187 results match your criteria: "Utrecht S.H.; and Maastricht University Medical Centre[Affiliation]"

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

N Engl J Med

April 2021

From Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospital (R.H.), King's College London (M.S.-H.), and Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), London, University of Oxford (A. Beane) and NHS Blood and Transplant (L.J.E.), Oxford, and University of Bristol, Bristol (C.A.B.) - all in the United Kingdom; Monash University (A.D.N., A. Buzgau, A.C.C., A.M.H., S.P.M., J.C.P., C.G., S.A.W.) and Alfred Health (A.D.N., A.C.C.), Melbourne, VIC, Fiona Stanley Hospital (E. Litton, K.O.) and University of Western Australia (E. Litton), Perth, WA, University of Sydney and Royal Prince Alfred Hospital, Sydney (A.E.P.), and St. John of God Hospital, Subiaco, WA (S.A.W.) - all in Australia; University College Dublin, Dublin (A.D.N.); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Hospital Raymond Poincaré (Assistance Publique-Hôpitaux de Paris) and Université Paris Saclay-Université de Versailles Saint-Quentin-en-Yvelines-INSERM, Garches, and Université de Versailles Saint-Quentin-en-Yvelines-Université Paris Saclay, Montigny-le-Bretonneux - all in France (D.A.); University Medical Center Utrecht, Utrecht (W.B.-P., M.J.M.B., H.L.L., E.R., L.P.G.D.), and Radboudumc, Nijmegen (F.L.V.) - both in the Netherlands; Berry Consultants, Austin, TX (L.R.B., M.A.D., M.F., E. Lorenzi, A.M., C.T.S., R.J.L., S.B.); St. Michael's Hospital Unity Health (Z.B., J.C.M., M.S.S.) and University Health Network and University of Toronto (P.R.L.), Toronto, Université de Sherbrooke, Sherbrooke, QC (F.L.), University of British Columbia, Vancouver (S.M.), University of Alberta, Edmonton (W.I.S.), Université Laval, Québec City (A.F.T.), and University of Manitoba, Winnipeg, MB (R.Z.) - all in Canada; Jena University Hospital, Jena, Germany (F.M.B.); Auckland City Hospital (E.J.D., T.E.H., S.P.M., R.L.P., C.J.M.), Middlemore Hospital (S.C.M.), and University of Auckland (R.L.P.), Auckland, and Medical Research Institute of New Zealand, Wellington (T.E.H., S.P.M., A.M.T.) - all in New Zealand; University of Antwerp, Wilrijk, Belgium (H.G.); University of Oxford, Bangkok, Thailand (R.H.); National Intensive Care Surveillance, Colombo, Sri Lanka (R.H.); UPMC Children's Hospital of Pittsburgh (C.M.H.) and University of Pittsburgh (K.M.L., F.B.M., B.J.M., S.K.M., C.W.S., D.C.A.), Pittsburgh; Queen's University Belfast and Royal Victoria Hospital, Belfast, Northern Ireland (D.F.M.); University of Helsinki and Helsinki University Hospital, Helsinki (V.P.); and Harbor-UCLA Medical Center, Torrance, CA (R.J.L.).

Background: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

Methods: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control).

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Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation.

Proc Natl Acad Sci U S A

February 2021

Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands;

Immunoglobulin (Ig) G molecules are essential players in the human immune response against bacterial infections. An important effector of IgG-dependent immunity is the induction of complement activation, a reaction that triggers a variety of responses that help kill bacteria. Antibody-dependent complement activation is promoted by the organization of target-bound IgGs into hexamers that are held together via noncovalent Fc-Fc interactions.

