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1. Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island

Author

Gilles Beullier, Liliane Cotte, Jean-Luc Alessandri, Brahim Boumahni, Isabelle Tiran-Rajaoefera, Alain Fourmaintraux, Irénée Boya, Olivier Rollot, Patrick Gérardin, Magali Carbonnier, Monique Kaminski, Sylvain Samperiz, Marie-Christine Jaffar-Bandjee, Xavier Fritel, Duksha Ramful, Tahir Noormahomed, Alain Michault, François Favier, Jocelyn Okoï, Marc Bintner, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-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), Immunopathology and Infection Research Grouping (IRG), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Gabriel Martin, Centre hospitalier de l'Est Réunion, Saint-Benoît, Clinique Sainte Clotilde, CAMSP La Rose, Clinique Durieux, Le Tampon, La Réunion, Centre hospitalier universitaire de Poitiers (CHU Poitiers), INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants, Institut National de la Santé et de la Recherche Médicale (INSERM) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Tenon [APHP] - CHU Cochin [APHP] - Université Paris-Sud - Paris 11 (UP11) - Université Paris Descartes - Paris 5 (UPD5) - Université Pierre et Marie Curie - Paris 6 (UPMC), Service de gynécologie et obstétrique [Poitiers], Université de Poitiers - CHU de Poitiers, CHU de Poitiers, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de la Réunion - Centre hospitalier Régional Site Félix Guyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion ( CIC-EC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -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 ), Immunopathology and Infection Research Grouping ( IRG ), Université de la Réunion ( UR ) -Centre hospitalier Régional Site Félix Guyon, Centre Hospitalier Gabriel-Martin, CH Gabriel-Martin, Clinique Sainte-Clotilde, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), and INSERM CIC 0802 ( INSERM CIC 0802, CHU de Poitiers )

Subjects
Pediatrics, Viral Diseases, Epidemiology, Developmental Disabilities, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Developmental and Pediatric Neurology, Rate ratio, Diagnostic Radiology, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Child Development, Infectious Diseases of the Nervous System, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Emerging Viral Diseases, Medicine and Health Sciences, Public and Occupational Health, Pregnancy Complications, Infectious, Pediatric Epidemiology, Cognitive Neurology, lcsh:Public aspects of medicine, Radiology and Imaging, Child Health, Gestational age, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Neurology, Arboviral Infections, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Behavioral and Social Aspects of Health, Chikungunya virus, Cohort study, Research Article, Neglected Tropical Diseases, medicine.medical_specialty, Pediatric Critical Care, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Cognitive Neuroscience, Neuroimaging, Microbiology, Infectious Disease Epidemiology, Cerebral palsy, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Developmental Neuroscience, Diagnostic Medicine, Virology, medicine, Humans, Retrospective Studies, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neonatal encephalopathy, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Biology and Life Sciences, Infant, Retrospective cohort study, lcsh:RA1-1270, medicine.disease, Tropical Diseases, Infectious Disease Transmission, Vertical, Health Care, Small for gestational age, Chikungunya Fever, Neonatology, business, Neurocognitive, Reunion, Viral Transmission and Infection, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Neuroscience
Abstract

Background Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. Methods The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ≤85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. Results The mean DQ score was 86.3 (95%CI: 81.0–91.5) in infected children compared to 100.2 (95%CI: 98.0–102.5) in uninfected peers (P, Author Summary Chikungunya virus (CHIKV), an alphaviral infection transmitted by day-biting Aedes mosquitoes, is widespread in Asia and in Africa. Usually, CHIKV causes a self-limiting arthritide, except in debilitated people and in neonates, for whom it can lead to severe disease. Mother-to-child perinatal transmission of CHIKV is a rare event that can occur in the setting of large-scale outbreaks when the risk of maternal viremia at the term of pregnancy becomes non-negligible. In that event, CHIKV can give rise to neonatal infection with a probability of 50%, and prostration and encephalopathy, the two leading clinical pictures in the neonate, represent a continuum in the gradation of an undiscovered central nervous system involvement. We have followed-up 33 children infected at birth between June 2005 and April 2006 on the island of La Réunion, Indian Ocean, and 135 uninfected controls, for assessing their neurodevelopmental performance around the age of two years. Fifty-one percent of infected children had a global neurodevelopmental delay compared to 15% of uninfected peers. Multivariate analysis and neuroradiology suggest without irrefutable evidence a causal relationship between CHIKV infection and neurocognitive outcomes. Our findings suggest that CHIKV infection, acquired in the perinatal period, can cause severe disease with lifelong expected disability.

