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3,195 results on '"Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)"'

1. Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills

Author: Doretta Caramaschi, Dheeraj Rai, Darina Czamara, Gwen Tindula, Isabella Annesi-Maesano, Maria De Agostini, Gemma C Sharp, Katri Räikkönen, Michael Deuschle, Jari Lahti, Maria Gilles, Jordi Sunyer, Caroline L Relton, Tabea Send, Lea Sirignano, Marie-France Hivert, Fabian Streit, Tuomas Kvist, Lea Zilich, Karen Huen, Marcella Rietschel, Brenda Eskenazi, Andres Cardenas, Janine F. Felix, Nour Baïz, Rosa H. Mulder, Stephanie H. Witt, Sheryl L. Rifas-Shiman, Muriel Ferrer, Henning Tiemeier, Charlotte A.M. Cecil, Josef Frank, Giancarlo Pesce, Samuli Tuominen, Silvia Alemany, Stephanie J. London, Alexandra Havdahl, Emily Oken, Alexander Neumann, Nina Holland, University of Bristol [Bristol], University of Exeter, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Montreal General Hospital, McGill University Health Center [Montreal] (MUHC), School of Public Health [Berkeley], University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), University of Heidelberg, Medical Faculty, Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Norwegian Institute of Public Health [Oslo] (NIPH), Medical Faculty [Mannheim], University of California (UC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Harvard Medical School [Boston] (HMS), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III [Madrid] (ISC), Leiden University Medical Center (LUMC), Cognata, Bérangère, Department of Psychology and Logopedics, University of Helsinki, Research Programs Unit, Developmental Psychology Research Group, Child and Adolescent Psychiatry / Psychology, Pediatrics, and Epidemiology
Subjects: [SDV]Life Sciences [q-bio], Intelligence, Medical and Health Sciences, 3124 Neurology and psychiatry, Epigenesis, Genetic, Epigenome, Cognition, 0302 clinical medicine, Pregnancy, Psychology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Child, Maternal smoking, Pediatric, Psychiatry, 0303 health sciences, education.field_of_study, Biological Sciences, 3. Good health, [SDV] Life Sciences [q-bio], Socioeconomic position, Psychiatry and Mental health, Blood, Mental Health, Meta-analysis, DNA methylation, Female, Clinical psychology, Pediatric Research Initiative, Population, Cohort profile, 03 medical and health sciences, Cellular and Molecular Neuroscience, Genetic, SDG 3 - Good Health and Well-being, Clinical Research, Behavioral and Social Science, Genetics, medicine, Humans, Cognitive skill, Epigenetics, education, Molecular Biology, Newborns, 030304 developmental biology, business.industry, Human Genome, Psychology and Cognitive Sciences, Infant, Newborn, 3112 Neurosciences, Infant, DNA Methylation, Newborn, medicine.disease, 1182 Biochemistry, cell and molecular biology, CpG Islands, business, 030217 neurology & neurosurgery, Epigenesis, Genome-Wide Association Study
Abstract: Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by the BBSRC (BBI025751/1 and BB/I025263/1). GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DCa is funded by the MRC (MC_UU_00011/1 and MC_UU_00011/5). GS is financially supported by the MRC [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1]. AH is supported by the South-Eastern Norway Regional Health Authority (2020022) and the Research Council of Norway (274611 and 288083). The POSEIDON work was supported by the German Research Foundation [DFG; grant FOR2107; RI908/11-2 and WI3429/3-2], the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent, under the auspices of the e:Med Programme [01ZX1314G; 01ZX1614G] through grants 01EE1406C, 01EE1409C and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” [01EW1810], through ERA-NET NEURON “Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention” [01EW1904] and by a grant of the Dietmar-Hopp Foundation. The general design of the Generation R Study is made possible by financial support from Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). AN and HT are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). AN is also supported by a Canadian Institutes of Health Research team grant. The work of HT is further supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). JFF has received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no. 529051022) and the European Union’s Horizon 2020 research and innovation programme (733206, LifeCycle; 633595, DynaHEALTH). The work of CAMC, JF and RM has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 848158 (EarlyCause Project). Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615) Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). The Project Viva work was supported by the US National Institutes of Health grants R01 HD034568, UH3 OD023286 and R01 ES031259. The CHAMACOS project was supported by grants from the Environmental Protection Agency [R82670901 and RD83451301], the National Institute of Environmental Health Science (NIEHS) [P01 ES009605, R01ES021369, R01ES023067, R24ES028529, F31ES027751], the National Institute on Drug Abuse (NIDA) [R01DA035300], the National Institutes of Health (NIH) [UG3OD023356] and the National Institute of Mental Health (NIMH) [T32MH112510]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the EPA, NIEHS, or NIH. We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale complementary health insurance (MGEN), French national agency for food security, French speaking association for the study of diabetes and metabolism (ALFEDIAM), grant # 2012/51290-6 Sao Paulo Research Foundation (FAPESP), EU funded MeDALL project. PREDO: The PREDO Study has been funded by the Academy of Finland (JL: 311617 and 269925, KR: 1312670 ja 128789 1287891), EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, Juho Vainio foundation, Yrjö Jahnsson foundation, Jalmari and Rauha Ahokas foundation, Sigrid Juselius Foundation granted to members of the Predo study board. Methylation assays were funded by the Academy of Finland (269925). SJL is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.
Published: 2022

2. 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

3. Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial

Author: Ashish Dugar, Eugenio Mercuri, Xiaodong Wang, Volker Straub, Baoguang Han, Daniela Leone, Navid Khan, Dan Wang, Erica Koenig, Laurent Servais, Andreea Mihaela Seferian, Michela Guglieri, Mariacristina Scoto, Francesco Muntoni, University of Oxford, 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), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, University College of London [London] (UCL), Great Ormond Street Hospital for Children [London] (GOSH), Sarepta Therapeutics, University of Oxford [Oxford], I-Motion Institut [CHU Trousseau], 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)-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), Università cattolica del Sacro Cuore [Roma] (Unicatt), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], and Gestionnaire, Hal Sorbonne Université
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Population, Oligonucleotides, Walk Test, golodirsen, Biochemistry, Dystrophin, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Internal medicine, Multicenter trial, Drug Discovery, Genetics, medicine, Clinical endpoint, Humans, education, Molecular Biology, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Exons, medicine.disease, Original Papers, Exon skipping, 3. Good health, Clinical trial, Muscular Dystrophy, Duchenne, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ambulatory, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular Medicine, business, 030217 neurology & neurosurgery, exon skipping
Abstract: The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled, dose-titration study followed by 9-week safety review. Part 2 was a 168-week, open-label evaluation of golodirsen 30 mg/kg. Part 1 primary endpoint was safety. Part 2 primary endpoints were dystrophin protein expression and 6-minute walk test (6MWT); secondary endpoints were percent predicted forced vital capacity (FVC%p) and safety. Post hoc ambulation analyses used mutation-matched external natural history controls. All patients from Part 1 (golodirsen, n = 8; placebo, n = 4) plus 13 additional patients entered Part 2; 23 completed the study. Adverse events were generally mild, nonserious, and unrelated to golodirsen, with no safety-related discontinuations or deaths. Golodirsen increased dystrophin protein (16.0-fold; P
Published: 2022

4. The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

Author: Antonio Gallo, Leopoldo Pérez de Isla, Sybil Charrière, Alexandre Vimont, Rodrigo Alonso, Ovidio Muñiz-Grijalvo, José L. Díaz-Díaz, Daniel Zambón, Philippe Moulin, Eric Bruckert, Pedro Mata, Sophie Béliard, Denis Angoulvant, Sophie Beliard, Franck Boccara, Bertrand Cariou, Valérie Carreau, Alain Carrie, Sybil Charrieres, Yves Cottin, Mathilde Di Filippo, Pierre Henri Ducluzeau, Sonia Dulong, Vincent Durlach, Michel Farnier, Emile Ferrari, Dorota Ferrieres, Jean Ferrieres, Philippe Giral, Sophie Gonbert, Regis Hankard, Jocelyn Inamo, Olga Kalmykova, Michel Krempf, Julie Lemale, François Paillard, Noel Peretti, Agnes Perrin, Alain Pradignac, Jean Pierre Rabes, Vincent Rigalleau, François Schiele, Ariane Sultan, Patrick Tounian, René Valero, Bruno Verges, Cecile Yelnik, Olivier Ziegler, Rocío Aguado, Ma Pilar Álvarez-Baños, Rosa Argüeso, Francisco Arrieta, Miguel Ángel Barba, Marta Casañas, José María Cepeda, Raimundo De Andrés, Gonzalo Díaz-Soto, Jose Luis Díaz-Diaz, Marta Dieguez, Ceferino Faedo, Francisco Fuentes, Juan A. Garrido, Aurora González, Pablo González-Bustos, Ma Dolores Mañas, Marta Mauri, Juan Diego Mediavilla, Alfredo Michán, Pablo Miramontes, Ovidio Muñiz, Leire Pérez, Leopoldo Perez De Isla, Xavier Pintó, Manuel J. Romero, Patricia Rubio, Juan F. Sánchez Muñoz-Torrero, Jose I. Vidal-Pardo, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), 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), Public Health Expertise [Paris, France], Hospital Universitario Virgen del Rocío [Sevilla], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), 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 de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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], Hospital Abente y Lago, Fundación Hipercolesterolemia Familiar, and ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Coronary Artery Disease, Disease, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Risk Assessment, Sudden death, Cohort Studies, Hyperlipoproteinemia Type II, risk prediction, 03 medical and health sciences, 0302 clinical medicine, cardiovascular disease, genetic disease, Predictive Value of Tests, Risk Factors, Interquartile range, Internal medicine, Humans, Medicine, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Vascular Calcification, Stroke, coronary artery calcium, ComputingMilieux_MISCELLANEOUS, familial hypercholesterolemia, business.industry, Proportional hazards model, nutritional and metabolic diseases, Middle Aged, Atherosclerosis, medicine.disease, 3. Good health, Coronary Calcium Score, Cardiology, Calcium, Cardiology and Cardiovascular Medicine, business, coronary imaging, Cohort study
Abstract: International audience; ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.
Published: 2021

5. Poor Correlation between Diaphragm Thickening Fraction and Transdiaphragmatic Pressure in Mechanically Ventilated Patients and Healthy Subjects

Author: Thomas Poulard, Jean-Luc Gennisson, Damien Bachasson, Martin Dres, Alexandre Demoule, Marie-Cécile Niérat, Jean-Yves Hogrel, Quentin Fossé, Laboratoire de physiologie et d'évaluation neuromusculaire, 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)-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), Unité BioMaps (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [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), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), 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), and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Diaphragm, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pressure, medicine, Humans, In patient, Prospective Studies, Poor correlation, Aged, business.industry, Transdiaphragmatic pressure, Healthy subjects, Repeated measures design, 030208 emergency & critical care medicine, Organ Size, Middle Aged, Respiration, Artificial, Healthy Volunteers, Respiratory Function Tests, Diaphragm (structural system), Anesthesiology and Pain Medicine, 030228 respiratory system, Breathing, Cardiology, Thickening, business
Abstract: Background The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients. Methods Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed. Results In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01). Conclusions Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2021

6. DICE: A Bayesian model for early dose finding in phase I trials with multiple treatment courses

Author: Lucie Biard, Moreno Ursino, Sylvie Chevret, 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), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and 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)
Subjects: Statistics and Probability, Oncology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Bayesian probability, Dice, Phase i trials, General Medicine, Bayesian inference, [STAT]Statistics [stat], Clinical trial, Dose finding, Maximum tolerated dose, Internal medicine, medicine, Statistics, Probability and Uncertainty, business, Cumulative effect
Abstract: International audience; Dose-finding clinical trials in oncology aim to determine the maximum tolerated dose (MTD) of a new drug, generally defined by the proportion of patients with short-term dose-limiting toxicities (DLTs). Model-based approaches for such phase I oncology trials have been widely designed and are mostly restricted to the DLTs occurring during the first cycle of treatment, although patients continue to receive treatment for multiple cycles. We aim to estimate the probability of DLTs over sequences of treatment cycles via a Bayesian cumulative modeling approach, where the probability of DLT is modeled taking into account the cumulative effect of the administered drug and the DLT cycle of occurrence. We propose a design, called DICE (Dose-fInding CumulativE), for dose escalation and de-escalation according to previously observed toxicities, which aims at finding the MTD sequence (MTS). We performed an extensive simulation study comparing this approach to the time-to-event continual reassessment method (TITE-CRM) and a benchmark. In general, our approach achieved a better or comparable percentage of correct MTS selection. Moreover, we investigated the DICE prediction ability.
Published: 2021

7. Size and Predictive Factors of Microscopic Tumor Extension in Locally Advanced Non-Small Cell Lung Cancer

Author: Nicolas Giraud, Claire Meynard, Catherine Durdux, Audrey Mansuet-Lupo, Armelle Guénégou-Arnoux, Diane Damotte, Geoffroy Boulle, P. Giraud, Paul Imbault, Antonio Bobbio, 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), 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 Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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 HAL-SU, Gestionnaire
Subjects: medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Cell, Planning target volume, Locally advanced, Magnification, Adenocarcinoma, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Computed Tomography, 0302 clinical medicine, Microscopic tumoral extension, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, Nodal status, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Lung cancer, Conformal radiation therapy, Neoplasm Staging, Retrospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, business.industry, MESH: Adenocarcinoma, MESH: Carcinoma, Squamous Cell, MESH: Retrospective Studies, MESH: Neoplasm Staging, medicine.disease, MESH: Lung Neoplasms, 3. Good health, Radiation therapy, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Non small cell, Radiology, business, Clinical Target Volume, MESH: Carcinoma, Non-Small-Cell Lung, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: Radiation therapy for locally advanced non-small cell lung cancer (NSCLC) should treat the whole tumor, including its microscopic extensions, and protect adjacent organs at risk as much as possible. The aim of our study is to evaluate the size of microscopic tumor extension (MEmax) in NSCLC, and search for potential predictive factors.Methods and materials: We retrospectively selected 70 patients treated with postoperative radiation therapy for a NSCLC with N2 nodal status, then 34 additional patients operated for a squamous cell lung cancer with N1 or N2 nodal status. On the digitized slides originating from the resected tumors of these 104 patients, we outlined the border of the tumor, as seen with the naked eye. We then searched for microscopic tumor extension outside of these borders with a magnification as high as 40 × and measured the maximum size of MEmax.Results: The median MEmax in the whole cohort was 0.85 mm (0-9.95). The MEmax was
Published: 2021