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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

N Engl J Med

February 2021

The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care (L.D., S. Carvalho, J.A., K.A.P., Q.W., M.K.B., J.D., B.D., N. Mavaddat, K. Michailidou, A.C.A., P.D.P.P., D.F.E.) and Oncology (C.L., P.A.H., C. Baynes, D.M.C., L.F., V.R., M. Shah, P.D.P.P., A.M.D., D.F.E.), University of Cambridge, Cambridge, the Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine (A. Campbell, D.J.P.), and the Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology (D.J.P.), University of Edinburgh, the Cancer Research UK Edinburgh Centre (D.A.C., J.F.), and the Usher Institute of Population Health Sciences and Informatics, University of Edinburgh Medical School (A. Campbell, J.F.), Edinburgh, the Divisions of Informatics, Imaging, and Data Sciences (E.F.H.), Cancer Sciences (A. Howell), Population Health, Health Services Research, and Primary Care (A. Lophatananon, K. Muir), and Evolution and Genomic Sciences, School of Biological Sciences (W.G.N., E.M.V., D.G.E.), University of Manchester, the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre, Wythenshawe Hospital (E.F.H., H.I.), Academic Health Science Centre and North West Genomics Laboratory Hub, and the Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust (W.G.N., E.M.V., D.G.E.), Manchester, the School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London (E.J.S.), the Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham (I.T.), and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford (I.T.) - all in the United Kingdom; the Human Genotyping-CEGEN Unit, Human Cancer Genetic Program (A.G.-N., M.R.A., N.Á., B.H., R.N.-T.), and the Human Genetics Group (V.F., A.O., J.B.), Spanish National Cancer Research Center, Centro de Investigación en Red de Enfermedades Raras (A.O., J.B.), Servicio de Oncología Médica, Hospital Universitario La Paz (M.P.Z.), and Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (M. de la Hoya), Madrid, the Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago (A. Carracedo, M.G.-D.), and Centro de Investigación en Red de Enfermedades Raras y Centro Nacional de Genotipado, Universidad de Santiago de Compostela (A. Carracedo), Santiago de Compostela, the Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galeo de Saúde, Vigo (J.E.C.), and Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo (J.I.A.P.) - all in Spain; the Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund (C. Wahlström, J.V., M.L., T. Törngren, Å.B., A.K.), the Department of Oncology, Örebro University Hospital, Örebro (C. Blomqvist), and the Departments of Medical Epidemiology and Biostatistics (K.C., M.E., M.G., P. Hall, W.H., K.H.), Oncology, Södersjukhuset (P. Hall, S. Margolin), Molecular Medicine and Surgery (A. Lindblom), and Clinical Science and Education, Södersjukhuset (S. Margolin, C. Wendt), Karolinska Institutet, and the Department of Clinical Genetics, Karolinska University Hospital (A. Lindblom), Stockholm - all in Sweden; the Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD (M.T.P., C.F., G.C.-T., A.B.S.), the Cancer Epidemiology Division, Cancer Council Victoria (G.G.G., R.J.M., R.L.M.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health (G.G.G., R.J.M., R.L.M.), and the Department of Clinical Pathology (M.C.S.), University of Melbourne, Anatomical Pathology, Alfred Hospital (C.M.), and the Cancer Epidemiology Division, Cancer Council Victoria (M.C.S.), Melbourne, VIC, and Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC (G.G.G., M.C.S., R.L.M.) - all in Australia; the Division of Molecular Pathology (R.K., S. Cornelissen, M.K.S.), Family Cancer Clinic (F.B.L.H., L.E.K.), Department of Epidemiology (M.A.R.), and Division of Psychosocial Research and Epidemiology (M.K.S.), the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center, Utrecht (M.G.E.M.A.), the Department of Clinical Genetics, Erasmus University Medical Center (J.M.C., A.M.W.O.), and the Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute (B.A.M.H.