Published
2014

2. Chikungunya Virus Infection during Pregnancy, Réunion, France, 2006

Author

Patrick Gérardin, Xavier Fritel, Marie-Christine Jaffar-Bandjee, Monique Kaminski, Jacques Bideault, Louis Lagarde, Olivier Rollot, Eric Orvain, Fabrice Cuillier, Sylvain Samperiz, Liliane Cotte, Barbara Dhuime, Alain Michault, Bernard-Alex Gaüzère, Duksha Ramful, Alain Fourmaintraux, Service de gynécologie et obstétrique [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM), Réanimation médicale néonatale et pédiatrique, CHR la Reunion site Sud, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Intercommunal Saint Benoît- Saint André, CHI de Saint-Benoit-Saint-André, Centre Hospitalier Gabriel Martin, Clinique Sainte Clotilde, Laboratoire de Bactériologie-Parasitologie-Virologie-Hygiène, Groupe Hospitalier Sud Réunion (GHSR), Recherches épidémiologiques en santé périnatale et santé des femmes, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Gabriel-Martin, CH Gabriel-Martin, and Clinique Sainte-Clotilde

Subjects
newborns, Epidemiology, viruses, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], lcsh:Medicine, Antibodies, Viral, medicine.disease_cause, Disease Outbreaks, 0302 clinical medicine, Pregnancy, Vertical, 030212 general & internal medicine, Chikungunya, Viral, Prospective Studies, Pregnancy Complications, Infectious, Réunion, Obstetrics, Transmission (medicine), Reverse Transcriptase Polymerase Chain Reaction, Infectious, Pregnancy Outcome, 3. Good health, Infectious Diseases, Population study, Female, France, Pregnancy Trimesters, Chikungunya virus, Microbiology (medical), medicine.medical_specialty, 030231 tropical medicine, Antibodies, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, medicine, Humans, lcsh:RC109-216, Alphavirus infection, business.industry, Alphavirus Infections, Research, lcsh:R, Infant, Newborn, Outbreak, Infant, medicine.disease, Newborn, Infectious Disease Transmission, Vertical, Pregnancy Complications, mothers, 030221 ophthalmology & optometry, business
Abstract

Except for prenatal hospital admissions for those infected, this virus had no effect on outcomes., Mother-to-child transmission of chikungunya virus was reported during the 2005–2006 outbreak on Réunion Island, France. To determine the effects of this virus on pregnancy outcomes, we conducted a study of pregnant women in Réunion in 2006. The study population was composed of 1,400 pregnant women (628 uninfected, 658 infected during pregnancy, 27 infected before pregnancy, and 87 infected on unknown dates). We compared pregnancy outcomes for 655 (628 + 27) women not infected during pregnancy with 658 who were infected during pregnancy. Infection occurred during the first trimester for 15% of the infected women, the second for 59%, and the third for 26%. Only hospital admission during pregnancy differed between infected and uninfected women (40% vs. 29%). Other outcomes (cesarean deliveries, obstetric hemorrhaging, preterm births, stillbirths after 22 weeks, birthweight, congenital malformations, and newborn admissions) were similar. This virus had no observable effect on pregnancy outcomes.

Published
2010

3. Altered high-density lipoprotein composition and functions during severe COVID-19

Author

Erick Vélia, Patrick Mavingui, Olivier Meilhac, Floran Begue, Philippe Montravers, Philippe Rondeau, Sébastien Tanaka, Tiphaine Robert, Marie Lagrange-Xelot, Zarouki Mouktadi, Alexy Tran-Dinh, Bryan Veeren, Nicolas Diotel, David Couret, Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de biochimie [CHU Bichat], 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), Clinique Sainte Clotilde, Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), 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), CHU Sud Saint Pierre [Ile de la Réunion], This research was funded by FEDER RE0001897 (EU—Région Réunion—French State national counterpart), by Université de La Réunion (COVID-19 emergency seed funding) as well as by the BIOST Fédération., Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Proteomics, Male, Apolipoprotein B, Proteome, Apoptosis, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Tandem Mass Spectrometry, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, biology, Middle Aged, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Tumor necrosis factor alpha, Female, France, Lipoproteins, HDL, medicine.medical_specialty, Science, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Serum amyloid A, Pandemics, Serum Amyloid A Protein, Mass spectrometry, Apolipoprotein A-I, business.industry, Aryldialkylphosphatase, Tumor Necrosis Factor-alpha, SARS-CoV-2, Paraoxonase, Case-control study, COVID-19, Endothelial Cells, Lipid metabolism, 030104 developmental biology, Endocrinology, chemistry, Viral infection, Case-Control Studies, alpha 1-Antitrypsin, biology.protein, high‑density lipoprotein, business, Biomarkers, Chromatography, Liquid
Abstract