8. Determinants of diaphragm inspiratory motion, diaphragm thickening, and its performance for predicting respiratory restrictive pattern in <scp>Duchenne</scp> muscular dystrophy

Author: Nicolas Mansencal, Abdallah Fayssoil, Frédéric Lofaso, H. Prigent, Robert Carlier, Karim Wahbi, Pascal Laforêt, Jean Bergounioux, Tanya Stojkovic, Helge Amthor, Anthony Behin, Guillaume Bassez, Guillaume Nicolas, Djillali Annane, Lee S. Nguyen, Rabah Ben Yaou, Sebastien Damez-Fontaine, David Orlikowski, Justine Zini, Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [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), Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), 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), CMC Ambroise Paré [Neuilly-sur-Seine], Service de physiologie et d'explorations fonctionnelles [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service d'Imagerie Médicale [Raymond-Poincaré], Hôpital Raymond Poincaré [AP-HP], Filière Neuromusculaire (FILNEMUS), 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), Analysis-Synthesis Approach for Virtual Human Simulation (MIMETIC), Université de Rennes 2 (UR2)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-RÉALITÉ VIRTUELLE, HUMAINS VIRTUELS, INTERACTIONS ET ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de biochimie et de génétique moléculaire [CHU Cochin], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), CIC Paris Est, Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris), Service de pharmacologie médicale [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), Dpt Radiologie [CHU Poincaré], Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-MEDIA ET INTERACTIONS (IRISA-D6), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Paris Est (CIC Paris-Est), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre régional de Pharmacovigilance [CHU Pitié] (CRPV Paris Pitié), Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Inria Rennes – Bretagne Atlantique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: Duchenne muscular dystrophy, medicine.medical_specialty, Vital capacity, pulmonary, Physiology, Vital Capacity, Pulmonary insufficiency, Inspiratory Capacity, 03 medical and health sciences, Cellular and Molecular Neuroscience, FEV1/FVC ratio, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Respiratory system, Retrospective Studies, 2. Zero hunger, ultrasound, business.industry, Area under the curve, medicine.disease, Respiratory Function Tests, 3. Good health, Diaphragm (structural system), Muscular Dystrophy, Duchenne, 030228 respiratory system, diaphragm, Cardiology, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Introduction/aims: Respiratory status is a key determinant of prognosis in patients with Duchenne muscular dystrophy (DMD). We aimed to evaluate the determinants of diaphragm ultrasound and its performance in predicting restrictive respiratory patterns in DMD.Methods: This was a retrospective study of DMD patients followed in our center and admitted for an annual checkup from 2015 to 2018. We included DMD patients who underwent diaphragm ultrasound and pulmonary functional tests.Results: This study included 74 patients with DMD. The right diaphragm thickening fraction (TF) was significantly associated with age (P = .001), Walton score (P = .012), inspiratory capacity (IC) (P = .004), upright forced vital capacity (FVC) (P < .0001), supine FVC (P = .038), and maximal inspiratory pressure (MIP) (P = .002). Right diaphragm excursion was significantly associated with age (P < .0001), steroid use (P = .008), history of spinal fusion (P < .0001), body mass index (BMI) (P = .002), Walton score (P < .0001), IC (P < .0001), upright FVC (P < .0001), supine FVC (P < .0001), and MIP (P < .0001). A right diaphragm TF >28% and a right diaphragm excursion>25.4 mm were associated with an FVC >50% with, respectively, an area under the curve (AUC) of 0.95 (P = .001) and 0.93 (P < .001). A left diaphragm TF >26.8% and a left diaphragm excursion >21.5 mm were associated with an FVC >50% with, respectively, an AUC of 0.95 (P = .011) and 0.97 (P < .001).Discussion: Diaphragm excursion and diaphragm TF can predict restrictive pulmonary insufficiency in DMD.
Published: 2021

9. External validation of prognostic scores for COVID-19: a multicenter cohort study of patients hospitalized in Greater Paris University Hospitals

Author: Lombardi, Yannis, Azoyan, Loris, Szychowiak, Piotr, Bellamine, Ali, Lemaitre, Guillaume, Bernaux, Mélodie, Daniel, Christel, Leblanc, Judith, Riller, Quentin, Steichen, Olivier, Ancel, Pierre-Yves, Bauchet, Alain, Beeker, Nathanael, Benoit, Vincent, Bey, Romain, Bourmaud, Aurélie, Bréant, Stéphane, Burgun, Anita, Carrat, Fabrice, Caucheteux, Charlotte, Champ, Julien, Cormont, Sylvie, Dubiel, Julien, Duclos, Catherine, Esteve, Loic, Frank, Marie, Garcelon, Nicolas, Gramfort, Alexandre, Griffon, Nicolas, Grisel, Olivier, Guilbaud, Martin, Hassen-Khodja, Claire, Hemery, François, Hilka, Martin, Jannot, Anne Sophie, Lambert, Jerome, Layese, Richard, Lebouter, Léo, Leprovost, Damien, Lerner, Ivan, Sallah, Kankoe Levi, Maire, Aurélien, Mamzer, Marie-France, Martel, Patricia, Mensch, Arthur, Moreau, Thomas, Neuraz, Antoine, Orlova, Nina, Paris, Nicolas, Rance, Bastien, Ravera, Hélène, Rozes, Antoine, Rufat, Pierre, Salamanca, Elisa, Sandrin, Arnaud, Serre, Patricia, Tannier, Xavier, Treluyer, Jean-Marc, van Gysel, Damien, Varoquaux, Gael, Vie, Jill-Jênn, Wack, Maxime, Wajsburt, Perceval, Wassermann, Demian, Zapletal, Eric, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Méthodes computationnelles et mathématiques pour comprendre la société et la santé à partir de données (SODA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), 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, 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 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), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et de 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 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], 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)-Centre National de la Recherche Scientifique (CNRS), Direction générale déléguée à l'innovation (DGD-I), Institut National de Recherche en Informatique et en Automatique (Inria), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Inria Siège, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Adult, Paris, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Original, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, law.invention, Cohort Studies, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, law, Anesthesiology, medicine, Humans, 030212 general & internal medicine, Mortality, Retrospective Studies, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Receiver operating characteristic, SARS-CoV-2, business.industry, External validation, COVID-19, Prognosis, University hospital, Intensive care unit, 3. Good health, Intensive Care Units, Editorial, SARS-CoV2, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Emergency medicine, Cohort, business, Cohort study
Abstract: Purpose The Coronavirus disease 2019 (COVID-19) has led to an unparalleled influx of patients. Prognostic scores could help optimizing healthcare delivery, but most of them have not been comprehensively validated. We aim to externally validate existing prognostic scores for COVID-19. Methods We used “COVID-19 Evidence Alerts” (McMaster University) to retrieve high-quality prognostic scores predicting death or intensive care unit (ICU) transfer from routinely collected data. We studied their accuracy in a retrospective multicenter cohort of adult patients hospitalized for COVID-19 from January 2020 to April 2021 in the Greater Paris University Hospitals. Areas under the receiver operating characteristic curves (AUC) were computed for the prediction of the original outcome, 30-day in-hospital mortality and the composite of 30-day in-hospital mortality or ICU transfer. Results We included 14,343 consecutive patients, 2583 (18%) died and 5067 (35%) died or were transferred to the ICU. We examined 274 studies and found 32 scores meeting the inclusion criteria: 19 had a significantly lower AUC in our cohort than in previously published validation studies for the original outcome; 25 performed better to predict in-hospital mortality than the composite of in-hospital mortality or ICU transfer; 7 had an AUC > 0.75 to predict in-hospital mortality; 2 had an AUC > 0.70 to predict the composite outcome. Conclusion Seven prognostic scores were fairly accurate to predict death in hospitalized COVID-19 patients. The 4C Mortality Score and the ABCS stand out because they performed as well in our cohort and their initial validation cohort, during the first epidemic wave and subsequent waves, and in younger and older patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06524-w.
Published: 2021

10. Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial

Author: Amélie Gatin, Pascal Saunier, Simon Henry, Astrid Vabret, Christèle Gras-Le Guen, Vanessa Degas-Bussiere, Thanh-Van Trieu, Dominique Ploin, Luigi Titomanlio, Jacques Brouard, Isabelle Durand-Zaleski, Delphine Regnard, François Angoulvant, Géraldine Patteau, Jean-Paul Teglas, Abdelilah Tahir, Jean Bouyer, Valérie Soussan-Banini, Yves Marot, Henri Panjo, Philippe Minodier, B. Vrignaud, Philippe Babe, Thibault Butel, Ralph Epaud, Antoine Filipovic-Pierucci, Philippe Flahaut, Mathilde Delebarre, Karen Milcent, Xavier Bellettre, Oussama Charara, Isabelle Claudet, Pierrick Cros, Vincent Gajdos, François Dubos, Amélie Ryckewaert, Cyril Schweitzer, Pascale Micheau, Loïc de Pontual, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)), 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), 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), AP-HP - Hôpital Antoine Béclère [Clamart], 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, Hôpital Robert Debré, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Verdier [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), CHU Lille, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Sud Francilien, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Rouen, Normandie Université (NU), Centre Hospitalier de Fontainebleau, Hôpitaux Pédiatriques de Nice Lenval (CHU-Lenval), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Necker - Enfants Malades [AP-HP], Hôpital Robert Debré Paris, CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), and Centre Hospitalier le Vinatier [Bron]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Epidemiology, Total cost, [SDV]Life Sciences [q-bio], law.invention, law, medicine, Humans, Child, First episode, business.industry, Infant, Asthma & early wheeze, Emergency department, medicine.disease, Intensive care unit, Economic evaluation, Hospitalization, Clinical trial, Bronchiolitis, Pediatrics, Perinatology and Child Health, Cohort, Emergency medicine, France, Emergency Service, Hospital, business
Abstract: International audience; Introduction: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED).Methods: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority.Results: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France.Discussion: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.
Published: 2021

11. Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes

Author: François Lifermann, Jean-Alain Martignoles, Anne Quinquenel, Vincent Parinet, Christine Lefebvre, Pierre Hirsch, Mélanie Martin, Sabine Defasque, Florence Nguyen-Khac, Matthieu Decamp, Laurence Simon, Dominique Penther, Nadia Ali-Ammar, Elise Chapiro, Odile Maarek, Chrystele Bilhou-Nabera, Baptiste Gaillard, Agathe Maillon, Jean-Baptiste Micol, Marine Baron, Nathalie Auger, Stéphanie Struski, Damien Roos-Weil, Sylvie Tondeur, Marie-Joelle Mozziconacci, Audrey Bidet, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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 Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Robert Debré, Service d'Hémato-oncologie [CHU Saint-Louis], 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 Hospitalier Universitaire [Grenoble] (CHU), Laboratoire CERBA [Saint Ouen l'Aumône], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier de Dax, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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], Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], 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), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), HAL-SU, Gestionnaire, École Pratique des Hautes Études (EPHE), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Oncology, Myeloid, [SDV]Life Sciences [q-bio], Chromosomal translocation, Translocation, Genetic, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, 12), In Situ Hybridization, Fluorescence, Aged, 80 and over, CHIC2, Middle Aged, Immunohistochemistry, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, medicine.anatomical_structure, RUNX1, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Cohort, Molecular Medicine, Female, Original Article, Chromosomes, Human, Pair 4, medicine.medical_specialty, IDH1, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, acute myeloid leukaemia, Genetic Association Studies, Aged, Chromosome Aberrations, Chromosomes, Human, Pair 12, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Original Articles, ETV6, Cell Biology, medicine.disease, myelodysplastic syndrome, t(4, chemistry, Fusion transcript, Myelodysplastic Syndromes, prognosis, business, 030215 immunology
Abstract: International audience; Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.
Published: 2021

12. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis

Author: Kosuke Matsumoto, Bettina E. Hansen, Hajime Takikawa, Toshiaki Nakano, Olivier Chazouillères, Atsushi Tanaka, Fabrice Carrat, Junko Hirohara, Christophe Corpechot, Teikyo University School of Medicine, Kansai Medical University, 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), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [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), University of Toronto, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], and HAL-SU, Gestionnaire
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Liver transplantation, Lower risk, Gastroenterology, Cohort Studies, Japan, Internal medicine, medicine, Humans, Proportional Hazards Models, Retrospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, Liver Cirrhosis, Biliary, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, Prognosis, Ursodeoxycholic acid, Transplantation, Treatment Outcome, Cohort, Number needed to treat, Female, Bezafibrate, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort.All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT).Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively.In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis.The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.
Published: 2021

13. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment

Author: Andrew Maltez Thomas, Aude Sirven, Filippo Pietrantonio, Romy Aarnoutse, Carlos Caldas, Sibille Everhard, Marine Fidelle, Valerio Iebba, Fanny Aprahamian, Stergios Christodoulidis, Sylvère Durand, Lisa Derosa, Sibylle Loibl, Janine Ziemons, François Ghiringhelli, Carsten Denkert, Suzette Delaloge, Nicola Segata, Edoardo Pasolli, Anne-Laure Martin, Nitharsshini Nirmalathasan, Safae Terrisse, Laurence Zitvogel, Fabrice Andre, Marjolein L. Smidt, Guido Kroemer, Ines Vaz-Luis, Bertrand Routy, Claudia Iglesias, Terrisse, Safae, Derosa, Lisa, Iebba, Valerio, Ghiringhelli, Françoi, Vaz-Luis, Ine, Kroemer, Guido, Fidelle, Marine, Christodoulidis, Stergio, Segata, Nicola, Thomas, Andrew Maltez, Martin, Anne-Laure, Sirven, Aude, Everhard, Sibille, Aprahamian, Fanny, Nirmalathasan, Nitharsshini, Aarnoutse, Romy, Smidt, Marjolein, Ziemons, Janine, Caldas, Carlo, Loibl, Sibylle, Denkert, Carsten, Durand, Sylvere, Iglesias, Claudia, Pietrantonio, Filippo, Routy, Bertrand, André, Fabrice, Pasolli, Edoardo, Delaloge, Suzette, Zitvogel, Laurence, Institut Gustave Roussy (IGR), Faculté de médecine de l'Université Paris-Sud [Kremlin Bicêtre, Paris], Université Paris-Saclay, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Biothérapie [Paris] (CICBT), Institut Curie [Paris], Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut de médecine génomique et d’immunothérapie (Genomic and Immunotherapy Medical Institute) (institut GIMI), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), 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), University of Trento [Trento], Università degli studi di Trieste = University of Trieste, Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), Maastricht University [Maastricht], University of Cambridge [UK] (CAM), Goethe-University Frankfurt am Main, Philipps Universität Marburg = Philipps University of Marburg, IRCCS Istituto Nazionale dei Tumori [Milano], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), University of Naples Federico II = Università degli studi di Napoli Federico II, ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Surgery, MUMC+: MA Heelkunde (9), UNICANCER-UNICANCER-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-FHU TRANSLAD (CHU de Dijon), 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 (UPC), University of Trieste, University of Naples Federico II, Ghiringhelli, François [0000-0002-5465-8305], Kroemer, Guido [0000-0002-9334-4405], Christodoulidis, Stergios [0000-0002-8773-1070], Segata, Nicola [0000-0002-1583-5794], Thomas, Andrew Maltez [0000-0001-5789-3354], Aarnoutse, Romy [0000-0002-8713-9747], Ziemons, Janine [0000-0002-4559-5488], Caldas, Carlos [0000-0003-3547-1489], Zitvogel, Laurence [0000-0003-1596-0998], Apollo - University of Cambridge Repository, Terrisse, S., Derosa, L., Iebba, V., Ghiringhelli, F., Vaz-Luis, I., Kroemer, G., Fidelle, M., Christodoulidis, S., Segata, N., Thomas, A. M., Martin, A. -L., Sirven, A., Everhard, S., Aprahamian, F., Nirmalathasan, N., Aarnoutse, R., Smidt, M., Ziemons, J., Caldas, C., Loibl, S., Denkert, C., Durand, S., Iglesias, C., Pietrantonio, F., Routy, B., Andre, F., Pasolli, E., Delaloge, S., and Zitvogel, L.
Subjects: Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], GUT MICROBIOME, THERAPY, Breast cancer, Breast Neoplasms, Female, Gastrointestinal Microbiome, Humans, Prognosis, Prospective Studies, Treatment Outcome, TUMOR-INFILTRATING LYMPHOCYTES, Prospective cohort study, Cancer, Early breast cancer, Microbiota, ADENOSINE, SOLID TUMORS, Intestinal Microbiome, Immunotherapy, PATHOLOGISTS, Adjuvant, Shotgun metagenomics, medicine.medical_specialty, CARCINOMA, CANTO study, Article, Immune system, STANDARDIZED METHOD, Internal medicine, medicine, Chemotherapy, Clinical significance, metagenomic, IMMUNOTHERAPY, Molecular Biology, metagenomics, business.industry, neoadjuvant, Cell Biology, Translational research, EFFICACY, networks, network, business
Abstract: The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.
Published: 2021

14. Postnatal Diagnostic Workup in Children With Arthrogryposis: A Series of 82 Patients

Author: Elise Leroy-Terquem, Robert Carlier, Antoine Neuraz, Judith Melki, Judith Chareyre, Alina Badina, Marie Hully, Isabelle Desguerre, Cyril Gitiaux, Christine Barnerias, Elsa Kermorvant-Duchemin, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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)), 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)-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), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Raymond Poincaré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM), 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 (UPC)-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 (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, Pediatrics, medicine.medical_specialty, Arthrogryposis multiplex congenita, Fetal akinesia, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Outcome, Arthrogryposis, Diagnostic strategy, 0303 health sciences, business.industry, 030305 genetics & heredity, Infant, Magnetic Resonance Imaging, 3. Good health, Pediatrics, Perinatology and Child Health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), medicine.symptom, business, ENMG, 030217 neurology & neurosurgery
Abstract: Objective:To describe a postnatal series of patients with arthrogryposis multiplex congenita by the causal mechanisms involved.Methods:In this single-center study, the local data warehouse was used to identify patients with arthrogryposis multiplex congenita. Patients were classified into different etiologic groups.Results:Of 82 patients included, the most frequent cause of arthrogryposis multiplex congenita was a neuromuscular disorder (39%), including skeletal muscle (n = 19), neuromuscular junction (n = 3), and peripheral nerve (n = 11) involvement. In other subgroups, 19 patients (23%) were classified by disorders in the central nervous system, 5 (6%) in connective tissue, 7 (8.5%) had mixed mechanisms, and 18 (22%) could not be classified. Contractures topography was not associated with a causal mechanism. Cerebral magnetic resonance imaging (MRI), electroneuromyography, and muscle biopsy were the most conclusive investigations. Metabolic investigations were normal in all the patients tested. Targeted or whole exome sequencing diagnostic rates were 51% and 71%, respectively. Thirty-three percent of patients died (early death occurred in patients with polyhydramnios, prematurity, and ventilatory dependency).Discussion:The benefits of a precise diagnosis in the neonatal period include more tailored management of arthrogryposis multiplex congenita and better genetic information.
Published: 2021

15. Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

Author: Franck Phan, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Joe-Elie Salem, Nadjia Kachenoura, Khaoula Bouazizi, Etienne Charpentier, Yasmine Niati, Hasnae Bekkaoui, Zahir Amoura, Alexis Mathian, Olivier Benveniste, Patrice Cacoub, Yves Allenbach, David Saadoun, Jean-Marc Lacorte, Salma Fourati, Suzanne Laroche, Agnes Hartemann, Olivier Bourron, Fabrizio Andreelli, Alban Redheuil, COVID-19 APHP.SU Group, Service de Diabétologie [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), 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), 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), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), HAL-SU, Gestionnaire, Service de diabétologie [CHU Pitié-Salpétrière], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030204 cardiovascular system & hematology, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mass index, 030212 general & internal medicine, Hospital Mortality, Original Investigation, Outcome, 2. Zero hunger, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cardiac adipose tissue, Diabetes, Heart, Organ Size, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Intensive Care Units, Adipose Tissue, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Median body, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiac computed tomography, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Intensive care, Severity of illness, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Angiology, Aged, Inflammation, business.industry, SARS-CoV-2, Interleukin-6, Myocardium, COVID-19, medicine.disease, Obesity, Diabetes Mellitus, Type 2, RC666-701, business, Tomography, X-Ray Computed
Abstract: BackgroundCOVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission.MethodsEighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined.ResultsOf the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2[IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2,p p = 0.01; OR = 4.86,p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p ConclusionsCardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission,a fortioriassociated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.
Published: 2021

16. Postoperative outcomes after laparoscopic or open gastrectomy. A national cohort study of 10,343 patients

Author: Ben Creavin, Alexandre Challine, Sandrine Katsahian, Andrea Lazzati, Bertrand Dousset, Thibault Voron, Jérémie H. Lefevre, Yann Parc, 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), Chirurgie digestive, hépato-biliaire et endocrinienne [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie générale et digestive [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), St Vincent's University Hospital, 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 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 Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, Reoperation, medicine.medical_specialty, Hospitals, Low-Volume, medicine.medical_treatment, Population, National cohort, Cohort Studies, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Oesophageal stricture, Gastrectomy, Stomach Neoplasms, Open approach, medicine, Humans, Mortality, education, Laparoscopy, Aged, Aged, 80 and over, Laparotomy, education.field_of_study, medicine.diagnostic_test, business.industry, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, General Medicine, Length of Stay, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Esophageal Stenosis, Female, 030211 gastroenterology & hepatology, Morbidity, Gastric cancer, business, Hospitals, High-Volume
Abstract: International audience; BackgroundLaparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical techniques comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy.MethodsA retrospective study (2013–2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG).ResultsA total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open = 39.4% vs. Laparoscopy = 32.6%, p = 0.01), length of stay (Open = 14[10–21] vs. Laparoscopy = 11[8–17] days, p
Published: 2021

17. A Fresh Perspective on Monoclonal Gammopathies of Renal Significance

Author: Pierre Ronco, Pierre Aucouturier, Vivette D. D'Agati, 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), Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Columbia University Medical Center (CUMC), Columbia University [New York], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Aucouturier, Pierre, Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunoglobulin Isotypes, 030232 urology & nephrology, Review, 030204 cardiovascular system & hematology, Bioinformatics, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, glomerulopathy, 03 medical and health sciences, 0302 clinical medicine, Medicine, immunoglobulin isotypes, immunoglobulin variable regions, business.industry, monoclonal gammopathy, monoclonalgammopathy, IgG3, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, monotypic deposits, 3. Good health, Monoclonal gammopathy, PGNMID, Nephrology, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Treatment strategy, medicine.symptom, business, Clone (B-cell biology)
Abstract: International audience; Monoclonal gammopathies of renal significance (MGRS) encompass a remarkable variety of kidney diseases that result from intrinsic nephrotoxic properties of certain monoclonal Igs or their subunits. Effective disease-modifying treatments rely on the targeting of a malignant B-cell clone that may be demonstrable but often is quite hypothetical. Hence, convincing arguments for the genuine monoclonal character of the causative mono-isotypic Ig tissue deposits is needed for design of appropriate treatment strategies. The purpose of this article was to critically analyze distinct situations of suspected MGRS that occur in the practice of pathologists, nephrologists, hematologists, and immunologists. A particular focus of interest is the group of conditions known as proliferative glomerulonephritis with mono-isotypic immunoglobulin deposits (PGNMIDs), which illustrates the difficulties and ambiguities surrounding a definitive assignment of MGRS status.
Published: 2021

18. Improved Cardiac Outcomes by Early Treatment with Angiotensin-Converting Enzyme Inhibitors in Becker Muscular Dystrophy

Author: Nawal Berber, Pascal Laforêt, Bertrand Fontaine, Marion Masingue, Leslie Motté, Malika Saadi, Anthony Behin, Sarah Leonard Louis, Denis Duboc, Rabah Ben Yaou, Guillaume Bassez, Karim Wahbi, Stéphane Ederhy, Caroline Stalens, Tanya Stojkovic, Gestionnaire, HAL Sorbonne Université 5, Association française contre les myopathies (AFM-Téléthon), 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), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Raymond Poincaré [AP-HP], 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), Service de Cardiologie [CHU Cochin], This study was funded by grants from AFM-Téléthon (Association Française contre les Myopathies)., Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Unité clinique de pathologie neuromusculaire [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), 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), Centre de Recherche en Myologie, and 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)-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)
Subjects: Adult, Male, medicine.medical_specialty, Management of heart failure, Cardiomyopathy, heart failure, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Ventricular Function, Left, Young Adult, 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, 030212 general & internal medicine, Retrospective Studies, Ejection fraction, biology, business.industry, Hazard ratio, Angiotensin-converting enzyme, Middle Aged, medicine.disease, inherited myopathy, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, Muscular Dystrophy, Duchenne, non-ischemic cardiomyopathy, Treatment Outcome, angiotensin-converting enzyme inhibitor, Neurology, Becker muscular dystrophy, Heart failure, Propensity score matching, biology.protein, Female, Neurology (clinical), Cardiomyopathies, business, Research Article
Abstract: International audience; Background: The latest practice guidelines from the American College of Cardiology/American Heart Association recommend the prescription of an ACE-i for patients presenting with non-ischemic cardiomyopathy when left ventricular ejection fraction (LVEF) falls below 40%. Objective: To determine if the initiation of treatment with an angiotensin-converting enzyme inhibitor (ACE-i) earlier than recommended by practice guidelines issued by professional societies improves the long-term cardiac outcomes of patients presenting with Becker muscular dystrophy (MD) cardiomyopathy. Methods: From a multicenter registry of Becker MD, we selected retrospectively patients presenting between January 1990 and April 2019 with a LVEF ≥40 and ≤49%. We used a propensity score analysis to compare the risk of a) hospitalization for management of heart failure (HF), and b) a decrease in LVEF to
Published: 2021

19. How do clinical and socioeconomic factors impact on work disability in early axial spondyloarthritis? Five-year data from the DESIR cohort

