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128 results on '"Berlin Institute of Health (BIH)"'

1. Characterization of Endogenous SERINC5 Protein as Anti-HIV-1 Factor

Author: Jens Bohne, Daniel Todt, Steppich K, Sergej Franz, Angelina Malassa, Thomas Zillinger, Eike Steinmann, Xu S, Nicoletta Casartelli, Passos, Christine Goffinet, Winfried Barchet, Wachs As, Oliver Schwartz, Schilling H, Kathrin Sutter, Ulf Dittmer, Centre for Experimental and Clinical Infection Research [Hanover] (TWINCORE), Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Institute of Clinical Chemistry and Clinical Pharmacology [Bonn, Allemagne], University of Bonn, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Ruhr University Bochum (RUB), University of Duisburg-Essen, German Centre for Infection Research (DZIF), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Vânia Passos and Sergej Franz are supported by the Infection Biology International Ph.D. Program of the Hannover Biomedical Research School. Vânia Passos is supported by the GABBA Ph.D. Program and the Fundação para a Ciência e Tecnologia (FCT). Thomas Zillinger and Winfried Barchet acknowledge Bonfor and DZIF funding and German Research Foundation (Deutsche Forschungsgemeinschaft [DFG]) grants EXC1023: ImmunoSensation and CRCs 670 and 704. This work is supported by DFG funding to Christine Goffinet (Collaborative Research Centre SFB900, Microbial Persistence and its Control, project C8 and Priority Program 1923, Innate Sensing and Restriction of Retroviruses, GO2153/4 grant) and funding from the HZI and the Berlin Institute of Health (BIH) to Christine Goffinet., Universidade do Porto = University of Porto, Universität Bonn = University of Bonn, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], and TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
Subjects: MESH: Gene Editing, MESH: CRISPR-Cas Systems, T-Lymphocytes, Mutant, Medizin, HIV Infections, Endogeny, Jurkat cells, Epitope, MESH: HIV-1, MESH: Genotype, Gene Knockout Techniques, SERINC5, MESH: nef Gene Products, Human Immunodeficiency Virus, MESH: Anti-HIV Agents, Internalization, media_common, MESH: Gene Knockout Techniques, Gene Editing, 0303 health sciences, human immunodeficiency virus, 030302 biochemistry & molecular biology, virus diseases, MESH: HIV Infections, MESH: Gene Expression Regulation, Virus-Cell Interactions, 3. Good health, Cell biology, interferons, MESH: HEK293 Cells, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Virion, MESH: Membrane Proteins, MESH: Interferon-alpha, Genotype, Anti-HIV Agents, media_common.quotation_subject, Immunology, Alpha interferon, Heterologous, Biology, Microbiology, Cell Line, 03 medical and health sciences, Virology, Nitriles, Humans, nef Gene Products, Human Immunodeficiency Virus, antiviral factor, CRISPR/Cas9, 030304 developmental biology, Nef, MESH: Humans, Cell Membrane, MESH: Host-Pathogen Interactions, Virion, Interferon-alpha, Membrane Proteins, Subcellular localization, MESH: Cell Line, HEK293 Cells, Pyrimidines, MESH: T-Lymphocytes, Gene Expression Regulation, Insect Science, HIV-1, Pyrazoles, CRISPR-Cas Systems, MESH: Pyrazoles, MESH: Cell Membrane
Abstract: SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions., When expressed in virus-producing cells, the cellular multipass transmembrane protein SERINC5 reduces the infectivity of HIV-1 particles and is counteracted by HIV-1 Nef. Due to the unavailability of an antibody of sufficient specificity and sensitivity, investigation of SERINC5 protein expression and subcellular localization has been limited to heterologously expressed SERINC5. We generated, via CRISPR/Cas9-assisted gene editing, Jurkat T-cell clones expressing endogenous SERINC5 bearing an extracellularly exposed hemagglutinin (HA) epitope [Jurkat SERINC5(iHA knock-in) T cells]. This modification enabled quantification of endogenous SERINC5 protein levels and demonstrated a predominant localization in lipid rafts. Interferon alpha (IFN-α) treatment enhanced cell surface levels of SERINC5 in a ruxolitinib-sensitive manner in the absence of modulation of mRNA and protein quantities. Parental and SERINC5(iHA knock-in) T cells shared the ability to produce infectious wild-type HIV-1 but not an HIV-1 Δnef mutant. SERINC5-imposed reduction of infectivity involved a modest reduction of virus fusogenicity. An association of endogenous SERINC5 protein with HIV-1 Δnef virions was consistently detectable as a 35-kDa species, as opposed to heterologous SERINC5, which presented as a 51-kDa species. Nef-mediated functional counteraction did not correlate with virion exclusion of SERINC5, arguing for the existence of additional counteractive mechanisms of Nef that act on virus-associated SERINC5. In HIV-1-infected cells, Nef triggered the internalization of SERINC5 in the absence of detectable changes of steady-state protein levels. These findings establish new properties of endogenous SERINC5 expression and subcellular localization, challenge existing concepts of HIV-1 Nef-mediated antagonism of SERINC5, and uncover an unprecedented role of IFN-α in modulating SERINC5 through accumulation at the cell surface. IMPORTANCE SERINC5 is the long-searched-for antiviral factor that is counteracted by the HIV-1 accessory gene product Nef. Here, we engineered, via CRISPR/Cas9 technology, T-cell lines that express endogenous SERINC5 alleles tagged with a knocked-in HA epitope. This genetic modification enabled us to study basic properties of endogenous SERINC5 and to verify proposed mechanisms of HIV-1 Nef-mediated counteraction of SERINC5. Using this unique resource, we identified the susceptibility of endogenous SERINC5 protein to posttranslational modulation by type I IFNs and suggest uncoupling of Nef-mediated functional antagonism from SERINC5 exclusion from virions.
Published: 2019

2. 2019 ARIA Care pathways for allergen immunotherapy

Author: Dana Wallace, Karin C. Lødrup Carlsen, M. T. Ventura, Igor Kaidashev, Stephen R. Durham, Motohiro Ebisawa, Oliver Pfaar, Hae-Sim Park, Daniel Laune, Wytske Fokkens, Antonella Muraro, Moises A. Calderon, Torsten Zuberbier, Mohamed H. Shamji, Mark S. Dykewicz, Roy Gerth van Wijk, Josep M. Antó, Samantha Walker, Petr Panzner, Giorgio Walter Canonica, Nelson Rosario, Juan Carlos Ivancevich, Holger J. Schünemann, Susanne Halken, Lorenzo Cecchi, Sinthia Bosnic-Anticevich, Violeta Kvedariene, Stefania La Grutta, João Fonseca, Marek L Kowalski, Tari Haahtela, Aziz Sheikh, Montserrat Fernandez-Rivas, Nhan Pham-Thi, Isabelle Bosse, Jean Bousquet, Lan Le, Despo Ierodiakonou, Tomohisa Iinuma, Lars Jacobsen, Christine Rolland, Gert Marien, Wienczyslawa Czarlewski, Glenis Scadding, Ioana Agache, Bolesław Samoliński, Olga Lourenço, Ludger Klimek, Yoshitaka Okamoto, Ulrich Wahn, Joaquim Mullol, Erkka Valovirta, Luigi Caraballo, Sanna Toppila-Salmi, Ioanna Tsiligianni, Derek K. Chu, Ruby Pawankar, Jean Luc Fauquert, Musa Khaitov, Jorg Kleine Tebbe, Jean-François Fontaine, Victoria Cardona, Désirée Larenas-Linemann, Thomas B. Casale, Omer Kalayci, Alvaro A. Cruz, Arunas Valiulis, Anna Bedbrook, Susanne Lau, Alkis Togias, H.-J. Malling, Claus Bachert, Dermot Ryan, Elísio Costa, Giovanni Passalacqua, Ignacio J. Ansotegui, Ana Todo Bom, Marek Jutel, Enrica Menditto, Piotr Kuna, Nikolaos G. Papadopoulos, Gregoire Mercier, Mario Sánchez-Borges, Karl-Christian Bergmann, Susan Waserman, Gunter J. Sturm, Maryline Valentin-Rostan, Arzu Yorgancioglu, Giovanni Battista Pajno, Jan Brozek, George Du Toit, Robyn E O'Hehir, Peter Hellings, Graham Roberts, uBibliorum, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Center for Rhinology and Allergology, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], Department of Allergy and Immunology, Hospital Quiròn Bizkaia Erandio, UPC Research Laboratories, Allergy Department, University of Crete [Heraklion] (UOC), Department of Allergy and Clinical Immunology, Transylvania University of Brasov, Universitat Pompeu Fabra [Barcelona] (UPF), Ghent University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology and Allergy [Berlin, Allemagne], Comprehensive Allergy Center [Berlin, Allemagne], Berlin Institute of Health (BIH)-Berlin Institute of Health (BIH), The University of Sydney, Woolcock Institute of Medical Research [Sydney], CHU Montpellier, Departments of Clinical Epidemiology and Biostatistics and Medicine [Ontario], Section of Allergy and Clinical Immunology [London, UK], Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Institute for Immunological Research (University of Cartagena), University of Cartagena, Allergy Section, Department of Internal Medicine, Vall d'Hebron University Hospital [Barcelona], Division of Allergy and Immunology, Department of Medicine, Creighton University, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada, Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), Universidade Federal da Bahia (UFBA), UCB Pharma, Colombes, Section of Allergy and Clinical Immunology, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], King‘s College London, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Department of Allergology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Helsinki University Hospital, Odense University Hospital, University Hospitals Leuven [Leuven], Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, Department of Clinical Immunology, Wroclaw Medical University, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Laboratory of Molecular Immunology [Moscow, Russian Federation] (National Research Center), Institute of Immunology [Moscow, Russian Federation]-Federal Medicobiological Agency [Moscow, Russian Federation], Hacettepe University = Hacettepe Üniversitesi, Allergy & Asthma Center Westend, Outpatient Clinic Hanf, Department of Immunology, Rheumatology and Allergy, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], CNR-IBIM : National Research Council-Institute of Biomedicine and Molecular Immunology, Department of Pediatric Pneumology and Immunology, Ho Chi Minh City University of Technology (HCMUT), University of Oslo (UiO), Faculty of Health Sciences and CICS-UB (Health Sciences Research Centre), 'Federico II' University of Naples Medical School, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Food Allergy Referral Centre Veneto Region [Padua, Italy], Universita degli Studi di Padova, Monash University [Melbourne], Department of Otorhinolaryngology, Department of Pediatrics, Allergy Unit, University of Messina, Ajou University School of Medicine, Department of Allergology and Clinical Immunology, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Allergy and Respiratory Diseases, University of Genoa (UNIGE), Saint Mary's Hospital [London], St Mary's Hospital [London], Department of Pediatrics, Nippon Medical School, Pediatrics, Universidade Federal do Paraná (UFPR), Medical Centre, Woodbrook Medical Centre, Medical University of Warsaw - Poland, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Medico-Docente La Trinidad, The Royal National Throat, Nose and Ear Hospital, Imperial College London, Centre for Population Health Sciences, University of Edinburgh, Medical University Graz, University of Coimbra [Portugal] (UC), Vilnius University Clinic of Children's Diseases, Suomen Terveystalo Allergy Clinic, Università degli studi di Bari Aldo Moro (UNIBA), Department for Pediatric Pneumology and Immunology, Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, (MRC), Guy's Hospital [London], Nova Southeastern University (NSU), Department of Pulmonology, Manisa Celal Bayar University, Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Association Asthme et Allergie, Internal Medicine, Bousquet, J., Pfaar, O., Togias, A., Schunemann, H. J., Ansotegui, I., Papadopoulos, N. G., Tsiligianni, I., Agache, I., Anto, J. M., Bachert, C., Bedbrook, A., Bergmann, K. -C., Bosnic-Anticevich, S., Bosse, I., Brozek, J., Calderon, M. A., Canonica, G. W., Caraballo, L., Cardona, V., Casale, T., Cecchi, L., Chu, D., Costa, E., Cruz, A. A., Czarlewski, W., Durham, S. R., Du Toit, G., Dykewicz, M., Ebisawa, M., Fauquert, J. L., Fernandez-Rivas, M., Fokkens, W. J., Fonseca, J., Fontaine, J. -F., Gerth van Wijk, R., Haahtela, T., Halken, S., Hellings, P. W., Ierodiakonou, D., Iinuma, T., Ivancevich, J. C., Jacobsen, L., Jutel, M., Kaidashev, I., Khaitov, M., Kalayci, O., Kleine Tebbe, J., Klimek, L., Kowalski, M. L., Kuna, P., Kvedariene, V., La Grutta, S., Larenas-Linemann, D., Lau, S., Laune, D., Le, L., Lodrup Carlsen, K., Lourenco, O., Malling, H. -J., Marien, G., Menditto, E., Mercier, G., Mullol, J., Muraro, A., O'Hehir, R., Okamoto, Y., Pajno, G. B., Park, H. -S., Panzner, P., Passalacqua, G., Pham-Thi, N., Roberts, G., Pawankar, R., Rolland, C., Rosario, N., Ryan, D., Samolinski, B., Sanchez-Borges, M., Scadding, G., Shamji, M. H., Sheikh, A., Sturm, G. J., Todo Bom, A., Toppila-Salmi, S., Valentin-Rostan, M., Valiulis, A., Valovirta, E., Ventura, M. -T., Wahn, U., Walker, S., CORBO UGULINO, Wallace, Waserman, S., Yorgancioglu, A., Zuberbier, T., Hospital Quirónsalud Bizkaia [Bilbao], Sagamihara National Hospital [Kanagawa, Japan], Universidade do Porto = University of Porto, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, Wrocław Medical University, Università degli Studi di Padova = University of Padua (Unipd), Charles University [Prague] (CU)-Medical Faculty in Pilsen, Università degli studi di Genova = University of Genoa (UniGe), Centro Médico Docente La Trinidad, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), and Hibade, Monique
Subjects: Cost effectiveness, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, Comorbidity, medicine.disease_cause, 0302 clinical medicine, Allergen, Cost of Illness, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Precision Medicine, mHealth, Children, media_common, Allergen immunotherapy, Rhinitis, Disease Management, 3. Good health, [SDV] Life Sciences [q-bio], rhiniti, Treatment Outcome, Practice Guidelines as Topic, Critical Pathways, [SDV.IMM]Life Sciences [q-bio]/Immunology, Disease Susceptibility, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Attitude of Health Personnel, Immunology, Clinical Decision-Making, 03 medical and health sciences, Pharmacotherapy, rhinitis, stratification, children, media_common.cataloged_instance, Animals, Humans, European union, Intensive care medicine, allergen immunotherapy, asthma, children, mHealth, rhinitis, stratification, Asthma, business.industry, Allergens, asthma, medicine.disease, Rhinitis, Allergic, Review article, 030228 respiratory system, Desensitization, Immunologic, allergen immunotherapy, Stratification, business, Biomarkers
Abstract: Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. This article is protected by copyright. All rights reserved.
Published: 2019

3. The molecular evolution of spermatogenesis across mammals

Author: Svante Pääbo, Henrik Kaessmann, Thoomke Brüning, Frank Grützner, Philipp Khaitovich, Francesco Lamanna, Mari Sepp, Meritxell Riera Belles, Julia Schmidt, Katharina Mößinger, Christian Conrad, Rüdiger Behr, Celine Schneider, Ronald E. Bontrop, Sofia B. Winge, Kristian Almstrup, Timo Trefzer, Florent Murat, Ivanela Kondova, Margarida Cardoso-Moreira, Evgeny Leushkin, Noe Mbengue, Mikkel H. Schierup, Tomas Marques-Bonet, Theoretical Biology and Bioinformatics, Sub Theoretical Biology, Center for Molecular Biology - Zentrum für Molekulare Biologie [Heidelberg, Germany] (ZMBH), Universität Heidelberg [Heidelberg], Aarhus University [Aarhus], University of Copenhagen = Københavns Universitet (KU), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], The Francis Crick Institute [London], Biomedical Primate Research Centre [Rijswijk] (BPRC), German Primate Center - Deutsches Primatenzentrum -- Leibniz Insitute for Primate Research -- [Göttingen, Allemagne] (GPC - DPZ), German Center for Cardiovascular Research (DZHK), Skolkovo Institute of Science and Technology [Moscow] (Skoltech), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, Institut de Biologia Evolutiva [Barcelona] (IBE / UPF - CSIC), Universitat Pompeu Fabra [Barcelona] (UPF), Institució Catalana de Recerca i Estudis Avançats (ICREA), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona (UAB), Robinson Research Institute, and University of Adelaide
Subjects: Male, [SDV]Life Sciences [q-bio], Gene Expression, Cell-adhesion, 0302 clinical medicine, Ecology,Evolution & Ethology, Origins, Sex-chromosomes, Features, X chromosome, X-chromosome, 0303 health sciences, Spermatogenic Cell, Human Biology & Physiology, Multidisciplinary, Chromatin/genetics, Sertoli cell, Gene expression profiling, Dynamics, Chromatin, medicine.anatomical_structure, Sexual selection, Genetics & Genomics, Macaque, Model organisms, Evolution, Mammals/genetics, Biology, Chromosomes, Evolutionary genetics, Evolution, Molecular, 03 medical and health sciences, Meiosis, Molecular evolution, medicine, Animals, mammals, General, 030304 developmental biology, Computational & Systems Biology, Spermatogenesis/genetics, Molecular, Chromosome, Evolutionary pressure, spermatogenesis, Genes, Meiosis/genetics, Evolutionary biology, Testis/metabolism, 030217 neurology & neurosurgery, Developmental Biology
Abstract: The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals1-6, probably owing to the evolutionary pressure on males to be reproductively successful7. However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from 11 species that cover the three main mammalian lineages (eutherians, marsupials and monotremes) and birds (the evolutionary outgroup), and include seven primates. We find that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions and new genes in late spermatogenic stages, probably facilitated by reduced pleiotropic constraints, haploid selection and transcriptionally permissive chromatin. We identify temporal expression changes of individual genes across species and conserved expression programs controlling ancestral spermatogenic processes. Genes predominantly expressed in spermatogonia (germ cells fuelling spermatogenesis) and Sertoli (somatic support) cells accumulated on X chromosomes during evolution, presumably owing to male-beneficial selective forces. Further work identified transcriptomal differences between X- and Y-bearing spermatids and uncovered that meiotic sex-chromosome inactivation (MSCI) also occurs in monotremes and hence is common to mammalian sex-chromosome systems. Thus, the mechanism of meiotic silencing of unsynapsed chromatin, which underlies MSCI, is an ancestral mammalian feature. Our study illuminates the molecular evolution of spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals. We thank all members of the Kaessmann group, S. Tirier for discussions and N. Trost for the administration of the Kaessmann laboratory server. Computations were performed on the Kaessmann laboratory server and the bwForCluster from the Heidelberg University Computational Center (supported by the state of Baden-Württemberg through bwHPC and the German Research Foundation grant no. INST 35/1134-1 FUGG). This research was supported by grants from the ERC (grant no. 615253, OntoTransEvol) and German Research Council (DFG, grant nos. SFB 873 and KA 1710/4-1) to H.K., by the CellNetworks Postdoc Fellowship and EMBO Long-Term Fellowship to F.M. (grant no. ALTF 591-2017), and by the Australian Research Council (grant no. FT160100267) to F.G. and by the Novo Nordisk Foundation (grant no. NNF21OC0069913) to K.A. and (grant no. NNF18OC0031004) to M.H.S. The use of all other mammalian samples for the type of work described in this study was approved by ERC ethics screening panels (ERC starting grant no. 242597, SexGenTransEvolution and ERC consolidator grant no. 615253, OntoTransEvol).
Published: 2023
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4. Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction

Author: Javed Butler, Milton Packer, Gerasimos Filippatos, Joao Pedro Ferreira, Cordula Zeller, Janet Schnee, Martina Brueckmann, Stuart J Pocock, Faiez Zannad, Stefan D Anker, BOZEC, Erwan, University of Mississippi Medical Center (UMMC), Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton, National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Attikon University Hospital, 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Boehringer Ingelheim International GmbH, University of Heidelberg, Medical Faculty, London School of Hygiene and Tropical Medicine (LSHTM), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Funding for the EMPEROR trials was provided by Boehringer Ingelheim and Eli Lilly and Company., and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Ejection fraction, animal structures, Empagliflozin, Stroke Volume, Heart failure, 030204 cardiovascular system & hematology, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, 03 medical and health sciences, 0302 clinical medicine, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Sex, 030212 general & internal medicine, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine
Abstract: Aims No therapy has shown to reduce the risk of hospitalization for heart failure across the entire range of ejection fractions seen in clinical practice. We assessed the influence of ejection fraction on the effect of the sodium–glucose cotransporter 2 inhibitor empagliflozin on heart failure outcomes. Methods and results A pooled analysis was performed on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9718 patients; 4860 empagliflozin and 4858 placebo), and patients were grouped based on ejection fraction: Conclusion The magnitude of the effect of empagliflozin on heart failure outcomes was clinically meaningful and similar in patients with ejection fractions Key Question How does ejection fraction influence the effects of empagliflozin in patients with heart failure and either a reduced or a preserved ejection fraction? Key Finding The magnitude of the effect of empagliflozin on heart failure outcomes and health status was similar in patients with ejection fractions Take Home Message The consistency of the response in patients with ejection fractions of
Published: 2021

5. Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction

Author: Subodh Verma, Milton Packer, Stefan D. Anker, Carolyn S.P. Lam, Daniel Cotton, Stuart J. Pocock, Martina Brueckmann, David Sim, Janet Schnee, Javed Butler, Egon Pfarr, Gerasimos Filippatos, João Pedro Ferreira, Hiroyuki Tsutsui, Faiez Zannad, Naveed Sattar, Cardiovascular Centre (CVC), National Heart Centre Singapore (NHCS), University Medical Center Groningen [Groningen] (UMCG), 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Boehringer Ingelheim International GmbH, Department of Cardiovascular Medicine, Kyushu University, Higashi-ku, Kyushu University [Fukuoka], Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Mississippi State University [Mississippi], Attikon University Hospital, National and Kapodistrian University of Athens (NKUA), London School of Hygiene and Tropical Medicine (LSHTM), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, St. Michael's Hospital, University of Toronto, University of Heidelberg, Medical Faculty, Boehringer Ingelheim Pharmaceuticals, Inc, Baylor University Medical Center, Baylor College of Medecine, Imperial College London, and The EMPEROR-Reduced trial was funded by Boehringer Ingelheim and Eli Lilly (EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977)
Subjects: Relative risk reduction, Ethnic group, Empagliflozin, Fast Track Clinical Research, Heart failure, 030204 cardiovascular system & hematology, Placebo, Racial differences, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Ethnicity, Medicine, Humans, In patient, AcademicSubjects/MED00200, 030212 general & internal medicine, Benzhydryl Compounds, 10. No inequality, Heart Failure and Cardiomyopathies, Ejection fraction, business.industry, Geographic differences, Stroke Volume, medicine.disease, 3. Good health, Cardiology and Cardiovascular Medicine, business, Demography
Abstract: Aims The aim of this article is to explore the influence of region and race/ethnicity on the effects of empagliflozin in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) trial. Methods and results Of 3730 patients, 1353 (36.3%) were enrolled in Europe, 1286 (34.5%) in Latin America, 425 (11.4%) in North America, and 493 (13.2%) in Asia; 2629 (70.5%) were White, 257 (6.9%) Black, and 672 (18.0%) Asian. Placebo event rates (per 100 patient-years) for cardiovascular death or heart failure (HF) hospitalization varied by region (Asia 27.7, North America 26.4, Latin America 21.4, and Europe 17.5) and race/ethnicity (Black 34.4, Asian 24.3, and White 18.7); driven by differences in HF hospitalization. The ratio of total HF hospitalization to cardiovascular death varied from 5.4 in Asia and 4.8 in North America to 2.1 in Europe; and from 4.8 in Black and 4.2 in Asian to 2.2 in White patients. Groups with the highest ratio had the greatest reduction in the primary outcome with empagliflozin. Inclusion of outpatient worsening HF episodes added more events in Europe vs. other regions; enhanced the placebo event rates in Europe vs. other regions; and increased the relative risk reduction with empagliflozin in Europe from 6% to 26%. Conclusions There were notable differences in the placebo event rates for major HF events across diverse regions and race/ethnic groups. The benefit of empagliflozin was most pronounced in groups with the highest ratio of HF hospitalization to cardiovascular death. Regional differences were attenuated when the definition of HF events was expanded to include outpatient worsening HF events., Graphical Abstract Effect of empagliflozin by region and race in EMPEROR-Reduced. Inclusion of outpatient events in the extended composite endpoint attenuated the between-region differences in the effect of empagliflozin seen in the primary outcome of EMPEROR-Reduced.
Published: 2021

6. Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure

Author: Gerasimos Filippatos, João Pedro Ferreira, Anne Pernille Ofstad, Waheed Jamal, Christoph Wanner, Javed Butler, Elke Schüler, Martina Brueckmann, Investigators, Stuart J. Pocock, Milton Packer, Faiez Zannad, EMPEROR-Reduced Trial Committees, Piotr Ponikowski, Stefan D. Anker, Michael Böhm, Felix Mahfoud, Saarland University [Saarbrücken], Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), London School of Hygiene and Tropical Medicine (LSHTM), Boehringer Ingelheim International GmbH, University of Heidelberg, Medical Faculty, Boehringer Ingelheim Norway KS, mainanalytics GmbH, Wroclaw Medical University, University Hospital of Würzburg, Baylor University Medical Center, Baylor College of Medecine, Imperial College London, BOZEC, Erwan, and Wrocław Medical University
Subjects: Male, systolic blood pressure, medicine.medical_specialty, animal structures, empagliflozin, heart failure, Blood Pressure, 030204 cardiovascular system & hematology, Cardiovascular death, 03 medical and health sciences, 0302 clinical medicine, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Empagliflozin, medicine, Humans, In patient, 030212 general & internal medicine, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, Ejection fraction, business.industry, kidney outcomes, Middle Aged, medicine.disease, cardiovascular outcomes, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Treatment Outcome, Blood pressure, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Cardiovascular outcomes, Glomerular Filtration Rate, Heart Failure, Systolic
Abstract: International audience; Background: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with reduced ejection fraction. Its interplay with systolic blood pressure (SBP) is not known.Objectives: The goal of this study was to evaluate the interplay of SBP and the effects of empagliflozin in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).Methods: Study patients (N = 3,730) were randomly assigned to groups according to SBP at baseline (130 mm Hg, n = 1,047). This study explored the influence of SBP on the effects of empagliflozin on cardiovascular death or HF hospitalization (primary outcome), as well as on total HF hospitalizations, rate of decline in estimated glomerular filtration rate, renal outcomes, and empagliflozin's effects and significance on SBP.Results: Over a median of 16 months considering only patients receiving placebo, baseline SBP and the risk of cardiovascular death or hospitalization for HF (P trend = 0.0015) were inversely related. Corrected for placebo, a slight early increase was observed in SBP at 130 mm Hg. These between-group differences were of borderline significance (P for interaction trend = 0.05-0.10) after 4 and 12 weeks but were not significant later. SBP at baseline did not influence the effect of empagliflozin to reduce the risk of HF events or renal endpoints. When treated with empagliflozin, patients with SBP
Published: 2021

7. COVID-19-related cardiac complications from clinical evidences to basic mechanisms: opinion paper of the ESC Working Group on Cellular Biology of the Heart

Author: Can Gollmann-Tepeköylü, Sabine Steffens, Ivan Tancevski, Sean M. Davidson, Maurizio Pesce, Joost P.G. Sluijter, Piergiuseppe Agostoni, Raffaele De Caterina, Sandrine Lecour, Bianca J.J.M. Brundel, Jean-Sébastien Hulot, Cinzia Perrino, Péter Ferdinandy, Hans-Erik Bøtker, Henrique Girão, Mariann Gyöngyösi, Rainer Schulz, Rosalinda Madonna, Carsten Tschöpe, Sophie Van Linthout, Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Università degli Studi di Milano = University of Milan (UNIMI), Aarhus University Hospital, Amsterdam UMC - Amsterdam University Medical Center, University College of London [London] (UCL), University of Pisa - Università di Pisa, Semmelweis University [Budapest], University of Coimbra [Portugal] (UC), Medizinische Universität Wien = Medical University of Vienna, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Cape Town, University of Naples Federico II = Università degli studi di Napoli Federico II, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Utrecht University [Utrecht], Ludwig-Maximilians-Universität München (LMU), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), The University of Texas Medical School at Houston, and HULOT, Jean-Sébastien
Subjects: 0301 basic medicine, Heart Diseases, Physiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Inflammation, Disease, 030204 cardiovascular system & hematology, Bioinformatics, Vascular occlusion, 03 medical and health sciences, 0302 clinical medicine, Viral entry, Physiology (medical), medicine, Coagulopathy, Animals, Humans, Myocytes, Cardiac, Blood Coagulation, Cause of death, Myocytes, Ventricular Remodeling, SARS-CoV-2, business.industry, COVID-19, Heart, medicine.disease, Omics, Disease modelling, Infection, Myocardial injury, Biomarkers, Fibrosis, Host-Pathogen Interactions, Inflammation Mediators, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cytokine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Cardiac
Abstract: The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.
Published: 2021

8. Clopidogrel vs. prasugrel vs. ticagrelor in patients with acute myocardial infarction complicated by cardiogenic shock: a pooled IABP-SHOCK II and CULPRIT-SHOCK trial sub-analysis

Author: Gilles Montalescot, Steffen Desch, Peter Clemmensen, Martin Orban, Paul M Haller, Steffen Schneider, Dariusz Dudek, Jan Kleeberger, Steffen Massberg, Uwe Zeymer, Holger Thiele, Alexander Neumer, Jörg Hausleiter, Anne Freund, Marko Noc, Kurt Huber, Georg Fuernau, Hans-Josef Feistritzer, Taoufik Ouarrak, Tobias Geisler, Ludwig-Maximilians-Universität München (LMU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Klinikum Ludwigshafen [Germany], Leipzig University, Universität zu Lübeck [Lübeck], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Sigmund Freud University (SFU), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Ticagrelor, medicine.medical_specialty, Prasugrel, [SDV]Life Sciences [q-bio], Myocardial Infarction, Shock, Cardiogenic, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, cardiovascular diseases, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Cardiogenic shock, Aged, Aged, 80 and over, Original Paper, Intra-Aortic Balloon Pumping, business.industry, Bleeding, General Medicine, Middle Aged, medicine.disease, Clopidogrel, 3. Good health, Shock (circulatory), Conventional PCI, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, ADP-receptor antagonists, Prasugrel Hydrochloride, Platelet Aggregation Inhibitors, Follow-Up Studies, medicine.drug
Abstract: Aims The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Methods and results For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24). Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution. Graphic abstract
Published: 2021

9. Quality of life in men and women with heart failure: association with outcome, and comparison between the Kansas City Cardiomyopathy Questionnaire and the EuroQol 5 dimensions questionnaire

Author: Nilesh J. Samani, João Pedro Ferreira, Kenneth Dickstein, Faiez Zannad, Sven Meyer, Marco Metra, John R. Teerlink, Carlo Lombardi, Chim C. Lang, Alice Ravera, Adriaan A. Voors, Iziah E Sama, Bernadet T. Santema, Valentina Carubelli, Stefan D. Anker, Dirk J. van Veldhuisen, University Medical Center Groningen [Groningen] (UMCG), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia = University of Brescia (UniBs), Carl Von Ossietzky Universität Oldenburg = Carl von Ossietzky University of Oldenburg (OFFIS), 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University of Dundee, Ninewells Hospital and Medical School [Dundee], University of Bergen (UiB), Stavanger University Hospital, Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), Cardiovascular Centre (CVC), BOZEC, Erwan, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Heart Center Oldenburg, Department of Cardiology, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, and Department of Cardiovascular Sciences, University of Leicester, NIHR (National Institute for Health Research) Leicester Biomedical Research Centre, Glenfield Hospital
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Heart failure, Outcome, Quality of life, Sex, Women, Female, Humans, Kansas, Quality of Life, Stroke Volume, Surveys and Questionnaires, Cardiomyopathies, Heart Failure, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Medicine, Ejection fraction, business.industry, medicine.disease, Tailored treatment, humanities, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Clinical trial, Kansas City Cardiomyopathy Questionnaire, Cardiology and Cardiovascular Medicine, business
Abstract: Aims: We sought to analyse quality of life (QoL) measures derived from two questionnaires widely used in clinical trials, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL 5 dimensions (EQ-5D), and to compare their prognostic value in men and women with heart failure and reduced ejection fraction (HFrEF).Methods and results: From the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) we compared KCCQ and EQ-5D at baseline and after 9 months in 1276 men and 373 women with new-onset or worsening symptoms of HFrEF, who were sub-optimally treated and in whom there was an anticipated up-titration of guideline-derived medical therapies. Women had significantly worse baseline QoL (median) as compared with men, both when assessed with KCCQ overall score (KCCQ-OS, 44 vs. 53, P < 0.001) and EQ-5D utility score (0.62 vs. 0.73, P < 0.001). QoL improved equally in women and men at follow-up. All summary measures of QoL were independently associated with all-cause mortality, with KCCQ-OS showing the most remarkable association with mortality up to 1 year compared to the EQ-5D scores (C-statistic 0.650 for KCCQ-OS vs. 0.633 and 0.599 for EQ-5D utility score and EQ-5D visual analogue scale, respectively). QoL was associated with all outcomes analysed, both in men and women (all P for interaction with sex >0.2).Conclusion: Amongst patients with HFrEF, women reported significantly worse QoL than men. QoL was independently associated with subsequent outcome, similarly in men and women. The KCCQ in general, and the KCCQ-OS in particular, showed the strongest independent association with outcome.
Published: 2021

10. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author: Martina Müller-Nurasyid, Jerome I. Rotter, David M. Evans, John P. Kemp, Emelia J. Benjamin, Graciela E. Delgado, Vilmundur Gudnason, Ann Hammarstedt, Panos Deloukas, Aroon D. Hingorani, Riccardo E. Marioni, David Stacey, Jenny van Dongen, Eric Boerwinkle, Joachim Heinrich, Yongmei Liu, S. Goya Wannamethee, Delilah Zabaneh, Braxton D. Mitchell, Marie Standl, Jackie F. Price, Maria G. Stathopoulou, Yoav Ben-Shlomo, Joris Deelen, Eero Kajantie, Mohammadreza Abdollahi, Christie M. Ballantyne, Johan G. Eriksson, Ilkka Seppälä, Elnaz Naderi, Barbara J. Jefferis, Richard W Morris, Nicholas J. Timpson, George Dedoussis, Sirpa Jalkanen, Mika Kivimäki, Perminder S. Sachdev, Diana van Heemst, Melanie Waldenberger, Gaurav Singhal, Elisabeth Thiering, Olli T. Raitakari, Anders Hamsten, Zoltán Kutalik, L. Bain, Eco J. C. de Geus, Tarunveer S. Ahluwalia, Yuri Milaneschi, Hubert Scharnagl, Juan P. Casas, Georg Homuth, Claes Ohlsson, Abbas Dehghan, Nicola J. Armstrong, Behrooz Z. Alizadeh, Terho Lehtimäki, Steve E. Humphries, Naveed Sattar, Bram P. Prins, Peter Rossing, Sophie Visvikis-Siest, Joana A. Revez, Ilja M. Nolte, Stella Trompet, Harold Snieder, Marian Beekman, Diana Marek, Beate St Pourcain, Thorkild I. A. Sørensen, Silvia Naitza, Karen A. Mather, Uwe Völker, Eline Slagboom, Tina Shah, Magdalene C. Jawahar, Jens Baumert, Alexander Teumer, Dorret I. Boomsma, Marcus E. Kleber, Peter Vollenweider, Wolfgang Koenig, Brenda W.J.H. Penninx, Kenneth Rice, Ian J. Deary, Pedro Marques-Vidal, Donna K. Arnett, Eleonora Porcu, Jouke-Jan Hottenga, Maria Sabater-Lleal, Bruce M. Psaty, Matthias Nauck, Dan Mellström, Joel Eriksson, Bernhard T. Baune, Debbie A Lawlor, Catherine Toben, Peter H. Whincup, Toshiko Tanaka, Stavroula Kanoni, Katri Räikkönen, Gonneke Willemsen, Bengt Sennblad, Julian N. Trollor, Yalda Jamshidi, Sarah E. Harris, Jari Lahti, Joshua C. Bis, Peter Durda, Yen Pei C. Chang, Jorgen Engmann, Tom R. Gaunt, Stella Aslibekyan, Anbupalam Thalamuthu, Mary F. Feitosa, Angela Silveira, Tine Jess, Stela McLachlan, J. Wouter Jukema, Chen Lu, Simon P. Mooijaart, Tim D. Spector, Harald Grallert, Winfried März, Alexandros M. Petrelis, Manuel A. R. Ferreira, Meena Kumari, Stochastics, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, CHARGE Inflammation Working Group, Epidemiology, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), University of Groningen [Groningen], Murdoch University, University of Alabama at Birmingham [ Birmingham] (UAB), QIMR Berghofer Medical Research Institute, University College of London [London] (UCL), Helmholtz-Zentrum München (HZM), Leiden University Medical Center (LUMC), University of Bristol [Bristol], University of Washington [Seattle], University of Maryland School of Medicine, University of Maryland System, Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], University of Heidelberg, Medical Faculty, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Sahlgrenska Academy at University of Gothenburg [Göteborg], National Institute for Health and Welfare [Helsinki], University of Helsinki, William Harvey Research Institute, Barts and the London Medical School, University of Queensland [Brisbane], School of Public Health [Boston], Boston University [Boston] (BU), MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, University of Edinburgh, Amsterdam UMC, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Karolinska Institutet [Stockholm], University of Tampere [Finland], Adelaide Medical School [Australia], University of Adelaide, Universität Greifswald - University of Greifswald, University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, Ludwig-Maximilians-Universität München (LMU), Baylor College of Medicine (BCM), Baylor University, Boston University School of Medicine (BUSM), VA Boston Healthcare System, Harokopio University of Athens, Max planck Institute for Biology of Ageing [Cologne], Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, University of Turku, St George's, University of London, Statens Serum Institut [Copenhagen], Medical Faculty [Mannheim], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Johannes Gutenberg - Universität Mainz (JGU), Vrije Universiteit Medical Centre (VUMC), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Medical University Graz, Uppsala Universitet [Uppsala], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Kentucky, Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Maryland [Baltimore], Queen Mary University of London (QMUL), University of Iceland [Reykjavik], Ludwig Maximilian University [Munich] (LMU), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Ulm (UUlm), University of Essex, Greifswald University Hospital, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), King‘s College London, University of Cambridge [UK] (CAM), Harbor UCLA Medical Center [Torrance, Ca.], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Genome Sequencing Center [Houston] (HGSC), Baylor University-Baylor University, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Department of Bacteriology and Immunology, Department of Public Health, Department of Psychology and Logopedics, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Doctoral Programme in Human Behaviour, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: AcademicSubjects/SCI01140, [SDV]Life Sciences [q-bio], Genome-wide association study, 030204 cardiovascular system & hematology, DISEASE, Pathogenesis, Cohort Studies, 0302 clinical medicine, cytokine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Association Studies Article, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Genetics, 0303 health sciences, ARCHITECTURE, CHRONIC INFLAMMATION, 1184 Genetics, developmental biology, physiology, General Medicine, RECEPTOR IL-6R GENE, C-REACTIVE PROTEIN, hla-drb1 gene, 3. Good health, Medical genetics, Medical Genetics, chromosomes, medicine.medical_specialty, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, anti-inflammatory agents, White People, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Interleukin 6, Molecular Biology, Medicinsk genetik, 030304 developmental biology, PRODUCE IL-6, Interleukin-6, Chromosome, Receptors, Interleukin-6, RHEUMATOID-ARTHRITIS, Interleukin 1 Receptor Antagonist Protein, Gene Expression Regulation, Genetic Loci, CELLS, biology.protein, 1182 Biochemistry, cell and molecular biology, Human genome, 3111 Biomedicine, Genome-Wide Association Study, HLA-DRB1 Chains, Interleukin-1
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

11. αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus

Author: Bernard Malissen, Joy Nakawesi, Julia Hütter, Sébastien This, Harry B. Greenberg, L. J. Gooday, A. Garcias López, V. Barateau, Katharina Lahl, K. Getachew Muleta, K. Fog Thomsen, Olivier Thaunat, M. Boucard-Jourdin, T. Defrance, Didier Poncet, Isabel Ulmert, H. Paidassi, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technical University of Denmark - Division of Biopharma - Institut for Health Tech - Kongens, Berlin Institute of Health (BIH), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stanford University School of Medicine [CA, USA], VA Palo Alto Health Care System, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), ANR-13-PDOC-0019,InteReg,Régulation de l'expression de l'intégrine alpha-v-beta-8 et son rôle dans le maintien de l'homéostasie immunitaire de l'intestin(2013), Biologie Moléculaire des Rotavirus (ROTA), Département Virologie (Dpt Viro), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Paul Scherrer Institute (PSI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Rotavirus, 0301 basic medicine, Integrins, HOMEOSTASIS, [SDV]Life Sciences [q-bio], Immunology, Integrin, Context (language use), Antibodies, Viral, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Rotavirus Infections, Virus, ACTIVATION, 03 medical and health sciences, 0302 clinical medicine, Antibody Specificity, INFECTION, TGF beta signaling pathway, medicine, Immunology and Allergy, Mesenteric lymph nodes, TGF-BETA-1, REGULATORY T-CELLS, ComputingMilieux_MISCELLANEOUS, TGF beta 1, biology, GROWTH-FACTOR-BETA, INDUCTION, TGF-BETA, Dendritic Cells, Immunoglobulin A, 3. Good health, Basic-Leucine Zipper Transcription Factors, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, B-CELLS, Host-Pathogen Interactions, Immunoglobulin A, Secretory, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Homeostasis, 030215 immunology
Abstract: International audience; Secretory intestinal IgA can protect from re-infection with rotavirus (RV), but very little is known about the mechanisms that induce IgA production during intestinal virus infections. Classical dendritic cells (cDCs) in the intestine can facilitate both T cell-dependent and -independent secretory IgA. Here, we show that BATF3-dependent cDC1, but not cDC2, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes. This depends on the selective expression of the TGF beta-activating integrin alpha v beta 8 by cDC1. In contrast, alpha v beta 8 on cDC1 is dispensible for steady state immune homeostasis. Given that cDC2 are crucial in driving IgA during steady state but are dispensable for RV-specific IgA responses, we propose that the capacity of DC subsets to induce intestinal IgA responses reflects the context, as opposed to an intrinsic property of individual DC subsets.
Published: 2021

12. The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Author: Job A.J. Verdonschot, JoÃo Pedro Ferreira, Anne Pizard, Pierpaolo Pellicori, Hans-Peter Brunner La Rocca, Andrew L. Clark, Franco Cosmi, Joe Cuthbert, Nicolas Girerd, Olivia J. Waring, Michiel H.T.M. Henkens, Beatrice Mariottoni, Johannes Petutschnigg, Patrick Rossignol, Mark R. Hazebroek, John G.F. Cleland, Faiez Zannad, Stephane R.B. Heymans, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], 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), 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), 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 ), University of Glasgow, University of Hull [United Kingdom], Cortona Hospital, Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement N° 305507 (HOMAGE). S.H.: This manuscript has been possible thanks to the support of the the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, MUMC+: MA Med Staf Artsass Cardiologie (9), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), and Department of Cardiology, Cortona Hospital
Subjects: Male, Proteomics, obesity, Cardiac & Cardiovascular Systems, heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, LEPTIN, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PEOPLE, Glucose Intolerance, Humans, Obesity, 030304 developmental biology, Mineralocorticoid Receptor Antagonists, 0303 health sciences, INSULIN-RESISTANCE, Science & Technology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, spironolactone, ADRENOMEDULLIN, FAT, Cardiovascular System & Cardiology, biomarker, Female, ADIPOKINE, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Biomarkers
Abstract: BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66). CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure. ispartof: JOURNAL OF CARDIAC FAILURE vol:28 issue:5 pages:778-786 ispartof: location:United States status: published
Published: 2022

13. The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart ‘OMics’ in AGEing (HOMAGE) randomized clinical trial

Author: Cleland, John, Ferreira, João Pedro, Mariottoni, Beatrice, Pellicori, Pierpaolo, Cuthbert, Joe, Verdonschot, Job, Petutschnigg, Johannes, Ahmed, Fozia, COSMI, FRANCO, Brunner La Rocca, Hans-Peter, Mamas, Mamas, Clark, Andrew, Edelmann, Frank, Pieske, Burkert, Khan, Javed, McDonald, Ken, Rouet, Philippe, Staessen, Jan, Mujaj, Blerim, González, Arantxa, Diez, Javier, Hazebroek, Mark, Heymans, Stephane, Latini, Roberto, Grojean, Stéphanie, Pizard, Anne, Girerd, Nicolas, Rossignol, Patrick, Collier, Tim, Zannad, Faiez, Atar, Dan, Kober, Lars, Dickstein, Kenneth, Lange, Theis, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: MA Med Staf Artsass Cardiologie (9), University of Glasgow, Robertson Centre for Biostatistics, University of Glasgow, Institute of Health and Wellbeing, University of Glasgow-Gartnavel General Hospital, Glasgow, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Cortona Hospital, Castle Hill Hospital, University of Hull [United Kingdom], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Keele University [Keele], University College Dublin [Dublin] (UCD), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Universitäts Klinikum Freiburg, Universidad de Navarra [Pamplona] (UNAV), Institute of Health Carlos III, Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain] (IdiSNA), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Fondation Force, Research and Consulting Department, EDDH, Centre de Médecine Préventive, and London School of Hygiene and Tropical Medicine (LSHTM)
Subjects: Male, Aging, Cardiac & Cardiovascular Systems, Spironolactone, 030204 cardiovascular system & hematology, Q1, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, Clinical endpoint, AcademicSubjects/MED00200, 030212 general & internal medicine, Mineralocorticoid Receptor Antagonists, Collagen markers, R735, Heart failure prevention, RC666, 16. Peace & justice, 3. Good health, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Procollagen, Cardiac function curve, medicine.medical_specialty, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, N-terminal telopeptide, Clinical Research, Internal medicine, medicine, Humans, Heart Failure and Cardiomyopathies, Aged, Heart Failure, Science & Technology, business.industry, medicine.disease, R1, Peptide Fragments, Procollagen peptidase, Blood pressure, chemistry, Heart failure, Cardiovascular System & Cardiology, ras Proteins, business, RA, Biomarkers
Abstract: Importance: Cardiovascular accumulation of collagen (fibrosis) may contribute to the progression from ventricular dysfunction to heart failure. Galectin-3, a potential marker of pro-fibrotic activity, might identify those at greater risk.\ud Objective: To investigate the effects of spironolactone, according to serum galectin-3 concentration, on serum markers of fibrosis and on cardiac structure and function, in people at increased risk of developing heart failure.\ud Design: Prospective, randomized, open-label, blinded endpoint (PROBE) trial.\ud Setting: Clinical research facilities in ten European hospitals.\ud Participants: People with, or at high-risk of, coronary disease with increased plasma concentrations of B-type natriuretic peptides (BNP or NT-proBNP).\ud Interventions: spironolactone (up to 50 mg/day) or control for up to nine months.\ud Main Outcomes and Measures: The primary outcome was the interaction between baseline serum galectin-3 and change in serum procollagen type-III N-terminal pro-peptide (PIIINP), a by-product of type-III collagen synthesis. Serum procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), respectively reflecting synthesis and degradation of type-I collagen, were also measured.\ud Results: Of 527 participants, the median age was 73 years and 26% were women. Median follow-up was 267 days. Changes in PIIINP were similar for those assigned to spironolactone and control (mean difference -0.15; 95% confidence interval [CI] -0.44 to 0.15 μg/L; p=0.32) and did not differ when serum galectin-3 was above or below median. Those assigned to spironolactone had greater declines in PICP (mean difference -8.1; -95% CI -11.9 to -4.3 μg/L; p
Published: 2020

14. Atypical clinical presentation of COVID-19 infection in residents of a long-term care facility

Author: Mylène Albrand, Stéphanie Miot, Jean Bousquet, Nadia Giacosa, Yves Rolland, Hubert Blain, Athanase Benetos, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], 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), Service de Gériatrie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt-Universität zu Berlin, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Humboldt University Of Berlin, and Herrada, Anthony
Subjects: Male, Pediatrics, Delayed Diagnosis, rRT-PCR, Testing for SARS-CoV-2, Disease, Polymerase Chain Reaction, Hypoxemia, MESH: Long-Term Care, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: COVID-19, Medicine, Infection control, MESH: Skilled Nursing Facilities, 030212 general & internal medicine, MESH: Aged, Aged, 80 and over, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Brief Report, MESH: Accidental Falls, 3. Good health, MESH: Diarrhea, Diarrhea, COVID-19 Nucleic Acid Testing, Female, medicine.symptom, Presentation (obstetrics), Long-term-care facility, MESH: Pandemics, medicine.medical_specialty, Health Personnel, Asymptomatic, MESH: COVID-19 Nucleic Acid Testing, 03 medical and health sciences, Humans, MESH: SARS-CoV-2, Pandemics, Aged, Skilled Nursing Facilities, MESH: Humans, 030214 geriatrics, SARS-CoV-2, business.industry, COVID-19, MESH: Polymerase Chain Reaction, Long-Term Care, MESH: Male, MESH: Delayed Diagnosis, Long-term care, MESH: Health Personnel, Delirium, Accidental Falls, business, MESH: Female
Abstract: Key summary points Aim To assess the magnitude of the infection in residents from—and staff working in—a long-term-care facility (LTCF) 7 days after the identification of one resident with confirmed COVID-19 infection and the clinical presentation of the infected residents. Findings Two weeks after the first case, 50.9% of residents and 27.5% of the workers were tested positive for SARS-CoV-2. Diarrhea, fall, delirium, and hypothermia can be initial symptoms of COVID-19 in LTCF residents. Message The rapid dissemination of a COVID-19 infection in a LTCF may be due to a delay in the diagnosis of the first case, whose presentation could be atypical in residents., Purpose To assess the magnitude of the infection in residents from—and staff working in—a long-term-care facility (LTCF) 7 days after the identification of one resident with confirmed COVID-19 infection and to assess the clinical presentation of the infected residents. Methods All residents and staff members of a LTCF were tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab. Residents were studied clinically 4 weeks after the first COVID diagnosis. Results Thirty-eight of the 79 residents (48.1%) tested positive for SARS-CoV-2. Respiratory symptoms were preceded by diarrhea (26.3%), a fall (18.4%), fluctuating temperature with hypothermia (34.2%) and delirium in one resident. Respiratory symptoms, including cough and oxygen desaturation, appeared after those initial symptoms or as the first sign in 36.8% and 52.2%, respectively. At any time of the disease, fever was observed in 65.8%. Twelve deaths occurred among the COVID-19 residents. Among the 41 residents negative for SARS-CoV-2, symptoms included cough (21.9%), diarrhea (7.3%), fever (21.9%), hypothermia (9.7%), and transient hypoxemia (9.8%). No deaths were observed in this group. 27.5% of the workers were also COVID-19 positive. Conclusion The rapid dissemination of the COVID-19 infection may be explained by the delay in the diagnosis of the first cases due to atypical presentation. Early recognition of symptoms compatible with COVID-19 may help to diagnose COVID-19 residents earlier and test for SARS-CoV-2 symptomatic and asymptomatic staff and residents earlier to implement appropriate infection control practices.
Published: 2020

15. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials

Author: Milton Packer, Waheed Jamal, Stefan D. Anker, Stuart J. Pocock, João Pedro Ferreira, Javed Butler, Anne Pernille Ofstad, Gerasimos Filippatos, Martina Brueckmann, Egon Pfarr, Faiez Zannad, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), London School of Hygiene and Tropical Medicine (LSHTM), Berlin Institute of Health (BIH), Department of Medicine, University of Washington [Seattle], and Imperial College London
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Type 2 diabetes, 030204 cardiovascular system & hematology, Body Mass Index, Angiotensin Receptor Antagonists, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glucosides, Cause of Death, Internal medicine, Diabetes mellitus, Empagliflozin, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Benzhydryl Compounds, Dapagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Aged, Heart Failure, Clinical Trials as Topic, Ejection fraction, business.industry, Hazard ratio, Stroke Volume, General Medicine, Middle Aged, medicine.disease, 3. Good health, Death, Hospitalization, Patient Outcome Assessment, Diabetes Mellitus, Type 2, chemistry, Case-Control Studies, Heart failure, Cardiology, Drug Therapy, Combination, Female, Neprilysin, business, Glomerular Filtration Rate
Abstract: Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials.We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model.Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race.The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF.Boehringer Ingelheim.
Published: 2020

16. Toward personalization of asthma treatment according to trigger factors

Author: Luis Caraballo, Susanne Greber-Platzer, W. Pohl, Bulent Enis Sekerel, Valérie Siroux, Elena S. Fedenko, Natalia Ilina, Paolo Maria Matricardi, Harald Renz, Petra Pazderova, Zhanat Ispayeva, Elopy Sibanda, Kian Fan Chung, Nikolaos G. Papadopoulos, Hugo Van Bever, Marianne van Hage, Alexander Emelyanov, S. G. Makarova, Roxana S. Bumbacea, Carmen Panaitescu, Erika von Mutius, Faith H. A. Osier, Sebastian L. Johnston, Jin Lyu Sun, Gary W.K. Wong, R S Fassakhov, Ludmila P. Sizyakina, Kristina Borochova, Jiu-Yao Wang, Evgeny Beltyukov, Zhongshan Gao, Kari C. Nadeau, Antonina Karsonova, Marco Idzko, Snezhana Bychkovskaya, A.N. Pampura, Katarzyna Niespodziana, Peter Errhalt, Tatiana Baranovskaya, Dmitry Kudlay, M. Gotua, Natalia Astafyeva, Thomas Schlederer, Marek L. Kowalski, Rezeda Fayzullina, Musa Khaitov, Tetiana Umanets, Ksenja Riabova, Leyla Namazova-Baranova, Pedro Giavina-Bianchi, Ruby Pawankar, Mohamed-Ridha Barbouche, Zsolt Szépfalusi, Sergii Zaikov, Hae-Sim Park, Guillermo Horacio Docena, Irina Evsegneeva, Mihaela Zidarn, Michael Levin, Adnan Custovic, Jean Bousquet, Elena Kovzel, Paul M. O'Byrne, Daria Fomina, Oleksandr Nazarenko, Elena Borzova, Thomas Eiwegger, Olga Naumova, Gunilla Hedlin, Omer Kalayci, Rudolf Valenta, Vanitha Sampath, Angelika Berger, Margarita Vasileva, Alexander Karaulov, Graduate School, Medical Microbiology and Infection Prevention, AII - Inflammatory diseases, Salvy-Córdoba, Nathalie, Medizinische Universität Wien = Medical University of Vienna, Saratov State Medical University, Partenaires INRAE, Belarusian Medical Academy of Post-Graduate Education [Minsk] (BelMAPGE), Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), South Ural State Medical University, Russian Medical Academy for Continuous Medical Education [Moscow], Pirogov Russian National Research Medical University, Sechenov First Moscow State Medical University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Humboldt University Of Berlin, Berlin Institute of Health (BIH), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Krasnoyarsk State Medical University (KrasSMU), Universidad de Cartagena [Cartagena de Indias], National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Universidad Nacional de la Plata [Argentine] (UNLP), The Hospital for sick children [Toronto] (SickKids), North-Western State Medical University [St Petersburg, Russia], Krems University Hospital, Kazan Federal University (KFU), Bashkir State University (BASHEDU), NRC Institute of immunology FMBA, Moscow Russian federation, Zhejiang Gongshang University [Hangzhou] (ZJSU), Universidade de São Paulo = University of São Paulo (USP), Tbilisi State University, Astrid Lindgren Children's Hospital, Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Al-Farabi Kazakh National University [Almaty] (KazNU), Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Nazarbayev University [Kazakhstan], Medical University of Łódź (MUL), University of Cape Town, Dmitry Rogachev National Research Center of Pediatric Hematology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, Pirogov Russian National Reasearch Medical University Moscow, National Academy of Medical Sciences of Ukraine, Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), Michael DeGroote School of Medicine [Hamilton, ON, Canada], Faculty of Health Sciences [Hamilton, ON, Canada], McMaster University [Hamilton, Ontario]-McMaster University [Hamilton, Ontario], KEMRI-Wellcome Trust Research Programme (KWTRP), Pius Branzeu Clinical Emergency Hospital (OncoGen), University of Manchester [Manchester], National and Kapodistrian University of Athens (NKUA), Ajou University, Nippon Medical School [Tokyo, Japon], Hietzing Hospital, Karl Landsteiner Institute for Dermatological Research, Landesklinikum St. Poelten, University of Giessen and Marburg Lung Center [Gießen, Germany] (UGMLC), German Center for Lung Research, University of Zimbawe [Harare] (UZ), University of Zimbawe, National University of Science and Technology [Bulawayo], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Southern Federal University [Rostov-on-Don] (SFEDU), Peking Union Medical College Hospital [Beijing] (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College, National University of Singapore (NUS), Center of Allergology and Clinical Immunology, Dr von Hauner Children's Hospital [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Helmholtz Centre Munich, German Centre for Lung Research, National Cheng Kung University Hospital [Tainan], The Chinese University of Hong Kong [Hong Kong], Respiratory and Allergic Diseases [Golnik, Slovenia], University Clinic of Respiratory and Allergic Diseases Golnik, University of Ljubljana, and Karl Landsteiner University of Health Sciences - Karl Landsteiner Privatuniversität für Gesundheitswissenschaften [Krems an der Donau, Austria]
Subjects: 0301 basic medicine, Allergy, MESH: Asthma, Rhinovirus, Asthma treatment, CHILDREN, EPITOPE, Disease, Microarray, medicine.disease_cause, sopenje, alergeni, Personalization, Atopy, 0302 clinical medicine, immune system diseases, astma, Immunology and Allergy, MESH: Animals, Precision Medicine, RISK, MESH: Rhinovirus, respiratorni znaki in simptomi, analiza mikromrež, Allergen, alergija in imunologija, SENSITIZATION, personalizirana medicina, Wheeze, rhinovirus, allergy and immunology, INFECTIONS, 1107 Immunology, wheeze, ATOPY, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, Life Sciences & Biomedicine, Bioquímica, medicine.medical_specialty, MESH: Allergens, [SDV.IMM] Life Sciences [q-bio]/Immunology, precision medicine, Immunology, udc:616-097, MESH: Precision Medicine, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, rinovirus, medicine, Animals, Humans, allergens, IMMUNOTHERAPY, Intensive care medicine, Asthma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, Science & Technology, business.industry, Allergens, asthma, respiratory, medicine.disease, respiratory tract diseases, signs and symptoms, 030104 developmental biology, ANTIBODY, 030228 respiratory system, Ciencias Médicas, MESH: Biomarkers, microarray analysis, business, Biomarkers, RESPONSES
Abstract: Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Exactas
Published: 2020