-G., A. Hollestelle, M.J.H.), Rotterdam, the Department of Clinical Genetics, Maastricht University Medical Center, Maastricht (E.B.G.G.), the Departments of Human Genetics (I.M.M.L., M.P.G.V., P.D.), Clinical Genetics (C.J.A.), and Pathology (P.D.), Leiden University Medical Center, Leiden, the Department of Human Genetics, Radboud University Medical Center, Nijmegen (A.R.M.), and the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen (J.C.O.) - all in the Netherlands; the Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute (B.D.), and the Division of Cancer Epidemiology and Genetics, National Cancer Institute (T.A., S.J.C., X.R.Y., M.G.-C.), National Institutes of Health, Bethesda, MD; the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School (B.D.), and the Department of Nutrition, Harvard T.H. Chan School of Public Health (R.M.V.D.), Boston; the Departments of Clinical Genetics (K.A.), Oncology (C. Blomqvist), and Obstetrics and Gynecology (H.N., M. Suvanto), Helsinki University Hospital, University of Helsinki, Helsinki, and the Unit of Clinical Oncology, Kuopio University Hospital (P. Auvinen), the Institute of Clinical Medicine, Oncology (P. Auvinen), the Translational Cancer Research Area (J.M.H., V.-M.K., A. Mannermaa), and the Institute of Clinical Medicine, Pathology, and Forensic Medicine (J.M.H., V.-M.K., A. Mannermaa), University of Eastern Finland, and the Biobank of Eastern Finland, Kuopio University Hospital (V.-M.K., A. Mannermaa), Kuopio - both in Finland; the N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (N.N.A., N.V.B.); the Department of Gynecology and Obstetrics and Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel (N.A.), the Institute of Medical Biometry and Epidemiology (H. Becher) and Cancer Epidemiology Group (T.M., J.C.-C.), University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, the Department of Gynecology and Obstetrics (M.W.B., P.A.F., L.H.) and Institute of Human Genetics (A.B.E.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen, the Division of Cancer Epidemiology (S.B., A. Jung, P.M.K., J.C.-C.), Molecular Epidemiology Group, C080 (B. Burwinkel, H.S.), Division of Pediatric Neurooncology (A.F.), and Molecular Genetics of Breast Cancer (U.H., M.M., M.U.R., D.T.), German Cancer Research Center, Molecular Biology of Breast Cancer, University Women's Clinic Heidelberg, University of Heidelberg (B. Burwinkel, A.S., H.S.), Hopp Children's Cancer Center (A.F.), Faculty of Medicine, University of Heidelberg (P.M.K.), and National Center for Tumor Diseases, University Hospital and German Cancer Research Center (A.S., C.S.), Heidelberg, the Department of Radiation Oncology (N.V.B., M. Bremer, H.C.) and the Gynecology Research Unit (N.V.B., T.D., P. Hillemanns, T.-W.P.-S., P.S.), Hannover Medical School, Hannover, the Institute of Human Genetics, University of Münster, Münster (N.B.-M.), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (H. Brauch, W.-Y.L.), iFIT-Cluster of Excellence, University of Tübingen, and the German Cancer Consortium, German Cancer Research Center, Partner Site Tübingen (H. Brauch), and the University of Tübingen (W.-Y.L.), Tübingen, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum (T.B.), Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig (C.E.), Center for Hereditary Breast and Ovarian Cancer (E.H., R.K.S.) and Center for Integrated Oncology (E.H., R.K.S.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, the Department of Internal Medicine, Evangelische Kliniken Bonn, Johanniter Krankenhaus, Bonn (Y.-D.K.), the Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich (A. Meindl), and the Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe (T.R.) - all in Germany; the Gynecological Cancer Registry, Centre Georges-François Leclerc, Dijon (P. Arveux), and the Center for Research in Epidemiology and Population Health, Team Exposome and Heredity, INSERM, University Paris-Saclay, Villejuif (E.C.