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Published
2021

4. Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Author

François Jourda, Christophe Saint-Etienne, Luc Christiaens, Grégoire Rangé, Benoit Lattuca, Philippe Brunel, Paul Guedeney, Hervé Le Breton, Marie Hauguel-Moreau, Eric Vicaut, Anne Bellemain-Appaix, Jean-Louis Georges, Guillaume Cayla, Christophe Pouillot, Christophe Caussin, Gregory Ducrocq, Ziad Boueri, Farzin Beygui, Johanne Silvain, Thibault Lhermusier, Gilles Montalescot, Jean-Noël Labèque, Jean-Philippe Collet, Zuzana Motovska, Franck Boccara, Mohamad El Kasty, Raphaelle Dumaine, Jean-Guillaume Dillinger, Mikael Laredo, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [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 cardiologie [Chartres], Les hôpitaux de Chartres [Chartres], 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 (UPC)-Université Sorbonne Paris Nord, Hôpital de Bastia, Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Clinique Sainte Clotilde, 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), Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de cardiologie [Centre Hospitalier de la Côte Basque, Bayonne], Centre Hospitalier de la Côte Basque, CHU Toulouse [Toulouse], Centre Hospitalier de Versailles André Mignot (CHV), Cardiology Department, Centre Hospitalier d'Antibes Juan les Pins, Antibes, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Institut Mutualiste de Montsouris (IMM), Hôpital d'Auxerre, Partenaires INRAE, Grand Hôpital de l'Est Francilien (GHEF), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, AstraZeneca France Novartis Daiichi-Sankyo Bristol-Myers Squibb, BMS Eli Lilly and Company Bayer AstraZeneca France Boston Scientific Corporation, BSC Abbott Laboratories Medtronic Biotronik Fédération Française de Cardiologie, FFC, The ALPHEUS and the Bio-ALPHEUS studies are funded by the Fond de dotation ACTION ( www.action-fonds.org ) and a grant from AstraZeneca . The Bio-ALPHEUS study is also funded by the Institute of Cardiometabolism and Nutrition . The first draft of the paper was developed by Dr Silvain and Dr Montalescot, and all authors subsequently contributed to its development and final content and are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. AstraZeneca reviewed the manuscript and was allowed to make suggestions, but final content was determined by the authors., Dr Silvain reports receiving consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, BPI France, Boehringer Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, Abbott Medical France SAS, and Zoll and is a stockholder of Pharmaseeds. Dr Cayla reports speaker or congress fees and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Beygui reports receiving consulting and lecture fees from Astrazeneca, Bristol-Myers Squibb, Medtronic, Biosensors, Boston Scientific Institutional and research grants from Medtronic, Biosensors, Acist, and Boston scientific. Dr Rangé reports receiving speaker’s and/or consulting fees from Abbott. Dr Lattuca has received research grants from Biotronik, Boston Scientific, Daiichi-Sankyo, Fédération Française de Cardiologie, and Institute of CardioMetabolism and Nutrition, consultant fees from Daiichi-Sankyo and Eli Lilly, and lecture fees from AstraZeneca, Medtronic, and Novartis. Dr Collet reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. Dr Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, and Sanofi and grants from Bayer, Bristol-Myers Squibb/Pfizer, and Biosensors. Dr Boueri reports receiving consulting and lecture fees from Novartis and Astra Zeneca. Dr Boccara reports consulting or speaker fees from Amgen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. Dr Christiaens reports consulting or speaker fees from Astra Zeneca. Dr Lhermusier reports consulting or speaker fees from Astra Zeneca, Boston Scientifics, and Abbott and a research grant from Astra Zeneca. Dr Georges reports consulting or speaker fees from AstraZeneca France, Sanofi-Aventis, Amgen, and Merck Sharpe and Dohme. Dr Bellemain-Appaix reports consulting or speaker fees from Astra Zeneca, Novartis, and Pfizer. Dr Saint-Etienne reports consulting or speaker fees from Abbott, Medtronic, Edwards, and Biotronik. Dr Motovska reports consulting or speaker fees from Astrazeneca. Dr Laredo reports fellowship grants from Medtronic, Biotronik, and Boston Scientific. Dr Ducrocq reports consulting or speaker fees from Amgen, Astra Zeneca, Bayer, BMS, Janssen, Sanofi, and Terumo, proctoring: Boston scientific, CEC: Novo Nordisk, and travel fees: Astra Zeneca, Bayer, and BMS. Dr Vicaut reports consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards, Pfizer, Sanofi, and Novartis. Dr Montalescot reports consulting or speaker fees from Abbott, AIM group, Amgen, Actelion, American College of Cardiology Foundation, Astrazeneca, Axis-Santé, Bayer, Boston-Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Fréquence Médicale, ICOM, Idorsia, Elsevier, Fédération Française de Cardiologie, Fréquence Médicale, Institute of Cardiometabolism and Nutrition, Lead-Up, Menarini, Medtronic, MSD, Novo-Nordisk, Pfizer, Quantum Genomics, Sanofi-Aventis, SCOR global life, Servier, and WebMD. Other authors have no conflict of interest to report., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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 de Paris (UP)-Université Sorbonne Paris Nord, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, 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)-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)-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 Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier d'Auxerre (CHA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
medicine.medical_specialty, Ticlopidine, medicine.medical_treatment, Myocardial Infarction, Coronary Disease, 030204 cardiovascular system & hematology, Coronary Angiography, Loading dose, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Aged, Aspirin, business.industry, Percutaneous coronary intervention, medicine.disease, Clopidogrel, 3. Good health, Conventional PCI, Cardiology, Purinergic P2Y Receptor Antagonists, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, Ticagrelor, Platelet Aggregation Inhibitors, medicine.drug
Abstract