17. Heart failure treatment up‐titration and outcome and age: an analysis of BIOSTAT‐CHF

Author: Kenneth Dickstein, Faiez Zannad, Adriaan A. Voors, Marco Metra, Ify R. Mordi, John G.F. Cleland, Nilesh J. Samani, Stefan D. Anker, Dirk J. van Veldhuisen, Chim C. Lang, Leong L. Ng, Wouter Ouwerkerk, Ninewells Hospital and Medical School [Dundee], University of Dundee, National Heart Centre Singapore (NHCS), Amsterdam UMC - Amsterdam University Medical Center, Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Imperial College London, University of Bergen (UiB), Stavanger University Hospital, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, University of Leicester, University Hospitals Leicester, University Medical Center Groningen [Groningen] (UMCG), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), NHS Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship. Grant Number: PCL/17/07, European Commission: FP7-242209-BIOSTAT-CHF, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), Cardiovascular Centre (CVC), Epidemiology and Data Science, and Dermatology
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, DIAGNOSIS, MORBIDITY, Angiotensin Receptor Antagonists, 03 medical and health sciences, Elderly, Up-titration, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ACE inhibitor, Internal medicine, Humans, Medicine, ESC GUIDELINES, Beta-blocker, cardiovascular diseases, Angiotensin receptor blocker, ELDERLY-PATIENTS, Beta blocker, Aged, Heart Failure, Ejection fraction, business.industry, BETA-BLOCKERS, MORTALITY, Incidence (epidemiology), Hazard ratio, Stroke Volume, Atrial fibrillation, medicine.disease, RANDOMIZED-TRIAL, Confidence interval, Treatment Outcome, HOSPITALIZATION, Heart failure, SYSTOLIC DYSFUNCTION, ATRIAL-FIBRILLATION, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Aims:\ud Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up‐titration of angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta‐blockers on outcome across the age spectrum in HFrEF patients.\ud \ud Methods and results:\ud We analysed HFrEF patients on sub‐optimal doses of ACEI/ARB and/or beta‐blockers from the BIOSTAT‐CHF study stratified by age. Patients underwent a 3‐month up‐titration period. We used inverse probability weighting to adjust for the likelihood of successful up‐titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow‐up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta‐blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI‐ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P
Published: 2020

18. Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial

Author: Andrew L. Clark, Javier Díez, Pierpaolo Pellicori, Investigators, Nicolas Girerd, Job A J Verdonschot, João Pedro Ferreira, Susana Ravassa, Frank Edelmann, Stephane Heymans, Beatrice Mariottoni, María U. Moreno, Homage Trial Committees, Franco Cosmi, Jan A. Staessen, Burkert Pieske, John G.F. Cleland, Faiez Zannad, Johannes Petutschnigg, Mark R. Hazebroek, Joe Cuthbert, Arantxa González, Begoña López, Erwan Bozec, Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain, CIBERCV, Carlos III Institute of Health, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary, Department of Cardiology, Cortona Hospital, Department of Cardiology, Maastricht University Medical Center, Cardiology Department, Castle Hill Hospital, University of Hull, Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, and German Centre for Cardiovascular research (DZHK), Partner Site Berlin, Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen (APPREMED), Biomedical Sciences Group, Faculty of Medicine, University of Leuven, Berlin Institute of Health (BIH), Departments of Nephrology and Cardiology, Clínica Universidad de Navarra, This work was supported by the European Commission HOMAGE project (grant 305507), JD and AG are supported by the Ministry of Science and Innovation, Spain (Instituto de Salud Carlos III: CB16/11/00483 and PI18/01469 co-financed by FEDER funds). MH is supported by a Kootstra Talented Post-doc Fellowship (Netherlands). JGFC and PP are supported by the British Heart Foundation Centre of Research Excellence (grant number RE/18/6/34217). PPREMED (URL: http://www.appremed.orf) received a non-binding grant from Omron Healthcare Co., Ltd., Kyoto, Japan., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)
Subjects: Cardiac function curve, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Heart failure, 030204 cardiovascular system & hematology, Spironolactone, EXERCISE CAPACITY, Atrial remodelling, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, N-terminal telopeptide, Left atrial, Collagen cross-linking, Internal medicine, MAGNETIC-RESONANCE, medicine, FIBROSIS, 030212 general & internal medicine, Science & Technology, Ejection fraction, business.industry, medicine.disease, DYSFUNCTION, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PRESERVED EJECTION FRACTION, chemistry, VOLUME, Cardiovascular System & Cardiology, SURVIVAL, Cardiology, Biomarker (medicine), FIBRILLATION, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Blood sampling
Abstract: Aims The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial.Methods and results Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean difference(sspiro/control): -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m(2); interaction p(across-tertiles) = 0.005; interaction p(third tertile) = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differences(spiro/control): -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction p(across-tertiles) = 0.09; interaction p(third tertile) < 0.001].Conclusions These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).[GRAPHICS]Patients at risk of heart failure from the HOMAGE clinical trial were classified according to the baseline degree of myocardial collagen cross-linking, non-invasively assessed by the serum collagen type I C-terminal telopeptide (CITP) to matrix metalloproteinase-1 (MMP-1) ratio (CITP:MMP-1). As highly cross-linked collagen fibres are more resistant to degradation and CITP is a cross-linked peptide, for a given MMP-1 quantity less CITP will be released and, subsequently, serum CITP:MMP-1 will be lower. Whereas patients with low collagen cross-linking (high CITP:MMP-1) benefit from the cardioprotective effects of treatment with spironolactone on left atrial remodelling [i.e. a decrease in left atrial volume index (LAVI)] and on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, these beneficial effects are not found in patients with higher collagen cross-linking (low CITP:MMP-1).
Published: 2022

19. Recent advances in cardio-oncology

Author: Christoph Maack, Stephan von Haehling, Alexander R. Lyon, Y N Belenkov, Sara Hadzibegovic, Hadi Skouri, Alessia Lena, Petar M. Seferovic, Rudolf A. de Boer, Markus S. Anker, Radek Pudil, Andrew J.S. Coats, Carlo G. Tocchetti, Zaza Iakobishvili, Dimitrios Farmakis, Jutta Bergler-Klein, Alain Cohen-Solal, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Sechenov First Moscow State Medical University, Medizinische Universität Wien = Medical University of Vienna, University Medical Center Groningen [Groningen] (UMCG), University of Cyprus [Nicosia] (UCY), National and Kapodistrian University of Athens (NKUA), Georg-August-University = Georg-August-Universität Göttingen, Tel Aviv University (TAU), University Hospital of Würzburg, University of Hradec Králové, American University of Beirut Faculty of Medicine and Medical Center (AUB), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Naples Federico II = Università degli studi di Napoli Federico II, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), University of Belgrade [Belgrade], Royal Brompton Hospital, Imperial College London, leboeuf, Christophe, Anker, M. S., Hadzibegovic, S., Lena, A., Belenkov, Y., Bergler-Klein, J., de Boer, R. A., Farmakis, D., von Haehling, S., Iakobishvili, Z., Maack, C., Pudil, R., Skouri, H., Cohen-Solal, A., Tocchetti, C., Coats, A. J. S., Seferovic, P. M., Lyon, A. R., and Cardiovascular Centre (CVC)
Subjects: IMMUNE CHECKPOINT INHIBITOR, CHRONIC KIDNEY-DISEASE, CARDIOTOXICITY, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, Palliative care, medicine.medical_treatment, Cardiology, Heart failure, Disease, 030204 cardiovascular system & hematology, ESC and HFA Paper, ESC and HFA Papers, Targeted therapy, PALLIATIVE CARE, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, BREAST-CANCER SURVIVORS, Neoplasms, medicine, INDEPENDENT PREDICTOR, CO-MORBIDITIES, Humans, 030212 general & internal medicine, Cardio oncology, Intensive care medicine, Cancer, Cardiotoxicity, business.industry, medicine.disease, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PREVALENCE, Radiation therapy, lcsh:RC666-701, Heart Failure Association Cardio-Oncology Study Group of the European Society of Cardiology, Position paper, Cardiology and Cardiovascular Medicine, business, ECHOCARDIOGRAPHY, Cardiotoxicity Heart failure Cancer, POSITION PAPER
Abstract: International audience; While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment.
Published: 2019

20. Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Author: Anthony P Carnicelli, Ruth Owen, Stuart J Pocock, David B Brieger, Satoshi Yasuda, Jose Carlos Nicolau, Shaun G Goodman, Mauricio G Cohen, Tabassome Simon, Dirk Westermann, Katarina Hedman, Karolina Andersson Sundell, Christopher B Granger, Duke University [Durham], London School of Hygiene and Tropical Medicine (LSHTM), The University of Sydney, Tohoku University [Sendai], Universidade de São Paulo (USP), University of Toronto, University of Miami Leonard M. Miller School of Medicine (UMMSM), Service de Pharmacologie clinique [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University Heart Center [Hamburg], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), and AstraZeneca
Subjects: Male, Time Factors, Myocardial Infarction, Administration, Oral, Coronary Artery Disease, 030204 cardiovascular system & hematology, Global Health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Atrial Fibrillation, Prevalence, Humans, 030212 general & internal medicine, Prospective Studies, Registries, health services, Aged, Anticoagulants, stroke, 3. Good health, Survival Rate, Quality of Life, Female, Cardiology and Cardiovascular Medicine, Follow-Up Studies
Abstract: ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.
Published: 2021

21. Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial

Author: Verdonschot, Job A. J., Ferreira, João Pedro, Pellicori, Pierpaolo, Brunner-La Rocca, Hans-Peter, Clark, Andrew L., Cosmi, Franco, Cuthbert, Joe, Girerd, Nicolas, Mariottoni, Beatrice, Petutschnigg, Johannes, Rossignol, Patrick, Cleland, John G. F., Zannad, Faiez, Heymans, Stephane R. B., HOMAGE \\'Heart Omics in AGEing\\' consortium, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University of Glasgow, Institute of Health and Wellbeing, University of Glasgow-Gartnavel General Hospital, Glasgow, Robertson Centre for Biostatistics & Clinical Trials Unit, University of Hull [United Kingdom], Castle Hill Hospital, Cortona Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the EuropeanUnion Commission’s Seventh Framework programme under Grant AgreementNo. 305507 (HOMAGE). S.H: This manuscript has been possible thanks to thesupport of the Netherlands Cardiovascular Research Initiative, an initiativewith support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10,CVON She-PREDICTS, Grant 2017-21., European Project: 305507, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)
Subjects: Male, Proteomics, Cardiac & Cardiovascular Systems, Time Factors, Proteome, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Spironolactone, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Natriuretic peptide, Prospective Studies, Original Investigation, Mineralocorticoid Receptor Antagonists, 0303 health sciences, Diabetes, Blood Proteins, GROWTH-DIFFERENTIATION FACTOR-15, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Biomarker (medicine), Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, medicine.drug_class, Heart failure, Risk Assessment, 03 medical and health sciences, Endocrinology & Metabolism, INFLAMMATION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Diseases of the circulatory (Cardiovascular) system, Humans, 030304 developmental biology, Aged, Proteomic Profile, Science & Technology, business.industry, Biomarker, medicine.disease, Omics, Fibrosis, Blood pressure, chemistry, RC666-701, Cardiovascular System & Cardiology, business, Biomarkers
Abstract: Background Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The “Heart OMics in AGEing” (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Methods Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Results Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Conclusions Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.
Published: 2021

22. Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial

Author: Faiez Zannad, Martina Brueckmann, João Pedro Ferreira, Milton Packer, Nicholas D. Gollop, Tomoko Iwata, Adriaan A. Voors, Javed Butler, Stefan D. Anker, Stuart J. Pocock, Gerasimos Filippatos, James L. Januzzi, John Gregson, London School of Hygiene and Tropical Medicine (LSHTM), 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Medizinische Fakultät Mannheim, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Baim Institute for Clinical Research Boston MA, University of Groningen [Groningen], Imperial College London, Baylor University Medical Center, Baylor College of Medecine, The EMPEROR-Reduced trial was funded by Boehringer Ingelheim and Eli Lilly, BOZEC, Erwan, and Cardiovascular Centre (CVC)
Subjects: medicine.medical_specialty, Peripheral edema, Heart failure, 030204 cardiovascular system & hematology, High-sensitivity cardiac troponin T, 03 medical and health sciences, 0302 clinical medicine, Troponin T, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Natriuretic Peptide, Brain, Heart rate, medicine, Humans, 030212 general & internal medicine, Framingham Risk Score, Ejection fraction, Proportional hazards model, business.industry, Stroke Volume, Prognosis, Brain natriuretic peptide, medicine.disease, Peptide Fragments, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Blood pressure, NT-proBNP, Cardiology, Risk score, Morbidity, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Aims The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (HFrEF). A risk model incorporating biomarkers and clinical variables has not been validated in contemporary heart failure (HF) trials. Methods and results In EMPEROR-Reduced, 33 candidate variables were pre-selected. Multivariable Cox regression models were developed using stepwise selection for: (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, and (iii) cardiovascular mortality. A total of 3730 patients were followed up for a median of 16 months, 823 (22%) patients had a primary outcome and 515 (14%) patients died, of whom 389 (10%) died from a cardiovascular cause. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last HF hospitalization, longer time since HF diagnosis, lower systolic blood pressure, New York Heart Association (NYHA) Class III or IV, higher heart rate and peripheral oedema were key predictors (eight variables in total, all P 9 times higher than those in the bottom 10th. Empagliflozin benefitted patients across risk levels for the primary outcome. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality, followed by NYHA Class III or IV and ischaemic aetiology (four variables in total, all P Conclusions The combination of NT-proBNP and hs-cTnT with a small number of readily available clinical variables provides prognostic assessment for patients with HFrEF. This predictive tool kit can be easily implemented for routine clinical use.
Published: 2021

23. Patiromer for the management of hyperkalaemia in patients receiving renin-angiotensin-aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial

Author: Carol Moreno Quinn, Javed Butler, Ileana L. Piña, Peter Szecsödy, Bertram Pitt, Fausto J. Pinto, Lars H. Lund, Udo-Michael Göhring, Gerasimos Filippatos, Stefan D. Anker, Fabio Dorigotti, Peter van der Meer, Tim Friede, Matthew R. Weir, Marco Metra, Andrew J.S. Coats, Patrick Rossignol, Tariq Jamal Siddiqi, Mikhail Kosiborod, Repositório da Universidade de Lisboa, BOZEC, Erwan, University of Mississippi Medical Center (UMMC), Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Department of Internal Medicine, Dow University of Health Sciences, University of Warwick [Coventry], Vifor Pharma Ltd [Glattbrugg, Switzerland], National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Attikon University Hospital, University Medical Center Göttingen (UMG), University of Missouri [Kansas City] (UMKC), University of Missouri System, Saint Luke's Mid America Heart Institute, Karolinska Institutet [Stockholm], Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, Central Michigan University (CMU), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Hospital de Santa Maria [Lisboa], 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University Medical Center Groningen [Groningen] (UMCG), University of Groningen [Groningen], University of Maryland School of Medicine, University of Maryland System, University of Michigan [Ann Arbor], University of Michigan System, This study was sponsored and funded by Vifor Pharma, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Università degli Studi di Brescia [Brescia], Universidade de Lisboa (ULISBOA), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Trial design, medicine.medical_specialty, Randomization, Polymers, Heart failure, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Placebo, GUIDELINES, Mineralocorticoid receptor antagonists, Renin-Angiotensin System, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Hyperkalaemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Adherence, Patiromer, Potassium, Renin-angiotensin-aldosterone system inhibitors, Humans, Stroke Volume, Heart Failure, Hyperkalemia, Renal Insufficiency, Chronic, Renin–angiotensin system, medicine, Clinical endpoint, QD, Renal Insufficiency, 030212 general & internal medicine, Chronic, Adverse effect, Ejection fraction, business.industry, medicine.disease, QP, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, chemistry, Cardiology, Cardiology and Cardiovascular Medicine, business, RC
Abstract: © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., Aims: In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+ ) binder, may improve serum K+ levels and adherence to RAASi. Methods: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12 weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. Conclusion: The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use.
Published: 2021

24. Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis

Author: Martijn Huisman, Catherine Helmer, Jong Bin Bae, Hans J. Grabe, Graziano Ceresini, Misa Imaizumi, J. Wouter Jukema, Jacobijn Gussekloo, Carole E. Aubert, Stella Trompet, Ulf Schminke, Mary H. Samuels, Wendy P. J. den Elzen, Leon Flicker, Bjørn Olav Åsvold, Jean-Marie Degryse, Ki Woong Kim, Oscar L. Lopez, Eystein Stordal, P. Eline Slagboom, Elisavet Moutzouri, Marlise E.A. Van Eersel, Bert Vaes, Michiko Yamada, Carsten Oliver Schmidt, Luigi Ferrucci, Anne R. Cappola, M. Arfan Ikram, Jae Hoon Moon, Jean-François Dartigues, Rudi G. J. Westendorp, Nicolien A. Van Vliet, Diana van Heemst, Hannie C. Comijs, Robin P. Peeters, Henry Völzke, Robin P. F. Dullaart, Osvaldo P. Almeida, Jim Parle, Ji Won Han, Lewis H. Kuller, Gerard J. Blauw, Linda E Barnes, Matthias Nauck, Douglas C. Bauer, Carol Brayne, Bu B. Yeap, Simon P. Mooijaart, Renate T. De Jongh, Nicolas Rodondi, Howard A Fink, Epidemiology, Internal Medicine, Barnes, Linda [0000-0003-2560-4997], Brayne, Carol [0000-0001-5307-663X], Apollo - University of Cambridge Repository, Leiden University Medical Center (LUMC), The University of Western Australia (UWA), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Department of Psychiatry [St. Olav's hospital, Trondheim], St. Olav's Hospital, Bern University Hospital [Berne] (Inselspital), University of Bern, University of Michigan [Ann Arbor], University of Michigan System, Seoul National University Bundang Hospital (SNUBH), University of Cambridge [UK] (CAM), University of California [San Francisco] (UCSF), University of California, University of Pennsylvania [Philadelphia], University Hospital of Parma [Parme, Italie], Vrije Universiteit Amsterdam [Amsterdam] (VU), 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), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Groningen [Groningen], Amsterdam UMC, Harbor Hospital, National Institute on Aging, Baltimore, VA Healthcare System, University of Minnesota [MN, USA], University of Medicine Greifswald, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Radiation Effects Research Foundation, ICIN - Netherlands Heart Institute, Seoul National University College of Natural Sciences, Seoul National University [Seoul] (SNU), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Pittsburgh School of Medicine, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Birmingham [Birmingham], Oregon Health and Science University [Portland] (OHSU), Max planck Institute for Biology of Ageing [Cologne], University of Copenhagen = Københavns Universitet (KU), Radiation Effects Research Foundation (RERF), Fiona Stanley Hospital [Murdoch], VU University Amsterdam, UCL - SSS/IRSS - Institut de recherche santé et société, Psychiatry, APH - Aging & Later Life, APH - Mental Health, Epidemiology and Data Science, APH - Societal Participation & Health, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Data Analysis, Male, Pediatrics, physiopathology [Cognitive Dysfunction], blood [Hypothyroidism], endocrine system diseases, psychology [Hypothyroidism], OLDER MEN, Thyroid Gland, Thyrotropin, Thyroid Function Tests, Hyperthyroidism, 0302 clinical medicine, SUBCLINICAL HYPOTHYROIDISM, Cognition, SERUM TSH LEVEL, 030212 general & internal medicine, Cognitive decline, Correlation of Data, Subclinical infection, Original Investigation, RISK, MINI-MENTAL STATE, DEMENTIA, Hazard ratio, physiology [Cognition], IMPAIRMENT, Mental Status and Dementia Tests, 3. Good health, Female, HEALTH, Thyroid function, methods [Thyroid Function Tests], Life Sciences & Biomedicine, THYROXINE REPLACEMENT, statistics & numerical data [Mental Status and Dementia Tests], medicine.medical_specialty, endocrine system, analysis [Thyrotropin], NORMATIVE DATA, blood [Hyperthyroidism], Context (language use), 610 Medicine & health, Risk Assessment, diagnosis [Hyperthyroidism], analysis [Thyroxine], 03 medical and health sciences, Medicine, General & Internal, Hypothyroidism, 360 Social problems & social services, General & Internal Medicine, mental disorders, medicine, Internal Medicine, Dementia, Online First, Humans, Cognitive Dysfunction, ddc:610, Aged, statistics & numerical data [Risk Assessment], physiopathology [Thyroid Gland], Science & Technology, Proportional hazards model, business.industry, Research, psychology [Hyperthyroidism], statistics & numerical data [Thyroid Function Tests], medicine.disease, diagnosis [Hypothyroidism], methods [Risk Assessment], Thyroxine, diagnosis [Cognitive Dysfunction], Strictly standardized mean difference, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery
Abstract: This individual participant data analysis assesses the cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia., Key Points Question Is thyroid dysfunction associated with cognitive decline? Findings In this individual participant data analysis of 23 cohorts including 74 565 participants with cognitive function and/or dementia measurements, subclinical thyroid dysfunction was not associated with global cognitive function at baseline (standardized mean difference, −0.02 for subclinical hyperthyroidism and 0.05 for subclinical hypothyroidism) or annual decline (standardized mean difference, −0.02 for subclinical hyperthyroidism and −0.00 for subclinical hypothyroidism). Meaning These findings do not support the need for screening for subclinical thyroid dysfunction for prevention of cognitive decline or dementia., Importance In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings. Objective To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia. Design, Setting, and Participants This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021. Exposures Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values. Main Outcomes and Measures The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated. Results Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism—cross-sectionally (−0.06 standardized mean difference in score; 95% CI, –0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, –0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia. Conclusions and Relevance In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
Published: 2021