-D., P.G., T. Truong) - both in France; the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences (M. Bermisheva, E.K.), the Department of Genetics and Fundamental Medicine, Bashkir State University (E.K., D.P., Y.V.), and the Ufa Research Institute of Occupational Health and Human Ecology (Y.V.), Ufa, Russia; the Department of Genetics and Pathology (K.B., A. Jakubowska, J. Lubiński, K.P.) and the Independent Laboratory of Molecular Biology and Genetic Diagnostics (A. Jakubowska), Pomeranian Medical University, Szczecin, Poland; the Copenhagen General Population Study, the Department of Clinical Biochemistry (S.E.B., B.G.N.), and the Department of Breast Surgery (H.F.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (S.E.B., B.G.N.) - both in Denmark; the Division of Cancer Prevention and Genetics, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (B. Bonanni), the Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (S. Manoukian), the Genome Diagnostics Program, FIRC Institute of Molecular Oncology (P.P.), and the Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (P.R.), Milan; the Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet (A.-L.B.-D., G.I.G.A., V.N.K.), and the Institute of Clinical Medicine, Faculty of Medicine, University of Oslo (A.-L.B.-D., V.N.K.), Oslo; Medical Faculty, Universidad de La Sabana (I.B.), and the Clinical Epidemiology and Biostatistics Department (F.G.) and Institute of Human Genetics (D.T.), Pontificia Universidad Javeriana, Bogota, Colombia; the Department of Internal Medicine and Huntsman Cancer Institute, University of Utah (N.J.C., M.J.M., J.A.W.), and the Intermountain Healthcare Biorepository and Department of Pathology, Intermountain Healthcare (M.H.C.), Salt Lake City; the David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California, Los Angeles (P.A.F.), and Moores Cancer Center (M.G.-D., M.E.M.) and the Department of Family Medicine and Public Health (M.E.M.), University of California San Diego, La Jolla; the Departments of Medical Oncology (V.G., D.M.) and Pathology (M.T.), University Hospital of Heraklion, Heraklion, and the Department of Oncology, University Hospital of Larissa, Larissa (E.S.) - both in Greece; the Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital (G.G., I.L.A.), the Departments of Laboratory Medicine and Pathobiology (A.M.M.) and Molecular Genetics (I.L.A.), University of Toronto, and the Laboratory Medicine Program, University Health Network (A.M.M.), Toronto, and the Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, QC (J.S.) - both in Canada; the Department of Electron Microscopy and Molecular Pathology (A. Hadjisavvas, K.K., M.A.L.), the Cyprus School of Molecular Medicine (A. Hadjisavvas, K.K., M.A.L., K. Michailidou), and the Biostatistics Unit (K. Michailidou), Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; the Saw Swee Hock School of Public Health (M. Hartman, R.M.V.D.) and the Department of Medicine, Yong Loo Lin School of Medicine (R.M.V.D.), National University of Singapore, the Department of Surgery, National University Health System (M. Hartman, J. Li), and the Human Genetics Division, Genome Institute of Singapore (J. Li), Singapore; the Department of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia (W.K.H.), and the Breast Cancer Research Programme, Cancer Research Malaysia (W.K.H., P.S.N., S.-Y.Y., S.H.T.), Selangor, and the Breast Cancer Research Unit, Cancer Research Institute (N.A.M.T.), and the Department of Surgery, Faculty of Medicine (N.A.M.T., P.S.N., S.H.T.), University Malaya, Kuala Lumpur - both in Malaysia; Surgery, School of Medicine, National University of Ireland, Galway (M.J.K., N. Miller); the Department of Surgery, Daerim Saint Mary's Hospital (S.-W.K.), the Department of Surgery, Ulsan University College of Medicine and Asan Medical Center (J.W.L.), the Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital (M.H.L.), Integrated Major in Innovative Medical Science, Seoul National University College of Medicine (S.K.P.), and the Cancer Research Institute, Seoul National University (S.K.P.), Seoul, South Korea; the Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M.U.R.); and the National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand (S.T.).