International audience; Background: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. Methods: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Published
2020

5. Large Extracellular Vesicle-Associated Rap1 Accumulates in Atherosclerotic Plaques, Correlates with Vascular Risks and Is Involved in Atherosclerosis

Author

Séverine Dubois, Liliana Perdomo, Gilles Simard, M. Carmen Martinez, Lucie Duluc, Olivier Meilhac, Alexandre Villard, Ramaroson Andriantsitohaina, Samir Henni, Jérôme Boursier, Florence Pinet, Raffaella Soleti, Soazig Le Lay, Maggy Chwastyniak, Frédéric Gagnadoux, Xavier Vidal-Gómez, Frank Lezoualc'h, Luisa Vergori, Ilya Khantalin, Malik Bisserier, Reuben Veerapen, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-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), 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 des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Clinique Sainte Clotilde, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), This work was supported by INSERM, Université d’Angers and CHU Angers, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Martinez, M. Carmen

Subjects
Male, Proteomics, Apolipoprotein E, Vascular smooth muscle, Mice, Knockout, ApoE, Physiology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, p38 Mitogen-Activated Protein Kinases, Muscle, Smooth, Vascular, 0302 clinical medicine, Cell Movement, Risk Factors, Phosphorylation, Endothelial dysfunction, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, [SDV.BA]Life Sciences [q-bio]/Animal biology, rap1 GTP-Binding Proteins, Extracellular vesicle, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Plaque, Atherosclerotic, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Endothelial stem cell, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, extracellular vesicles, Signal Transduction, Adult, medicine.medical_specialty, endocrine system, Myocytes, Smooth Muscle, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Risk Assessment, Article, Permeability, metabolic syndrome, Proinflammatory cytokine, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Extracellular, Animals, Humans, Mitogen-Activated Protein Kinase 7, Aged, Cell Proliferation, 030304 developmental biology, business.industry, Endothelial Cells, muscle cells, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, enzymes and coenzymes (carbohydrates), rap GTP-Binding Proteins, Endocrinology, inflammation, Case-Control Studies, atherosclerosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Rationale:Metabolic syndrome (MetS) is a cluster of interrelated risk factors for cardiovascular diseases and atherosclerosis. Circulating levels of large extracellular vesicles (lEVs), submicrometer-sized vesicles released from plasma membrane, from MetS patients were shown to induce endothelial dysfunction, but their role in early stage of atherosclerosis and on vascular smooth muscle cells (SMC) remain to be fully elucidated.Objective:To determine the mechanisms by which lEVs lead to the progression of atherosclerosis in the setting of MetS.Methods and Results:Proteomic analysis revealed that the small GTPase, Rap1 was overexpressed in lEVs from MetS patients compared with those from non-MetS subjects. Rap1 was in GTP-associated active state in both types of lEVs, and Rap1-lEVs levels correlated with increased cardiovascular risks, including stenosis. MetS-lEVs, but not non-MetS-lEVs, increased Rap1-dependent endothelial cell permeability. MetS-lEVs significantly promoted migration and proliferation of human aortic SMC and increased expression of proinflammatory molecules and activation of ERK (extracellular signal-regulated kinase) 5/p38 pathways. Neutralization of Rap1 by specific antibody or pharmacological inhibition of Rap1 completely prevented the effects of lEVs from MetS patients. High-fat diet-fed ApoE−/−mice displayed an increased expression of Rap1 both in aortas and circulating lEVs. lEVs accumulated in plaque atherosclerotic lesions depending on the progression of atherosclerosis. lEVs from high-fat diet-fed ApoE−/−mice, but not those from mice fed with a standard diet, enhanced SMC proliferation. Human atherosclerotic lesions were enriched in lEVs expressing Rap1.Conclusions:These data demonstrate that Rap1 carried by MetS-lEVs participates in the enhanced SMC proliferation, migration, proinflammatory profile, and activation of ERK5/p38 pathways leading to vascular inflammation and remodeling, and atherosclerosis. These results highlight that Rap1 carried by MetS-lEVs may be a novel determinant of diagnostic value for cardiometabolic risk factors and suggest Rap1 as a promising therapeutic target against the development of atherosclerosis.Graphical Abstract:A graphical abstract is available for this article.

Published
2020

6. Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial

Author

Johanne Silvain, Benoit Lattuca, Farzin Beygui, Grégoire Rangé, Zuzana Motovska, Jean-Guillaume Dillinger, Ziad Boueri, Philippe Brunel, Thibault Lhermusier, Christophe Pouillot, Elisa Larrieu-Ardilouze, Franck Boccara, Jean-Noël Labeque, Paul Guedeney, Mohamad El Kasty, Mikael Laredo, Raphaëlle Dumaine, Grégory Ducrocq, Jean-Philippe Collet, Guillaume Cayla, Katrien Blanchart, Petr Kala, Eric Vicaut, Gilles Montalescot, Johanne SILVAIN, Jean-Philippe COLLET, Gilles MONTALESCOT, Mathieu KERNEIS, Nassim BRAIK, Olivier BARTHELEMY, Gérard HELFT, Claude LEFEUVRE, Rémi CHOUSSAT, Marie HAUGUEL, Michel ZEITOUNI, Thomas CUISSET, Jean-Louis BONNET, Pierre DEHARO, Benoit LATTUCA, Guillaume CAYLA, Luc CORNILLET, Bertrand LEDERMANN, Clément LONJON, Laurent SCHMUTZ, Grégoire RANGE, Franck ALBERT, Thibault DEMICHELI, Laurent ROUSSEL, Reda BENSAID, Christophe THUAIRE, Jean-Guillaume DILLINGER, Patrick HENRY, Stéphane MANZO-SILBERMAN, Georgios SIDERIS, Damien LOGEART, Vincent SPAGNOLI, Léa CACOUB, Christophe POUILLOT, Jean Richard VI-FANE, Jens GLASENAPP, Karim BOUGRINI, Nicolas COMBARET, Pascal MOTREFF, Géraud SOUTEYRAND, Aimé AMONCHOT, Thomas MOUYEN, Thibault LHERMUSIER, Didier CARRIE, Frédéric BOUISSET, Thomas CHOLLET, Francisco CAMPELO-PARADA, Nicolas DELARCHE, François SCHIELE, Mathieu BESUTTI, Marie HAUGUEL-MOREAU, Rami EL MAHMOUD, Christophe CAUSSIN, Mami ZOHEIR, Aurelie VEUGEOIS, Alain DIBIE, Olivier VARENNE, Fabien PICARD, Alexandre LAFONT, Julien ADJEDJ, Philippe DEGRELL, Farzin BEYGUI, Rémi SABATIER, Vincent ROULE, Mathieux BIGNON, Katrien BLANCHART, Pierre ARDOUIN, Adrien LEMAITRE, Clément BRIET, Ziad BOUERI, Pascal GOUBE, Pierre COSTE, Laura CETRAN, Jérôme CLERC, Hervé LE BRETON, Dominique BOULMIER, Vincent AUFFRET, Jean-Noël LABEQUE, Jean-Luc BONAS, Jean-Louis GEORGES, Bernard LIVAREK, Elodie BLICQ, Nicolas BARON, Géraldine GIBAULT-GENTY, Yves COTTIN, Isabelle LHUILLIER, Carole RICHARD, Luc LORGIS, Philippe BUFFET, Christian SPAULDING, Nicole KARAM, Etienne PUYMIRAT, Marco MENNUNI, Emmanuel POULIDAKIS, Lionel BONNEVIE, Franck BOCCARA, Marion CHAUVET, Laurie DUFOUR, Yann ANCEDY, Stéphane EDERHY, Arnaud ETIENNEY, Anne BELLEMAIN-APPAIX, Nathaniel BITTON, Laurent JACQ, Christophe SAINT-ETIENNE, Florence LECLERCQ, François ROUBILLE, Gilles RIOUFOL, François DERIMAY, Marc GORALSKI, Wael YAFI, Emmanuelle FILIPPI, Alain KERMARREC, Christophe LE RAY, Antoine MERLET, Aurelie LOIRAT, Philippe BRUNEL, Damien BRUNET, Jack RAVISY, Laurent MOCK, Guillaume MOLINS, Max CARRE, Erwan BRESSOLLETTE, Luc CHRISTIAENS, Elisa LARRIEU-ARDILOUZE, Romain CADOR CADOR, Eric VAN BELLE, Gilles LEMESLE, Cédric DELHAYE, Flavien VINCENT, Sina POROUCHANI, Hugues SPILLEMAEKER, Katy PETIT, Olivier RESSENCOURT, Vincent HUMEAU, François JOURDA, Marc-Antoine ARNOULD, Stephen CHASSAING, Karl ISAAZ, Laurent PAYOT, Jacques MONTSEGU, Benjamin FAURIE, Michel PANSIERI, Marc METGE, Karim MOUSSA, Mathieu PANKERT, Olivier MOREL, Sébastien HESS, Luc MAILLARD, Thibault MANIGOLD, Vincent LETOCART, Julien PLESSIS, Pauline BERTHOME, Mickael BONIN, François HUCHET, Emmanuel TEIGER, Romain GALLET, Gauthier MOUILLET, Madjid BOUKANTAR, Mohammed NEJJARI, David ATTIAS, Mathieu STEINECKER, Zuzana MOTOVSKA, Martin KOZEL, Zdenko STELMACH, Ota HLINOMAZ, Michal REZEK, Martin NOVAK, Jan SITAR, Jiri SEMENKA, Petr KALA, Otakar BOCEK, Roman ŠTIPAL, Martin POLOCZEK, Jan KANOVSKÝ, Petr JERABEK, Jiří KARASEK, Sylvie HRUSKOVA, Marian BRANNY, Jan MROZEK, Tomas GREZL, Leos PLEVA, Pavel KUKLA, Martin PORZER, Lesnik, Philippe, Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de cardiologie et de pathologie vasculaire [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), Hôpital Louis Pasteur [Chartres], Charles University [Prague] (CU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Bastia (G2HC), Service de Cardiologie [Hôpital privé Dijon Bourgogne], Hôpital privé Dijon Bourgogne, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Clinique Sainte Clotilde, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Cardiologie [CHU Saint-Antoine], 