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1. Metabolic Effects of Medium-Chain Fatty Acids in Patients with Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Healthy Individuals (MEMCADD)

Author: Copenhagen Neuromuscular Center, Center of Inherited Metabolic Diseases, Copenhagen University Hospital Rigshospitalet, Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark, and Andreas Mæchel Fritzen, Associate Professor
Published: 2024

2. Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study

Author: The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet and Anders Fink-Jensen, MD, DMSci, Professor
Published: 2024

3. The SaVe Project-Sarcopenia and Vertigo in Aging Patients With Colorectal Cancer (SaVe)

Author: Copenhagen University Hospital - Rigshospitalet, Department of Occupational Therapy and Physiotherapy, Copenhagen University Hospital - Herlev and Gentofte Hospital, Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte Hospital, Department of Oncology, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Odense University Hospital, Department of Geriatric Medicine, Copenhagen University Hospital - Amager and Hvidovre Hospital, and Jan Christensen, Senior researcher, Head of research
Published: 2024

4. International Study for Treatment of High Risk Childhood Relapsed ALL 2010

Author: Australian & New Zealand Children's Haematology/Oncology Group, St. Anna Kinderkrebsforschung, CCRI (co-sponsor, Austria), European Organisation for Research and Treatment of Cancer - EORTC, University Hospital Motol (Co-Sponsor Czech Republic), Copenhagen University Hospital, Rigshospitalet (co-sponsor, Denmark), Turku University Central Hospital (co-sponsor, Finland), Centre Hospitalier Universitaire de Nice, Our Lady's Chilrden's Hospital (Co-Sponsor Ireland), Tel Aviv Sourasky Medical Centre (Co-Sponsor Israel), Ospedale Pediatrico Bambino (co-sponsor, Italy), Prinses Máxima Centrum (Co-Sponsor Netherlands), Oslo University Hospital (co-sponsor, Norway), Medical University of Wroclaw (Co-Sponsor Poland), Instituto Português de Oncologia de Lisboa (co-sponsor, Portugal), Karolinska University Hospital Stockholm (co-sponsor, Sweden), Spanish Society of Pediatric Hematology and Oncology (SEHOP) (Co-Sponsor Spain), University Children's Hospital, Zurich, Central Manchester University Hospitals NHS Foundation Trust (co-sponsor, UK), and PD Dr. Arend von Stackelberg, Prinicipal Investigator
Published: 2024

5. International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010

Author: Australian & New Zealand Children's Haematology/Oncology Group, St. Anna Kinderkrebsforschung (Co-Sponsor Austria), European Organisation for Research and Treatment of Cancer - EORTC, University Hospital Motol (Co-Sponsor Czech Republic), Copenhagen University Hospital (Rigshospitalet) (Co-Sponsor Copenhagen), Turku University (Co-Sponsor Finland), Centre Hospitalier Universitaire de Nice, Our Lady's Chilrden's Hospital (Co-Sponsor Ireland), Tel Aviv Sourasky Medical Centre (Co-Sponsor Israel), Ospedale Pediatrico Bambino Gesù (Co-Sponsor Italy), National Hospital Organization Nagoya Medical Center (Co-Sponsor Japan), Prinses Máxima Centrum (Co-Sponsor Netherlands), Oslo University Hospital (Co-Sponsor Oslo), Medical University of Wroclaw (Co-Sponsor Poland), Instituto Português de Oncologia de Lisboa (Co-Sponsor Lisboa), Spanish Society of Pediatric Hematology and Oncology (SEHOP) (Co-Sponsor Spain), University Children's Hospital, Zurich, Central Manchester University (Co-Sponsor United Kingdom), and PD Dr. Arend von Stackelberg, PD Dr. med. Arend von Stackelberg
Published: 2024

6. Oral-only Antibiotics for Bone and Joint Infections in Children (CHILD@HOME_BJI)

Author: The research foundation of Copenhagen University Hospital, Rigshospitalet, Copenhagen Health Science Partners, Innovation Fund Denmark, and Allan Bybeck Nielsen, Principal investigator
Published: 2023

7. Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder

Author: The Neurobiology Research Unit at Copenhagen University Hospital Rigshospitalet and Anders Fink-Jensen, MD, DMSci, Professor
Published: 2023

8. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia.

Author: 1*Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet ‡Section of Biostatistics, Department of Public Health ‡‡The Institute of Clinical medicine, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark †Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm ¶Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg ††Department of Pediatrics, Skåne University Hospital, Lund, Sweden §Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland ∥Division of Hematology-Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki **Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland #Department of Pediatrics, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, NY., Levinsen, Mette, Harila-Saari, Arja, Grell, Kathrine, Jonsson, Olafur Gisli, Taskinen, Mervi, Abrahamsson, Jonas, Vettenranta, Kim, Åsberg, Ann, Risteli, Juha, Heldrup, Jesper, Schmiegelow, Kjeld, 1*Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet ‡Section of Biostatistics, Department of Public Health ‡‡The Institute of Clinical medicine, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark †Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm ¶Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg ††Department of Pediatrics, Skåne University Hospital, Lund, Sweden §Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland ∥Division of Hematology-Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki **Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland #Department of Pediatrics, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, NY., Levinsen, Mette, Harila-Saari, Arja, Grell, Kathrine, Jonsson, Olafur Gisli, Taskinen, Mervi, Abrahamsson, Jonas, Vettenranta, Kim, Åsberg, Ann, Risteli, Juha, Heldrup, Jesper, and Schmiegelow, Kjeld
Abstract: To access publisher's full text version of this article click on the hyperlink at the bottom of the page, We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6/27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower extremity sensory pain in 1 liposomal cytarabine-treated patient, no permanent adverse neurological sequelae were observed. In intention-to-treat analysis, projected 5-year event-free survival (pEFS-5y) was borderline higher for patients in the liposomal cytarabine arm compared with the TIT arm (1.0 vs. 0.69, P=0.046). However, pEFS-5y and projected 5-year relapse-free survival did not differ signficantly between patients treated with liposomal cytarabine or TIT (1.0 vs. 0.73, P=0.10; 1.0 vs. 0.76, P=0.12). Larger prospective trials are needed to explore whether liposomal cytarabine should be used as first-line prevention of relapse.

9. Effect of Ivabradine on Exercise Capacity After Heart Transplantation (VANISH-CAV)

Author: Danish Heart Foundation, Rigshospitalet, Denmark, and Finn Gustafsson, MD, PhD, DMSci; Professor of Cardiology; Team Leader Advanced Heart Failure, Transplantation and Mechanical Circulatory Support; Department of Cardiology; The Heart Center; Copenhagen University Hospital; Rigshospitalet
Published: 2019

10. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets

Author: Heinz Wiendl, Klaus Schmierer, Suzanne Hodgkinson, Tobias Derfuss, Andrew Chan, Finn Sellebjerg, Anat Achiron, Xavier Montalban, Alexandre Prat, Nicola De Stefano, Frederik Barkhof, Letizia Leocani, Patrick Vermersch, Anita Chudecka, Claire Mwape, Kristina H. Holmberg, Ursula Boschert, Sanjeev Roy, Institut Català de la Salut, [Wiendl H] Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany. [Schmierer K] The Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK. Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK. [Hodgkinson S] Ingham Institute for Applied Medical Research, University of New South Wales Medicine, Sydney, NSW, Australia. [Derfuss T] Department of Neurology, University Hospital Basel, Basel, Switzerland. [Chan A] Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. [Sellebjerg F] Danish MS Center, Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. [Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Neuroinfection & -inflammation
Subjects: Multiple Sclerosis, Antigens, CD19, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], 610 Medicine & health, CD8-Positive T-Lymphocytes, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Antigens, CD20, Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents [CHEMICALS AND DRUGS], Neurology, Immunoglobulin M, Immunoglobulin G, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Leukocytes, Mononuclear, Humans, Cladribine, Neurology (clinical), Medicaments immunosupressors, 610 Medizin und Gesundheit, Esclerosi múltiple - Tractament, acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::inmunosupresores [COMPUESTOS QUÍMICOS Y DROGAS], Tablets
Abstract: Background and ObjectivesCladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS).MethodsImmunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+B cells, CD4+and CD8+T cells, CD16+natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed.ResultsThe full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%–87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period.DiscussionCladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence.Trial Registration InformationClinicalTrials.govIdentifier:NCT03364036. Date registered: December 06, 2017.
Published: 2023
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11. Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis

Author: Georgina Arrambide, Ingrid van der Mei, Raed Alroughani, Lars Forsberg, Rodden M. Middleton, Guilherme Sciascia do Olival, Nikola Lazovski, Rumen Ivanov, Alexander Stahmann, Tomas Kalincik, Helmut Butzkueven, Richard S. Nicholas, J. Hillert, Alice Estavo Dias, Edward De Brouwer, Amber Salter, Serkan Ozakbas, Nupur Nag, Doralina Guimarães Brum, Alexander Fidao, Anna Zabalza, Yves Moreau, Ricardo Alonso, Anneke Van Der Walt, Nick Rijke, Lotte Geys, Anibal Chertcoff, Arnfin Bergmann, Robert N. McBurney, Clare Walton, Anna Glaser, Tina Parciak, Gilles Edan, Clément Gautrais, Ashkan Pirmani, Maria Fernanda Mendes, Juan Ignacio Rojas, Melinda Magyari, Liesbet M. Peeters, Robert J. Fox, Hollie Schmidt, Amin Ardeshirdavanai, Steve Simpson-Yap, Stefan Braune, Giancarlo Comi, Johana Bauer, Tim Spelman, Zabalza, Ana/0000-0003-3860-5251, Simpson, Jr., Steve/0000-0001-6521-3056, Kalincik, Tomas/0000-0003-3778-1376, Simpson-Yap, Steve, DE BROUWER, Edward, Kalincik, Tomas, Rijke, Nick, Hillert, Jan A., Walton, Clare, Edan, Gilles, Moreau, Yves, Spelman, Tim, GEYS, Lotte, PARCIAK, Tina, Gautrais, Clement, Lazovski, Nikola, PIRMANI, Ashkan, Ardeshirdavanai, Amin, Forsberg, Lars, Glaser, Anna, McBurney, Robert, Schmidt, Hollie, Bergmann, Arnfin B., Braune, Stefan, Stahmann, Alexander, Middleton, Rodden, Salter, Amber, Fox, Robert J., van der Walt, Anneke, Butzkueven, Helmut, Alroughani, Raed, Ozakbas, Serkan, Rojas, Juan, I, van der Mei, Ingrid, Nag, Nupur, Ivanov, Rumen, do Olival, Guilherme Sciascia, Dias, Alice Estavo, Magyari, Melinda, Brum, Doralina, Mendes, Maria Fernanda, Alonso, Ricardo N., Nicholas, Richard S., Bauer, Johana, Chertcoff, Anibal Sebastian, Zabalza, Anna, Arrambide, Georgina, Fidao, Alexander, Comi, Giancarlo, PEETERS, Liesbet, Institut Català de la Salut, [Simpson-Yap S] Department of Medicine, and Neuroepidemiology Unit, Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia [De Brouwer E] University of Tasmania, Hobart, Australia. ESAT-STADIUS, KU Leuven, Belgium. [Kalincik T] Department of Neurology, Melbourne MS Centre, Royal Melbourne Hospital, Parkville, Australia. [Rijke N, Walton C] MS International Federation, London, UK. [Hillert JA] Department of Clinical Neuroscience, Swedish MS Registry, Stockholm, Sweden. [Zabalza A, Arrambide G] Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, and Neuroepidemiology Unit, Melbourne School of Population and Global Health, University of Tasmania, KU Leuven, Royal Melbourne Hospital, MS International Federation, Swedish MS Registry, CHU Pontchaillou, Karolinska Institutet, Hasselt University, University Medical Center, QMENTA, Molecular Unit, Accelerated Cure Project for MS, NeuroTransData, MS Forschungs- und Projektentwicklungs-gGmbH, Swansea University, COViMS, Washington University in St. Louis, Cleveland Clinic, Monash University, Kuwait City, Dokuz Eylul University, Hospital Universitario de CEMIC, RELACOEM, Bulgarian SmartMS COVID-19 Dataset, ABEM-Brazilian MS Patients Association, University Hospital Rigshospitalet, Universidade Estadual Paulista (UNESP), REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders, Irmandade da Santa Casa de Misericórdia de São Paulo, Ramos Mejia Hospital-EMA, Imperial College, Mental Health Area, EMA, Cemcat, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, and Ospedale San Raffaele
Subjects: Male, Dimethyl Fumarate, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], chemistry.chemical_compound, 0302 clinical medicine, Natalizumab, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, 10. No inequality, COVID-19 (Malaltia) - Complicacions, B-Lymphocytes, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Middle Aged, 3. Good health, Hospitalization, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Cohort, Female, Rituximab, Life Sciences & Biomedicine, Research Article, medicine.drug, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Clinical Neurology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Internal medicine, Humans, Risk factor, Aged, 030203 arthritis & rheumatology, Science & Technology, Expanded Disability Status Scale, SARS-CoV-2, business.industry, COVID-19, Odds ratio, Respiration, Artificial, Cross-Sectional Studies, Siponimod, chemistry, Ocrelizumab, Neurosciences & Neurology, Neurology (clinical), business, Esclerosi múltiple - Tractament, 030217 neurology & neurosurgery, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina
Published: 2021
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12. Multi-PGS enhances polygenic prediction: weighting 937 polygenic scores

Author: Clara Albiñana, Zhihong Zhu, Andrew J. Schork, Andrés Ingason, Hugues Aschard, Isabell Brikell, Cynthia M. Bulik, Liselotte V. Petersen, Esben Agerbo, Jakob Grove, Merete Nordentoft, David M. Hougaard, Thomas Werge, Anders D. Børglum, Preben Bo Mortensen, John J. McGrath, Benjamin M. Neale, Florian Privé, Bjarni J. Vilhjálmsson, Bioinformatics Research Center, Aarhus University [Aarhus], Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Metacohorts Consortium, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), IT University of Copenhagen (ITU), Statens Serum Institut [Copenhagen], Center for Genomics and Personalized Medicine [Aarhus, Denmark] (CGPM), Department of Genomics, and MR Solutions Guildford
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Abstract: The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increased prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R2 increases of up to 9-fold for attention-deficit/hyperactivity disorder (ADHD) compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions, with up to 15-fold increases in prediction accuracy. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks.
Published: 2022
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13. International BEAT-PCD Consensus Statement for Infection Prevention and Control for Primary Ciliary Dyskinesia in collaboration with ERN-LUNG PCD Core NETWORK and patient representatives

Author: Mieke Boon, Antonio Moreno-Galdó, Jane S. Lucas, Kim G. Nielsen, Bernhard Rindlisbacher, Woolf T. Walker, June K. Marthin, Bernard Maitre, Phil Robinson, Huda Mussaffi, Vendula Martinu, Panayiotis K. Yiallouros, Heymut Omran, Amparo Escribano, Gemma Marsh, Helle Krogh Johansen, Ernst Eber, Claire Hogg, Damien M.S. Destouches, Carmen Casaulta, Petr Pohunek, Eric G. Haarman, Deborah Snijders, Suzanne Crowley, Pediatrics, Amsterdam Reproduction & Development (AR&D), CCA - Cancer biology and immunology, Institut Català de la Salut, [Marthin JK] Danish PCD Centre Copenhagen, Paediatric Pulmonary Service, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [Lucas JS] Primary Ciliary Dyskinesia Centre, NIHR Respiratory Biomedical Research Centre, Clinical and Experimental Science, University of Southampton, Southampton, UK. [Boon M] Dept of Paediatrics, University Hospital Gasthuisberg, Leuven, Belgium. [Casaulta C] Division of Paediatric Respiratory Medicine, University Children’s Hospital, Bern, Switzerland. [Crowley S] Paediatric Dept of Allergy and Lung Diseases, Oslo University Hospital, Oslo, Norway. [Destouches DMS] Association des Patients Ayant une Dyskinésie Ciliaire Primitive, Limeil-Brevannes, France. [Moreno-Galdó A] Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER of Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], Infeccions respiratòries en els infants, Primary Ciliary Dyskinesia, Statement (logic), Respiratory System, MULTICENTER, RECOMMENDATIONS, 0302 clinical medicine, Original Research Articles, Pandemic, STENOTROPHOMONAS-MALTOPHILIA, Infection control, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic Disease [DISEASES], 030212 general & internal medicine, Primary ciliary dyskinesia, Malalties transmissibles - Transmissió, Environmental Health::Health::Environmental Illness::Communicable Diseases::Communicable Disease Control [PUBLIC HEALTH], FOUNDATION, biology, Transmission (medicine), Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Abnormalities, Multiple::Ciliopathies::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Ciliary Motility Disorders [DISEASES], afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedad crónica [ENFERMEDADES], salud ambiental::salud::enfermedad ambiental::enfermedades transmisibles::control de enfermedades transmisibles [SALUD PÚBLICA], medicine.anatomical_structure, Medicine, Patient representatives, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 610 Medicine & health, enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::anomalías múltiples::ciliopatías::enfermedades y anomalías neonatales congénitas y hereditarias::trastornos de la motilidad ciliar [ENFERMEDADES], Other subheadings::Other subheadings::/prevention & control [Other subheadings], 03 medical and health sciences, otorhinolaryngologic diseases, medicine, Intensive care medicine, Science & Technology, CYSTIC-FIBROSIS, Lung, business.industry, PSEUDOMONAS-AERUGINOSA, Malalties cròniques - Prevenció, CARE, EFFICACY, medicine.disease, biology.organism_classification, respiratory tract diseases, 030228 respiratory system, Nontuberculous mycobacteria, 610 Medizin und Gesundheit, business
Abstract: Introduction In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement. Methods A multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering diagnostic microbiology, infection prevention for specific pathogens considered indicated for treatment and segregation aspects. Using a modified Delphi process, consensus to a statement demanded at least 80% agreement within the PCD expert panel group. Patient organisation representatives were involved throughout the process. Results We present a consensus statement on 20 IP&C statements for PCD including suggested actions for microbiological identification, indications for treatment of Pseudomonas aeruginosa, Burkholderia cepacia and nontuberculous mycobacteria and suggested segregation aspects aimed to minimise patient-to-patient transmission of infections whether in-hospital, in PCD clinics or wards, or out of hospital at meetings between people with PCD. The statement also includes segregation aspects adapted to the current coronavirus disease 2019 (COVID-19) pandemic. Conclusion The first ever international consensus statement on IP&C intended specifically for PCD is presented and is targeted at clinicians managing paediatric and adult patients with PCD, microbiologists, patient organisations and not least the patients and their families., For the first time ever, an international consensus statement for infection prevention and control in PCD is presented. A total of 20 statements were developed in a collaboration of BEAT-PCD, COST Action, ERS CRC and ERN-LUNG PCD Core Network. https://bit.ly/3yuahKt
Published: 2021
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14. GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic, and platelet disorders: Communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis

Author: Juliana Perez Botero, Keith Gomez, Maha Othman, Willem H. Ouwehand, Kate Downes, Kathleen Freson, Marie-Christine Morel-Kopp, David-Alexandre Trégouët, Neil V. Morgan, José María Bastida, Shannon Brooks, Harald Schulze, Loredana Bury, José Rivera, Eva Leinoe, Karyn Megy, University of Cambridge [UK] (CAM), Cambridge University Hospitals - NHS (CUH), Royal North Shore Hospital (RNSH), The University of Sydney, Instituto de Investigación Biomédica de Salamanca [Salamanca, Spain] (IBSAL/CIC), Università degli Studi di Perugia (UNIPG), National University Hospital, Rigshospitalet, Copenhagen, Royal Free London NHS Foundation Trust, University of Birmingham [Birmingham], Queen's University [Kingston, Canada], Medical College of Wisconsin [Milwaukee] (MCW), Universidad de Murcia, University Hospital Wuerzburg, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)
Subjects: Platelets, Platelet disorder, Hemorrhage, Genomics, Computational biology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Resource (project management), blood, MANAGEMENT, Humans, Medicine, genes, thrombosis, 030304 developmental biology, Hemostasis, 0303 health sciences, Science & Technology, business.industry, Communication, Genetic variants, Thrombosis, Hematology, Pathogenicity, medicine.disease, 3. Good health, Blood, Genes, Peripheral Vascular Disease, Mutation, platelets, Cardiovascular System & Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Blood Platelet Disorders, hemorrhage, mutation, business, Life Sciences & Biomedicine
Abstract: The implementation of high-throughput sequencing (HTS) technologies in research and diagnostic laboratories has linked many new genes to rare bleeding, thrombotic, and platelet disorders (BTPD), and revealed multiple genetic variants linked to those disorders, many of them being of uncertain pathogenicity when considering the accepted evidence (variant consequence, frequency in control datasets, number of reported patients, prediction models, and functional assays). The sequencing effort has also resulted in resources for gathering disease-causing variants associated with specific genes, but for BTPD, such well-curated databases exist only for a few genes. On the other hand, submissions by individuals or diagnostic laboratories to the variant database ClinVar are hampered by the lack of a submission process tailored to capture the specific features of hemostatic diseases. As we move toward the implementation of HTS in the diagnosis of BTPD, the Scientific and Standardization Committee for Genetics in Thrombosis and Haemostasis has developed and tested a REDCap-based interface, aimed at the community, to submit curated genetic variants for diagnostic-grade BTPD genes. Here, we describe the use of the interface and the initial submission of 821 variants from 30 different centers covering 14 countries. This open-access variant resource will be shared with the community to improve variant classification and regular bulk data transfer to ClinVar. ispartof: JOURNAL OF THROMBOSIS AND HAEMOSTASIS vol:19 issue:10 pages:2612-2617 ispartof: location:England status: published
Published: 2021
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15. Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation : Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author: Marianne Ifversen, Roland Meisel, Petr Sedlacek, Krzysztof Kalwak, Luisa Sisinni, Daphna Hutt, Thomas Lehrnbecher, Adriana Balduzzi, Tamara Diesch, Andrea Jarisch, Tayfun Güngör, Jerry Stein, Isaac Yaniv, Halvard Bonig, Michaela Kuhlen, Marc Ansari, Tiago Nava, Jean-Hugues Dalle, Cristina Diaz-de-Heredia, Eugenia Trigoso, Ulrike Falkenberg, Mihaela Hartmann, Marco Deiana, Marta Canesi, Chiara Broggi, Alice Bertaina, Brenda Gibson, Gergely Krivan, Kim Vettenranta, Toni Matic, Jochen Buechner, Anita Lawitschka, Christina Peters, Akif Yesilipek, Koray Yalçin, Giovanna Lucchini, Shahrzad Bakhtiar, Dominik Turkiewicz, Riitta Niinimäki, Jacek Wachowiak, Simone Cesaro, Arnaud Dalissier, Selim Corbacioglu, Andre Manfred Willasch, Peter Bader, Children's Hospital, Lastentautien yksikkö, HUS Children and Adolescents, Ifversen, M, Meisel, R, Sedlacek, P, Kalwak, K, Sisinni, L, Hutt, D, Lehrnbecher, T, Balduzzi, A, Diesch, T, Jarisch, A, Gungor, T, Stein, J, Yaniv, I, Bonig, H, Kuhlen, M, Ansari, M, Nava, T, Dalle, J, Diaz-de-Heredia, C, Trigoso, E, Falkenberg, U, Hartmann, M, Deiana, M, Canesi, M, Broggi, C, Bertaina, A, Gibson, B, Krivan, G, Vettenranta, K, Matic, T, Buechner, J, Lawitschka, A, Peters, C, Yesilipek, A, Yalcin, K, Lucchini, G, Bakhtiar, S, Turkiewicz, D, Niinimaki, R, Wachowiak, J, Cesaro, S, Dalissier, A, Corbacioglu, S, Willasch, A, Bader, P, Institut Català de la Salut, [Ifversen M] Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [Meisel R] Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany. [Sedlacek P] Department of Pediatric Hematology and Oncology, Hospital Motol, Charles University, Prague, Czechia. [Kalwak K] Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. [Sisinni L] Pediatric Hematology, Oncology and Hematopoietic Stem Cell Transplantation Unit, Hospital Santa Creu i Sant Pau, Barcelona, Spain. [Hutt D] Division of Pediatric Hematology, Oncology and Bone Marrow Transplantation, The Edmond and Lily Safra Children's Hospital, Tel Aviv, Israel. [Diaz-de-Heredia C] Servei d’Oncologia i Hematologia Pediàtriques, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: medicine.medical_treatment, allogeneic hematological stem cell transplantation, CHILDREN, Hematopoietic stem cell transplantation, Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], GUIDELINES, Pediatrics, PROPHYLAXIS, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Antibiotic prophylactic therapy, Young adult, Children, antibiotic prophylactic therapy, Original Research, COMPLICATIONS, Hematology, ddc:618, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Transplantation Conditioning [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunosupresión::acondicionamiento para el trasplante [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Vaccination, Hematopoietic stem cell, allogeneic hematological stem cell transplantation, antibiotic prophylactic therapy, children, infection precaution, vaccination, CHEMOTHERAPY, CANCER, 3. Good health, Leukemia, medicine.anatomical_structure, surgical procedures, operative, 030220 oncology & carcinogenesis, Cohort, terapéutica::terapia biológica::tratamientos basados en células y tejidos::trasplante de células::trasplante de células madre::trasplante de células madre hematopoyéticas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.medical_specialty, Cirurgia - Complicacions, Isolation (health care), Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications [DISEASES], RJ1-570, 03 medical and health sciences, Internal medicine, medicine, Other subheadings::Other subheadings::/adverse effects [Other subheadings], PARTICULATE AIR FILTRATION, infection precaution, ddc:610, NEUTROPENIC DIET, Intensive care medicine, Donor selection, business.industry, Cèl·lules mare hematopoètiques - Trasplantació, medicine.disease, vaccination, afecciones patológicas, signos y síntomas::procesos patológicos::complicaciones posoperatorias [ENFERMEDADES], RECIPIENTS, Infection precaution, Pediatrics, Perinatology and Child Health, Sang - Malalties, Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell Transplantation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business, Allogeneic hematological stem cell transplantation, LEUKEMIA, 030215 immunology
Abstract: Terapia profiláctica antibiótica; Niños; Vacunación Teràpia profilàctica antibiòtica; Nens; Vacunació Antibiotic prophylactic therapy; Children; Vaccination Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
Published: 2021

16. Comparison of long-term outcome for AML patients alive free of disease 2 years after allogeneic hematopoietic cell transplantation with umbilical cord blood versus unrelated donor: a study from the ALWP of the EBMT

Author: Martin Bornhäuser, Gérard Socié, Maud Ngoya, Frédéric Baron, Arnold Ganser, Henrik Sengeloev, Annalisa Ruggeri, Hans Christian Reinhardt, Jan J. Cornelissen, Edouard Forcade, Mohamad Mohty, Arnon Nagler, Myriam Labopin, Nicolaus Kröger, Didier Blaise, Thomas Valerius, GIGA [Université Liège], Université de Liège, Centre Hospitalier Universitaire de Liège (CHU-Liège), CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hannover Medical School [Hannover] (MHH), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], National University Hospital, Rigshospitalet, Copenhagen, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medizinische Klinik und Poliklinik I [Dresden, Germany], Universitätsklinikum 'Carl Gustav Carus' Dresden, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), IRCCS San Raffaele Scientific Institute [Milan, Italie], Chaim Sheba Medical Center, and Hematology
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Transplantation Conditioning, Medizin, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Umbilical cord, Unrelated Donor, Internal medicine, Medicine, Humans, Retrospective Studies, Transplantation, Hematopoietic cell, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Fetal Blood, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Female, business, Unrelated Donors
Abstract: International audience; Since cord blood transplantation (CBT) has been associated with high graft-versus-leukemia effects and a low incidence of chronic graft-versus-host disease (GVHD), we hypothesized that long-term outcomes might be better in CBT patients than in those given grafts from unrelated donors (UD). Therefore, we performed a landmark study comparing long-term outcomes in acute myeloid leukemia (AML) patients alive and disease-free 2 years after transplantation who received grafts from either CBT or UD. A total of 364 CBT recipients, 2648 UD 10/10 patients and 681 patients given grafts from UD 9/10 were included. Median follow-up was 6.0 years. Five-year leukemia-free survival (LFS) from transplantation was 86% in CBT patients, 84% in UD 10/10 patients (P = 0.36) and 84% in UD 9/10 patients (P = 0.86). On multivariate analysis, donor type had no impact on LFS. Similarly, no impact of donor type was observed on relapse incidence or non-relapse mortality. Factors associated with poorer LFS on multivariate analysis included higher age at transplantation (P < 0.001), male gender (P < 0.001), second complete remission (CR2) versus CR1 (P = 0.05), secondary AML (P = 0.01), antecedent of chronic GVHD (P < 0.001) and poor-risk cytogenetics (P = 0.01). In conclusion, our study shows that long-term outcome for AML patients in CR two years after transplantation is not impacted by donor type.
Published: 2021
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17. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author: Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.
Subjects: Netherlands Twin Register (NTR), Alcoholism/genetics, Schizophrenia/genetics, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Medicine (miscellaneous), Genome-wide association study, Alcohol use disorder, Anorexia nervosa, Linkage Disequilibrium, ddc:616.89, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Tobacco Use Disorder/genetics, Substance-Related Disorders/genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Factors de risc en les malalties, Bulimia nervosa, Feeding and Eating Disorders/genetics, eating disorders, genetic correlation, substance use, Tobacco Use Disorder, 3. Good health, Fenotip, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Eating disorders, Phenotype, Schizophrenia, Drinking of alcoholic beverages, eating disorder, Consum d'alcohol, Major depressive disorder, medicine.symptom, Depressive Disorder, Major/genetics, eating disorders, genetic correlation, substance use, Clinical psychology, Substance abuse, Risk factors in diseases, Substance-Related Disorders, Polymorphism, Single Nucleotide, Article, Feeding and Eating Disorders, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Genetics, medicine, Humans, Trastorns de la conducta alimentària, 030304 developmental biology, Genetic association, Pharmacology, Depressive Disorder, Major, Binge eating, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SCCO] Cognitive science, medicine.disease, Comorbidity, Twin study, 030227 psychiatry, Abús de substàncies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Genètica, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
Published: 2021
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18. COVID-19 in people with multiple sclerosis: A global data sharing initiative

Author: Ruth Dobson, Lars Forsberg, Luc De Raedt, Doralina Guimarães Brum, Liesbet M. Peeters, Tomas Kalincik, Tina Parciak, Jeffrey A. Cohen, Robert McBurney, Gilles Edan, Helmut Butzkueven, Nick Rijke, Ingrid van der Mei, Clare Walton, Melinda Magyari, Guilherme Sciascia do Olival, Clément Gautrais, Kerstin Hellwig, Yves Moreau, Ashkan Pirmani, Edward De Brouwer, Lotte Geys, Paulo Rodrigues, Rodden M. Middleton, Hollie Schmidt, Juan Ignacio Rojas, Anibal Chertcoff, Nikola Lazovski, Rumen Ivanov, Arnfin Bergmann, Stefan Braune, Giancarlo Comi, Jan Hillert, Jérôme De Seze, Ricardo Alonso, Daniele Raimondi, Landon McKenna, Anneke van der Walt, Wim Van Hecke, Johana Bauer, Tim Spelman, Amber Salter, Alexander Stahmann, Céline Louapre, Bruce F. Bebo, Richard Nicholas, Yann Dauxais, Steve Simpson-Yap, Hasselt University, University Medical Center Göttingen, MS International Federation, KU Leuven, The University of Melbourne, CHU Pontchaillou, QMENTA, Swedish MS Registry, Accelerated Cure Project for MS, NeuroTransData, MS Forschungs- und Projektentwicklungs-gGmbH, UK MS Register, Washington University in St. Louis, USA/National Multiple Sclerosis Society, Hospital Universitario de CEMIC, Monash University, University of Tasmania, Bulgarian SmartMS COVID-19 Dataset, Katholisches Klinikum Bochum, Brazilian Multiple Sclerosis Association (ABEM), Cleveland Clinic, Icometrix – Icompanion, Queen Mary University of London, University Hospital Rigshospitalet, Universidade Estadual Paulista (Unesp), RELACOEM, EMA, Hospital Británico de Buenos Aires – EMA, Strasbourg University Hospital, COVISEP, Ospedale San Raffaele, Royal Melbourne Hospital, Sorbonne University, Imperial College London, Swansea University, Ramos Mejia Hospital – EMA, Magyari, Melinda/0000-0002-0972-5222, Pirmani, Ashkan/0000-0003-4549-1002, De Raedt, Luc/0000-0002-6860-6303, Walton, Clare/0000-0002-8128-6439, PEETERS, Liesbet, PARCIAK, Tina, Walton, Clare, GEYS, Lotte, Moreau, Yves, DE BROUWER, Edward, Raimondi, Daniele, PIRMANI, Ashkan, Kalincik, Tomas, Edan, Gilles, Simpson-Yap, Steve, DE RAEDT, Sylvie, Dauxais, Yann, Gautrais, Clement, Rodrigues, Paulo R., McKenna, Landon, Lazovski, Nikola, Hillert, Jan, Forsberg, Lars, SPELMANS, Nele, McBurney, Robert, Schmidt, Hollie, Bergmann, Arnfin, Braune, Stefan, Stahmann, Alexander, Middleton, Rodden, Salter, Amber, Bebo, Bruce F., Rojas, Juan, I, van der Walt, Anneke, Butzkueven, Helmut, van der Mei, Ingrid, Ivanov, Rumen, Hellwig, Kerstin, do Olival, Guilherme Sciascia, Cohen, Jeffrey A., Van Hecke, Wim, Dobson, Ruth, Magyari, Melinda, Brum, Doralina Guimaraes, Alonso, Ricardo, Nicholas, Richard, Bauer, Johana, Chertcoff, Anibal, de Seze, Jerome, Louapre, Celine, Comi, Giancarlo, and Rijke, Nick
Subjects: Gerontology, 2019-20 coronavirus outbreak, data collection, Coronavirus disease 2019 (COVID-19), International Cooperation, Information Dissemination, Clinical Neurology, Coronavirus Infections/complications, pandemics, Multiple sclerosis, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Risk Factors, medicine, 030212 general & internal medicine, humans, Future Perspectives, Data collection, Science & Technology, SARS-CoV-2, Neurosciences, COVID-19, registries, coronavirus 2, medicine.disease, Multiple Sclerosis/complications, 3. Good health, Clinical neurology, Data sharing, Treatment Outcome, Neurology, Neurology (clinical), Neurosciences & Neurology, Pneumonia, Viral/complications, Psychology, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Coronavirus Infections
Abstract: Made available in DSpace on 2020-12-12T02:15:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Multiple Sclerosis International Federation Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS. Biomedical Research Institute and Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Göttingen MS International Federation ESAT-STADIUS KU Leuven Biomedical Research Institute and Data Science Institute Hasselt University Diepenbeek Belgium/ESAT-STADIUS KU Leuven Clinical Outcomes Research (CORe) Unit The University of Melbourne Department of Neurology CHU Pontchaillou Neuroepidemiology Unit Melbourne School of Population Global Health The University of Melbourne Department of Computer Science and Leuven.AI KU Leuven QMENTA Department of Clinical Neuroscience Swedish MS Registry iConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData MS Forschungs- und Projektentwicklungs-gGmbH UK MS Register COViMS St Louis USA/ Division of Biostatistics Washington University in St. Louis COViMS USA/National Multiple Sclerosis Society Neurology Department Hospital Universitario de CEMIC MSBase Registry Department of Neuroscience Central Clinical School Monash University The Australian MS Longitudinal Study (AMSLS) Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset LEOSS Department of Neurology Katholisches Klinikum Bochum Brazilian Multiple Sclerosis Association (ABEM) Cleveland Clinic MS COVID-19 Registry Mellen MS Center Cleveland Clinic Icometrix – Icompanion OptimiseMS Preventive Neurology Unit Queen Mary University of London The Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders RELACOEM Mental Health Area EMA MS and Demyelinating Diseases Hospital Británico de Buenos Aires – EMA Department of Neurology Strasbourg University Hospital COVISEP Institute of Experimental Neurology Ospedale San Raffaele Melbourne MS Centre Department of Neurology Royal Melbourne Hospital Institut du Cerveau ICM APHP – Hôpital Pitié Salpêtrière Sorbonne University Menzies Institute for Medical Research University of Tasmania Imperial College London Swansea University Multiple Sclerosis University Center Ramos Mejia Hospital – EMA Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders
Published: 2020
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19. Serum Potassium in the PARADIGM-HF trial

Author: Jean-Lucien Rouleau, Milton Packer, John J.V. McMurray, Pardeep S. Jhund, Ulrik M. Mogensen, Michael R. Zile, Faiez Zannad, Patrick Rossignol, João Pedro Ferreira, Akshay S. Desai, Scott D. Solomon, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Montreal Heart Institute - Institut de Cardiologie de Montréal, Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, Baylor Heart and Vascular Institute, Baylor University Medical Center, Brigham and Women's Hospital [Boston], JPF is funded by an ESC research grant for collaboration with the University of Glasgow. All other authors report no specific funding for this project. JJVMcM and PSJ are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217, BOZEC, Erwan, and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Male, Potassium, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, outcomes, Ventricular Function, Left, Electrolytes, 0302 clinical medicine, Enalapril, hyperkalaemia, Research Articles, Randomized Controlled Trials as Topic, Ejection fraction, Aminobutyrates, potassium, Hazard ratio, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Drug Combinations, Cardiology, Valsartan, Female, Cardiology and Cardiovascular Medicine, medicine.drug, Research Article, medicine.medical_specialty, chemistry.chemical_element, Sudden death, 03 medical and health sciences, Angiotensin Receptor Antagonists, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, mineralocorticoid receptor antagonists, Aged, Heart Failure, business.industry, Biphenyl Compounds, Sacubitril–valsartan, Stroke Volume, hypokalaemia, medicine.disease, Confidence interval, chemistry, Heart failure, sacubitril/valsartan, business, Sacubitril, Valsartan
Abstract: Aims: The associations between potassium level and outcomes, the effect of sacubitril–valsartan on potassium level, and whether potassium level modified the effect of sacubitril–valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM‐HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non‐cardiovascular death and heart failure hospitalization, were examined. Methods and results: A total of 8399 patients were randomized to either enalapril or sacubitril–valsartan. Potassium level at randomization and follow‐up was examined as a continuous and categorical variable (≤3.5, 3.6–4.0, 4.1–4.9, 5.0–5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+ ≥5.5 mmol/L and hypokalaemia as K+ ≤3.5 mmol/L. Compared with potassium 4.1–4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84–3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10–1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non‐cardiovascular death and heart failure hospitalization. Sacubitril–valsartan had no effect on potassium overall. The benefit of sacubitril–valsartan over enalapril was consistent across the range of baseline potassium levels. Conclusions: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.
Published: 2020
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20. Time trends in the reporting of conflicts of interest, funding and affiliation with industry in intensive care research: a systematic review

