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1. Cytokines, chemokines and growth factors profile in human aqueous humor in idiopathic uveitis

Author: Marie-Hélène Errera, Ana Pratas, Sylvain Fisson, Thomas Manicom, Marouane Boubaya, Neila Sedira, Emmanuel Héron, Lilia Merabet, Alfred Kobal, Vincent Levy, Jean-Michel Warnet, Christine Chaumeil, Françoise Brignole-Baudouin, José-Alain Sahel, Pablo Goldschmidt, Bahram Bodaghi, Coralie Bloch-Queyrat, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Sorbonne Université (SU), Généthon, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Imagine - Institut des maladies génétiques (IHU) (Imagine - 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), UFR Pharmacie [Santé] - Université Paris Cité (UFR Pharmacie UPCité), Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Université Paris Cité - UFR Pharmacie [Santé] (UPCité UFR Pharmacie), Service d'Ophtalmologie [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), and Gestionnaire, Hal Sorbonne Université
Subjects: Eye Diseases, Sarcoidosis, Physiology, Inflammatory Diseases, Science, Immunology, MESH: Aqueous Humor, Uveitis, Aqueous Humor, Medical Conditions, Endocrinology, Signs and Symptoms, Rheumatology, Immune Physiology, Growth Factors, Medicine and Health Sciences, Immune Response, Inflammation, Innate Immune System, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Endocrine Physiology, Cataracts, Chemotaxis, Biology and Life Sciences, Cell Biology, Molecular Development, Ophthalmology, Cell Motility, Immune System, Lens Disorders, Cytokines, Medicine, Chemokines, Clinical Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Developmental Biology
Abstract: International audience; To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.
Published: 2022
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2. Development and real-life use assessment of a self-management smartphone application for patients with inflammatory arthritis. A user-centred step-by-step approach

Author: Beauvais, Catherine, Pham, Thao, Montagu, Guillaume, Gleizes, Sophie, Madrisotti, Francesco, Lafourcade, Alexandre, Vidal, Céline, Dervin, Guillaume, Baudard, Pauline, Desouches, Sandra, Tubach, Florence, Le Calvez, Julian, de Quatrebarbes, Marie, Lafarge, Delphine, Grange, Laurent, Alliot-Launois, Françoise, Jeantet, Henri, Antignac, Marie, Tropé, Sonia, Besset, Ludovic, Sellam, Jérémie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Aix Marseille Université (AMU), Laboratoire d'anthropologie sociale (LAS), École des hautes études en sciences sociales (EHESS)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), CERMES3 - Centre de recherche Médecine, sciences, santé, santé mentale, société (CERMES3 - UMR 8211 / U988 / UM 7), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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 Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), 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), Clinique Beau Soleil [Montpellier], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Association Française de Lutte Anti-Rhumatismale (AFLAR), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association Nationale de Défense contre l'Arthrite Rhumatoide (ANDAR), Pathologies articulaires associées aux maladies métaboliques et à l’âge [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), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Cross-Sectional Studies, [SDV]Life Sciences [q-bio], Antirheumatic Agents, Arthritis, Self-Management, Humans, Smartphone, Mobile Applications
Abstract: International audience; Background Mobile health applications (apps) are increasing in interest to enhance patient self-management. Few apps are actually used by patients and have been developed for patients with inflammatory arthritis (IA) treated with disease-modifying anti-rheumatic drugs which use entails risk of adverse effects such as infections. Objective To develop Hiboot, a self-management mobile app for patients with IA, by using a user-centred step-by-step approach and assess its real-life use. Methods The app development included first a qualitative study with semi-guided audiotaped interviews of 21 patients to identify the impact of IA on daily life and patient treatments practices and an online cross-sectional survey of 344 patients to assess their health apps use in general and potential user needs. A multidisciplinary team developed the first version of the app via five face-to-face meetings. After app launch, a second qualitative study of 21 patients and a users’ test of 13 patients and 3 rheumatologists led to the app’s current version. The number of app installations, current users and comments were collected from the Google Play store and the Apple store. Results The qualitative study revealed needs for counselling, patient–health professional partnership, and skills to cope with risk situations; 86.8% participants would be ready to use an app primarily on their rheumatologist’s recommendation. Six functionalities were implemented: a safety checklist before treatment administration, aids in daily life situations based on the French academic recommendations, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary. The Hiboot app was installed 20,500 times from September 2017 to October 2020, with 4300 regular current users. Scores were 4.4/5 stars at Android and iOS stores. Conclusion Hiboot is a free self-management app for patients with IA developed by a step-by-step process including patients and health professionals. Further evaluation of the Hiboot benefit is needed.
Published: 2021
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3. Screening for SARS-CoV-2 by RT-PCR: Saliva or nasopharyngeal swab? Rapid review and meta-analysis

Author: Dan Chaltiel, Catherine Hill, Gwénaël Le Teuff, Nusaïbah Ibrahimi, Jean-François Rupprecht, Marie-Claude Potier, Jean Yves Thuret, Agnès Delaunay-Moisan, Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-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, Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), CPT - E5 Physique statistique et systèmes complexes, Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-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), HAL-SU, Gestionnaire, 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], 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: RNA viruses, Viral Diseases, Saliva, Physiology, Coronaviruses, Artificial Gene Amplification and Extension, Polymerase Chain Reaction, Mathematical and Statistical Techniques, Medical Conditions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Nasopharynx, Medicine and Health Sciences, Screening method, Viral load, 030212 general & internal medicine, Pathology and laboratory medicine, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, Approximation Methods, Statistics, Medical microbiology, Research Assessment, Metaanalysis, Body Fluids, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, COVID-19 Nucleic Acid Testing, Meta-analysis, Viruses, Physical Sciences, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Medicine, Anatomy, Pathogens, SARS CoV 2, COVID 19, Research Article, medicine.medical_specialty, SARS coronavirus, Coronavirus disease 2019 (COVID-19), Concordance, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, Virus testing, Research and Analysis Methods, Sensitivity and Specificity, Microbiology, Specimen Handling, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Humans, Statistical Methods, Molecular Biology Techniques, Molecular Biology, Reverse transcriptase-polymerase chain reaction, SARS-CoV-2, 030306 microbiology, business.industry, Organisms, Viral pathogens, COVID-19, Biology and Life Sciences, Microbial pathogens, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Mathematics
Abstract: Background Diagnosis of COVID-19 in symptomatic patients and screening of populations for SARS-CoV-2 infection require access to straightforward, low-cost and high-throughput testing. The recommended nasopharyngeal swab tests are limited by the need of trained professionals and specific consumables and this procedure is poorly accepted as a screening method In contrast, saliva sampling can be self-administered. Methods In order to compare saliva and nasopharyngeal/oropharyngeal samples for the detection of SARS-CoV-2, we designed a meta-analysis searching in PubMed up to December 29th, 2020 with the key words “(SARS-CoV-2 OR COVID-19 OR COVID19) AND (salivary OR saliva OR oral fluid)) NOT (review[Publication Type]) NOT (PrePrint[Publication Type])” applying the following criteria: records published in peer reviewed scientific journals, in English, with at least 15 nasopharyngeal/orapharyngeal swabs and saliva paired samples tested by RT-PCR, studies with available raw data including numbers of positive and negative tests with the two sampling methods. For all studies, concordance and sensitivity were calculated and then pooled in a random-effects model. Findings A total of 377 studies were retrieved, of which 50 were eligible, reporting on 16,473 pairs of nasopharyngeal/oropharyngeal and saliva samples. Meta-analysis showed high concordance, 92.5% (95%CI: 89.5–94.7), across studies and pooled sensitivities of 86.5% (95%CI: 83.4–89.1) and 92.0% (95%CI: 89.1–94.2) from saliva and nasopharyngeal/oropharyngeal swabs respectively. Heterogeneity across studies was 72.0% for saliva and 85.0% for nasopharyngeal/oropharyngeal swabs. Interpretation Our meta-analysis strongly suggests that saliva could be used for frequent testing of COVID-19 patients and “en masse” screening of populations.
Published: 2021
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4. Use of volatile agents for sedation in the intensive care unit: A national survey in France

Author: Jean-Michel Constantin, Emmanuel Futier, Ruoyang Zhai, Jean-Etienne Bazin, Céline Lambert, Matthieu Jabaudon, Audrey Quinson, Thomas Godet, Bruno Pereira, Jules Audard, Raiko Blondonnet, Gestionnaire, Hal Sorbonne Université, CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service d'Anesthésie réanimation [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), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Health Knowledge, Attitudes, Practice, Critical Care and Emergency Medicine, Pulmonology, [SDV]Life Sciences [q-bio], Surveys, law.invention, Medical Conditions, 0302 clinical medicine, 030202 anesthesiology, law, Surveys and Questionnaires, Medicine and Health Sciences, Hypnotics and Sedatives, Medicine, Bronchial obstruction, Acute Respiratory Distress Syndrome, Multidisciplinary, Isoflurane, biology, Drugs, Pollution, Intensive care unit, Hospitals, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Research Design, Sedation, Anesthetics, Inhalation, Engineering and Technology, France, medicine.symptom, Research Article, Biotechnology, medicine.medical_specialty, Health Personnel, Science, MEDLINE, Intravenous sedation, Bioengineering, Acute respiratory distress, Research and Analysis Methods, Anaconda, Sevoflurane, Respiratory Disorders, 03 medical and health sciences, Respiratory Failure, Sedatives, Air Pollution, Humans, Pain Management, Adverse effect, Anesthetics, Pharmacology, Survey Research, business.industry, Ecology and Environmental Sciences, Biology and Life Sciences, 030208 emergency & critical care medicine, biology.organism_classification, Drug Utilization, Health Care, Health Care Facilities, Emergency medicine, Medical Devices and Equipment, business
Abstract: Background Current intensive care unit (ICU) sedation guidelines recommend strategies using non-benzodiazepine sedatives. This survey was undertaken to explore inhaled ICU sedation practice in France. Methods In this national survey, medical directors of French adult ICUs were contacted by phone or email between July and August 2019. ICU medical directors were questioned about the characteristics of their department, their knowledge on inhaled sedation, and practical aspects of inhaled sedation use in their department. Results Among the 374 ICUs contacted, 187 provided responses (50%). Most ICU directors (73%) knew about the use of inhaled ICU sedation and 21% used inhaled sedation in their unit, mostly with the Anaesthetic Conserving Device (AnaConDa, Sedana Medical). Most respondents had used volatile agents for sedation for Conclusion This survey highlights the widespread knowledge about inhaled ICU sedation in France but shows its limited use to date. Differences in education and knowledge, as well as the recent and relatively scarce literature on the use of volatile agents in the ICU, might explain the diverse practices that were observed. The low rate of mild adverse effects, as perceived by respondents, and the users’ satisfaction, are promising for this potentially important tool for ICU sedation.
Published: 2021
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5. Cardiac sarcoidosis: A long term follow up study