25. Pathophysiological pathways in patients with heart failure and atrial fibrillation

Author: Iziah E Sama, Carolyn S.P. Lam, Marco Metra, Michiel Rienstra, Vicente Artola Arita, Isabelle C. Van Gelder, Jozine M. ter Maaten, John G.F. Cleland, Mariëlle Kloosterman, Stefan D. Anker, Hans L A Nienhuis, Chim C. Lang, Peter van der Meer, Bernadet T. Santema, Adriaan A. Voors, Leong L. Ng, Gerasimos Filippatos, N J Samani, Maarten P. van den Berg, Dirk J. van Veldhuisen, Kenneth Dickstein, Faiez Zannad, University Medical Center Groningen [Groningen] (UMCG), 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Università degli Studi di Brescia [Brescia], Imperial College London, Royal Brompton Hospital, University of Glasgow, University Hospitals Leicester, University of Leicester, Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Dundee, Ninewells Hospital and Medical School [Dundee], University of Bergen (UiB), Stavanger University Hospital, National and Kapodistrian University of Athens (NKUA), Attikon University Hospital, Duke-National University of Singapore Graduate Medical School, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Università degli Studi di Brescia = University of Brescia (UniBs), and BOZEC, Erwan
Subjects: medicine.medical_specialty, Pathway analysis, Physiology, RATIONALE, Heart failure, Disease, 030204 cardiovascular system & hematology, CAPACITY, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Amyloid-beta, Atrial fibrillation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Somatomedins, Physiology (medical), Internal medicine, Biopsy, medicine, Humans, Sinus rhythm, CYTOSCAPE, medicine.diagnostic_test, business.industry, FACTOR-BINDING PROTEIN-7, BETA-BLOCKERS, ASSOCIATION, medicine.disease, Prognosis, Fold change, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, ALZHEIMERS-DISEASE, PRESERVED EJECTION FRACTION, AMYLOIDOSIS, Cohort, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Aims:\ud Atrial fibrillation (AF) and heart failure (HF) are two growing epidemics that frequently co-exist. We aimed to gain insights into underlying pathophysiological pathways in HF patients with AF by comparing circulating biomarkers using pathway overrepresentation analyses.\ud \ud Methods and Results:\ud From a panel of 92 biomarkers from different pathophysiological domains available in 1,620 patients with HF, we first tested which biomarkers were dysregulated in patients with HF and AF (n = 648) compared with patients in sinus rhythm (n = 972). Secondly, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in patients who had HF and AF. Findings were validated in an independent HF cohort (n = 1,219, 38% with AF). Patient with AF and HF were older, less often women, and less often had a history of coronary artery disease compared with those in sinus rhythm. In the index cohort, 24 biomarkers were upregulated in patients with AF and HF. In the validation cohort, 8 biomarkers were upregulated, which all overlapped with the 24 biomarkers found in the index cohort. The strongest up-regulated biomarkers in patients with AF were spondin-1 (fold change 1.18, p = 1.33x10−12), insulin-like growth factor-binding protein-1 (fold change 1.32, p = 1.08x10−8), and insulin-like growth factor-binding protein-7 (fold change 1.33, p = 1.35x10−18). Pathway overrepresentation analyses revealed that the presence of AF was associated with activation amyloid-beta metabolic processes, amyloid-beta formation, and amyloid precursor protein catabolic processes with a remarkable consistency observed in the validation cohort.\ud \ud Conclusion:\ud In two independent cohorts of patients with HF, the presence of AF was associated with activation of three pathways related to amyloid-beta. These hypothesis-generating results warrant confirmation in future studies.\ud \ud Translational Perspective:\ud Using an unbiased approach, we identified and validated dysregulation of three amyloid-beta related pathways in patients who had heart failure (HF) with concomitant atrial fibrillation (AF). Amyloid-beta depositions are a hallmark of Alzheimer’s disease, but might also play a role in pathophysiological processes outside the central nervous system. Biopsy studies are needed to confirm the pathophysiological role of amyloid-beta in patients with AF and HF. Diagnostic and therapeutic implications should be investigated in the light of potential pathophysiological overlap between the three aging-related epidemics: Alzheimer’s disease, AF and HF.
Published: 2021

26. Clinical diversity and treatment results in tegumentary leishmaniasis

Author: Diana N. J. Lockwood, Jean-Pierre Gangneux, Romain Guery, Mark S. Bailey, Andreas Neumayr, Stephen L. Walker, Christophe Ravel, Pierre Buffet, Gundel Harms, Jan Clerinx, Gert Van der Auwera, Laurence Lachaud, Johannes Blum, Leo G. Visser, Sara Karlsson Söbirk, Aldert Bart, Pieter P. A. M. van Thiel, APH - Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital privé du Confluent [Nantes], University College London Hospitals (UCLH), London School of Hygiene and Tropical Medicine (LSHTM), Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), James Cook University (JCU), Swiss Tropical and Public Health Institute [Basel], Universiteit van Amsterdam (UvA), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Tropical Medicine [Antwerp] (ITM), Lund University [Lund], Universiteit Leiden [Leiden], Hôpital Lapeyronie [Montpellier] (CHU), University of Basel (Unibas), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Chard-Hutchinson, Xavier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Humboldt University Of Berlin, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), and Universiteit Leiden
Subjects: Adult, Male, medicine.medical_specialty, Old World, Adolescent, [SDV]Life Sciences [q-bio], 030231 tropical medicine, RC955-962, Antiprotozoal Agents, Leishmaniasis, Cutaneous, law.invention, 03 medical and health sciences, Middle East, Young Adult, 0302 clinical medicine, Randomized controlled trial, Cutaneous leishmaniasis, law, Arctic medicine. Tropical medicine, Medicine, Humans, 030212 general & internal medicine, Young adult, Child, Aged, Leishmania, Travel, biology, business.industry, Transmission (medicine), Public Health, Environmental and Occupational Health, Leishmaniasis, Middle Aged, South America, medicine.disease, biology.organism_classification, Dermatology, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Infectious Diseases, Africa, Female, Leishmania infantum, Public aspects of medicine, RA1-1270, business, Research Article
Abstract: Background Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management. Methodology Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients. Principal findings Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%). Conclusion/Significance CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates., Author summary Cutaneous and muco-cutaneous leishmaniasis (CL and MCL) are disfiguring diseases caused by a worldwide distributed parasite called Leishmania and its 20 species. Clinical manifestations span a wide continuum from single nodular lesion to disseminated form with mucosal involvement. No randomized clinical trial has ever been done exclusively in travellers and medical management is poorly evidence-based or based very predominantly on data obtained in endemic countries. Articles and reviews almost invariably propose a dichotomic view, with Old World CL described as a benign disease in contrast to New World CL strongly associated with destructive mucosal lesions. Our study is the first prospective clinical study providing a detailed description of the clinical presentation and risk of mucosal involvement in CL in several hundreds of patients, with frequent formal identification of the infecting Leishmania species. The harmonized data collection in patients infected in many transmission foci worldwide enabled direct comparisons of clinical patterns induced by different Leishmania species, and on the outcome following treatment with either local or systemic regimens. The study is based on an international harmonized data collection that allowed a wide capture of parasitologically confirmed cases. In striking contrast with previous assumptions, the study shows that CL acquired in Europe displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised travellers. It also shows that when used as per recommendations, local therapy is associated with high cure rates.
Published: 2021

27. Effects of Sacubitril/Valsartan on Serum Lipids in Heart Failure With Preserved Ejection Fraction

Author: Senthil Selvaraj, Ziqiang Zhao, Scott D. Solomon, Martin Lefkowitz, Burkert Pieske, John J.V. McMurray, Victor Shi, Milton Packer, Faiez Zannad, Inder S. Anand, Brian Claggett, Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Imperial College London, Baylor College of Medecine, 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), University of Minnesota Medical School, University of Minnesota System, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Novartis, Shanghai China, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), and University of Glasgow-NHS Greater Glasgow and Clyde
Subjects: Male, Guanosine Monophosphate, Blood lipids, 030204 cardiovascular system & hematology, Sacubitril, 0302 clinical medicine, Natriuretic peptide, Prospective Studies, 030212 general & internal medicine, Original Research, Metabolic Syndrome, Aged, 80 and over, Aminobutyrates, 3. Good health, Lipoproteins, LDL, Drug Combinations, Cholesterol, Treatment Outcome, Valsartan, Creatinine, Cardiology, lipids (amino acids, peptides, and proteins), Female, Lipoproteins, HDL, Cardiology and Cardiovascular Medicine, medicine.drug, heart failure with preserved ejection fraction, medicine.medical_specialty, medicine.drug_class, lipids, Angiotensin Receptor Antagonists, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, Humans, Triglycerides, Aged, Glycemic, Heart Failure, business.industry, Biphenyl Compounds, Stroke Volume, medicine.disease, Treatment, RC666-701, sacubitril/valsartan, Heart failure with preserved ejection fraction, business, metabolism, Biomarkers, Sacubitril, Valsartan, Dyslipidemia
Abstract: Background Dyslipidemia is common in heart failure with preserved ejection fraction. Sacubitril/valsartan improves glycemic control and augments natriuretic peptide signaling, providing mechanisms by which sacubitril/valsartan may affect serum lipids. However, empiric data on these effects are lacking. Methods and Results We analyzed 4774 participants from PARAGON‐HF (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin‐Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) with available screening lipids. During follow‐up visits, we analyzed the treatment effect on lipid levels and assessed for interaction by baseline lipid levels. At the 16‐week visit, we adjusted these treatment effects for the change in several biomarkers (including hemoglobin A 1c and urinary cyclic guanosine monophosphate/creatinine [a biomarker of natriuretic peptide activation]). The average age was 73±8 years, 52% were women, 43% had diabetes mellitus, and 64% were on statin therapy. Compared with valsartan, sacubitril/valsartan reduced triglycerides −5.0% (95% CI, −6.6% to −3.5%), increased high‐density lipoprotein cholesterol +2.6% (95% CI, +1.7% to +3.4%), and increased low‐density lipoprotein cholesterol +1.7% (95% CI, +0.4% to +3.0%). Sacubitril/valsartan reduced triglycerides most among those with elevated baseline levels (triglycerides≥200 mg/dL) ( P ‐interaction Conclusions Sacubitril/valsartan significantly reduces triglycerides compared with valsartan, an effect that was nearly threefold stronger in those with elevated baseline triglycerides. Modest increases in high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol cholesterol were also observed with therapy. The underlying mechanism(s) of changes in high‐density lipoprotein cholesterol and triglycerides are related to sacubitril/valsartan’s effects on natriuretic peptide activity. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711.
Published: 2021

28. The genomics of heart failure: design and rationale of the HERMES consortium

Author: Svati H. Shah, Olle Melander, Neneh Sallah, Quinn S. Wells, Jerome I. Rotter, Faye Zhao, Charlotte Andersson, Guðmundur Thorgeirsson, Ghazaleh Fatemifar, Alex S. F. Doney, Michael E. Dunn, David E. Lanfear, Ian Ford, Eric Boersma, Sonia Shah, Christopher Newton-Cheh, Douglas L. Mann, Niek Verweij, Carolina Roselli, Laura M. Yerges-Armstrong, Jian Yang, Christian Torp-Pedersen, Veikko Salomaa, Mary L. Biggs, Alaa Shalaby, Christoph Nowak, Stefan Gross, Patrick T. Ellinor, Mari Liis Tammesoo, Diane T. Smelser, Peter M. Visscher, Hans L. Hillege, Ruth C. Lovering, Honghuang Lin, Colin N. A. Palmer, Louis Philippe Lemieux Perreault, Jeffrey Brandimarto, Uwe Völker, Perttu Salo, Andrea Koekemoer, Rebecca Gutmann, Åsa K. Hedman, Nilesh J. Samani, Heming Xing, Faiez Zannad, Jaison Jacob, Harry Hemingway, Michael R. Brown, Franco Giulianini, Anubha Mahajan, Xing Chen, Alexander Niessner, Peter Almgren, Daniel I. Swerdlow, Gunnar Engström, Lars Lind, Tõnu Esko, Tomasz Czuba, Anna Helgadottir, Harvey D. White, David J. Stott, Johan Ärnlöv, Lars Køber, Chim C. Lang, Krishna G. Aragam, Kent D. Taylor, Anders Mälarstig, Frederick K. Kamanu, Kenneth B. Margulies, Michelle L. O'Donoghue, Andrew D. Morris, Sahar Ghasemi, J. Wouter Jukema, Jessica van Setten, Abbas Dehghan, Guillaume Paré, Luca A. Lotta, Giorgio E. M. Melloni, Albert Henry, Bruce M. Psaty, Paul M. Ridker, David J. Carey, Marie-Pierre Dubé, John S. Gottdiener, Xiaosong Wang, Per H. Svensson, Xu Chen, Patrik K. E. Magnusson, Claudia Langenberg, Alexander Teumer, Vilmantas Giedraitis, Simon de Denus, Michael W. Nagle, Marcus Dörr, Thomas P. Cappola, André G. Uitterlinden, Michael Morley, Eliana Portilla-Fernandez, J. Gustav Smith, Abirami Veluchamy, Peter Weeke, Ify R. Mordi, Unnur Thorsteinsdottir, Naveed Sattar, Folkert W. Asselbergs, Daniel I. Chasman, Daníel F. Guðbjartsson, Jonathan H. Chung, Marcus E. Kleber, Raul Weiss, Christopher P. Nelson, Spiros Denaxas, Bing Yu, Simon P. R. Romaine, Nicholas A Marston, Anjali T. Owens, Cecilia M. Lindgren, John J.V. McMurray, Joshua D. Backman, Michael V. Holmes, Stella Trompet, Hilma Holm, Kerri L. Wiggins, Jian'an Luan, Stephan B. Felix, Yifan Yang, Jemma B. Wilk, Maryam Kavousi, Markus Perola, Christian T. Ruff, Jean-Claude Tardif, G Sveinbjörnsson, Samuel C. Dudley, Nicholas J. Wareham, Teemu J. Niiranen, Andrew P. Morris, Danny Tuckwell, Maris Teder-Laving, R. Thomas Lumbers, James P. Cook, Géraldine Asselin, William A. Chutkow, Winfried März, Steven A. Lubitz, John G.F. Cleland, Bill Kraus, Ramachandran S. Vasan, Christopher M. Haggerty, Olympe Chazara, Chris Finan, Heather L. Bloom, Hans-Peter Brunner-La Rocca, Francoise Fougerousse, Kenneth Rice, Craig L. Hyde, Graciela E. Delgado, Mark Chaffin, Marc S. Sabatine, Alanna C. Morrison, Kay-Tee Khaw, Kari Stefansson, Felix Vaura, Barry London, Isabella Kardys, Aroon D. Hingorani, Hongsheng Gui, Steen Stender, René Fouodjio, Mohsen Ghanbari, Pim van der Harst, Nicholas L. Smith, Karoline Kuchenbaecker, Adriaan A. Voors, Benoit Tyl, University College of London [London] (UCL), University College London Hospitals (UCLH), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Lund University [Lund], Pfizer, Karolinska Institutet [Stockholm], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Groningen [Groningen], University of Oxford [Oxford], Dalarna University, Massachusetts General Hospital [Boston], Montreal Heart Institute - Institut de Cardiologie de Montréal, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, University of Washington [Seattle], Emory University [Atlanta, GA], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania [Philadelphia], The University of Texas Health Science Center at Houston (UTHealth), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AstraZeneca, Novartis Institutes for BioMedical Research (NIBR), University of Glasgow, University of Liverpool, Université de Montréal (UdeM), Imperial College London, University of Heidelberg, Medical Faculty, University of Dundee, Universität Greifswald - University of Greifswald, University of Minnesota Medical School, University of Minnesota System, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Uppsala University, University of Maryland School of Medicine, University of Maryland System, University of Iceland [Reykjavik], deCODE genetics [Reykjavik], Henry Ford Hospital, Carver College of Medicine, University of Iowa, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), ICIN - Netherlands Heart Institute, Leiden University Medical Center (LUMC), Netherlands Heart Institute, Partenaires INRAE, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Leicester, Duke University [Durham], University of Iowa [Iowa City], Genentech, Inc., Genentech, Inc. [San Francisco], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Skane University Hospital [Malmo], University of Edinburgh, Medizinische Universität Wien = Medical University of Vienna, University of Turku, National Institute for Health and Welfare [Helsinki], McMaster University [Hamilton, Ontario], Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Harbor UCLA Medical Center [Torrance, Ca.], University Medical Center [Utrecht], University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), University of Tartu, Aalborg University [Denmark] (AAU), Leiden University, University of Queensland [Brisbane], Ohio State University [Columbus] (OSU), Auckland City Hospital, GlaxoSmithKline, Glaxo Smith Kline, University of Texas Health Science Center, 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 ), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Duke University Medical Center, Regeneron Pharmaceuticals [Tarrytown], Vanderbilt University [Nashville], European Project, Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Cardiology, University of Oxford, University of Pennsylvania, Universiteit Leiden, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Epidemiology, and Internal Medicine
Subjects: Male, Study Designs, Cardiomyopathy, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, AFRICAN ANCESTRY, Epidemiology, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, Cardiac and Cardiovascular Systems, AGING RESEARCH, RISK, Aged, 80 and over, 0303 health sciences, Kardiologi, Genomics, Middle Aged, Prognosis, 3. Good health, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Heart failure, CLASSIFICATION, Heart Failure/genetics, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Genetic model, medicine, Genetics, Diseases of the circulatory (Cardiovascular) system, Humans, Allele frequency, Genotyping, METAANALYSIS, 030304 developmental biology, Aged, Association studies, Study Design, business.industry, Odds ratio, ADULTS, COHORTS, medicine.disease, RC666-701, REPLICATION, business, Biomarkers, Genome-Wide Association Study
Abstract: Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
Published: 2021

29. Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial

Author: Milton Packer, Stuart J. Pocock, Subodh Verma, Dan Cotton, Faiez Zannad, Tomoko Iwata, Stefan D. Anker, Investigators, Janet Schnee, James L. Januzzi, Ola Vedin, Gerasimos Filippatos, Javed Butler, João Pedro Ferreira, Naveed Sattar, EMPEROR-Reduced Trial Committees, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Baim Institute for Clinical Research Boston MA, 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Attikon University Hospital, London School of Hygiene and Tropical Medicine (LSHTM), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, University of Toronto, St. Michael's Hospital, Boehringer Ingelheim AB, Boehringer Ingelheim Pharmaceuticals, Boehringer Ingelheim Pharma GmbH & Co. KG, Imperial College London, Baylor University Medical Center, Baylor College of Medecine, and BOZEC, Erwan
Subjects: Male, medicine.medical_specialty, animal structures, medicine.drug_class, heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Natriuretic Peptide, Brain, medicine, Empagliflozin, Natriuretic peptide, Humans, 030212 general & internal medicine, cardiovascular diseases, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, Ejection fraction, business.industry, Middle Aged, medicine.disease, Peptide Fragments, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, NT-proBNP, Heart failure, Cardiology, Female, prognosis, Cardiology and Cardiovascular Medicine, business, hormones, hormone substitutes, and hormone antagonists, Heart Failure, Systolic
Abstract: International audience; Background: The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported.Objectives: The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).Methods: Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP.Results: Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs
Published: 2021

30. The longitudinal association between early-life screen viewing and abdominal adiposity—findings from a multiethnic birth cohort study

Author: Yung Seng Lee, Suresh Anand Sadananthan, Carla Costa Lança, Seang-Mei Saw, Falk Müller-Riemenschneider, Shirong Cai, Fabian Yap, Mya-Thway Tint, Lynette Pei-Chi Shek, Johan G. Eriksson, Michael S. Kramer, Marielle V. Fortier, Keith M. Godfrey, Yap Seng Chong, Natarajan Padmapriya, Navin Michael, Jia Ying Toh, S. Sendhil Velan, Bozhi Chen, Peter D. Gluckman, Jonathan Y. Bernard, Kok Hian Tan, Mary Foong-Fong Chong, National University of Singapore (NUS), Saw Swee Hock School of Public Health [Singapore, Singapore], Agency for science, technology and research [Singapore] (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Singapore Eye Research Institute [Singapore] (SERI), KK Women's and Children's Hospital [Singapore], Duke-National University of Singapore Graduate Medical School, Khoo Teck Puat – National University Children’s Medical Institute (NUHkids) [Singapore] (KTP-NUCMI), National University Health System [Singapore] (NUHS), University of Auckland [Auckland], Duke-NUS Medical School [Singapore], Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Yong Loo Lin School of Medicine [Singapore], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, McGill University = Université McGill [Montréal, Canada], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Berlin Institute of Health (BIH), and Bernard, Jonathan
Subjects: Male, Pediatric Obesity, medicine.medical_specialty, Screen viewing, Endocrinology, Diabetes and Metabolism, Abdominal Fat, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, Article, Cohort Studies, Screen Time, 03 medical and health sciences, 0302 clinical medicine, Adverse Childhood Experiences, Risk Factors, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Correlation of Data, Singapore, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, Confounding, Magnetic resonance imaging, Magnetic Resonance Imaging, Early life, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Subcutaneous adipose tissue, business, Birth cohort, Cohort study
Abstract: Importance: screen-viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.Results: in the overall sample (n=307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.Conclusion: greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
Published: 2021

31. The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: The results of the AFFIRM-AHF study

Author: Marco Metra, Marcus Andreas Ohlsson, Basil S. Lewis, Wolfram Doehner, Peter van der Meer, Irakli Khintibidze, Hans Kragten, Bridget-Anne Kirwan, Jose C. Nicolau, Vincent Fabien, Tim Friede, Nicolas Danchin, Ewa A. Jankowska, Gerasimos Filippatos, Alain Cohen-Solal, Fabio Dorigotti, Hadi Skouri, Davor Miličić, Andre Keren, Alexander Parkhomenko, Jarosław Drożdż, David Sim, Stuart J. Pocock, Michael Motro, Javed Butler, Domingo A. Pascual-Figal, Theresa McDonagh, Henry J. Dargie, Josep Comín-Colet, Maria Dorobantu, Mikhail Kosiborod, Frank Ruschitzka, Stephan von Haehling, Piotr Ponikowski, Stefan D. Anker, Felipe Martinez, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), leboeuf, Christophe, Wrocław Medical University, Socar Research S.A. [Nyon, Switzerland] (SR), London School of Hygiene and Tropical Medicine (LSHTM), Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of Mississippi Medical Center (UMMC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], King‘s College London, Universitatea din Bucuresti (UB), Medical University of Łódź (MUL), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), Assuta Hospital in Ramat HaHayal [Tel Aviv-Yafo, Israel] (AHRH), Tbilisi State University, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Prague University of Economics and Business, Università degli Studi di Brescia = University of Brescia (UniBs), Civic Hospital of Brescia, University of Zagreb, Skane University Hospital [Malmo], Lund University [Lund], National Scientific Center 'M.D. Strazhesko Institute of Cardiology' [Kyiv, Ukraine] (NSC/MDSIC), Universidad de Murcia, University hospital of Zurich [Zurich], National Heart Centre Singapore (NHCS), American University of Beirut Faculty of Medicine and Medical Center (AUB), University Medical Center Groningen [Groningen] (UMCG), Rappaport faculty of Medicine, Technion - Israel Institute of Technology [Haifa], L’Hospitalet de Llobregat [Barcelona, Spain], Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University Medical Center Göttingen (UMG), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Glasgow, Tel Aviv University (TAU), Kfar Saba and Sackler School of Medicine, Vifor Pharma Ltd [Glattbrugg, Switzerland], and University College of London [London] (UCL)
Subjects: medicine.medical_specialty, Randomization, Heart diseases, Iron, Health-related quality of life, Population, Heart failure, 030204 cardiovascular system & hematology, Placebo, law.invention, Malalties del cor, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Clinical Research, Internal medicine, medicine, Humans, Clinical Trials, AcademicSubjects/MED00200, 030212 general & internal medicine, education, education.field_of_study, Ejection fraction, Dèficit de ferro, Anemia, Iron-Deficiency, business.industry, Iron deficiency, Acute heart failure, medicine.disease, Confidence interval, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Dietary Supplements, Intravenous ferric carboxymaltose therapy, Iron deficiency diseases, Randomized clinical trial, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. Methods and results The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. Conclusion In iron-deficient patients with HF and left ventricular ejection fraction, Graphical Abstract
Published: 2021

32. Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions

Author: Fabio Grizzi, Alberto Mantovani, Domenico Supino, Fabio Pasqualini, Marie-Astrid Boutet, Andrea Gianatti, Marina Sironi, Maria José Oliveira, Barbara Bottazzi, Silvia Carnevale, Matteo Stravalaci, Sarah N. Mapelli, Irene Mattiola, C. Pitzalis, Rémi Porte, Rita Silva-Gomes, Federico Colombo, Massimo Locati, Humanitas University [Milan] (Hunimed), Universidade do Porto, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Queen Mary University of London (QMUL), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Mucosal and Developmental Immunology [Berlin, Germany], IRCCS San Raffaele Scientific Institute [Milan, Italie], Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Milan, Federal University of Health Sciences of Porto Alegre = Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Universidade do Porto = University of Porto, Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Università degli Studi di Milano = University of Milan (UNIMI), and Jehan, Frederic
Subjects: rheumatoid arthritis, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Myeloid, Immunology, Population, Biology, Monocytes, 03 medical and health sciences, 0302 clinical medicine, monocytes/Mϕs, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Immunology and Allergy, Gene family, Humans, Family, education, 030304 developmental biology, Regulation of gene expression, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, education.field_of_study, MS4A6A, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MS4A3, COVID-19, Membrane Proteins, Cell Biology, Antigens, CD20, In vitro, 3. Good health, Cell biology, MS4A4A, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MS4A2, 030217 neurology & neurosurgery, Function (biology)
Abstract: The MS4A gene family encodes 18 tetraspanin-like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT-PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte-to-Mϕ differentiation in parallel with an increase in MS4A4A expression. Analysis of gene expression regulation revealed a strong induction of MS4A4A, MS4A6A, MS4A7, and MS4A4E by glucocorticoid hormones. Consistently with in vitro findings, MS4A4A and MS4A7 were expressed in tissue Mϕs from COVID-19 and rheumatoid arthritis patients. Interestingly, MS4A3, selectively expressed in myeloid precursors, was found to be a marker of immature circulating neutrophils, a cellular population associated to COVID-19 severe disease. The results reported here show that members of the MS4A family are differentially expressed and regulated during myelomonocytic differentiation, and call for assessment of their functional role and value as therapeutic targets.
Published: 2021

33. Anxiety and depression risk in patients with allergic rhinitis: a systematic review and meta-analysis

Author: Jean Bousquet, R Vaz, F Franco-Pego, J Rodrigues, K Raemdonck, B Sousa-Pinto, Hospital de São João [Porto], Universidade do Porto = University of Porto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and Herrada, Anthony
Subjects: MESH: Depression, Subgroup analysis, MESH: Comorbidity, Comorbidity, Anxiety, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Depression (differential diagnoses), MESH: Humans, MESH: Anxiety, Depression, business.industry, General Medicine, Odds ratio, medicine.disease, Anxiety Disorders, Rhinitis, Allergic, 030228 respiratory system, Otorhinolaryngology, Mood disorders, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Meta-analysis, MESH: Rhinitis, Allergic, Observational study, MESH: Anxiety Disorders, medicine.symptom, business, Clinical psychology
Abstract: International audience; Background: Allergic diseases appear to be associated with mood disorders. However, particularly regarding allergic rhinitis (AR), such association has not been adequately systematically reviewed. Therefore, we conducted a systematic review and meta-analysis to quantify the association between AR and depression and anxiety. Methodology: We performed an electronic search of PubMed, Web of Science and Scopus for observational studies assessing the association between AR and depression and anxiety. Such association was quantified by means of random-effects meta-analysis, with estimation of pooled odds ratio (OR). Sources of heterogeneity were explored by subgroup analysis. Results: We included a total of 24 primary studies, of which 23 assessed depression and 11 assessed anxiety. Of these, 12 studies presented OR from multivariable regression models and were included in our meta-analysis. AR was associated with higher odds of depression and anxiety. Conclusions: AR appears to be associated with high risk of depression and anxiety. While our results point to the importance of mental comorbidities among patients with AR, longitudinal studies are needed adopting uniform definitions and presenting results stratified by AR severity.
Published: 2021

34. Management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation: a consensus document of the ESC Working Group on Thrombosis and the European Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration with the ESC Council on Valvular Heart Disease

Author: Diana A. Gorog, Erik Lerkevang Grove, Dariusz Dudek, Andrea Rubboli, Julinda Mehilli, Jurriën M. ten Berg, Gemma Vilahur, Julia Grapsa, Lucia Torracca, Bianca Rocca, Adam Witkowski, Anna Sonia Petronio, Eric Van Belle, Patrizio Lancellotti, Jean-Philippe Collet, Dirk Sibbing, Martine Gilard, Bernard Chevalier, Cardiologie, RS: Carim - B04 Clinical thrombosis and Haemostasis, St. Antonius Hospital [Nieuwegein], Ludwig-Maximilians-Universität München [LMU], German Center for Cardiovascular Research [DZHK], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] [Unicatt], Institut Coeur Poumon [CHU Lille], Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011], Hôpital Privé Jacques Cartier [Massy], CHU Pitié-Salpêtrière [AP-HP], Groupe Action, Hôpital de la Cavale Blanche, Université de Brest [UBO], Imperial College London, University of Hertfordshire [Hatfield] [UH], Aarhus University Hospital, Centre Hospitalier Universitaire de Liège [CHU-Liège], University of Pisa - Università di Pisa, Hospital de la Santa Creu i Sant Pau, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Ludwig-Maximilians-Universität München (LMU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), CHU Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Jagiellonian University - Medical College (JUMC), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Maria Cecilia Hospital [Cotignola], Université de Brest (UBO), University of Hertfordshire [Hatfield] (UH), Guy's and St Thomas' NHS Foundation Trust [London, UK], Centre Hospitalier Universitaire de Liège (CHU-Liège), and National Institute of Cardiology [Varsovie, Pologne]
Subjects: medicine.medical_specialty, Percutaneous, Consensus, Settore BIO/14 - FARMACOLOGIA, [SDV]Life Sciences [q-bio], Heart Valve Diseases, 030204 cardiovascular system & hematology, Lower risk, law.invention, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Antithrombotic treatment, Transcatheter aortic valve implantation, Aged, Aortic Valve, Fibrinolytic Agents, Humans, Treatment Outcome, Aortic Valve Stenosis, Heart Valve Prosthesis Implantation, Thrombosis, Randomized controlled trial, law, Internal medicine, Antithrombotic, medicine, 030212 general & internal medicine, Adverse effect, Aortic Valve/surgery, ANTIPLATELET THERAPY, business.industry, Fibrinolytic Agents/therapeutic use, valvular heart disease, Thrombosis/drug therapy, medicine.disease, Stenosis, Aortic Valve Stenosis/drug therapy, Transcatheter Aortic Valve Replacement/adverse effects, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Transcatheter aortic valve implantation (TAVI) is effective in older patients with symptomatic severe aortic stenosis, while the indication has recently broadened to younger patients at lower risk. Although thromboembolic and bleeding complications after TAVI have decreased over time, such adverse events are still common. The recommendations of the latest 2017 ESC/EACTS Guidelines for the management of valvular heart disease on antithrombotic therapy in patients undergoing TAVI are mostly based on expert opinion. Based on recent studies and randomized controlled trials, this viewpoint document provides updated therapeutic insights in antithrombotic treatment during and after TAVI.
Published: 2021

35. Analysing different exposures identifies that wearing masks and establishing COVID-19 areas reduce secondary-attack risk in aged-care facilities

Author: Mircea T. Sofonea, Hubert Blain, Amandine Pisoni, Samuel Alizon, Christian Selinger, Bastien Reyné, Stéphanie Miot, Edouard Tuaillon, Jean Bousquet, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), EuroMov - Digital Health in Motion (Euromov DHM), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Montpellier (UM), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Génétique et évolution des maladies infectieuses (GEMI), and Alizon, Samuel
Subjects: Epidemiology, Generalised Linear Mixed Models, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Corrections, law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Infection control, aged care facilities, secondary-attack risk, 030212 general & internal medicine, aged-care facilities, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Likelihood Functions, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], secondary attack risk, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Masks, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Transmission (mechanics), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Environmental health, Humans, AcademicSubjects/MED00860, Aged care, Epidemics, mask wearing, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], SARS-CoV-2, business.industry, Outbreak, COVID-19, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, generalized linear mixed models, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, 030217 neurology & neurosurgery, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Background The COVID-19 epidemic has spread rapidly within aged-care facilities (ACFs), where the infection-fatality ratio is high. It is therefore urgent to evaluate the efficiency of infection prevention and control (IPC) measures in reducing SARS-CoV-2 transmission. Methods We analysed the COVID-19 outbreaks that took place between March and May 2020 in 12 ACFs using reverse transcription–polymerase chain reaction (RT–PCR) and serological tests for SARS-CoV-2 infection. Using maximum-likelihood approaches and generalized linear mixed models, we analysed the proportion of infected residents in ACFs and identified covariates associated with the proportion of infected residents. Results The secondary-attack risk was estimated at 4.1%, suggesting a high efficiency of the IPC measures implemented in the region. Mask wearing and the establishment of COVID-19 zones for infected residents were the two main covariates associated with lower secondary-attack risks. Conclusions Wearing masks and isolating potentially infected residents appear to be associated with a more limited spread of SARS-CoV-2 in ACFs.
Published: 2021

36. Predicting risk of cardiovascular events 1 to 3 years post‐myocardial infarction using a global registry

Author: Tigris Study Investigators, Christopher B. Granger, Katarina Hedman, Richard Grieve, Satoshi Yasuda, Kirsten L. Rennie, Shaun G. Goodman, John Gregson, Mauricio G. Cohen, Ji Y Chen, Dirk Westermann, Tabassome Simon, Karolina Andersson Sundell, Stuart J. Pocock, David Brieger, Jose C. Nicolau, Pocock, Stuart J [0000-0003-2212-4007], Brieger, David [0000-0001-6115-0326], Westermann, Dirk [0000-0002-7542-1956], Apollo - University of Cambridge Repository, London School of Hygiene and Tropical Medicine (LSHTM), The University of Sydney, University of Miami Leonard M. Miller School of Medicine (UMMSM), University of Toronto, St. Michael's Hospital, Duke University Medical Center, Universidade de São Paulo (USP), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and AstraZeneca
Subjects: Male, medicine.medical_specialty, Clinical Investigations, Myocardial Infarction, Infarction, 030204 cardiovascular system & hematology, Rate ratio, Risk Assessment, cardiac risk factors and prevention, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Registries, Risk factor, Stroke, Aged, Aged, 80 and over, business.industry, Unstable angina, Models, Cardiovascular, General Medicine, Middle Aged, medicine.disease, Prognosis, 3. Good health, Cardiovascular Diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Cardiology and Cardiovascular Medicine, business, coronary artery disease, Kidney disease
Abstract: International audience; Background: Risk prediction tools are lacking for patients with stable disease some years after myocardial infarction (MI).Hypothesis: A practical long‐term cardiovascular risk index can be developed.Methods: The long‐Term rIsk, Clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post‐myocardial infarction patients prospective global registry enrolled patients 1 to 3 years post‐MI (369 centers; 25 countries), all with ≥1 risk factor (age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, or chronic non‐end‐stage kidney disease [CKD]). Self‐reported health was assessed with EuroQoL‐5 dimensions. Multivariable Poisson regression models were used to determine key predictors of the primary composite outcome (MI, unstable angina with urgent revascularization [UA], stroke, or all‐cause death) over 2 years.Results: The primary outcome occurred in 621 (6.9%) of 9027 eligible patients: death 295 (3.3%), MI 195 (2.2%), UA 103 (1.1%), and stroke 58 (0.6%). All events accrued linearly. In a multivariable model, 11 significant predictors of primary outcome (age ≥65 years, diabetes, second prior MI, CKD, history of major bleed, peripheral arterial disease, heart failure, cardiovascular hospitalization (prior 6 months), medical management (index MI), on diuretic, and poor self‐reported health) were identified and combined into a user‐friendly risk index. Compared with lowest‐risk patients, those in the top 16% had a rate ratio of 6.9 for the primary composite, and 18.7 for all‐cause death (overall c‐statistic; 0.686, and 0.768, respectively). External validation was performed using the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events registry (c‐statistic; 0.748, and 0.849, respectively).Conclusions: In patients >1‐year post‐MI, recurrent cardiovascular events and deaths accrue linearly. A simple risk index can stratify patients, potentially helping to guide management.
Published: 2019