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

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Association of Circulating Metabolites in Plasma or Serum and Risk of Stroke: Meta-analysis From 7 Prospective Cohorts.

Neurology

February 2021

From the Department of Epidemiology (D.V., N.A., M.A.I., C.M.v.D.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Computational Medicine (M. Kalaoja, M.A.-K., J.K.), Faculty of Medicine, University of Oulu and Biocenter Oulu, Finland; Departments of Gerontology and Geriatrics (S.T.), and Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands; Estonian Genome Centre (K.F., N.T., T.E.), Institute of Genomics, and Institute of Molecular and Cell Biology (N.T.), University of Tartu, Estonia; Department of Epidemiology and Public Health (M.J.S., M. Kivimaki), UCL, London, UK; Department of Biostatistics (S.L., O.Y.), School of Public Health, Boston University, MA; Department of Public Health Solutions (A.S.H., M.P., V.S., P.J., J.K.), Finnish Institute for Health and Welfare; Institute for Molecular Medicine Finland (A.S.H., M.P.), University of Helsinki; BHF Glasgow Cardiovascular Research Centre (N.S.), Faculty of Medicine, UK; Department of Neurology (B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Framingham Heart Study (C.L.S., R.S.V., S.S.), MA; Department of Radiology and Nuclear Medicine (M.A.I.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Institute of Cardiovascular and Medical Sciences (D.J.S.), College of Medical, Veterinary and Life Sciences, University of Glasgow, UK; Systems Epidemiology (M.A.-K.), Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; NMR Metabolomics Laboratory (M.A.-K.), School of Pharmacy, University of Eastern Finland, Kuopio; Population Health Science (M.A.-K.), Bristol Medical School, and Medical Research Council Integrative Epidemiology Unit (M.A.-K.), University of Bristol, UK; Department of Epidemiology and Preventive Medicine (M.A.-K.), School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia; Netherlands Heart Institute (J.W.J.), Utrecht, the Netherlands; Department of Neurology (C.L.S., S.S.), Boston University School of Medicine; Broad Institute of MIT and Harvard (T.E.), Boston, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S.), UT Health San Antonio, TX; Nuffield Department of Population Health (C.M.v.D.), University of Oxford, UK. D.V. is currently at the Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, the Netherlands, and K.F. is currently at the Institute of Mathematics and Statistics, University of Tartu, Estonia.

Objective: To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings.

Methods: We investigated the association of metabolites with risk of stroke in 7 prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by nuclear magnetic resonance technology. The relationship between metabolites and stroke was assessed with Cox proportional hazards regression models.

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Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL).

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Diagnostic and treatment strategies for acute coronary syndrome have improved dramatically over the past few decades, but mortality and recurrent myocardial infarction rates remain high. An aging population with increasing co-morbidities heralds new clinical challenges. Therefore, in order to evaluate and improve current treatment strategies, detailed information on clinical presentation, treatment and follow-up in real-world patients is needed.

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Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity.

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Colchicine in Patients with Chronic Coronary Disease.

N Engl J Med

November 2020

From GenesisCare Western Australia (S.M.N., X.-F.X., M.A.I., D.L., A.W., R.H., P.S., I.T., A.G.T., A. Morton, P.L.T.), the Heart and Vascular Research Institute (S.M.N., P.L.T.) and the Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital, and the Faculty of Health and Medical Sciences (G.J.H., P.L.T.) and the School of Population and Global Health (C.A.B.), University of Western Australia, Perth, the Department of Cardiology, Fiona Stanley Hospital, Murdoch, WA (C.J.), and the Harry Perkins Institute of Medical Research, Nedlands, WA (P.L.T.) - all in Australia; the Dutch Network for Cardiovascular Research (A.T.L.F., A. Mosterd, A.S., S.H.K.T., T.L., P.H., A.J., P.N., H.S., J.S., A.F.M.K., M.W.J.H., M.D., M.A., J.H.C.), the Netherlands Heart Institute (A.T.L.F.), and the Department of Cardiology (A.T.L.F.) and the Julius Center for Health Sciences and Primary Care (A. Mosterd, M.A.), University Medical Center Utrecht, Utrecht, the Department of Cardiology, Meander Medical Center, Amersfoort (A. Mosterd), the Departments of Cardiology (T.S.J.O., M.D., J.H.C.) and Internal Medicine (W.A.B.), Northwest Clinics, Alkmaar, the Department of Cardiology, Radboud University Medical Center, Nijmegen (T.S.J.O., J.H.C.), the Department of Cardiology, Treant Zorggroep, Hoogeveen, Emmen, and Stadskanaal (S.H.K.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen and Sittard (T.L.), the Department of Cardiology, Isala Diaconessenhuis, Meppel (P.H.), the Department of Cardiology, Gelre Hospitals, Apeldoorn (A.J.), the Department of Cardiology, Franciscus Hospital (P.N.), and Cardialysis (J.G.P.T.), Rotterdam, the Department of Cardiology, D&A Research and Genetics, Sneek (H.S.), the Department of Cardiology, Amphia and Breda (J.S., M.A.), the Department of Cardiology, Spaarne Hospital, Haarlem and Hoofddorp (A.F.M.K.), the Department of Cardiology, Green Heart Hospital, Gouda (M.W.J.H.), and the Department of Cardiology, Amsterdam UMC, Amsterdam (J.G.P.T.) - all in the Netherlands; and the Department of Medicine, McMaster University, Hamilton, ON, Canada (J.W.E.).