Author: Patrice Cacoub, Matthieu Resche-Rigon, David Saadoun, Lucie Biard, Catherine Chapelon-Abric, Anne Claire Desbois, Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 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), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), 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)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], 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: Male, Epidemiology, [SDV]Life Sciences [q-bio], Gadolinium, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Gastroenterology, Diagnostic Radiology, Cohort Studies, 0302 clinical medicine, Medical Conditions, Recurrence, Medicine and Health Sciences, 030212 general & internal medicine, Routes of Administration, Multidisciplinary, Ejection fraction, Radiology and Imaging, Drugs, Middle Aged, Prognosis, Magnetic Resonance Imaging, Immunosuppressives, Progression-Free Survival, 3. Good health, Chemistry, Cohort, Physical Sciences, Medicine, Female, Cardiomyopathies, Immunosuppressive Agents, Cohort study, Research Article, Chemical Elements, Adult, medicine.medical_specialty, Paris, Sarcoidosis, Imaging Techniques, Science, Inflammatory Diseases, Cardiology, Lower risk, Research and Analysis Methods, 03 medical and health sciences, Rheumatology, Diagnostic Medicine, Internal medicine, Intravenous Injections, medicine, Humans, Progression-free survival, Survival rate, Cyclophosphamide, Retrospective Studies, Heart Failure, Pharmacology, business.industry, Retrospective cohort study, medicine.disease, Heart failure, Medical Risk Factors, business, Follow-Up Studies
Abstract: BackgroundPrognostic factors are lacking in cardiac sarcoidosis (CS), and the effects of immunosuppressive treatments are unclear.ObjectivesTo identify prognostic factors and to assess the effects of immunosuppressive drugs on relapse risk in patients presenting with CS.MethodsFrom a cohort of 157 patients with CS with a median follow-up of 7 years, we analysed all cardiac and extra-cardiac data and treatments, and assessed relapse-free and overall survival.ResultsThe 10-year survival rate was 90% (95% CI, 84-96). Baseline factors associated with mortality were the presence of high degree atrioventricular block (HR, 5.56, 95% CI 1.7-18.2, p = 0.005), left ventricular ejection fraction below 40% (HR, 4.88, 95% CI 1.26-18.9, p = 0.022), hypertension (HR, 4.79, 95% CI 1.06-21.7, p = 0.042), abnormal pulmonary function test (HR, 3.27, 95% CI 1.07-10.0, p = 0.038), areas of late gadolinium enhancement on cardiac magnetic resonance (HR, 2.26, 95% CI 0.25-20.4, p = 0.003), and older age (HR per 10 years 1.69, 95% CI 1.13-2.52, p = 0.01). The 10-year relapse-free survival rate for cardiac relapses was 53% (95% CI, 44-63). Baseline factors that were independently associated with cardiac relapse were kidney involvement (HR, 3.35, 95% CI 1.39-8.07, p = 0.007), wall motion abnormalities (HR, 2.30, 95% CI 1.22-4.32, p = 0.010), and left heart failure (HR 2.23, 95% CI 1.12-4.45, p = 0.023). After adjustment for cardiac involvement severity, treatment with intravenous cyclophosphamide was associated with a lower risk of cardiac relapse (HR 0.16, 95% CI 0.033-0.78, p = 0.024).ConclusionsOur study identifies putative factors affecting morbidity and mortality in cardiac sarcoidosis patients. Intravenous cyclophosphamide is associated with lower relapse rates.
Published: 2020
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6. Experiences with a new biplanar low-dose X-ray device for imaging the facial skeleton: A feasibility study

Author: Berg, Britt-Isabelle, Laville, Aurélien, Courvoisier, Delphine S., Rouch, Philippe, Schouman, Thomas, University Hospital Basel [Basel], Institut de Biomécanique Humaine Georges Charpak (IBHGC), Université Sorbonne Paris Nord-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), University Hospitals of Geneva, Service de Stomatologie et Chirurgie Maxillo-facial [CHU Pitié-Salpêtrière], 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), For this study, no author has received any funding. During the time this retrospective study took place, the institute/laboratory in which Prof. P. Rouch works and Dr. A. Laville worked received funding from the EOS-Imaging company for other EOS studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Nord, 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: Medical Doctors, [SDV]Life Sciences [q-bio], Health Care Providers, Mandible, Diagnostic Radiology, Medicine and Health Sciences, Medical Personnel, Musculoskeletal System, Radiology and Imaging, General Medicine, Middle Aged, humanities, Bone Imaging, Professions, Sciences du vivant, Medicine, Engineering and Technology, Anatomy, General Agricultural and Biological Sciences, Research Article, Adult, Adolescent, Imaging Techniques, Science, Equipment, Genetics and Molecular Biology, Surgical and Invasive Medical Procedures, Research and Analysis Methods, Radiation Dosage, General Biochemistry, Genetics and Molecular Biology, Facial Bones, Young Adult, Diagnostic Medicine, Physicians, Humans, Skeleton, Aged, Surgeons, Mouth, Imaging Equipment, X-Rays, Biology and Life Sciences, X-Ray Radiography, Health Care, Radiography, Face, General Biochemistry, People and Places, Feasibility Studies, Population Groupings, Head, Digestive System
Abstract: Methods We evaluated 48 biplanar radiographs from 12 patients (posteroanterior/lateral), originally taken for a scoliosis examination with a biplanar low-dose X-ray device. For this study, the images were further evaluated for the perceptibility of 38 facial skeleton landmarks. To determine the reliability and reproducibility of perceptibility, two independent observers determined the landmarks twice, during a time interval of at least two weeks. Results Both interoperator and intraoperator reliability were excellent for all landmarks [intraclass correlation coefficient (ICC) > 0.92]. Conclusions The biplanar low-dose X-ray device demonstrated good feasibility for precisely assessing the anatomical landmarks of the facial skeleton. Given its excellent precision, the biplanar low-dose X-ray device data sets should be forwarded from the treating orthopedic surgeon or neurosurgeon to the orthodontist or dentist for further assessment in their field. For this study, no author has received any funding. During the time this retrospective study took place, the institute/laboratory in which Prof. P. Rouch works and Dr. A. Laville worked received funding from the EOS-Imaging company for other EOS studies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2020
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7. Investigation of viral etiology in potentially malignant disorders and oral squamous cell carcinomas in non-smoking, non-drinking patients

Author: Nicolas Berthet, Antoine Gessain, Jean-Philippe Foy, Michaël Falguières, Nicole Corre-Catelin, Marie-Noëlle Ungeheuer, Chloé Bertolus, Valérie Caro, Isabelle Heard, Patrick Goudot, Philippe Pérot, Laurence Arowas, Hélène Laude, Marc Eloit, Pérot, Philippe, Découverte de Pathogènes - Pathogen Discovery, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain (CNR-HPV), Institut Pasteur [Paris] (IP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Stomatologie et Chirurgie Maxillo-facial [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), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), École nationale vétérinaire - Alfort (ENVA), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The French Institut National du Cancer - INCa - had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], École nationale vétérinaire d'Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Male, Epidemiology, Carcinogenesis, Cell, Artificial Gene Amplification and Extension, Alphapapillomavirus, Pathology and Laboratory Medicine, Polymerase Chain Reaction, law.invention, Transcriptome, 0302 clinical medicine, law, Genotype, Medicine and Health Sciences, Medicine, Papillomaviridae, Polymerase chain reaction, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multidisciplinary, Alcohol Consumption, Cancer Risk Factors, Smoking, Squamous Cell Carcinomas, Middle Aged, 3. Good health, medicine.anatomical_structure, Oncology, Medical Microbiology, 030220 oncology & carcinogenesis, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Carcinoma, Squamous Cell, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Mouth Neoplasms, Pathogens, Anatomy, Research Article, Adult, food.ingredient, Papillomaviruses, Alcohol Drinking, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Research and Analysis Methods, Microbiology, Carcinomas, Virus, 03 medical and health sciences, food, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tongue, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Nutrition, Aged, Mouth, Betapapillomavirus, Biology and life sciences, business.industry, Papillomavirus Infections, Organisms, Human Papillomavirus, Cancers and Neoplasms, Reverse Transcriptase-Polymerase Chain Reaction, Diet, stomatognathic diseases, 030104 developmental biology, Medical Risk Factors, Cancer research, business, DNA viruses, Digestive System
Abstract: International audience; Head and neck squamous cell carcinomas (HNSCC) are the seventh most frequent cancers. Among HNSCCs, oral squamous cell carcinomas (OSCCs) include several anatomical locations of the oral cavity, but exclude the oropharynx. The known risk factors for OSCCs are mainly alcohol consumption and tobacco use for at least 75-80% of cases. In addition to these risk factors, Human papillomavirus (HPV) types 16 and 18, classified as high-risk (HR) HPV genotypes, are considered as risk factors for oropharyngeal cancers, but their role in the development of OSCC remains unclear. We tested the hypothesis of viral etiology in a series of 68 well-characterized OSCCs and 14 potentially malignant disorders (PMD) in non-smoking, non-drinking (NSND) patients using broad-range, sensitive molecular methodologies. Deep-sequencing of the transcriptome did not reveal any vertebrate virus sequences other than HPV transcripts, detected in only one case. In contrast, HPV DNA was detected in 41.2% (28/68) and 35.7% (5/14) of OSCC and PMD cases, respectively. Importantly, 90.9% (30/33) of these belonged to the Betapapillomavirus genus, but no viral transcripts were detected. Finally, high-throughput sequencing revealed reads corresponding to transcripts of the Trichomonas vaginalis virus (TVV), which were confirmed by RT-PCR in two OSCCs. Our results strongly suggest that Alphapapillomavirus genotypes classified as HR are not involved in the development of OSCCs in NSND patients and that known oncogenic infectious agents are absent in these specific OSCCs. Any possible direct or indirect role of Betapapillomavirus genus members and TVV in OSCCs remains speculative and requires further investigation.
Published: 2020
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8. Using a new diagnostic tool to predict lymph node metastasis in advanced epithelial ovarian cancer leads to simple lymphadenectomy decision rules: A multicentre study from the FRANCOGYN group