Author: Elie Azoulay, Marie Warrer Petersen, Emmanuel Weiss, Michael Darmon, Charlotte Poussardin, Riccardo Pinciroli, Peter Buhl Hjortrup, Audrey De Jong, Bruna Brandao Barreto, Julie Helms, Stéphanie Sigaut, Anders Granholm, Morten Hylander Møller, Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), National University Hospital, Rigshospitalet, Copenhagen, Faculté de Médecine [Université Paris Diderot - Paris 7], Université Paris Diderot - Paris 7 (UPD7), Service d'anesthésie et de réanimation [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Strasbourg (UNISTRA), Zealand University Hospital, Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Darmon, M, Helms, J, De Jong, A, Hjortrup, P, Weiss, E, Granholm, A, Pinciroli, R, Poussardin, C, Petersen, M, Sigaut, S, Barreto, B, Moller, M, Azoulay, E, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], Periodicals as topic/standard, Disclosure, macromolecular substances, Bibliometrics, 0603 philosophy, ethics and religion, Critical Care and Intensive Care Medicine, Bibliometric, law.invention, 03 medical and health sciences, 0302 clinical medicine, Bias, Randomized controlled trial, law, Research Support as Topic, Bia, Intensive care, parasitic diseases, medicine, Humans, Industry, Conflicts of interest, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Editorial policies, Impact factor, Conflict of Interest, business.industry, fungi, Disclosure/statistics and numerical data, Conflict of interest, Editorial policie, 06 humanities and the arts, Intensive care unit, Research Personnel, 3. Good health, Incentive, Quartile, Family medicine, 060301 applied ethics, business, Journal impact factor, Periodicals as topic/standards
Abstract: International audience; Purpose : Conflict of interest (COI) may compromise, or have the appearance of compromising, a researcher’s judgment or integrity in conducting or reporting research. We sought to assess time trends of COI and funding statement reporting in the critical care literature.Methods : PubMed was searched by using Medical Subject Headings and the appropriate corresponding keywords: “INTENSIVE CARE UNIT” or “ICU” as a major topic. Four years in a 15-year time period (2001–2016) were arbitrarily chosen and one study month was randomly selected for each study period. Studies published during the selected months were included in the analysis.Results : Three hundred and seventy-four studies were evaluated, including five reviews (1.3%) and ten randomized clinical trials (RCTs) (2.7%). COI statements were available in 65% of the studies and 8% had declared COI. COI statement rate, declared COI and funding statements increased over time, while the number of authors affiliated with industry and the discordance between the lack of COI statement and affiliation with industry decreased. Declared COI were more frequent in 2011–2016 as compared to 2001–2010 (OR 4.06; 95% CI 1.15–25.79) and in the higher quartile of a journal’s impact factor (OR of 16.73; 95% CI 3.28–306.20). Surprisingly, focus of the study, country of the first author and/or endorsement of the study by a trial group were not associated with COI statements.Conclusion : Our study suggests COI reporting to have been unintuitive to most investigators and unreliable before ICMJE statements, and that strong incentives are needed to implement adequate reporting of COI.
Published: 2018
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21. Specific barriers to the conduct of randomised clinical trials on medical devices

Author: Michaela Eikermann, Janus Christian Jakobsen, Vittorio Bertele, Séverine Pitel, Dawid Pieper, Christian Gluud, Snezana Djurisic, Jacques Demotes-Mainard, Esther Jacobs, Cecilia Martinho, Christine Kubiak, Carsten Koenen, Silvio Garattini, Martine Laville, Doerthe Seidel, Edmund Neugebauer, Sunya Lee Antoine, Ana Rath, Brandenburg Medical School Theodor Fontane & Health Services Research Witten [Neuruppin, Germany], Universität Witten - Herdecke [Germany], Plateforme d'information et de services pour les maladies rares et les médicaments orphelins (Orphanet), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research in Operative Medicine [Cologne, Germany], Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Unité de Recherche en Diabétologie et Nutrition [Marseille] (QUALISSIMA Marseille Laboratoires pharmaceutiques), Qualissima (SARL) [Marseille], Association for Innovation and Biomedical Research on Light and Image (AIBILI), Copenhagen Trial Unit (CTU), Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, European Clinical Research Infrastructures Network [Paris] (ECRIN), Ecrin, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Department of Cardiology [Holbaek, Denmark], Holbæk Hospital [Denmark], The present review is founded by the European Commission through funding of the project European Clinical Research Infrastructures Network-Integrated Activity, Project reference: 284395, Funded under: FP7-INFRASTRUCTURES., European Project: 284395,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2011-1,ECRIN-IA(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Associação para Investigação Biomédica em Luz e Imagem [Coimbra, Portugal] (AIBILI), University of Coimbra [Portugal] (UC)-Institute for Biomedical Imaging and Life Sciences [Coimbra, Portugal], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BMC, BMC, European Clinical Research Infrastructures Network - Integrating Activity - ECRIN-IA - - EC:FP7:INFRA2012-01-01 - 2017-12-31 - 284395 - VALID, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: medicine.medical_specialty, Evidence-based medicine, Blinding, Time Factors, Endpoint Determination, [SDV]Life Sciences [q-bio], Alternative medicine, Medicine (miscellaneous), Context (language use), Review, Assessment, Risk Assessment, Evidence-based clinical practice, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Randomized Controlled Trials as Topic, Specific barriers, lcsh:R5-920, business.industry, Clinical study design, European Clinical Research Infrastructure Network, Randomised clinical trials, medicine.disease, Clinical trial, [SDV] Life Sciences [q-bio], Clinical research, Treatment Outcome, Equipment and Supplies, Learning curve, Research Design, Medical devices, Medical emergency, business, lcsh:Medicine (General), 030217 neurology & neurosurgery
Abstract: Background Medical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices. Methods Systematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Results In addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency. Conclusions The present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2168-0) contains supplementary material, which is available to authorized users.
Published: 2017
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22. Editor’s Choice - Acute Cardiovascular Care Association Position Paper on Intensive Cardiovascular Care Units: An update on their definition, structure, organisation and function

Author: Sigrun Halvorsen, Avi Shimony, Pranas Šerpytis, Zaza Iakobishvili, Robert Zukermann, Elia De Maria, Donna Fitzsimons, Gianni Casella, Ahmed Magdy, Eric Bonnefoy-Cudraz, François Roubille, Doron Zahger, Richard Rokyta, Elina Trendafilova, Héctor Bueno, Jorge Mimoso, Endre Zima, Christiaan J. Vrints, Marco Tubaro, Christian Hassager, David Walker, Toomas Marandi, Susana Price, Diana Tint, Maddalena Lettino, Alexander Parkhomenko, Janina Stępińska, Hospices Civils de Lyon (HCL), Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Cardiology, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Charles University Hospital, Charles University [Prague] (CU), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and University of Arizona
Subjects: medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Cardiology, Cardiovascular care, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Acute cardiovascular care, Unit (housing), 03 medical and health sciences, 0302 clinical medicine, Case mix index, Multidisciplinary approach, Critical care nursing, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Function (engineering), Societies, Medical, Management structure, media_common, ICCU, business.industry, Coronary Care Units, Disease Management, intensive cardiovascular care units, General Medicine, 3. Good health, Europe, Cardiovascular Diseases, Acute Disease, Position paper, Human medicine, Periodicals as Topic, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Acute cardiovascular care has progressed considerably since the last position paper was published 10 years ago. It is now a well-defined, complex field with demanding multidisciplinary teamworking. The Acute Cardiovascular Care Association has provided this update of the 2005 position paper on acute cardiovascular care organisation, using a multinational working group. The patient population has changed, and intensive cardiovascular care units now manage a large range of conditions from those simply requiring specialised monitoring, to critical cardiovascular diseases with associated multi-organ failure. To describe better intensive cardiovascular care units case mix, acuity of care has been divided into three levels, and then defining intensive cardiovascular care unit functional organisation. For each level of intensive cardiovascular care unit, this document presents the aims of the units, the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region/area. This update emphasises cardiologist training, referring to the recently updated Acute Cardiovascular Care Association core curriculum on acute cardiovascular care. The training of nurses in acute cardiovascular care is additionally addressed. Intensive cardiovascular care unit expertise is not limited to within the unit's geographical boundaries, extending to different specialties and subspecialties of cardiology and other specialties in order to optimally manage the wide scope of acute cardiovascular conditions in frequently highly complex patients. This position paper therefore addresses the need for the inclusion of acute cardiac care and intensive cardiovascular care units within a hospital network, linking university medical centres, large community hospitals, and smaller hospitals with more limited capabilities.
Published: 2017
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23. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

Author: Judd, A, Lodwick, R, Noguera‐Julian, A, Gibb, DM, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi‐Lepri, A, García, F, Brockmeyer, NH, Warszawski, J, Gonzalez‐Tome, MI, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, MA, Chene, G, Phillips, A, Mary Krause, Murielle, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Amo, Julia Del, Thorne, Claire, Kirk, Ole, Pérez‐Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Rojo, Pablo, Soriano‐Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Teira, Ramon, Garrido, Myriam, Haerry, David, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Frederiksen, Casper M., Friis‐Møller, Nina, Kjaer, Jesper, Salbøl Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Davies, Mary‐Anne, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, van der Valk, Marc, Wyss, Natasha, The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, APH - Global Health, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord., [Judd,A, Gibb,DM] MRC Clinical Trials Unit, University College London, London, UK. [ Lodwick,R, Sabin,C, Mocroft,A, Cozzi-Lepri,A, Phillips,A] Department of Infection and Population Health, University College London, London, UK. [Noguera-Julian,A] Institut de Recerca Pedi atrica Hospital Sant Joan de Deu, Barcelona, Spain. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiologıa y Salud Publica Ciberesp, Barcelona, Spain. [Butler,K] Department of Infectious Diseases and Immunology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland. [Costagliola,D] INSERM, UPMC Univ Paris 06, Institut Pierre Louis d’epidemiologie et de Sante Publique (IPLESP UMRS 1136), Sorbonne Universites, Paris, France. [van Sighem,A] Stichting HIV Monitoring, Amsterdam, The Netherlands. [Ledergerber,B] Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. [Torti,C] Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy. [Podzamczer,D[ HUV and STD Unit, Infectious Diseases Service, Hospital Universitari de Bellvitge. L’Hospitalet, Barcelona, Spain. [Dorrucci,M] Istituto Superiore di Sanit a, Rome, Italy. [De Wit,S] Departement of Infectious Diseases, Centre Hospitalier Saint-Pierre, Universite Libre de Bruxelles, Brussels, Belgium. [Obel,N] Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. [Dabis,F, Chene,D] NSERM U1219 – Centre Inserm Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. ISPED, Centre INSERM U1219-Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. [Garcia,F] Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigacion Biosanitaria ibs.Granada, Granada, Spain. [Brockmeyer,NH] Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany. [Warszawski,J] INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France. [Gonzalez-Tome,MI] HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. [Mussini,C] Infectious Diseases Clinics, University Hospital, Modena, Italy. [Touloumi,G] Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece. [Zangerle,R] Medical University Innsbruck, Innsbruck, Austria. [Ghosn,J] EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France. [Castagna,A] San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy. [Fätkenheuer,G] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. [Stephan,C] Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. [Meyer,L] NSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France. AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France. [Campbell,MA] Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark. [Chene,G]. CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France., Financial disclosure: The PLATO II project is funded by the UK Medical Research Council (award G0700832). The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), France, the HIV Monitoring Foundation, The Netherlands, and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The group has also received project-specific funding from the UK Medical Research Council and the Swiss Bridge Foundation., Judd, A, Lodwick, R, Noguera-Julian, A, Gibb, D, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi-Lepri, A, García, F, Brockmeyer, N, Warszawski, J, Gonzalez-Tome, M, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, M, Chene, G, Phillips, A, Puoti, M, Goethe-Universität Frankfurt am Main, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Copenhagen = Københavns Universitet (UCPH), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, University College of London [London] (UCL), Universitat Autònoma de Barcelona (UAB), Hospital Sant Joan de Déu [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Our Lady's Children's Hospital Crumlin (OLCHC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University hospital of Zurich [Zurich], Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Istituto Superiore di Sanita [Rome], Université libre de Bruxelles (ULB), Copenhagen University Hospital, Universidad de Granada = University of Granada (UGR), Ruhr-Universität Bochum [Bochum], Hospital Universitario 12 de Octubre [Madrid], Azienda Ospedaleria Universitaria di Modena, National and Kapodistrian University of Athens (NKUA), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University Hospital of Cologne [Cologne], HAL-SU, Gestionnaire, and The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord
Subjects: Male, HIV Infections, Pharmacologie, Santé publique, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual Behavior::Sexuality::Heterosexuality [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pharmacology (medical), Inhibidores de proteasas, Young adult, Europe, perinatal HIV infection, virological failure, young people, Adolescent, Adult, Anti-Retroviral Agents, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Time Factors, Treatment Failure, Young Adult, Drug Resistance, Viral, Population Groups, Pathologie maladies infectieuses, ComputingMilieux_MISCELLANEOUS, Adolescente, ADN polimerasa dirigida por ADN, Original Research, Health Policy, Enfermedades transmisibles, 3. Good health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings], G0700832, Young people, Viral load, Human, Factores de riesgo, medicine.medical_specialty, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], 03 medical and health sciences, Virological failure, Recién nacido, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings], Heterosexualidad, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Communicable Diseases [Medical Subject Headings], Perinatal HIV infection, RCUK, medicine.disease, Infecciones por VIH, Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Observational study, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], 0301 basic medicine, Pediatrics, Science et gestion hospitalières, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings], Anti-Retroviral Agents/therapeutic use, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Interquartile range, Epidemiology, HIV Infection, 030212 general & internal medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adulto, MRC, Infectious Diseases, Niño, Europa, VIH-1, Population Group, Time Factor, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Acquired immunodeficiency syndrome (AIDS), medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections::Acquired Immunodeficiency Syndrome [Medical Subject Headings], Persons::Persons::Age Groups::Child [Medical Subject Headings], ddc:610, Intervalos de confianza, Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings], business.industry, Inhibidores de la transcriptasa inversa, Confidence interval, Carga viral, Fármacos anti-VIH, Anti-Retroviral Agent, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published
Published: 2017
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24. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author: Leila Karhunen, Geòrgia Escaramís, Ingrid Meulenbelt, Yiran Guo, Matteo Cassina, Stephan Ripke, Alessandro Rotondo, Harry Brandt, Nicholas G. Martin, Andreas Birgegård, Cynthia M. Bulik, Sietske G. Helder, Julie K. O'Toole, Martien J H Kas, Julien Bryois, Nancy L. Pedersen, Philippe Courtet, Virpi M. Leppä, Konstantinos Hatzikotoulas, Liselotte Petersen, Paola Giusti-Rodríguez, André Scherag, Roger A.H. Adan, George Dedoussis, Laramie E. Duncan, John F. Pearson, Helena Gaspar, Andrew W. Bergen, Jurjen J. Luykx, Paul Lichtenstein, Jin P. Szatkiewicz, Lisa R. Lilenfeld, James L. Kennedy, Sébastien Guillaume, Angela Favaro, Artemis Tsitsika, Sara Marsal, Tõnu Esko, Joseph M. Boden, Janiece E. DeSocio, Stefan Ehrlich, Michael Strober, Laura M. Huckins, Alexandra Schosser, Katherine M. Kirk, Gun Peggy Knudsen, Dalila Pinto, Garret D. Stuber, Nicolas Ramoz, Dimitris Dikeos, Jochen Seitz, Stephanie Zerwas, Jolanta Lissowska, Jacques Pantel, Palmiero Monteleone, Katherine A. Halmi, Alessio Maria Monteleone, Scott D. Gordon, Ulrike Schmidt, Franziska Ritschel, Ted Reichborn-Kjennerud, Jennifer Jordan, Ina Giegling, Grant W. Montgomery, Morten Mattingsdal, Esther Walton, Andreas Karwautz, Federica Tozzi, Marion Roberts, Vladimir Janout, P. Eline Slagboom, Laura M. Thornton, Hana Papezova, Mikael Landén, Deborah Kaminská, Robert D. Levitan, Daniela Degortes, Manuel Föcker, Kirsty Kiezebrink, Wolfgang Herzog, Katharina Buehren, Benedetta Nacmias, Christopher Hübel, Eleftheria Zeggini, L. John Horwood, Maria La Via, Claes Norring, Karin Egberts, Nadia Micali, Filip Rybakowski, Monica Forzan, Katrin Männik, Konstantinos Tziouvas, Ioanna Tachmazidou, Thomas Werge, Tracey D. Wade, Raquel Rabionet, Scott J. Crow, Antonio Julià, Jonathan R. I. Coleman, Susana Jiménez-Murcia, Claudette Boni, Roland Burghardt, Christopher S. Franklin, Alfonso Tortorella, Fragiskos Gonidakis, Ioanna Ntalla, Anke Hinney, Jaakko Kaprio, Lenka Slachtova, Anu Raevuori, Sandro Sorbi, Richard Parker, Johanna Giuranna, Kirstin L. Purves, Stephan Zipfel, James J. Crowley, Hidetoshi Inoko, Janet Treasure, Shuyang Yao, Leonid Padyukov, Youl-Ri Kim, Monica Gratacos Mayora, Joanna Hauser, Manfred M. Fichter, Samuli Ripatti, Zeynep Yilmaz, Stephanie Le Hellard, Bochao Danae Lin, Wade H. Berrettini, Gursharan Kalsi, Anders Juréus, Oliver S. P. Davis, Ilka Boehm, Lars Klareskog, Lenka Foretova, Ken B. Hanscombe, Janne Tidselbak Larsen, Hunna J. Watson, Beate Herpertz-Dahlmann, Krista Fischer, Xavier Estivill, Vesna Boraska Perica, Karen S. Mitchell, Andreas J. Forstner, Stefan Herms, Eric F. van Furth, Kelly L. Klump, Anjali K. Henders, Fernando Fernández-Aranda, David C. Whiteman, Catherine M. Olsen, James E. Mitchell, Martina de Zwaan, Johannes Hebebrand, Manuel Mattheisen, Anne Farmer, Agnieszka Słopień, Christian Dina, Dong Li, Marie Navratilova, Sarah E. Medland, Steven Crawford, Elisa Docampo, Craig Johnson, Tetsuya Ando, Elena Tenconi, Roger D. Cone, Sara McDevitt, Allan S. Kaplan, Patrick F. Sullivan, Paolo Santonastaso, Gudrun Wagner, James I. Hudson, Mario Maj, Margarita C T Slof-Op 't Landt, Anna Keski-Rahkonen, Annemarie A. van Elburg, Marta Tyszkiewicz-Nwafor, Danielle M. Dick, Beata Świątkowska, Sven Cichon, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Stephen W. Scherer, Maurizio Clementi, Valdo Ricca, D. Blake Woodside, Roel A. Ophoff, Unna N. Danner, Aarno Palotie, Elisabeth Widen, Nicholas J. Schork, Jakob Grove, Philip Gorwood, Christian R. Marshall, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Hakon Hakonarson, Martin A. Kennedy, Dan Rujescu, Gerome Breen, Lars Alfredsson, Hartmut Imgart, Steven Gallinger, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Pierre J. Magistretti, Andres Metspalu, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Universitätsklinikum Bonn (UKB), National and Kapodistrian University of Athens (NKUA), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Tokai University, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of Helsinki, Rheumatology Unit, Karolinska Institutet [Stockholm], University of Bergen (UiB), The M Sklodowska-Curie Cancer Center and Institute of Oncology, Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Vanderbilt University School of Medicine [Nashville], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm - Paris Descartes), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charles University [Prague] (CU), Norwegian Institute of Public Health [Oslo] (NIPH), Department of Medical Epidemiology and Biostatistics (MEB), Medstar Research Institute, Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Molecular Epidemiology, The Jackson Laboratory [Bar Harbor] (JAX), Università degli Studi di Perugia (UNIPG), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Oregon Research Institute (ORI), Weill Medical College of Cornell University [New York], Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), University of California [San Diego] (UC San Diego), University of California, QIMR Berghofer Medical Research Institute, Department of Physics and Astronomy [Leicester], University of Leicester, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Aarhus University [Aarhus], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, National Centre for Register-based Research, School of Computing [Dublin], Dublin City University [Dublin] (DCU), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Queensland Institute of Medical Research, Department of Genomics, Leiden University Medical Center (LUMC), Watson, H. J., Yilmaz, Z., Thornton, L. M., Hubel, C., Coleman, J. R. I., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Medland, S. E., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Purves, K. L., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Baker, J. H., Berrettini, W. H., Boehm, I., Boni, C., Perica, V. B., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Mayora, M. G., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J. E., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Stuber, G. D., Gordon, S., Grove, J., Henders, A. K., Jureus, A., Kirk, K. M., Larsen, J. T., Parker, R., Petersen, L., Jordan, J., Kennedy, M., Montgomery, G. W., Wade, T. D., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Martin, N. G., Mortensen, P. B., Sullivan, P. F., Breen, G., Bulik, C. M., and Kas lab
Subjects: Male, Anorexia Nervosa, LD SCORE REGRESSION, Medizin, Genome-wide association study, MYC, VARIANTS, Body Mass Index, ddc:616.89, 0302 clinical medicine, POLYGENIC RISK, genetics, molecular biology, anorexia nervosa, Anorexia Nervosa/etiology/genetics/pathology, 0303 health sciences, Metabolic Diseases/complications/genetics, HERITABILITY, Mental Disorders, Anorèxia nerviosa, Genomics, metabo-psychiatric origins, Prognosis, 3. Good health, PREVALENCE, Eating disorders, INSIGHTS, Phenotype, Anorexia nervosa (differential diagnoses), Medical genetics, Female, GENETIC CORRELATIONS, Adult, medicine.medical_specialty, Quantitative Trait Loci, Biology, Article, 03 medical and health sciences, Metabolic Diseases, mental disorders, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Psychiatry, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Case-control study, EATING-DISORDERS, Anorexia nervosa, medicine.disease, Comorbidity, Genetic architecture, Genomics/methods, Genòmica, Case-Control Studies, Mental Disorders/complications/genetics, COMORBIDITY, Body mass index, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness 1, affecting 0.9–4% of women and 0.3% of men 2–4, with twin-based heritability estimates of 50–60% 5. Mortality rates are higher than those in other psychiatric disorders 6, and outcomes are unacceptably poor 7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) 8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
Published: 2019
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25. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis

Author: Uccelli, Antonio, Laroni, Alice, Brundin, Lou, Clanet, Michel, Fernandez, Oscar, Nabavi, Seyed Massood, Muraro, Paolo A., Oliveri, Roberto S., Radue, Ernst W., Sellner, Johann, Soelberg Sorensen, Per, Sormani, Maria Pia, Wuerfel, Jens Thomas, Battaglia, Mario A., Freedman, Mark S., Bonetti, Bruno, Rush, Carolina, Herrera, Concepción, Ramo Tello, Cristina, Miller, David, Szwajcer, David, Strunk, Dirk, Wall, Donna, Aguera-Morales, Eduardo, Rohde, Eva, Dazzi, Francesco, Comi, Giancarlo, Martino, Gianvito, Izquierdo Ayuso, Guillermo, Rabinovitch, H., MacLean, Heather, Marriott, James, Racosta, Juan, Arab, Leila, Gimona, Mario, Introna, Martino, Blinkenberg, Morten, Aghdami, Naser, Ali, Rehiana, Vosoughi, Reza, Nicholas, Richard, Marrie, Ruth Ann, Karimi, Shahedeh, The UK Stem Cell Foundation, Multiple Sclerosis Society, MESEMS study group, [Uccelli,A, Laroni,A] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy. [Uccelli,A, Laroni,A] IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Brundin,L] Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden [Clanet,M] CHU Toulouse, Université Paul Sabatier, Toulouse, France. [Fernandez,O] Instituto de Investigación Biomédica de Málaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain. [Nabavi,SM] Department of Brain and Cognitive Sciences, Royan Institute for Stem Cell Biology and Technology, Royan, Iran. [Nabavi,SM] ACCR, Iran and Regenerative Biomedicine Center, MS, Neurology Clinic and Research Unit, Tehran, Iran. [Muraro,PA] Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. [Oliveri,RS] Cell Therapy Unit, Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [Radue,EW, Wuerfel,JT] Medical Image Analysis Centre Basel (MIAC AG), Basel, Switzerland. [Sellner,J] Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria. [Soelberg Sorensen,P] Danish MS Center Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark. [Sormani,MP] Department of Health Sciences, University of Genoa, Genoa, Italy. [Wuerfel,JT] Department of Biomedical Engineering, University Basel, Basel, Switzerland. [Battaglia,MA] Italian Multiple Sclerosis Foundation, Genoa, Italy. [Battaglia,MA] Department of Life Sciences, University of Siena, Siena, Italy. [Freedman,MS] Department of Medicine (Neurology), University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., The MESEMS network received a grant from Fondazione Italiana Sclerosi Multipla (FISM, sponsor of the Italian Clinical Trial, of the CRO activities and of part of centralized MRI activities), European Committee for Multiple Sclerosis (ECTRIMS), Multiple Sclerosis International Foundation (MSIF) for centralized activities. Individual trials participating in the MESEMS network are funded by: FISM (Italy), The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria (Austria), ARSEP Foundation, AFM (France). The UK trial (London) is supported by a Collaborative Grant from the UK MS Society [938/10], by the NIHR Biomedical Research Centre funding scheme to Imperial College and by the NIHR Imperial Clinical Research Facility., Uccelli, A., Laroni, A., Brundin, L., Clanet, M., Fernandez, O., Nabavi, S. M., Muraro, P. A., Oliveri, R. S., Radue, E. W., Sellner, J., Soelberg Sorensen, P., Sormani, M. P., Wuerfel, J. T., Battaglia, M. A., Freedman, M. S., Bonetti, B., Rush, C., Herrera, C., Ramo Tello, C., Miller, D., Szwajcer, D., Strunk, D., Wall, D., Aguera-Morales, E., Rohde, E., Dazzi, F., Comi, G., Martino, G., Izquierdo Ayuso, G., Rabinovitch, H., Maclean, H., Marriott, J., Racosta, J., Arab, L., Gimona, M., Introna, M., Blinkenberg, M., Aghdami, N., Ali, R., Vosoughi, R., Nicholas, R., Marrie, R. A., and Karimi, S.
Subjects: Male, Time Factors, Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings], Mesenchymal stromal cells, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings], Medicine (miscellaneous), Phases of clinical research, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Transplantation, Autologous [Medical Subject Headings], NEUROLOGICAL DISEASES, Research & Experimental Medicine, Geographical Locations::Geographic Locations::Europe::Europe, Eastern [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Clinical Trials, Phase I as Topic [Medical Subject Headings], Study Protocol, Disability Evaluation, Clinical trial, Mesenchymal stem cells, Mesenchymal stromal cells, Multiple sclerosis, 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings], Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, Randomized Controlled Trials as Topic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic [Medical Subject Headings], Cross over, lcsh:R5-920, Cross-Over Studies, Clinical Trials, Phase I as Topic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Clinical Trials, Phase II as Topic [Medical Subject Headings], Middle Aged, Magnetic Resonance Imaging, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Disability Evaluation [Medical Subject Headings], Clinical trial, Europe, Treatment Outcome, Medicine, Research & Experimental, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Female, lcsh:Medicine (General), Autologous, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Multiple Sclerosis, Adolescent, Células madre mesenquimatosas, Check Tags::Male [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation [Medical Subject Headings], Phase I as Topic, Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings], Mesenchymal Stem Cell Transplantation, Placebo, Transplantation, Autologous, Persons::Persons::Age Groups::Adolescent [Medical Subject Headings], Double blind, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Double-Blind Method, General & Internal Medicine, Internal medicine, Ensayo clínico, medicine, Humans, Clinical Trials, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Science & Technology, TRANSPLANTATION, business.industry, Multiple sclerosis, Phase II as Topic, Mesenchymal stem cell, MESEMS study group, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], 1103 Clinical Sciences, Recovery of Function, medicine.disease, Phenomena and Processes::Biological Phenomena::Recovery of Function [Medical Subject Headings], Transplantation, Check Tags::Female [Medical Subject Headings], Cardiovascular System & Hematology, Esclerosis múltiple, Mesenchymal stem cells, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Cross-Over Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Double-Blind Method [Medical Subject Headings], business, 030217 neurology & neurosurgery
Abstract: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. Andalusia: NCT01745783 , registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010–024081–21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393 . Registered on September 12, 2014. Copenhagen: EudraCT, 2012–000518-13 . Registered on June 21, 2012. Italy: EudraCT, 2011–001295-19, and ClinicalTrials.gov, NCT01854957 . Retrospectively registered on May 16, 2013. London: Eudra CT 2012–002357-35, and ClinicalTrials.gov, NCT01606215 . Registered on May 25, 2012. Salzburg: EudraCT, 2015–000137-78 . Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547 . Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947 . Registered on March 31, 2015.
Published: 2019
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26. Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders

Author: Eoin P. Flanagan, Benjamin Greenberg, Olga Ciccarelli, Olaf Stüve, Jean-Philippe Ranjeva, Maria Pia Sormani, Regina Schlaerger, Myla D. Goldman, Jeffrey A. Cohen, Emmanuelle Waubant, Franz Fazekas, Ellen M. Mowry, Daniel S. Reich, Frederik Barkhof, Hans Lassmann, Anthony Traboulsee, Sandra Vukusic, Mar Tintoré, Bernard M. J. Uitdehaag, Anke Henning, Daniel Pelletier, Alan J. Thompson, Junqian Xu, Jorge Correale, Burkhard Becher, Stephen Reingold, Nicola De Stefano, Bruce F. Bebo, Izlem Izbudak, Claudia Chien, Stephen C. Reingold, Steven Galetta, Claudia Gandini Wheeler-Kingshott, Sebastien Ourselin, Alex Rovira, Mark S. Freedman, Brenda Banwell, Aaron E. Miller, Xavier Montalban, Cornelia Laule, Claudia F. Lucchinetti, Giancarlo Comi, Peter A. Calabresi, Hans-Peter Hartung, Maria Trojano, Ludwig Kappos, Bernhard Hemmer, Bruce D. Trapp, Brian G. Weinshenker, Kazuo Fujihara, Tanuja Chitnis, Jérôme De Seze, Francois Bethoux, Per Soelberg Sørensen, Fred D. Lublin, Alexander U. Brandt, Carsten Lukas, Wallace J Brownlee, Maria Pia Amato, Jeremy Chatway, David Miller, Friedemann Paul, Maria A. Rocca, Ruth Ann Marrie, Michael J. Levy, University of Pennsylvania, VU University Medical Center [Amsterdam], University College of London [London] (UCL), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Departamento de Neurologia, Instituto de Investigaciones Neurológicas 'Dr. Raul Carrea', Instituto de Investigaciones Neurológicas 'Dr. Raul Carrea', Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Dept. of Neurological and Behavioural Sciences, Siena, Department of Neurology [Austria], Medical University Graz, Ottawa Hospital Research Institute [Ottawa] (OHRI), Tohoku University Graduate School of Medicine, Munich Cluster of Systems Neurology (SyNery), Clinical Neuroimmunology, Department of Biomedicine, University of Basel, Basel, Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), St. Josef Hospital, Ruhr-University Bochum, Vall Hebron Research Institute (VHIR), Translational imaging group [London] (TIG), Centre for Medical Image Computing (CMIC), University College of London [London] (UCL)-University College of London [London] (UCL)-Department of Medical Physics and Biomedical Engineering (UCL), Max Delbrueck Centre for Molecular Medicine, Departments of Neurology and Immunobiology [Yale], Yale School of Medicine [New Haven, Connecticut] (YSM), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), National Institutes of Health [Bethesda] (NIH), Vall d'Hebron University Hospital [Barcelona], Dept. of Neurology, University Hospital Rigshospitalet, Centre d'Esclerosi Múltiple de Catalunya (CemCat), Division of Geriatric Medicine, University of British Columbia (UBC), Service de Neurologie [Lyon], CHU Lyon, Department of Neurology, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), NMR Research Unit [London], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pennsylvania [Philadelphia], Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Yale University School of Medicine, Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Spinal cord involvement, 03 medical and health sciences, Myelopathy, 0302 clinical medicine, medicine, Humans, Pathological, ComputingMilieux_MISCELLANEOUS, business.industry, Multiple sclerosis, Neuromyelitis Optica, Clinical course, medicine.disease, Spinal cord, 3. Good health, Clinical trial, 030104 developmental biology, medicine.anatomical_structure, Spinal Cord, Neuromyelitis Optica Spectrum Disorders, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Spinal cord involvement is an important cause of disability in patients with multiple sclerosis or neuromyelitis optica spectrum disorders (NMOSDs). Multiple sclerosis and NMOSDs can be distinguished from other disorders that cause myelopathy by results from laboratory and radiological investigations. However, limitations in the sensitivity and specificity of spinal cord imaging and poor correlation with disability megasures have impeded the understanding of the relationship between spinal cord involvement and clinical manifestations. Nevertheless, studies of the pathological features of multiple sclerosis and NMOSDs have shown that quantitatively different mechanisms lead to differences in clinical course and pattern of accrual of permanent disability in the two disorders. Better understanding of these mechanisms is necessary to develop more informative clinical measures, electrophysiological methods, fluid biomarkers, and imaging techniques to detect and monitor spinal cord involvement in the diagnosis and management of patients with multiple sclerosis or NMOSDs, and as outcome measures in clinical trials.
Published: 2019
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27. Highly prolific authors in critical care: which factors influence their scientific output?

Author: Julie Helms, Chiara Robba, Peter Buhl Hjortrup, Emmanuel Weiss, Audrey De Jong, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), AP-HP, Beaujon Hospital, Clichy, France, National University Hospital, Rigshospitalet, Copenhagen, Policlinico San Martino, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Strasbourg (UNISTRA), Strasbourg, France.
Subjects: medicine.medical_specialty, Biomedical Research, business.industry, Pain medicine, [SDV]Life Sciences [q-bio], [SHS.INFO]Humanities and Social Sciences/Library and information sciences, MEDLINE, 030208 emergency & critical care medicine, Bibliometrics, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Family medicine, Anesthesiology, medicine, Humans, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019
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28. Interplay of DDP4 and IP-10 as a Potential Mechanism for Cell Recruitment to Tuberculosis Lesions

Author: Thomas Blauenfeldt, Linda Petrone, Franca del Nonno, Andrea Baiocchini, Laura Falasca, Teresa Chiacchio, Vincent Bondet, Valentina Vanini, Fabrizio Palmieri, Gianni Galluccio, Armanda Casrouge, Jesper Eugen-Olsen, Matthew L. Albert, Delia Goletti, Darragh Duffy, Morten Ruhwald, Statens Serum Institut [Copenhagen], Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Ospedale San Camillo-Forlanini, Hvidovre Hospital, Genentech, Inc., Genentech, Inc. [San Francisco], MR and DG received funding from European Commission H2020 program (grant number TBVAC2020 643381) and Research Council Norway (GLOBVAC 248042/H10). DG received funding from Italian Minister of Health 'Ricerca Finalizzata': RF-2011-02349395., We are grateful for the kind help provided by Anders Johnsen, Department of Clinical Biochemistry at Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark for performing the MALDI-TOF analysis of CXCL10 truncation for initial method optimization (not included in the publication), and to Dr. Carolyn F. Deacon, department of Biological Sciences, Panum Institute for providing valuable input and protocols to setup the DPP4 enzyme activity assay. Finn Schou, Aahus University, and Ove Andersen, Copenhagen University Hospitals for kind support. Drs T. S. Hermansen, C. Drabe, L. de Thurah, and S. T. Hoff for invaluable assistance including controls for this study and to colleagues at the Center for Vaccine Research at SSI for constructive feedback., European Project: 643381,H2020,H2020-PHC-2014-single-stage,TBVAC2020(2015), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Chemokine, Tuberculosis, pulmonary, medicine.medical_treatment, Immunology, CXCR3, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Immune system, DPP4/CD26, Immunology and Allergy, Medicine, CXCL10, Original Research, bronchoalveolar lavage fluid, biology, business.industry, Immunotherapy, biology.organism_classification, medicine.disease, cytokines, 3. Good health, 030104 developmental biology, tuberculosis, Giant cell, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:RC581-607, business
Abstract: Introduction Mycobacterium tuberculosis is one of the world’s most successful pathogens equipped to establish itself within the human host as a subclinical infection without overt disease. Unable to eradicate the bacteria, the immune system contains the infection in a granuloma structure. Th1 cells that are essential for infection control are recruited to the site of infection directed by chemokines, predominantly CXCL10. It has previously been shown that CXCL10 in the plasma of patients chronically infected with hepatitis C virus is present primarily in an antagonist form. This is due to N-terminal truncation by the enzyme DPP4, which results in the antagonist form that is capable of binding its receptor CXCR3, but does not induce signaling. We aimed to explore whether such CXCL10 antagonism may have an impact on the pathogenesis of tuberculosis (TB). Results We measured plasma levels of agonist and antagonist CXCL10 by Simoa digital ELISA, as well as DPP4 enzyme activity in the plasma of 20 patients with active TB infection, 10 patients with pneumonia infection, and a group of 10 healthy controls. We found higher levels of total and antagonist CXCL10 and reduced DPP4 enzyme activity in the plasma of TB patients compared to controls. We traced the source of CXCL10 secretion using immunohistochemical and confocal analysis to multinucleated giant cells in the TB lesions, and variable expression by macrophages. Interestingly, these cells were associated with DPP4-positive T cells. Moreover, the analysis of lymphocytes at the site of TB infection (bronchoalveolar lavage) showed a reduced frequency of CXCR3+ T cells. Interpretation Our data suggests that CXCL10 antagonism may be an important regulatory mechanism occurring at the site of TB pathology. CXCL10 can be inactivated shortly after secretion by membrane bound DPP4 (CD26), therefore, reducing its chemotactic potential. Given the importance of Th1 cell functions and IFN-γ-mediated effects in TB, our data suggest a possible unappreciated regulatory role of DPP4 in TB. Perspectives DPP4 is the target for a class of enzyme inhibitors used in the treatment of diabetes, and the results from this study suggest that these drugs could be repurposed as an adjunct immunotherapy of patients with TB and MDR-TB.
Published: 2018
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29. Evidence-based practice within nutrition

Author: Janus Christian Jakobsen, Martine Laville, Yves Boirie, Vittorio Bertele, Snezana Djurisic, Ana Rath, Christine Kubiak, Jacques Demotes-Mainard, Carlo La Vecchia, Cristina Ruano-Rodríguez, Christian Gluud, Annemie M. W. J. Schols, Silvio Garattini, Berenice Segrestin, Michael J Hiesmayr, Lluis Serra-Majem, Edmund Neugebauer, Maud Alligier, BMC, BMC, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CIBER Fisiopatología de la Obesidad y Nutrición [Madrid, Spain] ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Nutrition Research Group [Las Palmas, Spain] (Research Institute of Biomedical and Health Sciences), University of Las Palmas de Gran Canaria [Spain] (ULPGC), Division of Cardiac, Thoracic, Vascular Anaesthesia and Intensive Care [Vienna, Austria], Vienna General Hospital Währinger Gürtel, Department of Respiratory Medicine [Maastricht, The Netherlands], University Medical Centre Maastricht-NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands], Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Service de Nutrition Clinique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Plateforme d'information et de services pour les maladies rares et les médicaments orphelins (Orphanet), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Brandenburg Medical School [Witten, Germany], Witten/Herdecke University, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], European Clinical Research Infrastructures Network [Paris] (ECRIN), Ecrin, Copenhagen Trial Unit -CTU [Copenhagen, Denmark] (Centre for Clinical Intervention Research), Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital-Copenhagen University Hospital, Department of Cardiology [Holbaek, Denmark], Holbæk Hospital [Denmark], The ECRIN-IA grant from the EU FP7 (GA 284395) provided support for meetings and for the conduct of this review. The Mario Negri Institute housed the ECRIN-IA meeting in February 2013., French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Instituto de Salud Carlos III (ISC), Università degli studi di Milano [Milano], Service de nutrition clinique [CHU Gabriel Montpied, Clermont-Ferrand], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Rigshospitalet [Copenhagen]-Copenhagen University Hospital, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Università degli Studi di Milano [Milano] (UNIMI), Copenhagen University Hospital-Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: 0301 basic medicine, Research design, Databases, Factual, [SDV]Life Sciences [q-bio], méthodologie de recherche, Medicine (miscellaneous), Review, Evidence-based clinical practice, 0302 clinical medicine, approche nutritionnelle, Medicine, EPIDEMIOLOGY, Nutritional Physiological Phenomena, Pharmacology (medical), Registries, 030212 general & internal medicine, Randomized Controlled Trials as Topic, 2. Zero hunger, RISK, lcsh:R5-920, Randomised clinical trials, CANCER, 3. Good health, [SDV] Life Sciences [q-bio], MEDITERRANEAN DIET, Treatment Outcome, Research Design, Evidence-based medicine, Assessment, Specific barriers, Nutrition, ECRIN, European Clinical Infrastructure Network, Alimentation et Nutrition, SURVIVAL, Nutrition Therapy, HEALTH, lcsh:Medicine (General), COUNTRIES, Blinding, Evidence-based practice, Endpoint Determination, Médecine humaine et pathologie, Context (language use), Clinical nutrition, 03 medical and health sciences, ADHERENCE, FOOD, Humans, Food and Nutrition, étude clinique, Medical education, 030109 nutrition & dietetics, business.industry, Clinical study design, Diet, Clinical trial, Nutrition Assessment, PROSPECTIVE COHORT, Human health and pathology, business
Abstract: Background Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements. Methods Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Results Many nutrients occur in multiple forms that differ in biological activity, and several factors can alter their bioavailability which raises barriers to their assessment. These include specific difficulties with blinding procedures, with assessments of dietary intake, and with selecting appropriate outcomes as patient-centred outcomes may occur decennia into the future. The methodologies and regulations for drug trials are, however, applicable to nutrition trials. Conclusions Research on clinical nutrition should start by collecting clinical data systematically in databases and registries. Measurable patient-centred outcomes and appropriate study designs are needed. International cooperation and multistakeholder engagement are key for success. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2160-8) contains supplementary material, which is available to authorized users.
Published: 2017
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30. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