Background: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.

Methods: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo.

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Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

N Engl J Med

October 2020

From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (J. Brouwer, V.J.N., J.P., D.R.P.P.C.P.Y., M.J.S., B.J.W.M.R., L.T., J.C.K., J.M.B.), the Department of Cardiology, Amsterdam University Medical Center, Amsterdam (R.D., J. Baan), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H.), the Department of Cardiology, Maastricht University Medical Center (W.H., L.V., A.W.J.H.) and the Cardiovascular Research Institute Maastricht (A.W.J.H., J.M.B.), Maastricht, the Department of Cardiology, Medisch Spectrum Twente, Enschede (G.K.H.), the Department of Cardiology, Leiden University Medical Center, Leiden (F.K.), the Department of Cardiology, Haga Hospital, The Hague (C.E.S.), the Department of Cardiology, University Medical Center Groningen, Groningen (P.H.), Erasmus School of Health Policy and Management, Erasmus University, Rotterdam (F.W.F.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), and the Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht (P.R.S.) - all in the Netherlands; the Department of Cardiology, University Hospital Leuven, Leuven (C.L.F.D.), Cardiovascular Center Aalst, Onze Lieve Vrouwe Clinic (B.D.B.), and the Department of Cardiology, Algemeen Stedelijk Hospital Aalst (I.B.), Aalst, the Department of Cardiology, Sint-Jan Hospital, Brugge (J.A.S.V.D.H.), the Department of Cardiology, Hospital Oost-Limburg, Genk (B.F.), and the Department of Cardiology, Imelda Hospital, Bonheiden (J.R.) - all in Belgium; the Department of Cardiology, Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg (P.F.); and the Department of Cardiology, University Hospital Královské Vinohrady and Third Medical Faculty, Charles University, Prague, Czech Republic (P.T.).

Background: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied.

Methods: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months.

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Background: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG.

Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg).

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Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.

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Recurrent sequence evolution after independent gene duplication.

BMC Evol Biol

August 2020

Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht, 3584, CH, The Netherlands.

Background: Convergent and parallel evolution provide unique insights into the mechanisms of natural selection. Some of the most striking convergent and parallel (collectively recurrent) amino acid substitutions in proteins are adaptive, but there are also many that are selectively neutral. Accordingly, genome-wide assessment has shown that recurrent sequence evolution in orthologs is chiefly explained by nearly neutral evolution.

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Idiopathic Scoliosis as a Rotatory Decompensation of the Spine.

J Bone Miner Res

October 2020

Académie Nationale de Médecine, Paris, France.

Many years of dedicated research into the etiology of idiopathic scoliosis have not led to one unified theory. We propose that scoliosis is a mechanical, rotatory decompensation of the human spine that starts in the transverse, or horizontal, plane. The human spine is prone to this type of decompensation because of its unique and individually different, fully upright sagittal shape with some preexistent transverse plane rotation.