Author: Arnaud Fauconnier, Matthieu Mezzadri, Sofiane Bendifallah, Jean Louis Benifla, Roman Rouzier, Yohan Kerbage, Vincent Lavoué, Xavier Paoletti, Geoffroy Canlorbe, Camille Mimoun, Charles Coutant, Cyrille Huchon, Lobna Ouldamer, Adrien Crestani, Cyril Touboul, Thomas Gaillard, Yohann Dabi, Alexandre Bricou, Lise Lecointre, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Gynécologie-obstétrique et médecine de la reproduction - Maternité [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), Service de gynécologie-obstétrique [Hôpital Jean Verdier], Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Service de gynécologie et obstétrique [Créteil], CHI Créteil, Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [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), Clinique de Gynécologie [Lille] (Hôpital Jeanne de Flandre), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de Gynécologie-Obstétrique [CHU Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Mines Paris - PSL (École nationale supérieure des mines de Paris), Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], and HAL UVSQ, Équipe
Subjects: Oncology, Epidemiology, medicine.medical_treatment, Cancer Treatment, Pelvic Lymphadenectomy, Lymph node metastasis, Carcinoma, Ovarian Epithelial, Logistic regression, Surgical planning, Metastasis, Mathematical and Statistical Techniques, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Basic Cancer Research, Medicine and Health Sciences, Blood and Lymphatic System Procedures, Medicine, Ovarian Neoplasms, 0303 health sciences, Multidisciplinary, Cancer Risk Factors, Statistics, Cytoreduction Surgical Procedures, Middle Aged, 3. Good health, Surgical Oncology, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Physical Sciences, Cohort, Female, France, Anatomy, Research Article, Clinical Oncology, medicine.medical_specialty, Science, Clinical Decision-Making, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Research and Analysis Methods, Lymphatic System, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Statistical Methods, Aged, Retrospective Studies, 030304 developmental biology, Internet, business.industry, Biology and Life Sciences, Lymphadenectomy, Decision rule, medicine.disease, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Logistic Models, Medical Risk Factors, Lymph Node Excision, Lymph Nodes, Clinical Medicine, business, Ovarian cancer, Mathematics, Forecasting
Abstract: Objective The aim of this study was to develop a new diagnostic tool to predict lymph node metastasis (LNM) in patients with advanced epithelial ovarian cancer undergoing primary cytoreductive surgery. Materials and method The FRANCOGYN group’s multicenter retrospective ovarian cancer cohort furnished the patient population on which we developed a logistic regression model. The prediction model equation enabled us to create LNM risk groups with simple lymphadenectomy decision rules associated with a user-friendly free interactive web application called shinyLNM. Results 277 patients from the FRANCOGYN cohort were included; 115 with no LNM and 162 with LNM. Three variables were independently and significantly (p Conclusion This new tool may prove useful for improving surgical planning and provide useful information for patients.
Published: 2021
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9. Rapid glycemic regulation in poorly controlled patients living with diabetes, a new associated factor in the pathophysiology of Charcot's acute neuroarthropathy

Author: Frederic Jaisser, Jocelyne M’Bemba, Agnès Hartemann, Jean-Michel Davaine, Franck Phan, Olivier Bourron, Georges Ha Van, Francois-Xavier Laborne, Dured Dardari, Fabienne Foufelle, Alfred Penfornis, 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 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), and Service de diabétologie [CHU Pitié-Salpétrière]
Subjects: Male, Diabetic neuropathy, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gastroenterology, Biochemistry, Diagnostic Radiology, 0302 clinical medicine, Endocrinology, Skeletal Joints, Active phase, Diabetes diagnosis and management, Diabetic Nephropathies, 030212 general & internal medicine, Musculoskeletal System, Multidisciplinary, Radiology and Imaging, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Magnetic Resonance Imaging, Pathophysiology, 3. Good health, Neurology, Medicine, Female, Anatomy, Research Article, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, HbA1c, Endocrine Disorders, Imaging Techniques, Science, 030209 endocrinology & metabolism, Research and Analysis Methods, 03 medical and health sciences, Hba1c level, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Humans, Hypoglycemic Agents, Hemoglobin, Glycemic, Aged, Retrospective Studies, Glycated Hemoglobin, Medicine and health sciences, Biology and life sciences, business.industry, Amyotrophic Lateral Sclerosis, Proteins, Retrospective cohort study, medicine.disease, Charcot neuroarthropathy, Diagnostic medicine, Neuropathy, Metabolic Disorders, business
Abstract: International audience; Objective: Aggressive antidiabetic therapy and rapid glycemic control are associated with diabetic neuropathy. Here we investigated if this is also the case for Charcot neuroarthropathy.Research design and methods: HbA1c levels and other relevant data were extracted from medical databases of 44 cases of acute Charcot neuroarthropathy.Results: HbA1c levels significantly declined from 8.25% (67mmol/mol) [7.1%-9.4%](54-79mmol/mol), at -6 months (M-6), to 7.40%(54mmol/mol) [6.70%-8.03%] (50-64 mmol/mol) during the six months preceding the diagnosis of Charcot neuroarthropathy (P
Published: 2020
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10. Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients

Author: Lecronier, Marie, Tashk, Parvine, Tamzali, Yanis, Tenaillon, Olivier, Denamur, Erick, Barrou, Benoit, Aron-Wisnewsky, Judith, Tourret, Jérôme, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie [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), Laboratoire de Génétique Moléculaire [Paris], 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), Sorbonne Université (SU), Service de Nutrition [Paris], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Équipe NutriOmics [Paris], JT was supported by an award from 'la Fondation du Rein' named 'Don de soi, don de vie'., Bodescot, Myriam, 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)-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), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, Physiology, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Feces, Endocrinology, Risk Factors, Medicine and Health Sciences, Renal Transplantation, Diabetes diagnosis and management, Genomics, Middle Aged, Physiological Parameters, Medical Microbiology, Medicine, Female, Research Article, DNA, Bacterial, HbA1c, Endocrine Disorders, Science, Surgical and Invasive Medical Procedures, Microbial Genomics, Microbiology, Urinary System Procedures, Verrucomicrobia, Diabetes Mellitus, Genetics, Humans, Obesity, Hemoglobin, Transplantation, Bacteria, Faecalibacterium prausnitzii, Gut Bacteria, Body Weight, Organisms, Biology and Life Sciences, Proteins, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Akkermansia, Organ Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diagnostic medicine, Gastrointestinal Microbiome, Lactobacillus, Diabetes Mellitus, Type 2, Metabolic Disorders, Microbiome
Abstract: Background The gut dysbiosis associated with diabetes acquired before or after kidney transplantation (KT) has not been explored. Methods Patients transplanted at our institution provided fecal samples before, and 3–9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR. Results 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p
Published: 2020
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11. Development of a multivariate prediction model of intensive care unit transfer or death: A French prospective cohort study of hospitalized COVID-19 patients

Author: Yves Allenbach, David Saadoun, Georgina Maalouf, Matheus Vieira, Alexandra Hellio, Jacques Boddaert, Hélène Gros, Joe Elie Salem, Matthieu Resche Rigon, Cherifa Menyssa, Lucie Biard, Olivier Benveniste, Patrice Cacoub, DIMICOVID, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], 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 - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Service de gériatrie [CHU Pitié-Salpêtrière], Hôpital Robert Ballanger [Aulnay-sous-Bois], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de biostatistiques et information médicale [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)-Université de Paris (UP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], 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), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Male, Viral Diseases, Epidemiology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Logistic regression, Biochemistry, law.invention, Diagnostic Radiology, White Blood Cells, 0302 clinical medicine, Medical Conditions, law, Animal Cells, Medicine and Health Sciences, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Lymphocytes, Prospective cohort study, Tomography, Aged, 80 and over, COVID-19, Ferritin, Medical risk factors, Troponin, Computed axial tomograph, Intensive care units, Oxygen, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Radiology and Imaging, Middle Aged, Prognosis, Intensive care unit, Patient Discharge, Hospitals, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Intensive Care Units, Chemistry, Infectious Diseases, Brier score, Physical Sciences, Medicine, Female, Cellular Types, Coronavirus Infections, Research Article, Chemical Elements, Patient Transfer, medicine.medical_specialty, Paris, Coronavirus disease 2019 (COVID-19), Imaging Techniques, Immune Cells, Science, Pneumonia, Viral, Immunology, MEDLINE, Neuroimaging, Real-Time Polymerase Chain Reaction, Research and Analysis Methods, 03 medical and health sciences, Betacoronavirus, Diagnostic Medicine, Internal medicine, medicine, Humans, Pandemics, Aged, Blood Cells, business.industry, SARS-CoV-2, Biology and Life Sciences, Proteins, Protein Complexes, Covid 19, Cell Biology, medicine.disease, Computed Axial Tomography, Health Care, Pneumonia, Cytoskeletal Proteins, Health Care Facilities, Medical Risk Factors, Observational study, business, Forecasting, Neuroscience
Abstract: International audience; Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.
Published: 2020
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12. Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

Author: Franck Phan, Anne-Caroline Jeannin, Carole E. Aubert, Ziad A. Massy, Agnès Hartemann, Joe-Elie Salem, M. Halbron, Chloé Amouyal, Christian Funck-Brentano, Olivier Bourron, Cees Vemeer, Sorbonne Université (SU), 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), 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bern, Maastricht University [Maastricht], 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), This work was supported by a fund from the Lilly Company. The research activities of C.E.A. were supported by a doctoral research scholarship from the University of Lausanne. A.C.J received a grant from Ministère français des Affaires Sociales et de la Santé (Bourse année recherche 2017/2018)., RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], 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], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Bodescot, Myriam, 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Vitamin K, Diabetic neuropathy, diagnosis, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organic chemistry, Type 2 diabetes, Biochemistry, BONE MORPHOGENETIC PROTEIN-2, Endocrinology, 0302 clinical medicine, Matrix gla protein, Medicine and Health Sciences, Diabetes diagnosis and management, Insulin, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Multidisciplinary, biology, Vitamins, nerve-conduction, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Type 2 Diabetes, 3. Good health, Physical sciences, Chemistry, Neurology, Optical Equipment, Engineering and Technology, Biomarker (medicine), Medicine, Research Article, Retinopathy, cardiovascular risk, medicine.medical_specialty, HbA1c, alpha, Endocrine Disorders, B vitamins, Science, prevalence, INHIBITION, Equipment, 610 Medicine & health, 030209 endocrinology & metabolism, Chemical compounds, 03 medical and health sciences, 360 Social problems & social services, Diabetes mellitus, Internal medicine, Organic compounds, Diabetes Mellitus, medicine, Hemoglobin, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Peripheral Neuropathy, Diabetic Endocrinology, Biology and life sciences, criteria, RECEPTOR, business.industry, Lasers, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Proteins, medicine.disease, Diagnostic medicine, Hormones, Neuropathy, Peripheral neuropathy, Metabolic Disorders, biology.protein, RISK-FACTORS, business, 030217 neurology & neurosurgery
Abstract: International audience; AIMS/HYPOTHESIS:Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP.METHODS:198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA.RESULTS:In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p
Published: 2020
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13. Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

