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182 results on '"Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970))"'

1. History of heart failure in patients with coronavirus disease 2019: Insights from a French registry

Author

Iris Ma, Orianne Weizman, Thibaut Pommier, Cyril Zakine, A. Darmon, Melchior Jonveaux, Nacim Ezzouhairi, Théo Pezel, Wassima Marsou, Laura Geneste, Delphine Mika, C Fauvel, Antoine Deney, Thomas Delmotte, Baptiste Duceau, Vassili Panagides, Thomas Levasseur, Julien Ternacle, Clément Karsenty, Guillaume Bonnet, Victor Waldmann, Flavien Vincent, Marine Mevelec, Sabir Attou, Joffrey Cellier, Ariel Cohen, Antonin Trimaille, Diane Chavignier, Willy Sutter, Nathalie Noirclerc, Benjamin Perin, Hôpital Nord [CHU - APHM], CHU Lille, Institut Coeur Poumon [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), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Hôpital Henri Mondor, Nouvel Hôpital Civil de Strasbourg, CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Amiens-Picardie, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Rouen, Normandie Université (NU), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Clinique Saint Gatien, Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Signalisation et physiopathologie cardiovasculaire (UMRS1180), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011], CHRU de Nancy, Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Hôpital Européen Georges Pompidou [APHP] [HEGP], Groupement des Hôpitaux de l'Institut Catholique de Lille [GHICL], Centre Hospitalier Universitaire de Toulouse [CHU Toulouse], Centre Hospitalier Universitaire de Reims [CHU Reims], Université de Bordeaux [UB], Centre Hospitalier Intercommunal Fréjus - St Raphaël [CHI Fréjus - St Raphaël], Centre Hospitalier Régional d'Orléans [CHRO], and Signalisation et physiopathologie cardiovasculaire [UMRS1180]

Subjects
Male, qSOFA, quick sequential organ failure assessment, [SDV]Life Sciences [q-bio], CHF, chronic heart failure, Comorbidity, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, HF, heart failure, 0302 clinical medicine, RAAS, renin-angiotensin-aldosterone system, Risk Factors, LVEF, left ventricular ejection fraction, Clinical endpoint, 030212 general & internal medicine, Hospital Mortality, Registries, Résultats, COVID-19, coronavirus disease 2019, Ejection fraction, Incidence, Hazard ratio, Confounding Factors, Epidemiologic, General Medicine, Stroke volume, Middle Aged, Treatment Outcome, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, HFpEF, heart failure with preserved ejection fraction, RT-PCR, real-time reverse transcriptase polymerase chain reaction, Heart failure, ACE2, angiotensin-converting enzyme 2, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, 03 medical and health sciences, Facteurs de risque, Clinical Research, COVID-19, Femme, HFpEF, HFrEF, RAAS inhibitors, SARS-COV 2, Internal medicine, medicine, Intubation, Intratracheal, Humans, HFrEF, heart failure with reduced ejection fraction, Aged, Retrospective Studies, business.industry, SARS-CoV-2, Retrospective cohort study, Stroke Volume, medicine.disease, business, Heart failure with preserved ejection fraction, Procedures and Techniques Utilization
Abstract

Summary Background Although cardiovascular comorbidities seem to be strongly associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), data regarding patients with preexisting heart failure are limited. Aims To investigate the incidence, characteristics and clinical outcomes of patients with COVID-19 with a history of heart failure with preserved or reduced ejection fraction. Methods We performed an observational multicentre study including all patients hospitalized for COVID-19 across 24 centres in France from 26 February to 20 April 2020. The primary endpoint was a composite of in-hospital death or need for orotracheal intubation. Results Overall, 2809 patients (mean age 66.4 ± 16.9 years) were included. Three hundred and seventeen patients (11.2%) had a history of heart failure; among them, 49.2% had heart failure with reduced ejection fraction and 50.8% had heart failure with preserved ejection fraction. COVID-19 severity at admission, defined by a quick sequential organ failure assessment score > 1, was similar in patients with versus without a history of heart failure. Before and after adjustment for age, male sex, cardiovascular comorbidities and quick sequential organ failure assessment score, history of heart failure was associated with the primary endpoint (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.06–1.90; P = 0.02). This result seemed to be mainly driven by a history of heart failure with preserved ejection fraction (HR: 1.61, 95% CI: 1.13–2.27; P = 0.01) rather than heart failure with reduced ejection fraction (HR: 1.19, 95% CI: 0.79–1.81; P = 0.41). Conclusions History of heart failure in patients with COVID-19 was associated with a higher risk of in-hospital death or orotracheal intubation. These findings suggest that patients with a history of heart failure, particularly heart failure with preserved ejection fraction, should be considered at high risk of clinical deterioration.

Published
2021
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2. Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Author

Dimitri Titeca-Beauport, Vincent Audard, Laurent Juillard, Marie-Noëlle Peraldi, Jean-François Subra, Eric Thervet, Jean-Michel Halimi, Thierry Lobbedez, Gabriel Choukroun, Mathilde Tamain, Marc Hazzan, Alexandre Ganea, Maité Daroux, Thomas Quemeneur, Dominique Guerrot, Pauline Caillard, Marie Essig, François Vrtovsnik, Jean-Michel Rebibou, Cécile Vigneau, R. Makdassi, Marion Rabant, Morgane Heitz, Vincent Vuiblet, Alexandre Hertig, Adnane Lamrani, Jonchère, Laurent, CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), 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 ), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), CHU Grenoble, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Rouen, Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, 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 ), 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 de Paris (UP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Lille, Inserm, Université de Lille, Lille Inflammation Research International Center - U 995 [LIRIC], Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)], Cardiovasculaire, métabolisme, diabétologie et nutrition [CarMeN], Institut Mondor de Recherche Biomédicale [IMRB], Université Paris Descartes - Paris 5 [UPD5], Centre de Recherche en Cancérologie Nantes-Angers [CRCNA], Centre Hospitalier Universitaire de Reims [CHU Reims], Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)], CHU Henri Mondor [Créteil], 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), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
medicine.medical_specialty, Urinary system, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, lcsh:Medicine, Disease, Anti-Glomerular Basement Membrane Disease, Gastroenterology, survival, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Stage (cooking), Adverse effect, anti-GBM disease, 030203 arthritis & rheumatology, urogenital system, business.industry, ANCA, Mortality rate, lcsh:R, Glomerulonephritis, General Medicine, medicine.disease, infection, 3. Good health, age, [SDV] Life Sciences [q-bio], Bacteremia, business
Abstract

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30&ndash, 71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8&ndash, 19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA ([HR] 1.62, 95% [95% CI] 1.07&ndash, 2.44], p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00&ndash, 1.21], p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24&ndash, 7.88], p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

Published
2020
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3. Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction

Author

Orianne Domengé, Albert A. Hagège, Michel Azizi, Etienne Puymirat, Elie Mousseaux, Mariana Mirabel, Laurence Amar, Anne-Sophie Jannot, Jean-Sébastien Hulot, Jean-Baptiste Carves, Eva Vermersch, Anne Blanchard, Claire Carette, Maxime Wack, Marine Livrozet, Julien Le Guen, Alexandre Karras, Marie-Cécile Bories, Antoine Fayol, 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 de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Jannot, Anne-Sophie, 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), 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), 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), 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), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), 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)-École pratique des hautes études (EPHE), 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)-École Pratique des Hautes Études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5

Subjects
medicine.medical_specialty, Heart failure with preserved ejection faction, [SDV]Life Sciences [q-bio], Comorbidity, Aetiologies, 030204 cardiovascular system & hematology, Ventricular Function, Left, 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, Humans, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, 10. No inequality, Heart Failure, Ejection fraction, business.industry, Proportional hazards model, Medical record, Mortality rate, Stroke Volume, Original Articles, medicine.disease, Prognosis, Classification, Obesity, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], Heart failure, RC666-701, Etiology, Cardiology, Female, Original Article, Cardiology and Cardiovascular Medicine, Heart failure with preserved ejection fraction, business
Abstract

Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis. Methods and results We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co‐morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non‐cardiac co‐morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF. Conclusions Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF., Condensed abstract The identification of specific aetiologies was possible in almost half of patients with heart failure with preserved ejection fraction (HFpEF). Compared with patients with secondary HFpEF, patients with idiopathic HFpEF were older, frequently female, and had a higher proportion of co‐morbidities and high crude mortality rates, but their prognosis was similar after adjustment for age and sex. Unsupervised cluster analysis, however, indicated that idiopathic HFpEF patients were mostly grouped into separate cluster with a better prognosis. Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.

Published
2022
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4. Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel–Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study

Author

Marc Bardou, Pierre Vabres, Laurence Faivre, Annabel Maruani, Victoria E R Parker, A. Phan, Christine Chiaverini, L. Martin, Jill Clayton-Smith, C. Fleck, Maxime Luu, Tristan Mirault, Fanny Morice-Picard, M. Carpentier, Marie-Line Jacquemont, Hervé Devilliers, Marjolaine Willems, A. Maurer, Romaric Loffroy, Didier Bessis, Florence Petit, Robert K. Semple, M. Yousfi, Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Référence des Maladies Génétiques à Expression Cutanée (MAGEC), Service de médecine interne et maladies systémiques (SOC 2) [CHU de Dijon], Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Institute of Applied Physics [Bern] (IAP), University of Bern, CHU Bordeaux [Bordeaux], Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Nord, Centre Hospitalier Universitaire de Lille (CHU de Lille), Hôpital Lapeyronie [Montpellier] (CHU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre national de référence des maladies vasculaires rares, 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), 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 de Paris (UP), University of Manchester [Manchester], CHU Dijon, AstraZeneca [Cambridge, UK], University of Edinburgh, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Adult, Klippel-Trenaunay-Weber Syndrome, medicine.medical_specialty, Klippel-Trenaunay syndrome, Syzygium, [SDV]Life Sciences [q-bio], Population, Overgrowth syndrome, Article, Phosphatidylinositol 3-Kinases, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, taselisib, medicine, Humans, education, Adverse effect, Genetics (clinical), education.field_of_study, business.industry, Imidazoles, clinical trial, PIK3CA, medicine.disease, 3. Good health, Clinical trial, Oxazepines, Tolerability, 030220 oncology & carcinogenesis, Mutation, Cohort, Quality of Life, mosaic, business, PROS treatment
Abstract

International audience; ABSTRACT Purpose PIK3CA pathogenic variants in the PIK3CA-related overgrowth spectrum (PROS) activate phosphoinositide 3-kinase signaling, providing a rationale for targeted therapy, but no drug has proven efficacy and safety in this population. Our aim was to establish the six-month tolerability and efficacy of low-dose taselisib, a selective class I PI3K inhibitor, in PROS patients. Methods Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multicenter, open-label single-arm trial (six patients at 1 mg/day of taselisib, then 24 at 2 mg/day). The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of (1) tissue volume at affected and unaffected sites, both clinically and on imaging; (2) cutaneous vascular outcomes when relevant; (3) biologic parameters; (4) quality of life; and (5) patient-reported outcomes. Results Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1 mg cohort ( n = 6). No significant reduction in affected tissue volume was observed (mean −4.2%; p = 0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement). Conclusion Despite functional improvement, the safety profile of low-dose taselisib precludes its long-term use.

Published
2021
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5. Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis

Author

Thomas Quemeneur, Cécile Couchoud, Xavier Puéchal, Philippe Brunet, Grégoire Couvrat-Desvergnes, Stéphane Burtey, Frédéric Lavainne, Maëlis Kauffmann, Mickaël Bobot, Noémie Jourde-Chiche, Stanislas Faguer, Benjamin Terrier, Thomas Robert, Alexandre Karras, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Polytechnique de Paris (IP Paris), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Polyclinique de l’Atlantique, Partenaires INRAE, Centre atlantique, Nantes, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Agence de la biomédecine [Saint-Denis la Plaine]

Subjects
Male, Epidemiology, medicine.medical_treatment, Microscopic Polyangiitis, Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Recurrence, Cause of Death, Neoplasms, Medicine, Registries, infections, end stage kidney diseasechronic dialysis, Aged, 80 and over, relapse, immunosuppression, ANCA, Incidence, cardiovascular, Incidence (epidemiology), Remission Induction, Immunosuppression, Middle Aged, Progression-Free Survival, Survival Rate, Editorial, Cardiovascular Diseases, Nephrology, Cohort, Female, France, Microscopic polyangiitis, Vasculitis, Immunosuppressive Agents, medicine.medical_specialty, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, Renal Dialysis, Internal medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Aged, Retrospective Studies, Transplantation, business.industry, Granulomatosis with Polyangiitis, Original Articles, medicine.disease, Kidney Transplantation, business, disease activity, Follow-Up Studies
Abstract

International audience; Background and objectives Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. Design, setting, participants, & measurements Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. Results In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation ( P =0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. Conclusions The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3

Published
2021
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6. Dynamic contrast enhanced magnetic resonance imaging: A review of its application in the assessment of placental function

Author

Yves Ville, Nathalie Siauve, Houman Mahallati, Mathilde Jacquier, Anne-Elodie Millischer-Bellaiche, C.J. Arthuis, D. Grevent, Laurent Salomon, C. Henry, L. Bussieres, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), EA fetus 7328 and LUMIERE Platform, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Calgary, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)

Subjects
Pathology, medicine.medical_specialty, Placenta, [SDV]Life Sciences [q-bio], Contrast Media, Blood volume, Placental insufficiency, Pregnancy, medicine, Humans, Fetal Growth Retardation, medicine.diagnostic_test, business.industry, Microcirculation, Obstetrics and Gynecology, Magnetic resonance imaging, Gold standard (test), Placental Insufficiency, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Reproductive Medicine, embryonic structures, Circulatory system, Female, Functional magnetic resonance imaging, business, Perfusion, Developmental Biology
Abstract

International audience; It is important to develop a better understanding of placental insufficiency given its role in common maternofetal complications such as preeclampsia and fetal growth restriction. Functional magnetic resonance imaging offers unprecedented techniques for exploring the placenta under both normal and pathological physiological conditions. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is an established and very robust method to investigate the microcirculatory parameters of an organ and more specifically its perfusion. It is currently a gold standard in the physiological and circulatory evaluation of an organ. Its application to the human placenta could enable to access many microcirculatory parameters relevant to the placental function such as organ blood flow, fractional blood volume, and permeability surface area, by the acquisition of serial images, before, during, and after administration of an intravenous contrast agent. Widely used in animal models with gadolinium-based contrast agents, its application to the human placenta could be possible if the safety of contrast agents in pregnancy is established or they are confirmed to not cross the placenta.

Published
2021
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7. Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause

Author

Sam O’Toole, Peyman Björklund, Samuel Backman, Per Hellman, Eva Wozniak, Sumedha Garg, Morris J. Brown, Emily Goodchild, Junhua Zhou, Alison Marker, Antoinette Tuthill, Giulia Argentesi, Caroline Joyce, Xilin Wu, Sheerazed Boulkroun, Celso E Gomez Sanchez, Russell Senanayake, Satyamaanasa Polubothu, Kate E Lines, Lou Metherell, Suzanne Jordan, Jyn Ling Kuan, Zenia Tiang, Laila Parvanta, Fiona E. Karet Frankl, Veronica A Kinsler, Rajesh V. Thakker, Elena A.B. Azizan, Fabio L. Fernandes-Rosa, Maria-Christina Zennaro, David Klinzing, Laurence Amar, Emily Cottrell, William Drake, Helen L Storr, Ada E. D. Teo, Juan Pablo Kaski, Roger Foo, Charles A. Mein, Tobias Åkerström, Daniel M. Berney, Claudia P. Cabrera, Anna K Gluck, Mark Gurnell, Queen Mary University of London (QMUL), National University of Malaysia [Bandar Baru Bangi] (UKM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Addenbrooke's Hospital, Cambridge University NHS Trust, Metabolic Research Laboratories [Cambridge, UK] (University of Cambridge), Wellcome Trust - MRC Cambridge-Addenbrooke’s Hospital [Cambridge, UK], Uppsala University, Royal Free Hospital [London, UK], University College of London [London] (UCL), University of Oxford, Cork University Hospital [Cork, Ireland] (CUH), University of Cambridge [UK] (CAM), National University of Singapore (NUS), St Bartholomew's Hospital (London), Agency for science, technology and research [Singapore] (A*STAR), University of Mississippi Medical Center (UMMC), and Fernandes Rosa, Fabio

Subjects
Adult, Male, endocrine system, medicine.medical_specialty, Adolescent, education, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, medicine.disease_cause, Article, Human chorionic gonadotropin, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Pregnancy, Internal medicine, Hyperaldosteronism, Genetics, medicine, Humans, Aldosterone, beta Catenin, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mutation, GNA11, Adrenal gland, Adrenal cortex, Puberty, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Adrenal Cortex Neoplasms, GTP-Binding Protein alpha Subunits, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, Endocrinology, chemistry, Zona glomerulosa, Adrenocortical Adenoma, GTP-Binding Protein alpha Subunits, Gq-G11, Female, Menopause, GNAQ
Abstract

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1. Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression.

Published
2021
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8. Cardiac performance in patients hospitalized with COVID‐19: a 6 month follow‐up study

Author

Antoine Fayol, Marine Livrozet, Pierre Boutouyrie, Hakim Khettab, Maureen Betton, Victoria Tea, Anne Blanchard, Rosa‐Maria Bruno, Jean‐Sébastien Hulot, French COVID cohort study group, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), and HULOT, Jean-Sébastien

Subjects
Male, medicine.medical_specialty, Myocarditis, Diastolic function, [SDV]Life Sciences [q-bio], Diastole, Heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Internal medicine, medicine.artery, Diabetes mellitus, Original Research Articles, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, Myocardial infarction, Original Research Article, Prospective Studies, Prospective cohort study, Aged, business.industry, SARS-CoV-2, COVID-19, Heart, Middle Aged, medicine.disease, [SDV] Life Sciences [q-bio], Pneumonia, Echocardiography, RC666-701, Pulmonary artery, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

International audience; Aims: Myocardial injury is frequently observed in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. Different cardiac abnormalities have been reported during the acute COVID-19 phase, ranging from infra-clinic elevations of myocardial necrosis biomarkers to acute cardiac dysfunction and myocarditis. There is limited information on late cardiac sequelae in patients who have recovered from acute COVID-19 illness. We aimed to document the presence and quantify the extent of myocardial functional alterations in patients hospitalized 6 months earlier for COVID-19 infection.Methods and results: We conducted a prospective echocardiographic evaluation of 48 patients (mean age 58 ± 13 years, 69% male) hospitalized 6 ± 1 month earlier for a laboratory-confirmed and symptomatic COVID-19. Thirty-two (66.6%) had pre-existing cardiovascular risks factors (systemic hypertension, diabetes, or dyslipidaemia), and three patients (6.2%) had a known prior myocardial infarction. Sixteen patients (33.3%) experienced myocardial injury during the index COVID-19 hospitalization as identified by a rise in cardiac troponin levels. Six months later, 60.4% of patients still reported clinical symptoms including exercise dyspnoea for 56%. Echocardiographic measurements under resting conditions were not different between patients with versus without myocardial injury during the acute COVID-19 phase. In contrast, low-level exercise (25W for 3 min) induced a significant increase in the average E/e' ratio (10.1 ± 4.3 vs. 7.3 ± 11.5, P = 0.01) and the systolic pulmonary artery pressure (33.4 ± 7.8 vs. 25.6 ± 5.3 mmHg, P = 0.02) in patients with myocardial injury during the acute COVID-19 phase. Sensitivity analyses showed that these alterations of left ventricular diastolic markers were observed regardless of whether of cardiovascular risk factors or established cardiac diseases indicating SARS-CoV-2 infection as a primary cause.Conclusions: Six months after the acute COVID-19 phase, significant cardiac diastolic abnormalities are observed in patients who experienced myocardial injury but not in patients without cardiac involvement.