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Purpose: To investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-μm and 100-μm drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model.

Materials And Methods: Twelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-μm (n = 5) or 100-μm (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24-72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia.

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Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

N Engl J Med

April 2020

From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (V.J.N., J. Brouwer, J.P., D.R.P.P.C.P.Y., M.J.S., B.J.W.M.R., L.T., J.C.K., J.M.B.), the Department of Cardiology, Amsterdam University Medical Centers, Location AMC, Amsterdam (R.D., J. Baan), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H.), the Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute, Maastricht (W.H., L.V., A.W.J.H.), the Department of Cardiology, Medisch Spectrum Twente, Enschede (G.K.H.), the Department of Cardiology, Leiden University Medical Center, Leiden (F.K.), the Department of Cardiology, Haga Hospital, The Hague (C.E.S.), the Department of Cardiology, University Medical Center Groningen, Groningen (P.H.), Erasmus School of Health Policy and Management, Erasmus University, Rotterdam (F.W.F.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), and the Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht (P.R.S.) - all in the Netherlands; the Department of Cardiology, University Hospital Leuven, Leuven (C.L.F.D.), the Department of Cardiology, Onze Lieve Vrouwe Hospital (B.D.B.), and the Department of Cardiology, Algemeen Stedelijk Hospital Aalst (I.B.), Aalst, the Department of Cardiology, Sint-Jan Hospital, Brugge (J.A.S.V.D.H.), the Department of Cardiology, Hospital Oost-Limburg, Genk (B.F.), and the Department of Cardiology, Imelda Hospital, Bonheiden (J.R.) - all in Belgium; the Department of Cardiology, Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg (P.F.); and the Department of Cardiology, University Hospital Královské Vinohrady and Third Medical Faculty, Charles University, Prague, Czech Republic (P.T.).

Background: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.

Methods: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months.

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Five-year Progression of Emphysema and Air Trapping at CT in Smokers with and Those without Chronic Obstructive Pulmonary Disease: Results from the COPDGene Study.

Radiology

April 2020

From the Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, PO 85500, Postbox E.03.511, Utrecht, Utrecht 3508 GA, the Netherlands (E.P.); Division of Biostatistics and Bioinformatics (M.S., B.J.M.), Department of Radiology (S.H., D.A.L.), Division of Rheumatology, Department of Medicine (E.A.R.), and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine (J.D.C.), National Jewish Health, Denver, Colo; Thirona, Nijmegen, the Netherlands (E.M.v.R.); Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (E.M.v.R., J.P.C.); Departments of Biomedical Engineering, Radiology, and Internal Medicine, University of Iowa, Iowa City, Iowa (E.A.H.); Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY (R.G.B.); Division of Pulmonary and Critical Care, University of Michigan Health System, Ann Arbor, Mich (M.K.H.); Department of Epidemiology, University of Colorado Denver, Denver, Colo (J.E.H.); and Channing Division of Network Medicine (E.K.S.) and Division of Pulmonary and Critical Care Medicine, Department of Medicine (E.K.S.), Brigham and Women's Hospital, Boston, Mass.

Background CT is used to quantify abnormal changes in the lung parenchyma of smokers that might overlap chronic obstructive pulmonary disease (COPD), but studies on the progression of expiratory air trapping in smokers are scarce. Purpose To evaluate the relationship between longitudinal changes in forced expiratory volume in 1 second (FEV) and CT-quantified emphysema and air trapping in smokers. Materials and Methods Cigarette smokers with and those without COPD participating in the multicenter observational COPDGene study were evaluated.

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Purpose: Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer.

Methods And Materials: In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy.

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Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting.