Author: E. Meriglier, Sandrine Dabernat, Alexandre Boyer, Isabelle Pellegrin, Sébastien Rubin, Aurélie Bedel, François Moreau-Gaudry, Pascale Trimoulet, Arnaud Desclaux, Didier Gruson, Arthur Orieux, Isabelle Garrigue, Charles Dupin, Marie Lise Bats, Etienne Rivière, Rana Alkouri, Tara Fleur, Brigitte Colombies, C. Rivoisy, Clément Chemin, Benoit Rucheton, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Biochimie Métabolique [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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Fondamentale et Pathogénicité (MFP), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, Viral Diseases, Physiology, [SDV]Life Sciences [q-bio], Aminotransferases, Comorbidity, 030204 cardiovascular system & hematology, Severity of Illness Index, Biochemistry, Body Mass Index, Medical Conditions, 0302 clinical medicine, Risk Factors, Epidemiology, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Virus Testing, Multidisciplinary, Framingham Risk Score, medicine.diagnostic_test, Middle Aged, C-Reactive Proteins, Hospitals, Enzymes, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, Physiological Parameters, Cardiovascular Diseases, Cohort, Female, Risk assessment, Research Article, Paris, medicine.medical_specialty, Science, Risk Assessment, 03 medical and health sciences, Diagnostic Medicine, Transferases, Albumins, Severity of illness, Humans, Blood test, Obesity, Aged, Retrospective Studies, Ferritin, SARS-CoV-2, business.industry, Body Weight, COVID-19, Biology and Life Sciences, Proteins, Protein Complexes, Covid 19, Retrospective cohort study, medicine.disease, Health Care, Health Care Facilities, Emergency medicine, Enzymology, business
Abstract: International audience; Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves.
Published: 2021
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14. Cross-cultural adaptation and psychometric evaluation of the French version of the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL)

Author: Isabelle Jalenques, Diane Cyrille, Philippe Derost, Andreas Hartmann, Sophie Lauron, Clara Jameux, Urbain Tauveron-Jalenques, Candy Guiguet-Auclair, Fabien Rondepierre, Syndrome de Gilles de La Tourette Study Group, CHU Clermont-Ferrand, Centre De Référence National 'Syndrome Gilles de la Tourette', Pôle des Maladies du Système Nerveux [CHU Pitié-Salpêtrière], 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), 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), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Questionnaires, Male, Psychometrics, Intraclass correlation, [SDV]Life Sciences [q-bio], Culture, Social Sciences, Tourette syndrome, 0302 clinical medicine, Sociology, Surveys and Questionnaires, Activities of Daily Living, Medicine and Health Sciences, Psychology, Reliability (statistics), Multidisciplinary, Middle Aged, humanities, Exploratory factor analysis, 3. Good health, Clinical Psychology, Convergent validity, Research Design, Compulsive Behavior, Medicine, Female, Research Article, Clinical psychology, Adult, Cross-Cultural Comparison, Social Psychology, Adolescent, Science, Research and Analysis Methods, World Health Organization, Young Adult, 03 medical and health sciences, Quality of life (healthcare), Cronbach's alpha, Cross-Cultural Studies, medicine, Humans, Survey Research, Cognitive Psychology, Biology and Life Sciences, medicine.disease, 030227 psychiatry, Health Care, Quality of Life, Cognitive Science, 030217 neurology & neurosurgery, Neuroscience, Tourette Syndrome
Abstract: IntroductionThe Gilles de la Tourette Syndrome–Quality of Life Scale (GTS-QOL) is a self-rated disease-specific questionnaire to assess health-related quality of life of subjects with GTS.Our aim was to perform the cross-cultural adaptation of the GTS-QOL into French and to assess its psychometric properties.MethodsThe GTS-QOL was cross-culturally adapted by conducting forward and backward translations, following international guidelines. The psychometric properties of the GTS-QOL-French were assessed in 109 participants aged 16 years and above with regard to factor structure, internal consistency, reliability and convergent validity with the MOVES (Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey) and the WHOQOL-BREF (World Health Organization Quality of Life Brief).ResultsExploratory factor analysis of the GTS-QOL-French resulted in a 6-factor solution and did not replicate the original structure in four subscales. The results showed good acceptability (missing values per subscale ranging from 0% to 0.9%), good internal consistency (Cronbach’s alpha ranging from 0.68 to 0.94) and good test–retest reliability (intraclass correlation coefficients ranging from 0.70 to 0.81). Convergent validity with the MOVES and WHOQOL-BREF scales showed high correlations.DiscussionOur study provides evidence of the good psychometric properties of the GTS-QOL-French. The cross-cultural adaptation and validation of this specific instrument will make it possible to assess health-related quality of life in French-speaking subjects with GTS. The GTS-QOL-French could be recommended for use in future research.
Published: 2020
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15. Diagnostic performance of chest computed tomography during the epidemic wave of COVID-19 varied as a function of time since the beginning of the confinement in France

Author: Olivier Lucidarme, Raphaële Renard-Penna, Joe-Elie Salem, Mathilde Wagner, Samia Boussouar, Victoria Donciu, Alban Redheuil, Stéphane Marot, Nicoletta Pasi, Yonathan Freund, 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), 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de pharmacologie 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), 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 Urgences [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Male, Viral Diseases, Pulmonology, Epidemiology, COVID19, [SDV]Life Sciences [q-bio], Chest ct, Artificial Gene Amplification and Extension, Computed tomography, 030204 cardiovascular system & hematology, Polymerase Chain Reaction, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Diagnostic Radiology, 030218 nuclear medicine & medical imaging, Medical Conditions, 0302 clinical medicine, Medicine and Health Sciences, Tomography, Virus Testing, Aged, 80 and over, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Radiology and Imaging, Middle Aged, Reference Standards, Prognosis, Pulmonary Imaging, 3. Good health, Infectious Diseases, Medicine, Female, France, Radiology, Research Article, Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Adolescent, Coronavirus disease 2019 (COVID-19), Imaging Techniques, Science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Neuroimaging, Research and Analysis Methods, Sensitivity and Specificity, Infectious Disease Epidemiology, Young Adult, 03 medical and health sciences, Computed Tomography, Diagnostic Medicine, medicine, Humans, Molecular Biology Techniques, education, Molecular Biology, Pandemics, Aged, Retrospective Studies, SARS-CoV-2, business.industry, Biology and Life Sciences, COVID-19, Covid 19, Reverse Transcriptase-Polymerase Chain Reaction, Pneumonia, medicine.disease, Mass Chest X-Ray, Computed Axial Tomography, Pulmonary imaging, Tomography, X-Ray Computed, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Neuroscience
Abstract: Objective To evaluate the diagnostic performance of the initial chest CT to diagnose COVID-19 related pneumonia in a French population of patients with respiratory symptoms according to the time from the onset of country-wide confinement to better understand what could be the role of the chest CT in the different phases of the epidemic. Material and method Initial chest CT of 1064 patients with respiratory symptoms suspect of COVID-19 referred between March 18th, and May 12th 2020, were read according to a standardized procedure. The results of chest CTs were compared to the results of the RT-PCR. Results 546 (51%) patients were found to be positive for SARS-CoV2 at RT-PCR. The highest rate of positive RT-PCR was during the second week of confinement reaching 71.9%. After six weeks of confinement, the positive RT-PCR rate dropped significantly to 10.5% (p Conclusion At the peak of the epidemic, chest CT had sufficiently high sensitivity and PPV to serve as a first-line positive diagnostic tool but at the end of the epidemic wave CT is more useful to exclude COVID-19 pneumonia.
Published: 2020
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16. Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry

Author: Marie Metzger, Cécile Couchoud, Lucile Mercadal, Christian Jacquelinet, Gabriel Choukroun, Oriane Lambert, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence de la biomédecine [Saint-Denis la Plaine], Nephrology, Dialysis & Transplantation Department [Amiens], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de néphrologie [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), The study was funded by the Agence de la Biomédecine in 2016 and by the Société Francophone Néphrologie Dialyse et Transplantation in 2017 (Baxter grant). Author LM received fees for a medical speech about the results of the study at an AMGEN conference., Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHU Pitié-Salpêtrière], 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Bodescot, Myriam
Subjects: Male, Cinacalcet, Physiology, medicine.medical_treatment, 030232 urology & nephrology, Organic chemistry, Sevelamer, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Medicine and Health Sciences, Renal Transplantation, Coronary Heart Disease, Longitudinal Studies, Registries, Vitamin D, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Multidisciplinary, Hazard ratio, Calcinosis, Vitamins, Middle Aged, 3. Good health, Physical sciences, Chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Nephrology, Medicine, Female, France, Hemodialysis, Research Article, Chemical Elements, medicine.drug, medicine.medical_specialty, Death Rates, Bone and Mineral Metabolism, Science, Cardiology, Urology, chemistry.chemical_element, Surgical and Invasive Medical Procedures, Calcium, Bone and Bones, Urinary System Procedures, Calcification, Chemical compounds, 03 medical and health sciences, Population Metrics, Lanthanum, Renal Dialysis, Medical Dialysis, Organic compounds, medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Aged, Proportional Hazards Models, Calcium metabolism, Transplantation, Population Biology, business.industry, Biology and Life Sciences, Organ Transplantation, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Hemodialysis Solutions, Metabolism, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Blood Vessels, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Physiological Processes, business
Abstract: International audience; Background: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival.Methods: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data.Results: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and
Published: 2020
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17. Diaphragm sniff ultrasound: Normal values, relationship with sniff nasal pressure and accuracy for predicting respiratory involvement in patients with neuromuscular disorders