Author: Paulo J. Magalhães, Juliette Saillard, David Leroy, Morten Duno, Marianne Schwartz, Søren Nørby, Erik Kann, Thomas Rosenberg, Head of the Department of Medical Genetics, ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), and National University Hospital Rigshospitalet
Subjects: 0301 basic medicine, Adult, Male, LEBER HEREDITARY OPTIC NEUROPATHY, Mitochondrial DNA, Pediatrics, medicine.medical_specialty, genetic structures, Adolescent, Genotype, Denmark, Prevalence, Pedigree chart, Optic Atrophy, Hereditary, Leber, DNA, Mitochondrial, Haplogroup, Danish, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Journal Article, Humans, Child, Aged, Aged, 80 and over, business.industry, Research Support, Non-U.S. Gov't, Infant, Newborn, Infant, Middle Aged, language.human_language, eye diseases, Mitochondria, Pedigree, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Cohort, Mutation, 030221 ophthalmology & optometry, language, Female, business
Abstract: PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012.METHODS: Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided.RESULTS: Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population.CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.
Published: 2016
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31. PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men

Author: Bruno Veyrand, Anna-Maria Andersson, Jean-Philippe Antignac, Niels E. Skakkebæk, Jørgen Holm Petersen, Philippe Marchand, Ulla Nordström Joensen, Bruno Le Bizec, Martin Blomberg Jensen, Niels Jørgensen, University Hospital Rigshospitalet, Partenaires INRAE, LUNAM Université [Nantes Angers Le Mans], Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Oniris, PRES Université Nantes Angers Le Mans (UNAM), European Commission (DEER) [FP7-2007-212844], Danish Agency for Science, Technology and Innovation [27107068, 09-067180], Rigshospitalet [961506336], University of Copenhagen, Danish Ministry of Health, Danish Environmental Protection Agency [MST-621-00013], Kirsten and Freddy Johansen Foundation [95-103-72087], European Project: 212844,EC:FP7:ENV,FP7-ENV-2007-1,DEER(2008), and Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Male, PFC, Denmark, [SDV]Life Sciences [q-bio], Endocrine Disruptors, 010501 environmental sciences, 01 natural sciences, 0302 clinical medicine, Sex hormone-binding globulin, Testosterone, Fluorocarbons, 0303 health sciences, education.field_of_study, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, biology, PFOA, Rehabilitation, Obstetrics and Gynecology, Blood Proteins, 3. Good health, Alkanesulfonic Acids, Androgens, Caprylates, Luteinizing hormone, Algorithms, Adult, medicine.medical_specialty, Adolescent, Population, Semen, Semen analysis, Young Adult, 03 medical and health sciences, Semen quality, semen quality, PFOS, Internal medicine, medicine, Humans, education, 030304 developmental biology, 0105 earth and related environmental sciences, Free androgen index, Reproducibility of Results, Environmental Exposure, Luteinizing Hormone, Semen Analysis, Cross-Sectional Studies, Endocrinology, Reproductive Medicine, testosterone, biology.protein, Environmental Pollution
Abstract: Erratum in: Hum Reprod. 2014 Jul;29(7):1600. The authors would like to apologise for a typing error in Table V of this article. The confidence interval of the regression co-efficient for the effect of perfluoro-n-nonanoic acid (PFNA) on estradiol should be −0.075 (−0.130, −0.019) rather than the wrongly stated −0.075 (−0.013, −0.019). The authors would like to assure readers that this does not affect the other content or the conclusions of the article.; International audience; Is exposure to perfluorinated compounds (PFCs) associated with testicular function (reproductive hormone levels and semen quality) in healthy men? PFOS levels were significantly negatively associated with serum testosterone (total and calculated free), but not with any other reproductive hormones or semen quality. In animals, some PFCs have endocrine disrupting potential, but few studies have investigated PFCs in relation to human testicular function. Previously, we and others have observed a negative association between serum PFC levels and sperm morphology. The potential associations with reproductive hormones remain largely unresolved. A cross-sectional study of 247 men was conducted during 2008-2009. Healthy men from the general population, median age of 19 years, gave serum and semen samples. Serum samples were analysed for total testosterone (T), estradiol (E), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin-B and 14 PFCs, including perfluorooctanesulfonate (PFOS). Semen samples were analysed according to the WHO criteria. PFOS levels were negatively associated with testosterone (T), calculated free testosterone (FT), free androgen index (FAI) and ratios of T/LH, FAI/LH and FT/LH. Other PFCs were found at lower levels than PFOS and did not exhibit the same associations. PFC levels were not significantly associated with semen quality. PFOS levels in these samples collected in 20082009 were lower than in our previous study of men participating in 2003. Results were robust to adjustment for relevant confounders; however, the possibility of chance associations due to multiple testing or effects of uncontrolled confounding cannot be ruled out. Our previous findings of decreased sperm morphology in the most highly PFC exposed men were not replicated, possibly due to a lack of highly exposed individuals; however, a recent independent study also did corroborate such an inverse association. The negative association between serum PFOS and testosterone indicates that testosterone production may be compromised in individuals with high PFOS exposure. The authors received financial support from the European Commission (DEER, FP7-2007-212844), the Danish Agency for Science, Technology and Innovation (grant nos. 27107068 and 09-067180), Rigshospitalet (grant no. 961506336), the University of Copenhagen, the Danish Ministry of Health and the Danish Environmental Protection Agency (MST-621-00013), and Kirsten and Freddy Johansen Foundation (grant no. 95-103-72087). The funding organizations played no role in the design and conduct of the study, in collection, management, analysis and interpretation of the data; or in the presentation, review or approval of the manuscript. The authors declare that they have no competing financial interests.
Published: 2012
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32. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Author: Ruth Dobson, P. Kleinova, Tessel F. Runia, H.-P. Hartung, Maria Trojano, A.D. Martinez, Viviana Annibali, Sreeram V. Ramagopalan, Florian Deisenhammer, Mohsen Khademi, Jens Kuhle, Jan Lycke, Mar Tintoré, Ludwig Kappos, Pietro Iaffaldano, Antonio Uccelli, Dana Horakova, Kjell-Morten Myhr, Cecilia Rajda, Konrad Rejdak, Stig Wergeland, Monica Marta, Roberto Furlan, Florian Lauda, Jean Pelletier, Romain Marignier, G. Comi, Giulio Disanto, Romy Roesler, Vita Direnzo, Özgür Yaldizli, N. Moll, Silvia Romano, Sergey V. Lapin, Sylvain Lehmann, Irena Dujmovic, Elio Scarpini, Tomas Olsson, Rogier Q. Hintzen, Raija L.P. Lindberg, E. P. Evdoshenko, Siegrid Fuchs, B. C. Kieseier, Henrik Larsson, Eric Thouvenot, Jonathan P. Bestwick, Maurizio Leone, László Vécsei, S. Saip, Pablo Villoslada, Roberto Bergamaschi, Xavier Montalban, Øivind Torkildsen, José C. Álvarez-Cermeño, Joanne Topping, Albert Saiz, Isabel Bosca, Hayrettin Tumani, Adriana Carrá, Joep Killestein, Sara Llufriu, N. Barizzone, Ute-Christiane Meier, Diego Franciotta, David Brassat, Christian Enzinger, Michael Khalil, Gavin Giovannoni, Timucin Avsar, Scott L. Rauch, Aksel Siva, N. Lazareva, Clas Malmeström, Jette L. Frederiksen, Harald Hegen, Ugur Uygunoglu, Luisa M. Villar, Lucia Bianchi, Marco Salvetti, Tobias Derfuss, Giovanni Castelnovo, Ayse Altintas, Rocco Adiutori, E. Colombo, G. Dalla Costa, Daniela Galimberti, Madeleine H. Sombekke, Vittorio Martinelli, Sandra D'Alfonso, Manuel Comabella, Eva Havrdova, Fredrik Piehl, Charlotte E. Teunissen, Til Menge, Jelena Drulovic, C. Picard, Alice Laroni, Christian Confavreux, Chiara Fenoglio, Neurology, Laboratory Medicine, NCA - Neuroinflamation, Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), National Oceanography Centre (NOC), Department of Anatomy and Structural Biology Albert Einstein College of Medicine, Albert Einstein College of Medicine [New York], Department of public health, University of Turin, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Water Environment Technology, Chalmers University of Technology [Göteborg], Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB), Leibniz Association, Department of Neurology, University of California [San Francisco] (UCSF), University of California-University of California, Center for Neuroimmunology, Service of Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Université européenne de Bretagne - European University of Brittany (UEB), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Azm Center for Biotechnology Research, Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut] (LU), FOI, Linköping University (LIU), Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, IRMP-Louvain, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' (DIA), University of Pisa - Università di Pisa, International Centre for Hydrology 'Dino Tonini' and Dipartimento IMAGE, Universita degli Studi di Padova, Dept. of Neurology, University Hospital Rigshospitalet, University of California [Berkeley], University of California, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, The Weizmann Institute, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Laboratory of Neuroimmunology, IRCCS, Neurological Institute 'C. Mondino', University of Pavia, Pa, University of Pavia, Department of Neurology, Albert Szent-Gyorgyi Clinical Centre, University of Szeged [Szeged], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universitat de Barcelona (UB)-Hospital Clinic, University of Ulm, Department of Neurology, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], University of Eastern Piedmont, Department of Medical Sciences, IRCAD, Novara, Vall d'Hebron University Hospital [Barcelona], Department of Public Health and Clinical Medicine, Umeå University, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Universitaire de Bâle, Laboratory of Molecular Virology, Université libre de Bruxelles (ULB), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), University of Oxford [Oxford], Blizard Institute of Cell and Molecular Science, Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), University of California [Berkeley] (UC Berkeley), University of California (UC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia = University of Pavia (UNIPV), University of Oxford, Direction des Applications Militaires ( DAM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), National Oceanography Centre, University of Southampton [Southampton], Albert Einstein College of Medicine, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Neuropsychiatrie : recherche épidémiologique et clinique, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Leibniz-Institute, University of California [San Francisco] ( UCSF ), Université européenne de Bretagne ( UEB ), Laboratoire de l'intégration, du matériau au système ( IMS ), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique ( CNRS ), Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut], Linköping University ( LIU ), Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy, Università di Bologna [Bologna] ( UNIBO ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' ( DIA ), Università di Pisa, Universita degli Studi di Padova = University of Padua = Université de Padoue, Educational Testing Service, Graduate School of Education, University of California at Berkeley, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), Universitat de Barcelona ( UB ) -Hospital Clinic, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), Kuhle, J., Disanto, G., Dobson, R., Adiutori, R., Bianchi, L., Topping, J., Bestwick, J. P., Meier, U. -C., Marta, M., Dalla Costa, G, Runia, T., Evdoshenko, E., Lazareva, N., Thouvenot, E., Iaffaldano, P., Direnzo, V., Khademi, M., Piehl, F., Comabella, M., Sombekke, M., Killestein, J., Hegen, H., Rauch, S., Dalfonso, S., Alvarez-Cermeno, J. C., Kleinova, P., Horakova, D., Roesler, R., Lauda, F., Llufriu, S., Avsar, T., Uygunoglu, U., Altintas, A., Saip, S., Menge, T., Rajda, C., Bergamaschi, R., Moll, N., Khalil, M., Marignier, R., Dujmovic, I., Larsson, H., Malmestrom, C., Scarpini, E., Fenoglio, C., Wergeland, S., Laroni, A., Annibali, V., Romano, S., Martinez, A. D., Carra, A., Salvetti, M., Uccelli, A., Torkildsen, O., Myhr, K. M., Galimberti, D., Rejdak, K., Lycke, J., Frederiksen, J. L., Drulovic, J., Confavreux, C., Brassat, D., Enzinger, C., Fuchs, S., Bosca, I., Pelletier, J., Picard, C., Colombo, E., Franciotta, D., Derfuss, T., Lindberg, R. L. P., Yaldizli, O., Vecsei, L., Kieseier, B. C., Hartung, H. P., Villoslada, P., Siva, A., Saiz, A., Tumani, H., Havrdova, E., Villar, L. M., Leone, M., Barizzone, N., Deisenhammer, F., Teunissen, C., Montalban, X., Tintore, M., Olsson, T., Trojano, M., Lehmann, S., Castelnovo, G., Lapin, S., Hintzen, R., Kappos, L., Furlan, R., Martinelli, V., Comi, G., Ramagopalan, S. V., and Giovannoni, G.
Subjects: Male, Pathology, serum 25-hydroxyvitamin D3 (25-OH-D), [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Gastroenterology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, sclerosis, clinically isolated syndrome (CIS), Vitamin D, 0303 health sciences, Clinically isolated syndrome, Nuclear Proteins, Prognosis, Magnetic Resonance Imaging, Neurology, Clinically definite multiple sclerosis (CDMS), Epstein-Barr nuclear antigen 1 (EBNA-1), oligoclonal bands (OCBs), Predictive value of tests, Cohort, Disease Progression, Female, Cohort study, Adult, medicine.medical_specialty, Multiple Sclerosis, clinic study, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Vitamin D and neurology, Humans, Survival analysis, 030304 developmental biology, business.industry, Multiple sclerosis, Oligoclonal Bands, Endonucleases, medicine.disease, Survival Analysis, chemistry, Immunoglobulin G, [ SHS.ANTHRO-BIO ] Humanities and Social Sciences/Biological anthropology, Neurology (clinical), business, Cotinine, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
Published: 2015
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33. The use of echocardiography in acute cardiovascular care: recommendations of the European Association of Cardiovascular Imaging and the Acute Cardiovascular Care Association

Author: Arnaud Ancion, Bernard Cosyns, Luna Gargani, Nuno Cardim, Susanna Price, Christian Hassager, Aleksandar Neskovic, Maurizio Galderisi, Gilbert Habib, Raluca Elena Dulgheru, Erwan Donal, Agnes Pasquet, José Luis Zamorano, Kristina H. Haugaa, Thor Edvardsen, Héctor Bueno, Patrizio Lancellotti, Frank A. Flachskampf, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Department of Cardiology, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Naples Federico II = Università degli studi di Napoli Federico II, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General Universitario 'Gregorio Marañón' [Madrid], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Groupe Interdisciplinaire de Génoprotéomique Appliquée ( GIGA-Research ), Université de Liège-Faculté de médecine vétérinaire, Università degli studi di Napoli Federico II, Service de cardiologie et maladies vasculaires, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Clinical sciences, Cardio-vascular diseases, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Jonchère, Laurent, Lancellotti, Patrizio, Price, Susanna, Edvardsen, Thor, Cosyns, Bernard, Neskovic, Aleksandar N, Dulgheru, Raluca, Flachskampf, Frank A, Hassager, Christian, Pasquet, Agne, Gargani, Luna, Galderisi, Maurizio, Cardim, Nuno, Haugaa, Kristina H, Ancion, Arnaud, Zamorano, Jose Lui, Donal, Erwan, Bueno, Héctor, Habib, Gilbert, and Cardiology
Subjects: medicine.medical_specialty, Critical Care, Heart Diseases, Critical Illness, Cardiovascular care, Disease, Recommendations, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Acute cardiovascular care, 03 medical and health sciences, critically ill patient, 0302 clinical medicine, Critically ill patients, Cardiac tamponade, medicine.artery, Ascending aorta, Endocarditis, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Myocardial infarction, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, 030212 general & internal medicine, Intensive care medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, valvular heart disease, General Medicine, medicine.disease, 3. Good health, Europe, Cardiovascular Diseases, Echocardiography, Heart failure, Acute Disease, cardiovascular system, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Clinical Competence, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Echocardiography is one of the most powerful diagnostic and monitoring tools available to the modern emergency/ critical care practitioner. Currently, there is a lack of specific European Association of Cardiovascular Imaging/Acute Cardiovascular Care Association recommendations for the use of echocardiography in acute cardiovascular care. In this document, we describe the practical applications of echocardiography in patients with acute cardiac conditions, in particular with acute chest pain, acute heart failure, suspected cardiac tamponade, complications of myocardial infarction, acute valvular heart disease including endocarditis, acute disease of the ascending aorta and post-intervention complications. Specific issues regarding echocardiography in other acute cardiovascular care scenarios are also described
Published: 2014
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34. Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy: Analysis of the Long-Term Follow-Up of Remodeling in Systolic Left Ventricular Dysfunction (REVERSE)

Author: Jeff Cerkvenik, Jay Dinerman, Jean-Claude Daubert, Christian Hassager, J. Harrison Hudnall, Michael R. Gold, Cecilia Linde, William T. Abraham, Division of cardiology, Medical University of South Carolina [Charleston] (MUSC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Cardiovascular Medicine and the Davis Heart and Lung Research Institute, Ohio State University [Columbus] (OSU), Department of Cardiology, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Cardiology, Karolinska University Hospital, Karolinska Institutet [Stockholm], The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, implantable, genetic structures, medicine.medical_treatment, Cardiac resynchronization therapy, cardiac resynchronization therapy, heart failure, 030204 cardiovascular system & hematology, law.invention, Ventricular Dysfunction, Left, 03 medical and health sciences, QRS complex, 0302 clinical medicine, Randomized controlled trial, Quality of life, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, law, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030212 general & internal medicine, cardiovascular diseases, Ventricular remodeling, Aged, Ventricular Remodeling, business.industry, Hazard ratio, Middle Aged, medicine.disease, equipment and supplies, Combined Modality Therapy, Defibrillators, Implantable, 3. Good health, Clinical trial, Heart failure, Multivariate Analysis, Quality of Life, Cardiology, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Follow-Up Studies, circulatory and respiratory physiology
Abstract: Background— Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT-D). However, there are little data comparing mortality between these 2 device types. Methods and Results— REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) was a multicenter, randomized trial of CRT among patients with mild heart failure. Long-term annual follow-up for 5 years was preplanned. The present analysis was confined to the 419 patients who were randomized to active CRT group. CRT-pacemakers or CRT-D devices were implanted based on national guidelines at the time of enrollment, with 74 patients receiving CRT pacemaker devices and the remaining 345 patients receiving CRT-D devices. After 12 months of CRT, changes in the clinical composite score, left ventricular end systolic volume index, 6-minute walk time, and quality of life indices were similar between CRT pacemaker and CRT-D patients. However, long-term follow-up showed lower morality in the CRT-D group. Specifically, multivariable analysis showed that CRT-D (hazard ratio, 0.35; P =0.003) was a strong independent predictor of survival. Female sex, longer unpaced QRS duration, and smaller baseline left ventricular end systolic volume index also were also associated with better survival. Conclusions— REVERSE demonstrated that the addition of implantable cardioverter-defibrillator therapy to CRT is associated with improved long-term survival compared with CRT pacing alone in mild heart failure. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique Identifier: NCT00271154.
Published: 2013
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35. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Author: Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. Madden, Jens Treutlein, Aarno Palotie, Robert Freedman, Sandra Meier, Bru Cormand, Nicholas J. Schork, Michele T. Pato, John R. Kelsoe, Vanessa Hus, Frans G. Zitman, Josephine Elia, David St Clair, Roel A. Ophoff, Peter McGuffin, Jonathan Pimm, Jonathan L. Haines, Wiepke Cahn, Matthew Flickinger, Steven P. Hamilton, Michael John Owen, Paul D. Shilling, Jeremy M. Silverman, David Craig, Mark J. Daly, Sarah E. Medland, Robert D. Oades, Marion Leboyer, Alan R. Sanders, Vihra Milanova, Chunyu Liu, Jobst Meyer, Dorret I. Boomsma, Evaristus A. Nwulia, Thomas B. Barrett, Jennifer L. Moran, Donald W. Black, Mònica Bayés, Witte J.G. Hoogendijk, Franziska Degenhardt, Benjamin M. Neale, Daniel L. Koller, Carlos N. Pato, Nicholas John Craddock, Richard Bruggeman, Enda M. Byrne, Edward G. Jones, Eco J. C. de Geus, Stéphane Jamain, Jubao Duan, Anne Farmer, Astrid M. Vicente, Grant W. Montgomery, Thomas Werge, Cathryn M. Lewis, Srdjan Djurovic, Phil Lee, Richard Anney, Elaine K. Green, Wade H. Berrettini, Peter P. Zandi, Susan L. Slager, Stephanie H. Witt, Ian W. Craig, Lisa Jones, Sven Cichon, Bruno Etain, Mark Lathrop, Hilary Coon, Robert C. Thompson, Lena Backlund, A. Jeremy Willsey, Andres Ingason, Christine M. Freitag, Sandra K. Loo, Guiomar Oliveira, Line Olsen, Edwin J. C. G. van den Oord, Geraldine Dawson, Joseph A. Sergeant, David A. Collier, Farooq Amin, Srinivasa Thirumalai, Manfred Uhr, Joseph Piven, Andrew M. McIntosh, Anjali K. Henders, Urban Ösby, Klaus-Peter Lesch, Tiffany A. Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - 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Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Ecology and Evolutionary Biology, Insitute of Neuroscience and Physiology, University of Gothenburg (GU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Developmental Brain and Behaviour Unit, University of Southampton, Division of Psychiatric Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Statistical Genetics Group, Department of Human Genetics, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry and Psychotherapy, Department of Mental Health, Johns Hopkins University and Hospital, W.M. Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology
Subjects: Netherlands Twin Register (NTR), Medizin, Inheritance Patterns, Social Sciences, AUTISM SPECTRUM DISORDERS, nosology, heritability, COMMON SNPS, 0302 clinical medicine, Crohn Disease, SCHIZOPHRENIA, Child, Psychiatric genetics, Genetics & Heredity, MAJOR DEPRESSIVE DISORDER, RISK, 0303 health sciences, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, 120 000 Neuronal Coherence, Mental Disorders, Variants, BIPOLAR DISORDER, ASSOCIATION, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], Psychiatric Disorders, CROHNS-DISEASE, 3. Good health, Schizophrenia, genetic association study, Medical genetics, Major depressive disorder, SNPs, Adult, medicine.medical_specialty, genetic etiology, medical genetics, DEFICIT HYPERACTIVITY DISORDER, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Heritability, Genetic Heterogeneity, 03 medical and health sciences, Prevalence of mental disorders, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Genome, Human, Genetic heterogeneity, medicine.disease, schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Published: 2013
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36. Reduction of Sr2MnO4 investigated by high temperature in situ neutron powder diffraction under hydrogen flow

Author: Thibault Broux, Colin Greaves, Serge Paofai, Thomas C. Hansen, Mona Bahout, Olivier Hernandez, Florent Tonus, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Phase transition, Chemistry, Reducing atmosphere, Analytical chemistry, 02 engineering and technology, Activation energy, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 7. Clean energy, 01 natural sciences, Isothermal process, 0104 chemical sciences, Inorganic Chemistry, Tetragonal crystal system, Reaction rate constant, Phase (matter), Physical and Theoretical Chemistry, 0210 nano-technology, Monoclinic crystal system
Abstract: International audience; This experiment emphasizes the first example of two-phase sequential Rietveld refinements throughout a solid/gas chemical reaction monitored by Neutron Powder Diffraction (NPD) at high temperature. The reduction of the n = 1 Ruddlesden-Popper (RP) oxide Sr(2)MnO(4) heated under a flow of 5% H(2)-He has been investigated throughout two heating/cooling cycles involving isothermal heating at 500 and 550 °C. Oxygen loss proceeds above T ∼ 470 °C and increases with temperature and time. When the oxygen deintercalated from the "MnO(2)" equatorial layers of the structure results in the Sr(2)MnO(3.69(2)) composition, the RP phase undergoes a first order I4/mmm → P2(1)/c, tetragonal to monoclinic phase transition as observed from time-resolved in situ NPD. The phase transition proceeds at 500 °C but is incomplete; the weight ratio of the P2(1)/c phase reaches ∼41% after 130 min of isothermal heating. The fraction of the monoclinic phase increases with increasing temperature and the phase transition is complete after 80 min of isothermal heating at 550 °C. The composition of the reduced material refined to Sr(2)MnO(3.55(1)) and does not vary on extended heating at 550 °C and subsequent cooling to room temperature (RT). The symmetry of Sr(2)MnO(3.55(1)) is monoclinic at 550 °C and therefore consistent with the RT structure determined previously for the Sr(2)MnO(3.64) composition obtained from ex situ reduction. Consequently, the stresses due to phase changes on heating/cooling in reducing atmosphere may be minimized. The rate constants for the reduction of Sr(2)MnO(4.00) determined from the evolution of weight ratio of the tetragonal and monoclinic phase in the time-resolved isothermal NPD data collected on the isotherms at 500 and 550 °C are k(500) = 0.110 × 10(-2) and k(550) = 0.516 × 10(-2) min(-1) giving an activation energy of ∼163 kJ mol(-1) for the oxygen deintercalation reaction.
Published: 2013
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37. Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure

Author: Tracy L. Bergemann, Claude Daubert, Cecilia Linde, William T. Abraham, Michael R. Gold, Stefano Ghio, Martin St. John Sutton, Christian Hassager, John M. Herre, Department of Cardiology, Karolinska University Hospital, Karolinska Institutet [Stockholm], CHU Pontchaillou [Rennes], Division of Cardiovascular Medicine and the Davis Heart and Lung Research Institute, Ohio State University [Columbus] (OSU), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Department of Cardiology, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Sentara Norfolk General Hospital, Medtronic, Division of cardiology, Medical University of South Carolina [Charleston] (MUSC), University of Pennsylvania, and Università degli Studi di Pavia = University of Pavia (UNIPV)
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Cardiac resynchronization therapy, cardiac resynchronization therapy, heart failure, 030204 cardiovascular system & hematology, Severity of Illness Index, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, cardiovascular diseases, Ventricular remodeling, Survival rate, End-systolic volume, Ejection fraction, Ventricular Remodeling, business.industry, Hazard ratio, Stroke Volume, Stroke volume, Middle Aged, medicine.disease, Prognosis, mortality, Europe, Survival Rate, Heart failure, North America, Cardiology, cardiovascular system, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, circulatory and respiratory physiology
Abstract: Background— Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction (LVEF) >30% were included. Methods and Results— The results of patients with baseline EF >30% (n=177) and those with EF ≤30% (n=431), as determined by a blinded core laboratory, were compared. In the LVEF >30% subgroup, there was a trend for improvement in the clinical composite response with CRT ON versus CRT OFF ( P =0.06) and significant reductions in LV end systolic volume index (−6.7±21.1 versus 2.1±17.6 mL/m 2 ; P =0.01) and LV mass (−20.6±50.5 versus 5.0±42.4 g; P =0.04) after 12 months. The time to death or first HF hospitalization was significantly prolonged with CRT (hazard ratio, 0.26; P =0.012). In the LVEF P =0.02), reverse remodeling parameters, and time to death or first HF hospitalization (hazard ratio, 0.58; P =0.047) were observed. After adjusting for important covariates, the CRT ON assignment remained independently associated with improved time to death or first HF hospitalization (hazard ratio, 0.54; P =0.035), whereas there was no significant interaction with LVEF. Conclusions— Among subjects with mild HF, QRS prolongation, and LVEF >30%, CRT produced reverse remodeling and similar clinical benefit compared with subjects with more severe LV systolic dysfunction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00271154.
Published: 2013
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38. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author: Antoniou, Antonis C., Kuchenbaecker, Karoline B., Penny, Soucy, Jonathan, Beesley, Xiaoqing, Chen, Lesley, Mcguffog, Andrew, Lee, Daniel, Barrowdale, Sue, Healey, Sinilnikova, Olga M., Caligo, Maria A., Niklas, Loman, Katja, Harbst, Annika, Lindblom, Brita, Arver, Richard, Rosenquist, Per, Karlsson, Kate, Nathanson, Susan, Domchek, Tim, Rebbeck, Anna, Jakubowska, Jan, Lubinski, Katarzyna, Jaworska, Katarzyna, Durda, Zlowocka Perlowska, E., Elzbieta Złowowcka Perłowska, Ana, Osorio, Mercedes, Duran, Raquel, Andres, Javier, Benitez, Ute, Hamann, Hogervorst, Frans B., Van, A., Van Os, Theo A., Senno, Verhoef, Meijers Heijboer, Hanne E. J., Juul, Wijnen, Gomez Garcia, Encarna B., Ligtenberg, Marjolijn J., Mieke, Kriege, Margriet Collee, J., Margreet Gem Ausems, Oosterwijk, Jan C., Susan, Peock, Debra, Frost, Ellis, Steve D., Radka, Platte, Elena, Fineberg, Gareth Evans, D., Fiona, Lalloo, Chris, Jacobs, Ros, Eeles, Julian, Adlard, Rosemarie, Davidson, Trevor, Cole, Jackie, Cook, Joan, Paterson, Fiona, Douglas, Carole, Brewer, Shirley, Hodgson, Morrison, Patrick J., Lisa, Walker, Rogers, Mark T., Alan, Donaldson, Huw, Dorkins, Godwin, Andrew K., Betsy, Bove, Dominique Stoppa Lyonnet, Claude, Houdayer, Bruno, Buecher, De Pauw, A., Antoine Pauw, D. E., Sylvie, Mazoyer, Alain, Calender, Melanie, Leone, Brigitte Bressac De Paillerets, Olivier, Caron, Hagay, Sobol, Marc, Frenay, Fabienne, Prieur, Sandra, Ferrer, Isabelle, Mortemousque, Saundra, Buys, Mary, Daly, Alexander, Miron, Terry, Mb, Terry, Mu, Mary, Terry, Hopper, John L., John, Em, Esther, John M., Melissa, Southey, David, Goldgar, Singer, Christian F., Anneliese Fink Retter, Muy Kheng Tea, Geschwantler Kaulich, D., Daphne, Kaulich, Hansen, Thomas V. O., Nielsen, Finn C., Barkardottir, Rosa B., Mia, Gaudet, Tomas, Kirchhoff, Joseph, V., Joseph, Vijai, Ana Dutra Clarke, Kenneth, Offit, Marion, Piedmonte, Judy, Kirk, David, Cohn, Jean, Hurteau, John, Byron, James, Fiorica, Toland, Amanda E., Marco, Montagna, Cristina, Oliani, Evgeny, Imyanitov, Claudine, Isaacs, Laima, Tihomirova, Ignacio, Blanco, Conxi, Lazaro, Alex, Teule, Del Valle, J., Gayther, Simon A., Kunle, Odunsi, Jenny, Gross, Karlan, Beth Y., Edith, Olah, Soo Hwang Teo, Ganz, Patricia A., Beattie, Mary S., Dorfling, Cecelia M., Jansen Van Rensburg, E., Elizabeth Van Rensburg, Orland, Diez, Ava, Kwong, Schmutzler, Rita K., Barbara, Wappenschmidt, Christoph, Engel, Alfons, Meindl, Nina, Ditsch, Norbert, Arnold, Simone, Heidemann, Dieter, Niederacher, Sabine Preisler Adams, Dorothea, Gadzicki, Raymonda Varon Mateeva, Helmut, Deissler, Andrea, Gehrig, Christian, Sutter, Karin, Kast, Britta, Fiebig, Dieter, Schafer, Trinidad, Caldes, Miguel De La Hoya, Heli, Nevanlinna, Muranen, Taru A., Bernard, Lesperance, Spurdle, Amanda B., Neuhausen, Susan L., Ding, Yuan C., Xianshu, Wang, Zachary, Fredericksen, Pankratz, Vernon S., Lindor, Noralane M., Paolo, Peterlongo, Siranoush, Manoukian, Bernard, Peissel, Daniela, Zaffaroni, Bernardo, Bonanni, Loris, Bernard, Riccardo, Dolcetti, Laura, Papi, Ottini, Laura, Paolo, Radice, Greene, Mark H., Loud, Jennifer T., Andrulis, Irene L., Hilmi, Ozcelik, Anna, Mulligan, Gord, Glendon, Mads, Thomassen, Anne Marie Gerdes, Jensen, Uffe B., Anne Bine Skytte, Kruse, Torben A., Georgia Chenevix Trench, Couch, Fergus J., Jacques, Simard, Easton, Douglas F., Swedish Breast, Cancer Study S. B., Facility, Research H., Study, E., Collaborators, Study G., Investigators, K., Swe Brca Cimba, Embrace, Hebon, Study Gemo Collaborators, Kconfab, Investigators, BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Genetics and Population Health Division, Queensland Institute of Medical Research, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Oncology, Lund University Hospital, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Department of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Sahlgrenska University Hospital [Gothenburg], Abramson Cancer Center, University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Postgraduate School of Molecular Medicine, Warsaw Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Institute of Biology and Molecular Genetics, Universidad de Valladolid [Valladolid] (UVa), Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Family Cancer Clinic, Netherlands Cancer Institute, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), VU Medical Center, Department of Clinical Genetics and GROM, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University [Nijmegen], Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Department of Genetics, VU University Medical Center [Amsterdam], Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Oncogenetics Team, The Institute of Cancer Research-Royal Marsden NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Addenbrookes Hospital, Institute of Human Genetics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Devon & Exeter Hospital, Medical Genetics Unit, University College of London [London] (UCL), Northern Ireland Regional Genetics Centre, Belfast Health and Social Care Trust, Department of Medical Genetics, Queen's University [Belfast] (QUB), Oxford Regional Genetics Service, Churchill Hospital Oxford Centre for Haematology, All Wales Medical Genetics Services, Singleton Hospital, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], Clinical Molecular Genetics Laboratory, Fox Chase Cancer Center, Service de Génétique Oncologique, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique, Institut Gustave Roussy (IGR), Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation de génétique, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Laboratoire de Génétique Chromosomique, CH Chambéry, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Internal Medicine, Huntsman Cancer Institute, Division of Population Science, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), Department of Epidemiology, Columbia University [New York], Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Cancer Prevention Institute of California, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Pathology, University of Iceland [Reykjavik]-Landspitali - University Hospital, Epidemiology Research Program, American Cancer Society, Department of Environmental Medicine, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Australia New Zealand (ANZGOG), Westmead Hospital [Sydney], Ohio State University [Columbus] (OSU), Evanston CCOP - NorthShore University Health System, University of Chicago, Southern Pines Women's Health Center, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Sarasota Memorial Healthcare, Tufts Medical Center, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, U.O.C. di Oncologia, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University [Washington] (GU), Latvian Biomedical Research and Study Centre [Rīga], Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Molecular Diagnostic Unit, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Department of Gynecologic Oncology, Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Jonsson Comprehensive Cancer Center at UCLA, Jonsson Comprehensive Cancer Center, UCSF Cancer Risk Program, University of California (UC), Departments of Medicine, Epidemiology, and Biostatistics, UCSF, Cancer Genetics Laboratory, University of Pretoria [South Africa], Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, Julius-Maximilians-Universität Würzburg (JMU)-Centre of Familial Breast and Ovarian Cancer, Heidelberg University Hospital [Heidelberg], University Hospital Carl Gustav Carus, Universität Regensburg (UR), University Hospital Frankfurt a.M., Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Hemato-oncology service, Hôpital du Sacré-Coeur de Montréal, Department of Population Sciences, Beckman Research Institute of City of Hope, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Clinical Genetics Branch, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Ontario Cancer Genetics Network, Cancer Care Ontario, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Skejby Hospital, Department of Laboratory Medicine and Pathology and Health Sciences Research, This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics, on behalf of CIMBA, SWE-BRCA, HEBON, EMBRACE, GEMO Study Collaborators and kConFab Investigators, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), Pediatric Surgery, Neurology, Medical Oncology, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Roswell Park Cancer Institute [Buffalo] (RPCI), Universität Leipzig, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], Pomeranian Medical University-International Hereditary Cancer Centre, Radboud university [Nijmegen], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Georgetown University, University of California, Westfälische Wilhelms-Universität Münster (WWU), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Centre of Familial Breast and Ovarian Cancer, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], RS: GROW - School for Oncology and Reproduction, Genetica & Celbiologie, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Human Genetics, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human genetics, and CCA - Oncogenesis
Subjects: Oncology, Medicin och hälsovetenskap, Estrogen receptor, Genome-wide association study, HORMONE-RELATED PROTEIN, Chromosomes, Human, Pair 9 - genetics, Medical and Health Sciences, 0302 clinical medicine, 610 Medical sciences Medicine, CDKN2A, Risk Factors, Genotype, INVESTIGATORS, Chromosomes, Human, Pair 12 - genetics, skin and connective tissue diseases, MAMMOGRAPHIC DENSITY, Medicine(all), 0303 health sciences, BRCA1 Protein, Middle Aged, BRCA2 Protein, 3. Good health, DNA-Binding Proteins, Hereditary Breast and Ovarian Cancer Syndrome - genetics, 030220 oncology & carcinogenesis, Hereditary Breast and Ovarian Cancer Syndrome, TUMOR SUBTYPES, Female, Chromosomes, Human, Pair 9, Research Article, Adult, Breast cancer, BRCA1, BRCA2, medicine.medical_specialty, Heterozygote, SUSCEPTIBILITY LOCI, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, OVARIAN-CANCER, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, ddc:610, GENOME-WIDE ASSOCIATION, ddc:611, Genetic Association Studies, 030304 developmental biology, Aged, Gynecology, Chromosomes, Human, Pair 12, CONSORTIUM, BRCA1 Protein - genetics, ALLELES, medicine.disease, BRCA2 Protein - genetics, Cancer and Oncology, GENETIC MODIFIERS, Ovarian cancer, Transcription Factors
Abstract: INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). METHODS: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. RESULTS: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). CONCLUSIONS: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers., published_or_final_version
Published: 2012
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39. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Author: Mulligan, Anna Marie, Couch, Fergus J, Barrowdale, Daniel, Domchek, Susan M, Eccles, Diana, Nevanlinna, Heli, Ramus, Susan J, Robson, Mark, Sherman, Mark, Spurdle, Amanda B, Wappenschmidt, Barbara, Lee, Andrew, McGuffog, Lesley, Healey, Sue, Sinilnikova, Olga M, Janavicius, Ramunas, Hansen, Thomas vO, Nielsen, Finn C, Ejlertsen, Bent, Osorio, Ana, Muñoz-Repeto, Iván, Durán, Mercedes, Godino, Javier, Pertesi, Maroulio, Benítez, Javier, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Cattaneo, Elisa, Bonanni, Bernardo, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Ottini, Laura, Savarese, Antonella, Bernard, Loris, Radice, Paolo, Hamann, Ute, Verheus, Martijn, Meijers-Heijboer, Hanne EJ, Wijnen, Juul, Gómez García, Encarna B, Nelen, Marcel R, Kets, C Marleen, Seynaeve, Caroline, Tilanus-Linthorst, Madeleine MA, van der Luijt, Rob B, van Os, Theo, Rookus, Matti, Frost, Debra, Jones, J Louise, Evans, D Gareth, Lalloo, Fiona, Eeles, Ros, Izatt, Louise, Adlard, Julian, Davidson, Rosemarie, Cook, Jackie, Donaldson, Alan, Dorkins, Huw, Gregory, Helen, Eason, Jacqueline, Houghton, Catherine, Barwell, Julian, Side, Lucy E, McCann, Emma, Murray, Alex, Peock, Susan, Godwin, Andrew K, Schmutzler, Rita K, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ruehl, Ina, Arnold, Norbert, Niederacher, Dieter, Sutter, Christian, Deissler, Helmut, Gadzicki, Dorothea, Kast, Karin, Preisler-Adams, Sabine, Varon-Mateeva, Raymonda, Schoenbuchner, Ines, Fiebig, Britta, Heinritz, Wolfram, Schäfer, Dieter, Gevensleben, Heidrun, Caux-Moncoutier, Virginie, Fassy-Colcombet, Marion, Cornelis, François, Mazoyer, Sylvie, Léoné, Mélanie, Boutry-Kryza, Nadia, Hardouin, Agnès, Berthet, Pascaline, Muller, Danièle, Fricker, Jean-Pierre, Mortemousque, Isabelle, Pujol, Pascal, Coupier, Isabelle, Lebrun, Marine, Kientz, Caroline, Longy, Michel, Sevenet, Nicolas, Stoppa-Lyonnet, Dominique, Isaacs, Claudine, Caldes, Trinidad, de la Hoya, Miguel, Heikkinen, Tuomas, Aittomäki, Kristiina, Blanco, Ignacio, Lazaro, Conxi, Barkardottir, Rosa B, Soucy, Penny, Dumont, Martine, Simard, Jacques, Montagna, Marco, Tognazzo, Silvia, D'Andrea, Emma, Fox, Stephen, Yan, Max, Rebbeck, Tim, Olopade, Olufunmilayo, Weitzel, Jeffrey N, Lynch, Henry T, Ganz, Patricia A, Tomlinson, Gail E, Wang, Xianshu, Fredericksen, Zachary, Pankratz, Vernon S, Lindor, Noralane M, Szabo, Csilla, Offit, Kenneth, Sakr, Rita, Gaudet, Mia, Bhatia, Jasmine, Kauff, Noah, Singer, Christian F, Tea, Muy-Kheng, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Mai, Phuong L, Greene, Mark H, Imyanitov, Evgeny, O'Malley, Frances P, Ozcelik, Hilmi, Glendon, Gordon, Toland, Amanda E, Gerdes, Anne-Marie, Thomassen, Mads, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Soller, Maria, Henriksson, Karin, Wachenfeldt, von Anna, Arver, Brita, Stenmark-Askmalm, Marie, Karlsson, Per, Ding, Yuan Chun, Neuhausen, Susan L, Beattie, Mary, Pharoah, Paul DP, Moysich, Kirsten B, Nathanson, Katherine L, Karlan, Beth Y, Gross, Jenny, John, Esther M, Daly, Mary B, Buys, Saundra M, Southey, Melissa C, Hopper, John L, Terry, Mary Beth, Chung, Wendy, Miron, Alexander F, Goldgar, David, Chenevix-Trench, Georgia, Easton, Douglas F, Andrulis, Irene L, Antoniou, Antonis C, Breast Cancer Family Registry, EMBRACE, GEMO Study Collaborators, HEBON, kConFab Investigators, Ontario Cancer Genetics Network, SWE-BRCA, CIMBA, Pediatric Surgery, Neurology, Medical Oncology, Surgery, Clinical Genetics, Department of Laboratory Medicine, St Michael's Hospital-Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Laboratory Medicine and Pathology, Mayo Clinic, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Medicine, University of Pennsylvania [Philadelphia]-Abramson Cancer Center, Faculty of Medicine, University of Southampton-University Hospital Southampton, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Preventive Medicine, University of Southern California (USC)-Keck School of Medicine [Los Angeles], University of Southern California (USC), Memorial Sloane Kettering Cancer Center [New York]-Weill Medical College of Cornell University [New York], Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Queensland Institute of Medical Research, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Oncology, Human Genetics Group, Spanish National Cancer Research Centre-Spain and the Spanish Network on Rare Diseases, Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Instituto de investigación sanitaria de Aragón (IIS), Hospital clinico Universitario 'Lozano Blesa', Molecular Diagnostics Laboratory, National Center for Scientific Research 'Demokritos' (NCSR)-IRRP, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Fondazione Istituto FIRC di Oncologia Molecolare, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Unit of Medical Genetics, Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, Department of Genetics, Biology and Biochemistry, University of Turin, Medical Genetics Unit, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Division of Medical Oncology, Regina Elena Cancer Institute, Department of Experimental Oncology, Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia. Milan, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, Netherlands Cancer Institute, Department of Clinical Genetics, VU Medical Center, Department of Human Genetics and Department of Clinical Genetics, Leiden University Medical Center (LUMC), Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Medical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Surgical Oncology, Department of Clinical Molecular Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Barts Cancer Institute, Queen Mary University of London (QMUL), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Clinical Genetics Department, St Michael's Hospital, North West Thames Regional Genetics Service, Kennedy-Galton Centre, North of Scotland Regional Genetics Service, University of Aberdeen-NHS Grampian, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Cheshire and Merseyside Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Leicestershire Clinical Genetics Service, University Hospitals Leicester, North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children [London] (GOSH), All Wales Medical Genetics Services, Singleton Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Lawrence], Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Klinikum Rechts der Isar, Ludwig-Maximillians University, University Hospital of Schleswig-Holstein (UKSH), University Hospital Düsseldorf, Institute of Human Genetics, Heidelberg University Hospital [Heidelberg], Universitätsklinikum Ulm - University Hospital of Ulm, Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), University Hospital Carl Gustav Carus, Westfälische Wilhelms-Universität Münster (WWU), Campus Virchov Klinikum, Department of Medical Genetic, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Universität Regensburg (UR), University Hospital, Frankfurt, Breakthrough Breast Cancer Research Centre, Institute of cancer research, Service de Génétique Oncologique, Institut Curie [Paris], Service de génétique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, CHU Clermont-Ferrand, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Unité d'oncogénétique, CRLCC Paul Strauss, Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lombardi Comprehensive Cancer Center, Georgetown University, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Hereditary Cancer Program, Institut Català d'Oncologia-Hospital Duran i Reynals, Department of Pathology, Landspitali University Hospital, University of Iceland [Reykjavik], Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Research Chair in Oncogenetics, Université Laval [Québec] (ULaval), Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Oncology and Surgical Sciences, Universita degli Studi di Padova, Peter MacCallum Cancer Centre, Peter MacCallum Cancer Center, Department of Anatomical Pathology, Prince of Wales Hospital, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Chicago, City of Hope Comprehensive Cancer Center and Department of Population Sciences, Beckman Research Institute, Departments of Medicine, and Preventive Medicine and Public Health, Creighton University, Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California-University of California, Department of Internal Medicine, The University of Texas Health Science Center at Houston (UTHealth)-Harold C. Simmons Comprehensive Cancer Center, Department of Pediatrics, The University of Texas Health Science Center at Houston (UTHealth), Department of Medical Genetics, University of Delaware [Newark], Epidemiology Research Program, American Cancer Society, Department of Obstetrics/Gynaecology and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Departments of Molecular VirologyImmunology and Medical Genetics and Internal Medicine, Ohio State University [Columbus] (OSU), University of Copenhagen = Københavns Universitet (KU)-Rigshospital, Odense University Hospital, Aarhus University Hospital, Vejle Hospital, Section of Genetic Oncology, University of Pisa - Università di Pisa, Lund University Hospital, Oncological Centre, Karolinska University Hospital [Stockholm], Department of Clinical and Experimental Medicine, Linköping University (LIU), Sahlgrenska University Hospital [Gothenburg], Department of Population Sciences, Beckman Research Institute of the City of Hope, UCSF Cancer Risk Program and Departments of Medicine and Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention Institute of California, Fox Chase Cancer Center, Department of Oncological Sciences, University of Utah-Huntsman Cancer Institute, Genetic Epidemiology Laboratory, University of Melbourne, Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Columbia University [New York], Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Dermatology, University of Utah School of Medicine [Salt Lake City], This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175). ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow., for Breast Cancer Family Registry, for EMBRACE, for Ontario Cancer Genetics Network, for SWE-BRCA, for CIMBA, European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), BMC, Ed., Collaborative Oncological Gene-environment Study - COGS - - EC:FP7:HEALTH2009-05-01 - 2014-01-31 - 223175 - VALID, University of Pennsylvania-Abramson Cancer Center, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Firenze = University of Florence (UniFI), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Consortium for Genomics Technology (Cogentech)-Istituto Europeo di Oncologia [Milano] (IEO), University of Kansas Medical Center [Kansas City, KS, USA], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Julius-Maximilians-Universität Würzburg (JMU)-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Georgetown University [Washington] (GU), Università degli Studi di Padova = University of Padua (Unipd), University of Pennsylvania-University of Pennsylvania, University of California (UC)-University of California (UC), Rigshospital-University of Copenhagen = Københavns Universitet (UCPH), Vejle Hospital [Danemark], University of California [San Francisco] (UC San Francisco), Lee, Andrew [0000-0003-0677-0252], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, University of Cambridge [UK] ( CAM ), University of Southampton [Southampton]-University Hospital Southampton, University of Southern California ( USC ) -Keck School of Medicine [Los Angeles], Memorial Sloan-Kettering Cancer Center-Weill Medical College of Cornell University [New York], National Cancer Institute ( NIH ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de investigación sanitaria de Aragón ( IIS ), National Center for Scientific Research 'Demokritos' ( NCSR ) -IRRP, IFOM, University of Florence, Università degli Studi di Roma 'La Sapienza' [Rome], Deutsches Krebsforschungszentrum ( DKFZ ), Erasmus University Medical Center-Family Cancer Clinic, University Medical Center Utrecht, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Queen Mary University of London ( QMUL ), Sheffield Children's Hospital, University Hospitals of Leicester, Great Ormond Street Hospital for Children [London] ( GOSH ), University of Kansas Medical Center, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, University Hospital Ulm, Hannover Medical School [Hannover] ( MHH ), Westfälische Wilhelms-Universität Münster ( WWU ), University Wurzburg-Institute of Human Genetics-Centre of Familial Breast and Ovarian Cancer, University Regensburg, INSTITUT CURIE, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire Clermont-Ferrand, Centre François Baclesse, Hôpital Bretonneau-CHRU Tours, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Validation et identification de nouvelles cibles en oncologie ( VINCO ), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laval University [Québec], University of Padua and Istituto Oncologico Veneto IOV - IRCCS, University of Pennsylvania Perelman School of Medicine, University of California at Los Angeles [Los Angeles] ( UCLA ), University of Texas at Houston [Houston] ( UTHealth ) -Harold C. Simmons Comprehensive Cancer Center, University of Texas Health Science, Medical University of Vienna, Mount Sinai Hospital, The Ohio State University Comprehensive Cancer Center, University of Copenhagen ( KU ) -Rigshospital, University of Pisa [Pisa], Linköping University ( LIU ), Sahlgrenska University Hospital, the Beckman Research Institute of the City of Hope, University of California [San Francisco] ( UCSF ), European Project : 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS ( 2009 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2, Human Genetics, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Universität Leipzig, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Roswell Park Cancer Institute [Buffalo] (RPCI)
Subjects: Risk, Heterozygote, endocrine system diseases, Population, Genes, BRCA2, Genes, BRCA1, Social Sciences, Estrogen receptor, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 610 Medical sciences Medicine, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Genotype, medicine, Humans, Genetic Predisposition to Disease, education, skin and connective tissue diseases, Estrogen Receptor Status, Alleles, 030304 developmental biology, Medicine(all), 0303 health sciences, education.field_of_study, Samhällsvetenskap, medicine.disease, 3. Good health, TOX3, Receptors, Estrogen, Cancer and Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Ovarian cancer, Receptors, Progesterone, Research Article
Abstract: [Introduction]: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. [Methods]: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. [Results]: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. [Conclusions]: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.
Published: 2011
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40. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Antoniou, A. C., Kartsonaki, C., Sinilnikova, O. M., Soucy, P., Mcguffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, Giuseppe, Laura Putignano, A., Varesco, L., Radice, P., Mai, P. L., Greene, M. H., Andrulis, I. L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A. M., Kruse, T. A., Jensen, U. B., Cruger, D. G., Caligo, M. A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K. L., Domchek, S. M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Cajal, T. R., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F. B., Rookus, M. A., Hooning, M. J., Nelen, M. R., Van Der Luijt, R. B., Van Os, T. A. M., Van Asperen, C. J., Devilee, P., Meijers Heijboer, H. E. J., Garcia, E. B. G., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D. G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K. R., Cook, J., Douglas, F., Paterson, J., John Kennedy, M., Miedzybrodzka, Z., Godwin, A., Stoppa Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., Pujol, P., Coupier, I., Frenay, M., Hopper, J. L., Daly, M. B., Terry, M. B., John, E. M., Buys, S. S., Yassin, Y., Miron, A., Goldgar, D., Singer, C. F., Tea, M. K., Pfeiler, G., Catharina Dressler, A., Hansen, T. V. O., Jonson, L., Ejlertsen, B., Barkardottir, R. B., Kirchhoff, T., Offit, K., Piedmonte, M., Rodriguez, G., Small, L., Boggess, J., Blank, S., Basil, J., Azodi, M., Toland, A. E., Montagna, M., Tognazzo, S., Agata, S., Imyanitov, E., Janavicius, R., Lazaro, C., Blanco, I., Pharoah, P. D. P., Sucheston, L., Karlan, B. Y., Walsh, C. S., Olah, E., Bozsik, A., Teo, S. H., Seldon, J. L., Beattie, M. S., Van Rensburg, E. J., Sluiter, M. D., Diez, O., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ruehl, I., Varon Mateeva, R., Kast, K., Deissler, H., Niederacher, D., Arnold, N., Gadzicki, D., Schonbuchner, I., Caldes, T., De La Hoya, M., Nevanlinna, H., Aittomaki, K., Dumont, M., Chiquette, J., Tischkowitz, M., Chen, X. Q., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Fredericksen, Z., Wang, X., Pankratz, V. S., Couch, F., Simard, J., Easton, D. F., Chenevix Trench, G., Karlsson, P., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark Askmalm, M., Liedgren, S., Borg, A., Olsson, H., Kristoffersson, U., Jernstrom, H., Henriksson, K., Von Wachenfeldt, A., Liljegren, A., Barbany Bustinza, G., Rantala, J., Gronberg, H., Stattin, E. L., Emanuelsson, M., Brandell, R. R., Dahl, N., Hogervorst, F. B. L., Verhoef, S., Verheus, M., Veer, L. V., Van Leeuwen, F. E., Collee, M., Van Den Ouweland, A. M. W., Jager, A., Tilanus Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., Aalfs, C. M., Van Os, T. A., Gille, J. J. P., Waisfisz, Q., Gomez Garcia, E. B., Van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., Van Der Hout, A. H., Mourits, M. J., Vasen, H. F., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Mckeown, C., Hoffman, J., Donaldson, A., Downing, S., Taylor, A., Murray, A., Rogers, M. T., Mccann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Taylor, J., Side, L., Male, A., Berlin, C., Eason, J., Collier, R., Claber, O., Jobson, I., Walker, L., Mcleod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Lucassen, A., Crawford, G., Mcbride, D., Smalley, S., University of Groningen, Clinical Genetics, Medical Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Queensland Institute of Medical Research, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Consortium for Genomics Technology (Cogentech), Department of Genetics, Biology and Biochemistry, University of Turin, Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Department of Experimental Medicine, Università degli Studi di Roma 'La Sapienza' [Rome], Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Ontario Cancer Genetics Network, Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital ( MSH ), Department of Clinical Genetics, Odense University Hospital, Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Oncology, Lund University Hospital, Karolinska University Hospital [Stockholm], Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Radiation Sciences and Oncology, Umeå University, Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine-Abramson Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, International Hereditary Cancer Center, Pomeranian Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Department of Medical Oncology, Hospital Sant Pau, Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum ( DKFZ ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Wessex Clinical Genetics Service, Princess Anne Hospital, West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Addenbrookes Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), génétique, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Service d'onco-hématologie et génétique, CHU Grenoble, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Santé Publique, Hôpital René HUGUENIN (Saint-Cloud)-INSTITUT CURIE, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut de recherche en cancérologie de Montpellier ( IRCM - U896 Inserm - UM1 ), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Consultation d'oncogénétique, CRLCC Antoine Lacassagne, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] ( HMS ), Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Division of Special Gynecology, Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Rigshospitalet [Copenhagen], Department of Pathology, Landspitali-University Hospital, Department of Environmental Medicine, New York University School of Medicine-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Genetic Counselling Unit, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximillians University, Charite berlin, University Hospital Carl Gustav Carus, University Hospital Ulm, University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] ( MHH ), University of Würzburg, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Genetics, Portuguese Oncology Institute, Department of Medical Genetics, Mayo Clinic, Department of Laboratory Medicine and Pathology, Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Tel Aviv University (TAU), Uppsala University, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Abramson Cancer Center-Perelman School of Medicine, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Pomeranian Medical University [Szczecin] (PUM), Hospital de la Santa Creu i Sant Pau, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universiteit Leiden-Universiteit Leiden, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Newcastle Upon Tyne Hospitals NHS Foundation Trust, University of Kansas Medical Center [Kansas City, KS, USA], Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry [Rigshospitalet], Copenhagen University Hospital, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Roswell Park Cancer Institute [Buffalo] (RPCI), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Hannover Medical School [Hannover] (MHH), Julius-Maximilians-Universität Würzburg (JMU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Universität Leipzig [Leipzig], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), University of Florence (UNIFI), Mount Sinai Hospital (MSH), Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Hôpital René HUGUENIN (Saint-Cloud), Technical University of Munich (TUM), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Human genetics, CCA - Oncogenesis, Human Genetics, Klinische Genetica, and RS: GROW - School for Oncology and Reproduction
Subjects: MESH : BRCA2 Protein, MESH : Aged, Estrogen receptor, Genome-wide association study, MESH : Breast Neoplasms, VARIANTS, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Chromosomes, Human, Pair 6, MESH: BRCA2 Protein, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Genotype, CONFER SUSCEPTIBILITY, Chromosomes, Human, MESH : Female, skin and connective tissue diseases, Genetics (clinical), POPULATION, MESH: Heterozygote, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Adult, Middle Aged, MESH : Risk Factors, 3. Good health, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, MESH : Mutation, Adult, MESH : Heterozygote, Heterozygote, MESH: Mutation, MESH: Chromosomes, Human, Pair 6, MESH: Chromosomes, Human, Pair 1, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Breast Neoplasms, Biology, MESH: Chromosomes, Human, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genetics, medicine, LOCUS, SNP, Humans, MESH : Middle Aged, MESH : BRCA1 Protein, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, Molecular Biology, Alleles, MESH: BRCA1 Protein, 030304 developmental biology, Aged, BRCA2 Protein, MESH: Humans, 2Q35, MESH: Alleles, MESH : Humans, MESH: Adult, medicine.disease, MESH : Chromosomes, Human, ESTROGEN-RECEPTOR, Mutation, Cancer research, MESH : Genetic Predisposition to Disease, GENETIC MODIFIERS, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms
Abstract: Item does not contain fulltext Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
Published: 2011
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41. McArdle Disease: a clinical review