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), Le CHCB, Centre Hospitalier de la Côte Basque, Grand Hôpital de l'Est Francilien (GHEF), Centre de Réadaptation Cardiaque Les Grands Prés [Villeneuve Saint Denis] (CRCLGP), Service de cardiologie [CHU Bichat], 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)-Université Paris Diderot, Sorbonne Paris Cité, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), University Hospital Brno, Masaryk University [Brno] (MUNI), Hopital Saint-Louis [AP-HP] (AP-HP), Erasmus University Medical Center [Rotterdam] (Erasmus MC), ALPHEUS investigators: Johanne Silvain, Jean-Philippe Collet, Gilles Montalescot, Mathieu Kerneis, Nassim Braik, Olivier Barthelemy, Gérard Helft, Claude Lefeuvre, Rémi Choussat, Marie Hauguel, Michel Zeitouni, Thomas Cuisset, Jean-Louis Bonnet, Pierre Deharo, Benoit Lattuca, Guillaume Cayla, Luc Cornillet, Bertrand Ledermann, Clément Lonjon, Laurent Schmutz, Grégoire Range, Franck Albert, Thibault Demicheli, Laurent Roussel, Reda Bensaid, Christophe Thuaire, Jean-Guillaume Dillinger, Patrick Henry, Stéphane Manzo-Silberman, Georgios Sideris, Damien Logeart, Vincent Spagnoli, Léa Cacoub, Christophe Pouillot, Jean Richard Vi-Fane, Jens Glasenapp, Karim Bougrini, Nicolas Combaret, Pascal Motreff, Géraud Souteyrand, Aimé Amonchot, Thomas Mouyen, Thibault Lhermusier, Didier Carrie, Frédéric Bouisset, Thomas Chollet, Francisco Campelo-Parada, Nicolas Delarche, François Schiele, Mathieu Besutti, Marie Hauguel-Moreau, Rami El Mahmoud, Christophe Caussin, Mami Zoheir, Aurelie Veugeois, Alain Dibie, Olivier Varenne, Fabien Picard, Alexandre Lafont, Julien Adjedj, Philippe Degrell, Farzin Beygui, Rémi Sabatier, Vincent Roule, Mathieux Bignon, Katrien Blanchart, Pierre Ardouin, Adrien Lemaitre, Clément Briet, Ziad Boueri, Pascal Goube, Pierre Coste, Laura Cetran, Jérôme Clerc, Hervé LE Breton, Dominique Boulmier, Vincent Auffret, Jean-Noël Labeque, Jean-Luc Bonas, Jean-Louis Georges, Bernard Livarek, Elodie Blicq, Nicolas Baron, Géraldine Gibault-Genty, Yves Cottin, Isabelle Lhuillier, Carole Richard, Luc Lorgis, Philippe Buffet, Christian Spaulding, Nicole Karam, Etienne Puymirat, Marco Mennuni, Emmanuel Poulidakis, Lionel Bonnevie, Franck Boccara, Marion Chauvet, Laurie Dufour, Yann Ancedy, Stéphane Ederhy, Arnaud Etienney, Anne Bellemain-Appaix, Nathaniel Bitton, Laurent Jacq, Christophe Saint-Etienne, Florence Leclercq, François Roubille, Gilles Rioufol, François Derimay, Marc Goralski, Wael Yafi, Emmanuelle Filippi, Alain Kermarrec, Christophe LE Ray, Antoine Merlet, Aurelie Loirat, Philippe Brunel, Damien Brunet, Jack Ravisy, Laurent Mock, Guillaume Molins, Max Carre, Erwan Bressollette, Luc Christiaens, Elisa Larrieu-Ardilouze, Romain Cador Cador, Eric VAN Belle, Gilles Lemesle, Cédric Delhaye, Flavien Vincent, Sina Porouchani, Hugues Spillemaeker, Katy Petit, Olivier Ressencourt, Max Carre, Vincent Humeau, François Jourda, Marc-Antoine Arnould, Stephen Chassaing, Karl Isaaz, Laurent Payot, Jacques Montsegu, Benjamin Faurie, Michel Pansieri, Marc Metge, Karim Moussa, Mathieu Pankert, Olivier Morel, Sébastien Hess, Luc Maillard, Thibault Manigold, Vincent Letocart, Julien Plessis, Pauline Berthome, Mickael Bonin, François Huchet, Emmanuel Teiger, Romain Gallet, Gauthier Mouillet, Madjid Boukantar, Rami El Mahmoud, Mohammed Nejjari, David Attias, Léa Cacoub, Mathieu Steinecker, François Huchet, Zuzana Motovska, Martin Kozel, Zdenko Stelmach, Ota Hlinomaz, Michal Rezek, Martin Novak, Jan Sitar, Jiri Semenka, Petr Kala, Otakar Bocek, Roman Štipal, Martin Poloczek, Jan KanovskÝ, Petr Jerabek, Jiří Karasek, Sylvie Hruskova, Marian Branny, Jan Mrozek, Tomas Grezl, Leos Pleva, Pavel Kukla, Martin Porzer., Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, Ticagrelor, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Percutaneous coronary intervention, General Medicine, Middle Aged, medicine.disease, Clopidogrel, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Action study, Elective Surgical Procedures, Anesthesia, Conventional PCI, Purinergic P2Y Receptor Antagonists, Female, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

International audience; Background: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.Methods: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290.Findings: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070).Interpretation: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI.Funding: ACTION Study Group and AstraZeneca.

Published
2020

7. Characteristics of the paralysed diaphragm studied by M-mode ultrasonography

Author

Philippe Blanc, Jean-Marie Gil, Laurent Poirette, Alain Boussuges, Fabienne Brégeon, 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), Aix Marseille Université (AMU), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Clinique Sainte Clotilde, Hôpital HIA Laveran, Leon Berard Hospital, Centre recherche en CardioVasculaire et Nutrition (C2VN), and COMBE, Isabelle

Subjects
Adult, Male, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], Diaphragm, Diaphragmatic breathing, 030204 cardiovascular system & hematology, Diaphragmatic paralysis, phrenic nerve, respiratory manoeuvres, Pulmonary function testing, 03 medical and health sciences, diaphragmatic motion, 0302 clinical medicine, Predictive Value of Tests, Sniffing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Physiology (medical), Paralysis, Humans, Medicine, Organ Motion, Lung, ComputingMilieux_MISCELLANEOUS, chest ultrasonography, Aged, Ultrasonography, Phrenic nerve, business.industry, Respiration, Reproducibility of Results, 030229 sport sciences, General Medicine, Middle Aged, Respiratory Paralysis, Respiratory Function Tests, Diaphragm (structural system), [SDV] Life Sciences [q-bio], Cardiothoracic surgery, Anesthesia, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.symptom, business
Abstract