Author: David Orlikowski, Frédéric Lofaso, Pascal Crenn, Adam Ogna, Anthony Behin, Robert Carlier, Hélène Prigent, Abdallah Fayssoil, Pascal Laforêt, Guillaume Bassez, Dominique Mompoint, Tanya Stojkovic, Paris Meng, Bruno Eymard, Bernard Clair, Djillali Annane, Lee S. Nguyen, Centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France [Paris], 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)-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 d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpital Raymond Poincaré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de physiologie et d'explorations fonctionnelles [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), 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), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-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), Bodescot, Myriam, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Vital capacity, Time Factors, Heredity, Genetic Linkage, Vital Capacity, Respiratory System, Velocity, Blood Pressure, Duchenne Muscular Dystrophy, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Vascular Medicine, Muscular Dystrophies, Diagnostic Radiology, 0302 clinical medicine, Thoracic Diaphragm, Ultrasound Imaging, Medicine and Health Sciences, Myotonic Dystrophy, Respiratory function, Respiratory system, Tidal volume, Multidisciplinary, Respiration, Physics, Radiology and Imaging, Ultrasound, Classical Mechanics, Neuromuscular Diseases, respiratory system, Middle Aged, musculoskeletal system, Diaphragm (structural system), medicine.anatomical_structure, Neurology, X-Linked Traits, Sex Linkage, Genetic Diseases, Physical Sciences, Cardiology, Medicine, Female, Anatomy, psychological phenomena and processes, Research Article, Adult, medicine.medical_specialty, Imaging Techniques, Science, Movement, Diaphragm, Nose, Research and Analysis Methods, Doppler Imaging, Thoracic diaphragm, 03 medical and health sciences, FEV1/FVC ratio, Motion, stomatognathic system, Diagnostic Medicine, Internal medicine, medicine, Pressure, Tidal Volume, Genetics, Humans, Clinical Genetics, business.industry, Biology and Life Sciences, Ultrasonography, Doppler, body regions, 030228 respiratory system, ROC Curve, Case-Control Studies, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: BackgroundIn patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders.PurposeWe aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency.Materials and methodsWe included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver.ResultsA total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p ConclusionSniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials.
Published: 2018
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18. Multi-parametric quantitative MRI reveals three different white matter subtypes

Author: Mathieu Santin, Olivier Mainberger, Julien Lamy, Paulo Loureiro de Sousa, Mathilde M Roser, Jack R. Foucher, Alexandre Vignaud, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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)-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 d'Imagerie BioMédicale (I2BM), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay
Subjects: Central Nervous System, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:Medicine, Biochemistry, Nervous System, 030218 nuclear medicine & medical imaging, Diagnostic Radiology, Corpus Callosum, Myelin, 0302 clinical medicine, Nuclear magnetic resonance, Nerve Fibers, Animal Cells, Cortex (anatomy), Medicine and Health Sciences, lcsh:Science, Neurons, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Chemistry, Radiology and Imaging, Physics, Radial diffusivity, Magnetism, Brain, Middle Aged, Condensed Matter Physics, Lipids, Magnetic Resonance Imaging, White Matter, medicine.anatomical_structure, Cholesterol, Diffusion Tensor Imaging, Frontal lobe, Physical Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Anatomy, Protons, Cellular Types, Research Article, Adult, Imaging Techniques, Brain Morphometry, Neuroimaging, Research and Analysis Methods, White matter, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, Nuclear Physics, Nucleons, Multi parametric, lcsh:R, Biology and Life Sciences, Magnetic resonance imaging, Cell Biology, Axons, Magnetic Fields, Cellular Neuroscience, lcsh:Q, 030217 neurology & neurosurgery, Diffusion MRI, Neuroscience
Abstract: International audience; Introduction: Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution.Materials and methods: Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (χm). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values.Results: Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10−18). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10−6). This was compatible with their larger χm and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration.Conclusions: Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.
Published: 2018
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19. Suggestion of self-(in)coherence modulates cognitive dissonance

Author: Lionel Naccache, Mariam Chammat, Joshua Hagège, Caroline Tandetnik, 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 Neurophysiologie [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), HAL UPMC, Gestionnaire, 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), 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: Adult, Male, Social psychology (sociology), Preference change, Sense of Coherence, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Memory, Episodic, lcsh:Medicine, 050109 social psychology, Models, Psychological, Choice Behavior, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognitive dissonance, Humans, 0501 psychology and cognitive sciences, lcsh:Science, Suggestion, Episodic memory, media_common, Multidisciplinary, lcsh:R, 05 social sciences, Coherence (philosophical gambling strategy), [SDV] Life Sciences [q-bio], Linear Models, lcsh:Q, Female, Consciousness, Psychology, 030217 neurology & neurosurgery, Photic Stimulation, Sense of coherence, Cognitive psychology, Cognitive Dissonance
Abstract: International audience; While cognitive dissonance is an influential concept of social psychology, its relations with consciousness and episodic memory remain strongly debated. We recently used the free-choice paradigm (FCP) to demonstrate the crucial role of conscious memory of previous choices on choice-induced preference change (CIPC). After choosing between two similarly rated items, subjects reevaluated chosen items as more attractive, and rejected items as less attractive. However such a CIPC was present exclusively for items that were correctly remembered as chosen or rejected during the choice stage, both in healthy controls and in amnesic patients. In the present work, we show that CIPC can be modulated by suggestive quotes promoting self-coherence or self-incoherence. In addition to the crucial role of memory of previous choices, we discovered that memory of the suggestive quotes was correlated to the modulation of CIPC. Taken together these results suggest that CIPC reflects a dynamic homeostatic regulation of self-coherence.
Published: 2018
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20. Aptamers as biomarkers for neurological disorders. Proof of concept in transgenic mice

Author: Simone Lista, Gregory Penner, Harald Hampel, Soizic Lecocq, Bruno Dubois, Katia Spinella, NeoNeuro SAS Paris, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), AXA Research Fund, AXA Reasearch Fund, HAL UPMC, Gestionnaire, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), 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)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Physiology, Molecular biology, lcsh:Medicine, Alzheimer's Disease, Biochemistry, Epitope, Database and Informatics Methods, Mice, 0302 clinical medicine, Blood serum, Sequencing techniques, Medicine and Health Sciences, DNA sequencing, lcsh:Science, Multidisciplinary, SELEX Aptamer Technique, Neurodegenerative Diseases, Animal Models, Genomics, Aptamers, Nucleotide, Body Fluids, Blood, Experimental Organism Systems, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, Sequence Analysis, Transcriptome Analysis, Research Article, Biotechnology, Next-Generation Sequencing, Bioinformatics, Aptamer, Transgene, Mouse Models, Mice, Transgenic, Biology, Research and Analysis Methods, 03 medical and health sciences, Model Organisms, Mental Health and Psychiatry, Genetics, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gene, Selection (genetic algorithm), lcsh:R, Wild type, Biology and Life Sciences, Computational Biology, Blood Serum, Genome Analysis, 030104 developmental biology, Molecular biology techniques, lcsh:Q, Dementia, Nervous System Diseases, 030217 neurology & neurosurgery, Biomarkers
Abstract: International audience; The act of selecting aptamers against blood serum leads to deep libraries of oligonucleotide sequences that bind to a range of epitopes in blood. In this study we developed an enriched aptamer library by performing positive selection against a pool of blood serum samples from transgenic mice (P301S) carrying the human tau gene and counter selecting against pooled blood serum from negative segregant (wild type) mice. We demonstrated that a large proportion of the aptamer sequences observed with next generation sequence (NGS) analysis were the same from selection round 5 and selection round 6. As a second step, we applied aliquots of the selection round 5 enriched library to blood serum from 16 individual mice for a single round of selection. Each of these individual libraries were characterized through NGS analysis and the changes in relative frequency in aptamers from transgenic mice versus wild type were used to construct a diagnostic fingerprint of the effect of the action of the transgene on the composition of blood serum. This study serves as a model for similar applications with human subjects.
Published: 2018
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21. Analysis of cell surface and intranuclear markers on non-stimulated human PBMC using mass cytometry

Author: Olivier Benveniste, Aurélien Corneau, Catherine Blanc, Gaëlle Dzangué-Tchoupou, Yves Allenbach, Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), 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), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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 UPMC, Gestionnaire
Subjects: 0301 basic medicine, Composite Particles, Cell Membrane Permeability, Tissue Fixation, B Cells, [SDV]Life Sciences [q-bio], Cell, lcsh:Medicine, Cell Separation, Epitope, Epitopes, White Blood Cells, 0302 clinical medicine, Isotopes, Animal Cells, Medicine and Health Sciences, lcsh:Science, Staining, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, Chemistry, Physics, Cell Staining, Regulatory T cells, Flow Cytometry, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Antigens, Surface, Physical Sciences, Cellular Types, Palladium, Research Article, Chemical Elements, Atoms, Immune Cells, Immunology, Population, T cells, Research and Analysis Methods, Peripheral blood mononuclear cell, Flow cytometry, Fixatives, 03 medical and health sciences, Antigen, medicine, Humans, Mass cytometry, Antibody-Producing Cells, Particle Physics, education, Cell Nucleus, Blood Cells, Staining and Labeling, Cell Membrane, lcsh:R, Biology and Life Sciences, Cell Biology, Molecular biology, Molecular Typing, Nuclear Staining, 030104 developmental biology, Specimen Preparation and Treatment, Leukocytes, Mononuclear, lcsh:Q, Biomarkers, Cytometry, 030215 immunology
Abstract: International audience; Mass cytometry is a powerful tool that allows simultaneous analysis of more than 37 markers at the single cell level. Mass cytometry is of particular interest in the identification of a wide variety of cell phenotypes in autoimmune diseases. Moreover, cells can be labelled with palladium isotopes and pooled before staining (barcoding). Nevertheless, immunolo-gists often face an important problem concerning the choice of markers to be included in a panel. This problem arises due to the incompatibility of different buffers used for the fixation and permeabilization of cells with various cell surface epitopes. In this study, we used a panel of 27 markers (19 surface markers and 8 intranuclear markers) to demonstrate disparities in the detection of cell surface antigens when comparing different buffers to stain unsti-mulated peripheral blood mononuclear cells. These disparities range from mild differences to very important differences in population frequencies depending on the buffers. Finally, we demonstrate the harmful effects of permeabilization prior to barcoding on the detection of some cell surface antigens. Here, we optimize a protocol that is suitable to use when targeting a large panel including both cell surface and intranuclear markers on unstimulated human peripheral blood mononuclear cells.
Published: 2018
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22. Factors associated with non-AIDS-defining cancers and non HCV-liver related cancers in HIV/HCV-coinfected patients- ANRS-CO13 HEPAVIH cohort