Blood Adv

December 2019

Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Article Synopsis
  • Prosurvival BCL-2 family proteins, such as MCL-1, are crucial for the survival of malignant plasma cells in multiple myeloma (MM) and their overexpression is linked to worse patient outcomes.
  • * In a study of human myeloma cell lines and newly diagnosed MM patients, it was found that cells with amplification of the 1q21 chromosomal region are significantly more sensitive to the MCL-1 inhibitor S63845.
  • * The research suggests that 1q21 amplification can serve as a predictive marker for selecting effective treatments, and combining S63845 with other inhibitors greatly enhances the effectiveness of the therapy.
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Effect of Insulin and Fasting Regimen on Blood Glucose Concentrations of Diabetic Dogs During Phacoemulsification.

J Am Anim Hosp Assoc

July 2021

From the Department of Clinical Science and Services, Royal Veterinary College, University of London, London, United Kingdom (C.A., R.S.H., P.M.); and Specialistische Dierenkliniek Utrecht (SDU), Utrecht, The Netherlands (R.F.S.).

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Chronic myeloid leukemia (CML) is rare in children and accounts for ≤15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph+ CML-CP.

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Current Insights into the Role of the Growth Hormone-Insulin-Like Growth Factor System in Short Children Born Small for Gestational Age.

Horm Res Paediatr

April 2020

Department of Paediatrics, Subdivision of Endocrinology, Erasmus University Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands.

Background: The reason for the insufficient catch-up growth seen in 10% of children born small for gestational age (SGA) is poorly understood. Disturbances in the growth hormone (GH) - insulin-like growth factor (IGF) axis might underlie this failure to show sufficient catch-up growth.

Conclusion: This review summarizes insights gained in the molecular and (epi) genetic mechanisms of the GH-IGF axis in short children born SGA.

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The Atherosclerosis Risk Variant rs2107595 Mediates Allele-Specific Transcriptional Regulation of via E2F3 and Rb1.

Stroke

October 2019

From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Germany (M.P., C.P.S., R.M., B.L., N.Z., M.L., Y.A., F.S., C.H., M.D.).

Background and Purpose- Genome-wide association studies have identified the (histone deacetylase 9) gene region as a major risk locus for atherosclerotic stroke and coronary artery disease in humans. Previous results suggest a role of altered expression levels as the underlying disease mechanism. rs2107595, the lead single nucleotide polymorphism for stroke and coronary artery disease resides in noncoding DNA and colocalizes with histone modification marks suggestive of enhancer elements.

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A Genotype-Guided Strategy for Oral P2Y Inhibitors in Primary PCI.

N Engl J Med

October 2019

From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (D.M.F.C., G.J.A.V., T.O.B., P.W.A.J., J.C.K., J.M.B.), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H., A.W.J.H.), the Department of Cardiology, University Medical Center Maastricht, Maastricht (A.W.J.H.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), the Department of Cardiology, University Medical Center Groningen (P.H., J.M.B.), the Department of Pharmacy, University of Groningen (M.J.P.), and the Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen (M.J.P., C.B.), Groningen, the Department of Cardiology, Rijnstate Hospital, Arnhem (R.M.T.J.G.), the Department of Cardiology, Division of Heart and Lungs (F.W.A.), and the Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics (V.H.M.D.), University Medical Center Utrecht, and the Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (A.B.), Utrecht University, Utrecht, the Department of Cardiology, Meander Medical Center, Amersfoort (A.M.), the Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (J.-P.R.H.), and the Department of Cardiology, Amphia Hospital, Breda (W.J.M.D.) - all in the Netherlands; the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy (E.B., C.M.); the Cardiovascular Research Center, Onze Lieve Vrouwe Hospital, Aalst (E.B.), and the Department of Cardiology, Imelda Hospital, Bonheiden (W.J.M.D.) - both in Belgium; and the Institute of Cardiovascular Science, Faculty of Population Health Sciences, and Health Data Research UK and Institute of Health Informatics, University College London, London (F.W.A.).

Background: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y inhibitors.

Methods: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y inhibitor on the basis of early genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of *2 or *3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel.

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