Author: Elena Nikiphorou, Bruno Fautrel, Pascal Richette, Robert Landewé, Annelies Boonen, Sofia Ramiro, Désirée van der Heijde, King‘s College London, Leiden University Medical Center (LUMC), King's College Hospital (KCH), Maastricht University [Maastricht], Service de Rhumatologie [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), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dpt of Clinical Immunology & Rheumatology [Amsterdam], Amsterdam and Atrium Medical Center, Zuyderland Hospital [Heerlen, The Netherlands], Gestionnaire, Hal Sorbonne Université, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, Interne Geneeskunde, MUMC+: MA Reumatologie (9), Clinical Immunology and Rheumatology, and AII - Inflammatory diseases
Subjects: work disability, medicine.medical_specialty, [SDV]Life Sciences [q-bio], socioeconomic factors, Severity of Illness Index, Cohort Studies, Rheumatology, QUALITY-OF-LIFE, Internal medicine, Spondylarthritis, medicine, Humans, axSpA, Spondylitis, Ankylosing, Pharmacology (medical), Axial spondyloarthritis, Socioeconomic status, Ankylosing spondylitis, PRODUCTIVITY, adverse work outcomes, Work disability, business.industry, Incidence (epidemiology), Desir cohort, ANKYLOSING-SPONDYLITIS, medicine.disease, [SDV] Life Sciences [q-bio], Cohort, FOLLOW-UP, business, BASFI, disease activity, Axial Spondyloarthritis
Abstract: Objectives To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA). Methods Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity and interaction tests guided subsequent multivariable time-varying Cox survival analyses. Results From 704 patients eligible for this study, the estimated incidence of WD among those identified as at risk (n = 663, 94%), and across the five years of DESIR, was 0.05 (95% CI 0.03, 0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the AS disease activity score (ASDAS) and the BASFI were significantly and independently associated with a higher hazard of WD [HR (95%CI) 1.79 (1.27, 2.54) and 1.42 (1.22, 1.65), respectively]. Conclusion WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were among the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA.
Published: 2021

20. Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID‐19: An Observational Multicenter Study

Author: Hoertel, Nicolas, Sánchez-Rico, Marina, Gulbins, Erich, Kornhuber, Johannes, Carpinteiro, Alexander, Lenze, Eric J., Reiersen, Angela M., Abellán, Miriam, de la Muela, Pedro, Vernet, Raphaël, Blanco, Carlos, Cougoule, Céline, Neuraz, Antoine, Gorwood, Philip, Alvarado, Jesús M., Meneton, Pierre, Limosin, Frédéric, Ancel, Pierre-Yves, Bauchet, Alain, Beeker, Nathanaël, Benoit, Vincent, Bernaux, Mélodie, Bellamine, Ali, Bey, Romain, Bourmaud, Aurélie, Breant, Stéphane, Burgun, Anita, Carrat, Fabrice, Caucheteux, Charlotte, Champ, Julien, Cormont, Sylvie, Daniel, Christel, Dubiel, Julien, Ducloas, Catherine, Esteve, Loic, Frank, Marie, Garcelon, Nicolas, Gramfort, Alexandre, Griffon, Nicolas, Grisel, Olivier, Guilbaud, Martin, Hassen-Khodja, Claire, Hemery, François, Hilka, Martin, Sophie Jannot, Anne, Lambert, Jerome, Layese, Richard, Leblanc, Judith, Lebouter, Léo, Lemaitre, Guillaume, Leprovost, Damien, Lerner, Ivan, Levi Sallah, Kankoe, Maire, Aurélien, Mamzer, Marie-France, Martel, Patricia, Mensch, Arthur, Moreau, Thomas, Orlova, Nina, Paris, Nicolas, Rance, Bastien, Ravera, Hélène, Rozes, Antoine, Salamanca, Elisa, Sandrin, Arnaud, Serre, Patricia, Tannier, Xavier, Treluyer, Jean-Marc, van Gysel, Damien, Varoquaux, Gaël, Vie, Jill Jen, Wack, Maxime, Wajsburt, Perceval, Wassermann, Demian, Zapletal, Eric, 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), Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of Duisburg-Essen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Hôpital Européen Georges Pompidou [APHP] (HEGP), National Institute on Drug Abuse [Bethesda] (NIDA), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [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 Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], 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, AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Institute on Drug Abuse [Bethesda], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, 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), Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, 'Entrepôt de Données de Santé' AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), 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), Imagine - Institut des maladies génétiques (IMAGINE - U1163), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, law.invention, Cohort Studies, COVID-19 Testing, medications, Randomized controlled trial, law, Clinical endpoint, Intubation, Pharmacology (medical), Enzyme Inhibitors, acid sphingomyelinase, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, treatment, Inverse probability weighting, Hazard ratio, Middle Aged, 3. Good health, Hospitalization, [SDV] Life Sciences [q-bio], Sphingomyelin Phosphodiesterase, Female, FIASMA, Adult, medicine.medical_specialty, Adolescent, intubation, Young Adult, Internal medicine, Intubation, Intratracheal, medicine, Humans, ceramide, Aged, Retrospective Studies, Pharmacology, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, mortality, Confidence interval, COVID-19 Drug Treatment, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Collaborators : AP-HP / Université de Paris / INSERM COVID-19 research collaboration, AP-HP COVID CDR Initiative, “Entrepôt de Données de Santé” AP-HP Consortium: Pierre-Yves Ancel, Alain Bauchet, Nathanaël Beeker, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Breant, Anita Burgun, Fabrice Carrat, Charlotte Caucheteux, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Anne Sophie Jannot, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Bastien Rance, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gaël Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal; International audience; Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p
Published: 2021

21. Energetic dysfunction in sepsis: a narrative review

Author: Guillaume Voiriot, Mehdi Oualha, Peter Radermacher, Sébastien Preau, Aurelien Flatres, Steve Lancel, Youenn Jouan, Stein Silva, Nicolas de Prost, Lara Zafrani, Eric Azabou, Dominique Vodovar, Jérémie Joffre, Fabrice Huel, Boris Jung, 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), CHU Necker - Enfants Malades [AP-HP], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), University of California, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, CHU Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), 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)-Hôpital Purpan [Toulouse], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitätsklinikum Ulm - University Hospital of Ulm, 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 de Tours (CHRU Tours), Université de Tours (UT)-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), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California [San Francisco] (UC San Francisco), University of California (UC), 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), Système immunitaire et neuroinflammation [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [AP-HP], SFB 1149 and GRK 2203/Deutsche Forschungsgemeinschaft, MORNET, Dominique, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Organ dysfunction, Cardiomyopathy, Review, 030204 cardiovascular system & hematology, Mitochondrion, Critical Care and Intensive Care Medicine, Bioinformatics, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, Septic shock, medicine, Energetic dysfunction, Immunodeficiency, business.industry, RC86-88.9, Acute kidney injury, Correction, Medical emergencies. Critical care. Intensive care. First aid, medicine.disease, 3. Good health, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, Metabolism, medicine.symptom, business, Infection, Mitochondrial dysfunction
Abstract: BackgroundGrowing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.Main textSepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.ConclusionsRecent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
Published: 2021

22. Low-income neighbourhood was a key determinant of severe COVID-19 incidence during the first wave of the epidemic in Paris

Author: Anne-Sophie, Jannot, Hector, Countouris, Alexis, Van Straaten, Anita, Burgun, Sandrine, Katsahian, Bastien, Rance, Eric, Zapletal, Département d’informatique médicale, de biostatistique et de santé publique [AP-HP Hôpital européen Georges-Pompidou], 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), Université de Paris (UP), 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), AP-HP/Universities/Inserm COVID-19 research collaboration: Pierre-Yves Ancel, Alain Bauchet, Vincent Benoit, Mélodie Bernaux, Ali Bellamine, Romain Bey, Aurélie Bourmaud, Stéphane Bréant, Fabrice Carrat, Julien Champ, Sylvie Cormont, Christel Daniel, Julien Dubiel, Catherine Ducloas, Loic Esteve, Marie Frank, Nicolas Garcelon, Alexandre Gramfort, Nicolas Griffon, Olivier Grisel, Martin Guilbaud, Claire Hassen-Khodja, François Hemery, Martin Hilka, Jerome Lambert, Richard Layese, Judith Leblanc, Léo Lebouter, Guillaume Lemaitre, Damien Leprovost, Ivan Lerner, Kankoe Levi Sallah, Aurélien Maire, Marie-France Mamzer, Patricia Martel, Arthur Mensch, Thomas Moreau, Antoine Neuraz, Nina Orlova, Nicolas Paris, Hélène Ravera, Antoine Rozes, Elisa Salamanca, Arnaud Sandrin, Patricia Serre, Xavier Tannier, Jean-Marc Treluyer, Damien Van Gysel, Gael Varoquaux, Jill Jen Vie, Maxime Wack, Perceval Wajsburt, Demian Wassermann, Eric Zapletal, 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), and Rance, Bastien
Subjects: Paris, Adolescent, Epidemiology, Population, communicable diseases, deprivation, Decile, 03 medical and health sciences, 0302 clinical medicine, cohort studies, Humans, Medicine, 030212 general & internal medicine, Epidemics, education, Socioeconomic status, Neighbourhood (mathematics), 030304 developmental biology, 0303 health sciences, education.field_of_study, SARS-CoV-2, business.industry, Incidence, Incidence (epidemiology), 1. No poverty, Public Health, Environmental and Occupational Health, COVID-19, Middle Aged, Census, healthcare disparities, 3. Good health, Socioeconomic Factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Residence, business, Demography, Cohort study
Abstract: BackgroundPrevious studies have demonstrated that socioeconomic factors are associated with COVID-19 incidence. In this study, we analysed a broad range of socioeconomic indicators in relation to hospitalised cases in the Paris area.MethodsWe extracted 303 socioeconomic indicators from French census data for 855 residential units in Paris and assessed their association with COVID-19 hospitalisation risk.FindingsThe indicators most associated with hospitalisation risk were the third decile of population income (OR=9.10, 95% CI 4.98 to 18.39), followed by the primary residence rate (OR=5.87, 95% CI 3.46 to 10.61), rate of active workers in unskilled occupations (OR=5.04, 95% CI 3.03 to 8.85) and rate of women over 15 years old with no diploma (OR=5.04, 95% CI 3.03 to 8.85). Of note, population demographics were considerably less associated with hospitalisation risk. Among these indicators, the rate of women aged between 45 and 59 years (OR=2.17, 95% CI 1.40 to 3.44) exhibited the greatest level of association, whereas population density was not associated. Overall, 86% of COVID-19 hospitalised cases occurred within the 45% most deprived areas.InterpretationStudying a broad range of socioeconomic indicators using census data and hospitalisation data as a readily available and large resource can provide real-time indirect information on populations with a high incidence of COVID-19.
Published: 2021

23. A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease

Author: Mark A. Schroeder, Steven M. Devine, Yi-Bin Chen, Andrejus Parfionovas, Yngvar Fløisand, Syed Quadri, Dominik Selleslag, Chunlin Chen, Ibrahim Yakoub-Agha, Patrice Chevallier, Mona Akbari, Mohamad Mohty, Johan Jansson, Anne S. Renteria, Oslo University Hospital [Oslo], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Centre hospitalier universitaire de Nantes (CHU Nantes), Center for International Blood and Marrow Transplant Research, Pathologies biliaires, fibrose et cancer du foie [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Millennium Pharmaceuticals, Massachusetts General Hospital [Boston], Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], 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)-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), and HAL-SU, Gestionnaire
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Ruxolitinib, Population, Graft vs Host Disease, Drug development, Antibodies, Monoclonal, Humanized, Graft-versus-host disease, Gastroenterology, Article, Vedolizumab, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, immune system diseases, law, hemic and lymphatic diseases, Internal medicine, medicine, Humans, education, Adverse effect, Transplantation, education.field_of_study, integumentary system, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Hematology, medicine.disease, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, surgical procedures, operative, Tolerability, Molecularly targeted therapy, 030220 oncology & carcinogenesis, Acute Disease, Steroids, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, 030215 immunology, medicine.drug
Abstract: Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn’s disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before termination, 17 participants had enrolled and an early response in intestinal aGvHD was observed in 11 and eight participants at days 15 and 28, respectively. All adverse events observed were consistent with those expected in a population with SR intestinal aGvHD. Overall, vedolizumab did not meet the primary efficacy endpoint (overall response at day 28), likely owing to premature study drug discontinuation, lack of efficacy, and the competing risks inherent with a population with advanced SR intestinal aGvHD. Nevertheless, this study provides valuable insights into the considerations needed when conducting studies in patients with SR intestinal aGvHD.
Published: 2021

24. Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children With Shock

Author: Damien Bonnet, Marion Grimaud, François Angoulvant, Maximilien Desvages, Julie Toubiana, David M. Smadja, Mehdi Oualha, Charlyne Brakta, Delphine Borgel, Dominique Lasne, Judith Chareyre, Richard Chocron, Sylvain Renolleau, Aurélien Philippe, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, 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), 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)), 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), 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 Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138))
Subjects: Male, Inotrope, [SDV]Life Sciences [q-bio], Online Brief Reports, shock, Critical Care and Intensive Care Medicine, Severity of Illness Index, Gastroenterology, Ventricular Function, Left, 0302 clinical medicine, Adrenal Cortex Hormones, Interquartile range, Vasoconstrictor Agents, Endothelial dysfunction, Child, endotheliopathy, Cardiogenic shock, Systemic Inflammatory Response Syndrome, Troponin, C-Reactive Protein, Distributive shock, Shock (circulatory), ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, medicine.symptom, severe acute respiratory syndrome coronavirus 2, medicine.medical_specialty, Cardiotonic Agents, Shock, Cardiogenic, Immunoglobulins, Intensive Care Units, Pediatric, Angiopoietin-2, 03 medical and health sciences, children, Internal medicine, Severity of illness, medicine, Humans, Lactic Acid, Retrospective Studies, multisystem inflammatory syndrome, Interleukin-6, SARS-CoV-2, business.industry, COVID-19, 030208 emergency & critical care medicine, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Systemic inflammatory response syndrome, 030228 respiratory system, business, Biomarkers
Abstract: Supplemental Digital Content is available in the text., TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5–11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35–45%), 261 ng/mL (131–390 ng/mL), and 3.2 mmol/L (2–4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5–28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814–11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987–192,499 pg/mL]), von Willebrand factor antigen (344% [288–378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472–1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.
Published: 2021

25. Relevance of treatment‐free remission recommendations in chronic phase chronic leukemia patients treated with frontline tyrosine kinase inhibitors

Author: Francois-Xavier Mahon, Marie-Pierre Fort, Béatrice Turcq, Laura Versmée, François Lifermann, Fanny Robbesyn, Marius Moldovan, Gabriel Etienne, Anais Charles-Nelson, Didier Adiko, Caroline Lenoir, Axelle Lascaux, Anna Schmitt, C. Fabères, Frédéric Bauduer, Stéphanie Dulucq, Emilie Klein, Sandrine Katsahian, Françoise Durrieu, Fontanet Bijou, Corinne Dagada, Samia Madene, Institut Bergonié [Bordeaux], UNICANCER, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Le CHCB, Centre Hospitalier de la Côte Basque, Centre Hospitalier Libourne, Centre Hospitalier Côte d'Argent [Dax], Polyclinique Bordeaux Nord Aquitaine, CHU Mont de Marsan, 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), 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 de Paris (UP), Université de Bordeaux (UB), Centre Hospitalier de Dax, Centre hospitalier de Pau, Centre Hospitalier Intercommunal Mont-de-Marsan-Pays des Sources, Centre Hospitalier de Périgueux, HAL-SU, Gestionnaire, 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)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, [SDV]Life Sciences [q-bio], Fusion Proteins, bcr-abl, tyrosine kinase inhibitor discontinuation, European LeukemiaNet, 0302 clinical medicine, Recurrence, RC254-282, Original Research, Aged, 80 and over, Remission Induction, molecular recurrence‐free survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Chronic phase chronic myeloid leukemia, Middle Aged, Third generation, Progression-Free Survival, 3. Good health, Oncology, Chronic leukemia, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Leukemia, Myeloid, Chronic-Phase, Imatinib Mesylate, Female, France, Tyrosine kinase, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines as Topic, Newly diagnosed, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, molecular recurrence-free survival, medicine, Humans, Radiology, Nuclear Medicine and imaging, Protein Kinase Inhibitors, Aged, business.industry, Patient Selection, Clinical Cancer Research, Imatinib, Discontinuation, 030104 developmental biology, Withholding Treatment, recommendations, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: Background Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia (CP‐CML) patients who had achieved a sustained deep molecular response. Based on the results of discontinuation trials, recommendations regarding patient selection for a treatment‐free remission (TFR) attempt had been proposed. The aims of this study were to evaluate the rate of patients eligible for TKI discontinuation and molecular recurrence‐free survival (MRFS) after stop according to recommendations. Methods Over a 10‐year period, newly diagnosed CP‐CML patients and treated with first‐line TKI in the nine French participating centers were included. Eligibility to treatment discontinuation and MRFS were analyzed and compared according to selection criteria defined by recommendations and first‐line treatments. Results From January 2006 to December 2015, 398 patients were considered. Among them, 73% and 27% of patients received imatinib or either second or third generation tyrosine kinase inhibitors as frontline treatment, respectively. Considering the selection criteria defined by recommendations, up to 55% of the patients were selected as optimal candidates for treatment discontinuation. Overall 95/398 (24%) discontinued treatment. MRFS was 51.8% [95% CI 41.41–62.19] at 2 years and 43.8% [31.45–56.15] at 5 years. Patients receiving frontline second‐generation TKI and fulfilling the eligibility criteria suggested by recommendations had the lowest probability of molecular relapse after TKI stop when compare to others. Conclusion One third of CP‐CML patients treated with TKI frontline fulfilled the selection criteria suggested by European LeukemiaNet TFR recommendations. Meeting selection criteria and second‐generation TKI frontline were associated with the highest MRFS., Tyrosine kinase inhibitors (TKI) can be safely discontinued in chronic phase chronic myeloid leukemia patients who had achieved a sustained deep molecular response. Several recommendations regarding the optimal selection of the patients before stop have been proposed. Based on these recommendations, we estimate that one third of the patients treated with frontline TKI will meet these criteria. Moreover, patients treated with frontline second generation TKI and selected as optimal candidate according to these recommendations have the highest probability of molecular recurrence‐free survival when compared to others.
Published: 2021

26. Clinical, biological and radiological features, 4-week outcomes and prognostic factors in COVID-19 elderly inpatients

Author: Olivier Paccoud, Alexandre Bleibtreu, Nagisa Godefroy, Y. Wakim, S. Boussouar, Romain Palich, M. Levy-Soussan, Cathia Soulié, Oula Itani, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie médicale [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), Gestionnaire, HAL Sorbonne Université 5, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Time Factors, Sars-CoV-2, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030204 cardiovascular system & hematology, Prognostic factors, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Respiratory system, Computed tomography, Aged, Retrospective Studies, Aged, 80 and over, Respiratory distress, business.industry, Mortality rate, After discharge, Prognosis, 3. Good health, Hospitalization, Elderly patients, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Prognostic factors Computed tomography, Radiological weapon, Infectious diseases department, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Covid-19, business
Abstract: International audience; ObjectiveTo describe clinical, biological, radiological presentation and W4 status in COVID-19 elderly patients.Patients and methodsAll patients ≥ 70 years with confirmed SARS-CoV-2 infection and hospitalized in the Infectious Diseases department of the Pitié-Salpêtrière hospital, Paris, France, from March 1st to April 15th 2020 were included. The primary outcome was death four weeks after hospital admission. Data on demographics, clinical features, laboratory tests, CT-scan findings, therapeutic management and complications were collected.ResultsAll in all, 100 patients were analyzed, including 49 patients ≥ 80 years. Seventy percent had ≥2 comorbidities. Respiratory features were often severe as 48% needed oxygen support upon admission. Twenty-eight out of 43 patients (65%) with a CT-scan had mild to severe parenchymal impairment, and 38/43 (88%) had bilateral impairment. Thirty-two patients presented respiratory distress requiring oxygen support ≥ 6 liters/minute. Twenty-four deaths occurred, including 21 during hospitalization in our unit, 2 among the 8 patients transferred to ICU, and one at home after discharge from hospital, leading to a global mortality rate of 24% at W4. Age, acute renal failure and respiratory distress were associated with mortality at W4.ConclusionA substantial proportion of elderly COVID-19 patients with several comorbidities and severe clinical features survived, a finding that could provide arguments against transferring the most fragile patients to ICU.
Published: 2021

27. Isoniazid-monoresistant tuberculosis in France: Risk factors, treatment outcomes and adverse events

Author: Nadine Lemaître, Jérôme Robert, N. Fortineau, C. Verdet, P. Morand, S. Gallien, O. Bouchaud, P. Sellier, K. Lacombe, Frédéric Schramm, A. Hummel, F. Mechaï, Valérie Pourcher, J.-L. Meynard, V. Delcey, J. Lourenco, J.-M. Molina, J.-W. Decousser, A. Ferroni, Christophe Rioux, T. Billard-Pomares, V. Lalande, B. Wyplosz, Dhiba Marigot-Outtandy, D. Le Dû, F. Cohen, G. Pialoux, C. Pierre-Audigier, H. Nunes, E. Catherinot, Lorenzo Guglielmetti, L. Lassel, B. Denis, M. Gominet, Nicolas Veziris, B. Crestani, V. Chambrin, Eric Caumes, L. Deconinck, R. Guéry, Yazdan Yazdanpanah, A.-L. Roux, C. Guillet, A.-L. Munier, B. Nebbad-Lechani, F. Morel, C. Le Jeunne, N. Grall, M. Lafaurie, Hugo Langris, E. Carbonnelle, E. Bille, N. Lemaitre, S. Abgrall, M. Pellan, Faiza Mougari, I. Bonnet, A.-S. Morin, P. Loulergue, Marwa Bachir, Sheila Chiesi, J. Jaffré, Alexandra Aubry, A.-L. Nardi, J. Dumoulin, S. Bulifon, C. Londner, N. Roche, M. Jachym, A. Canestri, J. Pavie, Simone Tunesi, A. Galy, N. De Castro, B. Fantin, J.D. Lelièvre, C. Dumesnil, Typhaine Billard-Pomares, E. Lecorché, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [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), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Strasbourg, CHU Amiens-Picardie, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Tuberculosis, [SDV]Life Sciences [q-bio], 030106 microbiology, Antitubercular Agents, Infectious and parasitic diseases, RC109-216, Drug resistance, World health, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Drug Resistance, Bacterial, Epidemiology, Isoniazid, medicine, Humans, 030212 general & internal medicine, Adverse effect, drug resistance, business.industry, Mycobacterium tuberculosis, General Medicine, Middle Aged, medicine.disease, 3. Good health, Factors treatment, [SDV] Life Sciences [q-bio], Treatment Outcome, Infectious Diseases, Streptomycin, Case-Control Studies, epidemiology, Female, France, business, medicine.drug
Abstract: Objectives Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.
Published: 2021

28. Partial recovery of visual function in a blind patient after optogenetic therapy

Author: Laure Blouin, Jean-Baptiste de Saint Aubert, Deniz Dalkara, Joseph N. Martel, Alexandre Delaux, Simona Degli Esposti, Serge Picaud, Emmanuel Gutman, Francesco Galluppi, Chloé Pagot, Caroline de Montleau, Magali Taiel, Botond Roska, José-Alain Sahel, Elise Boulanger-Scemama, Angelo Arleo, Jens Duebel, Isabelle Audo, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Streetlab [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), GenSight Biologics, Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, National Institute for Health Research Moorfields Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, INSERM-Centre d'Investigation Clinique 1423, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, F-75012 Paris, France, University of Basel (Unibas), ARLEO, Angelo, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-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)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Department of Ophthalmology, University of Basel, Basel, Switzerland
Subjects: Male, Retinal Ganglion Cells, 0301 basic medicine, Visual perception, genetic structures, Eye disease, Genetic Vectors, Review Article, Optogenetics, Blindness, Retinal ganglion, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Retinitis pigmentosa, Humans, Medicine, Photoreceptor Cells, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Vision, Ocular, ComputingMilieux_MISCELLANEOUS, Visual Cortex, Retina, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Genetic Therapy, General Medicine, Dependovirus, Middle Aged, medicine.disease, Brain Waves, eye diseases, 3. Good health, Light intensity, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Visual Perception, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], sense organs, Eye Protective Devices, business, Neuroscience, Retinitis Pigmentosa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Optogenetics may enable mutation-independent, circuit-specific restoration of neuronal function in neurological diseases. Retinitis pigmentosa is a neurodegenerative eye disease where loss of photoreceptors can lead to complete blindness. In a blind patient, we combined intraocular injection of an adeno-associated viral vector encoding ChrimsonR with light stimulation via engineered goggles. The goggles detect local changes in light intensity and project corresponding light pulses onto the retina in real time to activate optogenetically transduced retinal ganglion cells. The patient perceived, located, counted and touched different objects using the vector-treated eye alone while wearing the goggles. During visual perception, multichannel electroencephalographic recordings revealed object-related activity above the visual cortex. The patient could not visually detect any objects before injection with or without the goggles or after injection without the goggles. This is the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy.
Published: 2021

29. Acute Myocarditis Revealing Adult-Onset Still’s Disease

Author: Franck Boccara, Arsène Mekinian, Stéphane Ederhy, Raphael Cohen, Olivier Fain, Ariel Cohen, Clément Cholet, P Nhan, Vincent Jachiet, Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [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), Service de rhumatologie [CHU Saint-Antoine], Service de médecine interne [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], 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), HAL-SU, Gestionnaire, 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), 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Adult-onset Still's disease, medicine.medical_specialty, Myocarditis, TTE, transthoracic echocardiogram, Case Report, 030105 genetics & heredity, LVEF - Left ventricular ejection fraction, 03 medical and health sciences, 0302 clinical medicine, Clinical Case, Internal medicine, Troponin I, LVEF, left ventricular ejection fraction, medicine, Maculopapular rash, Palpitations, adult-onset Still’s disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, medicine.disease, Pharyngitis, 3. Good health, Acute myocarditis, Cardiology, AOSD, adult-onset Still’s disease, GLS, global longitudinal strain, medicine.symptom, myocarditis, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: A 34-year-old man presented with fever, palpitations, maculopapular rash, pharyngitis, left cheilitis, and bilateral gonalgia. High-sensitivity troponin I concentration was 4,900 ng/l. Transthoracic echocardiogram revealed reduced global longitudinal strain. Cardiac magnetic resonance imaging showed acute myocarditis. Adult-onset Still’s disease was diagnosed, and treatment with intravenous corticosteroids and tocilizumab was initiated. (Level of Difficulty: Beginner.), Central Illustration
Published: 2021

30. Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial

Author: Isaac Barroso, Isabel M. Miranda, Davide Carvalho, Paula Freitas, Maria Manuel Silva, Paul Picq, Eva Lau, Adelino Barbosa, Flora Correia, Joël Doré, Edi Prifti, Karine Clément, Cidália Pina Vaz, Eugeni Belda, Manuel Ferreira-Magalhães, Universidade do Porto = University of Porto, 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), Instituto de Investigação e Inovação em Saúde (I3S), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Universidade do Porto, 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), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), and Institut de Recherche pour le Développement (IRD [France-Nord])-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Sorbonne Université (SU)
Subjects: 0301 basic medicine, medicine.medical_specialty, Weight loss, RC620-627, Roux-en-Y gastric bypass, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Gut flora, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Randomized controlled trial, law, Internal medicine, Internal Medicine, Medicine, Microbiome, Nutritional diseases. Deficiency diseases, 2. Zero hunger, biology, business.industry, Research, Health sciences, Medical and Health sciences, Ciências médicas e da saúde, nutritional and metabolic diseases, medicine.disease, biology.organism_classification, Obesity, 3. Good health, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Medical and Health sciences, Ciências da Saúde, Ciências médicas e da saúde, medicine.symptom, business
Abstract: Background Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2). Methods DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. Results Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p p p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. Conclusions This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. Trial registration: ISRCTN53984585
Published: 2021

31. Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

Author: Rajagopal Krishnamoorthy, Philippe Beaune, Marion Leboyer, Ryad Tamouza, Bruno O. Villoutreix, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Drug, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, [SDV]Life Sciences [q-bio], phenothiazine, Drug resistance, Disease, Bioinformatics, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, chemoinformatics, high-throughput screening, antihistamine, 03 medical and health sciences, 0302 clinical medicine, Medicine, Adverse effect, 030304 developmental biology, media_common, Original Research, 0303 health sciences, drug repurposing, business.industry, COVID-19, Computer Science Applications, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Drug repositioning, 030104 developmental biology, Chemistry (miscellaneous), Advances and Applications in Bioinformatics and Chemistry, 030220 oncology & carcinogenesis, Antihistaminic drugs, prophylaxis, business, 030217 neurology & neurosurgery
Abstract: Bruno O Villoutreix,1 Rajagopal Krishnamoorthy,2 Ryad Tamouza,2 Marion Leboyer,2 Philippe Beaune3 1INSERM U1141, NeuroDiderot, Université de Paris, Hôpital Robert-Debré, Paris, F-75019, France; 2Université Paris Est Créteil, INSERM U955, IMRB, Laboratoire Neuropsychiatrie Translationnelle, AP-HP, Département Medico-Universitaire de Psychiatrie et d’Addictologie (DMU ADAPT), Hôpital Henri Mondor, Fondation FondaMental, Créteil, F-94010, France; 3INSERM U1138, Centre de Recherche des Cordeliers, Université de Paris, Paris, 75006, FranceCorrespondence: Bruno O Villoutreix Email bruno.villoutreix@inserm.frIntroduction: There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients.Objective: Based upon clinical observations, we proposed that some psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection. This observation is investigated in the light of experimental in vitro data on SARS-CoV-2.Methods: SARS-CoV-2 high-throughput screening results are available at the NCATS COVID-19 portal. We investigated the in vitro anti-viral activity of many psychotropic and antihistaminic drugs using chemoinformatics approaches.Results and Discussion: We analyze our clinical observations in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could be used as prophylactic drugs. Other cationic amphiphilic drugs used in other disease areas are also highlighted. Recent analyses of patient electronic health records reported by several research groups indicate that some of these molecules could be of interest at different stages of the disease progression. In addition, recently reported drug combination studies further suggest that it might be valuable to associate several cationic amphiphilic drugs. Taken together, these observations underline the need for clinical trials to fully evaluate the potentials of these molecules, some fitting in the so-called category of broad-spectrum antiviral agents. Repositioning orally available drugs that have moderate side effects and should act on molecular mechanisms less prone to drug resistance would indeed be of utmost importance to deal with COVID-19.Keywords: chemoinformatics, COVID-19, high-throughput screening, phenothiazine, prophylaxis, antihistamine, drug repurposing
Published: 2021

32. Dexamethasone use and mortality in hospitalized patients with coronavirus disease 2019: A multicentre retrospective observational study

Author: Alexandre Gramfort, Marina Sánchez-Rico, Ali Bellamine, Nicolas Hoertel, Christel Daniel, Nicolas Paris, Mélodie Bernaux, Guillaume Lemaitre, Nathanaël Beeker, Raphaël Vernet, Antoine Neuraz, Jesús M. Alvarado, Frédéric Limosin, Elisa Salamanca, Anita Burgun, Neuraz, Antoine, Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Université Paris Cité (UPCité), Hôpital Cochin [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 Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], 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, Laboratoire d'Informatique pour la Mécanique et les Sciences de l'Ingénieur (LIMSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Recherche en Informatique et en Automatique (Inria), Université Paris-Saclay, and École Pratique des Hautes Études (EPHE)
Subjects: Adult, medicine.medical_specialty, Efficacy, medicine.medical_treatment, 030226 pharmacology & pharmacy, SARS‐CoV‐2, Dexamethasone, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Internal medicine, medicine, Clinical endpoint, Humans, Pharmacology (medical), 030212 general & internal medicine, Mortality, Retrospective Studies, Pharmacology, Mechanical ventilation, SARS-CoV-2, Cumulative dose, business.industry, Proportional hazards model, Hazard ratio, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Comorbidity, Ventilation, COVID-19 Drug Treatment, Hospitalization, Oxygen, Treatment, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Original Article, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Coronavirus Infections, business, medicine.drug
Abstract: International audience; Background Health care professionals are caught between the wish of patients to speed up health-related communication via emails and the need for protecting health information. Objective We aimed to analyze the demographic characteristics of patients providing an email, and study the distribution of emails’ domain names. Methods We used the information system of the European Hospital Georges Pompidou (HEGP) to identify patients who provided an email address. We used a 1:1 matching strategy to study the demographic characteristics of the patients associated with the presence of an email, and described the characteristics of the emails used (in terms of types of emails—free, business, and personal). Results Overall, 4.22% (41,004/971,822) of the total population of patients provided an email address. The year of last contact with the patient is the strongest driver of the presence of an email address (odds ratio [OR] 20.8, 95% CI 18.9-22.9). Patients more likely to provide an email address were treated for chronic conditions and were more likely born between 1950 and 1969 (taking patients born before 1950 as reference [OR 1.60, 95% CI 1.54-1.67], and compared to those born after 1990 [OR 0.56, 95% CI 0.53-0.59]). Of the 41,004 email addresses collected, 37,779 were associated with known email providers, 31,005 email addresses were associated with Google, Microsoft, Orange, and Yahoo!, 2878 with business emails addresses, and 347 email addresses with personalized domain names. Conclusions Emails have been collected only recently in our institution. The importance of the year of last contact probably reflects this recent change in contact information collection policy. The demographic characteristics and especially the age distribution are likely the result of a population bias in the hospital: patients providing email are more likely to be treated for chronic diseases. A risk analysis of the use of email revealed several situations that could constitute a breach of privacy that is both likely and with major consequences. Patients treated for chronic diseases are more likely to provide an email address, and are also more at risk in case of privacy breach. Several common situations could expose their private information. We recommend a very restrictive use of the emails for health communication.
Published: 2021

33. HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients

Author: Ann M. Moyer, Petra Mrázová, Guillaume Canaud, Jack F.M. Wetzels, Nadhir Yousfi, Maryvonne Hourmant, Christophe Legendre, Manish J. Gandhi, Vladimir Tesar, Mariam P. Alexander, Ondrej Viklický, Christiane Mousson, Hanna Debiec, Pierre Ronco, Philippe Rieu, Valérie Dubois, Anne-Els van de Logt, Paul Brenchley, Sylvain Guibert, Vincent Vuiblet, Charlène Levi, Patrick Hamilton, Armando Torres, Bruno Moulin, Eric Letouzé, Josep M. Cruzado, José Aurelio Ballarín Castan, Lena Berchtold, Gabriel Choukroun, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Geneva University Hospital (HUG), 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), Mayo Clinic [Rochester], 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 de Paris (UP), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], University of Manchester [Manchester], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biospectroscopie Translationnelle - EA 7506 (BIOSPECT), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University of Barcelona, Universidad de La Laguna [Tenerife - SP] (ULL), Charles University [Prague] (CU), Institute for Clinical and Experimental Medicine (IKEM), Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Département de Néphrologie [CHU Necker], Service de néphrologie et de transplantation rénale [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), Gestionnaire, Hal Sorbonne Université, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Linkage disequilibrium, recurrence, HLA-D, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Locus (genetics), Single-nucleotide polymorphism, Glomerulonephritis, Membranous, Polymorphism, Single Nucleotide, genetic risk score, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Internal medicine, medicine, Humans, genetics, PLA2R1, Alleles, Retrospective Studies, Genetic testing, next generation sequencing, medicine.diagnostic_test, business.industry, Donor selection, Receptors, Phospholipase A2, membranous nephropathy, Retrospective cohort study, medicine.disease, Kidney Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, Nephrology, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, transplantation
Abstract: Contains fulltext : 234032.pdf (Publisher’s version ) (Closed access) Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
Published: 2021

34. Low level of baseline resistance in recently HCV-infected men who have sex with men with high-risk behaviours

Author: Marc-Antoine Valantin, Thomas L'Yavanc, Nesrine Day, Thuy Van Nguyen, Eve Todesco, Nadia Valin, Jean-Michel Molina, Corinne Amiel, Michel Ohayon, Gilles Pialoux, Anne-Geneviève Marcelin, Emmanuelle Netzer, Georges Kreplak, Vincent Calvez, Constance Delaugerre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et de 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 National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cerballiance, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Service de Maladies infectieuses et tropicales [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), and HAL-SU, Gestionnaire
Subjects: Male, 0301 basic medicine, Deep sequencing, viruses, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Men who have sex with men, Sexual and Gender Minorities, Pre-exposure prophylaxis, 0302 clinical medicine, Polymorphism (computer science), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Immunology and Allergy, Medicine, 030212 general & internal medicine, education.field_of_study, Hepatitis C virus, virus diseases, Hepatitis C, QR1-502, 3. Good health, HCV, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Population study, Microbiology (medical), 030106 microbiology, Immunology, Population, Pre-Exposure, Antiviral Agents, Microbiology, 03 medical and health sciences, Risk-Taking, Drug Resistance, Viral, Humans, Homosexuality, Male, NS5A, education, business.industry, Prophylaxis, Resistance transmission, Hepatitis C, Chronic, Virology, digestive system diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objectives Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP). Methods NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off. Results HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses. Conclusion A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.
Published: 2021

35. Impaired hypoxic ventilatory drive induced by diabetic autonomic neuropathy, a cause of misdiagnosed severe cardiac events: brief report of two cases

Author: Olivier Bourron, Agnès Hartemann, Suzanne Laroche, Franck Phan, Louis Schubert, HAL-SU, Gestionnaire, Service de Diabétologie [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), 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 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), 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), 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 de diabétologie [CHU Pitié-Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, Type 1 diabetes mellitus, 030209 endocrinology & metabolism, Case Report, 030204 cardiovascular system & hematology, Respiratory failure, Sudden cardiac death, Hypoxemia, 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, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Cardiopulmonary resuscitation, Hypoxia, Oxygen saturation (medicine), Diabetic Autonomic Neuropathy, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, business.industry, Hypoxia (medical), [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Pulmonary edema, Cardiac autonomic neuropathy, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, lcsh:RC666-701, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Background Sudden cardiac deaths are twice more frequent in diabetic patients with cardiac autonomic neuropathy. Sudden cardiac death etiologies remain unclear and no recommendations are made to identify factors associated with cardiorespiratory arrest in diabetic patients. We hypothesized, from two clinical cases, that impaired hypoxic ventilatory drive, induced by diabetic autonomic neuropathy, is a cause of misdiagnosed severe cardiac events. Case presentation We describe the cases of two patients with isolated low blood saturation on pulse oximeter during the systematic nurse check-up (77% and 85% respectively) contrasting with the absence of any complaint such as dyspnea, polypnea or other respiratory insufficiency signs observed during the clinical examination. Arterial blood gas measurements subsequently confirmed that blood oxygen saturation was low and both patients were indeed hypoxemic. Patient 1 suffered from vascular overload complicated by cardiac arrest caused by hypoxemia in light of the quick recovery observed after ventilation. Pulmonary edema was diagnosed in patient 2. The common denominator of these 2 cases described in this brief report is the absence of respiratory failure clinical signs contrasting with the presence of confirmed hypoxemia. Also, in both cases, such absence of precursory signs seems to be induced by an impaired ventilatory drive to hypoxemia. This appears to be related to the autonomic diabetic neuropathy encountered in those 2 patients. Conclusions Therefore, we describe, in this brief report, cardiac autonomic neuropathy as a cause of impaired hypoxic ventilatory drive involved in severe acute cardiorespiratory events in two type 1 diabetic patients. We assume that altered response to hypoxemia due to cardiac autonomic neuropathy and non-functional central neurological breathing command could play a key role in sudden deaths among diabetic patients. An important point is that hypoxemia can be easily missed since no clinical signs of respiratory failure are reported in these two clinical cases. Systematic screening of cardiac autonomic neuropathy in diabetic patients and proactive detection of impaired hypoxic ventilatory drive for early management (e.g. treatment of hypoxemia) should be systematically undertaken in diabetic patients to prevent its dramatic consequences such as cardiorespiratory arrest and death.
Published: 2021

36. IVIg increases interleukin-11 levels, which in turn contribute to increased platelets, VWF and FVIII in mice and humans