Author: Patrick Miailhes, Mathieu Chalouni, Eric Rosenthal, Hugues Aumaitre, Estibaliz Lazaro, Daniel Garipuy, François Raffi, Daniel Vittecoq, Cécile Goujard, Firouzé Bani-Sadr, Linda Wittkop, Alissa Naqvi, Oumar Billa, Dominique Salmon, Olivier Bouchaud, Karl Barange, David Zucman, Claudine Duvivier, Isabelle Poizot-Martin, Caroline Lascoux-Combe, Anne Simon, Karine Lacombe, Laurent Alric, Philippe Morlat, Stéphanie Dominguez, Didier Neau, Julie Chas, Christine Katlama, Laure Esterle, Camille Gilbert, Anne Gervais, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service d'Immuno-hématologie clinique [Hôpital Sainte Marguerite - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Hôpital Pellegrin, CHU Tenon [AP-HP], Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, CHU Saint-Antoine [AP-HP], Service d'infectiologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Hôpital Archet 2 [Nice] (CHU), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), DILTEC - Didactique des langues, des textes et des cultures - EA 2288 (DILTEC), Université Sorbonne Nouvelle - Paris 3, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Saint Jean de Perpignan, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Gestionnaire, Hal Sorbonne Université, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Maladies infectieuses et tropicales [CHU Tenon], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], 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), Service des maladies infectieuses et tropicales [CHU Tenon], CHU Toulouse [Toulouse], Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Purpan [Toulouse], Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Oncology, Liver Cirrhosis, Male, HIV Infections, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Medicine, Public and Occupational Health, Prospective Studies, Prospective cohort study, education.field_of_study, Multidisciplinary, Alcohol Consumption, Pharmaceutics, Coinfection, Liver Diseases, Liver Neoplasms, virus diseases, HIV diagnosis and management, Viral Load, Middle Aged, Vaccination and Immunization, Hepatitis C, 3. Good health, Cirrhosis, 030220 oncology & carcinogenesis, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious diseases, 030211 gastroenterology & hepatology, Female, Viral load, Research Article, Adult, medicine.medical_specialty, Science, Population, Immunology, Antiretroviral Therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology and Hepatology, Viral diseases, Microbiology, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Therapy, Antiviral Therapy, Internal medicine, Virology, Cancer Detection and Diagnosis, Humans, education, Nutrition, Medicine and health sciences, business.industry, Proportional hazards model, Cancer, Biology and Life Sciences, medicine.disease, Diagnostic medicine, digestive system diseases, Diet, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Preventive Medicine, business, Viral Transmission and Infection
Abstract: International audience; Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p
Published: 2018
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23. Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat

Author: Serge Carreira, Bruno Riou, Ghislaine Gayan-Ramirez, Catherine Coirault, Matthieu Le Dinh, Alexandre Demoule, Maud Beuvin, Julie Obert, Thomas Similowski, Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], 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), 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), 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, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service d'urgence de médecine et de chirurgie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Pneumologie, Médecine Intensive et Réanimation - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, 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), Centre de recherche en Myologie – U974 SU-INSERM, Thérapie des maladies du muscle strié, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Coirault, Catherine, Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), and Balse, Elise
Subjects: 0301 basic medicine, Lipopolysaccharides, Male, [SDV.BA] Life Sciences [q-bio]/Animal biology, Physiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Interleukin-1beta, Respiratory System, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Toxicology, Vascular Medicine, 0302 clinical medicine, Immune Physiology, Thoracic Diaphragm, Medicine and Health Sciences, Medicine, Protein Isoforms, lcsh:Science, Immune Response, Acidosis, Innate Immune System, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, [SDV.BA]Life Sciences [q-bio]/Animal biology, 3. Good health, Diaphragm (structural system), Body Fluids, [SDV] Life Sciences [q-bio], Cytokine, medicine.anatomical_structure, Blood, Cardiology, Cytokines, medicine.symptom, Anatomy, Injections, Intraperitoneal, Research Article, medicine.medical_specialty, Diaphragm, Immunology, Diaphragmatic breathing, Inflammation, Thoracic diaphragm, Blood Plasma, Proinflammatory cytokine, Sepsis, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Escherichia coli, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, Myosin Heavy Chains, business.industry, Interleukin-6, Tumor Necrosis Factor-alpha, lcsh:R, Biology and Life Sciences, Molecular Development, medicine.disease, Respiration, Artificial, Endotoxemia, Rats, 030104 developmental biology, Immune System, lcsh:Q, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract: BACKGROUND: Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation. METHOD: We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured. RESULTS: Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P
Published: 2017
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24. An in vitro diagnostic certified point of care single nucleotide test for IL28B polymorphisms

Author: Darragh Duffy, Stanislas Pol, Laurent Abel, Aurelie Baudin, Arnaud Fontanet, Alexandra Rohel, Muriel Vray, Tan-Phuc Buivan, Ioannis Theodorou, Ventzislava Petrov-Sanchez, Matthew L. Albert, Ben Reed, Gino Miele, Shaun Ainsworth, Estelle Mottez, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Centre d'Immunologie Humaine (CIH), Genedrive plc [Manchester], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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 Pasteur [Paris] (IP)-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), Centre d'enseignement Cnam Paris (CNAM Paris), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was financed by the European Commission FP7 project PoC-HCV (Grant agreement no 601851), European Project: 601851,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-2,POC-HCV(2013), Vougny, Marie-Christine, Point-of-care tests to revolutionise the clinical management of patients infected by Hepatitis C virus - POC-HCV - - EC:FP7:HEALTH2013-09-01 - 2016-08-31 - 601851 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle (CRT), Université Paris Descartes - Paris 5 (UPD5), AP-HP Groupe hospitalier Cochin (Paris), Epidémiologie des Maladies Emergentes, Institut Pasteur [Paris] - Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur de Dakar, Institut Pasteur de Dakar - Réseau International des Instituts Pasteur (RIIP), Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales, ANRS, Génétique Humaine des Maladies Infectieuses, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], and European Project : 601851, EC:FP7:HEALTH, FP7-HEALTH-2013-INNOVATION-2, POC-HCV(2013)
Subjects: 0301 basic medicine, RNA viruses, Male, Heredity, Physiology, [SDV]Life Sciences [q-bio], Buccal swab, lcsh:Medicine, Artificial Gene Amplification and Extension, Disease, Hepacivirus, Bioinformatics, Polymerase Chain Reaction, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Prospective cohort study, lcsh:Science, Pathology and laboratory medicine, Aged, 80 and over, Multidisciplinary, Hepatitis C virus, Physics, Melting, Medical microbiology, Middle Aged, Condensed Matter Physics, Clinical Laboratory Sciences, 3. Good health, Body Fluids, [SDV] Life Sciences [q-bio], Clinical Laboratories, Genetic Mapping, Blood, Physical Sciences, Viruses, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Pathogens, Anatomy, Phase Transitions, Research Article, Adult, Genotyping, [SDV.IMM] Life Sciences [q-bio]/Immunology, Point-of-Care Systems, Single-nucleotide polymorphism, Variant Genotypes, Research and Analysis Methods, Microbiology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Diagnostic Medicine, Genetics, SNP, Humans, Molecular Biology Techniques, Molecular Biology, Point of care, Aged, Demography, Flaviviruses, business.industry, Interleukins, lcsh:R, Organisms, Viral pathogens, Biology and Life Sciences, Reproducibility of Results, Hepatitis C, Chronic, Precision medicine, Hepatitis viruses, Microbial pathogens, 030104 developmental biology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], lcsh:Q, Interferons, business
Abstract: International audience; Numerous genetic polymorphisms have been identified as associated with disease or treatment outcome, but the routine implementation of genotyping into actionable medical care remains limited. Point-of-care (PoC) technologies enable rapid and real-time treatment decisions, with great potential for extending molecular diagnostic approaches to settings with limited medical infrastructure (e.g., CLIA certified diagnostic laboratories). With respect to resource-limited settings, there is a need for simple devices to implement biomarker guided treatment strategies. One relevant example is chronic hepatitis C infection, for which several treatment options are now approved. Single nucleotide polymorphisms (SNPs) in the IL-28B / IFNL3 locus have been well described to predict both spontaneous clearance and response to interferon based therapies. We utilized the Genedrive® platform to develop an assay for the SNP rs12979860 variants (CC, CT and TT). The assay utilizes a hybrid thermal engine, permitting rapid heating and cooling, enabling an amplification based assay with genetic variants reported using endpoint differential melting cure analysis in less than 60 minutes. We validated this assay using non-invasive buccal swab sampling in a prospective study of 246 chronic HCV patients, achieving 100% sensitivity and 100% specificity (95% exact CI: 98.8-100%)) in 50 minutes as compared to conventional lab based PCR testing. Our results provide proof of concept that precision medicine is feasible in resource-limited settings, offering the first CE-IVD (in vitro diagnostics) validated PoC SNP test. We propose that IL-28B genotyping may be useful for directing patients towards lower cost therapies, and rationing use of costly direct antivirals for use in those individuals showing genetic risk.
Published: 2017
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25. Can application and transfer of strategy be observed in low visibility condition?

Author: Kalliopi Christoforidis, Imen El Karoui, Lionel Naccache, HAL UPMC, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Service de Neurophysiologie [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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Physiology, lcsh:Medicine, Event-Related Potentials, Social Sciences, Neuropsychological Tests, Conflict, Psychological, 0302 clinical medicine, Cognition, Learning and Memory, Adaptation, Psychological, Medicine and Health Sciences, Psychology, lcsh:Science, Evoked Potentials, Behavioral adaptation, Clinical Neurophysiology, Brain Mapping, Multidisciplinary, 05 social sciences, Visibility (geometry), Electroencephalography, Electrophysiology, Bioassays and Physiological Analysis, Brain Electrophysiology, Physical Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Cognitive psychology, Research Article, Consciousness, Imaging Techniques, Permutation, Cognitive Neuroscience, Neurophysiology, Neuroimaging, Research and Analysis Methods, 050105 experimental psychology, 03 medical and health sciences, Reaction Time, Learning, Humans, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Behavior, Discrete Mathematics, lcsh:R, Electrophysiological Techniques, Cognitive Psychology, Biology and Life Sciences, Nontherapeutic Human Experimentation, Combinatorics, Conflict (Psychology), Stroop Test, Cognitive Science, lcsh:Q, Clinical Medicine, Metacognition, 030217 neurology & neurosurgery, Mathematics, Photic Stimulation, Stroop effect, Neuroscience
Abstract: International audience; It has been long assumed that cognitive control processes can only be applied on consciously visible stimuli, but empirical evidence is contradictory. In the present study, we investigated strategic adaptation to conflict both in unmasked and in low-visibility masked trials. Using a paradigm derived from the Stroop task, we studied the application of strategies, but also the transfer of a strategy developed in unmasked trials to masked trials, and the trial-to-trial dynamics of strategic processing. In unmasked trials, we found evidence of strategic adaptation to conflict, both in reaction times and in ERPs (N2 and P300). In masked trials we found no evidence of behavioral adaptation to conflict, but a modulation of the P300 was present in masked trials included in unmasked blocks, suggesting the existence of a transfer of strategy. Finally, trial-to-trial analyses in unmasked trials revealed a pattern suggestive of dynamic subjective adherence to the instructed strategy.
Published: 2017
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26. Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years