37. How to diagnose heart failure with preserved ejection fraction

Author: Frank Edelmann, Carolyn S.P. Lam, Adriaan A. Voors, Piotr Ponikowski, Alan G. Fraser, Frank Ruschitzka, Stefan D. Anker, Erwan Donal, Rudolf A. de Boer, Burkert Pieske, Carsten Tschöpe, Petar M. Seferovic, Marco Guazzi, Michael Fu, Walter Paulus, Eike Nagel, Daniel A. Morris, Scott D. Solomon, Gerasimos Filippatos, Patrizio Lancellotti, Elisabeth Pieske-Kraigher, Vojtech Melenovsky, Frans H. Rutten, Ramachandran S. Vasan, Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Groningen [Groningen], Cardiff University, 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), CHU Pontchaillou [Rennes], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University Medical Center Groningen [Groningen] (UMCG), GIGA [Université Liège], Université de Liège, Institute for Clinical and Experimental Medicine (IKEM), University of Wrocław [Poland] (UWr), Harvard Medical School [Boston] (HMS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), University Medical Center [Utrecht], University Heart Centre Freiburg - Bad Krozingen, Energy Research Centre of the Netherlands (ECN), University of Belgrade [Belgrade], University of Cyprus [Nicosia], Heart Failure Association, Cardiovascular Centre (CVC), University of Zurich, Pieske, Burkert, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of Cyprus [Nicosia] (UCY)
Subjects: Male, diagnosis, VENTRICULAR DIASTOLIC FUNCTION, Speckle tracking echocardiography, 030204 cardiovascular system & hematology, PULMONARY-HYPERTENSION, 0302 clinical medicine, CAPILLARY WEDGE PRESSURE, Natriuretic peptide, echocardiography, LEFT ATRIAL VOLUME, 030212 general & internal medicine, AMERICAN SOCIETY, Ejection fraction, GUANYLATE-CYCLASE STIMULATOR, IMPAIRED SYSTOLIC FUNCTION, Atrial fibrillation, Middle Aged, 3. Good health, Echocardiography, CARDIOVASCULAR MAGNETIC-RESONANCE, Practice Guidelines as Topic, cardiovascular system, Cardiology, 10209 Clinic for Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Cardiology and Cardiovascular Medicine, Algorithm, Algorithms, medicine.medical_specialty, Consensus, medicine.drug_class, Heart Ventricles, Clinical Decision-Making, Diastole, 610 Medicine & health, Heart failure, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, Internal medicine, SPECKLE TRACKING ECHOCARDIOGRAPHY, medicine, Humans, cardiovascular diseases, Pulmonary wedge pressure, Natriuretic Peptides, Aged, Heart Failure, Diastolic, exercise echocardiography, business.industry, biomarkers, Stroke Volume, medicine.disease, NATRIURETIC PEPTIDE LEVELS, HFpEF, Heart failure with preserved ejection fraction, business, natriuretic peptides
Abstract: Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.
Published: 2019

38. CKD

Author: Toralf Melsom, Marco van Londen, Hans Pottel, Bjørn Odvar Eriksen, Pierre Delanaye, Elke Schaeffner, François Gaillard, Gunnar Nordin, Maarten W. Taal, Arend Bökenkamp, Runolfur Palsson, Christine A. White, Markus van der Giet, Giovanni Gambaro, Kitty J. Jager, Richard J. Glassock, Olivier Moranne, Christophe Mariat, Laurence Dubourg, Andrew D. Rule, Anders Grubb, Olafur S. Indridason, Jan A.J.G. van den Brand, Anders Christensson, Centre Hospitalier Universitaire de Liège (CHU-Liège), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Vrije Universiteit Amsterdam [Amsterdam] (VU), Skane University Hospital [Malmo], Lund University [Lund], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), The Arctic University of Norway (UiT), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Verona (UNIVR), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Landspitali National University Hospital of Iceland, University Medical Center Groningen [Groningen] (UMCG), CHU Saint-Etienne, Université Jean Monnet [Saint-Étienne] (UJM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of Iceland [Reykjavik], Université Catholique de Louvain = Catholic University of Louvain (UCL), Mayo Clinic [Rochester], Humboldt University of Berlin, Berlin Institute of Health (BIH), University of Nottingham, UK (UON), Queen's University [Kingston, Canada], Radboud University Medical Center [Nijmegen], Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Global Health, and APH - Quality of Care
Subjects: CHRONIC KIDNEY-DISEASE, Pediatrics, medicine.medical_specialty, CARDIOVASCULAR MORTALITY, 030232 urology & nephrology, Renal function, Urine, 030204 cardiovascular system & hematology, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, GLOMERULAR-FILTRATION-RATE, 03 medical and health sciences, 0302 clinical medicine, Up Front Matters, Risk of mortality, medicine, Elderly people, Humans, Renal Insufficiency, Healthy aging, Renal Insufficiency, Chronic, Chronic, ESTIMATED GFR, Adverse effect, ALL-CAUSE MORTALITY, Kidney, glomerular filtration rate, business.industry, urogenital system, Age Factors, STAGE RENAL-DISEASE, General Medicine, medicine.disease, Prognosis, ELDERLY POPULATION, female genital diseases and pregnancy complications, REFERENCE VALUES, 3. Good health, medicine.anatomical_structure, Nephrology, COLLABORATIVE METAANALYSIS, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, HIGHER ALBUMINURIA, epidemiology and outcomes, chronic kidney disease, Kidney disease
Abstract: Item does not contain fulltext Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m(2) This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR
Published: 2019

39. Role of RXRβ in platelet function and arterial thrombosis

Author: Joachim Pircher, Enzo Lüsebrink, Steffen Massberg, Verena Warm, Pierre Chambon, Christian Schulz, Andreas Ehrlich, Zhe Zhang, Tobias Petzold, Jan Strecker, Klinikum der Universitat Munchen, Ludwig-Maximilians-Universität München (LMU), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: Blood Platelets, Male, retinoids, platelet function, RXR, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030204 cardiovascular system & hematology, Retinoid X receptor, Ferric Compounds, Thrombopoiesis, Mice, 03 medical and health sciences, 0302 clinical medicine, Chlorides, Megakaryocyte, In vivo, medicine, Animals, nuclear receptor, Platelet, Carotid Artery Thrombosis, Platelet activation, Receptor, thrombosis, Mice, Knockout, [SDV.GEN]Life Sciences [q-bio]/Genetics, Chemistry, Hematology, Platelet Activation, Cell biology, DNA-Binding Proteins, Mice, Inbred C57BL, medicine.anatomical_structure, Nuclear receptor, Knockout mouse, Female
Abstract: OBJECTIVE: Retinoid X receptors (RXR) are a family of nuclear receptors that play critical roles in the regulation of numerous fundamental biological processes including cell proliferation, differentiation, and death. Earlier studies suggested that treatment with RXR agonists attenuates platelet activation in all adults (male and femal) and mice; however, the underlying molecular mechanisms have remained insufficiently understood. To elaborate further on this issue, we characterized megakaryocyte and platelet-specific RXR knockout mice to study platelet function in vitro and arterial thrombosis in vivo. APPROACH AND RESULTS: First, we identified RXRbeta as the dominant RXR receptor in mouse platelets, prompting us to generate a megakaryocyte and platelet-specific PF4(Cre) ;RXRbeta(flox/flox) mouse. Second, we studied activation, spreading, and aggregation of platelets from C57Bl/6 wild-type mice (WT), PF4(Cre+) ;RXRbeta(flox/flox) mice, and PF4(Cre-) ;RXRbeta(flox/flox) littermate controls in the presence or absence of RXR ligands, that is, 9-cis-retinoic acid (9cRA) and methoprene acid (MA). We found that in vitro treatment with RXR ligands attenuates spreading and aggregation of platelets and increases proplatelet particle formation from megakaryocytes (MK). However, these effects are also observed in RXRbeta-deficient platelets and MKs and are thus independent of RXRbeta. Third, we investigated arterial thrombus formation in an iron chloride (FeCl3)-induced vascular injury model in vivo, which is also not affected by the absence of RXRbeta in platelets. CONCLUSIONS: Absence of the most abundant RXR receptor in mouse platelets, RXRbeta, does not affect platelet function in vitro and thrombus formation in vivo. Furthermore, RXR agonists' mediated effects on platelet function are independent of RXRbeta expression. Hence, our data do not support a significant contribution of RXRbeta to arterial thrombosis in mice.
Published: 2019

40. Molecular Profiling Reclassifies Adult Astroblastoma into Known and Clinically Distinct Tumor Entities with Frequent Mitogen-Activated Protein Kinase Pathway Alterations

Author: Franck Bielle, Mehdi Touat, Karima Mokhtari, Aurélien Nouet, Yannick Marie, Philipp Euskirchen, Audrey Rousseau, Luc Taillandier, William Boisseau, Justine Guegan, Marc Sanson, Caroline Dehais, Carine Karachi, Ahmed Idbaih, Nadine Martin-Duverneuil, Laurent Capelle, Khê Hoang-Xuan, Jean-Yves Delattre, Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Berlin Institute of Health (BIH), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Service de Neuropathologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER
Subjects: Adult, Male, Cancer Research, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Astroblastoma, Brain tumor, MN1‐BEND2, [SDV.CAN]Life Sciences [q-bio]/Cancer, DNA sequencing, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Neuro‐Oncology, Next‐generation sequencing, Aged, 030304 developmental biology, 0303 health sciences, biology, Brain Neoplasms, business.industry, Middle Aged, medicine.disease, Neoplasms, Neuroepithelial, 3. Good health, BRAF mutation, Oncology, Mitogen-activated protein kinase, Cancer research, biology.protein, Female, Mitogen-Activated Protein Kinases, business, 030217 neurology & neurosurgery, Recurrent Meningioma
Abstract: BackgroundAstroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined.Materials and MethodsWe performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM.ResultsStrikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma.ConclusionWe suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway.Implications for PracticeAstroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.
Published: 2019

41. Mo-derived perivascular macrophage recruitment protects against endothelial cell death in retinal vein occlusion

Author: Michel Paques, Elisa Dominguez, José-Alain Sahel, Florian Sennlaub, William Raoul, Xavier Guillonneau, Christophe Roubeix, Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Berlin Institute of Health (BIH), This work was supported by the grants from INSERM and LABEX LIFESENSES (ANR-10-LABEX-65)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Université de Tours (UT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Raoul, William, and Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID
Subjects: 0301 basic medicine, Pathology, Endothelial cells, Monocytes, lcsh:RC346-429, Mice, 0302 clinical medicine, Macrophage, Chemokine CCL2, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CD11b Antigen, Cell Death, Chemistry, General Neuroscience, Intercellular Adhesion Molecule-1, Vein occlusion, Endothelial stem cell, medicine.anatomical_structure, Neurology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, medicine.medical_specialty, Retinal Vein, [SDV.IMM] Life Sciences [q-bio]/Immunology, Receptors, CCR2, Immunology, Inflammation, Perivascular macrophages, 03 medical and health sciences, Cellular and Molecular Neuroscience, Retinal Vein Occlusion, medicine, Animals, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, lcsh:Neurology. Diseases of the nervous system, BRVO, Monocyte, Macrophages, Research, medicine.disease, Antigens, Differentiation, Disease Models, Animal, 030104 developmental biology, Apoptosis, Branch retinal vein occlusion, CCR2, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND:To decipher the role of monocyte-derived macrophages (Mφs) in vascular remodeling of the occluded vein following experimental branch retinal vein occlusion (BRVO).METHODS:The inflammation induced by laser-induced BRVO on mice retina was evaluated at different time points by RT-PCR looking at inflammatory markers mRNA level expression, Icam-1, Cd11b, F4/80, Ccl2, and Ccr2 and by quantification of Iba1-positive macrophage (Mφ) density on Iba1-stained retinal flatmount. Repeated intraperitoneal EdU injection combined with liposome clodronate-induced monocyte (Mo) depletion in wildtype mice was used to differentiate Mo-derived Mφs from resident Mφs. Liposome clodronate Mo-depleted wildtype mice and Ccr2-deficient mice were used to evaluate the role of all CCR2+ and CCR2neg Mo-derived Mφs on EC apoptosis in the occluded vein.RESULTS:cd11b, ICAM-1, F4/80, Ccl2, and Ccr2 mRNA expression were increased 1, 3, and 7 days after vein occlusion. The number of parenchymal (parMφs) and perivascular (vasMφs) macrophages was increased 3 and 7 days after BRVO. The systemic depletion of all circulating Mos decreased significantly the BRVO-induced parMφs and vasMφs macrophage accumulation, while the deletion of CCR2+-inflammatory Mo only diminished the accumulation of parMφs, but not vasMφs. Finally, apoptotic ECs of the vein were more numerous in fully depleted, liposome clodronate-treated mice, than in Ccr2-/- mice that only lack the recruitment of CCR2+ inflammatory Mos.CONCLUSIONS:BRVO triggers the recruitment of blood-derived parMφs and vasMφs. Interestingly, vasMφs accumulation was independent of CCR2. The observation that the inhibition of the recruitment of all infiltrating Mφs increases the vein EC apoptosis, while CCR2 deficiency does not, demonstrates that CCR2neg Mo-derived vasMφs protect the ECs against apoptosis in the occluded vein.
Published: 2019

42. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author: Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory
Subjects: 0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract: All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).
Published: 2019

43. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

Author: Magdalena Harakalova, Benjamin Meder, Philippe Charron, Manuel Gómez-Bueno, Jorg J. A. Calis, François Cambien, David-Alexandre Trégouët, Maurizia Grasso, Steven McGinn, Uwe Völker, Thomas Meitinger, Stefan Weiss, L. Duboscq-Bidot, Richard Dorent, Vera Regitz-Zagrosek, Folkert W. Asselbergs, Hélène Blanché, Olivier Dubourg, Patrick Lacolley, Pierre Boutouyrie, Delphine Bacq-Daian, Vincent Fontaine, Volker Ruppert, Marine Germain, K Lehnert, Jean-Noël Trochu, Stuart A. Cook, Angélique Curjol, Brendan J. Keating, Ibticem Raji, Anne Boland, J. Erdmann, Michael Morley, Jean-François Aupetit, Paloma Remior, Luigi Tavazzi, Gérard Roizès, Michal Mokry, Konstantin Strauch, Richard Isnard, Jean-Philippe Empana, Robert Olaso, Kenneth B. Marguiles, Zofia T. Bilińska, Stephan B. Felix, Marcus Dörr, Thomas P. Cappola, Stefan Blankenberg, Jan Haas, Céline Besse, Jean-François Deleuze, Christine E. Seidman, Christian Hengstenberg, Jessica van Setten, Hakon Hakonarson, Sanjay K Prasad, Daiane Hemerich, Pascal de Groote, Thomas Wichter, Alain van Mil, Michel Komajda, Renee Maas, Carole Proust, Declan P. O'Regan, Xavier Jouven, Ganapathi Varma Saripella, Georgios Kararigas, Eloisa Arbustini, Jin Li, Klaus Stark, Laurent Fauchier, Flavie Ader, Melanie Waldenberger, Martina Müller-Nurasyid, Eric Villard, Sophie Garnier, Cardiology, Imperial College Healthcare NHS Trust- BRC Funding, British Heart Foundation, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique-Hôpitaux de Paris, Fondation Leducq, Société Française de Cardiologie, Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München, Université de Bordeaux, Medical Research Council, ANR-10-LABX-0013,GENMED,Medical Genomics(2010), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Medical Center [Utrecht], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Pennsylvania, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), National Heart Centre Singapore (NHCS), Children’s Hospital of Philadelphia (CHOP ), University of Regensburg, Royal Brompton Hospital, Imperial College London, Istituti Clinici Scientifici Maugeri [Pavia] (IRCCS Pavia - ICS Maugeri), Helmholtz Zentrum München = German Research Center for Environmental Health, Ludwig-Maximilians-Universität München (LMU), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Medical Center of the Johannes Gutenberg-University Mainz, Perelman School of Medicine, Harvard Medical School [Boston] (HMS), University of Iceland [Reykjavik], Heidelberg University, Stanford University Medical School, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Universität zu Lübeck = University of Lübeck [Lübeck], Universitätklinikum Gießen und Marburg GmbH, Maria Cecilia Hospital [Cotignola], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Centre hospitalier Saint Joseph - Saint Luc [Lyon], National Institute of Cardiology [Varsovie, Pologne], University of Medicine Greifswald, Centre de Référence Maladies Cardiaques Héréditaires, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Swedish University of Agricultural Sciences (SLU), Centre d'Etude du Polymorphisme Humain (CEPH), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité), Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Paris Descartes - Paris 5 (UPD5), Groupe Hospitalier Paris Saint Joseph, Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), and University College of London [London] (UCL)
Subjects: Cardiac & Cardiovascular Systems, Cardiomyopathy, Dilated/genetics, [SDV]Life Sciences [q-bio], Signal Transducing/genetics, Dilated cardiomyopathy, Genome-wide association study, Adaptor Proteins, Signal Transducing/genetics, 030204 cardiovascular system & hematology, TAURINE, 0302 clinical medicine, GWAS, Medicine, POSITION STATEMENT, 1102 Cardiorespiratory Medicine and Haematology, Genetics, 0303 health sciences, education.field_of_study, Genetic Predisposition to Disease/genetics, Adaptor Proteins, 4C-sequencing, Polymorphism, Single Nucleotide/genetics, Genetic risk score, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Single Nucleotide/genetics, Cardiomyopathy, Dilated, Cardiomyopathy, Population, Locus (genetics), Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Chromosomes, 03 medical and health sciences, Systolic/genetics, Heart Failure, Systolic/genetics, SNP, Animals, Humans, Genetic Predisposition to Disease, Allele, Polymorphism, education, Imputation, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Heart Failure, Science & Technology, business.industry, WORKING GROUP, 1103 Clinical Sciences, medicine.disease, Genetic architecture, Cardiovascular System & Hematology, Dilated/genetics, Cardiovascular System & Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Apoptosis Regulatory Proteins, Heart Failure, Systolic, Genome-Wide Association Study
Abstract: Aims Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. Conclusion This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.
Published: 2021

44. Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts

Author: Laurent Elkrief, Sean Spinney, Daniel E. Vosberg, Tobias Banaschewski, Arun L. W. Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Zdenka Pausova, Tomáš Paus, Guillaume Huguet, Patricia Conrod, the IMAGEN consortium, Université de Montréal (UdeM), CHU Sainte Justine [Montréal], Universität Heidelberg [Heidelberg], Trinity College Dublin, King‘s College London, Heidelberg University, University of Mannheim, University of Vermont [Burlington], University of Nottingham, UK (UON), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Freie Universität Berlin, Berlin Institute of Health (BIH), Physikalisch-Technische Bundesanstalt [Berlin] (PTB), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université de Paris (UP), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-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), University Medical Center Göttingen (UMG), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Humboldt-Universität zu Berlin, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Mannheim, Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Humboldt University Of Berlin, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV]Life Sciences [q-bio], RC435-571, Alcohol use disorder, alcohol use disorder, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Gene interaction, MGLL, Medicine, DAGL, endocannabinoid system, Original Research, 030304 developmental biology, Psychiatry, 0303 health sciences, CNR1, Alcohol Use Disorders Identification Test, Multifactor dimensionality reduction, business.industry, Odds ratio, medicine.disease, cannabinoid receptor 1, Psychiatry and Mental health, Exact test, Cohort, business, 030217 neurology & neurosurgery, Demography
Abstract: Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14–18 years old) followed in the IMAGEN study (n = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) (n = 772). Case-control status is represented by a score of more than 7 on the Alcohol Use Disorder Identification Test (AUDIT). First a set-based test method was used to examine if a relationship between the eCB system and AUDIT case/control status exists at the gene level. Using only SNPs that are both independent and significantly associated to case-control status, we perform Fisher's exact test to determine SNP level odds ratios in relation to case-control status and then perform logistic regressions as post-hoc analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five eCB genes with positive AUDIT screen. While no gene-sets were significantly associated to AUDIT scores after correction for multiple tests, in the case/control analysis, 7 SNPs were significantly associated with AUDIT scores of > 7 (p < 0.05; ORCNR1 (pcorrected =0.042, OR = 0.73) and rs507961 in MGLL (pcorrected = 0.043, OR = 0.78). Logistic regression showed that both rs9353525 (CNR1) and rs507961 (MGLL) remained significantly associated with positive AUDIT screens (p < 0.01; OR < 1) after correction for multiple covariables and interaction of covariable × SNP. This result was not replicated in the SYS cohort. The GMDR model revealed a significant three-SNP interaction (p = 0.006) involving rs484061 (MGLL), rs4963307 (DAGLA), and rs7766029 (CNR1) predicted case-control status, after correcting for multiple covariables in the IMAGEN sample. A binomial logistic regression of the combination of these three SNPs by phenotype in the SYS cohort showed a result in the same direction as seen in the IMAGEN cohort (BETA = 0.501, p = 0.06). While preliminary, the present study suggests that the eCB system may play a role in the development of AUD in adolescents.
Published: 2021