Published
2021
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9. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers

Author

Camilo Jimenez, Henricus P. M. Kunst, Eric Baudin, Nicola Tufton, Philippe Herman, Rodney J. Hicks, Simon Aylwin, Mercedes Robledo, Henri J L M Timmers, Anne Paule Gimenez-Roqueplo, William F. Young, Massimo Mannelli, Roderick J. Clifton-Bligh, Patricia L. M. Dahia, Mitsuhide Naruse, Alexandre Buffet, Andrzej Januszewicz, Olivier Steichen, Scott Akker, Charlotte Lussey-Lepoutre, Karel Pacak, Martin Fassnacht, David R Taylor, Laurence Amar, Ashley B. Grossman, Giorgio Treglia, Jacques W.M. Lenders, Dylan Lewis, Nelly Burnichon, David Taïeb, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), St Bartholomew's Hospital, King's College Hospital (KCH), Institut Gustave Roussy (IGR), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Royal North Shore Hospital (RNSH), The University of Sydney, The University of Texas at San Antonio (UTSA), University of Würzburg, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Royal Free Hospital [London, UK], Barts & The London School of Medicine and Dentistry, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, The University of Texas M.D. Anderson Cancer Center [Houston], Radboud University Medical Center [Nijmegen], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kyoto Medical Center, National Hospital Organization, Spanish National Cancer Research Center (CNIO), Centro de Investigación Biomédica en Red de Enfermedades Raras - CIBERER [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), Universidade de Santiago de Compostela [Spain] (USC ), Hôpital de la Timone [CHU - APHM] (TIMONE), Ente Ospedaliero Cantonale (EOC), Lausanne University Hospital, Università della Svizzera italiana = University of Italian Switzerland (USI), Mayo Clinic, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service de médecine nucléaire [CHU Pitié-Salpétrière], 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), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, KNO, and MUMC+: MA Keel Neus Oorheelkunde (9)

Subjects
0301 basic medicine, PHEOCHROMOCYTOMA, Pediatrics, Internationality, SDHB, Endocrinology, Diabetes and Metabolism, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 0302 clinical medicine, Endocrinology, Mass Screening, CAROTID-BODY TUMORS, Child, HIGH-ALTITUDE, Molecular medicine, medicine.diagnostic_test, Genetic Carrier Screening, GASTROINTESTINAL STROMAL TUMORS, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Penetrance, 3. Good health, Succinate Dehydrogenase, PARAGANGLIOMA, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Algorithms, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, Heterozygote, PENETRANCE, medicine.medical_specialty, Consensus, Genetic counseling, Adrenal tumours, 03 medical and health sciences, Germline mutation, medicine, Humans, Genetic Testing, Germ-Line Mutation, Mass screening, Aged, Monitoring, Physiologic, Genetic testing, business.industry, CLINICAL UTILITY, GENE, METANEPHRINES, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Asymptomatic Diseases, MATERNAL TRANSMISSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SDHD, business
Abstract

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.

Published
2021
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10. Visual lung damage CT score at hospital admission of COVID-19 patients and 30-day mortality

Author

Kim Diep Dang Tran, Antoine Fayol, A. Hernigou, Teodor Grand, Jad Al Haddad, Guillaume Reverdito, Gilles Soulat, Olivier Clément, Jean-Sébastien Hulot, Anne Charpentier, Elie Mousseaux, Marine Livrozet, Etienne Charpentier, 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), Université Paris Descartes - Paris 5 (UPD5), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), 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), 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), and HULOT, Jean-Sébastien

Subjects
medicine.medical_specialty, Respiratory rate, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Tomography, x-ray computed, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Computed Tomography, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Respiratory system, Prospective cohort study, Lung, Tomography, Neuroradiology, x-ray computed, medicine.diagnostic_test, SARS-CoV-2, business.industry, COVID-19, Interventional radiology, Pneumonia, General Medicine, medicine.disease, Hospitals, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Severe acute respiratory syndrome, 030220 oncology & carcinogenesis, Radiology, business
Abstract

Objectives Chest CT has been widely used to screen and to evaluate the severity of COVID-19 disease in the early stages of infection without severe acute respiratory syndrome, but no prospective data are available to study the relationship between extent of lung damage and short-term mortality. The objective was to evaluate association between standardized simple visual lung damage CT score (vldCTs) at admission, which does not require any software, and 30-day mortality. Methods In a single-center prospective cohort of COVID-19 patients included during 4 weeks, the presence and extent of ground glass opacities(GGO), consolidation opacities, or both of them were visually assessed in each of the 5 lung lobes (score from 0 to 4 per lobe depending on the percentage and out of 20 per patient = vldCTs) after the first chest CT performed to detect COVID-19 pneumonia. Results Among 210 confirmed COVID-19 patients, the number of survivors and non-survivors was 162 (77%) and 48 (23%), respectively at 30 days. vldCTs was significantly higher in non-survivors, and the AUC of vldCTs to distinguish survivors and non-survivors was 0.72 (95%CI 0.628–0.807, p < 0.001); the best cut-off vldCTs value was 7. During follow-up, significant differences in discharges and 30-day mortality were observed between patients with vldCTs ≥ 7 versus vldCTs < 7: (98 [85.2%] vs 49 [51.6%]; p < 0.001 and 36 [37.9%] vs 12 [12.4%]; p < 0.001, respectively. The 30-day mortality increased if vldCTs ≥ 7 (HR, 3.16 (1.50–6.43); p = 0.001), independent of age, respiratory rate and oxygen saturation levels, and comorbidities at admission. Conclusions By using chest CT in COVID-19 patients, extensive lung damage can be visually assessed with a score related to 30-day mortality independent of conventional risk factors of the disease. Key Points • In non-selected COVID-19 patients included prospectively during 4 weeks, the extent of ground glass opacities(GGO) and consolidation opacities evaluated by a simple visual score was related to 30-day mortality independent of age, respiratory rate, oxygen saturation levels, comorbidities, and hs-troponin I level at admission. • This severity score should be incorporated into risk stratification algorithms and in structured chest CT reports requiring a standardized reading by radiologists in case of COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-07938-2.

Published
2021
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11. Intramuscular Vaccination in Adults with Therapeutic Anticoagulation in the Era of COVID-19 Vaccines Outbreak: A Practical Review

Author

Tristan Mirault, David Lebeaux, Nicolas Gendron, Christine Le Beller, Brigitte Sabatier, Luc Darnige, Benjamin Planquette, Agnès Lillo-Le Louët, Olivier Sanchez, Lina Khider, Germain Perrin, David M. Smadja, GHU AP-HP Centre Université de Paris, Université de Paris (UP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Innovations thérapeutiques en hémostase (IThEM - U1140), 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 de Paris (UP), F-Crin Innovte [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), and PERRIN, Germain

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Outbreak, 030204 cardiovascular system & hematology, 3. Good health, Vaccination, 03 medical and health sciences, 0302 clinical medicine, RC666-701, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, Intensive care medicine, business, Letter to the Editor, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021
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12. Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy—analysis of registry data

Author

Caroline Ovaert, Sylvie Tuffery-Giraud, Sarah Leonard-Louis, Anthony Béhin, Sophie Guillaumont, Maximilien Sochala, Emmanuelle Campana-Salort, Frédérique Audic, Michèle Mayer, Damien Bonnet, Raul Juntas Morales, Mireille Cossée, Isabelle Desguerre, Christophe Meune, Pascal Laforêt, Rabah Ben Yaou, Brigitte Chabrol, Djillali Annane, David Orlikowski, François Godart, Malika Saadi, Helge Amthor, Tanya Stojkovic, Ulrike Walther-Louvier, Frédéric Lofaso, Pascal Amedro, Raphaël Porcher, Céline Tard, Claire Delcourte, Vincent Tiffreau, Karim Wahbi, Christine Barnerias, Guillaume Bassez, Bertrand Fontaine, Arnaud Isapof, Gregoire De La Villeon, Guy Vaksmann, François Rivier, Denis Duboc, Henri Marc Bécane, Philippe Ravaud, Hélène Prigent, Emmanuelle Jaillette, Abdallah Fayssoil, Bruno Eymard, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Hôpital Cochin [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Filière Neuromusculaire (FILNEMUS), Infection et inflammation (2I), Université de Montpellier (UM), Centre Hospitalier de Versailles André Mignot (CHV), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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, Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Raymond Poincaré [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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)

Subjects
Duchenne muscular dystrophy, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Cardiomyopathy, Angiotensin-Converting Enzyme Inhibitors, Heart failure, Angiotensin-converting enzyme inhibitors, 030204 cardiovascular system & hematology, Lower risk, Ventricular Function, Left, Angiotensin Receptor Antagonists, 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, Humans, Registries, cardiovascular diseases, 030212 general & internal medicine, Medical prescription, Child, ComputingMilieux_MISCELLANEOUS, Heart Failure, biology, business.industry, Proportional hazards model, Hazard ratio, Angiotensin-converting enzyme, medicine.disease, Confidence interval, 3. Good health, Muscular Dystrophy, Duchenne, Treatment Outcome, Child, Preschool, biology.protein, Cardiology and Cardiovascular Medicine, business, cardiomyopathy
Abstract

Aims To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Published
2021
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13. Extracellular vesicles from adipose stromal cells combined with a thermoresponsive hydrogel prevent esophageal stricture after extensive endoscopic submucosal dissection in a porcine model

Author

Christophe Cellier, Olivier Clément, Florence Gazeau, Iris Marangon, Elise Coffin, Guillaume Perrod, Claire Wilhelm, Max Piffoux, Coralie L. Guerin, Thierry Lecomte, Amanda K. A. Silva, Imane Boucenna, Gabriel Rahmi, Leila M'Harzi, Anna Chipont, Alice Grangier, Arthur Berger, Jessica Assouline, 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 de Paris (UP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Curie [Paris], and Laboratoire MSC Matière et Systèmes Complexes, Université de Paris, CNRS UMR 7057, 75006 Paris, France.

Subjects
medicine.medical_specialty, Muscularis mucosae, Stromal cell, Endoscopic Mucosal Resection, Esophageal Neoplasms, Swine, [SDV]Life Sciences [q-bio], Urology, Adipose tissue, Endoscopic mucosal resection, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, medicine, Extracellular, Animals, General Materials Science, 030304 developmental biology, 0303 health sciences, Chemistry, Hydrogels, medicine.disease, 3. Good health, Adipose Tissue, Esophageal stricture, Esophageal Stenosis, 030211 gastroenterology & hepatology, Stromal Cells, Ex vivo
Abstract

International audience; In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic (R) F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were produced at a liter scale by a high-yielding turbulence approach from ADSCs 3D cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of the PF-127 gel was assessed by rheology. The pro-regenerative potency of ADSC EVs was investigated ex vivo in esophageal biopsies under starvation. In vivo tests were performed in a porcine model after extended esophageal endoscopic mucosal dissection (ESD). Pigs were randomized into 3 groups: control (n = 6), gel (n = 6) or a combination of 1.45 x 10(12) EVs + gel (n = 6). Application of gel +/- EVs was performed just after ESD with a follow-up finalized on day 21 post-ESD. There was a trend towards less feeding disorder in the EV + gel group in comparison with the gel and the control groups (16.67% vs. 66.7% vs. 83.33%, respectively) but without reaching a statistically significant difference. A significant decrease in the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EV + gel group. A decrease in the mean fibrosis area and larger regenerated muscularis mucosae were observed for the EV + gel group. In summary, the application of EVs + gel after extended esophageal endoscopic resection succeeded in preventing stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle an unmet medical need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.

Published
2021
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14. Targeted Metabolomics as a Tool in Discriminating Endocrine From Primary Hypertension

Author

Parminder Singh Reel, Anne Blanchard, Casper K Larsen, Paolo Mulatero, Guillaume Assié, Michael Conall Dennedy, Smarti Reel, Zoran Erlic, Cornelia Prehn, Martin Reincke, Anne-Paule Gimenez-Roqueplo, Alessio Pecori, Katharina Langton, Jaap Deinum, Jerzy Adamski, Christina Pamporaki, Felix Beuschlein, Maria-Christina Zennaro, Filippo Ceccato, Livia Lenzini, Laurence Amar, Martina Tetti, Matthias Kroiss, Carla Scaroni, Aleksander Prejbisz, Emily Jefferson, University of Zurich, Beuschlein, Felix, Universitätsspital Zürich (USZ), University of Dundee, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Università degli studi di Torino = University of Turin (UNITO), University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), National University of Singapore (NUS), National Institute of Cardiology [Varsovie, Pologne], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Würzburg, University of Würzburg = Universität Würzburg, Ludwig-Maximilians-Universität München (LMU), National University of Ireland [Galway] (NUI Galway), Radboud University Medical Center [Nijmegen], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), and HULOT, Jean-Sébastien

Subjects
Oncology, Male, 1303 Biochemistry, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 10265 Clinic for Endocrinology and Diabetology, Adrenal Gland Neoplasms, 030204 cardiovascular system & hematology, 1308 Clinical Biochemistry, Biochemistry, Cushing syndrome, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Primary aldosteronism, targeted metabolomics, arterial hypertension, pheochromocytoma, primary aldosteronism, screening, Area under the curve, Ornithine, Middle Aged, Hyperaldosteronism, ddc, 3. Good health, 1310 Endocrinology, [SDV] Life Sciences [q-bio], Europe, 2712 Endocrinology, Diabetes and Metabolism, Hypertension, Cushing Syndrome, Arterial Hypertension, Pheochromocytoma, Primary Aldosteronism, Screening, Targeted Metabolomics, Female, Essential Hypertension, AcademicSubjects/MED00250, Adult, medicine.medical_specialty, Context (language use), 030209 endocrinology & metabolism, 610 Medicine & health, 2704 Biochemistry (medical), Endocrine System Diseases, Diagnosis, Differential, Diagnostic Techniques, Endocrine, Paraganglioma, 03 medical and health sciences, Internal medicine, medicine, Endocrine system, Humans, Metabolomics, Clinical Research Articles, Aged, Retrospective Studies, Receiver operating characteristic, business.industry, Biochemistry (medical), medicine.disease, chemistry, business
Abstract

ContextIdentification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL], and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension.ObjectiveUse TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability.MethodsRetrospective analyses of PHT and EHT patients from a European multicenter study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a “classical approach” (CA) (performing a series of univariate and multivariate analyses) and a “machine learning approach” (MLA) (using random forest) were used.The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n = 59) and EHT (n = 223 with 40 CS, 107 PA, and 76 PPGL), respectively.ResultsFrom 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 16 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The receiver operating characteristic curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83).ConclusionTM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance.

Published
2021
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15. European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1—epidemiology, pathophysiology, and diagnosis

Author

Baigent, C., Windecker, S., Andreini, D., Arbelo, E., Barbato, E., Bartorelli, A.L., Baumbach, A., Behr, E.R., Berti, S., Bueno, H., Capodanno, D., Cappato, R., Chieffo, A., Collet, J.P., Cuisset, T., Simone, G. de, Delgado, V., Dendale, P., Dudek, D., Edvardsen, T., Elvan, A., Gonzalez-Juanatey, J.R., Gori, M., Grobbee, D., Guzik, T.J., Halvorsen, S., Haude, M., Heidbuchel, H., Hindricks, G., Ibanez, B., Karam, N., Katus, H., Klok, F.A., Konstantinides, S.V., Landmesser, U., Leclercq, C., Leonardi, S., Lettino, M., Marenzi, G., Mauri, J., Metra, M., Morici, N., Mueller, C., Petronio, A.S., Polovina, M.M., Potpara, T., Praz, F., Prendergast, B., Prescott, E., Price, S., Pruszczyk, P., Rodriguez-Leor, O., Roffi, M., Romaguera, R., Rosenkranz, S., Sarkozy, A., Scherrenberg, M., Seferovic, P., Senni, M., Spera, F.R., Stefanini, G., Thiele, H., Tomasoni, D., Torracca, L., Touyz, R.M., Wilde, A.A., Williams, B., Task Force Management Covid-19 Eur, Nuffield Department of Population Health [Oxford], University of Oxford, Bern University Hospital [Berne] (Inselspital), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Glasgow, Amsterdam UMC - Amsterdam University Medical Center, University College of London [London] (UCL), Baigent, C, Cardiology, Task Force for the management of COVID-19 of the European Society of, Cardiology, ACS - Heart failure & arrhythmias, Task Force Management Covid-19 Eur, University of Oxford [Oxford], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 (UPC), 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), delgado, victoria/0000-0002-9841-2737, BUENO, HECTOR/0000-0003-0277-7596, Karam, Nicole/0000-0002-3861-6914, Baigent, Colin/0000-0003-4856-7420, Behr, Elijah/0000-0002-8731-2853, Williams, Bryan/0000-0002-8094-1841, Rodriguez-Leor, Oriol/0000-0003-2657-5657, BUENO, HECTOR/0000-0003-0277-7596, Rodriguez-Leor, Oriol/0000-0003-2657-5657, Williams, Bryan/0000-0002-8094-1841, Karam, and Nicole/0000-0002-3861-6914

Subjects
ACE2, Arrhythmias, Biomarkers, Cardiogenic shock, COVID-19, Myocardial, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Physiology, Myocardial injury, Myocarditis, Non-invasive imaging, Humans, Pandemics, Prospective Studies, Cardiology, Cardiovascular Diseases, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Disease, Special Article, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), injury, Pandemic, Epidemiology, Medicine, AcademicSubjects/MED00200, Intensive care medicine, business.industry, Pathophysiology, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract

Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities., Graphical Abstract Graphical Abstract

Published
2022
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16. Obesity in Midlife Hampers Resting and Sensory‐Evoked Cerebral Blood Flow in Mice

Author

Hirac Gurden, Jean-Sébastien Silvestre, Christophe Magnan, Paolo Giacobini, Frédéric Pain, Haleh Soleimanzad, Mathilde Lemitre, Mireia Montaner, Nadim Kassis, Gaetan Ternier, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Laboratoire Charles Fabry / Biophotonique, Laboratoire Charles Fabry (LCF), Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut d'Optique Graduate School (IOGS), Gurden, Hirac, ANR-16-CE14-0026,Fat4Brain,Le métabolisme des lipides dans le cerveau est un regulateur essentiel de l'homéostasie énergétique(2016), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), and 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 de Paris (UP)

Subjects
Male, Cardiac function curve, Aging, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Endocrinology, Diabetes and Metabolism, Mice, Obese, Medicine (miscellaneous), 030209 endocrinology & metabolism, Sensory system, Diet, High-Fat, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Glucose Intolerance, medicine, Animals, Obesity, 030212 general & internal medicine, Nutrition and Dietetics, Ejection fraction, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Insulin sensitivity, medicine.disease, Olfactory Bulb, Olfactory bulb, Mice, Inbred C57BL, Smell, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Cerebral blood flow, Cerebrovascular Circulation, Odorants, Insulin Resistance, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Objective : This study aimed to investigate the effects of a high-fat diet (HFD) and aging on resting and activity-dependent cerebral blood flow (CBF).Methods: To run a comparison between obese and age-matched control animals, 6-week-old mice were fed either with regular chow or an HFD for 3 months or 8 months. Glucose tolerance and insulin sensitivity were assessed for metabolic phenotyping. Resting and odor-evoked CBF at the microvascular scale in the olfactory bulb (OB) was investigated by multiexposure speckle imaging. Immunolabeling-enabled imaging of solvent-cleared organs was used to analyze vascular density. The ejection fraction was studied by using cardioechography. Olfactory sensitivity was tested by using a buried-food test.Results: Glucose intolerance and compromised odor-evoked CBF were observed in obese mice in the younger group. Prolonged HFD feeding triggered insulin resistance and stronger impairment in activity-dependent CBF. Aging had a specific negative impact on resting CBF. There was no decrease in vascular density in the OB of obese mice, although cardiac function was impaired at both ages. In addition, decreased olfactory sensitivity was observed only in the older, middle-aged obese mice.Conclusions : OB microvasculature in obese mice showed a specific functional feature characterized by impaired sensory-evoked CBF and a specific deleterious effect of aging on resting CBF.

Published
2020
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17. Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology

Author

René Anxionnat, Myriam Edjlali-Goujon, Suzana Saleme, Hubert Desal, Nadya Pyatigorskaya, Stéphane Kremer, Douraied Ben Salem, Claire Boutet, Apolline Kazemi, Gregoire Boulouis, François Cotton, Olivier Clément, Basile Kerleroux, Jérôme Berge, Augustin Lecler, François Lersy, CCSD, Accord Elsevier, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Neuro-Radiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Lille, Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fondation Ophtalmologique Adolphe de Rothschild [Paris], CHU Limoges, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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 de Paris (UP), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Gadolinium, Gadolinium-based contrast agents, Contrast Media, chemistry.chemical_element, Neuroimaging, Recommendations, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Pituitary adenoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, Intracerebral hemorrhage, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], Venous thrombosis, chemistry, Nephrogenic systemic fibrosis, France, Neurology (clinical), Radiology, business, Brain MRI protocols, 030217 neurology & neurosurgery
Abstract

International audience; Gadolinium-based contrast agents (GBCAs) are used in up to 35% of magnetic resonance imaging (MRI) examinations and are associated with an excellent safety profile. Nevertheless, two main issues have arisen in the last two decades: the risk of nephrogenic systemic fibrosis and the risk of gadolinium deposition and retention. As a first step, this article reviews the different categories of GBCAs available in neuroradiology, their issues, and provides updates regarding the use of these agents in routine daily practice. Recent advances in MRI technology, as well as the development of new MRI sequences, have made GBCA injection avoidable in many indications, especially in patients with chronic diseases when iterative MRIs are required and when essential diagnostic information can be obtained without contrast enhancement. These recent advances also lead to changes in recommended MRI protocols. Thus, in a second step, this review focuses on consensus concerning brain MRI protocols in 10 common situations (acute ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, multiple sclerosis, chronic headache, intracranial infection, intra- and extra-axial brain tumors, vestibular schwannoma and pituitary adenoma). The latter allowing the standardization of practices in neuroradiology. Recommendations were also made concerning the use of GBCAs in neuroradiology, based on evidence in the literature and/or by consensus between the different coauthors.

Published
2020
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18. Non‐invasive recanalization of deep venous thrombosis by high frequency ultrasound in a swine model with follow‐up

Author

Mickael Tanter, Daniel Suarez, Mathieu Rémond, Emmanuel Messas, Mathieu Pernot, Costantino Del Giudice, Patrick Bruneval, Tristan Mirault, Marc Sapoval, Pierre Julia, Alexandre Houdouin, Lina Khider, A. Galloula, Guillaume Goudot, Université Paris Cité (UPCité), Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (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), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), Cardiawave SAS [Paris], and Goudot, Guillaume

Subjects
elastography, medicine.medical_specialty, Swine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Transducers, Femoral vein, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Thrombus, Vein, Ultrasonography, Venous Thrombosis, venous recanalization, Therapeutic ultrasound, business.industry, Ultrasound, Hematology, Femoral Vein, medicine.disease, Thrombosis, Pulmonary embolism, [SDV] Life Sciences [q-bio], Venous thrombosis, Treatment Outcome, medicine.anatomical_structure, therapeutic ultrasound, Radiology, business, Follow-Up Studies
Abstract

International audience; Aims: Pulsed cavitational ultrasound therapy (thombotripsy) allows the accurate fractionation of a distant thrombus. We aimed to evaluate the efficacy and safety of non-invasive thrombotripsy using a robotic assisted and high frequency ultrasound approach to recanalize proximal deep venous thrombosis (DVT) in a swine model. Methods: Occlusive thrombosis was obtained with a dual jugular and femoral endoveinous approach. The therapeutic device was composed of a 2.25 MHz focused transducer centered by a linear ultrasound probe, and a robotic arm. The feasibility, security, and efficacy (venous channel patency) assessment after thrombotripsy was performed on 13 pigs with acute occluded DVT. To assess the mid-term efficacy of this technique, 8 pigs were followed up for 14 days after thrombotripsy and compared with 8 control pigs. The primary efficacy endpoint was the venous patency. Safety was assessed by the search for local vessel wall injury and pulmonary embolism. Results: We succeeded in treating all pigs except two with no accessible femoral vein. After median treatment duration of 23 minutes of cavitation, all treated DVT were fully recanalized acutely. At 14 days, in the treated group, six of the eight pigs had a persistent patent vein and two pigs had a venous reocclusion. In the control group all pigs had a persistent venous occlusion. At sacrifice, no local vein nor arterial wall damage were observed as well as no evidence of pulmonary embolism in all pigs. Conclusion: High frequency thrombotripsy seems to be effective and safe for noninvasive venous recanalization of DVT.

Published
2020
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19. Sequential nephron blockade with combined diuretics improves diastolic function in patients with resistant hypertension

Author

Antoine Fayol, Anne Blanchard, David Fouassier, Jean-Sébastien Hulot, Pierre Boutouyrie, Guillaume Bobrie, Michel Azizi, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de médecine vasculaire et hypertension artérielle [CHU HEGP], 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), INSERM U652, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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 de Paris (UP)

Subjects
Cardiac function curve, Ramipril, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Blood Pressure, Heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Irbesartan, Clinical trials, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, Diuretics, Antihypertensive Agents, Pharmacology, business.industry, Nephrons, medicine.disease, 3. Good health, Pulse pressure, Resistant hypertension, Blood pressure, chemistry, Bisoprolol, RC666-701, Hypertension, Cardiology, Spironolactone, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

International audience; Aims Hypertension is a major contributor to cardiac diastolic dysfunction. Different therapeutics strategies have been proposed to control blood pressure (BP), but their independent impact on cardiac function remains undetermined. In patients with resistant hypertension, we compared the changes in cardiac parameters between two strategies based on sequential nephron blockade (NBD) with a combination of diuretics or sequential renin-angiotensin system blockade (RASB). Methods and results After a 4-week period where all patients received Irbesartan 300 mg/day + hydrochlorothiazide 12.5 mg/day + amlodipine 5 mg/day, 140 resistant hypertension patients (54.8 ± 11.1 years, 76% men, mean duration with hypertension: 13.1 ± 10.5 years, no previous history of heart failure or current symptoms of congestive heart failure) were randomized 1:1 to the NBD regimen or to the RASB regimen at week 0 (W0, baseline). Treatment intensity was increased at week 4, 8, or 10 if home BP was ≥135/85 mmHg, by sequentially adding 25 mg spironolactone, 20-40 mg furosemide, and 5 mg amiloride (NBD group) or 5-10 mg ramipril and 5-10 mg bisoprolol (RASB group). No other antihypertensive drug was allowed during the study. BP, BNP levels, and echocardiographic parameters were assessed at weeks 0 and 12. The baseline characteristics, laboratory parameters, and plasma hormones (BNP, renin, and aldosterone) and cardiac echocardiographic parameters did not significantly differ between the NBD and the RASB groups. Over 12 weeks, BNP levels significantly decreased in NBD but increased in RASB (mean [CI 95%] change in log-transformed BNP levels: À43% [À67%; À23%] vs. +55% [46%; 62%] in NBD vs. RASB, respectively, P < 0.0001). Similarly, the proportion of patients presenting ≥2 echocardiographic criteria of diastolic dysfunction decreased between baseline and W12 from 31% to 3% in NBD but increased from 19% to 32% in RASB (P = 0.0048). As compared with RASB, NBD induced greater decrease in ambulatory systolic BP (P < 0.0001), pulse pressure (P < 0.0001), and systemic vascular resistance (P < 0.005). In multivariable linear regression analyses, NBD treatment was significantly associated with decreased BNP levels (adjusted ß: À46.41 ± 6.99, P < 0.0001) independent of age, gender, renal function, and changes in BPs or heart rate. Conclusions In patients with resistant hypertension, nephron blockade with a combination of diuretics significantly improves cardiac markers of diastolic dysfunction independently of BP lowering.

Published
2020
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20. Interventional radiology for treatment of bone metastases

Author

B. Kastler, G. Hayek, 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), Université Paris Cité (UPCité), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CCSD, Accord Elsevier, Université de Paris (UP), and 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 de Paris (UP)

Subjects
medicine.medical_specialty, Radiofrequency ablation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Bone Neoplasms, Hemorrhage, Radiology, Interventional, Lytic Bone Lesion, Cryosurgery, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Humans, Radiology, Nuclear Medicine and imaging, Microwaves, Radiofrequency Ablation, Vertebroplasty, Cementoplasty, Ethanol, medicine.diagnostic_test, business.industry, Palliative Care, Microwave ablation, Bone Cements, Bone metastasis, Nerve Block, Cryoablation, Interventional radiology, Cancer Pain, medicine.disease, Embolization, Therapeutic, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, Fractures, Spontaneous, Oncology, 030220 oncology & carcinogenesis, Catheter Ablation, Solvents, Radiology, business, Anesthesia, Local
Abstract

Therapeutic advances in oncology have led to longer survival in many forms of cancer, including those complicated by bone metastases. When a bone metastasis is painful or when there is a risk of fracture, interventional radiology procedures can be carried out for pain control and/or stabilisation. All of these techniques can be performed under local anaesthesia. Cementoplasty and vertebroplasty are stabilisation procedures consisting in the percutaneous injection of acrylic cement into a lytic bone lesion. The effect on pain can be explained by the consolidation of weakened, fractured or pre-fractured bone, but also to a lesser extent by the toxic, chemical and thermal effect of the cement. Tumour ablation techniques include alcoholisation or thermal ablation (by heat with radiofrequency and microwave or cold by cryoablation). Percutaneous thermal ablation of bone tumours is most often performed as a palliative measure resulting in a significant and lasting reduction in symptoms. Radiofrequency ablation consists in placing needles through which an electrical current passes. Microwave ablation acts by causing very high frequency vibrations of water molecules. Cryoablation releases argon gas at the tip of the needle, forming an "ice ball" effectively destroying tumour cells. Any of these techniques can be combined to radiation therapy, performed before or after radiation. Finally, tumour embolisation can have a goal of pain control, or preparation of surgery to reduce the risk of peroperative haemorrhage.

Published
2020
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21. Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study

Author

A. Novara, E. Guerot, David M. Smadja, Jean Luc Diehl, Nicolas Gendron, Guillaume Goudot, Nicolas Peron, J. Langlais, Bertrand Hermann, Tristan Mirault, Richard Chocron, Jean Loup Augy, Benjamin Debuc, Caroline Hauw-Berlemont, R. Younan, J.-F. Fagon, Lina Khider, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Fondation Alain Carpentier - (Centre Médical International) [Paris] (FAC - CMI), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), and Goudot, Guillaume

Subjects
medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Respiratory physiology, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, ARDS COVID-19 Physiological dead-space Ventilatory ratio, Internal medicine, medicine, Lung volumes, Physiological dead-space, Respiratory system, Mechanical ventilation, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, Ventilatory ratio, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Pulmonary embolism, [SDV] Life Sciences [q-bio], Respiratory failure, Cardiology, medicine.symptom, business, Hypercapnia
Abstract

Rationale COVID-19 ARDS could differ from typical forms of the syndrome. Objective Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. Methods Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1–4] day after intubation (median [IQR]). Measurements and main results Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1–44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721–2434] mL. Gas exchanges were characterized by hypercapnia 55 [44–62] mmHg, high physiological dead-space (VD/VT): 75 [69–85.5] % and ventilatory ratio (VR): 2.9 [2.2–3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12–46] cells per mL and 1483 [999–2217] ng/mL, respectively. Conclusions We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Published
2020
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22. Apport du pathologiste dans les prédispositions héréditaires aux paragangliomes et phéochromocytomes

Author

Chloé Broudin, Tchao Meatchi, Virginie Verkarre, Judith Favier, 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), Service d'anatomo-pathologie [CHU HEGP], 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), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), and 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 de Paris (UP)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, business.industry, SDHB, [SDV]Life Sciences [q-bio], Early detection, Disease, medicine.disease, Medical care, 3. Good health, Pathology and Forensic Medicine, Pheochromocytoma, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Paraganglioma, 030220 oncology & carcinogenesis, medicine, Immunohistochemistry, business, Gene
Abstract

Hereditary predispositions are responsible for more than 30% of or paraganglioma. Their identification is essential to optimize medical care and to offer an appropriate screening to relatives. To date, there are more than 15 known paraganglioma/pheochromocytoma predisposing genes. The most frequently involved are those encoding the succinate dehydrogenase (SDHx), accounting for half of cases and the VHL gene, causing the Von Hippel Lindau syndrome and representing approximately 20% of genetically determined cases. Patients with SDHB genes mutations have a higher risk of metastatic disease. An oncogenetic counseling is recommended to all patients developing one or several paragangliomas, isolated or associated with other tumors. Apart from the clinical presentation and in particular the syndromic forms characterized by specific tumor spectra, there is no validated morphological criterion allowing to suspect a hereditary form. On the other hand, pathologists have now access to several immunohistochemical tools allowing the identification of some hereditary forms, in particular those linked to the SDHx, VHL and FH genes. Thus, the loss of expression in immunohistochemistry of the SDHB or FH proteins orientates respectively, towards SDHx and FH genes, while the membrane expression of carbonic anhydrase IX (CA-IX) is a sensitive and specific tool pointing towards a VHL anomaly. Other immunohistochemical markers are under evaluation. A systematic SDHB immunohistochemical staining is recommended on all paragangliomas/pheochromocytomas in order to allow an early detection of the most common hereditary forms and to contribute to the interpretation of the genetic results in these patients seen in oncogenetics consultation.

Published
2020
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23. Changes in segmental pulse wave velocity of the thoracic aorta with age and left ventricular remodelling. An MRI 4D flow study

Author

Gilles Soulat, Emmanuel Messas, Olivier Villemain, Nadjia Kachenoura, Pierre Boutouyrie, Elie Mousseaux, Stéphane Laurent, Umit Gencer, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Laboratoire d'Imagerie Biomédicale (LIB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Aortic arch, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Aorta, Thoracic, Pulse Wave Analysis, 030204 cardiovascular system & hematology, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Internal medicine, medicine.artery, Ascending aorta, Internal Medicine, medicine, Humans, Thoracic aorta, cardiovascular diseases, 030212 general & internal medicine, Pulse wave velocity, Aged, Aorta, Ventricular Remodeling, business.industry, Middle Aged, Magnetic Resonance Imaging, Sagittal plane, medicine.anatomical_structure, Descending aorta, cardiovascular system, Cardiology, End-diastolic volume, Female, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, circulatory and respiratory physiology
Abstract

International audience; Objectives: Pulse wave velocity (PWV) of the aortic arch is usually estimated by using 2D phase contrast in MRI. Thanks to 4D flow MRI, segmental PWV of the ascending and descending aorta, as well as PWV of the entire thoracic aorta can now be estimated within the same examination. Our objective is to compare PWVs obtained by 2D and 4D PC, through their relationships with carotid-femoral PWV (cf-PWV), age and left ventricular remodelling.Basic methods: MRI examinations were performed at 3 Tesla, including 2D PC acquisitions with through-plane velocity encoding and sagittal 4D phase contrast acquisitions covering the thoracic aorta volume. PWVs were calculated after estimating aortic lengths and flow transit times between the ascending aorta and descending aorta in 2D and between valve, isthmus and diaphragm in 4D resulting in 2D-PWV, 4D-TA-PWV; 4D-AA-PWV, 4D-DA-PWV.Main results: Fifty-seven healthy volunteers (25 men, age 51 years ± 17) were studied. All MRI-PWVs were correlated with cf-PWV (r = 0.67; r = 0.63: r = 0.47; r = 0.61 for 2D-PWV, 4D-TA-PWV; 4D-AA-PWV, 4D-DA-PWV, respectively, P < 0.001). 2D-PWV and 4D-TA-PWV were strongly related with age (r = 0.76 and r = 0.77, respectively). The highest correlation, between left ventricular thickness or LV mass/end diastolic volume (EDV) ratio and segmental PWVs of the thoracic aorta was found with 4D-AA-PWV (r = 0.43, P < 0.01 and r = 0.48, P < 0.01).Principal conclusions: Global and segmental PWV analysis of the thoracic aorta can be accurately assessed using 4D flow MRI. 4D-PWVs were highly correlated with ageing and cf-PWV. The strong association between the ascending aorta stiffness and the left ventricular remodelling in healthy volunteers is encouraging to better estimate left ventricular afterload.

Published
2020
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24. Is Bicuspid Aortic Valve Morphology Genetically Determined? A Family-Based Study

Author

Yonatan Levin, Shoshana Shpitzen, Noga Reshef, Guy Kelman, Dan Gilon, Juliette Albuisson, Jean-Michaël Mazzella, Donna R. Zwas, Idit Tessler, Galina Levin, Emmanuel Messas, Ronen Durst, Shai Carmi, Guillaume Goudot, Charles Cheng, Goudot, Guillaume, Hadassah Hebrew University Medical Center [Jerusalem], 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), Centre de Réféfence des Maladies Vasculaires Rares [HEGP, APHP] (CRMVR), 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)-Université Paris Descartes - Paris 5 (UPD5), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, and The Hebrew University of Jerusalem (HUJ)

Subjects
Adult, Male, medicine.medical_specialty, Heart disease, Concordance, [SDV]Life Sciences [q-bio], symbols.namesake, Bicuspid aortic valve, Bicuspid Aortic Valve Disease, Internal medicine, medicine, Humans, Mass Screening, Family, Intrafamilial variability, Aged, business.industry, Middle Aged, medicine.disease, Phenotype, [SDV] Life Sciences [q-bio], Echocardiography, Cohort, Cardiology, Mendelian inheritance, symbols, Female, Cardiology and Cardiovascular Medicine, Family based, business
Abstract

International audience; Bicuspid aortic valve (BAV) is a common congenital heart disease, with a 10-fold higher prevalence in first-degree relatives. BAV has different phenotypes based on the morphology of cusp fusion. These phenotypes are associated with different clinical courses and prognoses. Currently, the determinants of the valve phenotype are unknown. In this study we evaluated the role of genetics using familial cohorts. Patients with BAV and their first-degree relatives were evaluated by echocardiography. The concordance in BAV phenotype between pairs of family members was calculated and compared with the concordance expected by chance. We then performed a systematic literature review to identify additional reports and calculated the overall concordance rate. During the study period, 70 cases from 31 families and 327 sporadic cases were identified. BAV was diagnosed in 14% of the screened relatives. The proportions of the morphologies identified was: 12.3% for type 0, 66.2% for type 1-LR, 15.4% for type 1-RN, 4.6% for type 1-NL, and 1.5% for type 2. For the assessment of morphologic concordance, we included 120 pairs of first-degree relatives with BAV from our original cohort and the literature review. Concordance was found only in 62% of the pairs which was not significantly higher than expected by chance. In conclusion, our finding demonstrates intrafamilial variability in BAV morphology, suggesting that morphology is determined by factors other than Mendelian genetics. As prognosis differs by morphology, our findings may suggest that clinical outcomes may vary even between first-degree relatives.

Published
2022
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25. Incidence, Risk Factors, and Outcomes of Atrial Arrhythmias in Adult Patients With Atrioventricular Septal Defect

Author

Francis Bessière, Magalie Ladouceur, Emre Belli, Sandra Clavier, Eloi Marijon, Antoine Legendre, Arnaud Dulac, Jérôme Petit, Nicolas Combes, Laurence Iserin, Etienne Jacquemart, Anne-Sophie Jannot, Philippe Chevalier, Alice Maltret, Roland Henaine, Sarah Cohen, Sylvie Di Filippo, Kévin Gardey, Victor Waldmann, Reaksmei Ly, Sébastien Hascoët, CarMeN, laboratoire, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Lyon

Subjects
Adult, Heart Septal Defects, Ventricular, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, [SDV]Life Sciences [q-bio], atrial arrhythmia, Young Adult, Risk Factors, Internal medicine, Tachycardia, Supraventricular, medicine, adult congenital heart disease, Humans, atrial fibrillation, risk factors, cardiovascular diseases, Atrioventricular Septal Defect, atrioventricular septal defect, Retrospective Studies, Adult patients, business.industry, Heart Septal Defects, Incidence, Incidence (epidemiology), Background data, Atrial fibrillation, Atrial arrhythmias, Middle Aged, medicine.disease, [SDV] Life Sciences [q-bio], atrial flutter, cardiovascular system, Cardiology, Female, business, Atrial flutter
Abstract

International audience; OBJECTIVES: This study aimed to assess the incidence, associated factors, and outcomes of atrial arrhythmias in adults with atrioventricular septal defect (AVSD). BACKGROUND: Data regarding atrial arrhythmias in adults with AVSD are particularly scarce. METHODS: Data were analyzed from a multicentric cohort of adult patients with AVSD. Lifetime cumulative incidences of atrial arrhythmias were studied. Multiple logistic regression models were used to identify risk factors. RESULTS: A total of 391 patients (61.6% women) were enrolled with a mean age of 36.3 ± 16.3 years and a mean follow-up of 17.3 ± 14.2 years after initial surgical repair. Overall, 98 patients (25.1%) developed at least 1 episode of atrial arrhythmia at a mean age of 39.2 ± 17.2 years. The mean ages of patients at first episode of intra-atrial re-entrant tachycardia (IART)/ focal atrial tachycardia (FAT) and atrial fibrillation were 33.7 ± 15.3 and 44.3 ± 16.5 years, respectively. The lifetime risks for developing atrial arrhythmia to ages 20, 40, and 60 years were 3.7%, 17.8%, and 55.3%, respectively. IART/FAT was the leading arrhythmia until the age of 45, then atrial fibrillation surpassed IART/FAT. Age (odds ratio [OR]: 1.4; 95% confidence interval [CI]: 1.2-1.6), number of cardiac surgeries (OR: 4.1; 95% CI: 2.5-6.9), left atrial dilatation (OR: 3.1; 95% CI: 1.4-6.8), right atrial dilatation (OR: 4.1; 95% CI: 1.7-10.3), and moderate or severe left atrioventricular valve regurgitation (OR: 3.7; 95% CI: 1.2-11.7) were independently associated with a higher risk of atrial arrhythmias, whereas the type of AVSD and the age at repair were not. The occurrence of atrial arrhythmias was associated with pacemaker implantation (41.8% vs. 8.5%; P \textless 0.001), heart failure (24.5% vs. 1.0%; P \textless 0.001), and cerebrovascular accidents (11.2% vs. 3.4%; P = 0.007). CONCLUSIONS: The lifetime risk of atrial arrhythmias in patients with AVSD is considerable with more than half of patients developing ≥1 atrial arrhythmia by the age of 60 and is associated with a significant morbidity. The risk in partial/intermediate AVSD is as high as in complete AVSD and is not impacted by age at repair.

Published
2022
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26. Platelet activation in critically ill COVID-19 patients

Author

Jérôme Hadjadj, David M. Smadja, Darragh Duffy, Celia Azoulay, Frédéric Rieux-Laucat, Tristan Mirault, Jean-Luc Diehl, Benjamin Terrier, Bruno Charbit, Nader Yatim, Laura Barnabei, Aurélien Philippe, Coralie L. Guerin, Nicolas Gendron, T.-A. Szwebel, Lina Khider, Frédéric Pène, Nicolas Carlier, Richard Chocron, Jeremy Boussier, Solen Kernéis, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by a government grant managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (ANR-10-IAHU-01), and by grants from the Agence National de la Recherche: ANR-flash Covid19 'AIROCovid' and 'CoVarImm'. We also acknowledge funding from the Institut Pasteur for Covid19 research. J.H. is a recipient of an Institut Imagine MD-PhD fellowship program supported by the Fondation Bettencourt Schueller. L.B. is supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) program of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program. We thank AP-HP for promotion of the SARCODO Project. We thank the unit of clinical research URC HEGP CIC-EC1418 (Natacha Nohile, Pauline Jouany and Dr Juliette Djadi-Prat) and Helene Cart-Grandjean from AP-HP for their involvement in SARCODO project. SARCODO project was supported by grants of ANR (Fondation de France) and Appel d'offre AP-HP mécénat crise COVID-19 from GHU APHP.CUP., We would like to acknowledge all nurses, technicians and physicians involved in all department involved in COVID-19 patients management in APHP.CUP hospitals, for their help in taking care of patients and including them in the study, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Vougny, Marie-Christine, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Génétique et Epigénétique Nouvelle Ecole - - GENE2017 - ANR-17-EURE-0013 - EURE - VALID, and Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID

Subjects
0301 basic medicine, Platelets, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Disease, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, Thrombo-inflammation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Anesthesiology, Medicine, Intubation, Platelet, Platelet activation, Primary hemostasis, business.industry, Critically ill, RC86-88.9, Research, COVID-19, Medical emergencies. Critical care. Intensive care. First aid, 030104 developmental biology, Hemostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract

Background Microvascular, arterial and venous thrombotic events have been largely described during severe coronavirus disease 19 (COVID-19). However, mechanisms underlying hemostasis dysregulation remain unclear. Methods We explored two independent cross-sectional cohorts to identify soluble markers and gene-expression signatures that discriminated COVID-19 severity and outcomes. Results We found that elevated soluble (s)P-selectin at admission was associated with disease severity. Elevated sP-selectin was predictive of intubation and death (ROC AUC = 0.67, p = 0.028 and AUC = 0.74, p = 0.0047, respectively). An optimal cutoff value was predictive of intubation with 66% negative predictive value (NPV) and 61% positive predictive value (PPV), and of death with 90% NPV and 55% PPV. An unbiased gene set enrichment analysis revealed that critically ill patients had increased expression of genes related to platelet activation. Hierarchical clustering identified ITG2AB, GP1BB, PPBP and SELPLG to be upregulated in a grade-dependent manner. ROC curve analysis for the prediction of intubation was significant for SELPLG and PPBP (AUC = 0.8, p = 0.046 for both). An optimal cutoff value for PBPP was predictive of intubation with 100% NPV and 45% PPV, and for SELPLG with 100% NPV and 50% PPV. Conclusion We provide evidence that platelets contribute to COVID-19 severity. Plasma sP-selectin level was associated with severity and in-hospital mortality. Transcriptional analysis identified PPBP/CXCL7 and SELPLG as biomarkers for intubation. These findings provide additional evidence for platelet activation in driving critical COVID-19. Specific studies evaluating the performance of these biomarkers are required.

Published
2021
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27. Effectiveness of a ‘do not interrupt’ vest intervention to reduce medication errors during medication administration: a multicenter cluster randomized controlled trial

Author

Germain Perrin, Mathieu Depoisson, Laetitia Minh Mai Le, Thuy Tan Phan Thi, Yvonnick Bézie, Pierre Durieux, Jennifer Corny, Brigitte Sabatier, Claudine Guihaire, Nathalie Valin, Alexandre Karras, Sarah Berdot, Claudine Decelle, Aurélie Vilfaillot, Marion Berge, 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), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), 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)-École pratique des hautes études (EPHE), Hôpital Vaugirard-Gabriel Pallez, Hôpital Corentin Celton [Issy-les-Moulineaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by a grant from the French Ministry of Healthn(Direction Générale de l’Offre de Soins –DGOS) as the 'Programme de Recherche sur la Performance du Système de Soins' (N°15–027 PERMIS)., Groupe hospitalier Paris Saint-Joseph - Hôpital, This work was supported by a grant from the French Ministry of Health (Direction Générale de l’Offre de Soins –DGOS) as the 'Programme de Recherche sur la Performance du Système de Soins' (N°15–027 PERMIS)., 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), 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)-École pratique des hautes études (EPHE), Université Paris Descartes - Paris 5 (UPD5), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Chimie Analytique Pharmaceutique - Faculté de Pharmacie (Lip(Sys)2), Université Paris-Sud - Paris 11 (UP11), Malbec, Odile, 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), École Pratique des Hautes Études (EPHE), and 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)-École Pratique des Hautes Études (EPHE)

Subjects
medicine.medical_specialty, Hospital / organization & administration (MeSH), Vest, [SDV]Life Sciences [q-bio], RT1-120, Psychological intervention, Nursing, Disease cluster, law.invention, 03 medical and health sciences, 0302 clinical medicine, Safety management / organization & administration* (MeSH), Randomized controlled trial, law, Medicine, 030212 general & internal medicine, Nursing staff, Nursing management, General Nursing, Protocol (science), 030504 nursing, business.industry, Nursing research, Research, Medication errors/prevention and control (MeSH), Workload, 3. Good health, [SDV] Life Sciences [q-bio], [STAT]Statistics [stat], Interruptions, Physical therapy, VEST, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, business, Medication errors/nursing* (MeSH)
Abstract

Background The use of a ‘do not interrupt’ vest during medication administration rounds is recommended but there have been no controlled randomized studies to evaluate its impact on reducing administration errors. We aimed to evaluate the impact of wearing such a vest on reducing such errors. The secondary objectives were to evaluate the types and potential clinical impact of errors, the association between errors and several risk factors (such as interruptions), and nurses’ experiences. Methods This was a multicenter, cluster, controlled, randomized study (March–July 2017) in 29 adult units (4 hospitals). Data were collected by direct observation by trained observers. All nurses from selected units were informed. A ‘Do not interrupt’ vest was implemented in all units of the experimental group. A poster was placed at the entrance of these units to inform patients and relatives. The main outcome was the administration error rate (number of Opportunities for Error (OE), calculated as one or more errors divided by the Total Opportunities for Error (TOE) and multiplied by 100). Results We enrolled 178 nurses and 1346 patients during 383 medication rounds in 14 units in the experimental group and 15 units in the control group. During the intervention period, the administration error rates were 7.09% (188 OE with at least one error/2653 TOE) for the experimental group and 6.23% (210 OE with at least one error/3373 TOE) for the control group (p = 0.192). Identified risk factors (patient age, nurses’ experience, nurses’ workload, unit exposition, and interruption) were not associated with the error rate. The main error type observed for both groups was wrong dosage-form. Most errors had no clinical impact for the patient and the interruption rates were 15.04% for the experimental group and 20.75% for the control group. Conclusions The intervention vest had no impact on medication administration error or interruption rates. Further studies need to be performed taking into consideration the limitations of our study and other risk factors associated with other interventions, such as nurse’s training and/or a barcode system. Trial registration The PERMIS study protocol (V2–1, 11/04/2017) was approved by institutional review boards and ethics committees (CPP Ile de France number 2016-A00211–50, CNIL 21/03/2017, CCTIRS 11/04/2016). It is registered at ClinicalTrials.gov (registration number: NCT03062852, date of first registration: 23/02/2017).

Published
2021
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28. No SARS-CoV-2 reinfection among staff health-care workers: Prospective hospital-wide screening during the first and second waves in Paris

Author

Maxime Wack, Laurence Janot, Laurent Bélec, David Veyer, Hélène Péré, Benoit Vedie, Laure Izquierdo, Nathalie Demory-Guinet, Najiby Kassis-Chikhani, 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), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), HAL-SU, Gestionnaire, 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), and 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)

Subjects
medicine.medical_specialty, Protective immunity, Coronavirus disease 2019 (COVID-19), Epidemiology, Health Personnel, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), health care facilities, manpower, and services, Health-care workers, education, Serology, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Health care, medicine, Humans, Prospective Studies, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, SARS-CoV-2, Vaccination, COVID-19, Paper from the 21st ESCV meeting, virus diseases, Hospitals, 3. Good health, Infectious Diseases, Reinfection, Cohort, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Summary Objectives Risk of reinfection with SARS-CoV-2 among health-care workers (HCWs) is unknown. We assessed the incidence rate of SARS-CoV-2 reinfection in the real-life setting of a longitudinal observational cohort of HCWs from the Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, France, during the first and second waves of COVID-19 epidemic. Methods From March to December 2020, HCWs were subjected to molecular and serology testing of SARS-CoV-2. Reinfection was defined as a positive test result during the first wave, either by serology or PCR, followed by a positive PCR during the second wave. Evolution of COVID-19 status of HWCs was assessed by a Sankey diagram. Results A total of 7765 tests (4579 PCR and 3186 serology) were carried out and 4168 HCWs had at least one test result during the follow-up period with a positivity rate of 15.9%. No case of reinfection during the second wave could be observed among 102 positive HCWs of the first wave, nor among 175 HCWs found positive by PCR during the second wave who were negative during the first wave. Conclusions SARS-CoV-2 reinfection was not observed among HCWs, suggesting a protective immunity against reinfection that lasts at least 8 months post infection.

Published
2021
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29. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author