Author: Franck Pourcine, Karine Dahan, Fabrice Mihout, Marine Cachanado, Isabelle Brocheriou, Hanna Debiec, Pierre Ronco, Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Service de Néphrologie et Dialyses [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), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [CHU Tenon], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), This study was funded by grants from the European Research Council ERC-2012-ADG_20120314 (Grant Agreement 322947) and from 7th Framework Programme of the European Community Contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases). Rituximab was provided by Hoffmann–La Roche., European Project: 322947,EC:FP7:ERC,ERC-2012-ADG_20120314,OSAI(2013), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], CHU Tenon [AP-HP], 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), RONCO, Pierre, Membranous nephropathy : a model for solving organ-specific auto-immunity (OSAI) - OSAI - - EC:FP7:ERC2013-05-01 - 2018-04-30 - 322947 - VALID, European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Biopsy, Immunology, lcsh:Medicine, Surgical and Invasive Medical Procedures, Autoimmunity, Pathology and Laboratory Medicine, Research and Analysis Methods, Biochemistry, Glomerulonephritis, Membranous, Signs and Symptoms, Diagnostic Medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Albumins, Chronic Kidney Disease, Medicine and Health Sciences, Humans, Enzyme-Linked Immunoassays, Antigens, lcsh:Science, Immunoassays, Serum Albumin, Aged, Receptors, Phospholipase A2, lcsh:R, Biology and Life Sciences, Proteins, Renal System, Middle Aged, Prognosis, Antibodies, Anti-Idiotypic, ErbB Receptors, Proteinuria, Serology, Nephrology, Immunologic Techniques, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, Female, Anatomy, Thrombospondins, Research Article
Abstract: International audience; INTRODUCTION:Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers.METHODS:In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status.RESULTS:Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria.CONCLUSION:Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.
Published: 2017
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27. Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France

Author: André Dahlab, Marie Dalichampt, S. Guillo, Christine Bergeron, S Bénard, Hélène Borne, Xavier Bresse, Charlotte Cancalon, Yann De Rycke, Audrey Lajoinie, Florence Tubach, Alexandre Lafourcade, M. Uhart, 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 Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [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)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biostatistics consultant [Nantes], Sanofi Pasteur MSD, MSD Vaccins [Lyon], Laboratoire CERBA [Cergy-Pontoise], Gynecologist [Paris], stève consultants [Oullins], The study was supported by SPMSD / MSD Vaccins., Bodescot, Myriam, Unité de Recherche Clinique PSL-CFX [Paris], CHU Pitié-Salpêtrière [AP-HP], 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: Vaccination schedule, Conization, Uterine Cervical Neoplasms, Cervix Uteri, Endocervical curettage, Cervical Cancer, Pathology and Laboratory Medicine, Cervix, 0302 clinical medicine, Cancer screening, Medicine and Health Sciences, Mass Screening, 030212 general & internal medicine, Reproductive System Procedures, Early Detection of Cancer, Colposcopy, Cervical cancer, education.field_of_study, Multidisciplinary, Cervical screening, medicine.diagnostic_test, Obstetrics, Health Care Costs, Middle Aged, Hospitals, 3. Good health, medicine.anatomical_structure, Oncology, Medical Microbiology, Viral Pathogens, 030220 oncology & carcinogenesis, Viruses, Medicine, Female, France, Pathogens, Anatomy, Genital Anatomy, Cancer Screening, Research Article, Adult, medicine.medical_specialty, Papillomaviruses, Squamous Intraepithelial Lesions, Science, Population, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Microbiology, 03 medical and health sciences, Signs and Symptoms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Cancer Detection and Diagnosis, medicine, Humans, education, Microbial Pathogens, Aged, Vaginal Smears, Biology and life sciences, business.industry, Papillomavirus Infections, Organisms, Reproductive System, Cancers and Neoplasms, Human Papillomavirus, Uterine Cervical Dysplasia, medicine.disease, Health Care, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cross-Sectional Studies, Health Care Facilities, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Lesions, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, DNA viruses, business, Gynecological Tumors
Abstract: International audience; Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.
Published: 2020
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28. Small airway dysfunction in smokers with stable ischemic heart disease

Author: Claudia Llontop, Alberto Iglesias, Almudena Castro, Joan B. Soriano, Raúl Galera, Regina Dalmau, Elisabet Martínez-Cerón, Raquel Casitas, Cristina García-Quero, Francisco García-Río, 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), Instituto de Investigacion Hospital La Paz (IdiPAZ), Foundation for Biomedical Research, Hospital Universitario La Paz [Madrid, Spain]-Hospital Universitario La Paz [Madrid, Spain]-Hospital Universitario La Paz-School of Nursing Building, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Facultad de Medicina. Universidad Autónoma de Madrid, IISP Madrid, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Pulmonology, Physiology, Myocardial Ischemia, lcsh:Medicine, Disease, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, Pulmonary function testing, Habits, 0302 clinical medicine, Quality of life, Medicine and Health Sciences, Smoking Habits, Prevalence, Coronary Heart Disease, Respiratory Analysis, lcsh:Science, Multidisciplinary, medicine.diagnostic_test, Smoking, respiratory system, Middle Aged, C-Reactive Proteins, 3. Good health, Respiratory Function Tests, Bioassays and Physiological Analysis, Cardiology, Female, Research Article, Spirometry, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Respiratory physiology, Research and Analysis Methods, behavioral disciplines and activities, 03 medical and health sciences, Internal medicine, mental disorders, medicine, Humans, Respiratory Physiology, cardiovascular diseases, Aged, Behavior, Blood biochemistry, business.industry, lcsh:R, Biology and Life Sciences, Proteins, Health Care, Airway Obstruction, 030228 respiratory system, Quality of Life, lcsh:Q, Airway, Ischemic heart, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BackgroundA higher prevalence of airflow limitation (AL) has been described in patients with ischemic heart disease (IHD). Although small airway dysfunction (SAD) is an early feature of AL, there is little information about its occurrence in IHD patients. Our objective was to describe the prevalence of SAD in IHD patients, while comparing patient-related outcomes and future health risk among IHD patients with AL, SAD and normal lung function.MethodsIn 118 consecutive smoking patients with stable IHD, comorbidities, utilization of healthcare resources, current treatment, blood biochemistry and health status were recorded. SAD was evaluated by impulse oscillometry, and pre- and post-bronchodilator spirometry was performed.ResultsThe prevalence of AL and SAD were 20.3 (95% CI, 13.1–27.6%) and 26.3% (95% CI, 18.3–34.2%), respectively. Compared to the normal lung function group, patients with SAD and without AL had lower spirometric values, poorer quality of life and higher levels of C-reactive protein (CRP), as well as increased cardiovascular risk and more vascular age. In patients with normal spirometry, the presence of SAD was independently associated with pack-years, HDL-cholesterol and CRP levels.ConclusionIn patients with IHD, the presence of SAD is common and that it is associated with reduced health status and increased future cardiac risk.
Published: 2017
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29. Contribution of exome sequencing for genetic diagnostic in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Author: Fedida, Joel, Fressart, Veronique, Charron, Philippe, Surget, Elodie, Hery, Tiphaine, Richard, Pascale, Donal, Erwan, Keren, Boris, Duthoit, Guillaume, Hidden-Lucet, Françoise, Villard, Eric, Gandjbakhch, Estelle, Institut de cardiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CHU Pontchaillou [Rennes], HAL UPMC, Gestionnaire, Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN)
Subjects: Male, Genetic Screens, Molecular biology, Gene Identification and Analysis, lcsh:Medicine, Database and Informatics Methods, Sequencing techniques, Medicine and Health Sciences, Exome, Gene Regulatory Networks, DNA sequencing, lcsh:Science, Arrhythmogenic Right Ventricular Dysplasia, Sequence Deletion, RNA-Binding Proteins, Genomics, Middle Aged, Genomic Databases, Pedigree, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Deletion Mutation, Female, Cardiomyopathies, Research Article, Adult, Adolescent, Cardiology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Electron Transport Complex IV, Young Adult, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Presenilin-1, Genetics, Humans, Genetic Predisposition to Disease, Aged, lcsh:R, Dideoxy DNA sequencing, Biology and Life Sciences, Computational Biology, Human Genetics, Sequence Analysis, DNA, Genome Analysis, Research and analysis methods, Molecular biology techniques, Biological Databases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Mutation Databases, Trans-Activators, lcsh:Q, Plakophilins, Genome-Wide Association Study
Abstract: International audience; Background: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) is an inherited cardiomyopathy mainly caused by heterozygous desmosomal gene mutations, the major gene being PKP2. The genetic cause remains unknown in ~50% of probands with routine desmosomal gene screening. The aim of this study was to assess the diagnostic accuracy of whole exome sequencing (WES) in ARVC/D with negative genetic testing.Methods: WES was performed in 22 patients, all without a mutation identified in desmosomal genes. Putative pathogenic variants were screened in 96 candidate genes associated with other cardiomyopathies/channelopathies. The sequencing coverage depth of PKP2, DSP, DSG2, DSC2, JUP and TMEM43 exons was compared to the mean coverage distribution to detect large insertions/deletions. All suspected deletions were verified by real-time qPCR, Multiplex-Ligation-dependent-Probe-Amplification (MLPA) and cGH-Array. MLPA was performed in 50 additional gene-negative probands.Results: Coverage-depth analysis from the 22 WES data identified two large heterozygous PKP2 deletions: one from exon 1 to 14 and one restricted to exon 4, confirmed by qPCR and MLPA. MLPA identified 2 additional PKP2 deletions (exon 1–7 and exon 1–14) in 50 additional probands confirming a significant frequency of large PKP2 deletions (5.7%) in gene-negative ARVC/D. Putative pathogenic heterozygous variants in EYA4, RBM20, PSEN1, and COX15 were identified in 4 unrelated probands.Conclusion: A rather high frequency (5.7%) of large PKP2 deletions, undetectable by Sanger sequencing, was detected as the cause of ARVC/D. Coverage-depth analysis through next-generation sequencing appears accurate to detect large deletions at the same time than conventional putative mutations in desmosomal and cardiomyopathy-associated genes.
Published: 2017
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30. Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis

Author: Bernard Aguilaniu, Olivier Le Rouzic, Camille Rolland-Debord, Jonathan Giovannelli, Geraldine François, Abdellatif Tazi, Benoit Wallaert, Stéphanie Fry, Cécile Chenivesse, Alain Delobbe, Stéphane Dominique, Agnès Bellocq, Nicolas Bricout, Carole Langlois, Service de Pneumologie, Immunologie et Allergologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service pharmaceutique, CHU de Lille, Service de biostatistiques [CHU Lille], Service de Radiologie (LILLE - Radio), Faculté de médecine [Université Joseph-Fourrier], Université Joseph-Fourrier, Service d’Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée [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 Rouen, Normandie Université (NU), Hôpital de la Citadelle, CHU Amiens-Picardie, Centre de référence des Histiocytoses, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biostatistiques [CHRU Lille], Service d'Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Pulmonology, Anaerobic Threshold, lcsh:Medicine, Hyperpnea, 030204 cardiovascular system & hematology, Pulmonary function testing, Diagnostic Radiology, 0302 clinical medicine, Mathematical and Statistical Techniques, DLCO, Animal Cells, Ultrasound Imaging, Medicine and Health Sciences, Public and Occupational Health, lcsh:Science, Tomography, Principal Component Analysis, Multidisciplinary, Pulmonary Hypertension, Exercise Tolerance, Radiology and Imaging, Middle Aged, Sports Science, Respiratory Function Tests, Chemistry, Echocardiography, Physical Sciences, Cardiology, Female, medicine.symptom, Cellular Types, Anaerobic exercise, Statistics (Mathematics), Research Article, Chemical Elements, Adult, medicine.medical_specialty, Imaging Techniques, Immune Cells, Immunology, Antigen-Presenting Cells, Neuroimaging, Air trapping, Research and Analysis Methods, 03 medical and health sciences, FEV1/FVC ratio, Diagnostic Medicine, Internal medicine, medicine, Humans, Sports and Exercise Medicine, Statistical Methods, Exercise, Aerobic capacity, business.industry, lcsh:R, Biology and Life Sciences, Physical Activity, Cell Biology, Dendritic Cells, medicine.disease, Computed Axial Tomography, Oxygen, Histiocytosis, Langerhans-Cell, Dyspnea, 030228 respiratory system, Physical Fitness, Langerhans Cells, Multivariate Analysis, Physical therapy, lcsh:Q, Ventilatory threshold, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Mathematics, Neuroscience
Abstract: International audience; BackgroundReduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments.MethodsDyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V’O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V’O2 peak as the dependent variable and principal components as covariates.ResultsV’O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: “pseudorestriction”; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V’O2 peak. The 4 principal components were independently associated with V’O2 peak (βcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]).ConclusionImpaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea.
Published: 2017
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31. The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study

Author: Kutz, Alexander, Hausfater, Pierre, Amin, Devendra, Amin, Adina, Canavaggio, Pauline, Sauvin, Gabrielle, Bernard, Maguy, Conca, Antoinette, Haubitz, Sebastian, Struja, Tristan, Huber, Andreas, Mueller, Beat, Schuetz, Philipp, TRIAGE study group, Zeller, Tanja, De Geest, Sabina, Kantonsspital Aarau, Service des Urgences [CHU Pitié-Salpêtrière], 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Morton Plant Hospital Clearwater, Service de Biochimie Endocrinienne et Oncologie [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN)
Subjects: Male, Critical Care and Emergency Medicine, Medical Doctors, Physiology, Gastrointestinal Diseases, Health Care Providers, lcsh:Medicine, 030204 cardiovascular system & hematology, Biochemistry, Severity of Illness Index, Adrenomedullin, 0302 clinical medicine, Risk of mortality, Medicine and Health Sciences, Medicine, Prospective Studies, Prospective cohort study, lcsh:Science, Aged, 80 and over, education.field_of_study, Multidisciplinary, Applied Mathematics, Simulation and Modeling, Hematology, Middle Aged, Prognosis, Hospitals, 3. Good health, Body Fluids, Professions, Intensive Care Units, Blood, Cardiovascular Diseases, Physical Sciences, Female, Anatomy, Risk assessment, Infection, Emergency Service, Hospital, Algorithms, Research Article, medicine.medical_specialty, Population, Research and Analysis Methods, Infections, Risk Assessment, 03 medical and health sciences, Physicians, Severity of illness, Humans, education, Aged, business.industry, lcsh:R, Biology and Life Sciences, International Agencies, 030208 emergency & critical care medicine, Emergency department, Triage, Health Care, Health Care Facilities, Emergency medicine, People and Places, Observational study, lcsh:Q, Population Groupings, Nervous System Diseases, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, Mathematics
Abstract: INTRODUCTION: The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. METHODS: We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. RESULTS: Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75-1.5nmol/L, >1.5nmol/L, p ANOVA
Published: 2016
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32. A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus

Author: Barateau, A, Vadrot, N, Vicart, P, Ferreiro, A, Mayer, M, Heron, D, Vigouroux, C, Buendia, B, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], 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], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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), and ORANGE, Colette
Subjects: Confocal Microscopy, Lipodystrophy, LMNA-MUTATIONS, [SDV]Life Sciences [q-bio], LAMINOPATHIES, lcsh:Medicine, Gene Expression, Pathology and Laboratory Medicine, Biochemistry, Muscular Dystrophies, Histones, Myoblasts, Mice, A-TYPE LAMINS, Animal Cells, Medicine and Health Sciences, PRELAMIN-A, lcsh:Science, Cellular Senescence, Cytoskeleton, Skin, Connective Tissue Cells, Microscopy, integumentary system, Chromosome Biology, Stem Cells, Light Microscopy, Acetylation, Lamin Type A, Lamins, Chromatin, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Neurology, Connective Tissue, embryonic structures, SHAPE, Female, Epigenetics, Cellular Types, Anatomy, Cellular Structures and Organelles, Research Article, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Primary Cell Culture, ORGANIZATION, Research and Analysis Methods, Signs and Symptoms, Diagnostic Medicine, Genetics, Animals, Humans, Cell Nucleus, lcsh:R, A/C, Membrane Proteins, Biology and Life Sciences, Proteins, Cell Biology, Fibroblasts, HUTCHINSON-GILFORD-PROGERIA, Cytoskeletal Proteins, Biological Tissue, PARTIAL LIPODYSTROPHY, Mutation, lcsh:Q
Abstract: International audience; A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes ( progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p. R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy ( L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern. C2C12 myoblasts were transfected with a construct carrying the patient's mutation; R388P-lamin A ( LA) predominantly accumulated within the nucleoplasm and was depleted at the nuclear periphery, altering the anchorage of the inner nuclear membrane protein emerin and the nucleoplasmic protein LAP2-alpha. The mutant LA triggered a frequent and severe nuclear dysmorphy that occurred independently of prelamin A processing, as well as increased histone H3K9 acetylation. Nuclear dysmorphy was not significantly improved when transfected cells were treated with drugs disrupting microtubules or actin filaments or modifying the global histone acetylation pattern. Therefore, releasing any force exerted at the nuclear envelope by the cytoskeleton or chromatin did not rescue nuclear shape, in contrast to what was previously shown in Hutchinson-Gilford progeria due to other LMNA mutations. Our results point to the specific cytotoxic effect of the R388P-lamin A mutant, which is clinically related to a rare and severe multisystemic laminopathy phenotype.
Published: 2016
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33. Relations between Nonsuicidal Self-Injury and Suicidal Behavior in Adolescence: A Systematic Review

Author: Marie Rose Moro, Jonathan Lachal, Michel Spodenkiewicz, Diane De Labrouhe, Salomé Grandclerc, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris-Sud - Paris 11 (UP11)-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), Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Descartes - Paris 5 (UPD5), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Troubles du comportement alimentaire de l'adolescent ( UMR_S 669 ), Université Paris-Sud - Paris 11 ( UP11 ) -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 ), Université Paris-Sud - Paris 11 ( UP11 ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Université Paris Descartes - Paris 5 ( UPD5 ), Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut des Systèmes Intelligents et de Robotique ( ISIR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Poison control, lcsh:Medicine, Social Sciences, Suicide, Attempted, Adolescents, Suicide prevention, Developmental psychology, Cultural Anthropology, Self Harm, 0302 clinical medicine, Sociology, Risk Factors, Medicine and Health Sciences, lcsh:Science, Suicidal ideation, Multidisciplinary, Depression, Research Assessment, 3. Good health, Religion, Suicide, medicine.symptom, Psychology, Adolescent health, Research Article, medicine.medical_specialty, Attitude to Death, Systematic Reviews, Adolescent, Context (language use), Research and Analysis Methods, Personality Disorders, Suicidal Ideation, 03 medical and health sciences, Injury prevention, Mental Health and Psychiatry, medicine, Humans, Narrative, Psychiatry, Behavior, Mood Disorders, lcsh:R, Biology and Life Sciences, medicine.disease, Personality disorders, 030227 psychiatry, Age Groups, Adolescent Behavior, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anthropology, People and Places, lcsh:Q, Population Groupings, Self-Injurious Behavior, 030217 neurology & neurosurgery
Abstract: International audience; Nonsuicidal self-injury (NSSI) and suicidal behaviors, both important issues in adolescent health care, are frequently associated and possibly clinically related. Our objective was to explore the views of relations between nonsuicidal self-injury and suicidal behaviors during adolescence and young adulthood (11–25 years) expressed in the scientific (medical and psychological) literature. We adopted a textual approach to the process of synthesis to tell the story of the findings from the included studies. Our narrative systematic review of 64 articles found that they share the same risk factors. Integrated models envision nonsuicidal self-injury as a gateway enabling teens to acquire the capability for suicide. Because suicidal behavior short-circuits thought, it is difficult to conceive an intention to die during ado-lescents' acts of self-injury. Intention is constructed by the narrative of the act, influenced by numerous elements from the psychopathologic, cultural, religious, and philosophic context. Techniques of mentalizing-based treatments and work on the meaning that adolescents attribute to their behaviors might improve care.
Published: 2016
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34. Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

Author: Pierre-François Pradat, Anthony Behin, Mohamed-Mounir El Mendili, Pascal Laforêt, Raquel Guimarães-Costa, Vincent Meininger, Stéphane Lehéricy, François Salachas, Habib Benali, Nadine Le Forestier, Timothée Lenglet, Gaëlle Bruneteau, Tanya Stojkovic, Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [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 de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Muscle Physiology, Muscle Functions, Physiology, lcsh:Medicine, SMN1, Pathology and Laboratory Medicine, Nervous System, 030218 nuclear medicine & medical imaging, Diagnostic Radiology, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, lcsh:Science, Musculoskeletal System, Neurons, Motor Neurons, Multidisciplinary, Cervical spinal cord atrophy, Radiology and Imaging, Muscles, Anatomy, Muscle Analysis, SMA, Magnetic Resonance Imaging, medicine.anatomical_structure, Bioassays and Physiological Analysis, Spinal Cord, