by International Classification of Diseases-9 code 571.2, 571.5 571.6 were included. Primary outcomes included inpatient mortality, LOS, and hospital charges. Obesity as a predictor of mortality was defined by a predetermined obesity co-morbidity variable. ResultsA total of 32,605 patients were included. Crude mortality was lower for obese cirrhotic patients (2.7% vs 3.5%, P=0.02) than for non-obese cirrhotic patients. In contrast, median LOS was longer (4 vs 3days, P<0.001) and median hospital charges were higher for obese cirrhotic patients ($26803 vs $23447, P<0.001) In multivariate logistic regression, obesity was associated with a lower risk of inpatient mortality (OR=0.73, 95%CI: 0.55-0.95, P=0.02). ConclusionsIn the acute care setting, obese patients with cirrhosis have lower mortality than non-obese patients with cirrhosis, longer hospitalizations and higher healthcare cost, providing new evidence for the obesity paradox in cirrhosis. Obese cirrhotic patients are more likely to have enhanced nutritional reserve which may play a role in survival during acute illness. See Editorial on Page 1412 C1 [Karagozian, Raffi; Bhardwaj, Gaurav] Univ Connecticut, Sch Med, Farmington, CT 06105 USA. [Wakefield, Dorothy B.] UConn Hlth, Ctr Publ Hlth & Hlth Policy, Farmington, CT USA. [Baffy, Gyorgy] Harvard Med Sch, VA Boston Healthcare Syst, Div Gastroenterol & Hepatol, Boston, MA USA. RP Karagozian, R (reprint author), Univ Connecticut, Sch Med, Farmington, CT 06105 USA. EM raffikaragozian@gmail.com NR 29 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD OCT PY 2016 VL 36 IS 10 BP 1450 EP 1456 DI 10.1111/liv.13137 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DW3UI UT WOS:000383568200008 PM 27037497 ER PT J AU Ding, WH Chen, SP Wang, R Cai, J Cheng, Y Yu, L Li, QH Deng, F Zhu, SM Yu, WH AF Ding, Weihua Chen, Shuping Wang, Rong Cai, Jun Cheng, Yuan Yu, Liang Li, Qinghua Deng, Fang Zhu, Shengmei Yu, Wenhua TI Percutaneous radiofrequency thermocoagulation for trigeminal neuralgia using neuronavigation-guided puncture from a mandibular angle SO MEDICINE LA English DT Article DE mandibular angle; neuronavigation; radiofrequency thermocoagulation; trigeminal neuralgia ID FORAMEN OVALE; GASSERIAN GANGLION; TECHNICAL NOTE; NERVE; RADIOSURGERY; EXPERIENCE; RHIZOTOMY AB Percutaneous radiofrequency thermocoagulation (RFT) of the Gasserian ganglion is an effective treatment for primary trigeminal neuralgia (pTN). Currently Hartel anterior approach is the most commonly used method to access the Gasserian ganglion. However, this approach is associated with high recurrence rate and technical difficulties in certain patients with foramen ovale (FO) anatomical variations. In the present study, we assessed the feasibility of accessing the Gasserian ganglion through the FO from a mandibular angle under computed tomography (CT) and neuronavigation guidance.A total of 108 patients with TN were randomly divided into 2 groups (Group G and Group H) using a random number table. In Group H, Hartel anterior approach was used to puncture the FO; whereas in Group G, a percutaneous puncture through a mandibular angle was used to reach the FO. In both groups, procedures were guided by CT imaging and neuronavigation. The success rates, therapeutic effects, complications, and recurrence rates of the 2 groups were compared.The puncture success rates in Group H and Group G were 52/54 (96.30%) and 49/54 (90.74%), respectively (P=0.24). The 2 procedural failures in Group H were rescued by using submandibular trajectory, and the 5 failures in Group G were successfully reapproached by Hartel method. Therapeutic effects as measured by Barrow Neurological Institute (BNI) pain scale (P=0.03) and quality of life (QOL) scores (P=0.04) were significantly better in Group G than those in Group H at 36 months posttreatment. Hematoma developed in 1/54 (1.85%) cases in Group H, and no cases of hematoma were observed in Group G (P=0.33). In Group H, RFT resulted in injury to the unintended trigeminal nerve branches and motor fibers in 27/52 (51.92%) cases; in Group G, it resulted in the same type of injury in 7/49 cases (14.29%) (P<0.01). In Group H, the 24- and 36-month recurrence rates were 12/51 (23.53%) and 20/51 (39.22%), respectively; in Group G, these recurrence rates were 7/49 (12.24%) and 9/49 (16.33%, P=0.03), respectively.CT- and neuronavigation-guided puncture from a mandibular angle through the FO into the Gasserian ganglion can be safely and effectively used to deliver RFT for the treatment of pTN. This method may represent a viable option to treat TN in addition to Hartel approach. C1 [Ding, Weihua; Zhu, Shengmei] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Anesthesia & Pain Med, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China. [Ding, Weihua; Chen, Shuping; Cai, Jun; Cheng, Yuan; Yu, Liang; Li, Qinghua; Deng, Fang] Nanjing Med Univ, Hangzhou Peoples Hosp 1, Pain Clin, Hangzhou, Zhejiang, Peoples R China. [Ding, Weihua] Harvard Med Sch, Massachusetts Gen Hosp, Pain Med, Boston, MA USA. [Wang, Rong] Nanjing Med Univ, Hangzhou Peoples Hosp 1, Dept Radiol, Hangzhou, Zhejiang, Peoples R China. [Yu, Wenhua] Nanjing Med Univ, Hangzhou Peoples Hosp 1, Dept Neurosurg, 261 Huansha Rd, Hangzhou, Zhejiang, Peoples R China. RP Zhu, SM (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Anesthesia & Pain Med, 79 Qingchun Rd, Hangzhou, Zhejiang, Peoples R China.; Yu, WH (reprint author), Nanjing Med Univ, Hangzhou Peoples Hosp 1, Dept Neurosurg, 261 Huansha Rd, Hangzhou, Zhejiang, Peoples R China. EM smzhu20088@163.com; powerdwh@163.com FU Hangzhou Science and Technology Plan [20130633B02]; Hangzhou Medical Science and Technology Plan [(HWS) 2011A012]; Zhejiang Medical Science and Technology Plan [2011KYB064]; Traditional Chinese Medicine Administration of Zhejiang [2015ZA128]; key project of Zhejiang Province Medicine Health [2013ZDA010] FX This work was supported by Hangzhou Science and Technology Plan (no. 20130633B02), Hangzhou Medical Science and Technology Plan (no. (HWS) 2011A012), Zhejiang Medical Science and Technology Plan (no. 2011KYB064), Traditional Chinese Medicine Administration of Zhejiang (2015ZA128), and key project of Zhejiang Province Medicine & Health (#2013ZDA010). NR 28 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 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD OCT PY 2016 VL 95 IS 40 AR e4940 DI 10.1097/MD.0000000000004940 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EA1KL UT WOS:000386350900032 PM 27749549 ER PT J AU LaHue, SC Comella, CL Tanner, CM AF LaHue, Sara C. Comella, Cynthia L. Tanner, Caroline M. TI The best medicine? The influence of physical activity and inactivity on Parkinson's disease SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; exercise; metabolic syndrome; physical activity; disease modification ID BODY-MASS INDEX; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-LESIONED MOUSE MODEL; RANDOMIZED CONTROLLED-TRIAL; BASAL GANGLIA INJURY; TREADMILL EXERCISE; ECONOMIC-EVALUATION; METABOLIC SYNDROME; FUTURE RISK; PROSPECTIVE COHORT; COGNITIVE DECLINE AB The incidence of Parkinson's disease (PD) is expected to increase as our population ages and will likely strain the projected capacity of our health care system. Despite being the most common movement disorder, there have been few noninvasive therapeutic advances for people with PD since the first levodopa clinical trial in 1961. The study of PD pathogenesis, combined with an appreciation for the biochemical mechanisms by which physical activity and exercise may impact physiology, has resulted in emerging hypotheses for new modifiable risk factors for PD. Physical activity and exercise as a means of preventing PD, or maintaining the functionality of people with PD, are a promising area of investigation. Conversely, physical inactivity is implicated in many disease states, some of which are also correlated with the development of PD, such as metabolic syndrome. The primary relationship between these diseases is likely rooted in heightened inflammation and oxidative stress at the cellular level. Physical activity and exercise as a means of attenuating inflammation have led to increased interest in related potential therapeutic targets for PD. Ultimately, these findings may translate into low-cost, universally available therapies for PD disease modification or prevention. (c) 2016 International Parkinson and Movement Disorder Society C1 [LaHue, Sara C.] Kaiser Permanente San Francisco Med Ctr, San Francisco, CA USA. [Comella, Cynthia L.] Rush Presbyterian St Lukes Med Ctr, Neurol Sci, Chicago, IL USA. [Tanner, Caroline M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Tanner, CM (reprint author), Univ Calif San Francisco, Dept Neurol, Movement Disorders & Neuromodulat Ctr, 1635 Divisadero St,Suite 515, San Francisco, CA 94115 USA. EM caroline.tanner@ucsf.edu FU NIH [R01NS074343, U54NS065701]; Dystonia Medical Research Foundation; Allergan Inc.; Impax Pharmaceuticals; Ipsen Biopharmaceuticals, Inc; Medtronic Inc.; Merz Pharmaceuticals; US World Meds; Acadia Pharmaceuticals; Teva Neurosciences; Parkinson's Disease Foundation; Michael J. Fox Foundation; Department of Defense; National Institutes of Health FX Dr. LaHue has no disclosures. Dr. Comella serves on the editorial board of Clinical Neuropharmacology, Sleep Medicine, and Continuum. She receives research support from the NIH R01NS074343, U54NS065701, Dystonia Medical Research Foundation, Allergan Inc., Ipsen Biopharmaceuticals, Inc, and Merz Pharmaceutical. She receives compensation/honoraria for services as a consultant or an advisory committee member from Allergan, Inc, Impax Pharmaceuticals, Ipsen Biopharmaceuticals, Inc, Medtronic Inc., Merz Pharmaceuticals, US World Meds, Acadia Pharmaceuticals, and Teva Neurosciences. She receives royalties from Cambridge, Humana Press, and Wolters Kluwer. She receives research support from the Parkinson's Disease Foundation. Dr. Tanner, serves on the editorial boards of the Annals of Neurology, Journal of Parkinson's Disease, Parkinsonism and Related Disorders, and NPJ Parkinson's Disease. She serves on the Scientific Advisory Boards of the Michael J. Fox Foundation and the National Spasmodic Dysphonia Association as a voluntary consultant and has provided paid consulting services to Ultragenyx Pharmaceuticals, Neurocrine Biosciences, Cynapsus, and Adamas. She has received compensation for serving on Data Monitoring Committees from Biotie Therapeutics, Voyager Therapeutics, and Intec Pharma. She receives grant support from the Michael J. Fox Foundation, the Parkinson's Disease Foundation, the Department of Defense, and the National Institutes of Health. NR 118 TC 1 Z9 1 U1 17 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2016 VL 31 IS 10 BP 1444 EP 1454 DI 10.1002/mds.26728 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA DZ7MG UT WOS:000386049400003 PM 27477046 ER PT J AU Cermak, N Olcum, S Delgado, FF Wasserman, SC Payer, KR Murakami, MA Knudsen, SM Kimmerling, RJ Stevens, MM Kikuchi, Y Sandikci, A Ogawa, M Agache, V Baleras, F Weinstock, DM Manalis, SR AF Cermak, Nathan Olcum, Selim Delgado, Francisco Feijo Wasserman, Steven C. Payer, Kristofor R. Murakami, Mark A. Knudsen, Scott M. Kimmerling, Robert J. Stevens, Mark M. Kikuchi, Yuki Sandikci, Arzu Ogawa, Masaaki Agache, Vincent Baleras, Francois Weinstock, David M. Manalis, Scott R. TI High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays SO NATURE BIOTECHNOLOGY LA English DT Article ID LYMPHOCYTE-TRANSFORMATION TEST; SIZE CONTROL; IN-VITRO; CYCLE; VARIABILITY; HOMEOSTASIS; TOLERANCE; BACTERIA; TIME AB Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspension through a microfluidic channel with 10-12 resonant mass sensors distributed along its length, weighing each cell repeatedly over the 4-20 min it spends in the channel. Because multiple cells traverse the channel at the same time, we obtain growth rates for >60 cells/h with a resolution of 0.2 pg/h for mammalian cells and 0.02 pg/h for bacteria. We measure the growth of single lymphocytic cells,. mouse and human T cells, primary human leukemia cells, yeast, Escherichia coli and Enterococcus faecalis. Our system reveals subpopulations of cells with divergent growth kinetics and enables assessment of cellular responses to antibiotics and antimicrobial peptides within minutes. C1 [Cermak, Nathan; Manalis, Scott R.] MIT, Program Computat & Syst Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Olcum, Selim; Delgado, Francisco Feijo; Sandikci, Arzu; Manalis, Scott R.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Delgado, Francisco Feijo; Wasserman, Steven C.; Knudsen, Scott M.; Kimmerling, Robert J.; Manalis, Scott R.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Payer, Kristofor R.; Kikuchi, Yuki; Manalis, Scott R.] MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. [Murakami, Mark A.; Weinstock, David M.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Stevens, Mark M.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Ogawa, Masaaki] Innovat Micro Technol, Goleta, CA USA. [Agache, Vincent; Baleras, Francois] CEA LETI, Minatec Campus, Grenoble, France. [Weinstock, David M.] Broad Inst, Cambridge, MA USA. [Manalis, Scott R.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Kikuchi, Yuki] Hitachi High Technol Corp, Hitachinaka, Ibaraki, Japan. RP Manalis, SR (reprint author), MIT, Program Computat & Syst Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA.; Manalis, SR (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM srm@mit.edu FU Koch Institute for Integrative Cancer Research at MIT; Dana-Farber/Harvard Cancer Center; US Army Research Office (Institute for Collaborative Biotechnologies grant) [W911NF-09-D-0001]; US National Science Foundation [1129359]; Institut Merieux; US National Cancer Institute (Physical Sciences Oncology Center) [U54CA143874]; US National Cancer Institute (Cancer Center Support) [P30-CA14051, R33-CA191143]; MIT Poitras Fellowship; NCI institutional research training grant [T32 CA009172]; NIH/NIGMS Interdepartmental Biotechnology Training Program grant [T32 GM008334]; Bridge Project FX We thank G. Szeto for providing mouse spleen and lymph nodes, J.H. Kang for measuring the density of RPMI 1640 and A. Amon for a critical reading of the manuscript. This work was carried out in part through the use of the Microsystems Technology Laboratories at the Massachusetts Institute of Technology (MIT). Support was provided by the Bridge Project (a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center) to S.R.M. and D.M.W.; the US Army Research Office (Institute for Collaborative Biotechnologies grant W911NF-09-D-0001) to S.R.M.; the US National Science Foundation (1129359) to S.R.M.; Institut Merieux to S.R.M.; and the US National Cancer Institute (Physical Sciences Oncology Center U54CA143874 and Cancer Center Support grants P30-CA14051 and R33-CA191143) to S.R.M. N.C. acknowledges support from an MIT Poitras Fellowship. M.A.M. acknowledges support from NCI institutional research training grant T32 CA009172, awarded to the Department of Medical Oncology at Dana-Farber Cancer Institute. M.M.S. acknowledges support from the NIH/NIGMS T32 GM008334 Interdepartmental Biotechnology Training Program grant. D.M.W. is a Leukemia and Lymphoma Society Scholar. NR 35 TC 2 Z9 2 U1 26 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2016 VL 34 IS 10 BP 1052 EP 1059 DI 10.1038/nbt.3666 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EA0ZG UT WOS:000386317500020 PM 27598230 ER PT J AU Zukas, AM Bennani, N Chou, C Johnston, P O'Neill, B Nijland, M Batchelor, T Nayak, L Mrugala, M Schiff, D AF Zukas, A. M. Bennani, N. Chou, C. Johnston, P. O'Neill, B. Nijland, M. Batchelor, T. Nayak, L. Mrugala, M. Schiff, D. TI INTRAVASCULAR LYMPHOMA AFFECTING THE CENTRAL NERVOUS SYSTEM: FEATURES AND OUTCOMES IN A CASE SERIES OF THE PRIMARY CNS LYMPHOMA COLLABORATIVE GROUP (IPCG) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [Zukas, A. M.; Schiff, D.] Univ Virginia, Dept Neurooncol, Charlottesville, VA USA. [Bennani, N.; Chou, C.; Johnston, P.; O'Neill, B.] Mayo Clin, Rochester, MN USA. [Nijland, M.] Univ Med Ctr Groningen, Groningen, Netherlands. [Batchelor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nayak, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mrugala, M.] Univ Washington, Med Ctr, Seattle, WA 98195 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2016 VL 18 SU 4 MA OS5.8 BP 13 EP 13 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200044 ER PT J AU van den Bent, M Gan, H Reardon, DA Papadopoulos, KP Merrell, R Kumthekar, P Roberts-Rapp, L Holen, K Ansell, P Lassman, AB AF van den Bent, M. Gan, H. Reardon, D. A. Papadopoulos, K. P. Merrell, R. Kumthekar, P. Roberts-Rapp, L. Holen, K. Ansell, P. Lassman, A. B. TI TRANSCRIPTIONAL PROFILING TO IDENTIFY DETERMINANTS ASSOCIATED WITH RESPONSE TO ABT-414 IN PATIENTS WITH GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [van den Bent, M.] Erasmus MC, Canc Ctr, Rotterdam, Netherlands. [Gan, H.] Austin Hlth, Melbourne, Vic, Australia. [Gan, H.] Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Reardon, D. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Papadopoulos, K. P.] South Texas Accelerated Res Therapeut, San Antonio, TX USA. [Merrell, R.] NorthShore Univ HealthSyst, Evanston, IL USA. [Kumthekar, P.] Northwestern Univ, Chicago, IL 60611 USA. [Roberts-Rapp, L.; Holen, K.; Ansell, P.] AbbVie Inc, N Chicago, IL USA. [Lassman, A. B.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Lassman, A. B.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Med Ctr, New York, NY 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2016 VL 18 SU 4 MA P06.02 BP 27 EP 28 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200095 ER PT J AU Derks, J Dirkson, A Hamer, PCD Van Geest, Q Hulst, HE Barkhof, F Pouwels, PJW Geurts, JJG Reijneveld, JC Douw, L AF Derks, J. Dirkson, A. Hamer, P. C. De Witt Van Geest, Q. Hulst, H. E. Barkhof, F. Pouwels, P. J. W. Geurts, J. J. G. Reijneveld, J. C. Douw, L. TI HIGHER FUNCTIONAL HUB LOAD AT DIAGNOSIS IS ASSOCIATED WITH SHORTER SURVIVAL IN GLIOMA PATIENTS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [Derks, J.; Dirkson, A.; Van Geest, Q.; Hulst, H. E.; Geurts, J. J. G.; Douw, L.] Vrije Univ Amsterdam Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Derks, J.; Dirkson, A.; Hamer, P. C. De Witt; Reijneveld, J. C.] VUmc CCA Brain Tumor Ctr Amsterdam, Amsterdam, Netherlands. [Hamer, P. C. De Witt] Vrije Univ Amsterdam Med Ctr, Neurosurg Ctr Amsterdam, Amsterdam, Netherlands. [Barkhof, F.] Vrije Univ Amsterdam Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands. [Pouwels, P. J. W.] Vrije Univ Amsterdam Med Ctr, Dept Phys & Med Technol, Amsterdam, Netherlands. [Reijneveld, J. C.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands. Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2016 VL 18 SU 4 MA P07.08 BP 35 EP 35 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200121 ER PT J AU van den Bent, M Gan, HK Lassman, AB Kumthekar, P Butowski, N Lwin, Z Nabors, LB Simes, J Holen, K Reardon, DA AF van den Bent, M. Gan, H. K. Lassman, A. B. Kumthekar, P. Butowski, N. Lwin, Z. Nabors, L. B. Simes, J. Holen, K. Reardon, D. A. TI EFFICACY OF A NOVEL ANTIBODY-DRUG CONJUGATE (ADC), ABT-414, AS MONOTHERAPY IN EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AMPLIFIED, RECURRENT GLIOBLASTOMA (GBM) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [van den Bent, M.] Erasmus MC Canc Ctr, Rotterdam, Netherlands. [Gan, H. K.] Austin Hlth & Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia. [Lassman, A. B.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Lassman, A. B.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Kumthekar, P.] Northwestern Univ, Chicago, IL 60611 USA. [Butowski, N.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Lwin, Z.] Univ Queensland, Sch Med, Royal Brisbane & Womens Hosp, Dept Med Oncol, Rotterdambrisbane, Qld, Australia. [Nabors, L. B.] Univ Alabama Birmingham, Birmingham, AL USA. [Simes, J.] NHMRC Clin Trials Ctr, Camperdown, NSW, Australia. [Holen, K.] AbbVie Inc, N Chicago, IL USA. [Reardon, D. A.] Dana Farber Canc Inst, Boston, MA 02115 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2016 VL 18 SU 4 MA P08.19 BP 44 EP 44 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200154 ER PT J AU Jordan, JT Miller, JJ Cushing, T Curry, WT Shih, HA Nachtigall, L Loeffler, J Dietrich, J AF Jordan, J. T. Miller, J. J. Cushing, T. Curry, W. T. Shih, H. A. Nachtigall, L. Loeffler, J. Dietrich, J. TI TEMOZOLOMIDE FOR PROGRESSIVE PITUITARY ADENOMAS REFRACTORY TO SURGERY AND RADIATION: A CASE SERIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [Jordan, J. T.; Miller, J. J.; Cushing, T.; Dietrich, J.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Miller, J. J.] Dana Farber Inst, Boston, MA USA. [Curry, W. T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Shih, H. A.; Loeffler, J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. [Nachtigall, L.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2016 VL 18 SU 4 MA P21.07 BP 82 EP 83 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200297 ER PT J AU Turner, DP Golding, AN Houle, TT AF Turner, Dana P. Golding, Adrienne N. Houle, Timothy T. TI Using a graphical risk tool to examine willingness to take migraine prophylactic medications SO PAIN LA English DT Article DE Headache; Preventative treatment; Risk; Side effects ID HEADACHE; COMMUNICATION; ADHERENCE; EFFICACY AB Many migraine sufferers use daily prophylactic therapy to reduce the frequency of their headache attacks. The Food and Drug Administration has approved several different medications for migraine prophylaxis, but it is not clear whether sufferers perceive these treatments to provide clinically significant benefits given their side effect profiles. Three hundred headache sufferers were recruited from the community and local headache clinics using print and television advertising. Participants reported experiencing problematic headache attacks with a median (IQR) frequency of 7.0 (4-13) headache days per month. These sufferers participated in a cross-sectional, single-site, study that used a specially designed computer assessment task. Participants were instructed on the probability of experiencing the 3 most commonly experienced side effects for several blinded medication profiles: divalproex sodium, venlafaxine, gabapentin, propranolol, and topiramate. After learning the likelihood of experiencing side effect profiles of each medication, participants were asked whether they would be willing to take the medication for a given headache reduction level, which ranged from 0 to 7 days per month. The side effect profile for divalproex sodium was associated with the smallest willingness to take, with gabapentin, propranolol, and topiramate perceived to be much more agreeable. However, <60% of participants reported willingness to take any of these medications even if they provided a 50% reduction in headache frequency. Several general predictors of willingness to take were observed including high headache-related disability, depressive symptoms, and pain medication concerns including fear of tolerance. These findings suggest that if properly informed of the side effect profiles of these medications, many patients might opt for other treatments. C1 [Turner, Dana P.; Golding, Adrienne N.; Houle, Timothy T.] Wake Forest Sch Med, Dept Anesthesiol, Winston Salem, NC USA. [Turner, Dana P.; Houle, Timothy T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. RP Turner, DP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM DPTURNER@mgh.harvard.edu FU NINDS [RO1NS06525701] FX This study was supported by funding from the NINDS, RO1NS06525701. NR 26 TC 0 Z9 0 U1 9 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD OCT PY 2016 VL 157 IS 10 BP 2226 EP 2234 DI 10.1097/j.pain.0000000000000630 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DZ7AP UT WOS:000386015500012 PM 27820159 ER PT J AU Scholz, J Rathmell, JP David, WS Chad, DA Broderick, AC Perros, SG Shin, NS Wells, JL Davis, JB DiMaggio, CJ Wang, S Tate, SN AF Scholz, Joachim Rathmell, James P. David, William S. Chad, David A. Broderick, Alithia C. Perros, Stephen G. Shin, Naomi S. Wells, Jenna L. Davis, John B. DiMaggio, Charles J. Wang, Shuang Tate, Simon N. TI A standardized clinical evaluation of phenotypic diversity in diabetic polyneuropathy SO PAIN LA English DT Article DE Diabetic polyneuropathy; Neuropathic pain; Pain assessment; Phenotype ID NEUROPATHIC PAIN; POSTHERPETIC NEURALGIA; PERIPHERAL NEUROPATHY; SENSORIMOTOR POLYNEUROPATHY; DIAGNOSTIC-CRITERIA; NERVOUS-SYSTEM; DOUBLE-BLIND; HUMAN-SKIN; SYMPTOMS; MECHANISMS AB Diabetic polyneuropathy (DPN) is a major cause of neuropathic pain and a frequent target condition in analgesic treatment trials. Differences in the clinical symptoms and signs associated with DPN suggest distinct pathophysiological mechanisms underlying nerve damage and dysfunction that are likely to have therapeutic relevance. The aim of this study was to develop a tool for the bedside assessment of painful neuropathies such as DPN that captures the diversity of phenotypes. Sixty-one patients with type 2 diabetes and painful neuropathy, 19 patients with painless DPN, 25 patients with type 2 diabetes but no clinical evidence of neuropathy, and 20 healthy control subjects completed a structured interview (47 items) and a standardized physical examination (39 items). After analyzing critical features of pain and painless symptoms and examining the outcome of physical tests of sensory function, we determined principal components of the phenotypic variance among patients. Increased sensitivity to mechanical or thermal stimuli and, to a lesser extent, the sensory quality of pain or paresthesia were the most discriminating elements of DPN phenotypes. Correlation patterns of symptoms and signs indicated the involvement of functionally distinct nerve fiber populations. We combined interview questions and physical tests identifying these differences in a shortened assessment protocol that we named Standardized Evaluation of Pain and Somatosensory Function (StEPS). The protocol StEPS generates a phenotypic profile of patients with neuropathy. Separate intensity ratings for spontaneous painful symptoms and pain evoked by standard stimuli support a detailed documentation of neuropathic pain and its response to analgesic treatment. C1 [Scholz, Joachim; DiMaggio, Charles J.] Columbia Univ, Med Ctr, Dept Anesthesiol, 630 West 168th St,P&S Box 46, New York, NY 10032 USA. [Scholz, Joachim] Columbia Univ, Med Ctr, Dept Pharmacol, 630 West 168th St,P&S Box 46, New York, NY 10032 USA. [Rathmell, James P.] Brigham & Womens Hosp, Dept Anesthesia Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. [David, William S.; Chad, David A.; Wells, Jenna L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Broderick, Alithia C.; Perros, Stephen G.; Shin, Naomi S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Davis, John B.] Alzheimers Res UK Oxford Drug Discovery Inst, Oxford, England. [Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, 630 West 168th St,P&S Box 46, New York, NY 10032 USA. [Tate, Simon N.] Convergence Pharmaceut, Cambridge, England. RP Scholz, J (reprint author), Columbia Univ, Med Ctr, Dept Anesthesiol, 630 West 168th St,P&S Box 46, New York, NY 10032 USA. EM js3932@cumc.columbia.edu FU GlaxoSmithKline FX J. Scholz has received consultation fees from GlaxoSmithKline.; This work was supported by an unrestricted research grant from GlaxoSmithKline. NR 65 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD OCT PY 2016 VL 157 IS 10 BP 2297 EP 2308 DI 10.1097/j.pain.0000000000000648 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DZ7AP UT WOS:000386015500019 PM 27322439 ER PT J AU Patenaude, A AF Patenaude, Andrea TI Human Rights and Children with Cancer: Finding Solutions to Human Rights Issues Faced by Child Patients, Parents and Providers SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA. [Patenaude, Andrea] Harvard Med Sch, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 285 BP 99 EP 100 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700217 ER PT J AU Wakefield, C Georgiou, G McGill, B Fardell, J Signorelli, C Hanlon, L Tucker, K Patenaude, A Cohn, R AF Wakefield, Claire Georgiou, Gabrielle McGill, Brittany Fardell, Joanna Signorelli, Christina Hanlon, Lucy Tucker, Katherine Patenaude, Andrea Cohn, Richard TI Genetic testing for childhood cancer survivors' risk of late effects: Consumer understanding, acceptance and willingness-to-pay SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Wakefield, Claire; Georgiou, Gabrielle; McGill, Brittany; Fardell, Joanna; Signorelli, Christina; Hanlon, Lucy; Cohn, Richard] Univ New South Wales, Discipline Paediat, Sch Womens & Childrens Hlth, UNSW Med, Sydney, NSW, Australia. [Wakefield, Claire; Georgiou, Gabrielle; McGill, Brittany; Fardell, Joanna; Signorelli, Christina; Hanlon, Lucy; Cohn, Richard] Sydney Childrens Hosp, Kids Canc Ctr, Randwick, NSW, Australia. [Tucker, Katherine] Prince Wales Hosp, Dept Med Oncol, Hereditary Canc Clin, Randwick, NSW, Australia. [Tucker, Katherine] Univ New South Wales, Prince Wales Clin Sch, Sydney, NSW, Australia. [Patenaude, Andrea] Harvard Med Sch, Dept Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Dept Psychiat, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 307 BP 107 EP 108 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700235 ER PT J AU Morris, S Anderson, C Block, S AF Morris, Sue Anderson, Courtney Block, Susan TI Bereavement Risk Assessment: the Development of a Brief Screening Tool SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Morris, Sue; Anderson, Courtney; Block, Susan] Dana Farber Canc Inst, Boston, MA 02115 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 395 BP 134 EP 135 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700297 ER PT J AU Irwin, K AF Irwin, Kelly TI Addressing Inequities in Cancer Care for People with Severe Mental Illness: Collaborating across Disciplines in Research and Clinical Care SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Irwin, Kelly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Irwin, Kelly] Harvard Med Sch, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 399 BP 135 EP 137 PG 3 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700300 ER PT J AU Morris, S AF Morris, Sue TI Self-care for Clinicians - dealing with the 'burden' of care SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Morris, Sue] Dana Farber Canc Inst, Boston, MA 02115 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 445 BP 149 EP 149 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700334 ER PT J AU Minguez-Alarcon, L Gaskins, AJ Chiu, YH Souter, I Williams, PL Calafat, AM Hauser, R Chavarro, JE AF Minguez-Alarcon, Lidia Gaskins, Audrey J. Chiu, Yu-Han Souter, Irene Williams, Paige L. Calafat, Antonia M. Hauser, Russ Chavarro, Jorge E. CA EARTH Study Team TI Dietary folate intake and modification of the association of urinary bisphenol A concentrations with in vitro fertilization outcomes among women from a fertility clinic SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Bisphenol A; In vitro fertilization; Folate; Methyl donors ID FOOD-FREQUENCY QUESTIONNAIRE; ASSISTED REPRODUCTIVE TECHNOLOGIES; ESTROGEN-RECEPTOR-ALPHA; OF-THE-LITERATURE; SEMEN QUALITY; US ADULTS; PHTHALATE METABOLITES; NURSES HEALTH; EXPOSURE; OBESITY AB Experimental data in rodents suggest that the effects of bisphenol A (BPA) on oocyte development may be modified by dietary methyl donors. Whether the same interaction exists in humans is unknown. We evaluated whether intake of methyl donors modified the associations between urinary BPA concentrations and treatment outcomes among 178 women who underwent 248 IVF cycles at a fertility center in Boston between 2007 and 2012. Participants completed a validated food frequency questionnaire and provided up to two urine samples per treatment cycle. High urinary BPA concentrations were associated with a 66% lower probability of implantation (p = 0.007) among women who consumed <400 mu g/day of food folate, but not among women consuming >= 400 mu g/day (21% higher probability of implantation, p=0.18) (p,interaction=0.04). A similar pattern was observed for probability of clinical pregnancy (p,interaction=0.07) and live birth (p,interaction=0.16). These results are consistent with previous animal data but further evaluation in other human populations is needed. (C) 2016 Elsevier Inc. All rights reserved. C1 [Minguez-Alarcon, Lidia; Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Gaskins, Audrey J.; Chiu, Yu-Han; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Gaskins, Audrey J.; Chiu, Yu-Han; Williams, Paige L.; Hauser, Russ; Chavarro, Jorge E.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Souter, Irene; Hauser, Russ] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Souter, Irene; Hauser, Russ; Chavarro, Jorge E.] Harvard Med Sch, Boston, MA 02114 USA. [Williams, Paige L.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Calafat, Antonia M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. RP Minguez-Alarcon, L (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lminguez@hsph.harvard.edu FU NIH from the National Institute for Environmental Health Sciences [R01ES022955, R01ES009718, R01ES000002]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007703-16, P30DK46200] FX NIH grants R01ES022955, R01ES009718, R01ES000002 from the National Institute for Environmental Health Sciences, T32DK007703-16 and P30DK46200 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 72 TC 1 Z9 1 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD OCT PY 2016 VL 65 BP 104 EP 112 DI 10.1016/j.reprotox.2016.07.012 PG 9 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA DZ6RZ UT WOS:000385990900013 PM 27423903 ER PT J AU Roohipoor, R Sharifian, E Ghassemi, F Riazi-Esfahani, M Karkhaneh, R Fard, MA Zarei, M Modjtahedi, BS Moghimi, S AF Roohipoor, Ramak Sharifian, Elaheh Ghassemi, Fariba Riazi-Esfahani, Mohammad Karkhaneh, Reza Fard, Masoud Aghsaei Zarei, Mohammad Modjtahedi, Bobeck S. Moghimi, Sasan TI CHOROIDAL THICKNESS CHANGES IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION VERSUS PANRETINAL PHOTOCOAGULATION WITH INTRAVITREAL BEVACIZUMAB SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE bevacizumab; diabetes; diabetic retinopathy; panretinal photocoagulation; proliferative diabetic retinopathy; choroidal thickness; optical coherence tomography ID OPTICAL COHERENCE TOMOGRAPHY; GROWTH-FACTOR THERAPY; MACULAR EDEMA; LASER PHOTOCOAGULATION; EYES; DEGENERATION; INJECTION AB Purpose:To compare choroidal thickness (CT) and retinal thickness (RT) between eyes with proliferative diabetic retinopathy treated with panretinal photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB).Methods:Thirty-three patients with proliferative diabetic retinopathy were randomized to have one eye treated with PRP and the other with PRP + IVB. Change in CT was compared with baseline using enhanced depth imaging-optical coherence tomography at baseline and Months 1, 3, 6, and 10 after treatment. Change in RT was similarly assessed using spectral domain optical coherence tomography. Changes in both CT and RT were assessed in all nine macular areas as defined by Early Treatment Diabetic Retinopathy Study subfields.Results:The PRP + IVB group had a significant decrease in subfoveal CT at 3 and 10 months (323.9 62 m at baseline vs. 320.7 +/- 64.8 m at Month 3 [P = 0.024] and 304.7 +/- 65.6 m at Month 10 [P = 0.003]). Subfoveal CT significantly decreased at 10 months compared with baseline in the PRP group (320.8 +/- 57.7 at baseline to 297 +/- 66.3 m at 10 months, P = 0.01). Subfoveal CT was not significantly different between the 2 groups at 10 months. The best-corrected visual acuity did not change after treatment in the two groups, and there was no correlation between BCVA and CT changes (r = 0.222, P = 0.37 in the PRP group and r = 0.387, P = 0.12 in the PRP + IVB group). Significant increases in RT were seen in the PRP + IVB group at 6 months and in the PRP group at Months 1, 3, 6, and 10. A correlation between changes in CT and RT was only seen in the PRP group at 10 months after treatment.Conclusion:Eyes with proliferative diabetic retinopathy treated with PRP + IVB and PRP both had significant reduction in CT at 10 months; however, the eyes that were also treated with IVB also underwent an earlier but transient reduction at 3 months. Patients treated with IVB underwent less increase in RT. C1 [Roohipoor, Ramak; Sharifian, Elaheh; Ghassemi, Fariba; Riazi-Esfahani, Mohammad; Karkhaneh, Reza; Fard, Masoud Aghsaei; Zarei, Mohammad; Moghimi, Sasan] Univ Tehran, Eye Res Ctr, Farabi Eye Hosp, Med Sci, Tehran, Iran. [Roohipoor, Ramak; Zarei, Mohammad; Modjtahedi, Bobeck S.