Tove Fall, Anubha Mahajan, Dmitry Shungin, B. Balkau, Gerjan Navis, A. Metspalu, Anneli Pouta, Andrew A. Hicks, Ilja M. Nolte, Ian Ford, Aroon D. Hingorani, Stefan R Bornstein, Anuj Goel, Rona J. Strawbridge, Niek Verweij, Sarah H. Wild, Patricia B. Munroe, T.B. Harris, Jaana Lindström, Johnson Pcd., Nita G. Forouhi, Pierre Meneton, Patricia A. Peyser, Sarin A-P., Andrea Ganna, Timothy M. Frayling, Patrik K. E. Magnusson, Joanne M. Meyer, Yongmei Liu, Jeanette M. Stafford, Christian Herder, L Zudina, Maria G. Stathopoulou, May E. Montasser, Nicholas D. Hastie, Inês Barroso, Schwarz Peh., James B. Meigs, Perttu Salo, George Davey Smith, Gonneke Willemsen, Christopher J. Groves, Erik P A Van Iperen, M. A. Province, Veikko Salomaa, Naveed Sattar, Serena Sanna, Maria Dimitriou, Joop Jukema, Ulrika Krus, Albert V. Smith, Markku Laakso, James F. Wilson, George Nicholson, Loic Yengo, Tatijana Zemunik, Per Eriksson, Harold Snieder, Peter P. Pramstaller, Claudia Langenberg, R. Rauramaa, Alan R. Shuldiner, Pau Navarro, Veronique Vitart, Ross M. Fraser, Aaron Isaacs, C. Lecoeur, Jesper R. Gådin, Jackie F. Price, Letizia Marullo, L.F. Bielak, Sirkka Keinänen-Kiukaanniemi, Amélie Bonnefond, Michael Stumvoll, Alessia Faggian, Anke Tönjes, Tomohiro Tanaka, Wieland Kiess, Harry Campbell, Josée Dupuis, David Altshuler, João Fadista, Winfried März, G K Hovingh, Thomas Illig, Toby Johnson, H Grallert, Kari Stefansson, Reedik Mägi, Palmer Cna., de Geus Ejcn., Martina Müller-Nurasyid, Karen Kapur, Philippe Froguel, Dorret I. Boomsma, Anders Franco-Cereceda, Marcus E. Kleber, Boehnke M, Olga D. Carlson, Ozren Polasek, Andrew P. Morris, Alex S. F. Doney, Najaf Amin, Sara M. Willems, Vilmundur Gudnason, Jose C. Florez, Jeffery R. O'Connell, Nancy L. Pedersen, T. Saaristo, Wolffenbuttel Bhr., M. I. J. Uusitupa, Longda Jiang, Iva Miljkovic, James S. Pankow, Caroline Hayward, Hugh Watkins, Vasiliki Lagou, Johanna Kuusisto, Jaakko Tuomilehto, Alan F. Wright, Josephine M. Egan, Perry Jrb., C M van Duijn, Valeriya Lyssenko, Leif Groop, Stefania Bandinelli, Nigel W. Rayner, Tõnu Esko, Stela McLachlan, Momoko Horikoshi, Eric Boerwinkle, Rick Jansen, Richard N. Bergman, Gudmar Thorleifsson, Lyle J. Palmer, Vilmantas Giedraitis, Peter Kovacs, Nicholas J. Wareham, Luigi Ferrucci, N J Timpson, D Rybin, Anne U. Jackson, Tiinamaija Tuomi, Gonçalo R. Abecasis, Harst Pvd., Meena Kumari, Albert Hofman, Chiara Scapoli, Evelin Mihailov, Josine L. Min, Anders Hamsten, Hottenga J-J., Loos Rjf., Lars Lind, Ulf de Faire, Jaakko Kaprio, Guo Li, Beate St Pourcain, C Gieger, Amanda J. Bennett, Anna Ulrich, Nabila Bouatia-Naji, Satu Männistö, Antigone S. Dimas, Jarvelin M-R., Günther Silbernagel, F Karpe, A. Körner, David S. Siscovick, M Blüher, Rebecca J. Webster, Erik Ingelsson, Susan Campbell, Mika Kivimäki, Laura J. Rasmussen-Torvik, Heikki A. Koistinen, Sophie Visvikis-Siest, Bernhard O. Boehm, Inga Prokopenko, Ping An, Emmanouil T. Dermitzakis, Cecilia M. Lindgren, Kardia Slr., Richa Saxena, Igor Rudan, Richard M. Watanabe, Jian'an Luan, Marika Kaakinen, Shin S-Y., George Dedoussis, Panagiotis Deloukas, Mark I. McCarthy, Barbara Thorand, B.W.J.H. Penninx, Peter Vollenweider, Paul W. Franks, Leena Kinnunen, Markus Perola, Yvonne Boettcher, Timo A. Lakka, Nicole Soranzo, Stavroula Kanoni, Bakker Sjl., Winkelmann Br, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Genomics [Tartu, Estonia], University of Tartu, Vrije Universiteit Amsterdam [Amsterdam] (VU), Vrije Universiteit Medical Centre (VUMC), Helmholtz-Zentrum München (HZM), University of Cambridge [UK] (CAM), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), 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 National de la Recherche Scientifique (CNRS), 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 de Paris (UP), Università degli Studi di Ferrara (UniFE), Boston University [Boston] (BU), VU University Medical Center [Amsterdam], University of Bristol [Bristol], Biomedical Sciences Research Centre Alexander Fleming [Vari, Greece] (BSRC), Imperial College London, Karolinska Institutet [Stockholm], Institute for Molecular Bioscience, University of Queensland [Brisbane], Statens Serum Institut [Copenhagen], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, National Institute on Aging [Baltimore, MD, USA] (NIH), University of Michigan [Ann Arbor], University of Michigan System, University of Maryland School of Medicine, University of Maryland System, The University of Western Australia (UWA), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Wake Forest University, National Institute for Health and Welfare [Helsinki], The Wellcome Trust Sanger Institute [Cambridge], University of Iceland [Reykjavik], University of Washington [Seattle], University of Groningen [Groningen], University of Glasgow, William Harvey Research Institute, Barts and the London Medical School, Université de Lausanne (UNIL), deCODE genetics [Reykjavik], Northwestern University Feinberg School of Medicine, Uppsala Universitet [Uppsala], University of Edinburgh, Medical Faculty [Mannheim], University of Graz, Ludwig-Maximilians-Universität München (LMU), Johannes Gutenberg - Universität Mainz (JGU), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Umeå University, Skane University Hospital [Malmo], Lund University [Lund], RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), University Medical Center Groningen [Groningen] (UMCG), Universität Leipzig [Leipzig], Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Split, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of Eastern Finland, Harokopio University of Athens, European Academy Bozen/Bolzano (EURAC), University of Kuopio, German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Ninewells Hospital and Medical School [Dundee], University College of London [London] (UCL), University of Essex, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Helsinki, Leiden University Medical Center (LUMC), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Oulu, The University of Texas Health Science Center at Houston (UTHealth), University of Minnesota Medical School, University of Minnesota System, Keck School of Medicine [Los Angeles], University of Southern California (USC), Amsterdam UMC, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Universität Heidelberg [Heidelberg], King Abdulaziz University, Pirkanmaa Hospital District, Tampere University Hospital, Cedars-Sinai Medical Center, Danube University Krems, Harvard School of Public Health, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Hannover Medical School [Hannover] (MHH), Universität zu Lübeck [Lübeck], University of Exeter, Regeneron Pharmaceuticals [Tarrytown], University of Adelaide, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Harvard T.H. Chan School of Public Health, John Radcliffe Hospital [Oxford University Hospital], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Genève (UNIGE), Big Data Institute, University of Surrey (UNIS), University of Bergen (UiB), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, University of Liverpool, University of Manchester [Manchester], Institute of Biochemistry and Genetics of Ufa Scientific Centre, Russian Academy of Sciences [Moscow] (RAS), Experimental Vascular Medicine, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, SIEST, Sofia, PreciDIAB Institute, the holistic approach of personal diabets care - - PreciDIAB2018 - ANR-18-IBHU-0001 - IBHU - VALID, Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging - DYNAHEALTH - - H20202015-04-01 - 2019-03-31 - 633595 - VALID, Beyond the Genetics of Addiction - ADDICTION - - EC:FP7:ERC2011-12-01 - 2017-05-31 - 284167 - VALID, Rise of scientific excellence and collaboration for implementing personalised medicine in Estonia - ePerMed - - H20202016-01-01 - 2018-12-31 - 692145 - VALID, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), 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), Università degli Studi di Ferrara = University of Ferrara (UniFE), Université de Lausanne = University of Lausanne (UNIL), Karl-Franzens-Universität Graz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Amsterdam UMC - Amsterdam University Medical Center, Nanyang Technological University [Singapour], Universität zu Lübeck = University of Lübeck [Lübeck], Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Université de Genève = University of Geneva (UNIGE), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), European Project: 633595,H2020,H2020-PHC-2014-two-stage,DYNAHEALTH(2015), European Project: 284167,EC:FP7:ERC,ERC-2011-StG_20101124,ADDICTION(2011), European Project: 692145,H2020,H2020-TWINN-2015,ePerMed(2016), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Functional Genomics, APH - Mental Health, Sociology and Social Gerontology, APH - Methodology, Hottenga, Jouke- Jan [0000-0002-5668-2368], Bouatia-Naji, Nabila [0000-0001-5424-2134], Jansen, Rick [0000-0002-3333-6737], Min, Josine L. [0000-0003-4456-9824], Faggian, Alessia [0000-0002-3799-9722], Bonnefond, Amélie [0000-0001-9976-3005], Isaacs, Aaron [0000-0001-5037-4834], Willems, Sara M. [0000-0002-6803-3007], Navarro, Pau [0000-0001-5576-8584], Jackson, Anne U. [0000-0002-9672-2547], Bielak, Lawrence F. [0000-0002-3443-8030], Saxena, Richa [0000-0003-2233-1065], Smith, Albert V. [0000-0003-1942-5845], Verweij, Niek [0000-0002-4303-7685], Goel, Anuj [0000-0003-2307-4021], Johnson, Paul C. D. [0000-0001-6663-7520], Strawbridge, Rona J. [0000-0001-8506-3585], Fall, Tove [0000-0003-2071-5866], Fraser, Ross M. [0000-0003-0488-2592], Kanoni, Stavroula [0000-0002-1691-9615], Giedraitis, Vilmantas [0000-0003-3423-2021], Kleber, Marcus E. [0000-0003-0663-7275], Müller-Nurasyid, Martina [0000-0003-3793-5910], Luan, Jian’an [0000-0003-3137-6337], Sanna, Serena [0000-0002-3768-1749], Nolte, Ilja M. [0000-0001-5047-4077], Zemunik, Tatijana [0000-0001-8120-2891], Kovacs, Peter [0000-0002-0290-5423], Wild, Sarah H. [0000-0001-7824-2569], McLachlan, Stela [0000-0003-0480-6143], Egan, Josephine [0000-0002-8945-0053], Hicks, Andrew A. [0000-0001-6320-0411], Thorand, Barbara [0000-0002-8416-6440], Hingorani, Aroon [0000-0001-8365-0081], Kivimaki, Mika [0000-0002-4699-5627], Koistinen, Heikki A. [0000-0001-7870-070X], Bakker, Stephan J. L. [0000-0003-3356-6791], Palmer, Colin N. A. [0000-0002-6415-6560], Jukema, J. Wouter [0000-0002-3246-8359], Sattar, Naveed [0000-0002-1604-2593], Snieder, Harold [0000-0003-1949-2298], Magnusson, Patrik K. [0000-0002-7315-7899], Blüher, Matthias [0000-0003-0208-2065], Wolffenbuttel, Bruce H. R. [0000-0001-9262-6921], Abecasis, Goncalo R. [0000-0003-1509-1825], Meigs, James B. [0000-0002-2439-2657], Wilson, James F. [0000-0001-5751-9178], Schwarz, Peter E. H. [0000-0001-6317-7880], Boehm, Bernhard O. [0000-0002-2706-7710], Metspalu, Andres [0000-0002-3718-796X], Deloukas, Panos [0000-0001-9251-070X], Körner, Antje [0000-0001-6001-0356], Wareham, Nicholas J. [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Männistö, Satu [0000-0002-8668-3046], Franks, Paul W. [0000-0002-0520-7604], Hayward, Caroline [0000-0002-9405-9550], Vitart, Veronique [0000-0002-4991-3797], Kaprio, Jaakko [0000-0002-3716-2455], Visvikis-Siest, Sophie [0000-0001-8104-8425], Altshuler, David [0000-0002-7250-4107], Rudan, Igor [0000-0001-6993-6884], van Duijn, Cornelia M. [0000-0002-2374-9204], Pramstaller, Peter P. [0000-0002-9831-8302], Boehnke, Michael [0000-0002-6442-7754], Frayling, Timothy M. [0000-0001-8362-2603], Peyser, Patricia A. [0000-0002-9717-8459], Harst, Pim van der [0000-0002-2713-686X], Smith, George Davey [0000-0002-1407-8314], Forouhi, Nita G. [0000-0002-5041-248X], Loos, Ruth J. F. [0000-0002-8532-5087], Salomaa, Veikko [0000-0001-7563-5324], Soranzo, Nicole [0000-0003-1095-3852], Boomsma, Dorret I. [0000-0002-7099-7972], Groop, Leif [0000-0002-0187-3263], Tuomi, Tiinamaija [0000-0002-8306-6202], Munroe, Patricia B. [0000-0002-4176-2947], Gudnason, Vilmundur [0000-0001-5696-0084], Lecoeur, Cecile [0000-0003-0075-6417], Jarvelin, Marjo-Riitta [0000-0002-2149-0630], Stefansson, Kari [0000-0003-1676-864X], Dermitzakis, Emmanouil T. [0000-0002-9302-6490], Lindgren, Cecilia M. [0000-0002-4903-9374], Froguel, Philippe [0000-0003-2972-0784], Kaakinen, Marika A. [0000-0002-9228-0462], Watanabe, Richard M. [0000-0003-1015-0531], Ingelsson, Erik [0000-0003-2256-6972], Dupuis, Josée [0000-0003-2871-3603], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Epidemiology, University Hospital Mannheim | Universitätsmedizin Mannheim, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Universität Leipzig, Universiteit Leiden, Universität Heidelberg [Heidelberg] = Heidelberg University, Karl-Franzens-Universität [Graz, Autriche], Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, APH - Digital Health, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Value, Affordability and Sustainability (VALUE), Cardiovascular Centre (CVC), Hottenga, Jouke-Jan [0000-0002-5668-2368], Min, Josine L [0000-0003-4456-9824], Willems, Sara M [0000-0002-6803-3007], Jackson, Anne U [0000-0002-9672-2547], Bielak, Lawrence F [0000-0002-3443-8030], Smith, Albert V [0000-0003-1942-5845], Johnson, Paul CD [0000-0001-6663-7520], Strawbridge, Rona J [0000-0001-8506-3585], Fraser, Ross M [0000-0003-0488-2592], Kleber, Marcus E [0000-0003-0663-7275], Luan, Jian'an [0000-0003-3137-6337], Nolte, Ilja M [0000-0001-5047-4077], Wild, Sarah H [0000-0001-7824-2569], Hicks, Andrew A [0000-0001-6320-0411], Koistinen, Heikki A [0000-0001-7870-070X], Bakker, Stephan JL [0000-0003-3356-6791], Palmer, Colin NA [0000-0002-6415-6560], Jukema, J Wouter [0000-0002-3246-8359], Magnusson, Patrik K [0000-0002-7315-7899], Wolffenbuttel, Bruce HR [0000-0001-9262-6921], Abecasis, Goncalo R [0000-0003-1509-1825], Meigs, James B [0000-0002-2439-2657], Wilson, James F [0000-0001-5751-9178], Schwarz, Peter EH [0000-0001-6317-7880], Boehm, Bernhard O [0000-0002-2706-7710], Wareham, Nicholas J [0000-0003-1422-2993], Franks, Paul W [0000-0002-0520-7604], van Duijn, Cornelia M [0000-0002-2374-9204], Pramstaller, Peter P [0000-0002-9831-8302], Frayling, Timothy M [0000-0001-8362-2603], Peyser, Patricia A [0000-0002-9717-8459], Forouhi, Nita G [0000-0002-5041-248X], Loos, Ruth JF [0000-0002-8532-5087], Boomsma, Dorret I [0000-0002-7099-7972], Munroe, Patricia B [0000-0002-4176-2947], Dermitzakis, Emmanouil T [0000-0002-9302-6490], Lindgren, Cecilia M [0000-0002-4903-9374], Kaakinen, Marika A [0000-0002-9228-0462], Watanabe, Richard M [0000-0003-1015-0531], Tampere University, Tays Research Services, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), Fysiologie, RS: FHML MaCSBio, and RS: Carim - B01 Blood proteins & engineering

Subjects
Male, Anorexia Nervosa, medicine.medical_treatment, 45/43, Insulin Resistance/genetics, SUSCEPTIBILITY, Quantitative trait, Impaired glucose tolerance, 0302 clinical medicine, Architecture, LS2_1, IMPUTATION, Insulin, ComputingMilieux_MISCELLANEOUS, Fasting, Publisher Correction, 3. Good health, [SDV] Life Sciences [q-bio], Kruppel-Like Transcription Factors/blood, Endokrinologi och diabetes, Science & Technology - Other Topics, Adult, Blood Glucose, European Continental Ancestry Group, Female, Gene Expression, Genetic Loci, Genome-Wide Association Study, Glucose Intolerance, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Kruppel-Like Transcription Factors, Middle Aged, Phenotype, Sex Characteristics, Sex Factors, Waist-Hip Ratio, Sex characteristics, medicine.medical_specialty, Science, 631/208/205/2138, Endocrinology and Diabetes, General Biochemistry, Genetics and Molecular Biology, White People, Gender-differences, 03 medical and health sciences, SDG 3 - Good Health and Well-being, 692/53/2421, GLYCEMIC TRAITS, GENOME-WIDE ASSOCIATION, Glycemic, GENDER-DIFFERENCES, Science & Technology, IDENTIFICATION, 692/699/2743/2815, Blood Glucose/metabolism, Diagnostic markers, medicine.disease, Anorexia Nervosa/blood, 030104 developmental biology, Endocrinology, Glucose, Insulin/blood, Anorexia Nervosa/ethnology, Anorexia Nervosa/genetics, Anorexia Nervosa/physiopathology, Fasting/blood, Glucose Intolerance/blood, Glucose Intolerance/ethnology, Glucose Intolerance/genetics, Glucose Intolerance/physiopathology, Insulin Receptor Substrate Proteins/blood, Insulin Receptor Substrate Proteins/genetics, Kruppel-Like Transcription Factors/genetics, 0301 basic medicine, Identification, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Genome-wide association studies, Waist–hip ratio, LS4_5, RISK, ARCHITECTURE, Multidisciplinary, article, Type 2 diabetes, Multidisciplinary Sciences, MENDELIAN RANDOMIZATION, Pre-diabetes, Medical Genetics, Risk, PATHOPHYSIOLOGY, 030209 endocrinology & metabolism, 3121 Internal medicine, 692/163/2743/137/773, NO, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Mendelian randomization, 631/208/480, Medicinsk genetik, business.industry, General Chemistry, Impaired fasting glucose, business
Abstract

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Published
2021
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30. A multicenter cross-sectional French study of the impact of COVID-19 on neuromuscular diseases

Author

Vincent Laugel, Karim Wahbi, Lucie Isoline Pisella, Rabab Debs, Sarah Souvannanorath, Martial Mallaret, Thierry Kuntzer, Sylvain Nollet, Jean-Christophe Antoine, Maud Michaud, Rocío-Nur Villar-Quiles, Aude-Marie Grapperon, Sandrine Segovia-Kueny, Pascal Laforêt, Céline Tard, EL-Hadi Hammouda, Géraldine Merret, Kévin Bigaut, Juliette Svahn, Laurent Kremer, Armelle Magot, Jean-Baptiste Noury, Guillemette Beaudonnet, Louise Debergé, Aleksandra Nadaj-Pakleza, Diane Friedman, Yann Péréon, Emmanuelle Salort-Campana, Pascal Cintas, Sara Fernandes, David H. Adams, Annamaria Molon, Fanny Duval, Anthony Behin, Shahram Attarian, Frédérique Audic, Jean-Philippe Camdessanché, Isabelle Desguerre, Tanya Stojkovic, Françoise Bouhour, Marion Masingue, Guilhem Solé, Caroline Espil-Taris, Savine Vicart, Jean-Baptiste Chanson, Assistance Publique - Hôpitaux de Marseille (APHM), Groupe hospitalier Pellegrin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Lille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital Bicêtre, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Henri Mondor [Créteil], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Lausanne University Hospital, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Necker - Enfants Malades [AP-HP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Association française contre les myopathies (AFM-Téléthon), Admin, Oskar, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Thérapie des maladies du muscle strié, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), 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 de Paris (UP), Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]

Subjects
medicine.medical_specialty, Cross-sectional study, Population, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Health care, medicine, Humans, Pharmacology (medical), Risk factor, education, Myopathy, Pandemics, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, SARS-CoV-2, Research, COVID-19, General Medicine, medicine.disease, Prognosis, Myasthenia gravis, 3. Good health, Neuromuscular diseases, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Background Due to their health condition, patients with neuromuscular diseases (NMD) are at greater risk of developing serious complications with COVID-19. The objective of this study was to analyze the prevalence of COVID-19 among NMD patients and the risk factors for its impact and severity during the first wave of the pandemic. Clinical data were collected from NMD-COVID-19 patients, between March 25, 2020 and May 11, 2020 in an anonymous survey carried out by expert physicians from the French Health Care Network Filnemus. Results Physicians reported 84 patients, including: 34 with myasthenia gravis, 27 with myopathy and 23 with neuropathy. COVID-19 had no effect on NMD for 48 (58%) patients and 48 (58%) patients developed low COVID-19 severity. COVID-19 caused the death of 9 (11%) NMD patients. Diabetic patients were at greater risk of dying. Patients with diabetes, hypertension or severe forms of NMD had a higher risk of developing a moderate or severe form of COVID-19. In our cohort, corticosteroids and other immunosuppressants were not significantly associated with higher COVID-19 severity for acquired NMD. Conclusion During this period, a small percentage of French NMD patients was affected by COVID-19 compared to the general French population and COVID-19 had a limited short-term effect on them. Diabetes, hypertension and a severe degree of NMD were identified as risk factors of unfavorable outcome following COVID-19. Conversely, in our cohort of patients with acquired NMD, corticosteroids or other immunosuppressants did not appear to be risk factors for more severe COVID-19.

Published
2021
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31. Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis

Author

John Mendy, Annette Erhart, Lamin Drammeh, Suzanne T. Anderson, Samba Ceesay, Jonathan R. Carapetis, Lamin E. S. Jaiteh, Umberto D'Alessandro, Mariana Mirabel, London School of Hygiene and Tropical Medicine (LSHTM), Evelina London Children's Hospital, Ministry of Health and Social Welfare [Banjul, The Gambia] (MOHSW), The University of Western Australia (UWA), 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 de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), and Malbec, Odile

Subjects
Male, Pediatrics, Time Factors, Heart disease, Clinical presentation, [SDV]Life Sciences [q-bio], Pilot Projects, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Case fatality rate, Secondary Prevention, 030212 general & internal medicine, Young adult, Child, Rheumatic heart disease, Mortality rate, Medical record, Echocardiography, Doppler, 3. Good health, Cardiac surgery, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Case review, Treatment Outcome, Echocardiography, Child, Preschool, Disease Progression, Female, Gambia, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Adolescent, Evolution, Penicillins, Risk Assessment, Medication Adherence, 03 medical and health sciences, Young Adult, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, business.industry, Research, medicine.disease, The Gambia, Heart failure, RC666-701, business, Penicillin prophylaxis
Abstract

Background Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. Methods All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. Results Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9; 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. Conclusion This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.

Published
2021
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32. EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy

Author

Marie Wislez, Marie-Ange Massiani, Nathalie Théou-Anton, Jacques Cadranel, Xavier Mignard, Boris Duchemann, Isabelle Monnet, Elizabeth Fabre, Sylvie Friard, Karen Leroy, Solenn Brosseau, Etienne Giroux-Leprieur, Samy Chelabi, Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), Centre Hospitalier Intercommunal de Créteil (CHIC), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Hôpital Foch [Suresnes], Hôpital Avicenne [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Unité pneumologie et oncologie thoracique [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Theranoscan [CHU Tenon] (GRC 4), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), 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), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), and Gestionnaire, Hal Sorbonne Université

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, EGFR, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, NSCLC, chemotherapy, survival, Article, exon 20 insertion, 03 medical and health sciences, Exon, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Medicine, Clinical efficacy, Lung cancer, education, RC254-282, 030304 developmental biology, 0303 health sciences, Chemotherapy, education.field_of_study, Lung, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, TKI, 3. Good health, respiratory tract diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Non small cell, business, Progressive disease
Abstract

Simple Summary EGFR exon 20 insertions are rare genetic alterations in non-small-cell lung cancers (NSCLCs) that are usually unresponsive to approved EGFR tyrosine kinase inhibitors (TKIs), but data is limited about this population. We aim to describe clinical features, survival, and response to chemotherapy and TKIs in this patient population. Abstract EGFR exon 20 insertions are rare genetic alterations in non-small-cell lung cancers (NSCLCs) that are usually unresponsive to approved EGFR tyrosine kinase inhibitors (TKIs). In this paper, we describe the clinical characteristics, efficacy of EFGR TKIs and chemotherapy, and resulting survival in this population. We retrospectively collected patients with EGFR exon 20 insertions (Exon20ins) from 11 French genetic platforms and paired them (1:2 ratio) with classic Exon 19/21 EGFR mutation patients (controls). Between 2012 and 2017, 35 Exon20ins patients were included. These patients were younger at diagnosis than the controls. All Exon20ins patients who were treated with first-line EGFR TKIs (n = 6) showed progressive disease as the best tumor response. There was no significant difference in the tumor response or the disease control rate with first-line platinum-based chemotherapy between the two groups. A trend towards shorter overall survival was observed in Exon20ins vs. controls (17 months (14—not reach(NR) 95% confidence interval(CI) vs. 29 months (17–NR 95%CI), p = 0.09), respectively. A significant heterogeneity in amino acid insertion in EGFR exon 20 was observed. EGFR exon 20 insertions are heterogeneous molecular alterations in NSCLC that are resistant to classic EGFR TKIs, which contraindicates their use as a first-line treatment.

Published
2021
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33. Long-term mortality after ST-elevation myocardial infarction in the reperfusion and modern secondary prevention therapy era according to coronary artery disease extent: The FAST-MI registries

Author

Jean Ferrières, Thibault Lhermusier, O. Nallet, Thibaud Brunet, Jean-Noël Labèque, Etienne Puymirat, Laurent Bonello, Fast-Mi investigators, Victoria Tea, Romain Gallet, Nicolas Danchin, Chekrallah Chamandi, Francois Schiele, Franck Albert, Tabassome Simon, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École nationale vétérinaire - Alfort (ENVA), Centre Hospitalier de la Côte Basque (CHCB), Hôpitaux de Chartres [Chartres], European Atherosclerosis Society [Göteborg, Sweden] (EAS), Department of Cardiology B and Epidemiology, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Coronary Artery Disease, Disease, Acute myocardial infarction, Coronary artery disease, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, St elevation myocardial infarction, Internal medicine, Secondary Prevention, medicine, Humans, Registries, Myocardial infarction, Aged, Secondary prevention, Multivessel disease, business.industry, Hazard ratio, Primary percutaneous coronary intervention, Percutaneous coronary intervention, General Medicine, Middle Aged, medicine.disease, Confidence interval, Treatment Outcome, ST-elevation myocardial infarction, Reperfusion, Cardiology, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Background. - Historical cohorts have shown extent of coronary artery disease to be a predictor of poorer outcomes in ST-segment elevation myocardial infarction. However, contemporary data in the era of reperfusion and modern secondary prevention therapy are lacking.Aim. - To compare 3-year survival in patients with ST-segment elevation myocardial infarction with multivessel disease versus those with single-vessel disease.Methods. - Using data from the FAST-MI 2005, 2010 and 2015 registries, three nationwide French surveys, we included all patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention within 24 hours of symptom onset. Baseline characteristics, management and 3-year all-cause mortality were analysed according to coronary status (single-, two- and three-vessel disease).Results. - Among 3907 patients (mean age 62.4 +/- 13.7 years; 75.9% male), patients with multivessel disease (two- or three-vessel disease) accounted for 47.9%; overall, they were older, with higher cardiovascular risk profiles. In a multivariable adjusted Cox proportional hazard regression model, only patients with three-vessel disease had a higher rate of mortality at 3 years compared with those with single-vessel disease (hazard ratio 1.52, 95% confidence interval 1.68-2.26; P < 0.001). Finally, patients with multivessel disease with complete myocardial revascularization before discharge had a similar prognosis to patients with single-vessel disease (hazard ratio 1.17, 95% confidence interval 0.84-1.64; P = 0.35).Conclusions. - Multivessel disease still represents an important proportion of patients with ST-segment elevation myocardial infarction. Although three-vessel disease is associated with higher 3-year mortality, patients with multivessel disease and complete myocardial revascularization in the contemporary era have a 3-year risk of death similar to that in patients with single-vessel disease.

Published
2021
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34. Management of antithrombotics in situations with a gap in evidence: A national French survey focusing on patients with coronary artery disease and atrial fibrillation

Author

Eloi Marijon, Nicolas Danchin, Guillaume Cayla, Marjorie Richardson, Maxime Guenoun, Laurent Bonello, Sandro Ninni, Guillaume Schurtz, Serge Cohen, Franck Albert, Nicolas Lamblin, Gilles Lemesle, Christophe Bauters, Laurent Fauchier, 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), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mediterranean Association for Research and Studies in Cardiology (MARS cardio), Hôpital Nord [CHU - APHM], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Européen [Fondation Ambroise Paré - Marseille], Hôpitaux de Chartres [Chartres], CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, medicine.medical_specialty, Oral anticoagulation, Coronary Artery Disease, Scientific evidence, Coronary artery disease, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Fibrinolytic Agents, Antithrombotic, Atrial Fibrillation, medicine, Humans, In patient, cardiovascular diseases, business.industry, Antiplatelet therapy, Anticoagulants, Survey Evidence-based medicine, Atrial fibrillation, Mean age, Evidence-based medicine, medicine.disease, Homogeneous, Family medicine, Female, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Background: If several randomized studies allowed to better apprehend what should be the best antithrombotic strategy in patients with concomitant coronary artery disease (CAD) and atrial fibrillation (AF), there are still several clinical situations with a gap of evidence.Methods: We conducted a national French survey in September-October 2020 among cardiologists in order to assess what are daily practices regarding the antithrombotic management in several specific clinical settings where no or little scientific evidence is available. The questionnaires were built by a committee of 6 cardiologists routinely involved in the field of CAD and/or AF.Results: Among the 6388 French cardiologists, 483 (7.6%) cardiologists participated to the survey. The rate of participation was rather homogeneous across the country. The mean age of participants was 48 +/- 12.7. There were 134 women (27.7%) and 349 men. Altogether, 181 (37.5%) cardiologists worked in private, 153 (31.7%) in non-universitary public and 83 (17.2%) in universitary public centers. The remaining had shared activity. Among the participants, 150 were interventional (coronary) cardiologists (31.1%). Others were general cardiologists (n = 229), specialists in the field of rhythmology (n = 43), heart failure (n = 17) or imaging (n = 44). The survey consisted of 10 questions pertaining to 2 virtual clinical scenarios.Conclusions: The present survey is an illustration of how therapeutic decisions may vary in such situations with little or no scientific evidence. Such surveys may help experts to build consensus (answers with little variability) and to target the need for future trials and more research (answers with a lot of variability).

Published
2021
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35. Somatic mutations in adrenals from patients with primary aldosteronism not cured after adrenalectomy suggest common pathogenic mechanisms between unilateral and bilateral disease

Author

Kelly De Sousa, Laurence Amar, Fábio L. Fernandes-Rosa, Sheerazed Boulkroun, Inès Hacini, Maria-Christina Zennaro, Tchao Meatchi, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Fernandes Rosa, Fabio

Subjects
Adult, Male, medicine.medical_specialty, Adenoma, Physiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adrenal Gland Diseases, Context (language use), [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Gastroenterology, Germline, chemistry.chemical_compound, Endocrinology, Primary aldosteronism, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Adrenal Glands, Hyperaldosteronism, Internal Medicine, medicine, Humans, Steroid 11-beta-hydroxylase, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, Aldosterone, business.industry, Adrenalectomy, General Medicine, Middle Aged, Hyperplasia, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, chemistry, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Objective Primary aldosteronism (PA) is the most common form of secondary and curable hypertension. Different germline and somatic mutations are found in aldosterone-producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with APA; however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH. The objective of this study was to analyze clinical data of patients with APA without biochemical success after adrenalectomy as well as the histological and genetic characteristics of their adrenal glands. Design and methods Clinical data of 12 patients with partial and absent biochemical cure were compared to those from 39 PA patients with hormonal cure after surgery. Histological, morphological, and genetic characterization of the adrenals was carried out by CYP11B2 and CYP11B1 immunostaining and by CYP11B2-guided NGS. Results Patients with absent hormonal cure displayed a longer duration of arterial hypertension and lower lateralization index of aldosterone production. In ten patients, APAs expressing CYP11B2 were identified. No difference in histological and morphological characteristics was observed between patients with or without a hormonal cure. Somatic mutations in APA driver genes were identified in all CYP11B2 positive APAs; CACNA1D mutations were the most frequent genetic abnormality. Conclusions Patients with partial and absent biochemical cure were diagnosed later and exhibited a lower lateralization index of aldosterone production, suggesting asymmetric aldosterone production in the context of BAH. Somatic mutations in adrenal glands from those patients indicate common mechanisms underlying BAH and APA.

Published
2021
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36. Thrombus of the Aorta and SARS-CoV-2 Infection: Cause or Trigger?

Author

Rida El Ayoubi, Lina Khider, David M. Smadja, Guillaume Goudot, Paul Achouh, Tristan Mirault, Nicolas Gendron, Andréanne Durivage, Emmanuel Messas, Mourad Amrane, Alain Bel, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hématologie et Laboratoire de Recherches Biochirugicales [Fondation Carpentier] (SHLRB), 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), and Goudot, Guillaume

Subjects
Aortic arch, medicine.medical_specialty, [SDV]Life Sciences [q-bio], aortic arch, Cardiovascular Medicine, endothelial dysfunction, medicine.artery, Internal medicine, medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Thrombus, Endothelial dysfunction, Stroke, Original Research, Aorta, Cerebral infarction, business.industry, Fibrous cap, COVID-19, arterial thrombus, medicine.disease, Thrombosis, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, RC666-701, plaque erosion, Cardiology, cardiovascular system, Cardiology and Cardiovascular Medicine, business
Abstract

Objective: Coronavirus disease 19 is a well-established cause of rare arterial thrombosis. Nevertheless, the exact mechanism of arterial thrombosis remains to be elucidated. We herein report the case of a large floating thrombus of the aortic arch, its surgical management and histological analysis.Case: A 65-year-old patient presented to the emergency department with a suspected stroke. He was non-smoker, but presented cardiovascular risk factors, namely hypertension, type 2 diabetes and hyperlipidaemia. A computed tomography of the aorta revealed a large floating thrombus of the aortic arch, at the base of the brachiocephalic trunk, suspected to be the etiology of stroke. Therapeutic anticoagulation was immediately started. The decision was made to perform an open aortic replacement surgery because of the symptomatic thromboembolic event with recent cerebral infarction and the potential harmfulness of the thrombus due to its size. A mobile thrombus was observed at the base of the brachiocephalic trunk by echocardiography. It was attached to a small area of the upper aortic wall and had an irregular surface. Histology revealed a platelet-rich thrombus lying on an aortic atherosclerotic plaque without pronounced inflammation. No plaque ulceration was present but endothelial cell desquamation was observed consistent with plaque erosion.Conclusion: In our case, there was a thrombus lying on an atherosclerotic plaque with intact thick fibrous cap, but associated with a plaque erosion mechanism. The thrombus formation appeared more likely to relate to a very localized endothelial injury.

Published
2021
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37. Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia

Author

Anne-Sophie Jannot, Michel Azizi, David Lebeaux, Olivier Sanchez, Jean-Luc Diehl, Helena Pereira, Marine Livrozet, Nihar Masurkar, Sébastien Czernichow, Antoine Fayol, Gilles Châtellier, Sophie-Rym Hamada, Jean-Benoit Arlet, Geoffroy Volle, Caroline Hauw, Jean-Baptiste Carves, Claire Carette, Tristan Mirault, Bernard Cholley, Benjamin Planquette, Jean-Sébastien Hulot, Jannot, Anne-Sophie, 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), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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), Université Paris Cité (UPCité), 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 Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), 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)-École pratique des hautes études (EPHE), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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)-École Pratique des Hautes Études (EPHE), and Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140)

Subjects
cardiovascular risk factors, medicine.medical_specialty, obesity, hypertension, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], INFLUENZA PNEUMONIA, Article, Internal medicine, medicine, COPD, business.industry, Incidence (epidemiology), Cancer, COVID-19, General Medicine, medicine.disease, Obesity, Icu admission, respiratory tract diseases, [SDV] Life Sciences [q-bio], Pneumonia, Medicine, seasonal influenza, business
Abstract

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25, 95% CI 1.24–4.09, p = 0.0076) and receive diuretics (adjOR: 2.13, 95% CI 1.12–4.03, p = 0.021) but were less likely to be smokers (adjOR: 0.40, 95% CI 0.24–0.64, p = 0.0002), have COPD (adjOR: 0.25, 95% CI 0.11–0.56, p = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32–0.91, p = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% p &lt, 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.

Published
2021
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38. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author

Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesus, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G., Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L., Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Mehlal Sedkaoui, Souad, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Bigio, Benedetta, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Seeleuthner, Yoann, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Alkhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. 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Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, THORN, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Troya, Jesús, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, 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Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, De Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, 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Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Alavoine, Loubna, Behillil, Sylvie, Burdet, Charles, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geijtenbeek, Suzanne Geerlings Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos, Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés A., Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein S., Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Milner, Joshua D., Mironska, Kristina, Ng, Lisa F.P., Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., von Bernuth, Horst, Zawadzki, Pawel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Le Got, Stéphane, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Hôpital Avicenne [AP-HP], 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), 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], Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospices Civils de Lyon (HCL), 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), Grand Hôpital de l'Est Francilien (GHEF), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), 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), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Edouard Herriot [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], 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 Paris Cité (UPCité), 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), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, Howard Hughes Medical Institute, Rockefeller University, European Commission, Jeffrey Modell Foundation, Université de Bordeaux, Meath Foundation, National Human Genome Research Institute, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation du Souffle, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, St. Giles Foundation, Ministère des Solidarités et de la Santé, Sorbonne Université, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Meyer Foundation, Fondation de France, National Cancer Institute, European Regional Development Fund, Fundación DISA, Ministero della Salute, ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: IdEx Bordeaux (ANR-10-IDEX- 003-02), Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesu, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bonradenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Vandreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Members of the The Milieu Intérieur Consortium: Laurent Abel1 , Andres Alcover2 , Hugues Aschard2 , Philippe Bousso2 , Nollaig Bourke3 , Petter Brodin4 , Pierre Bruhns2 , Nadine Cerf-Bensussan5 , Ana Cumano2 , Christophe D’Enfert2 , Ludovic Deriano2 , Marie-Agnès Dillies2 , James Di Santo2 , Françoise Dromer2 , Gérard Eberl2 , Jost Enninga2 , Jacques Fellay6 , Ivo Gomperts-Boneca2 , Milena Hasan2 , Gunilla Karlsson Hedestam4 , Serge Hercberg7 , Molly A. Ingersoll2 , Olivier Lantz8 , Rose Anne Kenny3 , Mickaël Ménager5 , Frédérique Michel2 , Hugo Mouquet2 , Cliona O’Farrelly3 , Etienne Patin2 , Sandra Pellegrini2 , Antonio Rausell5 , Frédéric Rieux-Laucat5 , Lars Rogge2 , Magnus Fontes9 , Anavaj Sakuntabhai2 , Olivier Schwartz2 , Benno Schwikowski2 , Spencer Shorte2 , Frédéric Tangy2 , Antoine Toubert10 , Mathilde Touvier12 , Marie-Noëlle Ungeheuer2 , Christophe Zimmer2 , Matthew L. Albert11 , Darragh Duffy2 , Lluis Quintana-Murc, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Ministère des Solidarités et de la Santé (France), National Health and Medical Research Council (Australia), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Michailidis, Eleftherios, García-Prat, Marina, Paul, Stephanie, Metz, Christine N., Barreiros, Lucila, Domínguez-Garrido, Elena, Vidigal, Mateus, Beek, Diederik van der, Stepanovskyy, Yuriy, Tangye, Stuart G., Quintana-Murci, Lluis, Kan, Nelli, Nussenzweig, Michel C., Baris, Hagit N., Dyer, Adam, Bourke, Nollaig, Vinh, Donald C., Spaan, András N., Fellay, Jacques, Mane, Shrikant M., Anderson, MarK S., Andreakos, Evangelos, Haljasmägi, Liis, Mogensen, Trine, Lamballerie, Xavier de, Soler-Palacín, Pere, Martínez-Picado, Javier, Gregersen, Peter K., Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Prost, Nicolas de, Amador-Borrero, Blanco, Troya, Jesús, Rivière, Jacques G., Gentile, Stephanie, Rosen, Lindsey B., Tharaux, Pierre-Louis, Stépanian, Alain, Mégarbane, Bruno, Heath, James R., Franco, José Luis, Anaya, Juan Manuel, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Velez, Marcela, Planas, Anna M., Nussbaum, Robert, Bousfiha, Ahmed Aziz, Ramírez-Santana, Carolina, Intensive care medicine, Internal medicine, AII - Infectious diseases, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, Radiology and nuclear medicine, AMS - Rehabilitation & Development, VU University medical center, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anesthesiology, APH - Quality of Care, ACS - Heart failure & arrhythmias, Özçelik, Tayfun, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center, Admin, Oskar, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques 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Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Megarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Coulibaly, B, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Nussbaum, R, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de 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Marseglia, G.L., Batten, I., Reddy, C., McElheron, M., Noonan, C., Connolly, E., Fallon, A., Storgaard, M., Jørgensen, S., Erikstrup, C., Pedersen, O.B., Sørensen, E., Mikkelsen, S., Dinh, K.M., Larsen, MAH, Paulsen, I.W., Von Stemann, J.H., Hansen, M.B., Ostrowski, S.R., Townsend, L., Cheallaigh, C.N., Bergin, C., Martin-Loeches, I., Dunne, J., Conlon, N., Bourke, N., O'Farrelly, C., Abel, L., Allavena, C., Andrejak, C., Angoulvant, F., Azoulay, C., Bachelet, D., Bartoli, M., Basmaci, R., Behilill, S., Beluze, M., Benech, N., Benkerrou, D., Bhavsar, K., Bitker, L., Bouadma, L., Bouscambert-Duchamp, M., Paz, P.C., Cervantes-Gonzalez, M., Chair, A., Chirouze, C., Coelho, A., Cordel, H., Couffignal, C., Couffin-Cadiergues, S., d'Ortenzio, E., De Montmollin, E., Debard, A., Debray, M.P., Deplanque, D., Descamps, D., Desvallée, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V., Epaulard, O., Esperou, H., Esposito-Farese, M., Etienne, M., Garot, D., Gault, 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Briseño-Roa, L., Gribouval, O., Pelet, A., Alcover, A., Aschard, H., Bousso, P., Brodin, P., Bruhns, P., Cerf-Bensussan, N., Cumano, A., D'Enfert, C., Deriano, L., Dillies, M.A., Di Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hedestam, G.K., Hercberg, S., Ingersoll, M.A., Lantz, O., Kenny, R.A., Ménager, M., Michel, F., Patin, E., Rausell, A., Rieux-Laucat, F., Rogge, L., Fontes, M., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Zimmer, C., Albert, M.L., Duffy, D., Quintana-Murci, L., Alavoine, L., Behillil, S., Burdet, C., Charpentier, C., Dechanet, A., Ecobichon, J.L., Frezouls, W., Houhou, N., Lehacaut, J., Manchon, P., Nouroudine, M., Quintin, C., Thy, M., van der Werf, S., Vignali, V., Chahine, A., Waucquier, N., Migaud, M.C., Djossou, F., Mergeay-Fabre, M., Lucarelli, A., Demar, M., Bruneau, L., Gérardin, P., Maillot, A., Payet, C., Laviolle, B., Paris, C., Desille-Dugast, M., Fouchard, J., Pistone, T., Perreau, P., Gissot, V., Le Goas, C., Montagne, S., Richard, L., Bouiller, K., Desmarets, M., Meunier, A., Lefévre, B., Jeulin, H., Legrand, K., Lomazzi, S., Tardy, B., Gagneux-Brunon, A., Bertholon, F., Botelho-Nevers, E., Kouakam, C., Leturque, N., Roufai, L., Amat, K., Espérou, H., Hendou, S., van Agtmael, M., Algera, A.G., Appelman, B., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bonta, P., Bos, L., Botta, M., de Brabander, J., de Bree, G., de Bruin, S., Buis, DTP, Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Dijkstra, M., Dongelmans, D.A., Dujardin, RWG, Elbers, P., Fleuren, L., Geijtenbeek, SGT, Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., Lim, EHT, van Mourik, N., Nellen, J., Nossent, E.J., Paulus, F., Peters, E., Pina-Fuentes, DAI, van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., de Rotte, MCFJ, Schinkel, M., Schultz, M.J., Schrauwen, FAP, Schuurmans, A., Schuurmans, J., Sigaloff, K., Slim, M.A., Smeele, P., Smit, M., Stijnis, C.S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A.M., Tuinman, P.R., van der Valk, M., Veelo, D., Volleman, C., de Vries, H., Vught, L.A., van Vugt, M., Wouters, D., Zwinderman, AHK, Brouwer, M.C., Wiersinga, W.J., Vlaar, APJ, van de Beek, D., Al-Muhsen, S., Al-Mulla, F., Anderson, M.S., Andreakos, E., Arias, A.A., Biggs, C.M., Bogunovic, D., Bolze, A., Bryceson, Y., Bustamante, C.D., Butte, M.J., Chakravorty, S., Christodoulou, J., Condino-Neto, A., Constantinescu, S.N., Cooper, M.A., Desai, M., Drolet, B.A., El Baghdadi, J., Espinosa-Padilla, S., Franco, J.L., Froidure, A., Gregersen, P.K., Hagin, D., Heath, J.R., Henrickson, S.E., Hsieh, EWY, Husebye, E.S., Imai, K., Itan, Y., Jarvis, E.D., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Maródi, L., Milner, J.D., Mironska, K., Mogensen, T.H., Morio, T., Ng, LFP, Notarangelo, L.D., Novelli, A., Novelli, G., Okada, S., Ozcelik, T., Planas, A.M., Prando, C., Pujol, A., Renia, L., Resnick, I., Rodríguez-Gallego, C., Sancho-Shimizu, V., Seppänen, MRJ, Slaby, O., Snow, A.L., Spaan, A.N., Tancevski, I., Tangye, S.G., Abou Tayoun, A., Ramaswamy, S., Turvey, S.E., Uddin, KMF, Uddin, M.J., Vinh, D.C., von Bernuth, H., Zawadzki, P., Su, H.C., Casanova, J.L., Nadif, R., Goldberg, M., Ozguler, A., Henny, J., Lemonnier, S., Coeuret-Pellicer, M., Le Got, S., Zins, M., Tzourio, C., Debette, S., Dufouil, C., Soumaré, A., Lachaize, M., Fievet, N., Flaig, A., Martin, F., Bonneaudeau, B., Cannet, D., Gallian, P., Jeanne, M., Perroquin, M., Hamzeh-Cognasse, H., Bastard, Paul [0000-0002-5926-8437], Gervais, Adrian [0000-0002-1083-5787], Le Voyer, Tom [0000-0002-0630-8626], Rosain, Jérémie [0000-0002-2822-161X], Manry, Jérémy [0000-0001-5998-2051], Michailidis, Eleftherios [0000-0002-9907-4346], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Eto, Shohei [0000-0002-2885-7490], García-Prat, Marina [0000-0001-5387-1908], Bizien, Lucy [0000-0001-9163-9122], Parra-Martínez, Alba [0000-0002-9564-8912], Dorgham, Karim [0000-0001-9539-3203], Alkhater, Suzan [0000-0001-7315-6581], Rigo-Bonnin, Raúl [0000-0001-5511-074X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Ostrowski, Sisse Rye [0000-0001-5288-3851], Condino-Neto, Antonio [0000-0002-1069-3117], Prando, Carolina [0000-0002-9570-9770], Spaan, András N. [0000-0001-5981-7259], Gilardin, Laurent [0000-0001-9212-0859], Yang, Rui [0000-0003-4427-2158], Fellay, Jacques [0000-0002-8240-939X], Bilguvar, Kaya [0000-0002-7313-7652], Mane, Shrikant M. [0000-0002-3267-5139], Anderson, MarK S. [0000-0002-3093-4758], Boisson, Bertrand [0000-0001-5240-3555], Béziat, Vivien [0000-0002-4020-824X], Andreakos, Evangelos [0000-0001-5536-1661], Hermine, Olivier [0000-0003-2574-3874], Pujol, Aurora [0000-0002-9606-0600], Peterson, Pärt [0000-0001-6755-791X], Haljasmägi, Liis [0000-0001-7162-9808], Mogensen, Trine [0000-0002-1853-9704], Lamballerie, Xavier de [0000-0001-7895-2720], Zins, Marie [0000-0002-4540-4282], Soler-Palacín, Pere [0000-0002-0346-5570], Colobran, Roger [0000-0002-5964-536X], Gorochov, Guy [0000-0003-2097-9677], Solanich, Xavier [0000-0002-2572-2187], Susen, Sophie [0000-0001-5953-163X], Martínez-Picado, Javier [0000-0002-4916-2129], Gregersen, Peter K. [0000-0003-1613-1518], Migaud, Mélanie [0000-0003-3062-1214], Piemonti, Lorenzo [0000-0002-2172-2198], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Notarangelo, Luigi D. [0000-0002-8335-0262], Su, Helen C. [0000-0002-5582-9110], Kisand, Kai [0000-0002-5426-4648], Okada, Satoshi [0000-0002-4622-5657], Puel, Anne [0000-0003-2603-0323], Jouanguy, Emmanuelle [0000-0002-7358-9157], Tiberghien, Pierre [0000-0002-9310-8322], Zhang, Qian [0000-0002-9040-3289], Särekannu, Karita [0000-0002-5984-668X], Cobat, Aurélie [0000-0001-7209-6257], Abel, Laurent [0000-0001-7016-6493], Casanova, Jean-Laurent [0000-0002-7782-4169], Prost, Nicolas de [0000-0002-4833-4320], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Luyt, Charles-Edouard [0000-0001-7424-2705], Amador-Borrero, Blanco [0000-0001-6170-8721], Poissy, Julien [0000-0001-6017-5353], Richard, Pascale [0000-0003-1864-3824], Cognasse, Fabrice [0000-0001-8041-928X], Troya, Jesús [0000-0001-7323-114X], Trouillet-Assant, Sophie [0000-0001-6439-4705], Belot, Alexandre [0000-0003-4902-5332], Saker, Kahina [0000-0001-8825-5400], Rivière, Jacques G. [0000-0003-1055-2063], Gentile, Stephanie [0000-0003-3858-9503], Rosen, Lindsey B. [0000-0001-5894-3878], Shaw, Elana [0000-0001-9265-8026], Dalmau, David [0000-0003-1936-478X], Tharaux, Pierre-Louis [0000-0002-6062-5905], Stépanian, Alain [0000-0002-2942-0901], Mégarbane, Bruno [0000-0002-2522-2764], Triantafyllia, Vasiliki [0000-0001-5832-4014], Fekkar, Arnaud [0000-0001-9954-075X], Heath, James R. [0000-0001-5356-4385], Franco, José Luis [0000-0001-5664-6415], Anaya, Juan Manuel [0000-0002-6444-1249], Imberti, Luisa[0000-0002-2075-8391], Bonfanti, Paolo [0000-0001-7289-8823], Castagnoli, Riccardo [0000-0003-0029-9383], Snow, Andrew L. [0000-0002-8728-6691], Holland, Steven M. [0000-0003-3207-5464], Biggs, Catherine M. [0000-0002-4363-2660], Moncada-Velez, Marcela [0000-0002-3073-5345], Arias, Andrés Augusto [0000-0002-9478-8403], Lorenzo, Lazaro [0000-0001-6648-8684], Boucherit, Soraya [0000-0002-8819-7594], Anglicheau, Dany [0000-0001-5793-6174], Planas, Anna M. [0000-0002-6147-1880], Haerynck, Filomeen [0000-0001-9161-7361], Duvlis, Sotirija [0000-0001-8587-7386], Nussbaum, Robert [0000-0003-3445-8880], Bousfiha, Ahmed Aziz [0000-0002-5011-9873], El Bakkouri, Jalila [0000-0003-2303-3369], Ramírez-Santana, Carolina [0000-0003-2137-4899], Paul, Stephanie [0000-0002-8830-4273], Pan-Hammarström, Qiang [0000-0003-1990-8804], Hammarström, Lennart [0000-0002-8635-9609], Dupont, Annabelle [0000-0002-1554-9931], Kurolap, Alina [0000-0002-7005-3621], Metz, Christine N. [0000-0002-1013-1691], Aiuti, Alessandro [0000-0002-5398-1717], Casari, Giorgio [0000-0002-0115-8980], Lampasona, Vito [0000-0001-5162-8445], Ciceri, Fabio [0000-0003-0873-0123], Barreiros, Lucila [0000-0002-9818-2345], Domínguez-Garrido, Elena [0000-0002-2066-0511], Vidigal, Mateus [0000-0002-8895-652X], Zatz, Mayana [0000-0003-3970-8025], Beek, Diederik van der [0000-0002-4571-044X], Stepanovskyy, Yuriy [0000-0001-6339-5490], Boyarchuk, Oksana [0000-0002-1234-0040], Nukui, Yoko [0000-0002-6123-5212], Vidaur, Loreto [0000-0002-6720-4900], Tangye, Stuart G. [0000-0002-5360-5180], Burrel, Sonia [0000-0002-7783-2601], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Klocperk, Adam [0000-0002-1526-4557], Kan, Nelli [0000-0003-3564-6496], Shcherbina, Anna [0000-0002-3113-4939], Lau, Yu-Lung [0000-0002-4780-0289], Leung, Daniel [0000-0002-9360-6233], Coulongeat, Matthieu [0000-0003-1986-3546], Marlet, Julien [0000-0002-8645-8703], Koning, Rutger [0000-0003-3128-5072], Reyes, Luis Felipe [0000-0003-1172-6539], Venet, Fabienne [0000-0003-0462-4235], Monneret, Guillaume [0000-0002-9961-5739], Nussenzweig, Michel C. [0000-0003-0592-8564], Baris, Hagit N. [0000-0003-4065-7560], Hagin, David [0000-0003-2702-1031], Wauters, Joost [0000-0002-5983-3897], Meyts, Isabelle [0000-0003-1214-0302], Dyer, Adam [0000-0003-1356-510X], Bourke, Nollaig [0000-0003-4313-6859], Halwani, Rabih [0000-0002-6516-7771], and Sharif-Askari, Narjes Saheb [0000-0003-0482-6777]

Subjects
Interferon Type I/immunology, AUTOIMMUNITY, [SDV]Life Sciences [q-bio], Interferó, Gastroenterology, COVID-19 (Malaltia), Immunoglobulin G, Basic medicine, 0302 clinical medicine, Medicine and Health Sciences, 80 and over, Immunologia, Young adult, Child, Neutralizing, MYASTHENIA-GRAVIS PATIENTS, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, biology, General Medicine, Middle Aged, 3. Good health, COVID-19/immunology, Settore MED/03, 030220 oncology & carcinogenesis, Child, Preschool, Interferon Type I, Antibody, medicine.symptom, INTERFERON, Adult, medicine.medical_specialty, Adolescent, Critical Illness, Immunology, Population, Aged, Antibodies, Neutralizing, Autoantibodies, COVID-19, Case-Control Studies, Humans, Infant, Infant, Newborn, Interferon-alpha, Young Adult, Alpha interferon, Immunoglobulins, IMMUNITY, Asymptomatic, PATIENT, 03 medical and health sciences, Internal medicine, medicine, Preschool, education, Antibodies, Neutralizing/blood, HOMENS, 030304 developmental biology, ANTINUCLEAR, business.industry, Autoantibody, Case-control study, Antibodies, Neutralizing/immunology, Autoantibodies/blood, Autoantibodies/immunology, COVID-19/mortality, Immunoglobulin G/blood, Immunoglobulin G/immunology, Interferon-alpha/immunology, Newborn, DISTINCT FUNCTIONS, ALPHA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Immunoglobulines
Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University of Paris. P.B. was supported by the FRM (EA20170638020). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation

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2021
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39. Maintien de la perfusion corticale par la sphingosine 1-phosphate lors de la phase aiguë de l’accident vasculaire cérébral ischémique

Author

Anja Nitzsche, Ammar Benarab, Eric Camerer, Marine Poittevin, Philippe Bonnin, 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 de Paris (UP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences, EDP, 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], General Medicine, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Cerebral cortex, Internal medicine, Ischemic stroke, medicine, Cardiology, Sphingosine-1-phosphate, business, Perfusion, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021
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40. A French cohort for assessing COVID-19 vaccine responses in specific populations

Author

Benoit Barrou, David-Axel Laplaud, Odile Launay, Stéphanie Nguyen, Jean-Daniel Lelièvre, Jean-Yves Blay, Benjamin Terrier, Martine Laville, Anne Thiebaut, Jacques Morel, Xavier de Lamballerie, Béatrice Parfait, Bruno Laviolle, Jean-François Viallard, Linda Wittkop, François Vrtovsnik, Jean-Philippe Spano, Paul Loubet, Maryvonne Hourmant, Marie Lachâtre, Eric Tartour, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], 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), 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), Hôpital Cochin [AP-HP], 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), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Association Francaise d'Etudes et de Recherches sur l'Obesite, Partenaires INRAE, Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS00001S, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Service d'Urologie [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), HAL-SU, Gestionnaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université de Montpellier (UM), Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), Université de Paris (UP), Institut de Recherche pour le Développement (IRD), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Virulence Bactérienne et Infections Chroniques (VBIC), 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), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Grenoble, Université Paris Diderot - Paris 7 (UPD7), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- 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)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Adolescent, Coronavirus disease 2019 (COVID-19), Epidemiology, [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Cohort Studies, Immunocompromised Host, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Young adult, ComputingMilieux_MISCELLANEOUS, Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, Antibodies, Neutralizing, Virology, 3. Good health, Viral infection, 030220 oncology & carcinogenesis, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract

International audience; No abstract available

Published
2021
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41. Profound bilateral deafness complicating aortic arch surgery

Author

Elisabeth Mamelle, Fabienne Carré, Suzanne Ferrier, Paul Achouh, 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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 de Paris (UP), Unité d’Otologie, implants auditifs et chirurgie de la base du crâne [CHU Pitié-Salpêtrière], Service d'Oto-Rhino-Laryngologie [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 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), Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Male, Aortic arch, Elephant trunks, Aorta, Thoracic, Case Reports, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, law, MESH: Cochlea, Frozen elephant trunk, MESH: Aneurysm, Dissecting, MESH: Middle Aged, Cardiopulmonary bypass, Middle Aged, Cochlea, Cardiac surgery, MESH: Aortic Aneurysm, Thoracic, Circulatory arrest, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Presentation (obstetrics), medicine.symptom, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Hearing loss, MESH: Aorta, Thoracic, Bilateral Deafness, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Hearing Loss, Bilateral, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.artery, otorhinolaryngologic diseases, medicine, Humans, MESH: Humans, Aortic Aneurysm, Thoracic, business.industry, MESH: Blood Vessel Prosthesis Implantation, MESH: Hearing Loss, Bilateral, MESH: Male, Surgery, Aortic Dissection, 030228 respiratory system, Bilateral deafness, Complication, business
Abstract

Hearing loss is a rare complication of cardiac surgery; bilateral profound deafness has never been reported in this setting. A 45-year-old male presented with profound bilateral sudden deafness following arch surgery and frozen elephant trunk. Patient’s presentation, surgery details and aetiological mechanisms are discussed.

Published
2020
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42. The balance of thrombosis and hemorrhage in STEMI patients with or without associated cardiac arrest: An observational study

Author

Driss Laghlam, Fabien Picard, Marine Diefenbronn, Alain Cariou, Olivier Varenne, Jean-François Llitjos, Gabriel Seret, Anastasia Sokoloff, Florence Dumas, CCSD, Accord Elsevier, 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), and 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 de Paris (UP)

Subjects
Acute coronary syndrome, medicine.medical_specialty, Stent thrombosis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030204 cardiovascular system & hematology, Emergency Nursing, Cardiac-arrest, 03 medical and health sciences, 0302 clinical medicine, Angioplasty, Internal medicine, medicine, cardiovascular diseases, Myocardial infarction, Prospective cohort study, business.industry, Incidence (epidemiology), Bleeding, 030208 emergency & critical care medicine, Retrospective cohort study, medicine.disease, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], surgical procedures, operative, Emergency Medicine, Cardiology, Observational study, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; Background: Data is scarce on hemorrhagic and thrombotic complications in patients with ST-elevation myocardial infarction (STEMI) associated with out-of-hospital cardiac arrest (OHCA).Methods: This is a monocentric, retrospective study conducted from January 2012 to December 2017 in a tertiary university hospital, which serves as a cardiac arrest center for a large urban area. Over the study period, all consecutive patients who were treated with stent implantation for STEMI with or without OHCA were included. Baseline characteristics, treatments, hemorrhagic and thrombotic events were compared between STEMI patients with and without OHCA. Univariate and multivariate analysis were performed in order to identify predictors of 30-day mortality, occurrence of major bleeding (MB), and early stent thrombosis (ST).Results: A total of 549 patients treated for STEMI without OHCA and 146 patients for STEMI with OHCA were included. The incidence of definite ST and MB after coronary angioplasty was significantly higher in patients with OHCA (2.6% vs. 7.5%, p = 0.004 and 3.3% vs. 19.2%, p < 0.001, respectively). Independent predictors of MB in OHCA patients were anticoagulation therapy (HR = 3.11, 95%CI [1.22-7.98], p = 0.02) and the use of glycoprotein IIb/IIIa inhibitors (HR = 4.16, 95%CI [1.61-10.79], p = 0.003). Independent predictors of mortality in OHCA patients were age (HR = 1.05, 95%CI [1.02-1.09], p = 0.004) and ST (HR = 5.62, 95%CI [1.61-19.65], p = 0.007, with a protective effect of new anti-P2Y12 treatments (HR = 0.20, 95%CI [0.08-0.46], p < 0.001).Conclusion: Patients treated for STEMI associated with OHCA are at higher-risk of ST and MB than those who did not experience cardiac arrest. In this subset of patients, prospective studies are needed to better evaluate the balance of thrombosis and hemorrhage.

Published
2019
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43. HTA secondaires chez la femme

Author

Michel Azizi, Laurence Amar, 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 de Paris (UP), 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), and CCSD, Accord Elsevier

Subjects
Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, General Medicine, 030204 cardiovascular system & hematology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Sex factors, medicine, Aldosterone blood, Hypertension diagnosis, business, Postpartum period
Abstract

Resume Les deux principales etiologies non iatrogenes d’une HTA secondaire chez la femme en âge de procreer sont l’hyperaldosteronisme primaire et la dysplasie fibromusculaire renale. Il est recommande de rechercher une HTA secondaire chez les femmes qui restent hypertendues trois mois apres une grossesse, chez les patientes de moins de 40 ans ou chez les patientes ayant une HTA de grade 3 (PA ≥ 180/110 mm Hg) (accord professionnel). Il est suggere que le bilan initial d’une HTA secondaire chez la femme soit effectue par un specialiste de l’HTA ; il comportera un dosage de la renine et de l’aldosterone et un angioscanner des arteres renales (ou une angio-IRM en cas de contre-indication) (Grade C – Classe 2).

Published
2019
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44. Classical Ehlers‐Danlos syndrome with a propensity to arterial events: A new report on a French family with a COL1A1 p.(Arg312Cys) variant

Author

Etienne Charpentier, Anne Legrand, Sophie Dupuis-Girod, Xavier Jeunemaitre, Salma Adham, Jean-Michael Mazzella, CHU Rouen, Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Centre national de référence des maladies vasculaires rares, 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), 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), Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), World Meteorological Organization (WMO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), and 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 (UPC)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, 030105 genetics & heredity, Collagen Type I, Right external iliac artery, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Aged, 80 and over, business.industry, Genetic heterogeneity, Arteries, Middle Aged, medicine.disease, Pedigree, Collagen Type I, alpha 1 Chain, Dissection, Phenotype, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Arterial aneurysms, Ehlers–Danlos syndrome, Clinical diagnosis, Mutation, Cardiology, Ehlers-Danlos Syndrome, Female, business
Abstract

Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of connective tissue disorders. Overlapping features including arterial aneurysms/dissections in both classical and vascular EDS are a major challenge in the clinical diagnosis of these subtypes. The COL1A1 p.(Arg312Cys) variant leads to a phenotype of classical EDS with a propensity to arterial complications. Our report describes a two-generation family with one individual presenting with a dissection of the right external iliac artery. The primary suspicion of vascular EDS with the unsatisfactory identification of a COL3A1 benign variant was secondarily readjusted with the identification of COL1A1 p.(Arg312Cys) variant. This raises the question of the association of COL1A1 p.(Arg312Cys) with arterial complications and the need for a gene panel including not only the usual genes tested in search of classical or vascular EDS but also COL1A1.

Published
2019
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45. Management of stylohyoid syndrome: A systematic review following PRISMA guidelines

Author

F. Rubin, Ollivier Laccourreye, Pierre Bonfils, S. Guiquerro, Alfred Werner, Quentin Lisan, Université Paris Descartes - Paris 5 (UPD5), 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 de Paris (UP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and CCSD, Accord Elsevier

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Group ii, Logistic regression, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Styloidectomy, Humans, Medicine, 030223 otorhinolaryngology, Paresis, Pain syndrome, Surgical approach, Medical treatment, business.industry, Ossification, Heterotopic, Stylohyoid syndrome, Temporal Bone, Small sample, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], Otorhinolaryngology, 030220 oncology & carcinogenesis, Systematic review, medicine.symptom, Tomography, X-Ray Computed, business, Complication
Abstract

Objectives A systematic review of the literature on stylohyoid syndrome treatment was performed according to PRISMA guidelines. Material and methods Three hundred and forty-nine articles were retrieved in the PubMed and Cochrane databases using the search-terms “stylohyoid syndrome” and synonyms. Articles documenting treatment and outcome with more than 1 month's follow-up were selected. Treatment-related complications and rate of cure, defined as disappearance of symptoms and/or of revelatory complication, were analyzed. Overall analysis was performed for series and a mixed logistic regression model for case reports. Results Hundred and two articles (12 series, 90 case reports) were selected. The 12 series included 482 patients with pain syndrome managed by styloidectomy, with 84.2% and 73.7% cure rates for cervical and transoral approaches, respectively. There were no complications with the transoral approach, versus 1.2% transient facial paresis with the cervical approach. In the 90 case reports, 112 patients had pain syndrome (Group I) and 16 neurological deficit (Group II). Cure rate in Group I varied significantly (P = 0.005; OR 8.33, 95% CI [2.12–32.81]) from 64.3% following medical treatment (antiepileptics, muscle relaxants, analgesics, per os and/or locally injected anti-inflammatory drugs) to 91.8% following styloidectomy, without any significant impact of surgical approach (P = 0.1; OR 0.17, 95% CI [0.02–1.60]). In Group I, no complications occurred after medical treatment, versus 4.3% and 16.3% after transoral and cervical styloidectomy, respectively. In Group II, cure and complication rates were 87.5% and 6.2%, respectively. Due to the small sample size and heterogeneity of Group II, no statistical assessment of the contribution of styloidectomy to medical treatment (antiplatelet drugs, with or without stenting) was performed. Conclusion Styloidectomy appears to be the treatment of choice for stylohyoid syndrome. The surgical approach does not significantly influence the cure or complications rate.

Published
2019
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46. Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

Author

Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), 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), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, 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), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), 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 National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], 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), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, 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], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.

Published
2019
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47. Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Author

David Adlam, Timothy M. Olson, Nicolas Combaret, Jason C. Kovacic, Siiri E. Iismaa, Abtehale Al-Hussaini, Megan M. O'Byrne, Sara Bouajila, Adrien Georges, Ketan Mishra, Peter S. Braund, Valentina d’Escamard, Siying Huang, Marios Margaritis, Christopher P. Nelson, Mariza de Andrade, Daniella Kadian-Dodov, Catherine A. Welch, Stephani Mazurkiewicz, Xavier Jeunemaitre, Claire Mei Yi Wong, Eleni Giannoulatou, Michael Sweeting, David Muller, Alice Wood, Lucy McGrath-Cadell, Diane Fatkin, Sally L. Dunwoodie, Richard Harvey, Cameron Holloway, Jean-Philippe Empana, Xavier Jouven, Jeffrey W. Olin, Rajiv Gulati, Marysia S. Tweet, Sharonne N. Hayes, Nilesh J. Samani, Robert M. Graham, Pascal Motreff, Nabila Bouatia-Naji, Loïc Belle, Patrick Dupouy, Pierre Barnay, Nicolas Meneveau, Martine Gilard, Gilles Rioufol, Grégoire Range, Philippe Brunel, Nicolas Delarche, Emmanuelle Filippi, Louis Le Bivic, Brahim Harbaoui, Hakim Benamer, Guillaume Cayla, Olivier Varenne, Stephane Peggy Manzo-Silberman, Johanne Silvain, Christian Spaulding, Christophe Caussin, Edouard Gerbaud, Yann Valy, René Koning, Thibault Lhermusier, Stanislas Champin, Emmanuel Salengro, Arnaud Fluttaz, Amer Zabalawi, Yves Cottin, Emmanuel Teiger, Christophe Saint-Etienne, Grégory Ducrocq, Stéphanie Marliere, Emmanuel Boiffard, Pierre Aubry, Jean Louis Georges, Didier Bresson, Fabien De Poli, Gaëtan Karrillon, Vincent Roule, Laurent Bali, Mathieu Valla, Antoine Gerbay, David Houpe, Olivier Dubreuil, Arsène Monnier, Norbert Mayaud, Aurélie Manchuelle, Philippe Commeau, Marc Bedossa, Majid Nikpay, Anuj Goel, Hong-Hee Won, Leanne M. Hall, Christina Willenborg, Stavroula Kanoni, Danish Saleheen, Theodosios Kyriakou, Jemma C. Hopewell, Thomas R. Webb, Lingyao Zeng, Abbas Dehghan, Maris Alver, Sebastian M. Armasu, Kirsi Auro, Andrew Bjonnes, Daniel I. Chasman, Shufeng Chen, Ian Ford, Nora Franceschini, Christian Gieger, Christopher Grace, Stefan Gustafsson, Jie Huang, Shih-Jen Hwang, Yun Kyoung Kim, Marcus E. Kleber, King Wai Lau, Xiangfeng Lu, Yingchang Lu, Leo P. Lyytikäinen, Evelin Mihailov, Alanna Morrison, Natalia Pervjakova, Liming Qu, Lynda M. Rose, Elias Salfati, Richa Saxena, Markus Scholz, Albert V. Smith, Emmi Tikkanen, Andre Uitterlinden, Xueli Yang, Weihua Zhang, Wei Zhao, Paul S. de Vries, Natalie R. van Zuydam, Sonia S. Anand, Lars Bertram, Frank Beutner, George Dedoussis, Philippe Frossard, Dominique Gauguier, Alison H. Goodall, Omri Gottesman, Marc Haber, Bok-Ghee Han, Jianfeng Huang, Shapour Jalilzadeh, Thorsten Kessler, Inke R. König, Lars Lannfelt, Wolfgang Lieb, Lars Lind, Cecilia M. Lindgren, Maisa Lokki, Patrik K. Magnusson, Nadeem H. Mallick, Narinder Mehra, Thomas Meitinger, Fazal-ur-Rehman Memon, Andrew P. Morris, Markku S. Nieminen, Nancy L. Pedersen, Annette Peters, Loukianos S. Rallidis, Asif Rasheed, Maria Samuel, Svati H. Shah, Juha Sinisalo, Kathleen E. Stirrups, Stella Trompet, Laiyuan Wang, Khan S. Zaman, Diego Ardissino, Eric Boerwinkle, Ingrid B. Borecki, Erwin P. Bottinger, Julie E. Buring, John C. Chambers, Rory Collins, L Adrienne Cupples, John Danesh, Ilja Demuth, Roberto Elosua, Stephen E. Epstein, Tõnu Esko, Mary F. Feitosa, Oscar H. Franco, Maria Grazia Franzosi, Christopher B. Granger, Dongfeng Gu, Vilmundur Gudnason, Alistair S. Hall, Anders Hamsten, Tamara B. Harris, Stanley L. Hazen, Christian Hengstenberg, Albert Hofman, Erik Ingelsson, Carlos Iribarren, J Wouter Jukema, Pekka J. Karhunen, Bong-Jo Kim, Jaspal S. Kooner, Iftikhar J. Kullo, Terho Lehtimäki, Ruth J. Loos, Olle Melander, Andres Metspalu, Winfried März, Colin N. Palmer, Markus Perola, Thomas Quertermous, Daniel J. Rader, Paul M. Ridker, Samuli Ripatti, Robert Roberts, Veikko Salomaa, Dharambir K. Sanghera, Stephen M. Schwartz, Udo Seedorf, Alexandre F. Stewart, David J. Stott, Joachim Thiery, Pierre A. Zalloua, Christopher J. O'Donnell, Muredach P. Reilly, Themistocles L. Assimes, John R. Thompson, Jeanette Erdmann, Robert Clarke, Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Panos Deloukas, Heribert Schunkert, Martin Farrall, Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, Mayo Clinic [Rochester], Service de Cardiologie Maladies Vasculaires [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Victor Chang Cardiac Research Institute, University of New South Wales [Sydney] (UNSW), St. Vincent’s Clinical School [Sydney, Australia], UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW)-University of New South Wales [Sydney] (UNSW), Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, 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 de Paris (UP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de génétique [CHU HEGP], 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), Department of Cardiovascular Medicine, Mayo Clinic, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)

Subjects
Adult, Male, medicine.medical_specialty, Myocardial infarction, Coronary Vessel Anomalies, Fibromuscular dysplasia, 030204 cardiovascular system & hematology, 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, Prevalence, Fibromuscular Dysplasia, Humans, 030212 general & internal medicine, Vascular Diseases, Artery dissection, MESH: Australia, United Kingdom, USA, Coronary Vessel Anomalies / epidemiology, Endothelin-1 / genetics, Microfilament proteins / genetics, Genetic association, Aged, Endothelin-1, business.industry, Microfilament Proteins, Australia, Cardiovascular disease in women, Middle Aged, medicine.disease, R1, United States, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Case-Control Studies, Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, Cardiology and Cardiovascular Medicine, Scad, business
Abstract

Background: \ud Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.\ud \ud Objectives: \ud This study sought to test the association between the rs9349379 genotype and SCAD.\ud \ud Methods: \ud Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.\ud \ud Results: \ud The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.\ud \ud Conclusions: \ud The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Published
2019
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48. Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome

Author

Clément Lejealle, Onorina Bruno, Emmanuelle de Raucourt, Dominique Valla, Claire Francoz, François Durand, Valérie Vilgrain, Olivier Soubrane, Pierre Bedossa, Valérie Paradis, Didier Lebrec, Pierre-Emmanuel Rautou, Hervé Mal, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and 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 de Paris (UP)

Subjects
Liver Cirrhosis, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cirrhosis, Biopsy, Hypertension, Pulmonary, [SDV]Life Sciences [q-bio], Context (language use), Critical Care and Intensive Care Medicine, Gastroenterology, 03 medical and health sciences, Liver disease, Hepatic Artery, 0302 clinical medicine, Model for End-Stage Liver Disease, hemic and lymphatic diseases, Internal medicine, Multidetector Computed Tomography, Humans, Medicine, 030212 general & internal medicine, Hepatopulmonary syndrome, Lung, Retrospective Studies, integumentary system, Portal Vein, business.industry, Ultrasonography, Doppler, Middle Aged, respiratory system, medicine.disease, Thrombosis, eye diseases, 3. Good health, medicine.anatomical_structure, Liver, 030228 respiratory system, Regional Blood Flow, Case-Control Studies, Portal hypertension, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, Hepatopulmonary Syndrome, Liver Circulation, Artery
Abstract

Background Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown. This study aimed at describing imaging and pathology changes associated with HPS. Methods We performed a case-control study in candidates for transplant with suspicion of cirrhosis. Each patient with HPS (Pao2 ≤ 70 mm Hg) was matched to three control subjects for age, cause, and liver disease severity. Pretransplant thoracic and abdominal imaging and explanted livers were reviewed. Results CT scans and Doppler ultrasounds from 21 patients with HPS were compared with those from 63 control subjects. HPS was associated with a two- to threefold higher prevalence of obstructed intrahepatic portal branches, of slowed or hepatofugal portal blood flow, and of large abdominal portosystemic shunts. Hepatic artery diameter was also larger in patients with HPS. Explanted livers from 19 patients with HPS were compared with those from 57 control subjects. HPS was associated with a fourfold higher prevalence of portal venule thrombosis and a ninefold higher prevalence of extensive vascular proliferation within fibrous septa. Obstruction of centrilobular venules, sinusoidal dilatation, and liver parenchymal extinction were also more common in patients with HPS. Conclusions HPS is associated with intrahepatic vascular changes and with features suggesting severe portal hypertension. These results raise the hypothesis that intrahepatic vascular changes precipitate the development of HPS, opening new therapeutic perspectives for HPS.

Published
2019
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49. Study of Thoracic CT in COVID-19: The STOIC Project

Author

Audrey Milon, Sébastien Molière, Ines Saab, Laure Fournier, Marie-France Bellin, Dominique Mompoint, Thibaut Lapotre, Mostafa El Hajjam, Sébastien Bommart, Valérie Bousson, Carole Jalaber, Mathieu Lederlin, Severine Dangeard, Jules Gregory, Chahinez Hani, Isabelle Petit, Elisabeth Dion, Pascal Rousset, Constance de Margerie-Mellon, Jean-François Deux, Souhail Bennani, Marie-Pierre Debray, Marie-Pierre Revel, Hendy Abdoul, Raphaël Porcher, Antoine Khalil, Mickaël Ohana, Florian Bompard, Laurence Rocher, Pierre-Yves Brillet, Léa Jilet, Guillaume Chassagnon, Dominique Valeyre, Samia Boussouar, Alban Redheuil, Hôpital Cochin [AP-HP], 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), Hopital Saint-Louis [AP-HP] (AP-HP), Université de Rennes (UR), CHU Pontchaillou [Rennes], Université Paris-Saclay, Hôpital Raymond Poincaré [AP-HP], Sorbonne Université (SU), CHU Tenon [AP-HP], Université de Strasbourg (UNISTRA), Hôpital de Hautepierre [Strasbourg], Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Nouvel Hôpital Civil de Strasbourg, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Ambroise Paré [AP-HP], Université de Lorraine (UL), Hôpital Brabois, 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), Hôpital Avicenne [AP-HP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Antoine Béclère [Clamart], Hôpital Lariboisière-Fernand-Widal [APHP], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hôpital Beaujon [AP-HP], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Hôpital Hôtel-Dieu [Paris], Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [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 Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), MORNET, Dominique, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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 de Paris (UP), 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)-CHU Trousseau [APHP]

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Logistic regression, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, Intubation, Humans, Radiology, Nuclear Medicine and imaging, Lung, ComputingMilieux_MISCELLANEOUS, Original Research, Aged, Retrospective Studies, business.industry, SARS-CoV-2, COVID-19, Reproducibility of Results, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Coronary Calcium Score, [SDV] Life Sciences [q-bio], Pneumonia, Editorial, 030220 oncology & carcinogenesis, Radiological weapon, Observational study, Female, Radiology, business, Tomography, X-Ray Computed
Abstract

Background There are conflicting data regarding the diagnostic performance of chest CT for COVID-19 pneumonia. Disease extent at CT has been reported to influence prognosis. Purpose To create a large publicly available data set and assess the diagnostic and prognostic value of CT in COVID-19 pneumonia. Materials and Methods This multicenter, observational, retrospective cohort study involved 20 French university hospitals. Eligible patients presented at the emergency departments of the hospitals involved between March 1 and April 30th, 2020, and underwent both thoracic CT and reverse transcription-polymerase chain reaction (RT-PCR) testing for suspected COVID-19 pneumonia. CT images were read blinded to initial reports, RT-PCR, demographic characteristics, clinical symptoms, and outcome. Readers classified CT scans as either positive or negative for COVID-19 based on criteria published by the French Society of Radiology. Multivariable logistic regression was used to develop a model predicting severe outcome (intubation or death) at 1-month follow-up in patients positive for both RT-PCR and CT, using clinical and radiologic features. Results Among 10 930 patients screened for eligibility, 10 735 (median age, 65 years; interquartile range, 51-77 years; 6147 men) were included and 6448 (60%) had a positive RT-PCR result. With RT-PCR as reference, the sensitivity and specificity of CT were 80.2% (95% CI: 79.3, 81.2) and 79.7% (95% CI: 78.5, 80.9), respectively, with strong agreement between junior and senior radiologists (Gwet AC1 coefficient, 0.79). Of all the variables analyzed, the extent of pneumonia at CT (odds ratio, 3.25; 95% CI: 2.71, 3.89) was the best predictor of severe outcome at 1 month. A score based solely on clinical variables predicted a severe outcome with an area under the curve of 0.64 (95% CI: 0.62, 0.66), improving to 0.69 (95% CI: 0.6, 0.71) when it also included the extent of pneumonia and coronary calcium score at CT. Conclusion Using predefined criteria, CT reading is not influenced by reader's experience and helps predict the outcome at 1 month. ClinicalTrials.gov identifier: NCT04355507 Published under a CC BY 4.0 license.

Published
2021
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50. Cardiovascular complications of lipodystrophic syndromes – focus on laminopathies

Author

Isabelle Jéru, Marie-Christine Vantyghem, Héléna Mosbah, Karim Wahbi, Camille Vatier, B. Donadille, Corinne Vigouroux, Franck Boccara, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Recherche translationnelle sur le diabète - U 1190 (RTD), 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), Filière Neuromusculaire (FILNEMUS), 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), Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), Service de Cardiologie [CHU Saint-Antoine], Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université

Subjects
medicine.medical_specialty, Lipodystrophy, Endocrinology, Diabetes and Metabolism, LMNA, MESH: Laminopathies, MESH: Phenotype, Electrocardiography, Endocrinology, MESH: Lipodystrophy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Cardiovascular complications, MESH: Syndrome, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Focus (computing), MESH: Humans, business.industry, Laminopathies, MESH: Cardiovascular Diseases, General Medicine, Syndrome, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Electrocardiography, Phenotype, Cardiovascular Diseases, business
Abstract

International audience

Published
2021
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