Author: Claudio Bruno, Denise Cassandrini, S Ball, Ros Quinlivan, John B Winer, Morten Duno, Michael R. Rose, Mark Roberts, M. James, John Buckley, Caroline Sewry, A Twist, John Vissing, RJAH Orthopaedic NHS Trust, University of Chester, Birmingham Children's Hospital, National University Hospital, Rigshospitalet, Copenhagen, ospedale gaslini, Hope Hospital, Salford, University Hospital Birmingham, and King‘s College London
Subjects: Male, Databases, Factual, Biopsy, MYOPATHY, 0302 clinical medicine, Pregnancy, Age of Onset, Child, Wasting, Creatine Kinase, 0303 health sciences, education.field_of_study, medicine.diagnostic_test, Homozygote, Middle Aged, 3. Good health, Psychiatry and Mental health, Phenotype, Female, MUSCLE DISEASE, medicine.symptom, Glycogen storage disease type V, Adult, medicine.medical_specialty, Weakness, Heterozygote, Adolescent, Population, Physical examination, Motor Activity, MCARDLES DISEASE, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Myopathy, education, Exercise, 030304 developmental biology, business.industry, Myoglobinuria, medicine.disease, Pregnancy Complications, Physical therapy, Glycogen Storage Disease Type V, Surgery, Neurology (clinical), Age of onset, business, 030217 neurology & neurosurgery
Abstract: International audience; The clinical phenotype of 45 genetically confirmed McArdle patients is described. In the majority of patients (84%) the onset of symptoms was from early childhood but diagnosis was frequently delayed until after 30 years of age. Not all patients could recognise a second wind, although it was always seen with exercise assessment. A history of myoglobinuria was not universal and episodes of acute renal failure had occurred in a minority (11%). The condition does not appear to adversely affect pregnancy and childbirth. Clinical examination was normal in most patients, muscle hypertrophy was present in 24% and mild muscle wasting and weakness was seen only in patients over 40 years of age and was limited to shoulder girdle and axial muscles. The serum creatine kinase (CK) was elevated in all but one pregnant patient. Screening for mutations in p.Arg50X (R50X) and p.Gly205Ser (G205S) showed at least one mutated allele in 96% of Caucasian British patients, with an allele frequency of 77% for p.Arg50X in this population. A 12-minute walking test to evaluate patients is described, results demonstrated a wide spectrum of severity with the range of distance walked being 195-1980 metres, the mean distance walked was 512m suggesting significant functional impairment in most patients.
Published: 2010
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42. The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein

Author: Sylvie Bannwarth, C Caruba, C. Rouzier, Véronique Paquis-Flucklinger, Elsebet Ostergaard, S Le Guédard-Méreuze, Christian Richelme, C Espil, Valérie Serre, J Miro, Brigitte Chabrol, Sylvie Tuffery-Giraud, J-F Pellissier, Annabelle Chaussenot, Konstantina Fragaki, Service de génétique médicale, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Instabilité génétique : maladies rares et cancers (IGMRC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Clinical Genetics, National University Hospital Rigshospitalet, Service de neuropathologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, Service de neuropédiatrie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Nice-Hôpital l'Archet, Instabilité génétique : maladies rares et cancers ( IGMRC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Montpellier 1 - UFR de Médecine ( UM1 Médecine ), Université Montpellier 1 ( UM1 ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Pasteur [Nice] ( CHU ) -CHU Nice, Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Peer, Hal
Subjects: Male, Models, Molecular, medicine.medical_specialty, SUCLA2, Molecular Sequence Data, Mutation, Missense, methylmalonic aciduria, SUCLG1 mutation, Biology, Compound heterozygosity, medicine.disease_cause, Severity of Illness Index, 03 medical and health sciences, Exon, 0302 clinical medicine, Fatal Outcome, Western blot, respiratory chain defect, Mitochondrial Encephalomyopathies, Molecular genetics, Succinate-CoA Ligases, Genetics, medicine, Missense mutation, Humans, Amino Acid Sequence, minigene expression system, Child, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, medicine.diagnostic_test, mtDNA depletion, Infant, Molecular biology, 3. Good health, Phenotype, 030217 neurology & neurosurgery, Minigene, Methylmalonic Acid
Abstract: Background Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLA2 , the gene encoding a β subunit of succinate-CoA ligase, have been reported in 17 patients until now. Mutations in SUCLG1 , encoding the α subunit of the enzyme, have been described in two pedigrees only. Methods and findings In this study, two unrelated patients harbouring three novel pathogenic mutations in SUCLG1 were reported. The first patient had a severe disease at birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene expression system. The involvement of SUCLG1 was confirmed by western blot analysis, which showed absence of SUCLG1 protein in fibroblasts. The second patient has a milder phenotype, similar to that of patients with SUCLA2 mutations, and is still alive at 12 years of age. Western blot analysis showed some residual SUCLG1 protein in patient9s fibroblasts. Conclusions Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2 -like phenotype is found in patients with residual SUCLG1 protein. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.
Published: 2010
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43. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure

Author: Michael R. Gold, Cecilia Linde, William T. Abraham, Stefano Ghio, Ted Plappert, Martin St. John Sutton, John M. Herre, Christian Hassager, Claude Daubert, Luigi Tavazzi, Laura Scelsi, University of Pennsylvania Medical Center, University of Pennsylvania [Philadelphia], Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, GVM Hospitals of Care and Research, Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Division of Cardiovascular Medicine and the Davis Heart and Lung Research Institute, Ohio State University [Columbus] (OSU), Division of cardiology, Medical University of South Carolina [Charleston] (MUSC), Department of Cardiology, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Sentara Norfolk General Hospital, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], This study was supported by Medtronic Inc (Minneapolis, Minn) and the Medtronic Bakken Research Center B.V. in Maastricht, Netherlands., REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group, Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], and CHU Pontchaillou [Rennes]
Subjects: Male, MESH: Combined Modality Therapy, Heart disease, MESH: Echocardiography, Doppler, Cardiac Volume, medicine.medical_treatment, heart failure, cardiac resynchronization therapy, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Doppler echocardiography, Severity of Illness Index, ventricular remodeling, MESH: Stroke Volume, Electrocardiography, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Medicine, echocardiography, 030212 general & internal medicine, New York Heart Association Class I, MESH: Treatment Outcome, MESH: Aged, Ejection fraction, MESH: Middle Aged, medicine.diagnostic_test, Cardiac Pacing, Artificial, MESH: Angiotensin-Converting Enzyme Inhibitors, MESH: Adrenergic beta-Antagonists, MESH: Heart Failure, Systolic, Stroke volume, Middle Aged, Combined Modality Therapy, Echocardiography, Doppler, Treatment Outcome, Cardiology, cardiovascular system, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, medicine.medical_specialty, Adrenergic beta-Antagonists, Cardiac resynchronization therapy, MESH: Ventricular Remodeling, MESH: Cardiac Pacing, Artificial, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, MESH: Severity of Illness Index, Humans, cardiovascular diseases, Ventricular remodeling, Aged, MESH: Humans, business.industry, MESH: Angiotensin II Type 1 Receptor Blockers, MESH: Cardiac Volume, Stroke Volume, medicine.disease, MESH: Male, MESH: Electrocardiography, Heart failure, business, Angiotensin II Type 1 Receptor Blockers, MESH: Female, Heart Failure, Systolic
Abstract: Background— Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. Methods and Results— Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration ≥120 ms, LV end-diastolic dimension ≥55 mm, and LV ejection fraction ≤40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic ( r =0.11, P =0.31) or end-diastolic ( r =0.10, P =0.38) volume indexes or LV ejection fraction ( r =0.07, P =0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P P Conclusions— CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration— Clinicaltrials.gov Identifier: NCT00271154.
Published: 2009
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44. Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

Author: Raquel Hernandez, Hanna Johansson, Béatrice Barraud, Jane Byrne, Gabriele Dreier, Fernando de Andres-Trelles, Wolfgang Kuchinke, Siobhan Gaynor, Christine Kubiak, Arrigo Schieppati, Adeeba Asghar, Zsuzsa Temesvari, Jacques Demotes-Mainard, Charlotte Asker-Hagelberg, Gabriella Kardos, Sue Bourne, György Blaskó, Xina Grählert, Margaret Cooney, Christian Gluud, Christian Libersa, Steffen Thirstrup, Kate Whitfield, Timothy O'Brien, Nuria Sanz, Ruth Grychtol, Karl-Heinz Huemer, Jean-Marc Husson, Institut Thématique Santé Publique, Institut National de la Santé et de la Recherche Médicale (INSERM), Departemento de Farmacologia (Medicina), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), KKS-Duesseldorf (KKSD), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Medical University of Vienna (ATCRIN), Copenhagen Trial Unit (CTU), Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, KKS, Medizinische Fakultät Carl Gustav Carus, ZKS - Clinical Trials Centre, University Medical Centre Freiburg, Hungarian ECRIN Committee, Ministry of Health Social and Family Affairs-Medical Research Council (HECRIN), National University of Ireland [Galway] (NUI Galway), Molecular Medicine Ireland (ICRIN), Istituto di Ricerche Farmacologiche Mario Negri (IRFMN), Hospital Clinic i Provincial de Barcelona (SCReN), Karolinska Trial Alliance, UK Clinical Research Collaboration, Education and Research Centre, Wythenshawe Hospital, UK Clinical Research Network, European Forum for Good Clinical Practice, ECRIN is a project funded by the EU Sixth and Seventh Framework Programmes., and BMC, Ed.
Subjects: Pathology, medicine.medical_specialty, Biomedical Research, Knowledge management, MESH: Clinical Trials as Topic, MEDLINE, Alternative medicine, Medicine (miscellaneous), 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, Humans, Medicine, Pharmacology (medical), MESH: Data Collection, 030212 general & internal medicine, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Clinical Trials as Topic, lcsh:R5-920, Data collection, MESH: Humans, business.industry, Data Collection, Research, Gyógyszerészeti tudományok, MESH: Biomedical Research, Orvostudományok, 3. Good health, Europe, Transplantation, Clinical trial, Clinical research, Multinational corporation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, InformationSystems_MISCELLANEOUS, business, lcsh:Medicine (General)
Abstract: Background Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. Methods In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. Results The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. Conclusion The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and simplification of the regulatory requirements for clinical research in Europe.
Published: 2009
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45. Pure preovulatory follicular fluid promotes in vitro maturation of in vivo aspirated equine oocytes

Author: I.B. Bøgh, Nadine Gérard, J. Bezard, M Baltsen, Peter Daels, Torben Greve, G Duchamp, Royal Veterinary and Agricultural University = Kongelige Veterinær- og Landbohøjskole (KVL ), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Pluri-espèces d'Expérimentation Animale en Physiologie de la Reproduction et des Comportements (TOURS UPEA PRC), Institut National de la Recherche Agronomique (INRA), University Hospital Rigshospitalet, Partenaires INRAE, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ovulation, Cytoplasm, medicine.medical_specialty, endocrine system, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Suction, follicular synchronization, 03 medical and health sciences, 0302 clinical medicine, Human fertilization, Estrus, Ovarian Follicle, Food Animals, In vivo, follicular aspiration, Internal medicine, Follicular phase, medicine, Animals, Horses, Small Animals, Cells, Cultured, Cell Nucleus, Estrous cycle, cumulus expansion, 030219 obstetrics & reproductive medicine, Equine, Chemistry, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Oocyte, 040201 dairy & animal science, Follicular fluid, In vitro, Culture Media, Follicular Fluid, In vitro maturation, Meiosis, Endocrinology, medicine.anatomical_structure, nuclear maturation, Oocytes, Tissue and Organ Harvesting, Female, Animal Science and Zoology, Gonadotropins
Abstract: International audience; In the mare, rates of fertilization and development are low in oocytes matured in vitro, and a closer imitation of in vivo conditions during oocyte maturation might be beneficial. The aims of the present study were, therefore, to investigate whether (1) equine oocytes can be matured in vitro in pure equine preovulatory follicular fluid, (2) priming of the follicular fluid donor with crude equine gonadotrophins (CEG) before aspiration of preovulatory follicular fluid promotes the in vitro maturation rate, (3) the in vitro maturation rate differs between oocytes aspirated during estrus and those aspirated again 8 days after the initial follicular aspiration, and (4) high follicular concentrations of meiosis activating sterols (MAS) are beneficial for in vitro maturation of equine oocytes. During estrus, 19 pony mares were treated with 25 mg CEG. After 24 h (A1) and again after 8 days (A2), all follicles ≥4 mm were aspirated and incubated individually for 30 h in the following culture media: standard culture medium (SM), preovulatory follicular fluid collected before CEG containing low MAS concentrations (FF1), preovulatory follicular fluid collected before CEG containing high MAS concentrations (FF2) or preovulatory follicular fluid collected 35 h after administration of CEG containing low MAS concentrations (FF3). Cumulus expansion rate was significantly affected by culture medium. The overall nuclear maturation rate was significantly higher for oocytes collected at A1 (67%) than for oocytes collected at A2 (30%). For oocytes collected at A1, the maturation rates were 71% (FF1), 61% (FF2), 79% (FF3) and 56% (SM). An electrophoretic protein analysis of the culture media revealed the presence of a 200-kDa protein in FF3. The results demonstrate that (1) equine oocytes can be matured during culture in pure equine preovulatory follicular fluid, (2) preovulatory follicular fluid collected after gonadotrophin-priming seems superior in supporting in vitro maturation than standard culture medium, (3) oocytes aspirated 8 days after a previous aspiration are less competent for in vitro maturation than oocytes recovered during the initial aspiration, and (4) the regulation of meiotic resumption during in vitro culture of equine oocytes might be related to the presence of a 200-kDa protein.
Published: 2002
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46. Primary Progressive Aphasia Across Languages: Prevalence and Presentation of Phenotypes Are Shaped by Language-Specific Features.

Author: Nielsen TR and Kjaergaard D
Published: 2024
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47. Left atrial strain measured by three-dimensional echocardiography predicts atrial fibrillation in the general population.

Author: Yafasov M, Olsen FJ, Hauser R, Skaarup KG, Lassen MCH, Johansen ND, Lindgren FL, Søgaard P, Jensen GB, Schnohr P, Møgelvang R, and Biering-Sørensen T
Subjects: Humans, Male, Female, Middle Aged, Prospective Studies, Aged, Adult, Longitudinal Studies, Follow-Up Studies, Cohort Studies, Population Surveillance methods, Incidence, Prognosis, Atrial Fibrillation diagnostic imaging, Atrial Fibrillation physiopathology, Atrial Fibrillation epidemiology, Echocardiography, Three-Dimensional methods, Atrial Function, Left physiology, Predictive Value of Tests, Heart Atria diagnostic imaging, Heart Atria physiopathology
Abstract: Background: Left atrial (LA) strain by three-dimensional echocardiography (3DE), has been proposed as a more accurate measure of LA function, providing incremental prognostic benefits over traditional two-dimensional approaches., Objectives: Our aim was to evaluate the prognostic value of LA strain by 3DE in predicting incident atrial fibrillation (AF) in the general population., Methods: The study included 4466 participants from a prospective longitudinal cohort study in the general population, among these 3DE LA strain was analysed in 1935 participants. The endpoint was incident AF. Adjustments were made for the CHARGE-AF clinical risk score., Results: Mean age was 54 ± 17 years, 43 % were male. During a median follow-up time of 4.8 years (interquartile range 4.3-5.5 years) 59 participants (3.0 %) developed AF. In univariable analysis, all three parameters were associated with incident AF (p value for all <0.01). After multivariable adjustments, only LA reservoir strain (LASr) and LA contractile strain (LASct) were associated with incident AF (LASr: HR 1.12 (1.07-1.17), p < 0.001, per 1 % decrease; LASct: HR 1.16 (1.09-1.24), p < 0.001, per 1 % decrease), whereas LA conduit strain (LAScd) was not (HR 1.04 (0.98-1.10), p = 0.17, per 1 % decrease). Both LASr (continuous net reclassification index 0.37 ± 0.14; p = 0.003) and LASct (continuous net reclassification index 0.41 ± 0.14; p = 0.002) provided incremental prognostic information beyond the CHARGE-AF risk score., Conclusion: LASr and LASct measured by 3DE are independently associated with incident AF and provided incremental prognostic information beyond existing risk scores., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)
Published: 2024
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48. Response to: Comments on "Epidemiological trends and survival of oropharyngeal cancer in a high HPV-prevalent area: A Danish population-based study from 2000 to 2020".

Author: von Buchwald C, Lauritzen BB, Carlander AF, Jakobsen KK, Garset-Zamani M, Bendtsen SK, and Grønhøj C
Published: 2024
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49. Epidemiological trends and survival of oropharyngeal cancer in a high HPV-prevalent area: A Danish population-based study from 2000 to 2020.

Author: Lauritzen BB, Grønlund MW, Jakobsen KK, Justesen MM, Garset-Zamani M, Carlander AF, Rasmussen JH, Bendtsen SK, Kiss K, Andersen G, Rosenørn MR, Friborg J, Bentzen JKD, Grønhøj C, and von Buchwald C
Subjects: Humans, Male, Female, Denmark epidemiology, Middle Aged, Aged, Incidence, Prevalence, Adult, Aged, 80 and over, Squamous Cell Carcinoma of Head and Neck epidemiology, Squamous Cell Carcinoma of Head and Neck virology, Squamous Cell Carcinoma of Head and Neck mortality, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local virology, Oropharyngeal Neoplasms virology, Oropharyngeal Neoplasms epidemiology, Oropharyngeal Neoplasms mortality, Papillomavirus Infections epidemiology, Papillomavirus Infections virology, Papillomavirus Infections complications
Abstract: Denmark, alongside other Scandinavian countries, the United States, Canada, and the United Kingdom, has high prevalence of human papillomavirus (HPV). Our oropharyngeal squamous cell carcinoma (OPSCC) database includes all diagnosed cases in Eastern Denmark during a period of more than two decades. We investigated the incidence, survival, and recurrence of patients with OPSCC with combined p16- and HPV testing covering a consecutive 21-year period. Age-adjusted incidence rate (AAIR) per 100,000, survival models, and Cox proportional-hazards model were employed. Two thousand eight hundred thirty-four patients were included (57.5% HPV positive (HPV+)/p16 positive (p16+), 33.7% HPV negative (HPV-)/p16 negative (p16-), 4% HPV+/p16-, and 4.8% HPV-/p16+). The AAIR for all patients increased from 1.8 to 5.1 per 100,000 from 2000 to 2020 linked to an increasing AAIR of HPV+/p16+ OPSCCs from 0.9 to 3.5 per 100,000 from 2000 to 2020. The AAIR for the HPV-/p16- OPSCCs decreased from 1.6 to 1.4 from 2017 to 2020. HPV+/p16+ OPSCCs had a higher 5-year overall survival (OS) of 79.2% compared to the other subgroups (HPV+/p16- OS: 50.4%; HPV-/p16+ OS: 49.4%; HPV-/p16- OS: 35.1%). The AAIR of the total OPSCC group increased from year 2000 to 2020, driven by a rise in the HPV+/p16+ group. A decreasing incidence rate was observed for the HPV-/p16- OPSCCs from 2017 to 2020. The OS for HPV+/p16+ OPSCCs was significantly higher compared to all other HPV/p16 subgroups. Therefore, we recommend testing for combined HPV and p16 status in patients with OPSCC when selecting patients for clinical trials, especially in case of de-escalating/escalating., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Published: 2024
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50. The pattern of childhood infections during and after the COVID-19 pandemic.

Author: Nygaard U, Holm M, Rabie H, and Rytter M
Subjects: Humans, Child, SARS-CoV-2, Incidence, Child, Preschool, Pandemics, Adolescent, COVID-19 epidemiology
Abstract: The rates of most paediatric infectious diseases declined during the initial phase of the COVID-19 pandemic due to the implementation of non-pharmaceutical interventions. However, after the gradual release of these interventions, resurgences of infections occurred with notable variations in incidence, clinical manifestations, pathogen strains, and age distribution. This Review seeks to explore these changes and the rare clinical manifestations that were made evident during the resurgence of known childhood infections. The magnitude of resurgences was possibly caused by a profound population immunity debt to specific pathogens in combination with the coinciding reappearance of viral and bacterial infections, rather than novel pathogen variants, increased antimicrobial resistance, or altered childhood immune function. As the usual patterns of paediatric infectious diseases were disrupted during the COVID-19 pandemic, the consequences of a population immunity debt were unravelled, and new insights into pathogen transmissibility, disease pathogenesis, and rare clinical manifestations were revealed., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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