45. The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC

Author: José Luis Zamorano, Serge Boveda, Marco Metra, Mitja Lainscak, Ewa A. Jankowska, Theresa McDonagh, Jeroen J. Bax, Christian Mueller, Petar M. Seferovic, Andrew J.S. Coats, Thor Edvardsen, Andreas Baumbach, John G.F. Cleland, Claudio Muneretto, Ottavio Alfieri, Thomas Deneke, Mandeep R. Mehra, Jean-François Obadia, Fabien Praz, Lars Lund, Frank Ruschitzka, Dimitrios Farmakis, Alec Vahanian, Gerhard Hindricks, Hein Heidbuchel, Gerasimos Filippatos, Johann Bauersachs, Christoph Leclercq, Jelena Čelutkienė, Wilfried Mullens, Jörg Hausleiter, Nathan Mewton, Ralph Stephan von Bardeleben, Bernard Prendergast, Nikolaos Dagres, Stephan Windecker, Volker Rudolph, Piotr Ponikowski, Stefan D. Anker, Warwick Medical School, University of Warwick [Coventry], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Queen Mary University of London (QMUL), Yale University School of Medicine, IRCCS San Raffaele Scientific Institute [Milan, Italie], University Medical Center [Mainz], Hannover Medical School [Hannover] (MHH), Leiden University Medical Center (LUMC), Clinique Pasteur [Toulouse], Vilnius University [Vilnius], University of Glasgow, Universität Leipzig [Leipzig], University of Cyprus [Nicosia], National and Kapodistrian University of Athens (NKUA), University-Hospital Munich-Großhadern [München], University of Wrocław [Poland] (UWr), University of Ljubljana, CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Karolinska University Hospital [Stockholm], King‘s College London, Harvard Medical School [Boston] (HMS), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), University Hospital Basel [Basel], Ziekenhuis Oost-Limburg (ZOL), University of Brescia, Bern University Hospital [Berne] (Inselspital), Ruhr-Universität Bochum [Bochum], Université de Paris (UP), Universidad Carlos III de Madrid [Madrid] (UC3M), Oslo University Hospital [Oslo], Antwerp University Hospital [Edegem] (UZA), University of Belgrade [Belgrade], Guy's and St Thomas' Hospital [London], and Clinical sciences
Subjects: medicine.medical_specialty, Percutaneous, Functional mitral regurgitation, Heart failure, Secondary mitral regurgitation, Transcatheter mitral valve repair, 610 Medicine & health, 030204 cardiovascular system & hematology, law.invention, Special Article, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Mitral valve, medicine, AcademicSubjects/MED00200, 030212 general & internal medicine, Mitral regurgitation, Ejection fraction, business.industry, Guideline, medicine.disease, 3. Good health, medicine.anatomical_structure, Ventricle, Cardiology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology—the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)—presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach., Graphical abstract
Published: 2021

46. Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms

Author: Torsten Zuberbier, Julia Saueressig, Joaquim Mullol, Glenis Scadding, João Fonseca, G. Walter Canonica, Eric Van Ganse, Claus Bachert, Bolesław Samoliński, Olga Lourenço, Oliver Pfaar, Philippe Devillier, Ann-Kathrin Stroh, Wienczyslawa Czarlewski, Jean Bousquet, Ludger Klimek, Elísio Costa, Piotr Kuna, Detlef Schroder-Bernhardi, Victoria Cardona, Sophie Scheire, Nhan Pham Thi, Institut Català de la Salut, [Bousquet J] Charité Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany. University Hospital Montpellier, Montpellier, France. MACVIA-France, Montpellier, France. [Schröder-Bernhardi D] IQVIA Consumer Health, Frankfurt, Germany. [Bachert C] Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium. International Airway Research Center, First Affiliated Hospital Guangzou, Sun Yat-sen University, Guangzou, China. Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden. Department of ENT Diseases, Karolinska University Hospital, Stockholm, Sweden. [Canonica GW] Personalized Medicine Asthma, & Allergy Clinic-Humanitas University & Research Hospital, IRCCS-Milano, Milano, Italy. [Cardona V] Servei d’Al·lergologia, Servei de Medicina Interna, Vall d'Hebron Hospital Universitari, Barcelona, Spain. ARADyAL Research Network, Barcelona, Spain. [Costa EM] UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal, Vall d'Hebron Barcelona Hospital Campus, uBibliorum, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), IQVIA, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], IRCCS Istituto Nazionale dei Tumori [Milano], Vall d'Hebron University Hospital [Barcelona], Unidade de Ciencias Biomoleculares Aplicadas (UCIBIO), Requimte, Universidade do Porto = University of Porto-Departamento de Química (DQ), Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Faculdade de Ciências e Tecnologia = School of Science & Technology (FCT NOVA), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade do Porto = University of Porto-Departamento de Química (DQ), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Hôpital Foch [Suresnes], Universidade do Porto = University of Porto, University Medical Center [Mainz], Medical University of Łódź (MUL), University of Beira Interior [Portugal] (UBI), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Philipps Universität Marburg = Philipps University of Marburg, Institut de Recherche Biomédicale des Armées (IRBA), Medical University of Warsaw - Poland, University College of London [London] (UCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Retiveau, Nolwenn
Subjects: 0301 basic medicine, Allergy, IMPACT, Database analysis, Medications, costs, MESH: Allergy and Immunology, Medication, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Allergic rhinitis, 0302 clinical medicine, medications, MESH: Anti-Allergic Agents, Anti-Allergic Agents, Medicine and Health Sciences, Medicine, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Practice Patterns, Physicians', health care economics and organizations, International market, Medication use, Units, enfermedades respiratorias::enfermedades nasales::rinitis::rinitis alérgica [ENFERMEDADES], Medicaments - Prescripció - Europa, Europe, MESH: Rhinitis, Allergic, [SDV.IMM]Life Sciences [q-bio]/Immunology, preparados farmacéuticos::medicamentos por prescripción [COMPUESTOS QUÍMICOS Y DROGAS], localizaciones geográficas::Europa (continente) [DENOMINACIONES GEOGRÁFICAS], MIDAS, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Rinitis - Tractament - Europa, Healthcare system, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Respiratory Tract Diseases::Nose Diseases::Rhinitis::Rhinitis, Allergic [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Geographic Locations::Europe [GEOGRAPHICALS], Eu countries, PERSON-CENTERED CARE, Pharmacological treatment, 03 medical and health sciences, units, Environmental health, Allergy and Immunology, MANAGEMENT, Humans, Pharmaceutical Preparations::Prescription Drugs [CHEMICALS AND DRUGS], MESH: Humans, allergic rhinitis, OTC Medicines, business.industry, PATHWAYS, Al·lèrgia - Tractament - Europa, AIR-POLLUTION, medicine.disease, Rhinitis, Allergic, Costs, 030104 developmental biology, 030228 respiratory system, Analytics, Family medicine, MESH: Practice Patterns, Physicians', ASTHMA, MESH: Europe, business
Abstract: Rinitis al·lèrgica; Costos; Medicaments Rinitis alérgica; Costos; Medicamentos Allergic rhinitis; Costs; Medications Background The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. Methods We conducted a pharmaco-epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking—OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). Results Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. Discussion There are major differences between countries in terms of rhinoconjunctivitis medication usage.
Published: 2021

47. The value of spot urinary creatinine as a marker of muscle wasting in patients with new‐onset or worsening heart failure

Author: Kevin Damman, Pierpaolo Pellicori, John G.F. Cleland, Patrick Rossignol, Jozine M. ter Maaten, Marco Metra, Paloma Pandhi, Koen W. Streng, Stefan D. Anker, Chim C. Lang, Dirk J. van Veldhuisen, Kenneth Dickstein, Faiez Zannad, Leong L. Ng, Nilesh J. Samani, Gerasimos Filippatos, Adriaan A. Voors, University Medical Center Groningen [Groningen] (UMCG), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Glasgow, Robertson Centre for Biostatistics & Clinical Trials Unit, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Bergen (UiB), Stavanger University Hospital, Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Ninewells Hospital and Medical School [Dundee], University Hospitals Leicester, NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, 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), 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), 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 ), Università degli Studi di Brescia [Brescia], Attikon University Hospital, National and Kapodistrian University of Athens (NKUA), University of Cyprus (UCY), This work was supported by The Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014–11 RECONNECT] and a grant from the European Commission [FP7-242209-BIOSTAT-CHF]., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), 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), Università degli Studi di Brescia = University of Brescia (UniBs), University of Cyprus [Nicosia] (UCY), and Cardiovascular Centre (CVC)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Weight loss, Urinary system, Urology, Renal function, Diseases of the musculoskeletal system, Muscle wasting, Cachexia, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Acute heart failure, Urinary creatinine, Aged, Aged, 80 and over, Biomarkers, Creatinine, Humans, Middle Aged, Muscles, Heart Failure, Quality of Life, medicine, 80 and over, Orthopedics and Sports Medicine, Wasting, business.industry, QM1-695, Hazard ratio, Original Articles, medicine.disease, 3. Good health, 030104 developmental biology, RC925-935, chemistry, 030220 oncology & carcinogenesis, Human anatomy, Cohort, Original Article, medicine.symptom, business
Abstract: Background Muscle wasting and unintentional weight loss (cachexia) have been associated with worse outcomes in heart failure (HF), but timely identification of these adverse phenomena is difficult. Spot urinary creatinine may be an easily accessible marker to assess muscle loss and cachexia. This study investigated the association of urinary creatinine with body composition changes and outcomes in patients with new-onset or worsening HF (WHF).Methods In BIOSTAT-CHF, baseline spot urinary creatinine measurements were available in 2315 patients with new-onset or WHF in an international cohort (index cohort) and a validation cohort of 1431 similar patients from Scotland.Results Median spot urinary creatinine concentrations were 5.2 [2.7-9.6] mmol/L in the index cohort. Median age was 69 +/- 12 years and 73% were men. Lower spot urinary creatinine was associated with older age, lower height and weight, worse renal function, more severe HF, and a higher risk of >5% weight loss from baseline to 9 months (odds ratio = 1.23, 95% CI = 1.09-1.39 per log decrease; P = 0.001). Spot urinary creatinine was associated with Evans criteria of cachexia (OR = 1.26 per log decrease, 95% CI = 1.04-1.49; P = 0.016) and clustered with markers of heart failure severity in hierarchical cluster analyses. Lower urinary creatinine was associated with poorer exercise capacity and quality of life (both P < 0.001) and predicted a higher rate for all-cause mortality [hazard ratio (HR) = 1.27, 95% CI = 1.17-1.38 per log decrease; P < 0.001] and the combined endpoints HF hospitalization or all-cause mortality (HR = 1.23, 95% CI = 1.15-1.31 per log decrease; P < 0.001). Significance was lost after addition of the BIOSTAT risk model. Analyses of the validation cohort yielded similar findings.Conclusions Lower spot urinary creatinine is associated with smaller body dimensions, renal dysfunction, and more severe HF in patients with new-onset/WHF. Additionally, lower spot urinary creatinine is associated with an increased risk of weight loss and a poorer exercise capacity/quality of life. Urinary creatinine could therefore be a novel, easily obtainable marker to assess (risk of) muscle wasting in HF patients.
Published: 2021

48. Performance of antenatal imaging to predict placenta accreta spectrum degree of severity

Author: Morel, Olivier, van Beekhuizen, Heleen J., Braun, Thorsten, Collins, Sally, Pateisky, Petra, Calda, Pavel, Henrich, Wolfgang, Al Naimi, Ammar, Norgaardt, Lone Nikoline, Chalubinski, Kinga M., Sentilhes, Loic, Tutschek, Boris, Schwickert, Alexander, Stefanovic, Vedran, Bertholdt, Charline, International Society for Placenta accreta spectrum (IS-PAS), Gynecological Oncology, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital Area, Service d'Obstétrique et de Gynécologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), University of Oxford [Oxford], Medizinische Universität Wien = Medical University of Vienna, First Faculty of Medicine Charles University [Prague], Goethe-Universität Frankfurt am Main, Copenhagen University Hospital, CHU Bordeaux [Bordeaux], and Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
Subjects: medicine.medical_specialty, Multivariate analysis, Databases, Factual, Placenta accreta, severity, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Placenta Accreta, Imaging data, Sensitivity and Specificity, Severity of Illness Index, Ultrasonography, Prenatal, Cohort Studies, 03 medical and health sciences, placenta accreta spectrum, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Pregnancy, Original Research Articles, Prenatal Diagnosis, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 030212 general & internal medicine, Original Research Article, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, ultrasound, Ultrasound, Obstetrics and Gynecology, Magnetic resonance imaging, General Medicine, Odds ratio, medicine.disease, Magnetic Resonance Imaging, Confidence interval, United States, 3. Good health, Europe, abnormal invasive placenta, Female, Radiology, Ultrasonography, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction In cases of placenta accreta spectrum, a precise antenatal diagnosis of the suspected degree of invasion is essential for the planning of individual management strategies at delivery. The aim of this work was to evaluate the respective performances of ultrasonography and magnetic resonance imaging for the antenatal assessment of the severity of placenta accreta spectrum disorders included in the database. The secondary objective was to identify descriptors related to the severity of placenta accreta spectrum disorders. Material and methods All the cases included in the database for which antenatal imaging data were available were analyzed. The rates of occurrence of each ultrasound and magnetic resonance imaging descriptor were reported and compared between the Group “Accreta‐Increta” (FIGO grades 1 & 2) and the Group “Percreta” (FIGO grade 3). Results Antenatal imaging data were available for 347 women (347/442, 78.5%), of which 105 were included in the Group “Accreta – Increta” (105/347, 30.2%) and 213 (213/347, 61.4%) in the Group “Percreta”. Magnetic resonance imaging was performed in addition to ultrasound in 135 women (135/347, 38.9%). After adjustment for all ultrasound descriptors in multivariate analysis, only the presence of a bladder wall interruption was associated with a significant higher risk of percreta (Odds ratio 3.23, Confidence interval 1.33–7.79). No magnetic resonance imaging sign was significantly correlated with the degree of severity. Conclusions The performance of ultrasound and magnetic resonance imaging to discriminate mild from severe placenta accreta spectrum disorders is very poor. To date, the benefit of additional magnetic resonance imaging has not been demonstrated.
Published: 2021

49. Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial

Author: Stefan Koudstaal, Christoph Wanner, Javed Butler, Isabella Zwiener, Alicia Uijl, David Fitchett, Anne Pernille Ofstad, B. Schrage, Ola Vedin, Stefan D. Anker, Silvio E. Inzucchi, Faiez Zannad, Gianluigi Savarese, Folkert W. Asselbergs, Lars H. Lund, Karolinska Institutet [Stockholm], University Medical Center [Utrecht], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, University College of London [London] (UCL), Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), St. Michael's Hospital, University of Toronto, Yale University School of Medicine, Boehringer Ingelheim Norway KS, Boehringer Ingelheim AB, Stockholm, University Hospital of Würzburg, 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), 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), 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 ), Boehringer Ingelheim Pharma GmbH & Co. KG, University of Mississippi Medical Center (UMMC), and The EMPA-REG OUTCOME trial was funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.
Subjects: medicine.medical_specialty, heart failure with mildly reduced ejection fraction, type 2 diabetes mellitus, empagliflozin, 030204 cardiovascular system & hematology, Placebo, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucosides, Risk Factors, Internal medicine, medicine, Empagliflozin, Humans, Treatment effect, In patient, heart failure with reduced ejection fraction, 030212 general & internal medicine, Benzhydryl Compounds, Heart Failure, Ejection fraction, EMPA-REG OUTCOME, business.industry, Proportional hazards model, Stroke Volume, medicine.disease, Prognosis, 3. Good health, Hospitalization, Heart failure with preserved ejection fraction, Diabetes Mellitus, Type 2, Heart failure, heart failure with mid-range ejection fraction, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background: In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.Methods and results: We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF
Published: 2021

50. Impact of sequence type and field strength (1.5, 3, and 7T) on 4D flow MRI hemodynamic aortic parameters in healthy volunteers

Author: Sebastian Schmitter, Marcel Prothmann, Ning Jin, Michael Markl, Florian von Knobelsdorff-Brenkenhoff, Aylin Demir, Ashish Chawla, Andreas Greiser, Emilie Bollache, Carsten Schwenke, Jeanette Schulz-Menger, Stephanie Wiesemann, Gestionnaire, Hal Sorbonne Université, Max Delbrueck Center for Molecular Medicine, Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Physikalisch-Technische Bundesanstalt [Braunschweig] (PTB), Khoo Teck Puat Hospital (KTPH), Alexandra Health, Ludwig-Maximilians-Universität München (LMU), Siemens Healthcare, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Feinberg School of Medicine, and Northwestern University [Evanston]
Subjects: Aortic arch, MESH: Hemodynamics, 7T, cardiovascular magnetic resonance imaging, [SDV]Life Sciences [q-bio], 4D flow, Hemodynamics, Field strength, MESH: Imaging, Three-Dimensional, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, medicine.artery, medicine, Humans, Radiology, Nuclear Medicine and imaging, MESH: Healthy Volunteers, Equivalence (measure theory), Mathematics, standardization, MESH: Humans, medicine.diagnostic_test, non-invasive hemodynamics, Magnetic resonance imaging, MESH: Aorta, Blood flow, MESH: Blood Flow Velocity, Magnetic Resonance Imaging, Healthy Volunteers, [SDV] Life Sciences [q-bio], aorta, Flow (mathematics), Cardiovascular and Metabolic Diseases, Descending aorta, Blood Flow Velocity, 030217 neurology & neurosurgery, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Biomedical engineering
Abstract: International audience; Purpose: 4D flow magnetic resonance imaging (4D-MRI) allows time-resolved visualization of blood flow patterns, quantification of volumes, velocities, and advanced parameters, such as wall shear stress (WSS). As 4D-MRI enters the clinical arena, standardization and awareness of confounders are important. Our aim was to evaluate the equivalence of 4D flow-derived aortic hemodynamics in healthy volunteers using different sequences and field strengths.Methods: 4D-MRI was acquired in 10 healthy volunteers at 1.5T using three different prototype sequences, at 3T and at 7T (Siemens Healthineers). After evaluation of diagnostic quality in three segments (ascending-, descending aorta, aortic arch), peak velocity, flow volumes, and WSS were investigated. Equivalence limits for comparison of field strengths/sequences were based on the limits of Bland-Altman analyses of the intraobserver variability.Results: Non-diagnostic quality was found in 10/144 segments, 9/10 were obtained at 7T. Apart for the comparison of forward flow between sequence 1 and 3, the differences in measurements between field strengths/sequences exceeded the range of agreement. Significant differences were found between field strengths/sequences for forward flow (1.5T vs. 3T, 3T vs. 7T, sequence 1 vs. 3, 2 vs. 3 [P < .001]), WSS (1.5T vs. 3T [P < .05], sequence 1 vs. 2, 1 vs. 3, 2 vs. 3 [P < .001]), and peak velocity (1.5T vs. 7T, sequence 1 vs. 3 [P > .001]). All parameters at all field strengths/with all sequences correlated moderately to strongly (r ≥ 0.5).Conclusion: Data from all sequences could be acquired and resulting images showed sufficient quality for further analysis. However, the variability of the measurements of peak velocity, flow volumes, and WSS was higher when comparing field strengths/sequences as the equivalence limits defined by the intraobserver assessments.
Published: 2021

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