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Moghimi, S (reprint author), Univ Tehran, Eye Res Ctr, Farabi Eye Hosp, Med Sci, Tehran, Iran. EM sasanimii@yahoo.com OI Ghassemi, Fariba/0000-0001-9423-9650 NR 28 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 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2016 VL 36 IS 10 BP 1997 EP 2005 DI 10.1097/IAE.0000000000001027 PG 9 WC Ophthalmology SC Ophthalmology GA DZ6US UT WOS:000385998600037 PM 27046456 ER PT J AU Li, XB Thermenos, HW Wu, ZY Momura, Y Wu, K Keshavan, M Seidman, L DeLisi, LE AF Li, Xiaobo Thermenos, Heidi W. Wu, Ziyan Momura, Yoko Wu, Kai Keshavan, Matcheri Seidman, Lawrence DeLisi, Lynn E. TI Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Functional MRI; High-risk; Language; Verbal working memory; Spatial working memory ID ULTRA-HIGH RISK; 1ST-EPISODE SCHIZOPHRENIA; DIAGNOSTIC INTERVIEW; 1ST-DEGREE RELATIVES; WORKING-MEMORY; BRAIN IMAGES; FMRI; INDIVIDUALS; PSYCHOSIS; MOTION AB Background: Working memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal-and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. Methods: Functional MRI data acquired during a verbal-vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A-B), 4) spatial higher than verbal (B-A), 5) conjunction of brain regions that were activated during both A and B (A. B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. Results: Compared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A-B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. Conclusions: Our findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia. (C) 2016 Elsevier B.V. All rights reserved. C1 [Li, Xiaobo] New Jersey Inst Technol, Dept Biomed Engn, Newark, NJ 07102 USA. [Li, Xiaobo; Wu, Ziyan] New Jersey Inst Technol, Dept Elect & Comp Engn, Newark, NJ 07102 USA. [Thermenos, Heidi W.] VA Boston Healthcare Syst, Brockton, MA USA. [Momura, Yoko] CUNY Queens Coll, Dept Psychol, New York, NY USA. [Wu, Kai] South China Univ Technol, Sch Mat Sci & Engn, Dept Biomed Engn, Guangzhou, Guangdong, Peoples R China. [Keshavan, Matcheri; Seidman, Lawrence; DeLisi, Lynn E.] Harvard Med Sch, Boston, MA USA. [Keshavan, Matcheri; Seidman, Lawrence] Beth Israel Deakoness Hosp, Boston, MA USA. RP Li, XB (reprint author), New Jersey Inst Technol Univ Hts, Newark, NJ 07102 USA. EM xli.aecom@gmail.com FU NIMH [R21 MH071720] FX This project was partially supported by a grant from NIMH, R21 MH071720. NR 35 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2016 VL 176 IS 2-3 BP 100 EP 105 DI 10.1016/j.schres.2016.07.022 PG 6 WC Psychiatry SC Psychiatry GA DX1LZ UT WOS:000384130200003 PM 27481817 ER PT J AU Lee, JS Kima, CY Joo, YH Newell, D Bouix, S Shenton, ME Kubicki, M AF Lee, Jung Sun Kima, Chang-Yoon Joo, Yeon Ho Newell, Dominick Bouix, Sylvain Shenton, Martha E. Kubicki, Marek TI Increased diffusivity in gray matter in recent onset schizophrenia is associated with clinical symptoms and social cognition SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Gray matter; Diffusivity; MRI ID DENDRITIC-SPINE PATHOLOGY; 1ST EPISODE SCHIZOPHRENIA; SUPERIOR TEMPORAL SULCUS; TENSOR IMAGING DTI; HIGH GENETIC RISK; WHITE-MATTER; 1ST-EPISODE SCHIZOPHRENIA; CORPUS-CALLOSUM; PREFRONTAL CORTEX; MULTIPLE-SCLEROSIS AB Introduction: Diffusion weighted MRI (dMRI) is a method sensitive to pathological changes affecting tissue microstructure. Most dMRI studies in schizophrenia, however, have focused solely on white matter. There is a possibility, however, that subtle changes in diffusivity exist in gray matter (GM). Accordingly, we investigated diffusivity in GM in patients with recent onset schizophrenia. Methods: We enrolled 45 patients and 21 age and sex-matched healthy controls. All subjects were evaluated using the short form of the Wechsler Adult Intelligence Scale, the Positive and Negative Syndrome Scale (PANSS), and the video based social cognition scale. DMRI and T1W images were acquired on a 3 Tesla magnet, and mean Fractional Anisotropy (FA), Trace (TR) and volume were calculated for each of the 68 cortical GM Regions of Interest parcellated using Free Surfer. Results: There was no significant difference of FA and GM volume between groups after Bonferroni correction. For the dMRI measures, however, patients evinced increased TR in the left bank of the superior temporal sulcus, the right inferior parietal, the right inferior temporal, and the right middle temporal gyri. In addition, higher TR in the right middle temporal gyrus and the right inferior temporal gyrus, respectively, was associated with decreased social function and higher PANSS score in patients with schizophrenia. Conclusion: This study demonstrates high sensitivity of dMRI to subtle pathology in GM in recent onset schizophrenia, as well as an association between increased diffusivity in temporal GM regions and abnormalities in social cognition and exacerbation of psychiatric symptoms. (C) 2016 Elsevier B.V. All rights reserved. C1 [Lee, Jung Sun; Kima, Chang-Yoon; Joo, Yeon Ho] Univ Ulsan, Dept Psychiat, Asan Med Ctr, Coll Med, Seoul, South Korea. [Lee, Jung Sun; Newell, Dominick; Bouix, Sylvain; Shenton, Martha E.; Kubicki, Marek] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA. [Shenton, Martha E.; Kubicki, Marek] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. RP Kubicki, M (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. EM kubicki@bwh.harvard.edu FU National Research Foundation of Korea [NRF-2012R1A1A1006514]; Korean Society for Schizophrenia Research; National Institute of Mental Health [R01 MH102377, R01 MH074794]; VA merit Award [101 CX000176-06] FX This study was supported by the National Research Foundation of Korea (NRF-2012R1A1A1006514, JSL), Korean Society for Schizophrenia Research (2008 yr, JSL), National Institute of Mental Health (R01 MH102377, R01 MH074794, MK), and a VA merit Award (101 CX000176-06, MES). NR 104 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2016 VL 176 IS 2-3 BP 144 EP 150 DI 10.1016/j.schres.2016.08.011 PG 7 WC Psychiatry SC Psychiatry GA DX1LZ UT WOS:000384130200010 PM 27554199 ER PT J AU McCleery, A Lee, J Fiske, AP Ghermezi, L Hayata, JN Hellemann, GS Horan, WP Kee, KS Kern, RS Knowlton, BJ Subotnik, KL Ventura, J Sugar, CA Nuechterlein, KH Green, MF AF McCleery, Amanda Lee, Junghee Fiske, Alan P. Ghermezi, Livon Hayata, Jacqueline N. Hellemann, Gerhard S. Horan, William P. Kee, Kimmy S. Kern, Robert S. Knowlton, Barbara J. Subotnik, Kenneth L. Ventura, Joseph Sugar, Catherine A. Nuechterlein, Keith H. Green, Michael F. TI Longitudinal stability of social cognition in schizophrenia: A 5-year follow-up of social perception and emotion processing SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MSCEIT; RAD; Cross-lagged panel analyses; Psychosis; Illness duration; Social cognition ID FACIAL AFFECT RECOGNITION; BIPOLAR DISORDER; NEUROCOGNITION; METAANALYSIS; INTELLIGENCE; 1ST-EPISODE; RELIABILITY; IMPAIRMENT; PSYCHOSIS; SYMPTOMS AB Background: Individuals with schizophrenia exhibit marked and disproportional impairment in social cognition, which is associated with their level of community functioning. However, it is unclear whether social cognitive impairment is stable over time, or if impairment worsens as a function of illness chronicity. Moreover, little is known about the longitudinal associations between social cognition and community functioning. Method: Forty-one outpatients with schizophrenia completed tests of emotion processing (Mayer-Salovey-Caruso Emotional Intelligence Test, MSCEIT) and social perception (Relationships Across Domains, RAD) at baseline and approximately five years later. Stability of performance was assessed using paired t-tests and correlations. Longitudinal associations between social cognition and community functioning (Role Functioning Scale, RFS) were assessed using cross-lagged panel correlation analysis. Results: Performance on the two social cognition tasks were stable over follow-up. There were no significant mean differences between assessment points [p's >= 0.20, Cohen'sd's <= \0.20\], and baseline performance was highly correlated with performance at follow-up [rho's >= 0.70, ICC >= 0.83, p's < 0.001]. The contemporaneous association between social cognition and community functioning was moderately large at follow-up [rho = 0.49, p = 0.002]. However, baseline social cognition did not show a significant longitudinal influence on follow-up community functioning [z=0.31, p=0.76]. Conclusions: These data support trait-like stability of selected areas of social cognition in schizophrenia. Cross-lagged correlations did not reveal a significant unidirectional influence of baseline social cognition on community functioning five years later. However, consistent with the larger literature, a moderately large cross-sectional association between social cognition and community functioning was observed. Based on stability and cross-sectional associations, these results suggest that social cognition might have short-term implications for functional outcome rather than long-term consequences. (C) 2016 Elsevier B.V. All rights reserved. C1 [McCleery, Amanda; Lee, Junghee; Ghermezi, Livon; Hayata, Jacqueline N.; Hellemann, Gerhard S.; Horan, William P.; Kern, Robert S.; Subotnik, Kenneth L.; Ventura, Joseph; Sugar, Catherine A.; Nuechterlein, Keith H.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [McCleery, Amanda; Knowlton, Barbara J.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [McCleery, Amanda; Lee, Junghee; Horan, William P.; Kern, Robert S.; Sugar, Catherine A.; Green, Michael F.] Greater Los Angeles VA Healthcare Syst, MIRECC VISN 22, Los Angeles, CA USA. [Fiske, Alan P.] Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90024 USA. [Kee, Kimmy S.] Calif State Univ Channel Isl, Dept Psychol, Camarillo, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. RP McCleery, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Semel Inst Neurosci & Human Behav, 300 Med Plaza,Room 2240, Los Angeles, CA 90095 USA. EM amccleery@mednet.ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU National Institutes of Health (NIH) [T32MH096682-03]; NIH [P50MH066286, R01MH037705]; Janssen Scientific Affairs [RIS-NAP-4009] FX A. McCleery is supported by an institutional fellowship from the National Institutes of Health (NIH; T32MH096682-03). Subject recruitment and data collection were supported by grants P50MH066286 and R01MH037705 from NIH (K.H. Nuechterlein, PI) and RIS-NAP-4009 from Janssen Scientific Affairs (K.H. Nuechterlein, PI). NR 43 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2016 VL 176 IS 2-3 BP 467 EP 472 DI 10.1016/j.schres.2016.07.008 PG 6 WC Psychiatry SC Psychiatry GA DX1LZ UT WOS:000384130200060 PM 27443808 ER PT J AU Dykstra, B Lee, J Mortensen, LJ Yu, HX Wu, ZLL Lin, CP Rossi, DJ Sackstein, R AF Dykstra, Brad Lee, Jungmin Mortensen, Luke J. Yu, Haixiao Wu, Zhengliang L. Lin, Charles P. Rossi, Derrick J. Sackstein, Robert TI Glycoengineering of E-Selectin Ligands by Intracellular versus Extracellular Fucosylation Differentially Affects Osteotropism of Human Mesenchymal Stem Cells SO STEM CELLS LA English DT Article DE Mesenchymal stromal cell; HCELL; GPS; E-selectin; sialyl Lewis X; Fucosyltransferase; Exofucosylation; Modified mRNA; Intravital microscopy ID MODIFIED MESSENGER-RNA; STROMAL CELLS; BONE-MARROW; ENHANCES ENGRAFTMENT; P-SELECTIN; IN-VIVO; EXPRESSION; CXCR4; TRANSPLANTATION; PLURIPOTENCY AB Human mesenchymal stem cells (MSCs) hold great promise in cellular therapeutics for skeletal diseases but lack expression of E-selectin ligands that direct homing of blood-borne cells to bone marrow. Previously, we described a method to engineer E-selectin ligands on the MSC surface by exofucosylating cells with fucosyltransferase VI (FTVI) and its donor sugar, GDP-Fucose, enforcing transient surface expression of the potent E-selectin ligand HCELL with resultant enhanced osteotropism of intravenously administered cells. Here, we sought to determine whether E-selectin ligands created via FTVI-exofucosylation are distinct in identity and function to those created by FTVI expressed intracellularly. To this end, we introduced synthetic modified mRNA encoding FTVI (FUT6-modRNA) into human MSCs. FTVI-exofucosylation (i.e., extracellular fucosylation) and FUT6-modRNA transfection (i.e., intracellular fucosylation) produced similar peak increases in cell surface E-selectin ligand levels, and shear-based functional assays showed comparable increases in tethering/rolling on human endothelial cells expressing E-selectin. However, biochemical analyses revealed that intracellular fucosylation induced expression of both intracellular and cell surface E-selectin ligands and also induced a more sustained expression of E-selectin ligands compared to extracellular fucosylation. Notably, live imaging studies to assess homing of human MSC to mouse calvarium revealed more osteotropism following intravenous administration of intracellularly-fucosylated cells compared to extracellularly-fucosylated cells. This study represents the first direct analysis of E-selectin ligand expression programmed on human MSCs by FTVI-mediated intracellular versus extracellular fucosylation. The observed differential biologic effects of FTVI activity in these two contexts may yield new strategies for improving the efficacy of human MSCs in clinical applications. Stem Cells2016;34:2501-2511 C1 [Dykstra, Brad; Sackstein, Robert] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Dykstra, Brad; Sackstein, Robert] Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. [Dykstra, Brad; Sackstein, Robert] Boston Childrens Hosp, Program Excellence Glycosci, Boston, MA USA. [Lee, Jungmin; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Div Hematol Oncol, Boston, MA USA. [Lee, Jungmin; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Mortensen, Luke J.] Univ Georgia, Regenerat Biosci Ctr, Rhodes Ctr Anim & Dairy Sci, Athens, GA 30602 USA. [Mortensen, Luke J.] Univ Georgia, Coll Engn, Athens, GA 30602 USA. [Yu, Haixiao; Wu, Zhengliang L.] R&D Syst Inc, Biotechne, Minneapolis, MN USA. [Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sackstein, Robert] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Sackstein, R (reprint author), Harvard Inst Med, Room 671,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM rsackstein@partners.org OI Mortensen, Luke/0000-0002-4331-4099 FU NIH National Heart Lung Blood Institute (NHLBI) Program of Excellence in Glycosciences (PEG) grant [PO1-HL107146]; Team Jobie Fund; NIH [R01 EB017274, RO1HL107630, HL107440, UC4DK104218, U19HL1 29903]; Soft Bones Foundation Maher Family Research Grant; UGA OVPR Faculty Research grant; Leona M. and Harry B. Helmsley Charitable Trust; New York Stem Cell Foundation FX The authors thank the MGH Bone Marrow Transplant Cellular Processing Laboratory for provision of discarded bone marrow filters, and Conor Donnelly for expert technical assistance. R.S. is supported by the NIH National Heart Lung Blood Institute (NHLBI) Program of Excellence in Glycosciences (PEG) grant PO1-HL107146, and the Team Jobie Fund. C.L. is supported by NIH R01 EB017274. L.J.M. is supported by the Soft Bones Foundation Maher Family Research Grant and UGA OVPR Faculty Research grant. D.J.R. is supported by grants from the NIH (RO1HL107630, HL107440, UC4DK104218, and U19HL1 29903), the Leona M. and Harry B. Helmsley Charitable Trust, and the New York Stem Cell Foundation. NR 32 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD OCT PY 2016 VL 34 IS 10 BP 2501 EP 2511 DI 10.1002/stem.2435 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA DZ8XA UT WOS:000386154700005 PM 27335219 ER PT J AU Miller, CJ McInnes, DK Stolzmann, K Bauer, MS AF Miller, Christopher J. McInnes, D. Keith Stolzmann, Kelly Bauer, Mark S. TI Interest in Use of Technology for Healthcare Among Veterans Receiving Treatment for Mental Health SO TELEMEDICINE AND E-HEALTH LA English DT Article DE behavioral health; e-health; m-health; telehealth ID TELEMENTAL HEALTH; RECORD; INTERNET; VALIDITY; PROGRAM; TESTS; TRIAL AB Introduction:There is great interest in leveraging technology, including cell phones and computers, to improve healthcare. A range of e-health applications pertaining to mental health such as messaging for prescription refill or mobile device videoconferencing are becoming more available, but little is known about the mental health patient's interest in using these newer applications.Methods:We mailed a survey to 300 patients seen in the general mental health clinic of a local Veterans Affairs Medical Center. Survey questions focused on interest in use of cell phones, tablets, and other computers in patients' interactions with the healthcare system.Results:A total of 74 patients, primarily treated for depression, post-traumatic stress disorder, or anxiety disorders, returned completed surveys. Nearly all reported having a cell phone (72/74, 97%), but fewer than half reported having a smartphone (35/74, 47%). Overall, a substantial majority (64/74, 86%) had access to an Internet-capable device (smartphone or computer, including tablets). Respondents appeared to prefer computers to cell phones for some health-related communications, but did not express differential interest for other tasks (such as receiving appointment reminders). Interest in use was higher among younger veterans.Discussion:Most veterans with a mental health diagnosis have access to technology (including cell phones and computers) and are interested in using that technology for some types of healthcare-related communications.Conclusions:While there is capacity to utilize information technology for healthcare purposes in this population, interests vary widely, and a substantial minority does not have access to relevant devices. Although interest in using computers for health-related communication was higher than interest in using cell phones, single-platform technology-based interventions may nonetheless exclude crucial segments of the population. C1 [Miller, Christopher J.; Stolzmann, Kelly; Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 152M,150 S Huntington Ave, Boston, MA 02130 USA. [Miller, Christopher J.; Bauer, Mark S.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [McInnes, D. Keith] Edith Nourse Rogers Mem VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [McInnes, D. Keith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Miller, CJ (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 152M,150 S Huntington Ave, Boston, MA 02130 USA. EM christopher.miller8@va.gov FU Quality Enhancement Research Initiative (QUERI) RRP-Implementing Collaborative Care to Structure General Mental Health Teamsfrom the U.S. Department of Veterans Affairs, Health Services Research and Development Service [13-237] FX This work was supported by the Quality Enhancement Research Initiative (QUERI) RRP # 13-237-Implementing Collaborative Care to Structure General Mental Health Teamsfrom the U.S. Department of Veterans Affairs, Health Services Research and Development Service. The contents do not represent the views of the U.S. Department of Veterans Affairs or of the U.S. Government. NR 34 TC 2 Z9 2 U1 6 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD OCT PY 2016 VL 22 IS 10 BP 847 EP 854 DI 10.1089/tmj.2015.0190 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ9PR UT WOS:000386211100009 PM 26982279 ER PT J AU Bauer, MS Krawczyk, L Miller, CJ Abel, E Osser, DN Franz, A Brandt, C Rooney, M Fleming, J Godleski, L AF Bauer, Mark S. Krawczyk, Lois Miller, Christopher J. Abel, Erica Osser, David N. Franz, Aleda Brandt, Cynthia Rooney, Meghan Fleming, Jerry Godleski, Linda TI Team-Based Telecare for Bipolar Disorder SO TELEMEDICINE AND E-HEALTH LA English DT Article DE bipolar disorder; implementation; quality; telehealth ID STARTING ANTIDEPRESSANT TREATMENT; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; TELEMENTAL HEALTH-SERVICES; TELEPHONE CARE MANAGEMENT; COLLABORATIVE CARE; CHRONIC ILLNESS; II DISORDERS; VETERANS; SUICIDE AB Introduction:Numerous randomized controlled trials indicate that collaborative chronic care models improve outcome in a wide variety of mental health conditions, including bipolar disorder. However, their spread into clinical practice is limited by the need for a critical mass of patients and specialty providers in the same locale. Clinical videoconferencing has the potential to overcome these geographic limitations.Materials and Methods:A videoconference-based collaborative care program for bipolar disorder was implemented in the Department of Veterans Affairs. Program evaluation assessed experience with the first 400 participants, guided by five domains specified by the American Telemedicine Association: treatment engagement, including identification of subpopulations at risk for not being reached; participation in treatment; clinical impact; patient safety; and quality of care.Results:Participation rates resembled those for facility-based collaborative care. No participant characteristics predicted nonengagement. Program completers demonstrated significant improvements in several clinical indices, without evidence of compromise in patient safety. Guideline-based quality of care assessment after 1 year indicated increased lithium use, decreased antidepressant use, and increased prazosin use in individuals with comorbid post-traumatic stress disorder, but no impact on already high rates of lithium serum level monitoring.Discussion:Clinical videoconferencing can extend the reach of collaborative care models for bipolar disorder. The next step involves assessment of the videoconference-based collaborative care for other serious mental health conditions, investigation of barriers and facilitators of broad implementation of the model, and evaluation of the business case for deployment and sustainability in clinical practice. C1 [Bauer, Mark S.; Miller, Christopher J.] VA Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Bauer, Mark S.; Krawczyk, Lois; Miller, Christopher J.; Osser, David N.; Fleming, Jerry] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Bauer, Mark S.; Krawczyk, Lois; Miller, Christopher J.; Osser, David N.; Fleming, Jerry] VA Boston Healthcare Syst, Boston, MA USA. [Abel, Erica; Franz, Aleda; Brandt, Cynthia; Godleski, Linda] Yale Sch Med, West Haven, CT USA. [Abel, Erica; Franz, Aleda; Brandt, Cynthia; Godleski, Linda] VA Connecticut Healthcare Syst, West Haven, CT USA. [Rooney, Meghan] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Godleski, Linda] VA Cent Off, Off Telehlth Serv, West Haven, CT USA. RP Bauer, MS (reprint author), VA Boston Healthcare Syst, 152M,150 South Huntington Ave, Jamaica Plain, MA 02130 USA. EM mark.bauer@va.gov FU U.S. Department of Veterans Affairs; VA Health Services Research and Development center [CIN-13-403]; VA Quality Enhancement Research Initiative grant [QUE-15-289] FX Although this work was funded by the U.S. Department of Veterans Affairs, the views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. Government. The authors appreciate the comments of Eric Smith, MD, MPH, on a prior version of this article. This work was supported by clinical funds from the U.S. Department of Veterans Affairs and VA Health Services Research and Development center grant #CIN-13-403 and VA Quality Enhancement Research Initiative grant #QUE-15-289. NR 58 TC 0 Z9 0 U1 6 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD OCT PY 2016 VL 22 IS 10 BP 855 EP 864 DI 10.1089/tmj.2015.0255 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ9PR UT WOS:000386211100010 PM 26906927 ER PT J AU Ross, DS Burch, HB Cooper, DS Greenlee, MC Laurberg, P Maia, AL Rivkees, SA Samuels, M Sosa, JA Stan, MN Walter, MA AF Ross, Douglas S. Burch, Henry B. Cooper, David S. Greenlee, M. Carol Laurberg, Peter Maia, Ana Luiza Rivkees, Scott A. Samuels, Mary Sosa, Julie Ann Stan, Marius N. Walter, Martin A. TI 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis SO THYROID LA English DT Article ID AMIODARONE-INDUCED THYROTOXICOSIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; ANTITHYROID DRUG-THERAPY; ENDOGENOUS SUBCLINICAL HYPERTHYROIDISM; PERCUTANEOUS ETHANOL INJECTION; PEDIATRIC GRAVES-DISEASE; FLOW DOPPLER SONOGRAPHY; QUALITY-OF-LIFE; IODINE-INDUCED THYROTOXICOSIS; SECRETING PITUITARY-ADENOMAS AB Background: Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods: The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results: Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. Conclusions: One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice. C1 [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Burch, Henry B.] Walter Reed Natl Mil Med Ctr, Endocrinol Metab Serv, Bethesda, MD USA. [Cooper, David S.] Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD USA. [Greenlee, M. Carol] Western Slope Endocrinol, Grand Junction, CO USA. [Laurberg, Peter] Aalborg Univ, Dept Clin Med, Aalborg, Denmark. [Laurberg, Peter] Aalborg Univ, Dept Endocrinol, Aalborg, Denmark. [Laurberg, Peter] Aalborg Univ Hosp, Aalborg, Denmark. [Maia, Ana Luiza] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Thyroid Sect, Porto Alegre, RS, Brazil. [Rivkees, Scott A.] Univ Florida, Coll Med, Pediat Chairmans Off, Gainesville, FL USA. [Samuels, Mary] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. [Sosa, Julie Ann] Duke Univ, Sch Med, Sect Endocrine Surg, Durham, NC USA. [Stan, Marius N.] Mayo Clin, Div Endocrinol, Rochester, MN USA. [Walter, Martin A.] Univ Hosp Bern, Inst Nucl Med, Bern, Switzerland. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid ACC 730, 15 Parkman St, Boston, MA 02114 USA. EM dross@partners.org RI Walter, Martin/B-5203-2017 FU Novo Nordisk; AstraZeneca; GlaxoSmithKline; Eli Lilly FX Julie Ann Sosa discloses significant financial interests or other relationships as a Member, Data Monitoring Committee for Medullary Thyroid Cancer Registry supported by Novo Nordisk, AstraZeneca, GlaxoSmithKline, and Eli Lilly. The remaining authors disclose no significant financial interests or other relationships with commercial interests. NR 677 TC 10 Z9 10 U1 13 U2 13 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 OCT PY 2016 VL 26 IS 10 BP 1343 EP 1421 DI 10.1089/thy.2016.0229 PG 79 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ9SV UT WOS:000386220100001 PM 27521067 ER PT J AU Strickland, KC Vivero, M Jo, VY Lowe, AC Hollowell, M Qian, XH Wieczorek, TJ French, CA Teot, LA Sadow, PM Alexander, EK Cibas, ES Barletta, JA Krane, JF AF Strickland, Kyle C. Vivero, Marina Jo, Vickie Y. Lowe, Alarice C. Hollowell, Monica Qian, Xiaohua Wieczorek, Tad J. French, Christopher A. Teot, Lisa A. Sadow, Peter M. Alexander, Erik K. Cibas, Edmund S. Barletta, Justine A. Krane, Jeffrey F. TI Preoperative Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Prospective Analysis SO THYROID LA English DT Article ID BETHESDA SYSTEM; BRAF V600E; CARCINOMA; VARIANT; CYTOPATHOLOGY; MUTATION; MALIGNANCY; CANCER; IMPACT; RATES AB Background: The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been proposed to replace noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) in recognition of the indolent behavior of this tumor. The ability to differentiate NIFTP from classical papillary thyroid carcinoma (cPTC) by fine-needle aspiration (FNA) would facilitate conservative management for NIFTP. The aim of this study was to determine if NIFTP can be distinguished prospectively from cPTC. Methods: From June 2015 to January 2016, thyroid FNAs with a diagnosis of malignant or suspicious for malignancy were prospectively scored for features associated with NIFTP/FVPTC (microfollicular architecture) or cPTC (papillae, psammomatous calcifications, sheet-like architecture, and nuclear pseudoinclusions) and categorized as NIFTP/FVPTC, cPTC, or indeterminate. Results were correlated with subsequent histologic diagnoses. Results: The study included 52 patients with 56 resected nodules with a cytologic diagnosis of malignant (43/56) or suspicious for malignancy (13/56). Forty-nine patients (94%) underwent initial total thyroidectomy. Histopathologic diagnoses included 42 cPTC, 8 NIFTP, 3 invasive FVPTC, 2 follicular adenomas, and 1 poorly differentiated carcinoma. Excluding 7 indeterminate cases, 89% (8/9) of nodules classified as NIFTP/FVPTC on FNA demonstrated follicular-patterned lesions on histology (5 NIFTP, 1 invasive FVPTC, 2 follicular adenomas). Cytopathologists prospectively identified cPTC in 95% (38/40) of cases. Conclusions: In thyroid FNAs with cytologic features concerning for PTC, NIFTP/FVPTC can be distinguished from cPTC in most cases by assessing a limited number of features. Therefore, it is both feasible and appropriate to attempt to separate NIFTP/FVPTC from cPTC on FNA to promote appropriate clinical management. C1 [Strickland, Kyle C.; Vivero, Marina; Jo, Vickie Y.; Lowe, Alarice C.; Hollowell, Monica; Qian, Xiaohua; Wieczorek, Tad J.; French, Christopher A.; Teot, Lisa A.; Cibas, Edmund S.; Barletta, Justine A.; Krane, Jeffrey F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Alexander, Erik K.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Sadow, Peter M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Krane, JF (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jkrane@partners.org FU Scientific Advisory Board for Asuragen Inc.; Veracyte Inc.; Asuragen; Veracyte FX Erik K. Alexander has acted as a paid member of the Scientific Advisory Board for Asuragen Inc. and as a paid consultant for Veracyte Inc. In addition, his institution has received research support from both Asuragen and Veracyte. No competing financial interests exist for the other authors. NR 18 TC 4 Z9 4 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 OCT PY 2016 VL 26 IS 10 BP 1466 EP 1471 DI 10.1089/thy.2016.0280 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ9SV UT WOS:000386220100007 PM 27457786 ER PT J AU Ferguson, FM Ni, J Zhang, TH Tesar, B Sim, T Kim, ND Deng, XM Brown, JR Zhao, JJ Gray, NS AF Ferguson, Fleur M. Ni, Jing Zhang, Tinghu Tesar, Bethany Sim, Taebo Kim, Nam Doo Deng, Xianming Brown, Jennifer R. Zhao, Jean J. Gray, Nathanael S. TI Discovery of a Series of 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-ones as Selective PI3K-delta/gamma Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE PI3K-delta; PI3K-gamma; phosphatidylinositol-4,5-bisphosphate 3-kinase-delta; p110-delta; p110-gamma; kinase inhibitor ID PI3K-GAMMA INHIBITION; KINASE; P110-DELTA; POTENT; MODELS AB Dual inhibition of PI3K-delta and PI3K-gamma is an established therapeutic strategy for treatment of hematological malignancies. Reported molecules targeting PI3K-delta/gamma selectively are chemically similar and based upon isoquinolin-1(2H)-one or quinazolin-4(3H)-one scaffolds. Here we report a chemically distinct series of potent, selective PI3K-delta/gamma inhibitors based on a 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one scaffold with comparable biochemical potency and cellular effects on PI3K signaling. We envisage these molecules will provide useful leads for development of next-generation PI3K-delta/gamma targeting therapeutics. C1 [Ferguson, Fleur M.; Ni, Jing; Zhang, Tinghu; Deng, Xianming; Zhao, Jean J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Tesar, Bethany; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tesar, Bethany; Brown, Jennifer R.] Harvard Med Sch, Dept Med, Boston, MA 02215 USA. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 02792, South Korea. [Sim, Taebo] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul 02841, South Korea. [Kim, Nam Doo] Daegu Gyeongbuk Med Innovat Fdn, Daegu 41061, South Korea. [Deng, Xianming] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Xiamen 361102, Fujian, Peoples R China. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM nathanael_gray@dfci.harvard.edu NR 19 TC 0 Z9 0 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD OCT PY 2016 VL 7 IS 10 BP 908 EP 912 DI 10.1021/acsmedchemlett.6b00209 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DZ2RQ UT WOS:000385689300009 PM 27774127 ER PT J AU Ingham, OJ Paranal, RM Smith, WB Escobar, RA Yueh, H Snyder, T Porco, JA Bradner, JE Beeler, AB AF Ingham, Oscar J. Paranal, Ronald M. Smith, William B. Escobar, Randolph A. Yueh, Han Snyder, Tracy Porco, John A., Jr. Bradner, James E. Beeler, Aaron B. TI Development of a Potent and Selective HDAC8 Inhibitor SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Histone deacetylase; HDAC; histone deacetylase 8; HDAC8; triazole; epigenetic ID HISTONE DEACETYLASE INHIBITORS; CORNELIA; CANCER; CYCLOADDITION; DISORDERS; MUTATIONS; DISCOVERY; SPECTRUM; BINDING; DESIGN AB A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8. C1 [Ingham, Oscar J.; Escobar, Randolph A.; Yueh, Han; Snyder, Tracy; Porco, John A., Jr.; Beeler, Aaron B.] Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA. [Ingham, Oscar J.; Escobar, Randolph A.; Yueh, Han; Snyder, Tracy; Porco, John A., Jr.; Beeler, Aaron B.] Boston Univ, Ctr Mol Discovery BU CMD, 590 Commonwealth Ave, Boston, MA 02215 USA. [Paranal, Ronald M.; Smith, William B.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bradner, James E.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. RP Beeler, AB (reprint author), Boston Univ, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA.; Beeler, AB (reprint author), Boston Univ, Ctr Mol Discovery BU CMD, 590 Commonwealth Ave, Boston, MA 02215 USA. EM beelera@bu.edu FU Boston University; Center for Chemical Methodology and Library Development at Boston University [GM-067041]; NSF [CHE-0619339, CHE- 0443618]; [R24-GM111625] FX Financial support from Boston University and the Center for Chemical Methodology and Library Development at Boston University (GM-067041) are gratefully acknowledged. Work at the BU-CMD is supported by R24-GM111625. NMR (CHE-0619339) and MS (CHE- 0443618) facilities at Boston University are supported by the NSF. NR 31 TC 0 Z9 0 U1 3 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD OCT PY 2016 VL 7 IS 10 BP 929 EP 932 DI 10.1021/acsmedchemlett.6b00239 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DZ2RQ UT WOS:000385689300013 PM 27774131 ER PT J AU Dahal, A Bellows, BK Sonpavde, G Tantravahi, SK Choueiri, TK Galsky, MD Agarwal, N AF Dahal, Arati Bellows, Brandon K. Sonpavde, Guru Tantravahi, Srinivas K. Choueiri, Toni K. Galsky, Matthew D. Agarwal, Neeraj TI Incidence of Severe Nephrotoxicity With Cisplatin Based on Renal Function Eligibility Criteria Indirect Comparison Meta-analysis SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE meta-analysis; cisplatin; cancer; nephrotoxicity; indirect comparison ID CELL LUNG-CANCER; RANDOMIZED PHASE-II; GEMCITABINE PLUS CISPLATIN; ADVANCED COLORECTAL-CANCER; COOPERATIVE-ONCOLOGY-GROUP; ADVANCED GASTRIC-CARCINOMA; 1ST-LINE TREATMENT; CLINICAL-TRIALS; CONTINUOUS-INFUSION; ADVANCED MELANOMA AB Background: The objective of this meta-analysis was to indirectly compare incidence of nephrotoxicity in trials using cisplatin (CIS) for treatment of solid tumors when renal function was assessed using serum creatinine (SCr) or creatinine clearance (CrCl) for eligibility criteria. Methods: Randomized trials comparing CIS-containing with non-CIS-containing chemotherapy regimens were identified in PubMed. Included studies were performed from 1990 to 2010, used SCr or CrCl as an eligibility criterion, and reported incidence of grade >= 3 nephrotoxicity for both treatment arms using World Health Organization (WHO) or National Cancer Institute (NCI) toxicity criteria. The relative risk (RR) of grade >= 3 nephrotoxicity associated with CIS versus non-CIS regimens was examined. Subgroup analyses, adjusted indirect comparison, and metaregression were used to compare SCr and CrCl. Results: The literature search identified 2359 studies, 42 studies met all the inclusion criteria (N=9521 patients). SCr was used as an eligibility criterion in 20 studies (N=4704), CrCI was used in 9 studies (N=1650), and either was used in 13 studies (N=3167). The overall RR for developing nephrotoxicity with CIS versus non-CIS treatment was 1.75 (P=0.005). Subgroup analyses showed an increased risk when SCr was used (RR= 2.60, P=0.005) but not when CrCl was used (RR= 1.50, P=0.19). Both the adjusted indirect comparison and metaregression showed a nonsignificantly reduced risk of nephrotoxicity when CrCl was used. Conclusions: CIS-based therapy was associated with a significant increase in severe nephrotoxicity. The risk of severe nephrotoxicity appears to be lower when CrCl was used to determine whether people should be treated with CIS. C1 [Dahal, Arati] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Bellows, Brandon K.] Univ Utah, Pharmacotherapy Outcomes Res Ctr, 2000 Circle Hope,Ste 2123, Salt Lake City, UT 84112 USA. [Tantravahi, Srinivas K.; Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, 2000 Circle Hope,Ste 2123, Salt Lake City, UT 84112 USA. [Sonpavde, Guru] UAB Comprehens Canc Ctr, Birmingham, AL USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Choueiri, Toni K.] Harvard Med Sch, Boston, MA USA. [Galsky, Matthew D.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. RP Agarwal, N (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope,Ste 2123, Salt Lake City, UT 84112 USA. EM neeraj.agarwal@hci.utah.edu NR 62 TC 1 Z9 1 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2016 VL 39 IS 5 BP 497 EP 506 DI 10.1097/COC.0000000000000081 PG 10 WC Oncology SC Oncology GA DY7WH UT WOS:000385339500014 PM 24824144 ER PT J AU Elshaikh, MA Vance, S Gaffney, DK Biagioli, M Jhingran, A Jolly, S Kidd, E Lee, LJ Ll, LN Moore, DH Rao, GG Wahl, AO Williams, NL Yashar, CM Small, W AF Elshaikh, Mohamed A. Vance, Sean Gaffney, David K. Biagioli, Matthew Jhingran, Anuja Jolly, Shruti Kidd, Elizabeth Lee, Larissa J. Ll, Linna Moore, David H. Rao, Gautam G. Wahl, Andrew O. Williams, Ned L. Yashar, Catheryn M. Small, William, Jr. CA Expert Panel Radiation Oncology Gy TI ACR Appropriateness Criteria (R) Management of Recurrent Endometrial Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE endometrial cancer; recurrence; appropriateness criteria; salvage; multimodality; radiation treatment ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II TRIAL; DOSE-RATE BRACHYTHERAPY; ISOLATED VAGINAL RECURRENCES; TOTAL PELVIC EXENTERATION; RADIATION-THERAPY; RANDOMIZED-TRIAL; STAGE-I; INTERSTITIAL BRACHYTHERAPY; DEFINITIVE RADIOTHERAPY AB Objectives: In women with endometrial carcinoma (EC), tumor recurrences tend to occur in the 2- to 3-year period following surgical staging. Management of disease recurrence in EC poses significant challenges. These patients represent a heterogenous group where histologic subtypes, previous adjuvant management, interval since completion of adjuvant therapy, and size and site(s) of disease recurrence all have important implications on salvage therapies and prognosis. No randomized controlled trials have been published to determine optimal management in this group of patients. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients. Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Results: Five clinical variants were developed to address common scenarios in the management of women with recurrent EC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings. Conclusions: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with recurrent EC. C1 [Elshaikh, Mohamed A.; Vance, Sean] Henry Ford Hlth Syst, Detroit, MI USA. [Jolly, Shruti] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Gaffney, David K.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Williams, Ned L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Biagioli, Matthew] Florida Hosp, Inst Canc, Orlando, FL USA. [Jhingran, Anuja] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kidd, Elizabeth] Stanford Canc Ctr, Stanford, CA USA. [Yashar, Catheryn M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Lee, Larissa J.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Ll, Linna] Bryn Mawr Hosp, Bryn Mawr, PA USA. [Moore, David H.] Indiana Univ Sch Med, Amer Coll Obstetricians & Gynecologists, Indianapolis, IN 46202 USA. [Rao, Gautam G.] Univ Maryland, Sch Med, Amer Soc Clin Oncol, Baltimore, MD 21201 USA. [Wahl, Andrew O.] Univ Nebraska Med Ctr, Omaha, NE USA. [Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. RP Elshaikh, MA (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM melshai1@hfhs.org FU NCI NIH HHS [P30 CA008748] NR 77 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2016 VL 39 IS 5 BP 507 EP 515 DI 10.1097/COC.0000000000000318 PG 9 WC Oncology SC Oncology GA DY7WH UT WOS:000385339500015 PM 27400117 ER PT J AU Tschernichovsky, R Diver, EJ Schorge, JO Goodman, A AF Tschernichovsky, Roi Diver, Elisabeth J. Schorge, John O. Goodman, Annekathryn TI The Role of Lymphadenectomy Versus Sentinel Lymph Node Biopsy in Early-stage Endometrial Cancer A Review of the Literature SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE endometrial cancer; lymphadenectomy; sentinel lymph node biopsy; ultrastaging ID GYNECOLOGIC-ONCOLOGY-GROUP; UTERINE RISK-FACTORS; PARAAORTIC LYMPHADENECTOMY; SELECTIVE LYMPHADENECTOMY; TUMOR-CELLS; CARCINOMA; ADENOCARCINOMA; METASTASIS; TRIAL; MICROMETASTASES AB Objective: The objective of this study is to review existing data regarding the feasibility, diagnostic performance, and oncologic outcomes of sentinel lymph node biopsy (SLNB) versus lymphadenectomy (LND) in endometrial cancer. Materials and Methods: A PubMed search identified studies on different staging strategies in endometrial cancer, including routine LND, predictive models of selective nodal dissection, and SLNB. Results: There is ongoing controversy over the risk-benefit ratio of LND in assessing nodal involvement in presumed early-stage endometrial cancer. Current experience with sentinel node biopsy suggests high detection rates and low false-negative rates across most series, as well as the increased detection of occult metastatic disease overlooked by conventional pathology. Although data on the long-term oncologic outcomes of sentinel node biopsy in this setting are limited, short-term follow-up shows no immediate impairment of disease-free survival or overall survival rates when compared with LND. Conclusions: SLNB holds promise as a less-morbid and more accurate alternative to LND for determining nodal spread in early-stage endometrial cancer. Further studies are necessary to understand how lymph node status will guide postoperative management and impact survival of women with nodal metastases. C1 [Tschernichovsky, Roi] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. [Diver, Elisabeth J.; Schorge, John O.; Goodman, Annekathryn] Harvard Med Sch, Massachusetts Gen Hosp, Dept OB GYN, Div Gynecol Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. RP Goodman, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept OB GYN, Div Gynecol Oncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM agoodman@mgh.harvard.edu NR 66 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2016 VL 39 IS 5 BP 516 EP 521 DI 10.1097/COC.0000000000000302 PG 6 WC Oncology SC Oncology GA DY7WH UT WOS:000385339500016 PM 27281265 ER PT J AU Dubuc, AM Davids, MS Pulluqi, M Pulluqi, O Hoang, K Hernandez-Sanchez, JM Schlich, C Hernandez-Rivas, JM Brown, JR Dal Cin, P AF Dubuc, Adrian M. Davids, Matthew S. Pulluqi, Mirela Pulluqi, Olja Hoang, Kevin Hernandez-Sanchez, Jesus M. Schlich, Cathy Hernandez-Rivas, Jesus M. Brown, Jennifer R. Dal Cin, Paola TI FISHing in the dark: How the combination of FISH and conventional karyotyping improves the diagnostic yield in CpG-stimulated chronic lymphocytic leukemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; CHROMOSOMAL-ABNORMALITIES; INTERMEDIATE PROGNOSIS; COMPLEX KARYOTYPE; CLONAL EVOLUTION; 6Q DELETION; CLL; MUTATIONS; IMPACT; CYTOGENETICS AB Despite significant advances in molecular genetic approaches, fluorescence in situ hybridization (FISH) remains the gold standard for the diagnostic evaluation of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). Efforts to improve the diagnostic utility of molecular cytogenetic testing have led to the expansion of the traditional 4-probe CLL FISH panel. Not only do these efforts increase the cost of testing, they remain hindered by the inherent limitations of FISH studies - namely the inability to evaluate genomic changes outside of the targeted loci. While array-based profiling and next generation sequencing (NGS) have critically expanded our understanding of the molecular pathogenesis of CLL, these methodologies are not routinely used by diagnostic laboratories to evaluate copy number changes or the mutational profile of this disease. Mitogenic stimulation of CLL specimens with CpG-oligonucleotide (CpG-ODN) has been identified as a reliable and reproducible means of obtaining a karyotype, facilitating a low-resolution genome-wide analysis. Across a cohort of 1255 CpG-ODN-stimulated CLL specimens, we describe the clinical utility associated with the combinatorial use of FISH and karyotyping. Our testing algorithm achieves a higher diagnostic yield (similar to 10%) through the detection of complex karyotypes, well-characterized chromosomal aberrations not covered by the traditional CLL FISH panel and through the detection of concurrent secondary malignancies. Moreover, the single cell nature of this approach permits the evaluation of emerging new clinical concepts including clonal dynamics and clonal evolution. This approach can be broadly applied by diagnostic laboratories to improve the utility of traditional and molecular cytogenetic studies of CLL. (C) 2016 Wiley Periodicals, Inc. C1 [Dubuc, Adrian M.; Pulluqi, Mirela; Pulluqi, Olja; Schlich, Cathy; Dal Cin, Paola] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Dubuc, Adrian M.; Davids, Matthew S.; Brown, Jennifer R.; Dal Cin, Paola] Harvard Med Sch, Boston, MA USA. [Davids, Matthew S.; Hoang, Kevin; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hernandez-Sanchez, Jesus M.; Hernandez-Rivas, Jesus M.] Univ Salamanca, CSIC, Ctr Invest Canc, IBSAL,IBMCC, Salamanca 37007, Spain. [Hernandez-Rivas, Jesus M.] Hosp Univ Salamanca, Dept Hematol, Salamanca 37007, Spain. RP Dal Cin, P (reprint author), Brigham & Womens Hosp, Dept Pathol Cytogenet, 75 Francis St, Boston, MA 02115 USA. EM pdalcin@partners.org RI Hernandez Sanchez, Jesus M/I-8507-2016; Hernandez-Rivas, Jesus Maria/B-5459-2017 OI Hernandez Sanchez, Jesus M/0000-0003-1212-5954; Hernandez-Rivas, Jesus Maria/0000-0002-9661-9371 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 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2016 VL 91 IS 10 BP 978 EP 983 DI 10.1002/ajh.24452 PG 6 WC Hematology SC Hematology GA DY6TJ UT WOS:000385260900016 PM 27341486 ER PT J AU Castillo, JJ Gustine, J Meid, K Dubeau, T Hunter, ZR Treon, SP AF Castillo, Jorge J. Gustine, Joshua Meid, Kirsten Dubeau, Toni Hunter, Zachary R. Treon, Steven P. TI Histological transformation to diffuse large B-cell lymphoma in patients with Waldenstrom macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID END RESULTS DATABASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOPLASMACYTIC LYMPHOMA; INTERNATIONAL WORKSHOP; FOLLICULAR LYMPHOMA; INDOLENT LYMPHOMA; NAIVE PATIENTS; SEER DATABASE; DOUBLE-HIT; OUTCOMES AB Histological transformation to diffuse large B-cell lymphoma (DLBCL) rarely occurs in patients with Waldenstrom Macroglobulinemia (WM). We identified 20 patients out of a cohort of 1,466 WM patients who experienced histologic transformation. The 5, 10, and 15-year cumulative incidence rates were 1, 2.4, and 3.8%, respectively. Approximately half of the patients were naive to nucleoside analogues, and a quarter were previously untreated for WM at the time of transformation. More than 80% of patients presented with extranodal involvement, 65% with high IPI scores. DLBCL cells did not express CD10 but expressed BCL6 and BCL2. All patients were treated with chemoimmunotherapy. The median survival from histological transformation was 2.7 years. The median overall survival was shorter for transformed patients versus those who did not transform (estimated 9 vs. 16 years; P=0.09). Histological transformation to DLBCL is rare, and is associated with inferior survival in WM. (C) 2016 Wiley Periodicals, Inc. C1 [Castillo, Jorge J.; Gustine, Joshua; Meid, Kirsten; Dubeau, Toni; Hunter, Zachary R.; Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,Mayer 221, Boston, MA 02215 USA. EM Jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 FU Abbvie; Gilead; Millennium; Pharmacyclics; Janssen; Onyx FX JJC received honoraria from Alexion, Biogen, Celgene and Otsuka, and research funding from Abbvie, Gilead, Millennium, and Pharmacyclics. SPT received research funding and/or honoraria from Gilead, Janssen, Onyx, and Pharmacyclics. JG, KM, TD, and ZRH have no conflicts of interest to disclose. NR 29 TC 1 Z9 1 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 OCT PY 2016 VL 91 IS 10 BP 1032 EP 1035 DI 10.1002/ajh.24477 PG 4 WC Hematology SC Hematology GA DY6TJ UT WOS:000385260900025 PM 27415417 ER PT J AU Levin, SN de Gusmao, CM Etherton, MR Rondeau, MW Meredith, DM Folkerth, RD Klein, JP Nadeem, O Castillo, JJ AF Levin, Seth N. de Gusmao, Claudio M. Etherton, Mark R. Rondeau, M. Will Meredith, David M. Folkerth, Rebecca D. Klein, Joshua P. Nadeem, Omar Castillo, Jorge J. TI "All the soarings of my mind begin in my blood:" central nervous system complication of Waldenstrom macroglobulinemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Editorial Material ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; BING-NEEL SYNDROME; AIDS; HIV; INFECTION; DIAGNOSIS; MUTATION; DISEASE C1 [Levin, Seth N.; de Gusmao, Claudio M.; Etherton, Mark R.; Rondeau, M. Will; Klein, Joshua P.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Levin, Seth N.; de Gusmao, Claudio M.; Etherton, Mark R.; Meredith, David M.; Folkerth, Rebecca D.; Klein, Joshua P.; Castillo, Jorge J.] Harvard Med Sch, Boston, MA USA. [Meredith, David M.; Folkerth, Rebecca D.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Nadeem, Omar] Newton Wellesley Hosp, Dept Med Oncol, Newton, MA USA. [Castillo, Jorge J.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. RP Levin, SN (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM snlevin@partners.org OI Castillo, Jorge/0000-0001-9490-7532 NR 25 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 2016 VL 91 IS 10 BP 1057 EP 1060 DI 10.1002/ajh.24476 PG 4 WC Hematology SC Hematology GA DY6TJ UT WOS:000385260900029 PM 27414991 ER PT J AU Bledsoe, JR Redd, RA Hasserjian, RP Soumerai, JD Nishino, HT Boyer, DF Ferry, JA Zukerberg, LR Harris, NL Abramson, JS Sohani, AR AF Bledsoe, Jacob R. Redd, Robert A. Hasserjian, Robert P. Soumerai, Jacob D. Nishino, Ha T. Boyer, Daniel F. Ferry, Judith A. Zukerberg, Lawrence R. Harris, Nancy Lee Abramson, Jeremy S. Sohani, Aliyah R. TI The immunophenotypic spectrum of primary mediastinal large B-cell lymphoma reveals prognostic biomarkers associated with outcome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID GRAY-ZONE LYMPHOMA; CLASSICAL HODGKIN LYMPHOMA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; EXPRESSION; VINCRISTINE; DOXORUBICIN; PREDNISONE; CHOP; SURVIVAL; FEATURES AB Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) that shows overlap with classical Hodgkin lymphoma (CHL) and a favorable prognosis compared to mediastinal gray-zone lymphoma (MGZL). We performed immunohistochemistry on initial diagnostic specimens of 49 cases of uniformly treated PMBL to determine the frequency and clinical significance of expression of antigens commonly seen in CHL and MGZL, along with markers previously shown to be prognostic in DLBCL, not otherwise specified. The median age was 37 years with a female: male ratio of 2.3. After a median follow-up of 78 months, 24% of patients had relapsed or refractory disease and 22% had died; the 5-year PFS was 70%. Variable CD15 expression was seen in 31% of cases, but was not associated with adverse outcome. Hans cell-of-origin, proliferation index, and MYC/BCL2 coexpression were not associated with outcome, while low PDL1 (P=0.011) and high MUM1 (P=0.065) staining were each associated with shorter PFS. A biologic risk score (one point each for low PDL1 and high MUM1) stratified patients into three prognostic risk groups for PFS (P=0.001) and OS (P=0.032). On separate multivariate models, low PDL1 was independent of R-IPI risk group for PFS (HR 6.0, P=0.023), as was a biologic risk score of 2 (HR 5.6, P=0.011). Incorporation of the biologic risk score sub-stratified patients within R-IPI groups for both PFS (P < 0.001) and OS (P < 0.001). In summary, we characterize the immunophenotypic spectrum of PMBL and identify PDL1 and MUM1 as prognostic biomarkers for high-risk disease. (C) 2016 Wiley Periodicals, Inc. C1 [Bledsoe, Jacob R.; Hasserjian, Robert P.; Ferry, Judith A.; Zukerberg, Lawrence R.; Harris, Nancy Lee; Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. [Bledsoe, Jacob R.; Hasserjian, Robert P.; Ferry, Judith A.; Zukerberg, Lawrence R.; Harris, Nancy Lee; Sohani, Aliyah R.] Harvard Med Sch, Boston, MA USA. [Redd, Robert A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Soumerai, Jacob D.] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, 1275 York Ave, New York, NY 10021 USA. [Nishino, Ha T.] North Shore Med Ctr, Dept Pathol, Salem, MA USA. [Boyer, Daniel F.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Abramson, Jeremy S.] Harvard Med Sch, Dept Med, Boston, MA USA. RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM arsohani@partners.org FU MGH Department of Pathology; Harvard Medical School through the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine FX The would like to thank the MGH Histology and Immunohistochemistry Laboratories for their technical expertise in TMA construction and immunohistochemical staining, as well as Dr. Donna Neuberg for valuable commentary on the manuscript. ARS received salary support from the MGH Department of Pathology and Harvard Medical School through the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine. NR 44 TC 0 Z9 0 U1 2 U2 2 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 OCT PY 2016 VL 91 IS 10 BP E436 EP E441 DI 10.1002/ajh.24485 PG 6 WC Hematology SC Hematology GA DY6TJ UT WOS:000385260900002 PM 27419920 ER PT J AU Modjtahedi, BS van Zyl, T Pandya, HK Leonard, RE Eliott, D AF Modjtahedi, Bobeck S. van Zyl, Tave Pandya, Hemang K. Leonard, Robert E., II Eliott, Dean TI Endophthalmitis After Intravitreal Injections in Patients With Self-reported Iodine Allergy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TOPICAL POVIDONE-IODINE; CONTACT-DERMATITIS; CONTRAST-MEDIA; ANTISEPSIS; FLUOROQUINOLONES; ANAPHYLAXIS; PROPHYLAXIS; IRRIGATION; AGENTS; CHILD AB PURPOSE: To present cases of endophthalmitis following intravitreal injections where povidone-iodine (PI) was not used as part of the surgical preparation. DESIGN: Retrospective case series. METHODS: All cases of presumed injection-related endophthalmitis presenting to the Massachusetts Eye and Ear Infirmary between June 2008 and November 2014 and Dean McGee Eye Institute between January 2010 and January 2015 were identified. Patients who did not receive PI preparation owing to documented self-reported allergy to iodine, iodine-containing contrast material, or shellfish were identified and their injection histories and clinical courses reviewed. " RESULTS: The combined rate of postinjection endophthalmitis at these 2 centers was 0.019%. Among 42 patients with postinjection endophthalmitis, 5 (11.9%) did not receive PI prophylaxis. The mean number of intravitreal injections without PI before the development of endophthalmitis was 10.6 with a 9.4% rate of endophthalmitis (5 cases per 53 injections). All patients underwent tap-and-inject procedures with vancomycin 1 mg and ceftazidime 2 mg. Two patients did not receive PI at the time of tap and inject; 1 of these patients required subsequent pars plana vitrectomy for worsening clinical course. Cultures were positive in 4 of 5 cases; all positive cultures grew coagulase-negative Staphylococcus. All patients who received subsequent intravitreal injections received PI prophylaxis without allergic reactions, thus demonstrating a lack of true PI allergy. CONCLUSIONS: Avoiding PI owing to self-reported iodine "allergy" risks substantial ocular morbidity. Allergy testing can be pursued per patient request or in rare cases of suspected true PI allergy; however, in cases where delayed treatment would adversely affect visual outcome, the clinician should feel confident that minimal allergic risk exists. (C) 2016 Elsevier Inc. All rights reserved. C1 [Modjtahedi, Bobeck S.; van Zyl, Tave; Eliott, Dean] Harvard Med Sch, Dept Ophthalmol, Retina Serv, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. [Pandya, Hemang K.; Leonard, Robert E., II] Univ Oklahoma, Coll Med, Retina Serv, Dean McGee Eye Inst, Oklahoma City, OK 73190 USA. RP Eliott, D (reprint author), Harvard Med Sch, Dept Ophthalmol, Retina Serv, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Dean_Eliott@meei.harvard.edu 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2016 VL 170 BP 68 EP 74 DI 10.1016/j.ajo.2016.07.010 PG 7 WC Ophthalmology SC Ophthalmology GA DZ5KF UT WOS:000385900300010 PM 27448925 ER PT J AU Lee, CS Randhawa, S Lee, AY Lam, DL Van Gelder, RN AF Lee, Cecilia S. Randhawa, Sandeep Lee, Aaron Y. Lam, Deborah L. Van Gelder, Russell N. TI Patterns of Laboratory Testing Utilization Among Uveitis Specialists SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CARE AB PURPOSE: To examine the range of practice in laboratory testing utilization among a subset of uveitis specialists using a scenario-based survey. DESIGN: Cross-sectional survey. METHODS: A web-based survey consisting of 13 patient scenarios was presented to the Executive Committee and Trustees of the American Uveitis Society. The participants were allowed to choose preferred testing in a free-form manner. The patterns of test utilization were studied and the cost of the testing was calculated based on Noridian Medicare reimbursal rates for Seattle, Washington. RESULTS: Nearly all providers recommended some testing for all scenarios. Forty-five different tests, including laboratory investigations and imaging and diagnostic procedures, were ordered. The mean number of tests ordered per scenario per provider was 5.47 +/- 2.71. There was limited consensus among providers in test selection, with most tests in each scenario ordered by fewer than half of the providers. Average cost of testing per scenario per provider was $282.80, with 4 imaging tests (fluorescein angiography, magnetic resonance imaging, chest radiograph, and chest computed tomography) together contributing 59.9% of the total testing costs. CONCLUSIONS: Uveitis specialists have a high rate of laboratory testing utilization in their evaluation of new patients. There is substantial variability in the evaluations obtained between providers. Imaging tests account for the majority of evaluation cost. The low agreement on specific testing plans suggests need for evidence based practice guidelines for the evaluation of uveitis patients. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lee, Cecilia S.; Randhawa, Sandeep; Lee, Aaron Y.; Lam, Deborah L.; Van Gelder, Russell N.] Univ Washington, Sch Med, Dept Ophthalmol, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA. [Van Gelder, Russell N.] Univ Washington, Sch Med, Dept Biol Struct, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA. [Van Gelder, Russell N.] Univ Washington, Sch Med, Dept Pathol, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA. [Lee, Aaron Y.; Lam, Deborah L.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Randhawa, Sandeep] Oakland Univ, William Beaumont Sch Med, Dept Ophthalmol, Rochester, MN USA. RP Van Gelder, RN (reprint author), Univ Washington, Box 359608,325 Ninth Ave, Seattle, WA 98104 USA. EM russvg@uw.edu OI Van Gelder, Russell/0000-0001-5368-3659; Lee, Aaron/0000-0002-7452-1648 FU RESEARCH TO PREVENT BLINDNESS (NEW YORK, NY); NEI (Bethesda, MD) [K23EY024921, P30-EY001730] FX UNRESTRICTED GRANT FROM RESEARCH TO PREVENT BLINDNESS (NEW YORK, NY); NEI K23EY024921, P30-EY001730 (Bethesda, MD). NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2016 VL 170 BP 161 EP 167 DI 10.1016/j.ajo.2016.08.004 PG 7 WC Ophthalmology SC Ophthalmology GA DZ5KF UT WOS:000385900300021 PM 27521608 ER PT J AU Stagner, AM Afrogheh, AH Jakobiec, FA Iacob, CE Grossniklaus, HE Deshpande, V Maske, C Hiss, DC Faquin, WC AF Stagner, Anna M. Afrogheh, Amir H. Jakobiec, Frederick A. Iacob, Codrin E. Grossniklaus, Hans E. Deshpande, Vikram Maske, Christopher Hiss, Donovan C. Faquin, William C. TI p16 Expression Is Not a Surrogate Marker for High-Risk Human Papillomavirus Infection in Periocular Sebaceous Carcinoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; CYCLE-REGULATORY PROTEINS; IN-SITU HYBRIDIZATION; GLAND CARCINOMA; EYELID TUMORS; P53; CONJUNCTIVA; DNA; LESIONS; HEAD AB PURPOSE: To evaluate the role of high-risk human papillomavirus (HR-HPV) infection in periocular sebaceous carcinoma (SC) using multiple methods of detection, and to determine whether p16 overexpression is present and can be used as a surrogate marker for HR-HPV. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Unstained paraffin sections of 35 cases of periocular SC were analyzed with immunohistochemistry for p16 and subjected to polymerase chain reaction (PCR) for HR-HPV. A subset of 18 lesions that were p16-positive was further studied with a novel method of mRNA in situ hybridization (ISH) for the detection of transcriptionally active HR-HPV, an advanced technique with an enhanced sensitivity and specificity. RESULTS: The clinical findings were in keeping with those of comparable earlier studies. Strong immunohistochemical p16 positivity (meeting the criterion of > 70% nuclear and cytoplasmic staining) was present in 29 of 35 cases of periocular SC (82.9%). The selected 18 p16 positive cases tested were negative for HR-HPV using mRNA ISH. PCR yielded unequivocal results with adequate DNA isolated in 24 cases, 23 of which were negative for HR-HPV. One case was positive for HPV type 16, which was found to be a false positive as collaterally determined by mRNA ISH negativity. CONCLUSION: No evidence was found for HR-HPV as an etiologic agent in the development of periocular SC using multiple modalities to maximize sensitivity and specificity and reduce the limitations of any single test. p16 overexpression is common in periocular SC but unrelated to HR-HPV status. Although p16 may be used as a surrogate marker for HR-HPV status in other tissue sites, this interpretation of p16 positivity is not applicable to periocular SC. (C) 2016 Elsevier Inc. All rights reserved. C1 [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 328, Boston, MA 02114 USA. [Stagner, Anna M.; Jakobiec, Frederick A.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Afrogheh, Amir H.] Univ Western Cape, Dept Oral & Maxillofacial Pathol, Cape Town, South Africa. [Afrogheh, Amir H.] NHLS, Cape Town, South Africa. [Iacob, Codrin E.] New York Eye & Ear Infirm Mt Sinai, Dept Pathol, New York, NY USA. [Grossniklaus, Hans E.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Deshpande, Vikram; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Deshpande, Vikram; Faquin, William C.] Harvard Med Sch, Boston, MA USA. [Maske, Christopher] Lancet Labs, Mol Pathol Lab, Johannesburg, South Africa. [Hiss, Donovan C.] Univ Western Cape, Dept Med Biosci, Cape Town, South Africa. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu FU RESEARCH TO PREVENT BLINDNESS, INC, NEW YORK, NEW York, USA FX UNRESTRICTED DEPARTMENTAL GRANT FROM RESEARCH TO PREVENT BLINDNESS, INC, NEW YORK, NEW York, USA (Hans E. Grossniklaus). 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 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2016 VL 170 BP 168 EP 175 DI 10.1016/j.ajo.2016.07.012 PG 8 WC Ophthalmology SC Ophthalmology GA DZ5KF UT WOS:000385900300022 PM 27457256 ER PT J AU Van de Velde, SK Kernkamp, WA Hosseini, A LaPrade, RF van Arkel, ER Li, GA AF Van de Velde, Samuel K. Kernkamp, William A. Hosseini, Ali LaPrade, Robert F. van Arkel, Ewoud R. Li, Guoan TI In Vivo Length Changes of the Anterolateral Ligament and Related Extra-articular Reconstructions SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterolateral ligament; anterior cruciate ligament; biomechanics; biplane fluoroscopy ID ANTERIOR CRUCIATE-LIGAMENT; LATERAL COLLATERAL LIGAMENTS; KNEE-JOINT MOTION; ILIOTIBIAL TRACT; BIOMECHANICAL ANALYSIS; DEFICIENCY; ANATOMY AB Background: Both anatomic anterolateral ligament (ALL) and nonanatomic anterolateral reconstructions are performed to improve the stability of anterior cruciate ligament (ACL)-deficient patients. However, the in vivo length change patterns and isometry of these anterolateral reconstructions are unknown. Purpose: To measure the theoretical length change patterns of the ALL and various anterolateral extra-articular reconstructions in healthy and ACL-deficient knees during in vivo weightbearing flexion. Study Design: Controlled laboratory study. Methods: Ten patients with an ACL injury in 1 knee and the contralateral side intact were included. By use of magnetic resonance and dual fluoroscopic imaging techniques, the changes in length of the ALL, modeled with its femoral attachment either anterior or posterior-proximal to the fibular collateral ligament (FCL) attachment, and nonanatomic extra-articular reconstructions were measured as a function of knee flexion and were compared between the intact and ACL-deficient knees. Results: The ALL, with its femoral attachment anterior to the FCL attachment, showed a consistent length increase of approximately 50% from 0 degrees to 90 degrees of knee flexion. The length change of the ALL was 20% 6% when its femoral attachment was placed posterior-proximal to the FCL. ACL deficiency did not affect ALL length. Even minor shifts in position around the rotational axis of the femur resulted in contrary ligament kinematic patterns. An extra-articular reconstruction with the femoral attachment proximal to the lateral epicondyle and the tibial attachment on the Gerdy tubercle increased 15% 4% in length from 0 degrees to 60 degrees and shortened at 90 degrees of flexion. When the tibial fixation of the anatomic ALL with its femoral attachment posterior to the FCL was moved to the Gerdy tubercle, a 30% +/- 4% length increase over 90 degrees occurred, without the decrease in length at 90 degrees. A significant length increase of both theoretical reconstruction grafts was seen at 0 degrees in ACL-deficient knees. Conclusion: An anatomic ALL reconstruction as modeled based on recent anatomic studies was not isometric during in vivo knee flexion and was not affected by ACL deficiency. The nonanatomic extra-articular reconstructions demonstrated more biomechanically favorable length change patterns with the smallest percentage increase in elongation during knee flexion. Clinical Relevance: This study presents the first in vivo biomechanical data on the ALL, in both healthy and ACL-deficient knees, and provides surgical information that may be valuable for restoring normal anterolateral stability. C1 [Van de Velde, Samuel K.; Kernkamp, William A.; Hosseini, Ali; LaPrade, Robert F.; van Arkel, Ewoud R.; Li, Guoan] Med Ctr Haaglanden, Lijnbaan 32, NL-2512 VA The Hague, Netherlands. [Hosseini, Ali; Li, Guoan] Harvard Med Sch, Bioengn Lab, Massachusetts Gen Hosp, Boston, MA USA. [LaPrade, Robert F.] Steadman Philippon Res Inst, Vail, CO USA. RP Van de Velde, SK (reprint author), Med Ctr Haaglanden, Lijnbaan 32, NL-2512 VA The Hague, Netherlands. EM svandevelde@post.harvard.edu FU Smith Nephew; Arthrex; Health East Norway; Ossur; National Institutes of Health FX One or more of the authors has declared the following potential conflict of interest or source of funding: R.F.L. has disclosed financial relationships with Smith & Nephew, Arthrex, Health East Norway, Ossur, and the National Institutes of Health. G.L. has disclosed financial relationships with the National Institutes of Health, Stryker/Mako, and K2M. NR 30 TC 1 Z9 1 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 EI 1552-3365 J9 AM J SPORT MED JI Am. J. Sports Med. PD OCT PY 2016 VL 44 IS 10 BP 2557 EP 2562 DI 10.1177/0363546516651431 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA DY8JC UT WOS:000385374900019 PM 27338618 ER PT J AU Gonzalez, JS Tanenbaum, ML Commissariat, PV AF Gonzalez, Jeffrey S. Tanenbaum, Molly L. Commissariat, Persis V. TI Psychosocial Factors in Medication Adherence and Diabetes Self-Management: Implications for Research and Practice SO AMERICAN PSYCHOLOGIST LA English DT Article DE diabetes; adherence; self-management; glycemic control; psychosocial factors ID OF-THE-LITERATURE; GLYCEMIC CONTROL; HEALTH LITERACY; BLOOD-GLUCOSE; SOCIOECONOMIC-STATUS; LONGITUDINAL COHORT; ILLNESS PERCEPTIONS; METABOLIC-CONTROL; PERSONAL MODELS; CARE ACTIVITIES AB Diabetes is a chronic illness that places a significant self-management burden on affected individuals and families. Given the importance of health behaviors-such as medication adherence, diet, physical activity, blood glucose self-monitoring-in achieving optimal glycemic control in diabetes, interventions designed and delivered by psychologists hold promise in assisting children, adolescents, and adults with diabetes in improving their health status and lowering their risk of serious complications. This article first provides an overview of diabetes self-management and associated challenges and burdens. Socioeconomic status factors that may influence diabetes management and outcomes are briefly highlighted. We then review the evidence base for select psychosocial factors that may be implicated in diabetes self-management. Modifiable targets of psychological intervention are presented across 3 overarching domains: (a) knowledge, beliefs, and related cognitive constructs; (b) emotional distress and well-being; and (c) behavioral skills and coping. Important methodological issues facing future research are discussed, along with opportunities for psychologists in improving the care and treatment outcomes of individuals and families living with diabetes. In conclusion, we advocate for continued research emphasis on improving psychosocial aspects of living with diabetes, with greater attention to the situational context in which the self-regulatory processes underlying self-management occur. Psychologists have important roles to play in reducing emotional distress, improving patient knowledge, and providing training in behavioral skills to promote successful self-management and to support patient-centered diabetes care. C1 [Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. [Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Diabet Res Ctr, New York, NY USA. [Tanenbaum, Molly L.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Commissariat, Persis V.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Gonzalez, JS (reprint author), Yeshiva Univ, Ferkauf Grad Sch Psychol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jeffrey.gonzalez@einstein.yu.edu OI Tanenbaum, Molly/0000-0003-4222-4224 FU National Institute of Diabetes and Digestive and Kidney Diseases [R18 DK098742, R01 DK104845] FX Jeffrey S. Gonzalez's efforts on this article were partially supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R18 DK098742 and R01 DK104845). We thank Naomi Kane, Deborah Binko, Lauren Klayman, Joslyn Kenowitz, Gabrielle Frackman, and Amit Shapira for their contributions to the literature search for this review. NR 120 TC 4 Z9 4 U1 16 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2016 VL 71 IS 7 SI SI BP 539 EP 551 DI 10.1037/a0040388 PG 13 WC Psychology, Multidisciplinary SC Psychology GA DZ0YV UT WOS:000385566500003 PM 27690483 ER PT J AU Krishnan, S Karg, PE Boninger, ML Vodovotz, Y Constantine, G Sowa, GA Brienza, DM AF Krishnan, Shilpa Karg, Patricia E. Boninger, Michael L. Vodovotz, Yoram Constantine, Greg Sowa, Gwendolyn A. Brienza, David M. TI Early Detection of Pressure Ulcer Development Following Traumatic Spinal Cord Injury Using Inflammatory Mediators SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Biomarkers; Early diagnosis; Pressure ulcer; Rehabilitation; Risk factors; Spinal cord injuries ID RISK-FACTORS; WOUND FLUID; EXPRESSION; CYTOKINES; ALPHA; MODEL; INTERLEUKIN-10; NEUTROPHILS; RECOVERY; BLOOD AB Objective: To identify changes in concentrations of inflammatory mediators in plasma and urine after traumatic spinal cord injury (SCI) and before the occurrence of a first pressure ulcer. Design: Retrospective; secondary analysis of existing data. Setting: Acute hospitalization and inpatient rehabilitation sites at a university medical center. Participants: Individuals with a pressure ulcer and plasma samples (n=17) and individuals with a pressure ulcer and urine samples (n=15) were matched by age and plasma/urine sample days to individuals with SCI and no pressure ulcer (N= 35). Interventions: Not applicable. Main Outcome Measures: Plasma and urine samples were assayed in patients with SCI, capturing samples within 4 days after the SCI to a week before the formation of the first pressure ulcer. The Wilcoxon signed-rank test was performed to identify changes in the inflammatory mediators between the 2 time points. Results: An increase in concentration of the chemokine interferon-gamma-induced protein of 10kd/CXCL10 in plasma (P<.01) and a decrease in concentration of the cytokine interferon-alpha in urine (P =.01) were observed before occurrence of a first pressure ulcer (similar to 4d) compared with matched controls. Conclusions: Altered levels of inflammatory mediators in plasma and urine may be associated with pressure ulcer development after traumatic SCI. These inflammatory mediators should be explored as possible biomarkers for identifying individuals at risk for pressure ulcer formation. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Krishnan, Shilpa; Karg, Patricia E.; Boninger, Michael L.; Brienza, David M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. [Boninger, Michael L.; Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael L.; Brienza, David M.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Boninger, Michael L.; Vodovotz, Yoram; Constantine, Greg] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Vodovotz, Yoram] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Constantine, Greg; Brienza, David M.] Univ Pittsburgh, Dept Math, Pittsburgh, PA USA. [Sowa, Gwendolyn A.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15261 USA. [Krishnan, Shilpa] Univ Texas Med Branch, Div Rehabil Sci, 301 Univ Blvd, Galveston, TX 77555 USA. RP Krishnan, S (reprint author), Univ Texas Med Branch, Div Rehabil Sci, 301 Univ Blvd, Galveston, TX 77555 USA. EM shikrish@utmb.edu OI Brienza, David/0000-0001-6335-2925; Boninger, Michael/0000-0001-6966-919X; Krishnan, Shilpa/0000-0002-9419-0495 FU National Institute on Disability and Rehabilitation Research (NIDRR), Rehabilitation Engineering Research Center on Spinal Cord Injury [H133E070024]; NIDRR [H133P110012]; U.S. Agency for Healthcare Research and Quality [1R24HS022134]; National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90SI5008] FX Supported primarily by the National Institute on Disability and Rehabilitation Research (NIDRR), Rehabilitation Engineering Research Center on Spinal Cord Injury (grant no. H133E070024); and by the NIDRR (grant no. H133P110012) and the U.S. Agency for Healthcare Research and Quality (grant no. 1R24HS022134).; The contents of this publication were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant no. 90SI5008). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this publication do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 39 TC 1 Z9 1 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2016 VL 97 IS 10 BP 1656 EP 1662 DI 10.1016/j.apmr.2016.01.003 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DY7TX UT WOS:000385333300008 PM 26820323 ER PT J AU Hogaboom, NS Worobey, LA Boninger, ML AF Hogaboom, Nathan S. Worobey, Lynn A. Boninger, Michael. L. TI Transfer Technique Is Associated With Shoulder Pain and Pathology in People With Spinal Cord Injury: A Cross-Sectional Investigation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Rehabilitation; Shoulder pain; Spinal cord injuries; Tendinopathy; Wheelchairs ID MANUAL WHEELCHAIR USERS; ROTATOR CUFF; INDEX WUSPI; INDIVIDUALS; PARAPLEGIA; PREVALENCE; IDENTIFICATION; TETRAPLEGIA; ULTRASOUND; KINETICS AB Objectives: To evaluate how transfer technique and subject characteristics relate to ultrasound measures of shoulder soft tissue pathology and self-reported shoulder pain during transfers in a sample of wheelchair users with spinal cord injury (SCI). Design: Cross-sectional observational study. Setting: Research laboratory, national and local veterans' wheelchair sporting events. Participants: A convenience sample of wheelchair users (N=76) with nonprogressive SCI. Participants were aged >18 years, >1 year postinjury, and could complete repeated independent wheelchair transfers without the use of their leg muscles. Interventions: Not applicable. Main Outcome Measures: Transfer pain items from the Wheelchair User's Shoulder Pain Index; transfer technique assessed using the Transfer Assessment Instrument (TM); and shoulder pathology markers examined using the Ultrasound Shoulder Pathology Rating Scale (USPRS). Results: Better transfer technique (higher TAI) correlated with less injury (lower USPRS) (partial eta(2)=.062, P<.05) and less pain during transfers (partial eta(2)=.049, P<.10). Greater age was the strongest predictor of greater pathology (USPRS total: partial eta(2)=.225, supraspinatus grade: partial eta(2)=.174, P<.01). An interaction between technique and weight was found (P<.10): participants with lower body weights showed a decrease in pathology markers with better transfer technique (low weight: R-2=.422, P<.05; middle weight: R-2=.200, P<.01), while those with higher weight showed little change with technique (R-2=.018, P>.05). Conclusions: Participants with better transfer technique exhibited less shoulder pathology and reported less pain during transfers. The relationship between technique and pathology was strongest in lower-weight participants. While causation cannot be proven because of study design, it is possible that using a better transfer technique and optimizing body weight could reduce the incidence of shoulder pathology and pain. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Hogaboom, Nathan S.; Worobey, Lynn A.; Boninger, Michael. L.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Hogaboom, Nathan S.; Boninger, Michael. L.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Worobey, Lynn A.; Boninger, Michael. L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Boninger, ML (reprint author), Human Engn Res Labs, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Worobey, Lynn/0000-0001-8795-6061; Boninger, Michael/0000-0001-6966-919X FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [H133N110011]; National Science Foundation Graduate Research Fellowship [1247842] FX This material is the result of work supported with resources and the use of facilities at the Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System. The contents of this paper do not represent the views of the Department of Veterans Affairs or the United States Government. This project was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (grant no. H133N110011). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). This material is based on work supported by the National Science Foundation Graduate Research Fellowship (grant no. 1247842). The contents of this publication do not necessarily reflect the view of the National Science Foundation or the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 33 TC 1 Z9 1 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2016 VL 97 IS 10 BP 1770 EP 1776 DI 10.1016/j.apmr.2016.03.026 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DY7TX UT WOS:000385333300022 PM 27117384 ER PT J AU Worobey, LA Kirby, RL Heinemann, AW Krobot, EA Dyson-Hudson, TA Cowan, RE Pedersen, JP Shea, M Boninger, ML AF Worobey, Lynn A. Kirby, R. Lee Heinemann, Allen W. Krobot, Emily A. Dyson-Hudson, Trevor A. Cowan, Rachel E. Pedersen, Jessica Presperin Shea, Mary Boninger, Michael. L. TI Effectiveness of Group Wheelchair Skills Training for People With Spinal Cord Injury: A Randomized Controlled Trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Motor skills; Rehabilitation; Spinal cord injuries; Wheelchairs ID LENGTH-OF-STAY; MANUAL WHEELCHAIR; MEDICAL REHABILITATION; PROGRAM; COMMUNITY; USERS; CLINICIAN; EFFICACY; MOBILITY; OUTCOMES AB Objective: To assess the effectiveness of group wheelchair skills training to elicit improvements in wheelchair skills. Design: Randomized double-blinded controlled trial. Setting: Four Spinal Cord Injury Model Systems Centers. Participants: Manual wheelchair users with spinal cord injury (N=114). Intervention: Six 90-minute group Wheelchair Skills Training Program (WSTP) classes or two 1-hour active control sessions with 6 to 10 people per group. Main Outcome Measures: Baseline (t1) and 1-month follow-up (t2) Wheelchair Skills Test Questionnaire (WST-Q) (Version 4.2) for capacity and performance and Goal Attainment Scale (GAS) score. Results: Follow-up was completed by 79 participants (WSTP: n=36, active control: n=43). No differences were found between missing and complete cases. Many users were highly skilled at baseline with a WST-Q capacity interquartile range of 77% to 97%. There were no differences between groups at baseline in WST-Q measures or demographics. Compared with the active control group, the WSTP group improved in WST-Q capacity advanced score (P=.02) but not in WST-Q capacity or WST-Q performance total scores (P=.068 and P=.873, respectively). The average GAS score (0% at t1) for the WSTP group at t2 was 65.6%+/- 34.8%. Higher GAS scores and WST-Q capacity scores were found for those who attended more classes and had lower baseline skills. Conclusions: Group training can improve advanced wheelchair skills capacity and facilitate achievement of individually set goals. Lower skill levels at baseline and increased attendance were correlated with greater improvement. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Worobey, Lynn A.; Krobot, Emily A.; Boninger, Michael. L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Kirby, R. Lee] Dalhousie Univ, Div Phys Med & Rehabil, Halifax, NS, Canada. [Heinemann, Allen W.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Heinemann, Allen W.; Pedersen, Jessica Presperin] Rehabilitat Inst Chicago, Chicago, IL USA. [Dyson-Hudson, Trevor A.] Kessler Fdn, W Orange, NJ USA. [Dyson-Hudson, Trevor A.] Rutgers New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ USA. [Cowan, Rachel E.] Univ Miami, Dept Neurol Surg, Miami, FL USA. [Shea, Mary] Kessler Inst Rehabil, W Orange, NJ USA. RP Worobey, LA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM law93@pitt.edu OI Worobey, Lynn/0000-0001-8795-6061; Heinemann, Allen/0000-0003-2782-7326 FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0025] FX Supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (grant no. 90DP0025). NR 21 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2016 VL 97 IS 10 BP 1777 EP 1784 DI 10.1016/j.apmr.2016.04.006 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DY7TX UT WOS:000385333300023 PM 27153762 ER PT J AU Tsai, CY Boninger, ML Hastings, J Cooper, RA Rice, L Koontz, AM AF Tsai, Chung-Ying Boninger, Michael. L. Hastings, Jennifer Cooper, Rory A. Rice, Laura Koontz, Alicia M. TI Immediate Biomechanical Implications of Transfer Component Skills Training on Independent Wheelchair Transfers SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Activities of daily living; Rehabilitation; Shoulder pain; Spinal cord injuries; Training support; Wheelchairs ID SPINAL-CORD-INJURY; SITTING PIVOT TRANSFERS; UPPER EXTREMITY PAIN; UPPER-LIMB FUNCTION; SHOULDER PAIN; NERVE ENTRAPMENTS; JOINT KINEMATICS; USERS; INDIVIDUALS; KINETICS AB Objective: To evaluate the immediate effects of transfer training based on the Transfer Assessment Instrument (TM) on the upper limb biomechanics during transfers. Design: Pre-post intervention. Setting: Biomechanics laboratory. Participants: Full-time manual wheelchair users (N=24) performed 5 transfers to a level height bench, while their natural transfer skills were scored using the TM, and their biomechanical data were recorded. Intervention: Participants with 2 or more component skill deficits were invited to return to receive personalized transfer training. Main Outcome Measures: TM part 1 summary scores and biomechanical variables calculated at the shoulder, elbow, and wrist joints were compared before and immediately after transfer training. Results: Sixteen of the 24 manual wheelchair users met the criteria for training, and 11 manual wheelchair users came back for the revisit. Their TM part 1 summary scores improved from 6.31.98 to 9.92.25. They had significantly smaller elbow range of motion, shoulder resultant moment, and rates of rise of elbow and wrist resultant forces on their trailing side during transfers after training (P<.05). On the leading side, shoulder maximum internal rotation and elevation angles, and shoulder resultant moments and rates of rise of shoulder resultant force and moment decreased after training (P<.04). Conclusions: The TAI-based training showed short-term beneficial biomechanical effects on wheelchair users' upper limbs, such as better shoulder positioning and lower joint loadings. If the skills are practiced longer-term, they may help protect the upper limbs from developing pain and injuries. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Tsai, Chung-Ying; Boninger, Michael. L.; Cooper, Rory A.; Koontz, Alicia M.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Tsai, Chung-Ying; Boninger, Michael. L.; Cooper, Rory A.; Koontz, Alicia M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael. L.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Boninger, Michael. L.; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Hastings, Jennifer] Univ Puget Sound, Dept Phys Therapy, Tacoma, WA 98416 USA. [Rice, Laura] Univ Illinois, Coll Appl Hlth Sci, Dept Kinesiol & Community Hlth, Champaign, IL 61820 USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU Department of Veterans Affairs [B7149I]; National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90SI5008] FX Supported by the Department of Veterans Affairs (grant no. B7149I).; The contents of this publication were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90SI5008). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this paper do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government NR 48 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2016 VL 97 IS 10 BP 1785 EP 1792 DI 10.1016/j.apmr.2016.03.009 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DY7TX UT WOS:000385333300024 PM 27084267 ER PT J AU Rico-Jimenez, JJ Campos-Delgado, DU Villiger, M Otsuka, K Bouma, BE Jo, JA AF Rico-Jimenez, Jose J. Campos-Delgado, Daniel U. Villiger, Martin Otsuka, Kenichiro Bouma, Brett E. Jo, Javier A. TI Automatic classification of atherosclerotic plaques imaged with intravascular OCT SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO AB Intravascular optical coherence tomography (IV-OCT) allows evaluation of atherosclerotic plaques; however, plaque characterization is performed by visual assessment and requires a trained expert for interpretation of the large data sets. Here, we present a novel computational method for automated IV-OCT plaque characterization. This method is based on the modeling of each A-line of an IV-OCT data set as a linear combination of a number of depth profiles. After estimating these depth profiles by means of an alternating least square optimization strategy, they are automatically classified to predefined tissue types based on their morphological characteristics. The performance of our proposed method was evaluated with IV-OCT scans of cadaveric human coronary arteries and corresponding tissue histopathology. Our results suggest that this methodology allows automated identification of fibrotic and lipid-containing plaques. Moreover, this novel computational method has the potential to enable high throughput atherosclerotic plaque characterization. (C) 2016 Optical Society of America C1 [Rico-Jimenez, Jose J.; Jo, Javier A.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX USA. [Campos-Delgado, Daniel U.] Univ Autonoma San Luis Potosi, Fac Ciencias, Slp, Mexico. [Villiger, Martin; Otsuka, Kenichiro; Bouma, Brett E.] Harvard Med Sch, Wellman Ctr Photomed, Boston, MA USA. [Villiger, Martin; Otsuka, Kenichiro; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jo, JA (reprint author), Texas A&M Univ, Dept Biomed Engn, College Stn, TX USA. EM javierjo@tamu.edu OI Rico-Jimenez, Jose J./0000-0003-4022-3228 FU National Heart, Lung, and Blood Institute (NHLBI) [1R01HL111361]; National Institute of Biomedical Imaging and Bioengineering (NIBIB)(Center for Biomedical OCT Research and Translation) [P41EB015903] FX National Heart, Lung, and Blood Institute (NHLBI) (1R01HL111361); National Institute of Biomedical Imaging and Bioengineering (NIBIB)(Center for Biomedical OCT Research and Translation, P41EB015903). NR 29 TC 1 Z9 1 U1 3 U2 3 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 OCT 1 PY 2016 VL 7 IS 10 BP 4069 EP 4085 DI 10.1364/BOE.7.004069 PG 17 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DY8YJ UT WOS:000385418200022 PM 27867716 ER PT J AU Kim, M An, J Kim, KS Choi, M Humar, M Kwok, SJJ Dai, TH Yun, SH AF Kim, Moonseok An, Jeesoo Kim, Ki Su Choi, Myunghwan Humar, Matjaz Kwok, Sheldon J. J. Dai, Tianhong Yun, Seok Hyun TI Optical lens-microneedle array for percutaneous light delivery SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID TRANSDERMAL DRUG-DELIVERY; POLYMER MICRONEEDLES; PHOTODYNAMIC THERAPY; VACCINATION; HYDROGELS; PATCHES; FIBER; SKIN AB The limited penetration depth of light in skin tissues is a practical bottleneck in dermatologic applications of light-induced therapies, including anti-microbial blue light therapy and photodynamic skin cancer therapy. Here, we demonstrate a novel device, termed optical microneedle array (OMNA), for percutaneous light delivery. A prototype device with a 11 by 11 array of needles at a spacing of 1 mm and a length of 1.6 mm was fabricated by press-molding poly-(lactic acid) (PLA) polymers. The device also incorporates a matched microlens array that focuses the light through the needle tips at specific points to achieve an optimal intensity profile in the tissue. In experiments done with bovine tissues, the OMNA enabled us to deliver a total of 7.5% of the input photons at a wavelength of 491 nm, compared to only 0.85% without the device. This 9-fold enhancement of light delivery was close to the prediction of 10.8 dB by ray-tracing simulation and is expected to increase the effective treatment depth of anti-microbial blue light therapy significantly from 1.3 to 2.5 mm in human skin. (C) 2016 Optical Society of America C1 [Kim, Moonseok; An, Jeesoo; Kim, Ki Su; Choi, Myunghwan; Humar, Matjaz; Kwok, Sheldon J. J.; Dai, Tianhong; Yun, Seok Hyun] Harvard Med Sch, Cambridge, MA 02139 USA. [Kim, Moonseok; An, Jeesoo; Kim, Ki Su; Choi, Myunghwan; Humar, Matjaz; Kwok, Sheldon J. J.; Dai, Tianhong; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Kim, Moonseok] Korea Univ, Dept Phys, Seoul 136701, South Korea. [Choi, Myunghwan] Sungkyunkwan Univ, Dept Biomed Engn, Ctr Neurosci & Imaging Res, Inst Basic Sci, Suwon, South Korea. [Humar, Matjaz] J Stefan Inst, Condensed Matter Dept, Jamova 39, SI-1000 Ljubljana, Slovenia. [Humar, Matjaz] Univ Ljubljana, Fac Math & Phys, Jadranska 19, SI-1000 Ljubljana, Slovenia. [Kwok, Sheldon J. J.; Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yun, SH (reprint author), Harvard Med Sch, Cambridge, MA 02139 USA.; Yun, SH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA.; Yun, SH (reprint author), Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. EM syun@mgh.harvard.edu FU U.S. National Institutes of Health [R01-CA192878, R01-AI123312, P41-EB015903]; Department of Defense [FA9550-11-1-0331]; MGH Research Scholar Program; CIMIT under U.S. Army Medical Research Acquisition Activity Cooperative Agreement (CIMIT) [14-1894]; National Research Foundation of Korea [2013R1A1A2062808]; Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme [627274] FX U.S. National Institutes of Health (R01-CA192878, R01-AI123312, P41-EB015903); Department of Defense (FA9550-11-1-0331); MGH Research Scholar Program, and CIMIT under U.S. Army Medical Research Acquisition Activity Cooperative Agreement (CIMIT No. 14-1894); National Research Foundation of Korea (2013R1A1A2062808); Marie Curie International Outgoing Fellowship 627274 within the 7th European Community Framework Programme. NR 23 TC 0 Z9 0 U1 18 U2 18 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 OCT 1 PY 2016 VL 7 IS 10 BP 4220 EP 4227 DI 10.1364/BOE.7.004220 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA DY8YJ UT WOS:000385418200033 PM 27867727 ER PT J AU Choi, HR Agrawal, K Bedair, H AF Choi, H-R. Agrawal, K. Bedair, H. TI The diagnostic thresholds for synovial fluid analysis in late periprosthetic infection of the hip depend on the duration of symptoms SO BONE & JOINT JOURNAL LA English DT Article ID PROSTHETIC JOINT INFECTION; INTERNATIONAL CONSENSUS; MARK-COVENTRY; ARTHROPLASTY; EXCLUSION; KNEE; CELL AB Aims We hypothesised that the synovial white blood cell (WBC) count in patients with a late periprosthetic joint infection (PJI) of the hip would depend on the duration of a patient's symptoms, and that the optimal diagnostic threshold would also depend on this period of time. Patients and Methods The synovial WBC count and percentage of polymorphonuclear cells (%PMN), and the serum CRP and ESR levels obtained > six weeks after primary THA were compared between 50 infected and 88 non-infected THAs, and in patients with symptoms for more than or less than two weeks. Diagnostic thresholds for the synovial WBC count were calculated using area under the curve calculation. Results The synovial WBC count was significantly higher in patients with symptoms for <= two weeks compared with those with symptoms for > two weeks (p = 0.03). The optimal threshold for diagnosing PJI for the synovial WBC count was 5750 cells/mu L (sensitivity 94; specificity 100; PPV 100%; NPV 89%; AUC 99%) and 1556 cells/mu L (sensitivity 91; specificity 94; PPV 87% and NPV 97%; AUC 95%), respectively. The thresholds for the cut-offs based on duration of symptoms improved the diagnostic performance of this test. Conclusion This study shows that the diagnostic thresholds for synovial fluid analysis in late periprosthetic infection following THA may depend on duration of symptoms. C1 [Choi, H-R.; Agrawal, K.; Bedair, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bedair, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hbedair@mgh.harvard.edu NR 24 TC 1 Z9 1 U1 2 U2 2 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2049-4394 J9 BONE JOINT J JI Bone Joint J. PD OCT PY 2016 VL 98B IS 10 BP 1355 EP 1359 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DY7VR UT WOS:000385337900009 PM 27694589 ER PT J AU Konopleva, M Pollyea, DA Potluri, J Chyla, B Hogdal, L Busman, T McKeegan, E Salem, AH Zhu, M Ricker, JL Blum, W DiNardo, CD Kadia, T Dunbar, M Kirby, R Falotico, N Leverson, J Humerickhouse, R Mabry, M Stone, R Kantarjian, H Letai, A AF Konopleva, Marina Pollyea, Daniel A. Potluri, Jalaja Chyla, Brenda Hogdal, Leah Busman, Todd McKeegan, Evelyn Salem, Ahmed Hamed Zhu, Ming Ricker, Justin L. Blum, William DiNardo, Courtney D. Kadia, Tapan Dunbar, Martin Kirby, Rachel Falotico, Nancy Leverson, Joel Humerickhouse, Rod Mabry, Mack Stone, Richard Kantarjian, Hagop Letai, Anthony TI Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ISOCITRATE-DEHYDROGENASE 1; INTENSIVE CHEMOTHERAPY; NAVITOCLAX ABT-263; BCL-2 INHIBITION; STEM-CELLS; MUTATIONS; ABT-199; ABT-737 AB We present a phase II, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated antileukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response or complete response with incomplete blood count recovery. Six (19%) patients had BCL2-sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. SIGNIFICANCE: Venetoclax monotherapy demonstrated clinical activity in patients with AML (relapsed/refractory or unfit for intensive chemotherapy) with a tolerable safety profile in this phase II study. Predictive markers of response consistent with BCL2 dependence were identified. Clinical and preclinical findings provide a compelling rationale to evaluate venetoclax combined with other agents in AML. (C) 2016 AACR. C1 [Konopleva, Marina; DiNardo, Courtney D.; Kadia, Tapan; Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Potluri, Jalaja; Chyla, Brenda; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L.; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack] AbbVie Inc, Chicago, IL USA. [Hogdal, Leah; Stone, Richard; Letai, Anthony] Dana Farber Canc Inst, Mayer 430,450 Brookline Ave, Boston, MA 02215 USA. [Salem, Ahmed Hamed] Ain Shams Univ, Fac Pharm, Cairo, Egypt. [Blum, William] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Mayer 430,450 Brookline Ave, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu FU AbbVie; Genentech; Leukemia and Lymphoma Society Translational Award; NIH [P01 CA066996] FX AbbVie and Genentech provided financial support for this study and participated in the design, study conduct, and analysis and interpretation of data, as well as the writing, review, and approval of the manuscript. Venetoclax (ABT-199/GDC-0199) is being developed in collaboration between AbbVie and Genentech. A. Letai gratefully acknowledges grant support from a Leukemia and Lymphoma Society Translational Award and NIH P01 CA066996. NR 40 TC 14 Z9 14 U1 9 U2 9 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 OCT PY 2016 VL 6 IS 10 BP 1106 EP 1117 DI 10.1158/2159-8290.CD-16-0313 PG 12 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200021 PM 27520294 ER PT J AU Gainor, JF Dardaei, L Yoda, S Friboulet, L Leshchiner, I Katayama, R Dagogo-Jack, I Gadgeel, S Schultz, K Singh, M Chin, E Parks, M Lee, D DiCecca, RH Lockerman, E Huynh, T Logan, J Ritterhouse, LL Le, LP Muniappan, A Digumarthy, S Channick, C Keyes, C Getz, G Dias-Santagata, D Heist, RS Lennerz, J Sequist, LV Benes, CH Iafrate, AJ Mino-Kenudson, M Engelman, JA Shaw, AT AF Gainor, Justin F. Dardaei, Leila Yoda, Satoshi Friboulet, Luc Leshchiner, Ignaty Katayama, Ryohei Dagogo-Jack, Ibiayi Gadgeel, Shirish Schultz, Katherine Singh, Manrose Chin, Emily Parks, Melissa Lee, Dana DiCecca, Richard H. Lockerman, Elizabeth Huynh, Tiffany Logan, Jennifer Ritterhouse, Lauren L. Le, Long P. Muniappan, Ashok Digumarthy, Subba Channick, Colleen Keyes, Colleen Getz, Gad Dias-Santagata, Dora Heist, Rebecca S. Lennerz, Jochen Sequist, Lecia V. Benes, Cyril H. Iafrate, A. John Mino-Kenudson, Mari Engelman, Jeffrey A. Shaw, Alice T. TI Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer SO CANCER DISCOVERY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; POSITIVE NSCLC PATIENTS; ACQUIRED-RESISTANCE; CRIZOTINIB RESISTANCE; SOLID TUMORS; CERITINIB; EML4-ALK; MUTATION; ALECTINIB; CELLS AB Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALK(G1202R), increases significantly after treatment with second-generation agents. To investigate strategies to overcome resistance to second-generation ALK inhibitors, we examine the activity of the third-generation ALK inhibitor lorlatinib in a series of ceritinib-resistant, patient-derived cell lines, and observe that the presence of ALK resistance mutations is highly predictive for sensitivity to lorlatinib, whereas those cell lines without ALK mutations are resistant. SIGNIFICANCE: Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. (C) 2016 AACR. C1 [Gainor, Justin F.; Dardaei, Leila; Yoda, Satoshi; Friboulet, Luc; Katayama, Ryohei; Dagogo-Jack, Ibiayi; Schultz, Katherine; Singh, Manrose; Chin, Emily; Parks, Melissa; Lee, Dana; DiCecca, Richard H.; Lockerman, Elizabeth; Logan, Jennifer; Channick, Colleen; Keyes, Colleen; Heist, Rebecca S.; Sequist, Lecia V.; Benes, Cyril H.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, 32 Fruit St, Boston, MA 02114 USA. [Friboulet, Luc] Univ Paris Saclay, INSERM U981, Gustave Roussy Canc Campus, Paris, France. [Leshchiner, Ignaty; Getz, Gad] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Katayama, Ryohei] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo, Japan. [Gadgeel, Shirish] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Huynh, Tiffany; Ritterhouse, Lauren L.; Le, Long P.; Dias-Santagata, Dora; Lennerz, Jochen; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Muniappan, Ashok] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Dept Med, 32 Fruit St, Boston, MA 02114 USA.; Engelman, JA (reprint author), Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA. EM jeffrey.engelman@novartis.com; ashaw1@partners.org FU NCI [5R01CA164273, C06CA059267]; National Foundation for Cancer Research; Be a Piece of the Solution; Evan Spirito Foundation; Lung-Strong FX This work was supported by grants from the NCI (5R01CA164273 to J.A. Engelman and A.T. Shaw; C06CA059267 to J.F. Gainor) and by the National Foundation for Cancer Research (to A.T. Shaw), Be a Piece of the Solution, the Evan Spirito Foundation, and Lung-Strong. NR 53 TC 17 Z9 17 U1 1 U2 1 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 OCT PY 2016 VL 6 IS 10 BP 1118 EP 1133 DI 10.1158/2159-8290.CD-16-0596 PG 16 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200022 PM 27432227 ER PT J AU Le, XN Antony, R Razavi, P Treacy, DJ Luo, F Ghandi, M Castel, P Scaltriti, M Baselga, J Garraway, LA AF Le, Xiuning Antony, Rajee Razavi, Pedram Treacy, Daniel J. Luo, Flora Ghandi, Mahmoud Castel, Pau Scaltriti, Maurizio Baselga, Jose Garraway, Levi A. TI Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; KINASE PATHWAY; PIM-1 KINASE; MEDIATES RESISTANCE; CONFERS RESISTANCE; CLINICAL-TRIALS; RAF INHIBITION; LUNG-CANCER; MUTATIONS; PHOSPHORYLATION AB PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naive breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. SIGNIFICANCE: PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. (C) 2016 AACR. C1 [Le, Xiuning; Antony, Rajee; Treacy, Daniel J.; Luo, Flora; Ghandi, Mahmoud; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1542, Boston, MA 02115 USA. [Le, Xiuning; Antony, Rajee; Treacy, Daniel J.; Luo, Flora; Ghandi, Mahmoud; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Le, Xiuning] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Oncol, Boston, MA 02215 USA. [Razavi, Pedram; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. [Razavi, Pedram] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Scaltriti, Maurizio] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Garraway, Levi A.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1542, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu OI Ghandi, Mahmoud/0000-0003-1897-2265 FU National Cancer Institute [R35 CA197737, P30 CA0087748, R01CA190642-01A1]; Starr Cancer Consortium; Gerstner Foundation; DFCI-NOVARTIS Drug Discovery Program; Claudia Adams Barr Program for Innovative Cancer Research; Stand Up To Cancer (SU2C); V foundation (TVF) Scholar Award; American Society of Clinical Oncology (ASCO) Young Investigator Award; Peter and Deborah Weinberg Family Fund; Breast Cancer Research Foundation Tory Burch Award; Geoffrey Beene Cancer Research Center FX This work was supported by National Cancer Institute grants R35 CA197737 (L.A. Garraway), P30 CA0087748, R01CA190642-01A1 (J. Baselga); the Starr Cancer Consortium (L.A. Garraway); the Gerstner Foundation (L.A. Garraway); the DFCI-NOVARTIS Drug Discovery Program (L.A. Garraway); the Claudia Adams Barr Program for Innovative Cancer Research (X. Le); Stand Up To Cancer (SU2C) and the V foundation (TVF) Scholar Award (X. Le); American Society of Clinical Oncology (ASCO) Young Investigator Award (X. Le); the Peter and Deborah Weinberg Family Fund (P. Razavi); the Breast Cancer Research Foundation Tory Burch Award (M. Scaltriti); and the Geoffrey Beene Cancer Research Center (M. Scaltriti). NR 50 TC 1 Z9 1 U1 4 U2 4 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 OCT PY 2016 VL 6 IS 10 BP 1134 EP 1147 DI 10.1158/2159-8290.CD-16-0305 PG 14 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200023 PM 27604488 ER PT J AU Okada, T Lee, AY Qin, LX Agaram, N Mimae, T Shen, YW O'Connor, R Lopez-Lago, MA Craig, A Miller, ML Agius, P Molinelli, E Socci, ND Crago, AM Shima, F Sander, C Singer, S AF Okada, Tomoyo Lee, Ann Y. Qin, Li-Xuan Agaram, Narasimhan Mimae, Takahiro Shen, Yawei O'Connor, Rachael Lopez-Lago, Miguel A. Craig, Amanda Miller, Martin L. Agius, Phaedra Molinelli, Evan Socci, Nicholas D. Crago, Aimee M. Shima, Fumi Sander, Chris Singer, Samuel TI Integrin-alpha 10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma SO CANCER DISCOVERY LA English DT Article ID SMALL-MOLECULE INHIBITOR; SOFT-TISSUE SARCOMA; DEDIFFERENTIATED LIPOSARCOMA; CLINICOPATHOLOGICAL ANALYSIS; SINGLE INSTITUTION; PROGNOSTIC-FACTORS; TUMOR PROGRESSION; RATIONAL DESIGN; SOLID TUMORS; CANCER AB Myxofibrosarcoma is a common mesenchymal malignancy with complex genomics and heterogeneous clinical outcomes. Through gene-expression profiling of 64 primary high-grade myxofibrosarcomas, we defined an expression signature associated with clinical outcome. The gene most significantly associated with disease-specific death and distant metastasis was ITGA10 (integrin-alpha 10). Functional studies revealed that myxofibrosarcoma cells strongly depended on integrin-alpha 10, whereas normal mesenchymal cells did not. Integrin-alpha 10 transmitted its tumor-specific signal via TRIO and RICTOR, two oncoproteins that are frequently co-overexpressed through gene amplification on chromosome 5p. TRIO and RICTOR activated RAC/PAK and AKT/mTOR to promote sarcoma cell survival. Inhibition of these proteins with EHop-016 (RAC inhibitor) and INK128 (mTOR inhibitor) had antitumor effects in tumor-derived cell lines and mouse xenografts, and combining the drugs enhanced the effects. Our results demonstrate the importance of integrin-alpha 10/TRIO/RICTOR signaling for driving myxofibrosarcoma progression and provide the basis for promising targeted treatment strategies for patients with high-risk disease. SIGNIFICANCE: Identifying the molecular pathogenesis for myxofibrosarcoma progression has proven challenging given the highly complex genomic alterations in this tumor type. We found that integrin-alpha 10 promotes tumor cell survival through activation of TRIO-RAC-RICTOR-mTOR signaling, and that inhibitors of RAC and mTOR have antitumor effects in vivo, thus identifying a potential treatment strategy for patients with high-risk myxofibrosarcoma. (C) 2016 AACR. C1 [Okada, Tomoyo; Lee, Ann Y.; Mimae, Takahiro; Shen, Yawei; O'Connor, Rachael; Craig, Amanda; Agius, Phaedra; Crago, Aimee M.; Singer, Samuel] Mem Sloan Kettering Canc Ctr, Sarcoma Dis Management Program, Dept Surg, Sarcoma Biol Lab, 1275 York Ave, New York, NY 10021 USA. [Qin, Li-Xuan] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA. [Agaram, Narasimhan] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Lopez-Lago, Miguel A.] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, 1275 York Ave, New York, NY 10021 USA. [Miller, Martin L.; Molinelli, Evan; Socci, Nicholas D.; Sander, Chris] Weill Cornell Med Coll, Dept Surg, New York, NY USA. [Crago, Aimee M.; Singer, Samuel] Kobe Univ, Grad Sch Sci Technol & Innovat, Kobe, Hyogo, Japan. [Lee, Ann Y.] NYU, Sch Med, New York, NY USA. [Craig, Amanda] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Miller, Martin L.] Univ Cambridge, Canc Res UK, Cambridge Inst, Cambridge CB2 1TN, England. [Agius, Phaedra] New York Genome Ctr, New York, NY USA. [Molinelli, Evan] BioDigital Inc, New York, NY USA. [Sander, Chris] Harvard Med Sch, cBio Ctr, Dana Farber Canc Inst, Boston, MA USA. [Sander, Chris] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. RP Singer, S (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Howard 1205, New York, NY 10065 USA.; Okada, T (reprint author), Mem Sloan Kettering Canc Ctr, Zuckerman Res Ctr, 417 East 68th St,ZRC445B, New York, NY 10065 USA. EM t-okada@ski.mskcc.org; singers@mskcc.org FU SPORE in Soft Tissue Sarcoma [P50 CA140146]; MSK Cancer Center Support Grant/Core Grant [P30 CA008748]; Siskind Family Sarcoma Fund; MFH Research Fund FX This work was supported by the SPORE in Soft Tissue Sarcoma (P50 CA140146, to S. Singer, L.-X. Qin, and C. Sander), by the MSK Cancer Center Support Grant/Core Grant (P30 CA008748), and by donations from the Siskind Family Sarcoma Fund and the MFH Research Fund. NR 60 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 OCT PY 2016 VL 6 IS 10 BP 1148 EP 1165 DI 10.1158/2159-8290.CD-15-1481 PG 18 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200024 PM 27577794 ER PT J AU Kuhn, MWM Song, E Feng, ZH Sinha, A Chen, CW Deshpande, AJ Cusan, M Farnoud, N Mupo, A Grove, C Koche, R Bradner, JE de Stanchina, E Vassiliou, GS Hoshii, T Armstrong, SA AF Kuhn, Michael W. M. Song, Evelyn Feng, Zhaohui Sinha, Amit Chen, Chun-Wei Deshpande, Aniruddha J. Cusan, Monica Farnoud, Noushin Mupo, Annalisa Grove, Carolyn Koche, Richard Bradner, James E. de Stanchina, Elisa Vassiliou, George S. Hoshii, Takayuki Armstrong, Scott A. TI Targeting Chromatin Regulators Inhibits Leukemogenic Gene Expression in NPM1 Mutant Leukemia SO CANCER DISCOVERY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MLL-REARRANGED LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; TUMOR-SUPPRESSOR MENIN; CYTOPLASMIC NUCLEOPHOSMIN; PROGNOSTIC-SIGNIFICANCE; H3K79 METHYLATION; NORMAL KARYOTYPE; DOT1L INHIBITOR; FUNCTIONAL-ROLE AB Homeobox (HOX) proteins and the receptor tyrosine kinase FLT3 are frequently highly expressed and mutated in acute myeloid leukemia (AML). Aberrant HOX expression is found in nearly all AMLs that harbor a mutation in the Nucleophosmin (NPM1) gene, and FLT3 is concomitantly mutated in approximately 60% of these cases. Little is known about how mutant NPM1 (NPM1(mut)) cells maintain aberrant gene expression. Here, we demonstrate that the histone modifiers MLL1 and DOT1L control HOX and FLT3 expression and differentiation in NPM1(mut) AML. Using a CRISPR/Cas9 genome editing domain screen, we show NPM1(mut) AML to be exceptionally dependent on the menin binding site in MLL1. Pharmacologic small-molecule inhibition of the menin-MLL1 protein interaction had profound antileukemic activity in human and murine models of NPM1(mut) AML. Combined pharmacologic inhibition of menin-MLL1 and DOT1L resulted in dramatic suppression of HOX and FLT3 expression, induction of differentiation, and superior activity against NPM1(mut) leukemia. SIGNIFICANCE: MLL1 and DOT1L are chromatin regulators that control HOX, MEIS1, and FLT3 expression and are therapeutic targets in NPM1(mut) AML. Combinatorial small-molecule inhibition has synergistic on-target activity and constitutes a novel therapeutic concept for this common AML subtype. (C) 2016 AACR. C1 [Kuhn, Michael W. M.; Song, Evelyn; Feng, Zhaohui; Sinha, Amit; Chen, Chun-Wei; Deshpande, Aniruddha J.; Cusan, Monica; Farnoud, Noushin; Koche, Richard; Hoshii, Takayuki; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. [Kuhn, Michael W. M.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 3, Mainz, Germany. [Mupo, Annalisa; Vassiliou, George S.] Wellcome Trust Sanger Inst, Cambridge, England. [Grove, Carolyn] PathWest Sir Charles Gairdner Hosp, Dept Haematol, Nedlands, WA, Australia. [Grove, Carolyn] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia. [Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [de Stanchina, Elisa] Mem Sloan Kettering Canc Ctr, Antitumor Assessment Facil, 1275 York Ave, New York, NY 10021 USA. [Armstrong, Scott A.] Harvard Med Sch, Boston Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA. [Armstrong, Scott A.] Harvard Med Sch, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. RP Armstrong, SA (reprint author), Harvard Med Sch, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM scott_armstrong@dfci.harvard.edu FU NIH [CA66996, CA140575, CA176745, P30 CA008748]; Leukemia and Lymphoma Society; German Research Foundation (DFG) [KU 2688/1-1] FX This study was supported by grants (to S.A. Armstrong) from the NIH (CA66996, CA140575, and CA176745) and the Leukemia and Lymphoma Society. E. de Stanchina was supported by an NIH grant (P30 CA008748). M.W.M. Kuhn was supported by the German Research Foundation (DFG; KU 2688/1-1). NR 50 TC 1 Z9 1 U1 8 U2 8 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 OCT PY 2016 VL 6 IS 10 BP 1166 EP 1181 DI 10.1158/2159-8290.CD-16-0237 PG 16 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200025 PM 27535106 ER PT J AU de Velasco, G Miao, D Voss, MH Hakimi, AA Hsieh, JJ Tannir, NM Tamboli, P Appleman, LJ Rathmell, WK Van Allen, EM Choueiri, TK AF de Velasco, Guillermo Miao, Diana Voss, Martin H. Hakimi, A. Ari Hsieh, James J. Tannir, Nizar M. Tamboli, Pheroze Appleman, Leonard J. Rathmell, W. Kimryn Van Allen, Eliezer M. Choueiri, Toni K. TI Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID CTLA-4 BLOCKADE; LUNG-CANCER; NIVOLUMAB; MELANOMA AB Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Non-synonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genesgranzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. (C) 2016 AACR. C1 [de Velasco, Guillermo; Miao, Diana; Van Allen, Eliezer M.; Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Miao, Diana; Van Allen, Eliezer M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Voss, Martin H.; Hsieh, James J.] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA. [Hakimi, A. Ari] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA. [Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Tamboli, Pheroze] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Appleman, Leonard J.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA. [Rathmell, W. Kimryn] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. RP Choueiri, TK (reprint author), Harvard Med Sch, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu FU NCI NIH HHS [P30 CA008748, P50 CA101942] NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2016 VL 4 IS 10 BP 820 EP 822 DI 10.1158/2326-6066.CIR-16-0110 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA DZ1WR UT WOS:000385632900002 PM 27538576 ER PT J AU Wu, XQ Giobbie-Hurder, A Liao, XY Lawrence, D McDermott, D Zhou, J Rodig, S Hodi, FS AF Wu, Xinqi Giobbie-Hurder, Anita Liao, Xiaoyun Lawrence, Donald McDermott, David Zhou, Jun Rodig, Scott Hodi, F. Stephen TI VEGF Neutralization Plus CTLA-4 Blockade Alters Soluble and Cellular Factors Associated with Enhancing Lymphocyte Infiltration and Humoral Recognition in Melanoma SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ADHESION MOLECULE-1 EXPRESSION; METASTATIC MELANOMA; T-CELLS; MALIGNANT-MELANOMA; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; IMMUNE CELLS; CANCER; INFLAMMATION; IPILIMUMAB AB Immune recognition of tumor targets by specific cytotoxic lymphocytes is essential for the effective rejection of tumors. A phase I clinical trial of ipilimumab (an antibody that blocks CTLA-4 function) in combination with bevacizumab (an antibody that inhibits angiogenesis) in patients with metastatic melanoma found favorable clinical outcomes were associated with increased tumor endothelial activation and lymphocyte infiltration. To better understand the underlying mechanisms, we sought features and factors that changed as a function of treatment in patients. Ipilimumab plus bevacizumab (Ipi-Bev) increased tumor vascular expression of ICAM1 and VCAM1. Treatment also altered concentrations of many circulating cytokines and chemokines, including increases of CXCL10, IL1 alpha, TNF alpha, CXCL1, IFN alpha 2, and IL8, with decreases in VEGF-A in most patients. IL1 alpha and TNF alpha induced expression of E-selectin, CXCL1, and VCAM1 on melanoma tumor-associated endothelial cells (TEC) in vitro and promoted adhesion of activated T cells onto TEC. VEGFA inhibited TNF alpha-induced expression of ICAM1 and VCAM1 and T-cell adhesion, which was blocked by bevacizumab. CXCL10 promoted T-cell migration across TEC in vitro, was frequently expressed by melanoma cells, and was upregulated in a subset of tumors in treated patients. Robust upregulation of CXCL10 in tumors was accompanied by increased T-cell infiltration. Ipi-Bev also augmented humoral immune responses recognizing targets in melanoma, tumor endothelial, and tumor mesenchymal stem cells. Our findings suggest that Ipi-Bev therapy augments immune recognition in the tumor microenvironment through enhancing lymphocyte infiltration and antibody responses. IL1 alpha, TNF alpha, and CXCL10, together with VEGF neutralization, contribute to Ipi-Bev-induced melanoma immune recognition. (C) 2016 AACR. C1 [Wu, Xinqi; Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. [Wu, Xinqi; Giobbie-Hurder, Anita; Liao, Xiaoyun; Zhou, Jun; Rodig, Scott; Hodi, F. Stephen] Harvard Med Sch, Boston, MA USA. [Giobbie-Hurder, Anita; Liao, Xiaoyun; Rodig, Scott] Dana Farber Canc Inst, Ctr Immunooncol, 450 Brookline Ave, Boston, MA 02215 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat, 450 Brookline Ave, Boston, MA 02215 USA. [Liao, Xiaoyun; Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Lawrence, Donald] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU NCI NIH HHS [R21 CA143832] NR 50 TC 5 Z9 5 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2016 VL 4 IS 10 BP 858 EP 868 DI 10.1158/2326-6066.CIR-16-0084 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA DZ1WR UT WOS:000385632900006 PM 27549123 ER PT J AU Patel, YM Park, SL Han, YH Wilkens, LR Bickeboller, H Rosenberger, A Caporaso, N Landi, MT Bruske, I Risch, A Wei, YY Christiani, DC Brennan, P Houlston, R McKay, J McLaughlin, J Hung, R Murphy, S Stram, DO Amos, C Le Marchand, L AF Patel, Yesha M. Park, Sunghim L. Han, Younghun Wilkens, Lynne R. Bickeboeller, Heike Rosenberger, Albert Caporaso, Neil Landi, Maria Teresa Brueske, Irene Risch, Angela Wei, Yongyue Christiani, David C. Brennan, Paul Houlston, Richard McKay, James McLaughlin, John Hung, Rayjean Murphy, Sharon Stram, Daniel O. Amos, Christopher Le Marchand, Loic TI Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; NICOTINE METABOLISM; SUSCEPTIBILITY LOCUS; ETHNIC/RACIAL GROUPS; SMOKING-BEHAVIOR; COMPLEX TRAITS; METAANALYSIS; VARIANTS; GENOTYPE; GLUCURONIDATION AB Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. We conducted a genome-wide association study (GWAS) of CYP2A6 activity, as measured by the urinary ratio of trans-3'-hydroxycotinine and its glucuronide conjugate over cotinine (total 3HCOT/COT), among 2,239 smokers in the Multiethnic Cohort (MEC) study. We identified 248 CYP2A6 variants associated with CYP2A6 activity (P < 5 x 10(-8)). CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). When we examined the effect of these variants on lung cancer risk in the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium GWAS dataset (13,479 cases and 43,218 controls), we found that the vast majority of these individual effects were directionally consistent and associated with an increased lung cancer risk. Two hundred and twenty-six of the 248 variants associated with CYP2A6 activity in the MEC were available in TRICL. Of them, 81% had directionally consistent risk estimates, and six were globally significantly associated with lung cancer. When conditioning on nine known functional variants and two deletions, the top two SNPs (rs56113850 in MEC and rs35755165 in TRICL) remained significantly associated with CYP2A6 activity in MEC and lung cancer in TRICL. The present data support the hypothesis that a greater CYP2A6 activity causes smokers to smoke more extensively and be exposed to higher levels of carcinogens, resulting in an increased risk for lung cancer. Although the variants identified in these studies may be used as risk prediction markers, the exact causal variants remain to be identified. (C) 2016 AACR. C1 [Patel, Yesha M.; Park, Sunghim L.; Stram, Daniel O.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Patel, Yesha M.; Park, Sunghim L.; Stram, Daniel O.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Han, Younghun; Amos, Christopher] Dartmouth Coll, Dept Biomed Data Sci, Hanover, NH 03755 USA. [Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany. [Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brueske, Irene] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany. [Risch, Angela] Salzburg Univ, Dept Mol Biol, Salzburg, Austria. [Wei, Yongyue] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Brennan, Paul; McKay, James] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France. [Houlston, Richard] Inst Canc Res, Div Genet & Epidemiol, London, England. [McLaughlin, John] Publ Hlth Ontario, Toronto, ON, Canada. [Hung, Rayjean] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Murphy, Sharon] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Murphy, Sharon] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. RP Le Marchand, L (reprint author), Univ Hawaii, Ctr Canc, 701 Ilalo St,Room 530, Honolulu, HI 96813 USA. EM loic@cc.hawaii.edu RI Risch, Angela/H-2669-2013 OI Risch, Angela/0000-0002-8026-5505 FU CCR NIH HHS [N01RC37004]; NCI NIH HHS [K07 CA160753, N01 CN045165, N01 CN25404, N01 CN25476, N01 CN25511, N01 CN25512, N01 CN25513, N01 CN25514, N01 CN25515, N01 CN25516, N01 CN25518, N01 CN25522, N01 CN25524, N01 CN75022, P01 CA138338, P20 CA090578, P30 CA023108, P50 CA070907, P50 CA090578, R01 CA055769, R01 CA074386, R01 CA092039, R01 CA092824, R01 CA111703, R01 CA121197, R01 CA127219, R01 CA133996, U01 CA063673, U01 CA164973, U19 CA148127, UM1 CA167462]; NHGRI NIH HHS [HHSN268200782096C, U01 HG004438, U01 HG004446] NR 50 TC 2 Z9 2 U1 5 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 19 BP 5768 EP 5776 DI 10.1158/0008-5472.CAN-16-0446 PG 9 WC Oncology SC Oncology GA DZ1UD UT WOS:000385625500021 PM 27488534 ER PT J AU Tessmer, MS Anderson, KC AF Tessmer, Marlowe S. Anderson, Kenneth C. TI AACR Cancer Progress Report 2016: Improving Lives Through Research SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Tessmer, Marlowe S.] Amer Assoc Canc Res, 18 Tremont St,17th Floor, Boston, MA 02108 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RP Tessmer, MS (reprint author), Amer Assoc Canc Res, 18 Tremont St,17th Floor, Boston, MA 02108 USA.; Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM marlowe.tessmer@aacr.org; kenneth_anderson@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2016 VL 22 IS 19 BP 4759 EP 4759 DI 10.1158/1078-0432.CCR-16-2102 PG 1 WC Oncology SC Oncology GA DZ1VV UT WOS:000385630500001 PM 27697990 ER PT J AU Xu, R Shimizu, F Hoyinga, K Beal, K Karimi, S Droms, L Peck, KK Gutin, P Iorgulescu, JB Kaley, T DeAngelis, L Pentsova, E Nolan, C Grommes, C Chan, T Bobrow, D Hormigo, A Cross, JR Wu, N Takebe, N Panageas, K Ivy, P Supko, JG Tabar, V Omuro, A AF Xu, Ran Shimizu, Fumiko Hoyinga, Koos Beal, Kathryn Karimi, Sasan Droms, Leif Peck, Kyung K. Gutin, Philip Iorgulescu, J. Bryan Kaley, Thomas DeAngelis, Lisa Pentsova, Elena Nolan, Craig Grommes, Christian Chan, Timothy Bobrow, Dylan Hormigo, Adilia Cross, Justin R. Wu, Nian Takebe, Naoko Panageas, Katherine Ivy, Percy Supko, Jeffrey G. Tabar, Viviane Omuro, Antonio TI Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase O/I Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID GAMMA-SECRETASE INHIBITOR; ADVANCED SOLID TUMORS; NEWLY-DIAGNOSED GLIOBLASTOMA; CANCER STEM-CELLS; SIGNALING PATHWAY; INITIATING CELLS; RO4929097; ANGIOGENESIS; COMBINATION; GROWTH AB Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role. Experimental Design: In this phase O/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic as trocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood-brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment. Results: Treatment was well tolerated and no dose-limiting toxicities were observed. 1FIC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133(+) CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors. Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood-brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. (C) 2016 AACR. C1 [Xu, Ran; Shimizu, Fumiko; Hoyinga, Koos; Droms, Leif; Gutin, Philip; Iorgulescu, J. Bryan; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10065 USA. [Xu, Ran; Shimizu, Fumiko; Hoyinga, Koos; Droms, Leif; Gutin, Philip; Iorgulescu, J. Bryan; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, 1275 York Ave, New York, NY 10021 USA. [Xu, Ran] Charite, Dept Neurosurg, Berlin, Germany. [Beal, Kathryn; Chan, Timothy] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. [Karimi, Sasan; Peck, Kyung K.] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. [Kaley, Thomas; DeAngelis, Lisa; Pentsova, Elena; Nolan, Craig; Grommes, Christian; Bobrow, Dylan; Hormigo, Adilia; Omuro, Antonio] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Cross, Justin R.] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, 1275 York Ave, New York, NY 10021 USA. [Wu, Nian] Mem Sloan Kettering Canc Ctr, Analyt Pharmacol Core, 1275 York Ave, New York, NY 10021 USA. [Wu, Nian] LipoSeuticals Inc, Princeton, NJ USA. [Takebe, Naoko] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Panageas, Katherine] Mem Sloan Kettering Canc Ctr, Epidemiol & Stat, 1275 York Ave, New York, NY 10021 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Supko, Jeffrey G.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Iorgulescu, J. Bryan] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Tabar, V (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10065 USA. EM tabarv@mskcc.org FU NIH/NCI (NCI Cancer Clinical Investigator Team Leadership Award) [3P30CA008748-47S2, U01CA069856]; B*Cured Foundation; Philadelphia Foundation; Have a Chance Foundation FX The study was partially funded by NIH/NCI through grants 3P30CA008748-47S2 (NCI Cancer Clinical Investigator Team Leadership Award; to A.M.P. Omuro) and U01CA069856. Additional funding was provided by B*Cured Foundation, Philadelphia Foundation, and Have a Chance Foundation. NR 36 TC 5 Z9 6 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2016 VL 22 IS 19 BP 4786 EP 4796 DI 10.1158/1078-0432.CCR-16-0048 PG 11 WC Oncology SC Oncology GA DZ1VV UT WOS:000385630500006 PM 27154916 ER PT J AU Zhu, AX Kang, YK Rosmorduc, O Evans, TRJ Santoro, A Ross, P Gane, E Vogel, A Jeffers, M Meinhardt, G Pena, CEA AF Zhu, Andrew X. Kang, Yoon-Koo Rosmorduc, Olivier Evans, T. R. Jeffry Santoro, Armando Ross, Paul Gane, Edward Vogel, Arndt Jeffers, Michael Meinhardt, Gerold Pena, Carol E. A. TI Biomarker Analyses of Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib with or without Erlotinib in the SEARCH Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III; FACTOR-C; CANCER; EXPRESSION; MET; ANGIOGENESIS AB Purpose: Sorafenib is the current standard therapy for advanced hepatocellular carcinoma, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in hepatocellular carcinoma patients from the phase III SEARCH trial. Experimental Design: A total of 720 patients were randomized to receive oral sorafenib 400 mg twice daily plus erlotinib 150 mg once daily or placebo. Fifteen growth factors relevant to the treatment regimen and/or to hepatocellular carcinoma were measured in baseline plasma samples. Results: Baseline plasma biomarkers were measured in 494 (69%) patients (sorafenib plus erlotinib, n = 243; sorafenib plus placebo, n = 251). Treatment arm-independent analyses showed that elevated hepatocyte growth factor [HGF; HR, 1.687 (high vs. low expression); endpoint multiplicity adjusted (e-adj) P = 0.0001] and elevated plasma VEGFA (HR, 1.386; e-adj P = 0.0377) were significantly associated with poor overall survival (OS) in multivariate analyses, and low plasma KIT [HR, 0.75 (high vs. low); P = 0.0233; e-adj P = 0.2793] tended to correlate with poorer OS. High plasma VEGFC independently correlated with longer TTP (HR, 0.633; e-adj P = 0.0010) and trended toward associating with improved disease control rate (univariate: OR, 2.047; P = 0.030; e-adj P = 0.420). In 67% of evaluable patients (339/494), a multimarker signature of HGF, VEGFA, KIT, EPGN, and VEGFC correlated with improved median OS in multivariate analysis (HR, 0.150; P < 0.00001). No biomarker predicted efficacy from erlotinib. Conclusions: Baseline plasma HGF, VEGFA, KIT, and VEGFC correlated with clinical outcomes in hepatocellular carcinoma patients treated with sorafenib with or without erlotinib. These biomarkers plus EPGN constituted a multimarker signature for improved OS. (C) 2016 AACR. C1 [Zhu, Andrew X.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Rosmorduc, Olivier] Sorbonne Univ, Hop La Pitie Salpetriere, Dept Hepatol, Paris, France. [Evans, T. R. Jeffry] Univ Glasgow, Inst Canc Sci, Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Santoro, Armando] Humanitas Canc Ctr, Rozzano Milan, Italy. [Ross, Paul] Kings Coll Hosp London, London, England. [Gane, Edward] Univ Auckland, New Zealand Liver Transplant Unit, Auckland, New Zealand. [Vogel, Arndt] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. [Jeffers, Michael; Meinhardt, Gerold; Pena, Carol E. A.] Bayer Hlth Care Pharmaceut, Whippany, NJ USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM azhu@mgh.harvard.edu RI Vogel, Arndt/A-8437-2012 FU Bayer HealthCare Pharmaceuticals; Onyx Pharmaceuticals, an Amgen subsidiary FX The study was supported by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, an Amgen subsidiary. NR 24 TC 2 Z9 2 U1 5 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2016 VL 22 IS 19 BP 4870 EP 4879 DI 10.1158/1078-0432.CCR-15-2883 PG 10 WC Oncology SC Oncology GA DZ1VV UT WOS:000385630500014 PM 27220960 ER PT J AU Gibson, CJ Thurston, RC Matthews, KA AF Gibson, Carolyn J. Thurston, Rebecca C. Matthews, Karen A. TI Cortisol dysregulation is associated with daily diary-reported hot flashes among midlife women SO CLINICAL ENDOCRINOLOGY LA English DT Article ID MENOPAUSAL VASOMOTOR SYMPTOMS; OLDER POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; SALIVARY CORTISOL; FUTURE-DIRECTIONS; MINERAL DENSITY; TRANSITION; FLUSHES; HEALTH; INFLAMMATION AB Objective Hot flashes are reported by 70-80% of women during the menopause transition. It has been proposed that cortisol dysregulation is involved in hot flashes, but the relationship between cortisol and hot flashes has received little empirical attention. This study examined the relationship between cortisol and daily self-reported hot flashes. Design For 7 days, participants used electronic diaries to report their hot flash frequency, severity and bothersomeness, along with mood and health behaviours, multiple times each day. Participants also provided hair samples for cortisol assays at baseline and morning and bedtime saliva samples for salivary cortisol collection over 3 days during the observation period. Hierarchical linear regression was used to examine the relationships between cortisol and hot flashes. Participants Forty-four women (41% African American, 39% non-Hispanic White) who reported daily hot flashes were enrolled. Measurements Salivary cortisol, hair cortisol and the frequency, severity and bothersomeness of daily diary-reported hot flashes were measured in this study. Results Controlling for health and demographic variables, higher hair cortisol was associated with a higher frequency of hot flashes (beta = 0.05, P = 0.01). A flatter diurnal cortisol slope was associated with greater hot flash severity (beta = 0.09, P = 0.03) and bother (beta = 0.10, P = 0.01). Hair cortisol was no longer significant after adjusting for depression or disturbed sleep; all other associations persisted. Conclusion Cortisol dysregulation was related to more frequent, severe and bothersome daily self-reported hot flashes. These findings support a potential role of the HPA axis in the aetiology and phenomenology of these common menopause symptoms. C1 [Gibson, Carolyn J.] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. [Gibson, Carolyn J.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Thurston, Rebecca C.; Matthews, Karen A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Thurston, Rebecca C.; Matthews, Karen A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Thurston, Rebecca C.; Matthews, Karen A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Gibson, CJ (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM Carolyn.Gibson2@va.gov FU University of Pittsburgh Department of Psychology; American Psychological Society Dissertation Award; University of Pittsburgh Institute for Clinical Research Education Predoctoral Fellowship in Clinical and Translational Research [8 TL1 TR 145-7] FX Support for this study came from small grants from the University of Pittsburgh Department of Psychology, the American Psychological Society Dissertation Award and the University of Pittsburgh Institute for Clinical Research Education Predoctoral Fellowship in Clinical and Translational Research (8 TL1 TR 145-7) (CJG). NR 36 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2016 VL 85 IS 4 BP 645 EP 651 DI 10.1111/cen.13076 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DZ4IH UT WOS:000385821400020 PM 27059154 ER PT J AU Lee, CT Chen, YW Starr, JR Chuang, SK AF Lee, Chun-Teh Chen, Ya-Wei Starr, Jacqueline R. Chuang, Sung-Kiang TI Survival analysis of wide dental implant: systematic review and meta-analysis SO CLINICAL ORAL IMPLANTS RESEARCH LA English DT Review DE dental implants; evidence-based dentistry; meta-analysis; survival analysis; treatment outcome ID MOLAR EXTRACTION SOCKETS; FINITE-ELEMENT-ANALYSIS; LIFE-TABLE ANALYSIS; OF-THE-LITERATURE; 5-YEAR FOLLOW-UP; DIAMETER IMPLANTS; 5-MM-DIAMETER IMPLANTS; EDENTULOUS PATIENTS; TITANIUM IMPLANTS; BODY IMPLANTS AB ObjectiveWide-diameter implants are frequently placed in molar sites to obtain appropriate restoration profiles, to rescue implants that lack stability, and to engage bone in extraction sites. However, studies of wide-diameter implant placement have provided conflicting evidence regarding clinical outcomes. This systematic review aims to analyze survival rates of wide-diameter implants (platform diameter 5mm) and assess clinical variables potentially affecting failure rates. Material and methodsElectronic search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE from January 1980 to October 2014. Publication screening, data extraction, and quality assessment were performed. Failure rate per implant-year was analyzed using mix-effects Poisson regression model to obtain summary estimates of the 5-year survival rate. Relative risk (RR) was calculated to evaluate the association of different clinical variables with estimated failure rates. ResultsEleven retrospective studies and eight prospective studies having at least 1-year follow-up period were included in the analysis. The estimated 5-year survival rate was 92.67% (95% confidence interval: [79.60, 97.50]) in the retrospective studies and 97.76% (Confidence interval: [93.25, 99.27]) in the prospective studies. Implant surface and implant diameter were significantly associated with the failure events in the retrospective studies. ConclusionsPlacement of wide-diameter implants demonstrated a promising survival rate during 5-year follow-up. Further controlled trials with the control group and longer follow-up period are needed to provide the direct evidence comparing survival rates of wide implants with survival rates of narrower implants. C1 [Lee, Chun-Teh] Univ Texas Hlth Sci Ctr Houston, Dept Periodont & Dent Hyg, Houston, TX 77030 USA. [Chen, Ya-Wei] Taipei Vet Gen Hosp, Dept Stomatol, Oral & Maxillofacial Surg, Taipei, Taiwan. [Chen, Ya-Wei] Natl Yang Ming Univ, Sch Dent, Taipei, Taiwan. [Starr, Jacqueline R.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Chen, Ya-Wei; Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Sch Dent Med, Boston, MA USA. RP Chuang, SK (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp,Chestnut Hill Stn, Oral & Maxillofacial Surg,Dept Oral & Maxillofaci, POB 67376, Chestnut Hill, MA 02467 USA. EM sungkiangchuang@gmail.com NR 84 TC 1 Z9 1 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-7161 EI 1600-0501 J9 CLIN ORAL IMPLAN RES JI Clin. Oral Implant. Res. PD OCT PY 2016 VL 27 IS 10 BP 1251 EP 1264 DI 10.1111/clr.12730 PG 14 WC Dentistry, Oral Surgery & Medicine; Engineering, Biomedical SC Dentistry, Oral Surgery & Medicine; Engineering GA DZ2WX UT WOS:000385704200009 PM 26705937 ER PT J AU Li, L Sheen, J AF Li, Lei Sheen, Jen TI Dynamic and diverse sugar signaling SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Review ID UNCOUPLES HEXOKINASE1-DEPENDENT SUGAR; ARABIDOPSIS-THALIANA; TRANSCRIPTION FACTOR; PLANT-GROWTH; HEXOKINASE 1; PROTEIN-PHOSPHORYLATION; TREHALOSE 6-PHOSPHATE; SUCROSE SYNTHASE; O-GLCNACYLATION; GENE-EXPRESSION AB Sugars fuel life and exert numerous regulatory actions that are fundamental to all life forms. There are two principal mechanisms underlie sugar 'perception and signal transduction'. in biological systems. Direct sensing and signaling is triggered via sugar-binding sensors with a broad range of affinity and specificity, whereas sugar-derived bioenergetic molecules and metabolites modulate signaling proteins and indirectly relay sugar signals. This review discusses the emerging sugar signals and potential sugar sensors discovered in plant systems. The findings leading to informative understanding of physiological regulation by sugars are considered and assessed. Comparative transcriptome analyses highlight the primary and dynamic sugar responses and reveal the convergent and specific regulators of key biological processes in the sugar-signaling network. C1 [Li, Lei; Sheen, Jen] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA. [Li, Lei; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Li, Lei; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Sheen, J (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIH; NSF; WJC Special Project RDA-Korea FX We thank Matthew McCormack for guidance in transcriptom analyses. Funding by the NIH and NSF grants and WJC Special Project RDA-Korea to J.S. supports the research projects on the sugar signaling networks. NR 108 TC 3 Z9 3 U1 26 U2 26 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 EI 1879-0356 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD OCT PY 2016 VL 33 BP 116 EP 125 DI 10.1016/j.pbi.2016.06.018 PG 10 WC Plant Sciences SC Plant Sciences GA DY7TR UT WOS:000385332700017 PM 27423125 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Infections With Biologics in Rheumatoid Arthritis and Related Conditions: a Scoping Review of Serious or Hospitalized Infections in Observational Studies SO CURRENT RHEUMATOLOGY REPORTS LA English DT Review DE Serious infection; Hospitalized infection; Infection; Biologics; Tumor-necrosis factor inhibitors; TNFi; Non-TNF biologic; Etanercept; Infliximab; Adalimumab; Golimumab; Certolizumab pegol; Rituximab; Abatacept; Tocilizumab ID RADIOGRAPHIC JOINT DAMAGE; NECROSIS FACTOR THERAPY; ANTI-TNF; WORK DISABILITY; INCREASED RISK; DISEASE; ETANERCEPT; REGISTER; AGENTS AB Biologic use is a major advance in the treatment of several autoimmune conditions, including rheumatoid arthritis. In this review, we summarize key studies of serious/hospitalized infections in rheumatoid arthritis (RA). RA is a risk factor for infections. High RA disease activity is associated with higher risk of serious infection. The risk of serious infections with tumor necrosis factor inhibitor (TNFi) biologics is increased in the first 6 months of initiating therapy, and this risk was higher compared to the use of traditional disease-modifying anti-rheumatic drugs (DMARDs). Emerging data also suggest that biologics may differ from each other regarding the risk of serious or hospitalized infections. Past history of serious infections, glucocorticoid dose, and older age were other important predictors of risk of serious infections in patients treated with biologics. C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Sch Med, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA.; Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA.; Singh, JA (reprint author), Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. EM Jasvinder.md@gmail.com FU UAB Division of Rheumatology; Birmingham VA Medical Center FX This material is the result of work supported by research funds from UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center. NR 28 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 EI 1534-6307 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD OCT PY 2016 VL 18 IS 10 AR 61 DI 10.1007/s11926-016-0609-5 PG 9 WC Rheumatology SC Rheumatology GA DY8UN UT WOS:000385407000001 PM 27613285 ER PT J AU Waldman, A Arndt, KA Avram, MM Brown, MR Dover, JS Fabi, SG Friedmann, DP Geronemus, RG Goldberg, DJ Goldman, MP Green, JB Ibrahimi, OA Jones, DH Kilmer, SL McDaniel, DH Obagi, S Ortiz, AE Rohrer, TE Taylor, MB Torres, A Weinkle, SH Weiss, MA Weiss, ET Weiss, RA Poon, E Alam, M AF Waldman, Abigail Arndt, Kenneth A. Avram, Mathew M. Brown, Mariah R. Dover, Jeffrey S. Fabi, Sabrina G. Friedmann, Daniel P. Geronemus, Roy G. Goldberg, David J. Goldman, Mitchel P. Green, Jeremy B. Ibrahimi, Omar A. Jones, Derek H. Kilmer, Suzanne L. McDaniel, David H. Obagi, Suzan Ortiz, Arisa E. Rohrer, Thomas E. Taylor, Mark B. Torres, Abel Weinkle, Susan H. Weiss, Margaret A. Weiss, Eduardo T. Weiss, Robert A. Poon, Emily Alam, Murad TI ASDS Cosmetic Dermatologic Surgery Fellowship Milestones SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND The American Council of Graduate Medical Education, which oversees much of postgraduate medical education in the United States, has championed the concept of "milestones," standard levels of achievement keyed to particular time points, to assess trainee performance during residency. OBJECTIVE To develop a milestones document for the American Society for Dermatologic Surgery (ASDS) Cosmetic Dermatologic Surgery (CDS) fellowship program. METHODS An ad hoc milestone drafting committee was convened that included members of the ASDS Accreditation Work Group and program directors of ASDS-approved Cosmetic Dermatologic Surgery (CDC) fellowship training programs. Draft milestones were circulated through email in multiple rounds until consensus was achieved. RESULTS Thirteen milestones were developed in the 6 Accreditation Council for Graduate Medical Education (ACGME) competency areas, with 8 of these being patient-care milestones. Additional instructions for milestone administration more specific to the CDS fellowship than general ACGME instructions were also approved. Implementation of semiannual milestones was scheduled for the fellowship class entering in July 2018. CONCLUSION Milestones are now available for CDS fellowship directors to implement in combination with other tools for fellow evaluation. C1 [Waldman, Abigail; Poon, Emily; Alam, Murad] Northwestern Univ, Mcgaw Med Ctr, Dept Dermatol, Chicago, IL 60611 USA. [Arndt, Kenneth A.; Dover, Jeffrey S.; Rohrer, Thomas E.] SkinCare Phys, Chestnut Hill, MA USA. [Avram, Mathew M.] Massachusetts Gen Hosp, Dermatol Laser & Cosmet Ctr, Boston, MA 02114 USA. [Brown, Mariah R.] Univ Colorado, Sch Med, Dept Dermatol, Aurora, CO USA. [Fabi, Sabrina G.; Goldman, Mitchel P.] Goldman Butterwick Groff Fabi & Wu, Cosmet Laser Dermatol, San Diego, CA USA. [Friedmann, Daniel P.] Westlake Dermatol & Cosmet Surg, Austin, TX USA. [Geronemus, Roy G.] Laser & Skin Surg Ctr New York, New York, NY USA. [Goldberg, David J.] Skin Laser & Surg Specialists NY & NJ, Hackensack, NJ USA. [Goldberg, David J.] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Green, Jeremy B.] Skin Associates South Florida, Coral Gables, FL USA. [Green, Jeremy B.] Univ Miami, Dept Dermatol & Cutaneous Surg, Coral Gables, FL 33124 USA. [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT USA. [Ibrahimi, Omar A.] HarvardMed Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Jones, Derek H.] Skin Care & Laser Phys Beverly Hills, Beverly Hills, CA USA. [Kilmer, Suzanne L.] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA. [McDaniel, David H.] McDaniel Laser & Cosmet Ctr, Virginia Beach, VA USA. [Obagi, Suzan] Univ Pittsburgh, UPMC Cosmet Surg & Skin Hlth Ctr, Dept Dermatol, Sewickley, PA USA. [Ortiz, Arisa E.] Univ Calif San Diego, Dept Dermatol, Laser & Cosmet Dermatol, San Diego, CA 92103 USA. [Taylor, Mark B.] Gateway Aesthet Inst & Laser Ctr, Salt Lake City, UT USA. [Torres, Abel] Case Western Reserve Univ, Dept Dermatol, MetroHlth Syst, Cleveland, OH 44106 USA. [Weinkle, Susan H.] Univ S Florida, Dept Dermatol, Tampa, FL USA. [Weiss, Margaret A.; Weiss, Robert A.] Maryland Laser Skin & Vein Inst, Hunt Valley, MD USA. [Weiss, Eduardo T.] Hollywood Dermatol & Cosmet Surg Specialists, Hollywood, FL USA. [Alam, Murad] Northwestern Univ, Feinberg Sch Med, Dept Otolaryngol, Chicago, IL 60611 USA. [Alam, Murad] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL USA. RP Alam, M (reprint author), Dept Dermatol, 676 N St Clair St,Suite 1600, Chicago, IL 60611 USA. EM m-alam@northwestern.edu NR 5 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2016 VL 42 IS 10 BP 1164 EP 1173 DI 10.1097/DSS.0000000000000860 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA DZ2IX UT WOS:000385666600006 PM 27661429 ER PT J AU Schuster, RM Hanly, A Gilman, J Budney, A Vandrey, R Evins, AE AF Schuster, Randi Melissa Hanly, Ailish Gilman, Jodi Budney, Alan Vandrey, Ryan Evins, A. Eden TI A contingency management method for 30-days abstinence in non-treatment seeking young adult cannabis users SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Contingency management; Cannabis; Marijuana; Young adults; Abstinence; Methodology ID MARIJUANA DEPENDENCE; USE DISORDERS; DRUG-USE; CLINICAL-TRIAL; SUBSTANCE USE; OUTCOMES; ALCOHOL; INTERVENTION; ADOLESCENCE; INCENTIVES AB Background: Rates of young adult cannabis use are rising, perceived harm is at its historical nadir, and most users do not want to quit. Most studies evaluating effects of cannabis use in young adults are cross-sectional, limiting causal inference. A method to reliably induce abstinence periods in cannabis users would allow assessment of the effects of abstinence and resumption of use on a variety of outcomes in a within-subjects, repeated measures design. Methods: We examined the efficacy and feasibility of a voucher-based contingency management procedure for incentivizing one month of continuous cannabis abstinence among young adults who reported at least weekly cannabis use, volunteered to participate in a laboratory study, and did not express a desire to discontinue cannabis use long-term. Continuous cannabis abstinence was reinforced with an escalating incentive schedule, and self-report of abstinence was confirmed by frequent quantitative assays of urine cannabis metabolite (THCCOOH) concentration. New cannabis use during the abstinence period was determined using an established algorithm of change in creatinine-adjusted cannabis metabolite concentrations between study visits. Results: Thirty-eight young adults, aged 18-25 years, enrolled and 34 (89.5%) attained biochemically confirmed 30-day abstinence. Among those who attained abstinence, 93.9% resumed regular use within two-weeks of incentive discontinuation. Conclusion: Findings support the feasibility and efficacy of contingency management to elicit short-term, continuous cannabis abstinence among young adult, non-treatment seeking, regular cannabis users. Further work should test the effectiveness of this contingency management procedure for cannabis abstinence in periods longer than one month, which may be required to evaluate some effects of abstinence. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Schuster, Randi Melissa; Hanly, Ailish; Gilman, Jodi; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA. [Schuster, Randi Melissa; Gilman, Jodi; Evins, A. Eden] Harvard Med Sch, Boston, MA USA. [Budney, Alan] Dartmouth Coll, Geisel Sch Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. [Vandrey, Ryan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Schuster, RM (reprint author), 60 Staniford St, Boston, MA 02114 USA. EM rschuster@mgh.harvard.edu FU Harvard Medical School Norman E. Zinberg and Livingston Fellowships; Louis V. Gerstner III Research Scholar Award; [K24 DA030443]; [K01DA034093] FX This publication was made possible by support from K24 DA030443 (Evins), K01DA034093 (Gilman), by the Harvard Medical School Norman E. Zinberg and Livingston Fellowships (Schuster), and by a Louis V. Gerstner III Research Scholar Award (Schuster). NR 69 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2016 VL 167 BP 199 EP 206 DI 10.1016/j.drugalcdep.2016.08.622 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DY7QT UT WOS:000385325100027 PM 27590742 ER PT J AU Thorup, AAE Seidman, LJ Conus, P AF Thorup, Anne A. E. Seidman, Larry J. Conus, Philippe TI Familial High Risk Studies - Why Are They Still Relevant? The Danish High Risk and Resilience Study - Status, Results and Perspectives SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Thorup, Anne A. E.] Univ Copenhagen, Fac Hlth & Med Sci, Inst Clin Med, DK-1168 Copenhagen, Denmark. [Seidman, Larry J.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Conus, Philippe] Univ Lausanne, DP CHUV, Lausanne, Switzerland. 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 4 EP 4 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800005 ER PT J AU Glynn, S Gingerich, S Mueser, K Cather, C Kane, J AF Glynn, Shirley Gingerich, Susan Mueser, Kim Cather, Cori Kane, John TI The Role of Family Intervention in the RAISE Early Treatment Program SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Glynn, Shirley] Univ Calif Los Angeles, Semel Inst Neurosci & Brain Behav, Los Angeles, CA USA. [Mueser, Kim] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Cather, Cori] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cather, Cori] Harvard Med Sch, Boston, MA USA. [Kane, John] Zucker Hillside Hosp, North Shore Long Isl Jewish Hlth Syst, Div Psychiat Res, New York, NY 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 17 EP 17 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800042 ER PT J AU Landa, Y Mueser, K Jacobs, M Jespersen, R Wyka, K AF Landa, Yulia Mueser, Kim Jacobs, Michael Jespersen, Rachel Wyka, Katarzyna TI Adaptation of CBT for Psychosis Training for Family Caregivers of Youth at Risk for Psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Landa, Yulia; Jacobs, Michael; Jespersen, Rachel] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Landa, Yulia; Jespersen, Rachel] James J Peter Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN 3, Bronx, NY USA. [Landa, Yulia; Jespersen, Rachel; Wyka, Katarzyna] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Mueser, Kim] Boston Univ, Boston, MA 02215 USA. [Wyka, Katarzyna] CUNY, Sch Publ Hlth, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 18 EP 18 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800044 ER PT J AU Addington, J Cadenhead, KS Cannon, TD Cornblatt, BA McGlashan, TH Perkins, DO Seidman, LJ Walker, EF Woods, S Bearden, CE Mathalon, D Buchy, L AF Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Walker, Elaine F. Woods, Scott Bearden, Carrie E. Mathalon, Daniel Buchy, Lisa TI Cannabis Use in Individuals at Clinical High Risk of Psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Addington, Jean; Buchy, Lisa] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Cadenhead, Kristin S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott] Yale Univ, New Haven, CT USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, New York, NY USA. [Perkins, Diana O.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Seidman, Larry J.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA. NIMH, Bethesda, MD 20892 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Mathalon, Daniel] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 30 EP 30 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800084 ER PT J AU Loewy, R Fisher, M Schlosser, D Carter, C Niendam, T Ragland, JD Biaganti, B Amirfathi, F Vinogradov, S AF Loewy, Rachel Fisher, Melissa Schlosser, Danielle Carter, Cameron Niendam, Tara Ragland, J. Daniel Biaganti, Bruno Amirfathi, Felix Vinogradov, Sophia TI Improved Cognition and Positive Symptoms with Targeted Auditory Processing Training in Recent-Onset Schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Loewy, Rachel; Schlosser, Danielle; Biaganti, Bruno; Amirfathi, Felix] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fisher, Melissa; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. [Carter, Cameron; Niendam, Tara; Ragland, J. Daniel] Univ Calif Davis, Davis, CA 95616 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 114 EP 114 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800338 ER PT J AU Fallah, A Weil, AG Wang, S Lewis, E Baca, CB Mathern, GW AF Fallah, Aria Weil, Alexander G. Wang, Shelly Lewis, Evan Baca, Christine B. Mathern, Gary W. TI Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with Tuberous Sclerosis Complex SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Seizures; Tuberous Sclerosis Complex; Antiseizure drugs; Ketogenic diet; Vagal nerve stimulator; Resective surgery ID VAGUS NERVE-STIMULATION; GIANT-CELL ASTROCYTOMAS; TERM-FOLLOW-UP; KETOGENIC DIET; INTRACTABLE EPILEPSY; REFRACTORY EPILEPSY; SURGERY; PREDICTORS; EFFICACY; AGE AB Background: The management of drug-resistant epilepsy in children with Tuberous Sclerosis Complex (TSC) is challenging because of the multitude of treatment options, wide range of associated costs, and uncertainty of seizure outcomes. The most cost-effective approach for children whose epilepsy has failed to improve with first-line medical therapy is uncertain. Methods: A review of MEDLINE from 1990 to 2015 was conducted. A cost-utility analysis, from a third-party payer perspective, was performed for children with drug-resistant epilepsy that had failed to improve with 2 antiseizure drugs (ASDs) and that was amenable to resective epilepsy surgery, across a time-horizon of 5 years. Four strategies were included: (1) resective epilepsy surgery, (2) vagus nerve stimulator (VNS) implantation, (3) ketogenic diet, and (4) addition of a third ASD (specifically, carbamazepine). The incremental cost per quality-adjusted life year (QALY) gained was analyzed. Results: Given a willingness-to-pay (WTP) of $100,000 per QALY, the addition of a third ASD ($6600 for a gain of 4.14 QALYs) was the most cost-effective treatment strategy. In a secondary analysis, if the child whose epilepsy had failed to improve with 3 ASDs, ketogenic diet, addition of a fourth ASD, and resective epilepsy surgery were incrementally cost-effective treatment strategies. Vagus nerve stimulator implantation was more expensive yet less effective than alternative strategies and should not be prioritized. Conclusions: The addition of a third ASD is a universally cost-effective treatment option in the management of children with drug-resistant epilepsy that has failed to improve with 2 ASDs. For children whose epilepsy has failed to improve with 3 ASDs, the most cost-effective treatment depends on the health-care resources available reflected by the WTP. (C) 2016 Elsevier Inc. All rights reserved. C1 [Fallah, Aria; Mathern, Gary W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, 300 Stein Plaza,Suite 525, Los Angeles, CA 90095 USA. [Fallah, Aria; Mathern, Gary W.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [Weil, Alexander G.] Univ Montreal, Dept Surg, Div Pediat Neurosurg, Montreal, PQ, Canada. [Wang, Shelly] Univ Toronto, Dept Surg, Div Neurosurg, Toronto, ON, Canada. [Wang, Shelly] Harvard TH Chan Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. [Lewis, Evan] Univ Toronto, Hosp Sick Children, Div Pediat Neurol, Toronto, ON, Canada. [Baca, Christine B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Baca, Christine B.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. RP Fallah, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, 300 Stein Plaza,Suite 525, Los Angeles, CA 90095 USA. EM afallah@mednet.ucla.edu FU Davies/Randall endowed chair for epilepsy research at UCLA; RE children's project FX Gary W. Mathern was supported in part by the Davies/Randall endowed chair for epilepsy research at UCLA and the RE children's project. NR 48 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 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2016 VL 63 BP 79 EP 88 DI 10.1016/j.yebeh.2016.07.034 PG 10 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA DZ0LO UT WOS:000385531100014 PM 27591681 ER PT J AU Vardeny, O Claggett, B Packer, M Zile, MR Rouleau, J Swedberg, K Teerlink, JR Desai, AS Lefkowitz, M Shi, V McMurray, JJ Solomon, SD AF Vardeny, Orly Claggett, Brian Packer, Milton Zile, Michael R. Rouleau, Jean Swedberg, Karl Teerlink, John R. Desai, Akshay S. Lefkowitz, Martin Shi, Victor McMurray, John J. V. Solomon, Scott D. CA Prospective Comparison ARNI ACEI D TI Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Chronic heart failure; Neprilysin inhibitor; Clinical trial; Sacubitril; Valsartan ID BETA-BLOCKER THERAPY; INHIBITION; NEPRILYSIN; OUTCOMES AB AimsIn this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. Methods and resultsIn a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001). ConclusionsIn PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. C1 [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Pharm Practice Div, 425 N Charter St, Madison, WI 53706 USA. [Claggett, Brian; Desai, Akshay S.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02445 USA. [Packer, Milton] Baylor Univ, Med Ctr, Div Cardiol, Dallas, TX USA. [Packer, Milton] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA. [Zile, Michael R.] Med Univ South Carolina, Charleston, NC USA. [Zile, Michael R.] Ralph H Johnston Vet Adm Med Ctr, Charleston, NC USA. [Rouleau, Jean] Univ Montreal, Inst Cardiol Montreal, Montreal, PQ, Canada. [Swedberg, Karl] Univ Gothenburg, Gothenburg, Sweden. [Swedberg, Karl] Imperial Coll, Natl Heart & Lung Inst, London, England. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lefkowitz, Martin; Shi, Victor] Novartis Pharmaceut, E Hanover, NJ USA. [McMurray, John J. V.] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02445 USA. EM ssolomon@rics.bwh.harvard.edu OI mcmurray, john/0000-0002-6317-3975 FU NHLBI NIH HHS [R01 HL123478] NR 13 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2016 VL 18 IS 10 BP 1228 EP 1234 DI 10.1002/ejhf.580 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ2ZB UT WOS:000385710500004 PM 27283779 ER PT J AU Ye, SQ Qian, M Zhao, B Buchsbaum, R Sacco, RL Levin, B Di Tullio, MR Mann, DL Pullicino, PM Freudenberger, RS Teerlink, JR Mohr, JP Graham, S Labovitz, AJ Estol, CJ Lok, DJ Ponikowski, P Anker, SD Lip, GYH Thompson, JLP Homma, S AF Ye, Siqin Qian, Min Zhao, Bo Buchsbaum, Richard Sacco, Ralph L. Levin, Bruce Di Tullio, Marco R. Mann, Douglas L. Pullicino, Patrick M. Freudenberger, Ronald S. Teerlink, John R. Mohr, J. P. Graham, Susan Labovitz, Arthur J. Estol, Conrado J. Lok, Dirk J. Ponikowski, Piotr Anker, Stefan D. Lip, Gregory Y. H. Thompson, John L. P. Homma, Shunichi CA WARCEF Investigators TI CHA(2)DS(2)-VASc score and adverse outcomes in patients with heart failure with reduced ejection fraction and sinus rhythm SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Warfarin; Sinus rhythm; Stroke; Bleeding ID ATRIAL-FIBRILLATION; STROKE; RISK; WARFARIN; ASPIRIN; TRIAL; THROMBOEMBOLISM; RATIONALE; DESIGN; WARCEF AB AimsThe aim of this study was to determine whether the CHA(2)DS(2)-VASc score can predict adverse outcomes such as death, ischaemic stroke, and major haemorrhage, in patients with systolic heart failure in sinus rhythm. Methods and resultsCHA(2)DS(2)-VASc scores were calculated for 1101 patients randomized to warfarin and 1123 patients randomized to aspirin. Adverse outcomes were defined as death or ischaemic stroke, death alone, ischaemic stroke alone, and major haemorrhage. Using proportional hazards models, we found that each 1-point increase in the CHA(2)DS(2)-VASc score was associated with increased hazard of death or ischaemic stroke events [hazard ratio (HR) for the warfarin arm = 1.21, 95% confidence interval (CI) 1.13-1.30, P < 0.001; for aspirin, HR = 1.20, 95% CI 1.11-1.29, P < 0.001]. Similar increased hazards for higher CHA(2)DS(2)-VASc scores were observed for death alone, ischaemic stroke alone, and major haemorrhage. Overall performance of the CHA(2)DS(2)-VASc score was assessed using c-statistics for full models containing the risk score, treatment assignment, and score-treatment interaction, with the c-statistics for the full models ranging from 0.57 for death to 0.68 for major haemorrhage. ConclusionsThe CHA(2)DS(2)-VASc score predicted adverse outcomes in patients with systolic heart failure in sinus rhythm, with modest prediction accuracy. C1 [Ye, Siqin; Di Tullio, Marco R.; Homma, Shunichi] Columbia Univ, Dept Med, Med Ctr, Div Cardiol, New York, NY USA. [Qian, Min; Zhao, Bo; Buchsbaum, Richard; Levin, Bruce; Thompson, John L. P.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Mann, Douglas L.] Washington Univ, Dept Med, St Louis, MO USA. [Pullicino, Patrick M.] Univ Kent, Kent Inst Med & Hlth Sci, Canterbury, Kent, England. [Freudenberger, Ronald S.] Lehigh Valley Hosp, Div Cardiol, Dept Med, Allentown, PA USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Mohr, J. P.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Graham, Susan] SUNY Upstate Med Univ, Dept Med, Div Cardiol, Buffalo, NY USA. [Labovitz, Arthur J.] Univ S Florida, Dept Cardiovasc Med, Tampa, FL USA. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. [Lok, Dirk J.] Deventer Hosp, Dept Cardiol, Deventer, Netherlands. [Ponikowski, Piotr] Wroclaw Med Univ, Mil Hosp, Dept Heart Dis, Wroclaw, Poland. [Anker, Stefan D.] Univ Med Ctr Gottingen, Dept Cardiol & Pneumol, Innovat Clin Trials, Gottingen, Germany. [Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. RP Ye, SQ (reprint author), Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, 622 West 168th St,PH 9-320, New York, NY 10032 USA. EM sy2357@cumc.columbia.edu RI Ponikowski, Piotr/O-6454-2015 OI Ponikowski, Piotr/0000-0002-3391-7064 FU NHLBI NIH HHS [K23 HL121144]; NINDS NIH HHS [U01 NS039143, U01 NS043975] NR 18 TC 4 Z9 4 U1 3 U2 3 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 OCT PY 2016 VL 18 IS 10 BP 1261 EP 1266 DI 10.1002/ejhf.613 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ2ZB UT WOS:000385710500010 PM 27444219 ER PT J AU Grubisha, MJ Lin, CW Tseng, GC Penzes, P Sibille, E Sweet, RA AF Grubisha, Melanie J. Lin, Chien-Wei Tseng, George C. Penzes, Peter Sibille, Etienne Sweet, Robert A. TI Age-dependent increase in Kalirin-9 and Kalirin-12 transcripts in human orbitofrontal cortex SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dendritic complexity; human ageing; Kalirin; postmortem ID GDP/GTP EXCHANGE FACTOR; SPINE MORPHOGENESIS; PREFRONTAL CORTEX; DENDRITIC SPINES; EXPRESSION; BRAIN; SCHIZOPHRENIA; DISEASE; PLASTICITY; REGRESSION AB KALRN (KAL) is a Rho GEF that is highly involved in regulation of the actin cytoskeleton within dendrites. There are several isoforms of the protein that arise from differential splicing of KALRN's 66 exons. KAL isoforms have different functions in development. For example, overexpression of the KAL9 and KAL12 isoforms induce dendritic elongation in early development. However, in mature neurons KAL9 overexpression reduces dendritic length, a phenotype also observed in normal human ageing. We therefore hypothesized that KAL9 would have increased expression with age, and undertook to evaluate the expression of individual KALRN exons throughout the adult lifespan. Postmortem human brain grey matter from Brodmann's area (BA) 11 and BA47 derived from a cohort of 209 individuals without psychiatric or neurodegenerative disease, ranging in age from 16 to 91 years, were analysed for KALRN expression by Affymetrix exon array. Analysis of the exon array data in an isoform-specific manner, as well as confirmatory isoform-specific qPCR studies, indicated that the longer KAL9 and KAL12 isoforms demonstrated a statistically significant, but modest, increase with age. The small magnitude of the age effect suggests that inter-individual factors other than age likely contribute to a higher degree to KAL9 and KAL12 expression. In contrast to KAL9 and KAL12, global KALRN expression did not increase with age. Our work suggests that global measures of KALRN gene expression may be misleading and future studies should focus on isoform-specific quantification. C1 [Grubisha, Melanie J.; Sibille, Etienne] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Lin, Chien-Wei; Tseng, George C.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Physiol, Chicago, IL 60611 USA. [Penzes, Peter] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Sibille, Etienne] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Sibille, Etienne] Univ Toronto, Campbell Family Mental Hlth Res Inst, Dept Psychiat, CAMH, Toronto, ON, Canada. [Sibille, Etienne] Univ Toronto, Campbell Family Mental Hlth Res Inst, Dept Pharmacol, CAMH, Toronto, ON, Canada. [Sibille, Etienne] Univ Toronto, Campbell Family Mental Hlth Res Inst, Dept Toxicol, CAMH, Toronto, ON, Canada. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA.; Sweet, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Biomed Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU NIH [MH071533, AG027224]; VAPHS [BX000542, MH093723, MH071316, MH097216] FX This work was supported by NIH grants MH071533 (RAS), AG027224 (RAS), VAPHS grant BX000542 (RAS), MH093723 (ES), MH071316 (PP) and MH097216 (PP). We thank Dr. C. Sue Johnston for assistance with the clinical data and the research staff of the Translational Neuroscience Program for technical assistance. These results were presented, in part, at the 2015 Annual Meeting of the Society of Biological Psychiatry, Toronto, ON, as well as at the 2015 American Psychiatric Association's Research Colloquium for Junior Investigators in Toronto, ON. NR 33 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2016 VL 44 IS 7 BP 2483 EP 2492 DI 10.1111/ejn.13351 PG 10 WC Neurosciences SC Neurosciences & Neurology GA DY8QE UT WOS:000385394100010 PM 27471199 ER PT J AU Wehrfritz, A Schaefer, S Troester, A Noel, N Bessiere, B Apiou-Sbirlea, G Simonnet, G Schuettler, J Richebe, P AF Wehrfritz, A. Schaefer, S. Troester, A. Noel, N. Bessiere, B. Apiou-Sbirlea, G. Simonnet, G. Schuettler, J. Richebe, P. TI A randomized phase I trial evaluating the effects of inhaled 50-50% N2O-O-2 on remifentanil-induced hyperalgesia and allodynia in human volunteers SO EUROPEAN JOURNAL OF PAIN LA English DT Article ID OPIOID-INDUCED HYPERALGESIA; LONG-LASTING HYPERALGESIA; NITROUS-OXIDE ANESTHESIA; HUMAN SKIN; POSTOPERATIVE HYPERALGESIA; FISCHER RATS; PAIN; KETAMINE; FENTANYL; TOLERANCE AB BackgroundOpioids are known to relieve pain, and also aggravate pre-existing hyperalgesia. In animal studies, the N-methyl-d-aspartate-receptor antagonist nitrous oxide (N2O) was able to prevent hyperalgesia. The present study evaluated the effect of N2O on hyperalgesia after remifentanil infusion in healthy volunteers. MethodsTwenty-one healthy volunteers were enrolled in this placebo-controlled cross-over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia. Each volunteer underwent the following four sessions: (1) 50-50% N-2-O-2 and i.v. saline; (2) 50-50% N-2-O-2 and i.v. remifentanil 0.1g/kg/min; (3) 50-50% N2O-O-2 and i.v. saline; (4) 50-50% N2O-O-2 and i.v. remifentanil 0.1g/kg/min. Inhaled gas mixtures lasted for 60min, i.v. drug administration for 30min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and touch-evoked allodynia were assessed repeatedly for 160min. ResultsData of 19 volunteers were analysed. There were significant time and treatment effects regarding areas of hyperalgesia and allodynia (p<0.02). The area of hyperalgesia was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (35.8822.37 vs. 43.5518.48cm(2), p=0.004). The area of allodynia was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (29.95 +/- 16.15 vs. 34.80 +/- 15.35cm(2), p=0.008). The pain intensity was significantly reduced in the N2O+remifentanil session compared to the remifentanil session (37.96 +/- 12.78 vs. 42.15 +/- 13.34mm, p<0.0001). ConclusionsNitrous oxide significantly reduced hyperalgesia, allodynia and pain intensity aggravated after remifentanil administration in a human volunteer model. What does this study add?This study brings the evidence that N2O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well-known model of electrical pain. N2O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model. C1 [Wehrfritz, A.; Schaefer, S.; Troester, A.; Schuettler, J.] Univ Erlangen Nurnberg, Dept Anaesthesiol, Erlangen, Germany. [Richebe, P.] Univ Montreal, Dept Anaesthesiol, Maisonneuve Rosemont Hosp, Montreal, PQ, Canada. [Noel, N.; Bessiere, B.] Air Liquide Sante Int, Med R&D, Les Loges En Josas, France. [Apiou-Sbirlea, G.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Apiou-Sbirlea, G.] Harvard Med Sch, Dept Dermatol, Boston, MA USA. [Simonnet, G.] Univ Bordeaux, CNRS, INCIA UMR 5287, Bordeaux, France. RP Wehrfritz, A (reprint author), Univ Erlangen Nurnberg, Dept Anaesthesiol, Erlangen, Germany. EM andreas.wehrfritz@kfa.imed.uni-erlangen.de FU Air Liquide FX This work was sponsored by Air Liquide. NR 34 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1090-3801 EI 1532-2149 J9 EUR J PAIN JI Eur. J. Pain PD OCT PY 2016 VL 20 IS 9 BP 1467 EP 1477 DI 10.1002/ejp.870 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA DW4PY UT WOS:000383626700010 PM 27029459 ER PT J AU Mehra, R Udager, AM Ahearn, TU Cao, XH Feng, FY Loda, M Petimar, JS Kantoff, P Mucci, LA Chinnaiyan, AM AF Mehra, Rohit Udager, Aaron M. Ahearn, Thomas U. Cao, Xuhong Feng, Felix Y. Loda, Massimo Petimar, Joshua S. Kantoff, Philip Mucci, Lorelei A. Chinnaiyan, Arul M. TI Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE SChLAP1; Metastatic prostate cancer; long noncoding RNA; In situ hybridization; Lethal prostate cancer ID RADICAL PROSTATECTOMY; PROGRESSION; COHORT AB The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score >= 100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. Patient summary: We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Mehra, Rohit; Udager, Aaron M.; Chinnaiyan, Arul M.] Univ Michigan Hlth Syst, Dept Pathol, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. [Mehra, Rohit; Feng, Felix Y.; Chinnaiyan, Arul M.] Univ Michigan Hlth Syst, Ctr Comprehens Canc, Ann Arbor, MI USA. [Mehra, Rohit; Cao, Xuhong; Feng, Felix Y.; Chinnaiyan, Arul M.] Michigan Ctr Translat Pathol, Ann Arbor, MI USA. [Ahearn, Thomas U.; Petimar, Joshua S.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Feng, Felix Y.] Univ Michigan Hlth Syst, Dept Radiat Oncol, Ann Arbor, MI USA. [Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Kantoff, Philip] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chinnaiyan, Arul M.] Howard Hughes Med Inst, Ann Arbor, MI USA. RP Mehra, R; Chinnaiyan, AM (reprint author), Univ Michigan Hlth Syst, Dept Pathol, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.; Mehra, R; Chinnaiyan, AM (reprint author), Ctr Comprehens Canc, 1400 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mrohit@med.umich.edu; arul@med.umich.edu FU Prostate Cancer Foundation; National Cancer Institute Prostate SPORE [P50CA186786, P50 CA090381]; Early Detection Research Network [UO1 CA113913]; National Cancer Institute [P01 CA055075, R01 CA133891, R01 CA141298, UM1 CA167552] FX This work was supported in part by the Prostate Cancer Foundation (R.M., F.Y.F., L.A.M., and A.M.C.), as well as the National Cancer Institute Prostate SPORE (P50CA186786 to A.M.C. and P50 CA090381 to P.W.K. and L.A.M.) and Early Detection Research Network (UO1 CA113913 to A.M.C.). Additional support for the PHS and HPFS cohorts is provided by the National Cancer Institute (P01 CA055075, R01 CA133891, R01 CA141298, and UM1 CA167552). The sponsors played a role in the design and conduct of the study. NR 10 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD OCT PY 2016 VL 70 IS 4 BP 549 EP 552 DI 10.1016/j.eururo.2015.12.003 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DZ0CB UT WOS:000385503700002 PM 26724257 ER PT J AU Daskalakis, NP Cohen, H Nievergelt, CM Baker, DG Buxbaum, JD Russo, SJ Yehuda, R AF Daskalakis, Nikolaos P. Cohen, Hagit Nievergelt, Caroline M. Baker, Dewleen G. Buxbaum, Joseph D. Russo, Scott J. Yehuda, Rachel TI New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility SO EXPERIMENTAL NEUROLOGY LA English DT Review DE PTSD; Stress; Individual differences; Glucocorticoids; Immune system; Biomarkers; Novel treatments ID PERIPHERAL MONONUCLEAR LEUKOCYTES; CHILDHOOD SEXUAL ABUSE; GENE-EXPRESSION; ANIMAL-MODEL; HPA-AXIS; INDIVIDUAL-DIFFERENCES; PSYCHIATRIC-DISORDERS; SYNAPTIC PLASTICITY; CYTOKINE PRODUCTION; RECEPTOR PATHWAY AB Although biological systems have evolved to promote stress-resilience, there is variation in stress-responses. Understanding the biological basis of such individual differences has implications for understanding Posttraumatic Stress Disorder (PTSD) etiology, which is a maladaptive response to trauma occurring only in a subset of vulnerable individuals. PTSD involves failure to reinstate physiological homeostasis after traumatic events and is due to either intrinsic or trauma-related alterations in physiological systems across the body. Master homeostatic regulators that circulate and operate throughout the organism, such as stress hormones (e.g., glucocorticoids) and immune mediators (e.g., cytokines), are at the crossroads of peripheral and central susceptibility pathways and represent promising functional biomarkers of stress-response and target for novel therapeutics. (C) 2016 Elsevier Inc. All rights reserved. C1 [Daskalakis, Nikolaos P.; Buxbaum, Joseph D.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Daskalakis, Nikolaos P.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Mental Hlth Patient Care Ctr, Bronx, NY USA. [Cohen, Hagit] Ben Gurion Univ Negev, Fac Hlth Sci, Minist Hlth Mental Hlth Ctr, Anxiety & Stress Res Unit, Beer Sheva, Israel. [Nievergelt, Caroline M.; Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Nievergelt, Caroline M.; Baker, Dewleen G.] Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.; Russo, Scott J.; Yehuda, Rachel] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. RP Daskalakis, NP (reprint author), Dept Psychiat, One Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM nikolaos.daskalakis@mssm.edu OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU U.S. Army Medical Research and Materiel Command [W81XWH-08-2-0021, W81XWH-13-1-0071]; Brain & Behavior Research Foundation grant [NARSAD 23670]; Marine Corps; Navy Bureau of Medicine and Surgery (BUMED); VA Health Research and Development (HSRD); Navy BUMED; US National Institute of Mental Health [RO1 MH090264, RO1 MH104559]; Johnson & Johnson International Mental Health Research Organization Rising Star Award, an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award FX This work was supported by U.S. Army Medical Research and Materiel Command grants W81XWH-08-2-0021 and W81XWH-13-1-0071 (to RY) and Brain & Behavior Research Foundation grant NARSAD 23670 (to NPD). MRS and MRS-II (including RNA-seq) were funding by the Marine Corps, Navy Bureau of Medicine and Surgery (BUMED), VA Health Research and Development (HSR&D) and Navy BUMED, respectively (DGB, CMN). SJR was supported by US National Institute of Mental Health grants RO1 MH090264 and RO1 MH104559, the Johnson & Johnson International Mental Health Research Organization Rising Star Award, an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award. RY is a co-inventor of the following patent: Genes associated with posttraumatic-stress disorder. WO 2010029176 A1". NR 94 TC 1 Z9 1 U1 11 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2016 VL 284 SI SI BP 133 EP 140 DI 10.1016/j.expneurol.2016.07.024 PN B PG 8 WC Neurosciences SC Neurosciences & Neurology GA DY7UJ UT WOS:000385334500003 PM 27481726 ER PT J AU Hendrickson, RC Raskind, MA AF Hendrickson, Rebecca C. Raskind, Murray A. TI Noradrenergic dysregulation in the pathophysiology of PTSD SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Prazosin; Posttraumatic stress disorder (PTSD); Noradrenergic ID POSTTRAUMATIC-STRESS-DISORDER; SALIVARY ALPHA-AMYLASE; CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; HEART-RATE-VARIABILITY; COMBAT-RELATED PTSD; REDUCES ALCOHOL-DRINKING; LOCUS-COERULEUS ACTIVITY; PITUITARY-ADRENAL AXIS; TRAUMATIC BRAIN-INJURY AB A central role for noradrenergic dysregulation in the pathophysiology of post-traumatic stress disorder (PTSD) is increasingly suggested by both clinical and basic neuroscience research. Here, we integrate recent findings from clinical and animal research with the earlier literature. We first review the evidence for net upregulation of the noradrenergic system and its responsivity to stress in individuals with PTSD. Next, we trace the evidence that the o noradrenergic receptor antagonist prazosin decreases many of the symptoms of PTSD from initial clinical observations, to case series, to randomized controlled trials. Finally, we review the basic science work that has begun to explain the mechanism for this efficacy, as well as to explore its possible limitations and areas for further advancement. We suggest a view of the noradrenergic system as a central, modifiable link in a network of interconnected stress-response systems, which also includes the amygdala and its modulation by medial prefrontal cortex. Particular attention is paid to the evidence for bidirectional signaling between noradrenaline and corticotropin-releasing factor (CRF) in coordinating these interconnected systems. The multiple different ways in which the sensitivity and reactivity of the noradrenergic system may be altered in PTSD are highlighted, as is the evidence for possible heterogeneity in the pathophysiology of PTSD between different individuals who appear clinically similar. We conclude by noting the importance moving forward of improved measures of noradrenergic functioning in clinical populations, which will allow better recognition of clinical heterogeneity and further assessment of the functional implications of different aspects of noradrenergic dysregulation. Published by Elsevier Inc. C1 VISN 20 Northwest Network, MIRECC, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hendrickson, RC (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S116 MIRECC, Seattle, WA 98108 USA. EM rhend@uw.edu FU Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the Puget Sound Veterans Affairs Health Care System; Puget Sound Veterans Affairs Health Care System Mental Illness Research, Education, and Clinical Center (MIRECC); Department of Defense [W81XWH-12-2-0094] FX The writing of this manuscript was supported by the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the Puget Sound Veterans Affairs Health Care System, the Puget Sound Veterans Affairs Health Care System Mental Illness Research, Education, and Clinical Center (MIRECC) and the Department of Defense (W81XWH-12-2-0094). NR 177 TC 1 Z9 1 U1 11 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2016 VL 284 SI SI BP 181 EP 195 DI 10.1016/j.expneurol.2016.05.014 PN B PG 15 WC Neurosciences SC Neurosciences & Neurology GA DY7UJ UT WOS:000385334500007 PM 27222130 ER PT J AU Ghorbanhoseini, M Ghaheri, A Walley, KC Kwon, JY AF Ghorbanhoseini, Mohammad Ghaheri, Azadeh Walley, Kempland C. Kwon, John Y. TI Superior Tuber Displacement in Intra-articular Calcaneus Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE intra-articular calcaneus fracture; talo-tuber angle; talo-tuber distance; calcaneal tuber superior displacement; triceps surae weakness ID HUMAN TRICEPS SURAE; WOUND COMPLICATIONS; OPERATIVE TREATMENT; INTERNAL-FIXATION; BOHLERS ANGLE; MUSCLE LENGTH; RISK-FACTORS; RADIOGRAPHS; REDUCTION; FORCE AB Background: Intra-articular calcaneus fractures result in heel shortening, widening, varus malalignment, and loss of height. Little has been written regarding superior displacement of the calcaneal tuber, which warrants consideration as previous literature has demonstrated issues arising from a shortened triceps surae. We sought to determine the amount of tuber elevation seen in calcaneus fractures as compared to normal calcanei and propose 2 new measurements that aid in quantifying displacement and may aid in the surgical management of calcaneus fractures. Methods: Lateral radiographs of 220 normal calcanei were examined. Two novel measurements, the talo-tuber angle and talo-tuber distance, were used to establish normative data for calcaneal tuber positioning. Lateral radiographs of 50 calcaneus fractures treated operatively were examined and the same measurements were obtained before and after surgery to determine the amount of superior tuber elevation. Results: Normative data demonstrated a mean of 38.6 degrees (SD = 4.3, range: 26.2-58.4) when using the talo-tuber angle and 54.5 mm (SD = 7.3, range: 36.2-72.6) when using the talo-tuber distance in normal calcanei. Patients sustaining calcaneus fractures demonstrated a mean of 29.5 degrees (+/- SD = 5.9, range: 20-46.4) for the talo-tuber angle and 39.0 mm (+/- SD = 9.4, range: 24.0-62.9) for the talo-tuber distance. These values changed to a mean of 37 degrees (+/- SD = 5.2, range: 26.4-50) for the talo-tuber angle and 51.8 mm (+/- SD = 8.6, range: 33.2-75.7) for the talo-tuber distance after surgery. There was a statistically significant difference (P value < .01) for both talo-tuber angle and distance between normal and fractured calcanei. Inter- and intra-observer agreement was excellent. Conclusion: Superior displacement of the calcaneal tuber is a deformity seen in intra-articular calcaneus fractures that has been poorly described that warrants increased awareness and correction at the time of surgery. We propose 2 novel measurements with associated normative data that may aid surgeons in quantifying this deformity and assessing anatomic reduction. Level of Evidence: Level III, comparative study. C1 [Ghorbanhoseini, Mohammad; Walley, Kempland C.; Kwon, John Y.] Harvard Med Sch, BIDMC, Carl J Shapiro Dept Orthopaed, 330 Brookline Ave, Boston, MA 02215 USA. [Ghaheri, Azadeh] ACECR, Royan Inst Reprod Biomed, Reprod Epidemiol Res Ctr, Dept Epidemiol & Reprod Hlth, Tehran, Iran. RP Ghorbanhoseini, M (reprint author), Harvard Med Sch, BIDMC, Carl J Shapiro Dept Orthopaed, 330 Brookline Ave, Boston, MA 02215 USA. EM mghorban@bidmc.harvard.edu NR 35 TC 0 Z9 0 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD OCT PY 2016 VL 37 IS 10 BP 1076 EP 1083 DI 10.1177/1071100716651965 PG 8 WC Orthopedics SC Orthopedics GA DY7YN UT WOS:000385345300007 PM 27283153 ER PT J AU VanValkenburg, S Hsu, RY Palmer, DS Blankenhorn, B Den Hartog, BD DiGiovanni, CW AF VanValkenburg, Scott Hsu, Raymond Y. Palmer, Daniel S. Blankenhorn, Brad Den Hartog, Bryan D. DiGiovanni, Christopher W. TI Neurologic Deficit Associated With Lateralizing Calcaneal Osteotomy for Cavovarus Foot Correction SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE lateralizing calcaneal osteotomy; tibial nerve palsy; cavovarus deformity ID NEUROPATHY; MANAGEMENT; CAVUS AB Background: Lateralizing calcaneal osteotomy (LCO) is a frequently used technique to correct hindfoot varus deformity. Tibial nerve palsy following this osteotomy has been described in case reports but the incidence has not been quantified. Methods: Eighty feet in 72 patients with cavovarus foot deformity were treated over a 6-year span by 2 surgeons at their respective institutions. Variations of the LCO were employed for correction per surgeon choice. A retrospective chart review analyzed osteotomy type, osteotomy location, amount of translation, and addition of a tarsal tunnel release in relation to the presence of any postoperative tibial nerve palsy. Tibial nerve branches affected and the time to resolution of any deficits was also noted. Results: The incidence of neurologic deficit following LCO was 34%. With an average follow-up of 19 months, a majority (59%) resolved fully at an average of 3 months. There was a correlation between the development of neurologic deficit and the location of the osteotomy in the middle third as compared to the posterior third of the calcaneal tuber. We found no relationship between the osteotomy type, amount of correction, or addition of a tarsal tunnel release and the incidence of neurologic injury. Conclusions: Tibial nerve palsy was not uncommon following LCO. Despite the fact that deficits were found to be transient, physicians should be more aware of this potential problem and counsel patients accordingly. To decrease the risk of this complication, we advocate extra caution when performing the osteotomy in the middle one-third of the calcaneal tuberosity. Although intuitively the addition of a tarsal tunnel release may protect against injury, no protective effect was demonstrated in this retrospective study. Level of Evidence: Level III, retrospective cohort study. C1 [VanValkenburg, Scott] Upstate Bone & Joint Ctr, East Syracuse, NY USA. [Hsu, Raymond Y.; Blankenhorn, Brad] Brown Univ, Warren Alpert Sch Med, 593 Eddy St, Providence, RI 02903 USA. [Hsu, Raymond Y.; Blankenhorn, Brad] Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. [Palmer, Daniel S.; Den Hartog, Bryan D.] Des Moines Orthopaed Surg, W Des Moines, IA USA. [DiGiovanni, Christopher W.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Hsu, RY (reprint author), Brown Univ, Warren Alpert Sch Med, 593 Eddy St, Providence, RI 02903 USA.; Hsu, RY (reprint author), Rhode Isl Hosp, 593 Eddy St, Providence, RI 02903 USA. EM raymond_hsu@brown.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD OCT PY 2016 VL 37 IS 10 BP 1106 EP 1112 DI 10.1177/1071100716655206 PG 7 WC Orthopedics SC Orthopedics GA DY7YN UT WOS:000385345300011 PM 27340259 ER PT J AU Mossman, JA Tross, JG Li, N Wu, ZJ Rand, DM AF Mossman, Jim A. Tross, Jennifer G. Li, Nan Wu, Zhijin Rand, David M. TI Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila SO GENETICS LA English DT Article DE mtDNA; epistasis; Drosophila; transcriptome; mitonuclear; retrograde signaling ID RESPIRATORY COMPLEX I; GENETIC REFERENCE PANEL; REAL-TIME PCR; NEURODEGENERATIVE DISEASES; OXIDATIVE-PHOSPHORYLATION; EXPRESSION ANALYSIS; SPERM MOTILITY; DNA MOLECULES; TRANSFER-RNA; MELANOGASTER AB The assembly and function of mitochondria require coordinated expression from two distinct genomes, the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mutations in either genome can be a source of phenotypic variation, yet their coexpression has been largely overlooked as a source of variation, particularly in the emerging paradigm of mitochondrial replacement therapy. Here we tested how the transcriptome responds to mtDNA and nDNA variation, along with mitonuclear interactions (mtDNA 3 nDNA) in Drosophila melanogaster. We used two mtDNA haplotypes that differ in a substantial number of single nucleotide polymorphisms, with >100 amino acid differences. We placed each haplotype on each of two D. melanogaster nuclear backgrounds and tested for transcription differences in both sexes. We found that large numbers of transcripts were differentially expressed between nuclear backgrounds, and that mtDNA type altered the expression of nDNA genes, suggesting a retrograde, trans effect of mitochondrial genotype. Females were generally more sensitive to genetic perturbation than males, and males demonstrated an asymmetrical effect of mtDNA in each nuclear background; mtDNA effects were nuclear-background specific. mtDNA-sensitive genes were not enriched in male-or female-limited expression space in either sex. Using a variety of differential expression analyses, we show the responses to mitonuclear covariation to be substantially different between the sexes, yet the mtDNA genes were consistently differentially expressed across nuclear backgrounds and sexes. Our results provide evidence that the main mtDNA effects can be consistent across nuclear backgrounds, but the interactions between mtDNA and nDNA can lead to sex-specific global transcript responses. C1 [Mossman, Jim A.; Tross, Jennifer G.; Rand, David M.] Brown Univ, Dept Ecol & Evolutionary Biol, Box G, Providence, RI 02912 USA. [Li, Nan; Wu, Zhijin] Brown Univ, Dept Biostat, Providence, RI 02912 USA. [Tross, Jennifer G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tross, Jennifer G.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Tross, Jennifer G.] Harvard Med Sch, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. RP Mossman, JA; Rand, DM (reprint author), Brown Univ, Dept Ecol & Evolutionary Biol, Box G, Providence, RI 02912 USA. EM Jim_Mossman@brown.edu; david_rand@brown.edu FU National Institutes of Health [R01 GM-067862, AG-027849] FX We thank Christoph Schorl for assistance in the processing of RNA sequencing libraries, and Mark Howison for demultiplexing the samples. Jason Wood provided scripting help and Leann Biancani provided assistance with fly husbandry. A.-M. Hernandez gave critical comments on the manuscript. This work was conducted using computational resources and services at the Center for Computation and Visualization, Brown University. This project was funded by National Institutes of Health grants R01 GM-067862 and AG-027849 to D.M.R. NR 92 TC 1 Z9 1 U1 8 U2 8 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 OCT PY 2016 VL 204 IS 2 BP 613 EP + DI 10.1534/genetics.116.192328 PG 42 WC Genetics & Heredity SC Genetics & Heredity GA DZ4ZP UT WOS:000385871400019 PM 27558138 ER PT J AU Plitt, A Ruff, CT Giugliano, RP AF Plitt, Anna Ruff, Christian T. Giugliano, Robert P. TI Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Atrial fibrillation; NOAC; Dabigatran; Rivaroxaban; Apixaban; Edoxaban ID FACTOR XA INHIBITOR; DIRECT THROMBIN INHIBITOR; MECHANICAL HEART-VALVES; DABIGATRAN ETEXILATE; CLINICAL-PRACTICE; RENAL-FUNCTION; RISK-FACTORS; ROCKET AF; WARFARIN; TRIAL AB For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described. C1 [Plitt, Anna] Mt Sinai Hosp, Dept Internal Med, One Gustave L Levy Pl, New York, NY 10029 USA. [Ruff, Christian T.; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU American College of Cardiology; Boehringer-Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Janssen Pharmaceuticals; Merck; Portola; Pfizer; Sanofi; Bayer; Boehringer Ingelheim; Astra Zeneca; Eisai; Intarcia FX A. Plitt reports no conflict of interest. Dr R.P. Giugliano reports receiving consulting fees from the American College of Cardiology, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, Merck, Portola, and Pfizer; lecture fees from Bristol-Myers Squibb, Daiichi Sankyo, Merck, and Sanofi; and grant support through his institution from Daiichi Sankyo and Merck. Dr C.T. Ruff reports receiving consulting fees from Bayer, Daiichi Sankyo, Portola, and Boehringer Ingelheim and grant support through his institution from Daiichi Sankyo, Astra Zeneca, Eisai, and Intarcia. NR 56 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 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2016 VL 30 IS 5 BP 1019 EP + DI 10.1016/j.hoc.2016.05.002 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA DY9QH UT WOS:000385469700005 PM 27637305 ER PT J AU Hu, CH Hua, X Ying, J Thompson, PM Fakhri, GE Li, QZ AF Hu, Chenhui Hua, Xue Ying, Jun Thompson, Paul M. Fakhri, Georges E. Li, Quanzheng TI Localizing Sources of Brain Disease Progression with Network Diffusion Model SO IEEE JOURNAL OF SELECTED TOPICS IN SIGNAL PROCESSING LA English DT Article DE Alzheimer's disease; brain morphology; inverse problem; magnetic resonance imaging (MRI); network diffusion; sources of dementia ID MILD COGNITIVE IMPAIRMENT; TENSOR-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; PROPAGATION; CONNECTIVITY; DEMENTIA; DYNAMICS; ATROPHY; MRI AB Pinpointing the sources of dementia is crucial to the effective treatment of neurodegenerative diseases. In this paper, we propose a diffusion model with impulsive sources over the brain connectivity network to model the progression of brain atrophy. To reliably estimate the atrophy sources, we impose sparse regularization on the source distribution and solve the inverse problem with an efficient gradient descent method. We localize the possible origins of Alzheimer's disease (AD) based on a large set of repeated magnetic resonance imaging (MRI) scans in Alzheimer's Disease Neuroimaging Initiative database. The distribution of the sources averaged over the sample population is evaluated. We find that the dementia sources have different concentrations in the brain lobes for AD patients and mild cognitive impairment (MCI) subjects, indicating possible switch of the dementia driving mechanism. Moreover, we demonstrate that we can effectively predict changes of brain atrophy patterns with the proposed model. Our work could help understand the dynamics and origin of dementia, as well as monitor the progression of the diseases in an early stage. C1 [Hu, Chenhui] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Hu, Chenhui] Microsoft, Cambridge, MA 02142 USA. [Hua, Xue] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hua, Xue] M3 Biotechnol, Seattle, WA 98195 USA. [Ying, Jun] Chinese Peoples Liberat Army Gen Hosp, Hosp 301, Beijing 100853, Peoples R China. [Thompson, Paul M.] Univ Southern Calif, Imaging Genet Ctr, Neurol & Psychiat, Los Angeles, CA 90032 USA. [Fakhri, Georges E.; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. RP Hu, CH (reprint author), Microsoft, Cambridge, MA 02142 USA. EM hu4@seas.harvard.edu; xue.hua@ini.usc.edu; yingjun301@sina.com; pthomp@usc.edu; elfakhri@pet.mgh.harvard.edu; li.quanzheng@mgh.harvard.edu OI Hu, Chenhui/0000-0003-1838-2484 FU National Institutes of Health [R01EB013293] FX This work was supported in part by the National Institutes of Health under Grant R01EB013293. The guest editor coordinating the review of this manuscript and approving it for publication was Dr. Andrew Zalesky. NR 49 TC 0 Z9 0 U1 3 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1932-4553 EI 1941-0484 J9 IEEE J-STSP JI IEEE J. Sel. Top. Signal Process. PD OCT PY 2016 VL 10 IS 7 BP 1214 EP 1225 DI 10.1109/JSTSP.2016.2601695 PG 12 WC Engineering, Electrical & Electronic SC Engineering GA DZ1CK UT WOS:000385576200009 ER PT J AU Karlsson, P Cole, BF Price, KN Gelber, RD Coates, AS Goldhirsch, A Castiglione, M Colleoni, M Gruber, G AF Karlsson, Per Cole, Bernard F. Price, Karen N. Gelber, Richard D. Coates, Alan S. Goldhirsch, Aron Castiglione, Monica Colleoni, Marco Gruber, Guenther CA Int Breast Canc Study Grp TI Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID COMPETING RISK; RADIOTHERAPY; DELAY; OUTCOMES; TIME AB Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87- 1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82- 1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61- 1.46) in trial VI and 1.51 (95% CI 0.77- 2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80- 1.63) and 1.08 (95% CI 0.69- 1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT. (C) 2016 Elsevier Inc. All rights reserved. C1 [Karlsson, Per] Univ Gothenburg, Sahlgrenska Univ Hosp, Sahgrenska Acad, Dept Oncol,Inst Clin Sci, Bla Straket 2, S-41345 Gothenburg, Sweden. [Cole, Bernard F.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Int Breast Canc Study Grp, Ctr Stat, Boston, MA USA. [Gelber, Richard D.] Harvard TF Chan Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Dana Farber Canc Inst,Stat Ctr, Dept Biostat & Computat Biol,Int Breast Canc Stud, Boston, MA USA. [Coates, Alan S.] Int Breast Canc Study Grp, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW, Australia. [Goldhirsch, Aron] European Inst Oncol, Breast Canc, Milan, Italy. [Goldhirsch, Aron] Int Breast Canc Study Grp, Milan, Italy. [Colleoni, Marco] Int Breast Canc Study Grp, Bern, Switzerland. [Colleoni, Marco] European Inst Oncol, Div Med Senol, Milan, Italy. [Gruber, Guenther] Klin Hirslanden, Inst Radiotherapy, Zurich, Switzerland. RP Karlsson, P (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Sahgrenska Acad, Dept Oncol,Inst Clin Sci, Bla Straket 2, S-41345 Gothenburg, Sweden. EM per.karlsson@oncology.gu.se FU Swedish Cancer Society; Cancer Council Australia; Australia and New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research; US National Institutes of Health [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland FX The International Breast Cancer Study Group received no industry support for the conduct or the long-term follow-up of these trials. The International Breast Cancer Study Group received funding from the Swedish Cancer Society, The Cancer Council Australia, Australia and New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, US National Institutes of Health grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland. NR 19 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2016 VL 96 IS 2 BP 273 EP 279 DI 10.1016/j.ijrobp.2016.06.2448 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DZ0IO UT WOS:000385521900006 PM 27598802 ER PT J AU Muralidhar, V Rose, BS Chen, YW Nezolosky, MD Nguyen, PL AF Muralidhar, Vinayak Rose, Brent S. Chen, Yu-Wei Nezolosky, Michelle D. Nguyen, Paul L. TI Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID STAGE BREAST-CANCER; FACILITY AB Objective: To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. Methods and Materials: We identified 222,804 patients diagnosed with National-Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Results: Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living <= 5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or > 15 miles away, respectively (P<. 001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (<= 25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; > 75 miles: 23.8%; P<. 05 in all cases). These trends were also presentwhen each risk group was analyzed separately. Conclusion: Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for localized prostate cancer. (C) 2016 Elsevier Inc. All rights reserved. C1 [Muralidhar, Vinayak] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Rose, Brent S.; Chen, Yu-Wei; Nezolosky, Michelle D.; Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. [Rose, Brent S.; Chen, Yu-Wei; Nezolosky, Michelle D.; Nguyen, Paul L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. RP Muralidhar, V (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM vmuralidhar@partners.org FU Prostate Cancer Foundation; Fitz's Cancer Warriors; David and Cynthia Chapin; Hugh Simons in Honor of Frank and Anne Simons; Scott Forbes and Gina Ventre Fund; Jeffrey Campbell in Honor of Joan Campbell FX This work was supported by the Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, the Scott Forbes and Gina Ventre Fund, Jeffrey Campbell in Honor of Joan Campbell, and a grant from an anonymous family foundation. NR 9 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2016 VL 96 IS 2 BP 313 EP 317 DI 10.1016/j.ijrobp.2016.05.022 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DZ0IO UT WOS:000385521900011 PM 27496390 ER PT J AU Sperduto, PW Yang, TJ Beal, K Pan, H Brown, PD Bangdiwala, A Shanley, R Yeh, N Gaspar, LE Braunstein, S Gaspar, LE Braunstein, S Sneed, P Boyle, J Kirkpatrick, JP Mak, KS Shih, HA Engelman, A Roberge, D Arvold, ND Alexander, B Awad, MM Contessa, J Chiang, V Hardie, J Ma, D Lou, E Sperduto, W Mehta, MP AF Sperduto, Paul W. Yang, T. Jonathan Beal, Kathryn Pan, Hubert Brown, Paul D. Bangdiwala, Ananta Shanley, Ryan Yeh, Norman Gaspar, Laurie E. Braunstein, Steve Gaspar, Laurie E. Braunstein, Steve Sneed, Penny Boyle, John Kirkpatrick, John P. Mak, Kimberley S. Shih, Helen A. Engelman, Alex Roberge, David Arvold, Nils D. Alexander, Brian Awad, Mark M. Contessa, Joseph Chiang, Veronica Hardie, John Ma, Daniel Lou, Emil Sperduto, William Mehta, Minesh P. TI The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT ASTRO Meeting CY NOV 13, 2015 CL San Diego, CA SP ASTRO ID RADIATION-THERAPY; STEREOTACTIC RADIOSURGERY; RANDOMIZED-TRIAL; SINGLE METASTASES; PHASE-3 TRIAL; CANCER; CHEMOTHERAPY; ERLOTINIB; EGFR; RADIOTHERAPY AB Purpose: Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods: A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results: Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR, ALK, and KRAS, respectively. The time from primary diagnosis to BM for EGFR-/+ was 10/15 months (P = .02) and for ALK-/+ was 10/20 months (P<.01), respectively. The MS for the group overall (n=1521) was 15 months. The MS from first treatment for BM for EGFR and ALK-, EGFR+, ALK+ were 14, 23 (P<.01), and 45 (P<.0001) months, respectively. The MS after BM for EGFR+ patients who did/did not receive TKI before BM was 17/30 months (P<.01), respectively, but the risk of death was not statistically different between TKI-naive patients who did/did not receive TKI after the diagnosis of BM (EGFR/ALK hazard ratios: 1.06 [P = .84]/1.60 [P = .45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion: EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD. (C) 2016 Elsevier Inc. All rights reserved. C1 [Sperduto, Paul W.] Minneapolis Radiat Oncol, Minneapolis, MN USA. [Sperduto, Paul W.] Univ Minnesota, Gamma Knife Ctr, Minneapolis, MN USA. [Yang, T. Jonathan; Beal, Kathryn] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Pan, Hubert; Brown, Paul D.] MD Anderson Canc Ctr, Houston, TX USA. [Bangdiwala, Ananta; Shanley, Ryan] Univ Minnesota, Mason Canc Ctr, Biostat, Minneapolis, MN USA. [Yeh, Norman; Gaspar, Laurie E.] Univ Colorado, Denver, CO 80202 USA. [Braunstein, Steve; Sneed, Penny] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boyle, John; Kirkpatrick, John P.; Sperduto, William] Duke Univ, Durham, NC USA. [Mak, Kimberley S.; Shih, Helen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Engelman, Alex; Mehta, Minesh P.] Univ Maryland, Baltimore, MD 21201 USA. [Roberge, David] Univ Montreal, CHUM, Montreal, PQ, Canada. [Arvold, Nils D.; Alexander, Brian; Awad, Mark M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Contessa, Joseph; Chiang, Veronica] Yale Univ, New Haven, CT USA. [Hardie, John; Ma, Daniel] Mayo Clin, Rochester, NY USA. [Lou, Emil] Univ Minnesota, Dept Hematol Oncol, Minneapolis, MN USA. RP Sperduto, PW (reprint author), Radiat Oncol, 560 South Maple St,Suite 10, Waconia, MN 55387 USA. EM psperduto@mropa.com OI mehta, minesh/0000-0002-4812-5713 NR 23 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2016 VL 96 IS 2 BP 406 EP 413 DI 10.1016/j.ijrobp.2016.06.006 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DZ0IO UT WOS:000385521900024 PM 27598807 ER PT J AU Song, MY Fung, TT Hu, FB Willett, WC Longo, VD Chan, AT Giovannucci, EL AF Song, Mingyang Fung, Teresa T. Hu, Frank B. Willett, Walter C. Longo, Valter D. Chan, Andrew T. Giovannucci, Edward L. TI Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality SO JAMA INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIALS; CARBOHYDRATE-DIET SCORE; WEIGHT-LOSS DIETS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; SKELETAL-MUSCLE; SWEDISH WOMEN; ENERGY-INTAKE AB IMPORTANCE Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research. Although the amount of protein may have specific effects, from a broader dietary perspective, the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome. OBJECTIVE To examine the associations of animal and plant protein intake with the risk for mortality. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study of US health care professionals included 131 342 participants from the Nurses' Health Study (1980 to end of follow-up on June 1, 2012) and Health Professionals Follow-up Study (1986 to end of follow-up on January 31, 2012). Animal and plant protein intake was assessed by regularly updated validated food frequency questionnaires. Data were analyzed from June 20, 2014, to January 18, 2016. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for all-cause and cause-specific mortality. RESULTS Of the 131 342 participants, 85 013 were women (64.7%) and 46 329 were men (35.3%) (mean [SD] age, 49 [9] years). The median protein intake, as assessed by percentage of energy, was 14% for animal protein (5th-95th percentile, 9%-22%) and 4% for plant protein (5th-95th percentile, 2%-6%). After adjusting for major lifestyle and dietary risk factors, animal protein intake was not associated with all-cause mortality (HR, 1.02 per 10% energy increment; 95% CI, 0.98-1.05; P for trend =.33) but was associated with higher cardiovascular mortality (HR, 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend =.04). Plant protein was associated with lower all-cause mortality (HR, 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend <.001) and cardiovascular mortality (HR, 0.88 per 3% energy increment; 95% CI, 0.80-0.97; P for trend =.007). These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking, heavy alcohol intake, overweight or obesity, and physical inactivity, but not evident among those without any of these risk factors. Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg. CONCLUSIONS AND RELEVANCE High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality, especially among individuals with at least 1 lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source. C1 [Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Clin & Translat Epidemiol Unit, Bartlett Hall Extens,Room 906,55 Fruit St, Boston, MA 02114 USA. [Song, Mingyang; Hu, Frank B.; Willett, Walter C.; Chan, Andrew T.; Giovannucci, Edward L.] Harvard Med Sch, Bartlett Hall Extens,Room 906,55 Fruit St, Boston, MA 02114 USA. [Song, Mingyang; Fung, Teresa T.; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Fung, Teresa T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hu, Frank B.; Willett, Walter C.; Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Longo, Valter D.] Univ Southern Calif, Sch Gerontol, Longev Inst, Dept Biol Sci, Los Angeles, CA 90089 USA. [Longo, Valter D.] FIRC Italian Fdn Canc Res, Inst Mol Oncol, Milan, Italy. [Chan, Andrew T.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. RP Song, MY (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Clin & Translat Epidemiol Unit, Bartlett Hall Extens,Room 906,55 Fruit St, Boston, MA 02114 USA.; Song, MY (reprint author), Harvard Med Sch, Bartlett Hall Extens,Room 906,55 Fruit St, Boston, MA 02114 USA. EM msong2@mgh.harvard.edu FU National Institutes of Health [UM1 CA186107, P01 CA87969, UM1 CA167552] FX This study was supported by the grants UM1 CA186107, P01 CA87969, and UM1 CA167552 from the National Institutes of Health. NR 50 TC 7 Z9 7 U1 14 U2 14 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 OCT PY 2016 VL 176 IS 10 BP 1453 EP 1463 DI 10.1001/jamainternmed.2016.4182 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DZ1ZU UT WOS:000385642000010 PM 27479196 ER PT J AU Bass, JL Gartley, T Kleinman, R AF Bass, Joel L. Gartley, Tina Kleinman, Ronald TI Unintended Consequences of Current Breastfeeding Initiatives SO JAMA PEDIATRICS LA English DT Editorial Material C1 [Bass, Joel L.; Gartley, Tina] Newton Wellesley Hosp, Dept Pediat, 2014 Washington St, Newton, MA 02462 USA. [Kleinman, Ronald] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Bass, JL (reprint author), Newton Wellesley Hosp, Dept Pediat, 2014 Washington St, Newton, MA 02462 USA. EM jbass@partners.org NR 9 TC 9 Z9 9 U1 3 U2 3 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 OCT PY 2016 VL 170 IS 10 BP 923 EP 924 DI 10.1001/jamapediatrics.2016.1529 PG 2 WC Pediatrics SC Pediatrics GA DZ2AB UT WOS:000385643000004 PM 27548387 ER PT J AU Silverberg, ND Iverson, GL McCrea, M Apps, JN Hammeke, TA Thomas, DG AF Silverberg, Noah D. Iverson, Grant L. McCrea, Michael Apps, Jennifer N. Hammeke, Thomas A. Thomas, Danny G. TI Activity-Related Symptom Exacerbations After Pediatric Concussion SO JAMA PEDIATRICS LA English DT Article ID SPORT-RELATED CONCUSSION; TRAUMATIC BRAIN-INJURY; BED REST; ADOLESCENTS; CHILDREN; RECOVERY; EXERCISE; TRIAL; YOUTH AB IMPORTANCE Recovery from concussion generally follows a trajectory of gradual improvement, but symptoms can abruptly worsen with exertion. This phenomenon is poorly understood. OBJECTIVES To characterize the incidence, course, and clinical significance of symptom exacerbations (spikes) in children after concussion. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of clinical trial data analyzes 63 eligible participants prospectively recruited from an emergency department who were asked to complete a postconcussion symptom scale and record their activities in a structured diary for the next 10 days. They completed standardized assessments of symptoms (postconcussion symptom scale), cognition (Immediate Post-Concussion Assessment and Cognitive Testing), and balance (Balance Error Scoring System) 10 days following the injury. Eligible participants were aged 11 to 18 years and sustained a concussion (according to the Centers for Disease Control and Prevention criteria) that did not result in an abnormal computed tomography scan or require hospital admission. The trial was conducted from May 2010 to December 2012, and the analysis was conducted from November 2015 to February 2016. MAIN OUTCOME AND MEASURE The occurrence of symptom spikes, defined as an increase of 10 or more points on the postconcussion symptom scale over consecutive days. RESULTS Of the 63 participants, there were 41 boys (65.1%) and 22 girls (34.9%), and the mean (SD) age was 13.8 (1.8) years. Symptom spikes occurred in one-third of the sample (20 participants [31.7%]). Symptom spikes tended to partially resolve within 24 hours. An abrupt increase in mental activity (ie, returning to school and extracurricular activities) from one day to the next increased the risk of a symptom spike (relative risk, 0.81; 95% CI, 0.21-3.21), but most symptom spikes were not preceded by a documented increase in physical or mental activity. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period but did not differ from the group without symptom spikes on cognition or balance 10 days following injury. CONCLUSIONS AND RELEVANCE Certain patients appeared susceptible to high and variable symptom reporting. Symptom spikes may not themselves be detrimental to recovery. The present findings support clinical guidelines for adolescents to return to school and activities gradually after concussion. C1 [Silverberg, Noah D.] Univ British Columbia, Dept Med, Div Phys Med & Rehabil, Vancouver, BC, 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. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] MassGen Hosp, Children Sports Concuss Program, Boston, MA USA. [McCrea, Michael] Med Coll Wisconsin, Dept Neurosurg, Clement J Zablocki VA Med Ctr, Milwaukee, WI 53226 USA. [Apps, Jennifer N.; Hammeke, Thomas A.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Thomas, Danny G.] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. RP Thomas, DG (reprint author), Childrens Hosp Wisconsin, Dept Pediat, Emergency Med, Corp Ctr, 999 N 92nd St,Ste C550, Milwaukee, WI 53226 USA. EM dthomas@mcw.edu FU Injury Research Center of the Medical College of Wisconsin; Vancouver Coastal Health Research Institute; Mooney-Reed Charitable Foundation FX Dr Thomas received the Advancing A Healthier Wisconsin Seed Grant from the Injury Research Center of the Medical College of Wisconsin. Dr Silverberg received salary support from the Vancouver Coastal Health Research Institute. Dr Iverson received funding from the Mooney-Reed Charitable Foundation. NR 32 TC 0 Z9 0 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2016 VL 170 IS 10 BP 946 EP 953 DI 10.1001/jamapediatrics.2016.1187 PG 8 WC Pediatrics SC Pediatrics GA DZ2AB UT WOS:000385643000013 PM 27479847 ER PT J AU Dhabangi, A Ainomugisha, B Cserti-Gazdewich, C Ddungu, H Kyeyune, D Musisi, E Opoka, R Stowell, CP Dzik, WH AF Dhabangi, Aggrey Ainomugisha, Brenda Cserti-Gazdewich, Christine Ddungu, Henry Kyeyune, Dorothy Musisi, Ezra Opoka, Robert Stowell, Christopher P. Dzik, Walter H. TI Cerebral Oximetry in Ugandan Children With Severe Anemia Clinical Categories and Response to Transfusion SO JAMA PEDIATRICS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; SICKLE-CELL-DISEASE; SYSTEMATIC ANALYSIS; TISSUE OXYGENATION; BLOOD-TRANSFUSION; PRETERM INFANTS; SATURATION; ACCURACY; MALARIA; AFRICA AB IMPORTANCE Severe anemia, defined as a hemoglobin level of less than 5.0 g/dL, affects millions of children worldwide. The brain has a high basal demand for oxygen and is especially vulnerable to hypoxemia. Previous studies have documented neurocognitive impairment in children with severe anemia. Data on cerebral tissue oxygenation in children with severe anemia and their response to blood transfusion are limited. OBJECTIVE To measure hemoglobin saturation in cerebral tissue (cerebral tissue oxygen saturation [tSO(2)]) before, during, and after blood transfusion in a cohort of children presenting to hospital with severe anemia. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, observational cohort study conducted from February 2013 through May 2015 and analyzed in July 2015 at a university hospital pediatric acute care facility in Kampala, Uganda, of 128 children, ages 6 to 60 months who were enrolled in a larger clinical trial, with a presenting hemoglobin level of less than 5.0 g/dL and a blood lactate level greater than 5mM. Most children had either malaria or sickle cell disease. EXPOSURES Red blood cell (RBC) transfusion given as 10 mL/kg over 120 minutes. MAIN OUTCOMES AND MEASURES Clinical and laboratory characteristics of children with pretransfusion cerebral tSO(2) levels less than 65%, 65% to 75%, and greater than 75%. Change in cerebral tSO(2) as a result of transfusion. RESULTS Of 128 children included in the study, oximetry results in 8 cases were excluded owing to motion artifacts; thus, 120 were included in this analysis. Cerebral tSO(2) values prior to transfusion ranged from 34% to 87%(median, 72%; interquartile range [IQR], 65%-76%). Eighty-one children (67%) demonstrated an initial cerebral tSO(2) level (<= 75%) corresponding to an oxygen extraction ratio greater than 0.36. Patients with sickle cell disease (n = 17) and malaria (n = 15) contributed in nearly equal numbers to the subgroup with an initial cerebral tSO(2) (< 65%). The level of consciousness, hemoglobin concentration, blood lactate level, and thigh muscle tSO(2) level were poor predictors of cerebral oxygen saturation. Following RBC transfusion, the median (IQR) cerebral tSO(2) level increased to 78%(73%-82%) (P < .001), but 21% of children failed to achieve a tSO(2) level greater than 75%. CONCLUSIONS AND RELEVANCE Severe anemia in children is frequently associated with low cerebral oxygenation levels as measured by near-infrared spectroscopy. Hemoglobin level and lactate concentration did not predict low cerebral tSO(2) levels. Cerebral tSO(2) levels increase with RBC transfusion with different patterns of response. More studies are needed to evaluate the use of noninvasive cerebral tissue oximetry in the care of children with severe anemia. C1 [Dhabangi, Aggrey] Makerere Univ, Child Hlth & Dev Ctr, Dept Pediat, Kampala, Uganda. [Ainomugisha, Brenda] Mulago Hosp, Dept Pediat, Kampala, Uganda. [Cserti-Gazdewich, Christine] Univ Toronto, Univ Hlth Network Lab Med, Toronto, ON, Canada. [Ddungu, Henry] Makerere Univ, Uganda Canc Inst, Kampala, Uganda. [Kyeyune, Dorothy; Musisi, Ezra] Uganda Natl Blood Transfus Serv, Kampala, Uganda. [Opoka, Robert] Mulago Hosp, Dept Pediat, Kampala, Uganda. [Opoka, Robert] Makerere Univ, Kampala, Uganda. [Stowell, Christopher P.; Dzik, Walter H.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA USA. RP Dzik, WH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St,Room J-224, Boston, MA 02114 USA. EM sdzik@mgh.harvard.edu FU US National Institutes of Health [1R21HL109518-01A1] FX This study was funded by the US National Institutes of Health 1R21HL109518-01A1. Nonin Medical Inc supplied the EQUANOX device and pediatric optodes used in the study. NR 31 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2016 VL 170 IS 10 BP 995 EP 1002 DI 10.1001/jamapediatrics.2016.1254 PG 8 WC Pediatrics SC Pediatrics GA DZ2AB UT WOS:000385643000019 PM 27532507 ER PT J AU McCoy, TH Castro, VM Roberson, AM Snapper, LA Perlis, RH AF McCoy, Thomas H., Jr. Castro, Victor M. Roberson, Ashlee M. Snapper, Leslie A. Perlis, Roy H. TI Improving Prediction of Suicide and Accidental Death After Discharge From General Hospitals With Natural Language Processing SO JAMA PSYCHIATRY LA English DT Article ID DECISION CURVE ANALYSIS; MENTAL-HEALTH; MODELS; RISK; PREVALENCE; ENTERPRISE; MARKERS; RECORDS AB IMPORTANCE Suicide represents the 10th leading cause of death across age groups in the United States (12.6 cases per 100 000) and remains challenging to predict. While many individuals who die by suicide are seen by physicians before their attempt, they may not seek psychiatric care. OBJECTIVE To determine the extent to which incorporating natural language processing of narrative discharge notes improves stratification of risk for death by suicide after medical or surgical hospital discharge. DESIGN, SETTING, AND PARTICIPANTS In this retrospective health care use study, clinical data were analyzed from individuals with discharges from 2 large academic medical centers between January 1, 2005, and December 31, 2013. MAIN OUTCOMES AND MEASURES The primary outcome was suicide as a reported cause of death based on Massachusetts Department of Public Health records. Regression models for prediction of death by suicide or accidental death were compared relying solely on coded clinical data and those using natural language processing of hospital discharge notes. RESULTS There were 845 417 hospital discharges represented in the cohort, including 458 053 unique individuals. Overall, all-cause mortality was 18% during 9 years, and the median follow-up was 5.2 years. The cohort included 235 (0.1%) who died by suicide during 2.4 million patient-years of follow-up. Positive valence reflected in narrative notes was associated with a 30% reduction in risk for suicide in models adjusted for coded sociodemographic and clinical features (hazard ratio, 0.70; 95% CI, 0.58-0.85; P < .001) and improved model fit (chi(2)(2) = 14.843, P < .001 by log-likelihood test). The C statistic was 0.741 (95% CI, 0.738-0.744) for models of suicide with or without inclusion of accidental death. CONCLUSIONS AND RELEVANCE Multiple clinical features available at hospital discharge identified a cohort of individuals at substantially increased risk for suicide. Greater positive valence expressed in narrative discharge summaries was associated with substantially diminished risk. Automated tools to aid clinicians in evaluating these risks may assist in identifying high-risk individuals. C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Ctr Human Genet Res, 185 Cambridge St,Sixth Floor,Simches Res Bldg, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Sixth Floor,Simches Res Bldg, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Ctr Human Genet Res, 185 Cambridge St,Sixth Floor,Simches Res Bldg, Boston, MA 02114 USA.; Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,Sixth Floor,Simches Res Bldg, Boston, MA 02114 USA. EM rperlis@partners.org OI McCoy, Thomas/0000-0002-5624-0439 FU National Institute of Mental Health [R25MH094612, P50 MH106933, R01MH106577]; National Human Genome Research Institute [P50 MH106933] FX Dr McCoy is supported in part by a Stanley Center fellowship and grant R25MH094612 from the National Institute of Mental Health. Dr Perlis is supported in part by grants P50 MH106933 and R01MH106577 from the National Institute of Mental Health and by grant P50 MH106933 from the National Human Genome Research Institute. NR 34 TC 0 Z9 0 U1 7 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD OCT PY 2016 VL 73 IS 10 BP 1064 EP 1071 DI 10.1001/jamapsychiatry.2016.2172 PG 8 WC Psychiatry SC Psychiatry GA DZ5QG UT WOS:000385916000012 PM 27626235 ER PT J AU Eddy, KT Kim, Y AF Eddy, Kamryn T. Kim, Yongjoo TI Dieting to Disordered Restricting SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material ID EATING-DISORDERS; ANOREXIA-NERVOSA C1 [Eddy, Kamryn T.; Kim, Yongjoo] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Eddy, Kamryn T.] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. [Kim, Yongjoo] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA.; Eddy, KT (reprint author), Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. NR 11 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 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2016 VL 59 IS 4 BP 369 EP 370 DI 10.1016/j.jadohealth.2016.07.015 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA DY9HI UT WOS:000385444100001 PM 27664462 ER PT J AU Goldstein, MA Alinsky, R Medeiros, C AF Goldstein, Mark A. Alinsky, Rachel Medeiros, Cathryn TI Males With Restrictive Eating Disorders: Barriers to Their Care SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material ID ANOREXIA-NERVOSA; BONE; PREVALENCE C1 [Goldstein, Mark A.] MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Goldstein, Mark A.; Alinsky, Rachel] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. [Alinsky, Rachel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Alinsky, Rachel] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Alinsky, Rachel] Harvard Med Sch, Dept Med, Boston, MA USA. [Medeiros, Cathryn] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. RP Goldstein, MA (reprint author), MassGen Hosp Children, Div Adolescent & Young Adult Med, Boston, MA 02114 USA.; Goldstein, MA (reprint author), Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2016 VL 59 IS 4 BP 371 EP 372 DI 10.1016/j.jadohealth.2016.07.022 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA DY9HI UT WOS:000385444100002 PM 27664463 ER PT J AU Khurshid, S Liang, JJ Owens, A Lin, D Schaller, R Epstein, AE Marchlinski, FE Frankel, DS AF Khurshid, Shaan Liang, Jackson J. Owens, Anjali Lin, David Schaller, Robert Epstein, Andrew E. Marchlinski, Francis E. Frankel, David S. TI Longer Paced QRS Duration is Associated With Increased Prevalence of Right Ventricular Pacing-Induced Cardiomyopathy SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE cardiomyopathy; heart failure; pacing; pacing induced cardiomyopathy; right ventricular pacing ID CONGESTIVE-HEART-FAILURE; SICK-SINUS SYNDROME; CARDIAC-RESYNCHRONIZATION THERAPY; PREMATURE DEPOLARIZATION; NODE DYSFUNCTION; ATRIAL; PREDICTORS; TRIAL; BLOCK AB Paced QRS and RV Pacing-Induced Cardiomyopathy IntroductionPacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients exposed to frequent right ventricular (RV) pacing. While echocardiography is diagnostic, the optimal surveillance strategy remains unknown. We sought to identify clinical and electrocardiographic factors associated with the presence of PICM to guide further testing. Methods and ResultsWe retrospectively studied 1,750 consecutive patients undergoing pacemaker implantation 2003-2012. Patients were included if baseline LVEF was normal, single chamber ventricular or dual chamber pacemaker (but not ICD or cardiac resynchronization therapy device) was implanted, frequent (20%) RV pacing was present and repeat echocardiogram was available following implantation. PICM was defined as 10% decrease in LVEF, resulting in LVEF <50%. Patients with alternative causes of cardiomyopathy were excluded. Clinical and electrocardiographic indicators of PICM were identified using multivariate logistic regression. Of 184 patients meeting study criteria, 42 (22.8%) developed PICM, with decrease in mean LVEF from 62.1% to 35.3% over mean follow-up 2.5 years. Longer follow-up paced QRS duration was associated with the presence of PICM (multivariate odds ratio 1.34 per 10 millisecond increase, 95% CI 1.06-1.63, p = 0.01). Paced QRS duration 150 milliseconds was 95% sensitive for PICM. Only half of patients with PICM had heart failure signs or symptoms at the time of echocardiographic diagnosis. ConclusionPatients with frequent RV pacing and paced QRS duration 150 milliseconds should be screened by echocardiogram to assess for PICM. Patients with paced QRS duration <150 milliseconds likely do not require screening, in the absence of heart failure signs or symptoms. C1 [Khurshid, Shaan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Liang, Jackson J.; Owens, Anjali; Lin, David; Schaller, Robert; Epstein, Andrew E.; Marchlinski, Francis E.; Frankel, David S.] Univ Penn, Perelman Sch Med, Div Cardiovasc, Electrophysiol Sect, Philadelphia, PA 19104 USA. RP Frankel, DS (reprint author), 9 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM david.frankel@uphs.upenn.edu FU Richard T. and Angela Clark Innovation Fund in Cardiac Electrophysiology; F. Harlan Batrus Research Fund FX This study is supported in part by The Richard T. and Angela Clark Innovation Fund in Cardiac Electrophysiology and The F. Harlan Batrus Research Fund. NR 21 TC 2 Z9 2 U1 2 U2 2 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 OCT PY 2016 VL 27 IS 10 BP 1174 EP 1179 DI 10.1111/jce.13045 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ4PN UT WOS:000385840900007 PM 27457998 ER PT J AU Ahmad, ZS Andersen, RL Andersen, LH O'Brien, EC Kindt, I Shrader, P Vasandani, C Newman, CB deGoma, EM Baum, SJ Hemphill, LC Hudgins, LC Ahmed, CD Kullo, IJ Gidding, SS Duffy, D Neal, W Wilemon, K Roe, MT Rader, DJ Ballantyne, CM Linton, MF Duell, PB Shapiro, MD Moriarty, PM Knowles, JW AF Ahmad, Zahid S. Andersen, Rolf L. Andersen, Lars H. O'Brien, Emily C. Kindt, Iris Shrader, Peter Vasandani, Chandna Newman, Connie B. deGoma, Emil M. Baum, Seth J. Hemphill, Linda C. Hudgins, Lisa C. Ahmed, Catherine D. Kullo, Iftikhar J. Gidding, Samuel S. Duffy, Danielle Neal, William Wilemon, Katherine Roe, Matthew T. Rader, Daniel J. Ballantyne, Christie M. Linton, MacRae F. Duell, P. Barton Shapiro, Michael D. Moriarty, Patrick M. Knowles, Joshua W. TI US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Familial hypercholesterolemia; Simon Broome; Dutch lipid clinic network; MEDPED; Hypercholesterolemia ID PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; DOUBLE-BLIND; ASSOCIATION; MANAGEMENT; POPULATION; INHIBITION; EVOLOCUMAB; EFFICACY; GUIDANCE AB BACKGROUND: In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. OBJECTIVE: To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. METHODS: We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: "clinical diagnosis," MEDPED, Simon Broome, DLCN, and other. RESULTS: Most adults enrolled in CASCADE FH (55.0%) received a "clinical diagnosis." The most commonly used formal criteria was Simon-Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P <.0001. Of the patients with only a "clinical diagnosis," 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. CONCLUSIONS: Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention. (C) 2016 National Lipid Association. All rights reserved. C1 [Ahmad, Zahid S.; Vasandani, Chandna] Univ Texas Southwestern, Div Nutr & Metab Dis, Dept Internal Med, Dallas, TX USA. [Andersen, Rolf L.; Andersen, Lars H.] Lancaster Gen Hlth Penn Med, Lancaster, PA USA. [O'Brien, Emily C.; Shrader, Peter; Roe, Matthew T.] Duke Clin Res Inst, Dept Med, Durham, NC USA. [Kindt, Iris; Ahmed, Catherine D.; Wilemon, Katherine] FH Fdn, South Pasadena, CA USA. [Newman, Connie B.] NYU, Sch Med, Dept Med, New York, NY USA. [deGoma, Emil M.; Rader, Daniel J.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Baum, Seth J.] Prevent Cardiol Inc, Boca Raton, FL USA. [Hemphill, Linda C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hudgins, Lisa C.] Rogosin Inst, New York, NY USA. [Kullo, Iftikhar J.] Mayo Clin, Rochester, MN USA. [Gidding, Samuel S.] Nemours Cardiac Ctr, Dept Pediat, Wilmington, DE USA. [Duffy, Danielle] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA. [Neal, William] West Virginia Univ, Dept Pediat, Morgantown, WV USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Linton, MacRae F.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Duell, P. Barton; Shapiro, Michael D.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Moriarty, Patrick M.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Knowles, Joshua W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. RP Knowles, JW (reprint author), Falk CVRC, Cardiovasc Med, Room CV273,MC 5406,300 Pasteur Dr, Stanford, CA 94305 USA. EM knowlej@stanford.edu OI Newman, Connie/0000-0001-9144-056X FU CASCADE-FH Registry; Amgen; AZ; Aegerion; Sanofi/Regeneron; Pfizer; National Institutes of Health (NIH) (UT Southwestern site) [K23 HL114884]; AHA National Innovative Research [15IRG222930034] FX Sponsors for the CASCADE-FH Registry include Amgen, AZ, Aegerion, Sanofi/Regeneron, and Pfizer. The work was also supported by grants National Institutes of Health (NIH) K23 HL114884 (UT Southwestern site, PI: ZA). Knowles is supported by an AHA National Innovative Research Grant 15IRG222930034. NR 28 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 1933-2874 EI 1876-4789 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD OCT PY 2016 VL 10 IS 5 BP 1223 EP 1229 DI 10.1016/j.jac1.2016.07.011 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DZ5LN UT WOS:000385903700021 PM 27678440 ER PT J AU Baniasadi, N Paschalis, EI Haghzadeh, M Ojha, P Elze, T Mahd, M Chen, TC AF Baniasadi, Neda Paschalis, Eleftherios I. Haghzadeh, Mahdi Ojha, Pallavi Elze, Tobias Mahd, Mufeed Chen, Teresa C. TI Patterns of Retinal Nerve Fiber Layer Loss in Different Subtypes of Open Angle Glaucoma Using Spectral Domain Optical Coherence Tomography SO JOURNAL OF GLAUCOMA LA English DT Article DE glaucoma; optical coherence tomography; retinal nerve fiber layer ID NORMAL-TENSION GLAUCOMA; SCANNING LASER POLARIMETRY; STANDARD AUTOMATED PERIMETRY; VISUAL-FIELD LOSS; MACULAR THICKNESS; DIAGNOSTIC CAPABILITY; DAMAGE; PROGRESSION; PARAMETERS; OCT AB Purpose of the Study: The purpose of the study was to determine whether there are different patterns of retinal nerve fiber layer (RNFL) thinning as measured by spectral domain optical coherence tomography (SD-OCT) for 4 subtypes of open angle glaucoma (OAG): primary OAG (POAG), normal tension glaucoma (NTG), pseudoexfoliation glaucoma (PXG), and pigmentary glaucoma (PDG) and to compare them with normal controls. Materials and Methods: SD-OCT RNFL thickness values were measured for 4 quadrants and for 4 sectors (ie, superior-nasal, superior-temporal, inferior-nasal, and inferior-temporal). Differences in RNFL thickness values between groups were analyzed using analysis of variance. Paired t tests were used for quadrant comparisons. Results: Two hundred eighty-five participants (102 POAG patients, 33 with NTG, 48 with PXG, 13 with PDG, and 89 normal patients) were included in this study. All 4 subtypes of OAG showed significant RNFL thinning in the superior, inferior, and nasal quadrants as well as the superior-temporal and inferior-temporal sectors (all P-values < 0.0001) compared with normals. POAG and NTG patients had greater RNFL thinning inferiorly and inferior-temporally than superiorly (P-values: 0.002 to 0.018 and 0.006, respectively) compared with PXG patients. In contrast, PDG patients had greater RNFL thinning superiorly and superior-nasally than inferiorly compared with other OAG subtypes (ie, POAG, NTG, PXG groups, with P-values: 0.009, 0.003, 0.009, respectively). Of the 4 OAG subtypes, PXG patients exhibited the greatest degree of inter-eye RNFL asymmetry. Conclusions: This study suggests that SD-OCT may be able to detect significant differences in patterns of RNFL thinning for different subtypes of OAG. C1 [Baniasadi, Neda; Ojha, Pallavi; Chen, Teresa C.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. [Baniasadi, Neda; Paschalis, Eleftherios I.; Elze, Tobias] Harvard Med Sch, Schepens Eye Res Inst, Boston, MA USA. [Baniasadi, Neda] Univ Massachusetts, Dept Biomed Engn & Biotechnol, Lowell, MA USA. [Haghzadeh, Mahdi; Mahd, Mufeed] Univ Massachusetts, Dept Elect & Comp Engn, Lowell, MA USA. RP Chen, TC (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM Teresa_Chen@meei.harvard.edu NR 91 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 2016 VL 25 IS 10 BP 865 EP 872 DI 10.1097/IJG.0000000000000534 PG 8 WC Ophthalmology SC Ophthalmology GA DY9FT UT WOS:000385440000030 PM 27599175 ER PT J AU Claessen, FMAP Heesters, BA Chan, JJ Kachooei, AR Ring, D AF Claessen, Femke M. A. P. Heesters, Balthasar A. Chan, Jimmy J. Kachooei, Amir Reza Ring, David TI A Meta-Analysis of the Effect of Corticosteroid Injection for Enthesopathy of the Extensor Carpi Radialis Brevis Origin SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Corticosteroid; tennis elbow; enthesopathy of the extensor carpi radialis brevis; meta-analysis ID RANDOMIZED CONTROLLED-TRIAL; LATERAL EPICONDYLITIS; TENNIS ELBOW; LOCAL INJECTION; CLINICAL-TRIAL; SALINE INJECTION; DOUBLE-BLIND; PAIN; HYDROCORTISONE; PHYSIOTHERAPY AB Purpose The null hypothesis that there is no effect of corticosteroid injection on visual analog scale for pain in patients with enthesopathy of the extensor carpi radialis brevis (eECRB) origin 6 months after treatment was tested. Our secondary hypotheses were that there is no effect of corticosteroid injection on pain intensity at 1 and 3 months after treatment; that there is no effect of corticosteroid injection on grip strength at 1, 3, and 6 months after treatment; and that there is no effect of corticosteroid injection on Disabilities of the Arm, Shoulder, and Hand scores at 1, 3 and 6 months after treatment. Methods EMBASE, PubMed Publisher, MEDLINE, OvidSP, Web of Science, Google Scholar, and the Cochrane Central were searched for relevant studies. Studies were eligible if there was (1) a description of corticosteroid injection treatment for eECRB; (2) randomized placebo injection controlled trials with at least 10 adults included with eECRB; (3) a full-text article available with data describing the mean differences between the corticosteroid and the control groups and the outcome measures used; and (4) follow-up of at least 1 month. In total, 7 randomized controlled trials comparing the effect of corticosteroid injection with a placebo injection on symptoms of eECRB were included in our meta-analysis. Results We found no difference in pain intensity 6 months after injection of corticosteroids or placebo. Pain intensity was slightly, but significantly, lower 1 month, but not 3 months, after steroid injection. There were no significant differences in grip strength or Disabilities of the Arm, Shoulder, and Hand score at any time point. Conclusions This meta-analysis showed that there is no difference in pain intensity between corticosteroid injection and placebo 6 months after injection. We interpret the weight of evidence to date as suggesting that corticosteroid injections are neither meaningfully palliative nor disease modifying when used to treat eECRB. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved. C1 [Claessen, Femke M. A. P.; Chan, Jimmy J.; Kachooei, Amir Reza] Harvard Med Sch, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. [Ring, David] Harvard Med Sch, Massachusetts Gen Hosp, Dept Hand Surg, Boston, MA USA. [Heesters, Balthasar A.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA USA. RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, 1400 Barbara Jordan Blvd,Suite 2-834,MC R1800, Austin, TX 78723 USA. EM david.ring@austin.utexas.edu OI Ring, David/0000-0002-6506-4879 NR 31 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 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2016 VL 41 IS 10 BP 988 EP 998 DI 10.1016/j.jhsa.2016.07.097 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DY7WP UT WOS:000385340300006 PM 27546443 ER PT J AU Warren, HR Surendran, P Manning, AK van den Berg, ME van der Harst, P Verweij, N Eijgelsheim, M Stricker, BHC Lindgren, CM Howson, JMM Munroe, PB AF Warren, Helen R. Surendran, Praveen Manning, Alisa K. van den Berg, Marten E. van der Harst, Pim Verweij, Niek Eijgelsheim, Mark Stricker, Bruno H. Ch Lindgren, Cecilia M. Howson, Joanna M. M. Munroe, Patricia B. CA CHARGE Consortium EKG Working Grp T2D-GENES Consortium CHARGE Consortium GoT2DGenes Consortium CHD Exome Consortium ExomeBP Consortium TI Novel loci discovery for blood pressure and heart rate using the Exome chip SO JOURNAL OF HUMAN HYPERTENSION LA English DT Meeting Abstract C1 [Warren, Helen R.; Munroe, Patricia B.] William Harvey Res Inst, London, England. [Warren, Helen R.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, London, England. [Surendran, Praveen; Howson, Joanna M. M.] Univ Cambridge, Cambridge CB2 1TN, England. [Manning, Alisa K.] Harvard Med Sch, Boston, MA USA. [Manning, Alisa K.; Lindgren, Cecilia M.] Broad Inst & Harvard, Cambridge, MA USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [van den Berg, Marten E.; Stricker, Bruno H. Ch] Erasmus MC, Rotterdam, Netherlands. [van der Harst, Pim; Verweij, Niek; Eijgelsheim, Mark] Univ Groningen, NL-9700 AB Groningen, Netherlands. [Stricker, Bruno H. Ch] Netherlands Consortium Hlth Ageing, Netherlands Genom Initiat, Rotterdam, Netherlands. [Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands. [Lindgren, Cecilia M.] Univ Oxford, Oxford OX1 2JD, England. RI Verweij, Niek/A-4499-2017 NR 0 TC 0 Z9 0 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 EI 1476-5527 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD OCT PY 2016 VL 30 IS 10 SI SI MA P-26 BP 653 EP 653 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DZ3ZY UT WOS:000385797000054 ER PT J AU Singh, V Damluji, AA Mendirichaga, R Alfonso, CE Martinez, CA Williams, D Heldman, AW De Marchena, EJ O'Neill, WW Cohen, MG AF Singh, Vikas Damluji, Abdulla A. Mendirichaga, Rodrigo Alfonso, Carlos E. Martinez, Claudia A. Williams, Donald Heldman, Alan W. De Marchena, Eduardo J. O'Neill, William W. Cohen, Mauricio G. TI Elective or Emergency Use of Mechanical Circulatory Support Devices During Transcatheter Aortic Valve Replacement SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article ID IMPLANTATION; COMPLICATIONS; MORTALITY; STENOSIS AB ObjectiveEvaluate the use of mechanical circulatory support (MCS) devices in high-risk patients undergoing transcatheter aortic valve replacement (TAVR). BackgroundThe use of MCS devices in elderly patients with multiple comorbidities undergoing TAVR is underexplored. MethodsAll patients undergoing TAVR at a single tertiary academic center who required MCS during index procedure between 2008 and 2015 were included in a prospective database. ResultsMCS was used in 9.4% (54/577) of all TAVRs (n=52 Edwards Sapien and n=2 CoreValves) of which 68.5% (n=37) were used as part of a planned strategy, and 31.5% (n=17) were used in emergency bail-out situations. IABP was the most commonly used device (87%) followed by Impella and ECMO (6% each). Among the MCS group, 22% required cardiopulmonary resuscitation during the procedure (n=4 elective [11%] vs. n=8 emergent [47%]) and 15% upgrade to a second device (Impella or CPB after IABP; n=5 elective [14%] vs. n=3 emergent [18%]). Median duration of support was 1-day. Device related complications were low (4%). In-hospital mortality in this extremely high-risk population was 24% (13/54) (11% [4/37] for elective cases and 53% [9/17] for emergency cases). Cardiogenic shock (50%) was the most common cause of in-hospital death. Cumulative all-cause 1-year mortality was 35% (19/54) (19% 97/370 for elective and 71% [12/17] for emergency cases). ConclusionEmergent use of MCS during TAVR in extremely high-risk population is associated with high short and long-term mortality rates. Early identification of patients at risk for hemodynamic compromise may rationalize elective utilization of MCS during TAVR. C1 [Singh, Vikas] Harvard Med Sch, Massachusetts Gen Hosp, Intervent Cardiol, Boston, MA USA. [Damluji, Abdulla A.; Mendirichaga, Rodrigo; Alfonso, Carlos E.; Martinez, Claudia A.; Williams, Donald; Heldman, Alan W.; De Marchena, Eduardo J.; Cohen, Mauricio G.] Univ Miami, Miller Sch Med, Cardiovasc Div, 1400 NW 12th Ave,Suite 1179, Miami, FL 33136 USA. [Damluji, Abdulla A.; Mendirichaga, Rodrigo; Alfonso, Carlos E.; Martinez, Claudia A.; Williams, Donald; Heldman, Alan W.; De Marchena, Eduardo J.; Cohen, Mauricio G.] Univ Miami Hosp, Elaine & Sydney Sussman Cardiac Catheterizat Lab, Miami, FL USA. [O'Neill, William W.] Henry Ford Hosp, Div Cardiovasc, Detroit, MI 48202 USA. RP Cohen, MG (reprint author), Univ Miami, Miller Sch Med, 1400 NW 12th Ave,Suite 1179, Miami, FL 33136 USA. EM mgcohen@med.miami.edu OI Damluji, Abdulla/0000-0002-8774-6416; Cohen, Mauricio/0000-0003-2038-6070 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 0896-4327 EI 1540-8183 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD OCT PY 2016 VL 29 IS 5 BP 513 EP 522 DI 10.1111/joic.12323 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DY9CN UT WOS:000385430600010 PM 27550213 ER PT J AU Smith, AW Rohrer, B Wheless, L Samantaray, S Ray, SK Inoue, J Azuma, M Banik, NL AF Smith, Amena W. Rohrer, Baerbel Wheless, Lee Samantaray, Supriti Ray, Swapan K. Inoue, Jun Azuma, Mitsuyoshi Banik, Naren L. TI Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE axonal degeneration; calpain and cell death; oligodendrocytes; optic nerve; retinal ganglion cells; visual acuity ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MAJOR DEPRESSIVE DISORDER; MULTIPLE-SCLEROSIS; AXONAL INJURY; PATTERN ELECTRORETINOGRAM; NEUROFILAMENT PROTEINS; COHERENCE TOMOGRAPHY; NEUTRAL PROTEINASE; IN-VITRO; SYSTEM AB Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with multiple sclerosis. ON pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells, and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE) was utilized to study the onset and progression of ON and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ 1945. EAE was actively induced in B10. PL mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ 1945 from Day 9 until sacrificing (Day 26). Visual function was determined by electroretinogram recordings and daily measurement of optokinetic responses (OKR) to a changing pattern stimulus. Optic nerve and retinal histopathology was investigated by immunohistochemical and luxol fast blue staining. EAE mice manifested losses in OKR thresholds, a measurement of visual acuity, which began early in the disease course. There was a significant bias toward unilateral OKR impairment among EAE-ON eyes. Treatment with SNJ 1945, initiated after the onset of OKR threshold decline, improved visual acuity, pattern electroretinogram amplitudes, and paralysis, with attenuation of retinal ganglion cell death. Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of early, unilateral visual impairment in EAE-ON parallels the clinical presentation of ON exacerbations associated with multiple sclerosis. Calpain inhibition may represent an ideal candidate therapy for the preservation of vision in clinical ON. C1 [Smith, Amena W.; Rohrer, Baerbel] Med Univ South Carolina, Dept Neurosci, 96 Jonathan Lucas St,MSC606, Charleston, SC 29425 USA. [Rohrer, Baerbel; Banik, Naren L.] Med Univ South Carolina, Dept Ophthalmol, 96 Jonathan Lucas St,MSC606, Charleston, SC 29425 USA. [Rohrer, Baerbel; Banik, Naren L.] Alex Pharmaceut, Cheshire, CT USA. [Rohrer, Baerbel; Ray, Swapan K.] Univ South Carolina, Sch Med, Dept Pathol Microbiol & Immunol, 96 Jonathan Lucas St,MSC606, Columbia, SC 29425 USA. [Wheless, Lee] Med Univ South Carolina, Med Div Biostat & Epidemiol, Charleston, SC USA. [Samantaray, Supriti; Banik, Naren L.] Med Univ South Carolina, Dept Neurol & Neurosurg, Charleston, SC USA. [Inoue, Jun; Azuma, Mitsuyoshi] Senju Pharmaceut Co Ltd, Kobe, Hyogo, Japan. [Banik, Naren L.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. RP Banik, NL (reprint author), Med Univ South Carolina, 96 Jonathan Lucas St,MSC606, Charleston, SC 29425 USA.; Rohrer, B (reprint author), MUSC, 167 Ashley Ave,SEI614, Charleston, SC 29425 USA. EM rohrer@musc.edu FU BLRD VA [I01 BX002349]; NEI NIH HHS [R01 EY019320]; NINDS NIH HHS [R01 NS041088, R01 NS056176, R01 NS065456]; RRD VA [I01 RX000444] NR 66 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2016 VL 139 IS 2 BP 270 EP 284 DI 10.1111/jnc.13770 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DZ3SJ UT WOS:000385769200012 PM 27513991 ER PT J AU Jacobson, JO Earle, C Neuss, M AF Jacobson, Joseph O. Earle, Craig Neuss, Michael TI Four Years Running: The ASCO Quality Care Symposium SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Jacobson, JO (reprint author), Dana Farber Canc Inst, Dana 1018,450 Brookline Ave, Boston, MA 02215 USA. EM joseph_jacobson@dfci.harvard.edu NR 0 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 OCT PY 2016 VL 12 IS 10 BP 831 EP + DI 10.1200/JOP.2016.015891 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ6NF UT WOS:000385978500003 PM 27531375 ER PT J AU Romine, PE Harkins, SK Gray, SW AF Romine, Perrin E. Harkins, Sophie K. Gray, Stacy W. TI Quality in the Age of Precision Medicine: The Clinician Perspective SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DECISION AID; CANCER SUSCEPTIBILITY; OVARIAN-CANCER; BREAST-CANCER; UNITED-STATES; KNOWLEDGE; ATTITUDES; WOMEN; CHEMOTHERAPY C1 Univ Washington, Sch Med, Seattle, WA USA. Harvard Med Sch, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Gray, SW (reprint author), Dana Farber Canc Inst, Ctr Populat Sci, Dept Med Oncol, 450 Brookline Ave,Dana 1123-a, Boston, MA 02215 USA. EM stacyw_gray@dfci.harvard.edu NR 31 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 OCT PY 2016 VL 12 IS 10 BP 839 EP + DI 10.1200/JOP.2016.015321 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ6NF UT WOS:000385978500005 PM 27650835 ER PT J AU Ryan, DP Hong, TS AF Ryan, David P. Hong, Theodore S. TI Understanding the Paradigm Shift in Pancreatic Cancer SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID ADENOCARCINOMA; GEMCITABINE; FLUOROURACIL; CHEMOTHERAPY; FOLFIRINOX; TRIAL C1 [Ryan, David P.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dpryan@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 2016 VL 12 IS 10 BP 926 EP + DI 10.1200/JOP.2016.017079 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ6NF UT WOS:000385978500030 PM 27858558 ER PT J AU Schultz, KAP Harris, AK Schneider, DT Young, RH Brown, J Gershenson, DM Dehner, LP Hill, DA Messinger, YH Frazier, AL AF Schultz, Kris Ann P. Harris, Anne K. Schneider, Dominik T. Young, Robert H. Brown, Jubilee Gershenson, David M. Dehner, Louis P. Hill, D. Ashley Messinger, Yoav H. Frazier, A. Lindsay TI Ovarian Sex Cord-Stromal Tumors SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Review ID GRANULOSA-CELL TUMOR; PLEUROPULMONARY BLASTOMA REGISTRY; SOMATIC DICER1 MUTATIONS; CHILDREN; BEVACIZUMAB; ADOLESCENTS; WOMEN AB Ovarian sex cord-stromal tumors are clinically significant heterogeneous tumors that include several pathologic types. These tumors are often found in adolescents and young adults and can present with hormonal manifestations as well as signs and symptoms of a pelvic mass. Serum tumor markers may assist in preoperative diagnosis and surveillance. Several subtypes are associated with genetic predisposition, including those observed in patients with Peutz-Jegher syndrome. Recent studies have elucidated the relationship between Sertoli-Leydig cell tumors and DICER1 mutations. When classified as International Federation of Gynecology and Obstetrics stage Ia, most subtypes may be treated with surgery alone. Higher stage or recurrent tumors have variable prognoses that range from a usually rapid course in poorly differentiated Sertoli-Leydig cell tumor to an often prolonged course in adult granulosa cell tumors. New understanding of the molecular pathogenesis of these tumors may pave the way for novel therapeutics. C1 Childrens Hosp & Clin Minnesota, Minneapolis, MN 55404 USA. Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. Dana Farber Canc Ctr Childrens Canc Care, Boston, MA USA. Carolinas Med Ctr, Levine Canc Inst, Charlotte, NC 28203 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Washington Univ, Med Ctr, St Louis, MO USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Res Inst, Med Genet Res Ctr, Washington, DC USA. Pediat Clin, Dortmund, Germany. RP Schultz, KAP (reprint author), Childrens Hosp & Clin Minnesota, Dept Oncol, Int OTST Registry, 2530 Chicago Ave S CSC-175, Minneapolis, MN 55404 USA. EM krisann.schultz@childrensmn.org FU NCI NIH HHS [R01 CA143167] NR 39 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD OCT PY 2016 VL 12 IS 10 BP 940 EP + DI 10.1200/JOP.2016.016261 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DZ6NF UT WOS:000385978500034 PM 27858560 ER PT J AU Cooke, KJ Franklin, JE Painter, J Rodgers, J AF Cooke, Kelly J. Franklin, John E. Painter, John Rodgers, James TI Effects of Combat and Military Training on End-of-Life Care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Letter C1 [Cooke, Kelly J.] ProHlth Care, Dept Palliat Med, Waukesha, WI USA. [Franklin, John E.] Charleston Vet Affairs Med Ctr, Dept Geriatr & Palliat Med, Charleston, SC USA. [Painter, John] Charleston Vet Affairs Med Ctr, Dept Palliat Med, Charleston, SC USA. [Rodgers, James] Houston Vet Affairs Med Ctr, Dept Psychol, Houston, TX USA. [Cooke, Kelly J.] Cent Texas Vet Affairs Med Ctr, Temple, TX USA. RP Cooke, KJ (reprint author), ProHealthcare, Dept Palliat Med, 721 Amer Ave,Suite 508, Waukesha, WI 53188 USA. EM kelly.cooke@phci.org NR 9 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2016 VL 19 IS 10 BP 1025 EP 1027 DI 10.1089/jpm.2015.0363 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DY8JQ UT WOS:000385376500002 ER PT J AU Muriel, AC Wolfe, J Block, SD AF Muriel, Anna C. Wolfe, Joanne Block, Susan D. TI Pediatric Palliative Care and Child Psychiatry: A Model for Enhancing Practice and Collaboration SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE; ADVANCED CANCER; NATIONAL-SURVEY; END; CONSULTATION; SERVICES; RECOGNITION; ASSOCIATION; ADOLESCENTS; DEPRESSION AB As the field of Pediatric Palliative Care continues to develop, it is important to consider the scope of practice and the utility of collaboration with other specialties, including child and adolescent psychiatry. The integration of psychiatry and palliative medicine has been explored in adult practice, but has not yet been elaborated in pediatrics. This article proposes a clinical model of care that highlights the overlapping and unique expertise that each discipline brings, in a continuum of collaboration, and proposes an integrated care model for the most complex patients and families. Case examples are used to define specific professional skills and roles, and to describe shared and distinct clinical approaches used by pediatric palliative care and child psychiatry. Effective collaboration provides opportunities for cross-disciplinary educational exchange and enhanced care of children and families with comorbid mental health issues and serious illness. C1 [Muriel, Anna C.; Wolfe, Joanne; Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Muriel, Anna C.; Wolfe, Joanne; Block, Susan D.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Muriel, Anna C.; Wolfe, Joanne] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA. [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. RP Muriel, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW 350, Boston, MA 02115 USA. EM amuriel@partners.org NR 33 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2016 VL 19 IS 10 BP 1032 EP 1038 DI 10.1089/jpm.2015.0354 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DY8JQ UT WOS:000385376500006 ER PT J AU Blankenship, JC Abbott, BG Lindenfeld, J Wiegers, SE Rosenfield, K AF Blankenship, James C. Abbott, Brian G. Lindenfeld, Joann Wiegers, Susan E. Rosenfield, Ken TI Multi-Society Presidents' Page: The Value of Membership in Your Sub-Specialty Society SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material C1 [Blankenship, James C.] Geisinger Med Ctr, Dept Cardiol, Soc Cardiovasc Angiog & Intervent, Danville, PA 17822 USA. [Abbott, Brian G.] Amer Soc Nucl Cardiol, Cardiovasc Inst, East Greenwich, RI USA. [Lindenfeld, Joann] Vanderbilt Univ, Sch Med, Heart Failure Soc Amer, Div Cardiovasc Med, Nashville, TN 37212 USA. [Wiegers, Susan E.] Temple Univ, Lewis Katz Sch Med, Amer Soc Echocardiog, Philadelphia, PA 19122 USA. [Rosenfield, Ken] Massachusetts Gen Hosp, Soc Cardiovasc Angiog & Intervent, Boston, MA 02114 USA. RP Blankenship, JC (reprint author), Geisinger Med Ctr, Dept Cardiol, Danville, PA 17822 USA. EM jblankenship@geisinger.edu NR 2 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 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2016 VL 29 IS 10 BP 23A EP 24A DI 10.1016/j.echo.2016.08.018 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ5TN UT WOS:000385924500001 ER PT J AU Pierce, EL Rabbah, JPM Thiele, K Wei, QF Vidakovic, B Jensen, MO Hung, J Yoganathan, AP AF Pierce, Eric L. Rabbah, Jean Pierre M. Thiele, Karl Wei, Qifeng Vidakovic, Brani Jensen, Morten O. Hung, Judy Yoganathan, Ajit P. TI Three-Dimensional Field Optimization Method: Gold-Standard Validation of a Novel Color Doppler Method for Quantifying Mitral Regurgitation SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Mitral regurgitation; Flow convergence; Three-dimensional echocardiography; Doppler ultrasound; Diagnostic ID ISOVELOCITY SURFACE-AREA; VENA-CONTRACTA AREA; IN-VITRO; QUANTIFICATION; SEVERITY; ECHOCARDIOGRAPHY; VISUALIZATION; SIMULATOR; ORIFICE; REPAIR AB Background: Accurate diagnosis of mitral regurgitation (MR) severity is central to proper treatment. Although numerous approaches exist, an accurate, gold-standard clinical technique remains elusive. The authors previously reported on the initial development and demonstration of the automated three-dimensional (3D) field optimization method (FOM) algorithm, which exploits 3D color Doppler ultrasound imaging and builds on existing MR quantification techniques. The aim of the present study was to extensively validate 3D FOM in terms of accuracy, ease of use, and repeatability. Methods: Three-dimensional FOM was applied to five explanted ovine mitral valves in a left heart simulator, which were systematically perturbed to yield a total of 29 unique regurgitant geometries. Three-dimensional FOM was compared with a gold-standard flow probe, as well as the most clinically prevalent MR volume quantification technique, the two-dimensional (2D) proximal isovelocity surface area (PISA) method. Results: Overall, 3D FOM overestimated and 2D PISA underestimated MR volume, but 3D FOM error had smaller magnitude (5.2 6 +/- 9.9 mL) than 2D PISA error (-6.9 6 +/- 7.7 mL). Two-dimensional PISA remained superior in diagnosis for round orifices and especially mild MR, as predicted by ultrasound physics theory. For slit-type orifices and severe MR, 3D FOM showed significant improvement over 2D PISA. Three-dimensional FOM processing was technically simpler and significantly faster than 2D PISA and required fewer ultrasound acquisitions. Three-dimensional FOM did not show significant interuser variability, whereas 2D PISA did. Conclusions: Three-dimensional FOM may provide increased clinical value compared with 2D PISA because of increased accuracy in the case of complex or severe regurgitant orifices as well as its greater repeatability and simpler work flow. C1 [Pierce, Eric L.; Rabbah, Jean Pierre M.; Vidakovic, Brani; Jensen, Morten O.; Yoganathan, Ajit P.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Pierce, Eric L.; Rabbah, Jean Pierre M.; Vidakovic, Brani; Jensen, Morten O.; Yoganathan, Ajit P.] Emory Univ, Atlanta, GA 30322 USA. [Thiele, Karl; Wei, Qifeng] Philips Hlth Tech, Andover, MA USA. [Hung, Judy] Massachusetts Gen Hosp, Echocardiog Lab, Boston, MA 02114 USA. RP Yoganathan, AP (reprint author), 387 Technol Circle NW,Suite 200, Atlanta, GA 30313 USA. EM ajit.yoganathan@bme.gatech.edu FU National Science Foundation Graduate Research Fellowship [DGE-1148903] FX This work was partially supported by the National Science Foundation Graduate Research Fellowship (E.L.P.) under Grant DGE-1148903. Drs. Thiele and Wei are employed by Philips Health Tech. No financial support was provided by Philips Health Tech for this study. NR 27 TC 3 Z9 3 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2016 VL 29 IS 10 BP 917 EP 925 DI 10.1016/j.echo.2016.05.009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ5TN UT WOS:000385924500003 PM 27354250 ER PT J AU Tan, TC Zeng, X Jiao, Y Wang, L Wei, QF Thiele, K Salgo, I Mehta, V Andrawes, M Picard, MH Hung, J AF Tan, Timothy C. Zeng, Xin Jiao, Yuan Wang, Lin Wei, Qifeng Thiele, Karl Salgo, Ivan Mehta, Vipin Andrawes, Michael Picard, Michael H. Hung, Judy TI Three-Dimensional Field Optimization Method: Clinical Validation of a Novel Color Doppler Method for Quantifying Mitral Regurgitation SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Proximal isovelocity surface area; Three-dimensional echocardiography; Mitral regurgitation ID ISOVELOCITY SURFACE-AREA; FLOW CONVERGENCE; ORIFICE AREA; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; VENA CONTRACTA; QUANTIFICATION; SEVERITY; VOLUME; REPRODUCIBILITY AB Background: Assessment of mitral regurgitation (MR) severity by echocardiography is important for clinical decision making, but MR severity can be challenging to quantitate accurately and reproducibly. The accuracy of effective regurgitant orifice area (EROA) and regurgitant volume (RVol) calculated using two-dimensional (2D) proximal isovelocity surface area is limited by the geometric assumptions of proximal isovelocity surface area shape, and both variables demonstrate interobserver variability. The aim of this study was to compare a novel automated three-dimensional (3D) echocardiographic method for calculating MR regurgitant flow using standard 2D techniques. Methods: A sheep model of ischemic MR and patients with MR were prospectively examined. Patients with a range of severity of MR were examined. EROA and RVol were calculated from 3D color Doppler acquisitions using a novel computer-automated algorithm based on the field optimization method to measure EROA and RVol. For an independent comparison group, the 3D field optimization method was compared with 2D methods for grading MR in an experimental ovine model of MR. Results: Fifteen 3D data sets from nine sheep (open-chest transthoracic echocardiographic data sets) and 33 transesophageal data sets from patients with MR were prospectively examined. For sheep data sets, mean 2D EROA was 0.16 +/- 0.05 cm(2), and mean 2D RVol was 21.84 +/- 8.03 mL. Mean 3D EROA was 0.09 +/- 0.04 cm(2), and mean 3D RVol was 14.40 +/- 5.79 cm(3). There was good correlation between 2D and 3D EROA (R = 0.70) and RVol (R = 0.80). For patient data sets, mean 2D EROA was 0.35 +/- 0.35 cm(2), and mean 2D RVol was 58.9 +/- 52.9 mL. Mean 3D EROA was 0.34 +/- 0.29 cm(2), and mean 3D RVol was 54.6 +/- 36.5 mL. There was excellent correlation between 2D and 3D EROA (R = 0.94) and RVol (R = 0.84). Bland-Altman analysis revealed greater interobserver variability for 2D RVol measurements compared with 3D RVol using the 3D field optimization method measurements, but variability was statistically significant only for RVol. Conclusions: Direct automated measurement of proximal isovelocity surface area region for EROA calculation using real-time 3D color Doppler echocardiography is feasible, with a high correlation to current 2D EROA methods but less variability. This novel automated method provides an accurate and highly reproducible method for calculating EROA. C1 [Tan, Timothy C.; Zeng, Xin; Jiao, Yuan; Picard, Michael H.; Hung, Judy] Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Tan, Timothy C.; Zeng, Xin; Jiao, Yuan; Picard, Michael H.; Hung, Judy] Harvard Med Sch, Boston, MA USA. [Wang, Lin] St Francis Hosp, Roslyn, NY USA. [Wei, Qifeng; Thiele, Karl; Salgo, Ivan] Philips Healthcare, Andover, MA USA. [Mehta, Vipin; Andrawes, Michael] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU Philips Healthcare FX This study was an investigator-led study supported by a grant from Philips Healthcare. Philips Healthcare did not have any input into the design and conduct of the study; the collection, analysis, and interpretation of the data; or review or approval of the manuscript. Mr. Thiele, Dr. Wei, and Dr. Salgo are employees of Philips Healthcare but did not have any input into the design and conduct of the study; the collection, analysis, and interpretation of the data. NR 33 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2016 VL 29 IS 10 BP 926 EP 934 DI 10.1016/j.echo.2016.05.011 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DZ5TN UT WOS:000385924500004 PM 27405591 ER PT J AU Zhao, T Mejaddam, AY Chang, YC DeMoya, MA King, DR Yeh, DD Kaafarani, HMA Alam, HB Velmahos, GC AF Zhao, Ting Mejaddam, Ali Y. Chang, Yuchiao DeMoya, Marc A. King, David R. Yeh, Daniel D. Kaafarani, Haytham M. A. Alam, Hasan B. Velmahos, George C. TI Admissions for isolated nonoperative mild head injuries: Sharing the burden among trauma surgery, neurosurgery, and neurology SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the New-England-Surgical-Society CY SEP, 2014 CL Stowe, VT SP New England Surg Soc DE Mild head injuries; trauma surgery; neurosurgery; neurology ID BRAIN-INJURY; UNITED-STATES; EPIDEMIOLOGY; VISITS; CT AB BACKGROUND Isolated nonoperative mild head injuries (INOMHI) occur with increasing frequency in an aging population. These patients often have multiple social, discharge, and rehabilitation issues, which far exceed the acute component of their care. This study was aimed to compare the outcomes of patients with INOMHI admitted to three services: trauma surgery, neurosurgery, and neurology. METHODS Retrospective case series (January 1, 2009 to August 31, 2013) at an academic Level I trauma center. According to an institutional protocol, INOMHI patients with Glasgow Coma Scale (GCS) of 13 to 15 were admitted on a weekly rotational basis to trauma surgery, neurosurgery, and neurology. The three populations were compared, and the primary outcomes were survival rate to discharge, neurological status at hospital discharge as measured by the Glasgow Outcome Score (GOS), and discharge disposition. RESULTS Four hundred eighty-eight INOMHI patients were admitted (trauma surgery, 172; neurosurgery, 131; neurology, 185). The mean age of the study population was 65.3 years, and 58.8% of patients were male. Seventy-seven percent of patients has a GCS score of 15. Age, sex, mechanism of injury, Charlson Comorbidity Index, Injury Severity Score, Abbreviated Injury Scale in head and neck, and GCS were similar among the three groups. Patients who were admitted to trauma surgery, neurosurgery and neurology services had similar proportions of survivors (98.8% vs 95.7% vs 94.7%), and discharge disposition (home, 57.0% vs 61.6% vs 55.7%). The proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma (97.7% vs 93.0% vs 92.4%). In a logistic regression model adjusting for Charlson Comorbidity Index CCI and Abbreviated Injury Scale head and neck scores, patients who were admitted to neurology or neurosurgery had significantly lower odds being discharged with GOS 4 or 5. While the trauma group had the lowest proportion of repeats of brain computed tomography (61.6%), the neurosurgery group had the highest proportion of intensive care unit admission (29.8%), and the neurology group had the longest emergency department stay (7.5 hours), there were no significant differences in duration of hospital stay, in-hospital complications, and readmission within 30 days. CONCLUSIONS Although there were differences in use of health care resources, and the proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma, most clinical outcomes were similar in INOMHI patients admitted to trauma surgery, neurosurgery, or neurology in our institution. A rotational policy of admitting INOMHI patients is feasible among services with expertise in and commitment to the care of these patients. LEVEL OF EVIDENCE Therapeutic/care management study, level IV. C1 [Zhao, Ting; Mejaddam, Ali Y.; Chang, Yuchiao; DeMoya, Marc A.; King, David R.; Yeh, Daniel D.; Kaafarani, Haytham M. A.; Velmahos, George C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Alam, Hasan B.] Univ Michigan Hosp, Dept Surg, Ann Arbor, MI 48109 USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@mgh.harvard.edu NR 23 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD OCT PY 2016 VL 81 IS 4 BP 743 EP 747 DI 10.1097/TA.0000000000001088 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA DZ2FX UT WOS:000385658800017 PM 27116408 ER PT J AU Dariushnia, SR Walker, TG Silberzweig, JE Annamalai, G Krishnamurthy, V Mitchell, JW Swan, TL Wojak, JC Nikolic, B Midia, M AF Dariushnia, Sean R. Walker, T. Gregory Silberzweig, James E. Annamalai, Ganesan Krishnamurthy, Venkataramu Mitchell, Jason W. Swan, Timothy L. Wojak, Joan C. Nikolic, Boris Midia, Mehran CA Soc Interventional Radiology Stand TI Quality Improvement Guidelines for Percutaneous Image-Guided Management of the Thrombosed or Dysfunctional Dialysis Circuit SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID HEMODIALYSIS VASCULAR ACCESS; CUTTING BALLOON ANGIOPLASTY; CENTRAL VENOUS STENOSIS; STENT-GRAFT PLACEMENT; ARTERIOVENOUS-FISTULA STENOSIS; CEPHALIC ARCH STENOSIS; RANDOMIZED CLINICAL-TRIAL; SINGLE-CENTER EXPERIENCE; LONG-TERM OUTCOMES; ENDOVASCULAR TREATMENT C1 [Dariushnia, Sean R.] Emory Univ, Dept Radiol, Div Intervent Radiol & Image Guided Med, 1364 Clifton Rd, Atlanta, GA 30322 USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Silberzweig, James E.] Intervent Radiol PC, New York, NY USA. [Annamalai, Ganesan] Mt Sinai Hosp, Dept Med Imaging, Toronto, ON, Canada. [Krishnamurthy, Venkataramu] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Mitchell, Jason W.] Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. [Swan, Timothy L.] Marshfield Clin Fdn Med Res & Educ, Dept Radiol, Marshfield, WI USA. [Wojak, Joan C.] Our Lady Lourdes Reg Med Ctr, Dept Radiol, Lafayette, LA USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. [Midia, Mehran] McMaster Univ, Dept Diagnost Imaging, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada. RP Dariushnia, SR (reprint author), Emory Univ, Dept Radiol, Div Intervent Radiol & Image Guided Med, 1364 Clifton Rd, Atlanta, GA 30322 USA. EM dariushnia1@yahoo.com NR 175 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2016 VL 27 IS 10 BP 1518 EP 1530 DI 10.1016/j.jvir.2016.07.015 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DY9UB UT WOS:000385479500007 PM 27622727 ER PT J AU Prabhakar, AM Misono, AS Hemingway, J Hughes, DR Duszak, R AF Prabhakar, Anand M. Misono, Alexander S. Hemingway, Jennifer Hughes, Danny R. Duszak, Richard, Jr. TI Medicare Utilization of CT Angiography from 2001 through 2014: Continued Growth by Radiologists SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID MR-ANGIOGRAPHY; TRENDS; DISEASE AB Purpose: To examine changes in utilization of computed tomography (CT) angiography nationally and changing relative specialty roles in examination interpretation. Materials and Methods: Service-specific claims data for region-specific CT angiography examinations were identified using Medicare Physician Supplier Procedure Summary Master Files from 2001 through 2014. Longitudinal national utilization rates were calculated using annual Medicare enrollment data for 2001-2013. Procedure volumes by specialty group and site of service were analyzed. Results: Total annual claims for CT angiography for Medicare fee for service beneficiaries increased from 64,846 to 1,709,088 (compound annual growth rate [CAGR] 29%) between 2001 and 2014 Per 1,000 beneficiaries, overall CT angiography utilization increased annually from 2.1 in 2001 to 47.6 in 2013. Overall interpretation market share increased 4%(91%-95%) for radiology. Cardiology increased from 1% in 2001 to 6% in 2007 but decreased annually to 2% in 2014. Vascular surgery market share remained < 1% throughout the study period. Growth of CT angiography in the emergency department (ED) outpaced all other sites of service, increasing from 1.1% to 28% (CAGR 38%). The Chest was the dominant body region imaged with CT angiography, increasing from 36,984 to 914,086,(CAGR 28%). Conclusions: Utilization of CT angiography in the Medicare population increased markedly for 2001-2014, particularly in the ED, with radiologists remaining dominant providers. The chest is the most common body region imaged with CT angiography. C1 [Prabhakar, Anand M.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiovasc Imaging, 55 Fruit St,Gray 2, Boston, MA 02114 USA. [Misono, Alexander S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Gray 2, Boston, MA 02114 USA. [Hemingway, Jennifer; Hughes, Danny R.; Duszak, Richard, Jr.] Harvey L Neiman Hlth Policy Inst, Reston, VA USA. [Hughes, Danny R.] George Mason Univ, Dept Hlth Adm & Policy, Fairfax, VA 22030 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol & Imaging Sci, Atlanta, GA USA. RP Prabhakar, AM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiovasc Imaging, 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu FU NCATS NIH HHS [UL1 TR001425] NR 13 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2016 VL 27 IS 10 BP 1554 EP 1560 DI 10.1016/j.jvir.2016.05.031 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA DY9UB UT WOS:000385479500013 PM 27461587 ER PT J AU Wu, H Wang, A Qi, Z Li, X Chen, C Yu, K Zou, F Hu, C Wang, W Zhao, Z Wu, J Liu, J Liu, X Wang, L Wang, W Zhang, S Stone, RM Galinsky, IA Griffin, JD Weinstock, D Christodoulou, A Wang, H Shen, Y Zhai, Z Weisberg, EL Liu, J Liu, Q AF Wu, H. Wang, A. Qi, Z. Li, X. Chen, C. Yu, K. Zou, F. Hu, C.