Author: H. De Boysson, Anupama Karnam, Mikael Ebbo, Samuel Deshayes, Laurent Magy, Alexandre Nguyen, Sébastien Lacroix-Desmazes, G. Maigné, Jagadeesh Bayry, Sandrine Delignat, Y. Repesse, Jean-Michel Vallat, Olivier Benveniste, Yves Allenbach, Achille Aouba, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Limoges, Service de pneumologie [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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de médecine interne [CHU Caen], Immunopathologie et immunointervention thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie et immunointervention thérapeutique (CRC - Inserm U1138), 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)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et immuno-intervention thérapeutique, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Blood Platelets, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunology, Mice, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, von Willebrand Factor, Von Willebrand disease, medicine, Animals, Humans, Immunology and Allergy, Platelet, Thrombopoietin, Retrospective Studies, Megakaryopoiesis, Factor VIII, biology, business.industry, Growth factor, Immunoglobulins, Intravenous, Interleukin, Original Articles, Middle Aged, Interleukin-11, medicine.disease, Mice, Inbred C57BL, Interleukin 11, 030104 developmental biology, biology.protein, Female, Antibody, business, 030215 immunology
Abstract: SummaryThe mechanisms of action of intravenous immunoglobulins (IVIg) in autoimmune diseases are not fully understood. The fixed duration of efficacy and noncumulative effects of IVIg in immune thrombocytopenia (ITP) and acquired von Willebrand disease (AVWD) suggest other mechanisms besides immunological ones. Additionally to the peripheral destruction of platelets in ITP, their medullary hypoproduction emerged as a new paradigm with rescue of thrombopoietin receptor agonists (TPO-RA). In an ITP mouse model, interleukin (IL)-11 blood levels increase following IVIg. IL-11 stimulates the production of platelets and other haemostasis factors; recombinant IL-11 (rIL-11) is thus used as a growth factor in post-chemotherapy thrombocytopenia. We therefore hypothesized that IVIg induces IL-11 over-production, which increases platelets, VWF and factor VIII (FVIII) levels in humans and mice. First, in an ITP mouse model, we show that IVIg or rIL-11 induces a rapid increase (72 h) in platelets, FVIII and VWF levels, whereas anti-IL-11 antibody greatly decreased this effect. Secondly, we quantify for the first time in patients with ITP, AVWD, inflammatory myopathies or Guillain–Barré syndrome the dramatic IL-11 increase following IVIg, regardless of the disease. As observed in mice, platelets, VWF and FVIII levels increased following IVIg. The late evolution (4 weeks) of post-IVIg IL-11 levels overlapped with those of VWF and platelets. These data may explain thrombotic events following IVIg and open perspectives to monitor post-IVIg IL-11/thrombopoietin ratios, and to assess rIL-11 use with or without TPO-RA as megakaryopoiesis co-stimulating factors to overcome the relative hypoproduction of platelets or VWF in corresponding autoimmune diseases, besides immunosuppressant.
Published: 2021

37. Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia

Author: Mathieu Mahevas, Alain Combes, Ignacio Fernandes, Armand Mekontso-Dessap, Nicolas de Prost, Karim Dorgham, Slim Fourati, Guy Gorochov, Jean-Laurent Casanova, Romain Arrestier, Paul Bastard, Sonia Burrel, Charles-Edouard Luyt, Iname Azzaoui, Yacine Tandjaoui-Lambiotte, CHU Henri Mondor, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Service de Virologie [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), 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 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 Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), 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), Service de Réanimation Médicale [CHU Pitié-Salpétrière], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Immunology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Internal medicine, Intensive care, medicine, Humans, Immunology and Allergy, Prospective Studies, Prospective cohort study, Aged, Autoantibodies, Plasma Exchange, biology, SARS-CoV-2, business.industry, Autoantibody, COVID-19, medicine.disease, Pneumonia, 030104 developmental biology, medicine.anatomical_structure, type I interferons, plasma exchanges, Interferon Type I, biology.protein, Original Article, Female, Antibody, business, Viral load, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Respiratory tract
Abstract: Purpose To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. Methods Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. Results Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. Conclusions PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-00994-9.
Published: 2021

38. Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

Author: Julien Puech, Marie-Laure Lucas, Simon Pernot, Raphael Vernet, David Veyer, Laurence Weiss, Cécile Badoual, Bastien Rance, Nicolas Robillard, Hélène Péré, Laurent Bélec, Sonia Lameiras, Alain Nicolas, Maxime Wack, Juliette Pavie, 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), Institut Bergonié [Bordeaux], UNICANCER, Hôtel-Dieu, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Curie [Paris], Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Gestionnaire, Hal Sorbonne Université, 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), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-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 de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Science, Context (language use), Virus, Article, Metastasis, Tumour biomarkers, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Carcinoma, Medicine, Humans, Tumour virus infections, Neoplasm Metastasis, Prospective cohort study, Retrospective Studies, Whole genome sequencing, Human papillomavirus 16, Multidisciplinary, medicine.diagnostic_test, business.industry, Papillomavirus Infections, Anal Squamous Cell Carcinoma, virus diseases, Translational research, medicine.disease, Anus Neoplasms, female genital diseases and pregnancy complications, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Carcinoma, Squamous Cell, business, Biomarkers
Abstract: Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.
Published: 2021

39. Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU

Author: Sophie Demeret, Alexandre Lampros, Antoine Monsel, Corentin Poignon, Arnaud Fekkar, Anne-Geneviève Marcelin, Jean-Michel Constantin, Julien Mayaux, Marion Blaize, Charles-Edouard Luyt, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Neurophysiologie [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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 [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), 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), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and 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]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary Fungal Infections, Coronavirus disease 2019 (COVID-19), viruses, Disease, Critical Care and Intensive Care Medicine, medicine.disease_cause, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, aspergillosis, In patient, 030212 general & internal medicine, Significant risk, Coronavirus, SARS-CoV-2, business.industry, fungal infection, aspergillus, COVID-19, virus diseases, Retrospective cohort study, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business
Abstract: International audience; Rationale:Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19.Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications.Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male (n = 104; 72%), were overweight (n = 99; 68%), and had hypertension (n = 83; 57%) and diabetes (n = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half (n = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio, = 4.66; interquartile range, 1.98–7.34; P = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%).Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2–related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.
Published: 2021

40. Repenser la place des lymphocytes B et des structures lymphoïdes tertiaires dans l’immunothérapie des cancers

Author: Hélène Kaplon, Marie-Caroline Dieu-Nosjean, Claire Germain, Invectys [Paris], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 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), Sciences, EDP, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)
Subjects: 0303 health sciences, business.industry, [SDV]Life Sciences [q-bio], General Medicine, Molecular biology, General Biochemistry, Genetics and Molecular Biology, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

41. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard?

Author: Amélie Guihot, Madalina Uzunov, Sophie Demeret, Agnès Bellanger, David Saadoun, Damien Roos-Weil, Claire Deback, Valérie Pourcher, Ahmed Idbaih, Nicolas Weiss, Natalia Shor, Veronique Leblond, Damien Galanaud, Caroline Houillier, Bruno Eymard, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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 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), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Oncology, medicine.medical_specialty, Neurology, business.industry, medicine.drug_class, Progressive multifocal leukoencephalopathy, medicine.medical_treatment, Immunosuppression, Context (language use), medicine.disease, Monoclonal antibody, Myasthenia gravis, Immune system, Internal medicine, medicine, Neurology (clinical), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Encephalitis
Abstract: Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML. We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14–33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML. Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
Published: 2021

42. Emergence of pollen food allergy syndrome in asthmatic children in Paris

Author: Stéphanie Wanin, Nathalie Cottel, M. Bourgoin-Heck, Christine Loraud, Jocelyne Just, Charlotte Thibaut de Ménonville, Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, HAL Sorbonne Université 5, and Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR)
Subjects: Paris, Immunology, Pollen‐food‐allergy syndrome, Cross Reactions, medicine.disease_cause, Immunoglobulin E, Allergic rhinitis, Pollen-food allergy, 03 medical and health sciences, 0302 clinical medicine, Food allergy, Pollen, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, Betula, Sensitization, Retrospective Studies, Asthma, biology, business.industry, Betv1 specific IgE, Allergens, Antigens, Plant, medicine.disease, 3. Good health, Asthmatic children, Birch pollen, Cross-Sectional Studies, medicine.anatomical_structure, 030228 respiratory system, Pediatrics, Perinatology and Child Health, biology.protein, business, Food Hypersensitivity, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: International audience; BackgroundOver the last few decades, the level of pollen from birch and homologous trees has increased in parts of Europe. Sensitization to birch pollen allergens (principally Bet v 1) has been associated with food cross‐reactivity called pollen‐food‐allergy syndrome (PFAS).ObjectiveTo evaluate changes in allergic diseases due to IgE sensitization over 25 years in asthmatic children.MethodsThis was a cross‐sectional retrospective study conducted in Paris. We analyzed two cohorts of asthmatic children with similar characteristics explored between 1993‐1999 (old cohort=OC) and 2012‐2018 (recent cohort=RC).Results121 children were in the OC and 120 in the RC. An increase in sensitization to tree pollens was found especially for birch pollen which was 11.6% in the OC and 31% in the RC (p=0.0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, p
Published: 2021

43. Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study

Author: Rabab Debs, Jean-Yves Hogrel, Gaëlle Bruneteau, Nadine Le Forestier, Peter Bede, Pascal Laforêt, Sophie Blancho, Anthony Behin, Timothée Lenglet, Véronique Marchand-Pauvert, François Salachas, Giorgia Querin, Pierre-François Pradat, Tanya Stojkovic, Maria del Mar Amador, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Etudes sur les sciences et les techniques (EST), Université Paris-Saclay, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Hôpital Raymond Poincaré [AP-HP], 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), H&R BLOCK, HRB: EIA-2017-019 Association Française contre les Myopathies, AFM Health Research Board, HRB Iris O'Brien Foundation Irish Institute of Clinical Neuroscience, IICN AFM-Téléthon: NCT0288587, This study was sponsored by the Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen., We are grateful for the generosity of all SMA patients who have kindly participated in this study. This study was supported by the Association Française contre les Myopathies (AFM-Téléthon). We also thank the Institut pour la Recherche sur la Moelle Épinière et l’Encephale (IRME) for their support of this the study. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. The rest of the authors have no specific sponsors to declare., Supported by the Association Française contre les Myopathies (AFM-Téléthon, NCT0288587)., 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), Centre de Recherche en Myologie, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), 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), and Association française contre les myopathies (AFM-Téléthon). Dr. Giorgia Querin, Dr. Timothée Lenglet, Dr. Rabab Debs, Dr. Tanya Stojkovic, Dr. Anthony Behin, Dr. François Salachas, Dr. Nadine Le Forestier, Dr. Maria del Mar Amador, Dr. Gaëlle Bruneteau, Dr. Sophie Blancho, Dr. Véronique Marchand-Pauvert: report no disclosures. Prof Pascal Laforêt receives funding for research and as an advisor or speaker from Sanofi Genzyme and Spark Therapeutics. Dr. Peter Bede is supported by the Health Research Board (HRB EIA-2017-019), the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), the Irish Motor Neuron Disease Association (IMNDA) and the Iris O'Brien Foundation. Dr. Jean-Yves Hogrel is co-inventor of the Myogrip and MyoPinch devices and did consultancy for Biogen and Sarepta. Dr Pierre- François Pradat receives funding as an advisor and speaker from Biogen.
Subjects: Adult, medicine.medical_specialty, Longitudinal study, Neurology, [SDV]Life Sciences [q-bio], Deltoid curve, Spinal Muscular Atrophies of Childhood, Outcome measures, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Outcome Assessment, Health Care, Humans, Medicine, Longitudinal Studies, Muscle Strength, 030212 general & internal medicine, Muscle, Skeletal, Neuroradiology, Longitudinal progression, business.industry, SMA, Spinal cord, 3. Good health, Clinical trial, medicine.anatomical_structure, Sample size determination, Adult SMA, Neurology (clinical), business, 030217 neurology & neurosurgery, MUNIX
Abstract: International audience; Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials. Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later. Longitudinal comparisons were conducted using the Wilcoxon-test for matched data. Responsiveness was estimated using standardized response means (SRM) and a composite score was generated based on the three most significant variables. Results: Significant functional decline was observed based on SMAFRS (p = 0.019), pinch and knee flexion strength (p = 0.030 and 0.027), MUNIX and MUSIX value in the ADM (p = 0.0006 and 0.043) and in TA muscle (p = 0.025). No significant differences were observed based on cervical MRI measures. A significant reduction was detected in the composite score (p = 0.0005, SRM = −1.52), which was the most responsive variable and required a smaller number of patients than single variables in the estimation of sample size for clinical trials. Conclusions: Quantitative strength testing, SMAFRS and MUNIX readily capture disease progression in adult SMA patients. Composite multimodal scores increase predictive value and may reduce sample size requirements in clinical trials.
Published: 2021

44. Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes

Author: Giulia Barcia, Cyril Mignot, Edor Kabashi, Marie Hully, Rima Nabbout, Tommaso Lo Barco, Claude Cances, Isabelle Desguerre, Anna Kaminska, Nicolas Garcelon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Service de Génétique Cytogénétique et Embryologie [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was supported by funding from The French National Research Agency (ANR) under 'Inverstissements d’Avenir' programs (reference ANR-10-IAHU-01)., and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Computer science, [SDV]Life Sciences [q-bio], MEDLINE, 030105 genetics & heredity, computer.software_genre, Brief Communication, 03 medical and health sciences, Data Warehousing, Kv1.2 Potassium Channel, Data Mining, Electronic Health Records, Humans, Medical diagnosis, Child, Computational Biology, Infant, Newborn, Syndrome, Exome, Genetics (clinical), business.industry, Infant, Unstructured data, Newborn, Similitude, Data warehouse, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Vector space model, Identification (biology), Artificial intelligence, business, computer, Natural language processing
Abstract: International audience; Purpose: Electronic health records are gaining popularity to detect and propose interdisciplinary treatments for patients with similar medical histories, diagnoses, and outcomes. These files are compiled by different nonexperts and expert clinicians. Data mining in these unstructured data is a transposable and sustainable methodology to search for patients presenting a high similitude of clinical features.Methods: Exome and targeted next-generation sequencing bioinformatics analyses were performed at the Imagine Institute. Similarity Index (SI), an algorithm based on a vector space model (VSM) that exploits concepts extracted from clinical narrative reports was used to identify patients with highly similar clinical features.Results: Here we describe a case of "automated diagnosis" indicated by Dr. Warehouse, a biomedical data warehouse oriented toward clinical narrative reports, developed at Necker Children's Hospital using around 500,000 patients' records. Through the use of this warehouse, we were able to match and identify two patients sharing very specific clinical neonatal and childhood features harboring the same de novo variant in KCNA2.Conclusion: This innovative application of database clustering clinical features could advance identification of patients with rare and common genetic conditions and detect with high accuracy the natural history of patients harboring similar genetic pathogenic variants.
Published: 2021

45. Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial

Author: A Azbekyan, Waly Dioh, J Mariani, Serge Camelo, René Lafont, M. Chabane, C. Tourette, Pierre J. Dilda, S. Agus, Mathilde Latil, C Morelot-Panzini, M Lins, Tony Whitehouse, Stanislas Veillet, G B Nair, L A Hajjar, Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Universidade de São Paulo (USP), Sint Maartenskliniek, Oakland University, Queens Elizabeth Hospital [Birmingham], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biosynthèse des Signaux Peptidiques [IBPS] (IBPS-BIOSIPE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Acute respiratory Distress Syndrome, medicine.medical_specialty, Letter, Randomization, [SDV]Life Sciences [q-bio], Mas receptor, Medicine (miscellaneous), Placebo, Renin Angiotensin System, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Risk of mortality, Clinical endpoint, Pharmacology (medical), Respiratory function, 030212 general & internal medicine, Inflammation, lcsh:R5-920, business.industry, COVID-19, Interim analysis, angiotensin converting enzyme-2, BIO101, Tolerability, Emergency medicine, SARS-CoV2, 20-hydroxyecdysone, business, lcsh:Medicine (General), randomised controlled trial, 030217 neurology & neurosurgery
Abstract: Objectives As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. Trial design Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive – to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. Participants Inclusion criteria Age: 45 and above A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days With evidence of pneumonia based on all of the following: Clinical findings on a physical examination Respiratory symptoms developed within the past 7 days With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: Tachypnea: ≥25 breaths per minute Arterial oxygen saturation ≤92% A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion Without a significant deterioration in liver function tests: ALT and AST ≤ 5x upper limit of normal (ULN) Gamma-glutamyl transferase (GGT) ≤ 5x ULN Total bilirubin ≤ 5×ULN Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR Have a negative urine pregnancy test at screening Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. For France only: Being affiliated with a European Social Security. Exclusion criteria Not needing or not willing to remain in a healthcare facility during the study Moribund condition (death likely in days) or not expected to survive for >7 days – due to other and non-COVID-19 related conditions Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). In France only: Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients’ participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. Intervention and comparator Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., ‘negative’ or ‘positive’ event). Participants who are officially discharged from hospital care will no longer receive study medication. Main outcomes Primary study endpoint: The proportion of participants with ‘negative’ events up to 28 days. ‘Negative’ events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with ‘positive’ events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A ‘positive’ event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. Randomization Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). Blinding (masking) Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacy data, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). Trial Status The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. Trial registration The trial was registered before trial start in trial registries: EudraCT, No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728, registered July 15, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Published: 2021

46. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus

Author: Thierry Poynard, Guillaume Lassailly, Juliette Foucher, Manh-Thông Dao, Xavier Duval, Isabelle Hourmand-Ollivier, Séverine Hommel, Vincent Di Martino, Pierre-Henri Bernard, Dominique Larrey, Nathalie Boyer, Anais Labrunie, Marc Bardou, Paul Carrier, Marilyne Debette-Gratien, Marie Essig, Eric Nguyen-Khac, Armand Abergel, Victor de Ledinghen, Véronique Loustaud-Ratti, Claire Vanlemmens, Nathalie Ganne-Carrié, Anne Gervais, Jean-Baptiste Hiriart, Fouchard-Hubert Isabelle, Christine Aurières, Pauline Pinet, Thierry Thevenot, Jérémie Jacques, Philippe Mathurin, Dominique Thabut, Christophe Renou, Daniel Cohen, Marianne Maynard, Valérie Canva, Julien Vergniol, Bertrand Hanslik, Anaïs Brayette, Sophie Alain, Matthieu Schnee, Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pôle Universitaire d’Addictologie en Limousin, CH Esquirol [Limoges] (CH Esquirol), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Plate forme de bioinformatique et biostatistique (CEBIMER), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hepatology, Hopital, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Services de Maladies Infectieuses et Tropicales [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), CHU Bordeaux [Bordeaux], Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], Service d'Hépato-Gastro-Enterologie et Nutrition [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), Paris School of Economics (PSE), Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Normandie Université (NU), Service d'Hépatologie [CHRU Besançon], Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, 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), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Hôpital Saint-Éloi [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], 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 (UPC)-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 (UPC), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Hepatitis B virus, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Renal function, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Nucleoside analogues, Internal medicine, medicine, Cumulative incidence, Renal insufficiency, education, education.field_of_study, Hepatology, business.industry, Proximal tubulopathy, Incidence (epidemiology), Hazard ratio, Entecavir, Hepatitis B, medicine.disease, 030220 oncology & carcinogenesis, Prospective Study, 030211 gastroenterology & hepatology, business, Biomarkers, medicine.drug
Abstract: International audience; BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naive, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS Of the 196 patients analyzed, 138 (84 naive, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naive and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m(2) or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naive, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naive group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naive, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naive patients. SPT in the naive population suggests that HBV can induce renal tubular toxicity.
Published: 2020

47. Severe central apnea secondary to cerebellar dysplasia in a child: look past Joubert syndrome

Author: Guillaume Aubertin, Chiara Sileo, Diana Rodriguez, Harriet Corvol, Stéphanie Valence, Nicole Beydon, Jessica Taytard, Plamen Bokov, Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], 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 National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Service de physiologie, unité fonctionnelle d’explorations respiratoires [CHU Trousseau], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Mucoviscidose: physiopathologie et phénogénomique [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: MESH: Kidney Diseases, Cystic, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, MESH: Abnormalities, Multiple, Central sleep apnea, Cerebellar dysplasia, Central apnea, Case Reports, Polysomnography, Tachypnea, central sleep apnea, Joubert syndrome, MESH: Magnetic Resonance Imaging, children, MESH: Child, Female patient, medicine, MESH: Syndrome, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, medicine.diagnostic_test, business.industry, MESH: Retina, medicine.disease, MESH: Eye Abnormalities, Sleep in non-human animals, MESH: Cerebellum, respiratory tract diseases, 3. Good health, Neurology, MESH: Sleep Apnea, Central, cerebellar dysplasia, Neurology (clinical), medicine.symptom, business, MESH: Female, tachypnea, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We report the case of a female patient aged 12 years referred to our pediatric sleep unit with a history of central sleep apnea associated with transient episodes of tachypnea on polysomnography recordings. The patient was otherwise healthy, with no personal or family medical history, and had a normal physical and neuropsychological examination. Brain magnetic resonance imaging showed signs of cerebellar vermis dysplasia but without the classical features of the molar tooth sign. The rest of the workup (genetic tests, blood tests, cardiac investigations) was normal except for an increased peripheral chemosensitivity to carbon dioxide and oxygen. The patient was successfully treated with bilevel positive airway pressure. This case report highlights the importance of performing brain magnetic resonance imaging in patients with central sleep apnea to study the cerebellum, beyond the brainstem area. Cerebellar malformations can be found even in the absence of any other neurological condition. CITATION: Taytard J, Valence S, Sileo C, et al. Severe central apnea secondary to cerebellar dysplasia in a child: look past Joubert syndrome. J Clin Sleep Med. 2020;16(12):2113–2116.
Published: 2020

48. COVID‐19 and its Severity in Bariatric Surgery‐Operated Patients

Author: Charpentier, Etienne, Redheuil, Alban, Bourron, Olivier, Boussouar, Samia, Lucidarme, Olivier, Zarai, Mohamed, Kachenoura, Nadjia, Bouazizi, Khaoula, Salem, Joe-Elie, Hekimian, Guillaume, Kerneis, Matthieu, Amoura, Zahir, Allenbach, Yves, Hatem, Stephane, Jeannin, Anne-Caroline, Andreelli, Fabrizio, Phan, Franck, Tilmont, Romain, Chenu, Romain, Meyfroit, Louise, Pasi, Nicoletta, Larbi-Messaoud, Schahrazed, Laroche, Suzanne, Ciangura, Cécile, Popelier, Marc, Jacqueminet, Sophie, Halbron, Marine, Hartemann, Agnès, Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [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), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de chirurgie digestive et viscérale [CHU Pitié-Salpêtrière], Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Gestionnaire, Hal Sorbonne Université, Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord-Institut National Agronomique Paris-Grignon (INA P-G)-Sorbonne Université (SU)-CETAF-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Weight loss, Diabetes mellitus, Severity of illness, medicine, 030212 general & internal medicine, Risk factor, Nutrition and Dietetics, business.industry, Retrospective cohort study, medicine.disease, Obesity, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], medicine.symptom, business
Abstract: International audience; Objective: Obesity is a major risk factor for severe forms of coronavirus disease (COVID-19), but little is known about the post-bariatric surgery (BS) setting. The prevalence of likely COVID-19 and its risk factors in patients followed up after BS was assessed.Methods: A total of 738 patients who underwent BS and were followed up at a university medical center were surveyed. A retrospective comparison of characteristics at baseline, 1 year after BS, and at the time of lockdown was performed between patients with COVID-19-likely events (CL) based on a combination of reported symptoms and those for whom COVID-19 was unlikely.Results: CL occurred in 62 (8.4%) patients, among whom 4 (6.4%) had a severe form requiring hospitalization and 1 (1.6%) died. The CL group had a higher proportion of persistent type 2 diabetes (T2D) at last follow-up (36.2% vs. 20.3%, P = 0.01). BMI at the time of lockdown was lower in the CL group (30.2 ± 5.1 vs. 32.8 ± 6.5 kg/m2 ; P < 0.01) with higher percent weight loss since BS in the CL group. Severe forms of COVID-19 requiring hospitalization were associated with persistent T2D at the last follow-up visit.Conclusions: In BS patients, CL were associated with persistent T2D and lower BMI.
Published: 2020

49. Persistent Coronavirus Disease 2019 (COVID-19) in an Immunocompromised Host Treated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific Monoclonal Antibodies

Author: Anne Laure Clairet, Ana Berceanu, Laurie Spehner, Etienne Daguindau, Solène Marty-Quinternet, Karine Lacombe, Benoit Bailly, Kevin Bouiller, Jean-Laurent Casanova, Julien Puech, Sandrine Imbeaud, Quentin Lepiller, Marie Kroemer, Pauline Roux, Brigitte Autran, Catherine Chirouze, Xavier de Lamballerie, David Veyer, Paul Bastard, Fanny Angelot Delettre, Olivier Hermine, Hélène Péré, Nicolas Robillard, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), 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)-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), Service d'Hématologie [CHRU Besançon], Hôpital JeanMinjoz, LITTORAL (LITTORAL), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), 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), 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), 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), Rockefeller University [New York], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), CHU Pitié-Salpêtrière [AP-HP], 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier Lons le Saunier, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), and Howard Hughes Medical Institute (HHMI)
Subjects: Microbiology (medical), 0303 health sciences, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), 030306 microbiology, business.industry, Host (biology), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Monoclonal antibody, Virology, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Medicine, 030212 general & internal medicine, business
Abstract: International audience; No abstract available
Published: 2022

50. TGFβ-induced FOXS1 controls epithelial-mesenchymal transition and predicts a poor prognosis in liver cancer

Author: Raphael Pineau, Stefano Caruso, David Gilot, Kevin Bévant, Cédric Coulouarn, Gaëlle Angenard, Panagiotis Papoutsoglou, Matthis Desoteux, Jessica Zucman-Rossi, L Sulpice, Corentin Louis, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), 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), CHU Pontchaillou [Rennes], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], 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), Supported by Fondation ARC pour la Recherche sur le Cancer, IREB, Institut National Du Cancer, Prix René and Andrée Duquesne–Comité de Paris Ligue Contre le Cancer, Coup d’Elan de la Fondation Bettencourt-Schueller, Raymond Rosen Award from the Fondation pour le Recherche Médicale, Université de Rennes 1, ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé) dans le cadre du Plan Cancer (C18007NS), Labex OncoImmunology (Investissement d’Avenir), Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer (CD22, CD35, and CD85), Ligue Nationale Contre le Cancer, Région Bretagne, Fondation Mérieux, and SIRIC CARPEM., École pratique des hautes études (EPHE), Gestionnaire, HAL Sorbonne Université 5, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Dublin Institute for Advanced Studies (DIAS)
Subjects: Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, SMAD, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Medicine, Humans, Epithelial–mesenchymal transition, Transcription factor, 030304 developmental biology, 0303 health sciences, Hepatology, biology, business.industry, Liver Neoplasms, Forkhead Transcription Factors, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Transforming growth factor beta, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Biomarker (medicine), Mothers against decapentaplegic, business, Transforming growth factor
Abstract: International audience; Transforming growth factor beta (TGFβ) plays a key role in tumor progression, notably as a potent inducer of epithelial-mesenchymal transition (EMT). However, all of the molecular effectors driving TGFβ-induced EMT are not fully characterized. Here, we report that forkhead box S1 (FOXS1) is a SMAD (mothers against decapentaplegic)dependent TGFβ-induced transcription factor, which regulates the expression of genes required for the initial steps of EMT (e.g., snail family transcription repressor 1) and to maintain a mesenchymal phenotype in hepatocellular carcinoma (HCC) cells. In human HCC, we report that FOXS1 is a biomarker of poorly differentiated and aggressive tumor subtypes. Importantly, FOXS1 expression level and activity are associated with a poor prognosis (e.g., reduced patient survival), not only in HCC but also in colon, stomach, and kidney cancers. Conclusion: FOXS1 constitutes a clinically relevant biomarker for tumors in which the pro-metastatic arm of TGFβ is active (i.e., patients who may benefit from targeted therapies using inhibitors of the TGFβ pathway). (Hepatology Communications 2021;0:1-15).
Published: 2022

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