International audience; Background M-mode ultrasonography might be useful for detecting hemidiaphragm paralysis. The objective of the present study was to describe the motion recorded by M-mode ultrasonography of both diaphragmatic leaves in patients with a pre-established diagnosis of hemidiaphragm paralysis. Methods A study was conducted in 26 patients (18 men, 8 women) with unilateral diaphragmatic paralysis. They were referred to two different rehabilitation centres after thoracic surgery in 23 cases and cardiac interventional procedures in three cases. The pulmonary function tests and the study of the diaphragmatic motion using M-mode ultrasonography were recorded. Results The pulmonary function tests showed a restrictive pattern. The M-mode ultrasonography reported either the absence of motion or a weak paradoxical (cranial) displacement (less than 0 center dot 5 cm) of the paralysed hemidiaphragm during quiet breathing. A paradoxical motion was recorded in all patients during voluntary sniffing, reaching around -1 cm. During deep breathing, a paradoxical motion at the beginning of the inspiration was observed. Thereafter, a re-establishment of the motion in the craniocaudal direction was recorded. The excursions measured on the healthy side, during quiet breathing and voluntary sniffing, were increased in patients suffering from contralateral hemidiaphragm paralysis, when compared with 170 healthy volunteers. Conclusions To detect diaphragmatic dysfunction in patients at risk, it would be useful to study diaphragmatic motion by M-mode ultrasonography during quiet breathing, voluntary sniffing and deep breathing.

Published
2019

8. Is Pregnancy Outcome Influenced by Chikungunya Infection? A Case-Control Study in 1401 Pregnant Women Enrolled in the CHIMERE Cohort

Author

Fritel, Xavier, Fourmaintraux, Alain, Rollot, Olivier, Bideault, Jacques, Lagarde, Louis, Dhuime, Barbara, Gabrielle, Marc, Jaffar-Bandjee, Marie-Christine, Michault, Alain, Ramful, Duska, Samperiz, Sylvain, Cotte, Liliane, Gérardin, Patrick, Favier, François, The Chimere Team, And, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Groupe Hospitalier Sud Réunion (GHSR), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Saint Benoît- Saint André, CHI de Saint-Benoit-Saint-André, Centre Hospitalier Gabriel Martin, Clinique Sainte Clotilde, PHRC 2006, and Fritel, Xavier

Subjects
Microbiology (medical), medicine.medical_specialty, Birth weight, Population, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.disease_cause, Serology, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Medicine, 030212 general & internal medicine, Chikungunya, Seroconversion, education, 0303 health sciences, education.field_of_study, 030306 microbiology, business.industry, Obstetrics, Mother-to-child transmission, General Medicine, medicine.disease, 3. Good health, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Infectious Diseases, Cohort, business, Cohort study
Abstract

International audience; Background: In 2005—06 a Chikungunya virus outbreak infected 38% of Runion Island population. Forty-two cases of mother to child transmission were described for the first time. The purpose of the CHIMERE cohort study was to determine the consequences of Chikungunya infection on pregnancy outcomes. Methods: In 2006, 1401 pregnant women were enrolled in the CHIMERE cohort. The diagnosis of Chikungunya was based either on serology (IgM & IgG Chikungunya specific serology) planned at inclusion and at delivery, or RT-PCR performed in case of symptoms. We determined that 584 women were not infected by the virus at delivery (IgM− and IgG−), 648 were infected antepartum (IgM+, RT-PCR+, or IgG seroconversion) and 27 before pregnancy, date of infection was imprecise for 50 and assessment was incomplete for 92. We compared pregnancy outcome (prenatal hospitalization, fetal-loss and stillbirth, premature delivery, mode of delivery, birth weight, fetal malformations, newborn hospitalization) between the 584 women free of Chikungunya infection and the 648 infected during pregnancy. This prospective multicentric study has been approved by IRB (CPP de Tours, France). Results: For the 648 women infected by Chikungunya during pregnancy, the infection occurred during the first, second, and third trimester for 15, 59 and 26%, respectively; 50% presented fever, 94% arthralgia and 75% skin rash. The only difference between non-infected and infected women was the number of hospitalization during pregnancy (28 versus 42%, p = 0.0001). Other outcomes, fetal loss and stillbirth (2.2 versus 2.0%), premature delivery (12 versus 10%), cesarean rates (18 versus 16%), birth weight (3067 versus 3121 g), fetal malformations (5.0 versus 5.7%) and newborn hospitalization (6.7 versus 7.4%) were similar. Conclusion: We do not find any impact of Chikungunya infection on pregnancy outcomes except for the number of prenatal hospitalizations.

Published
2008

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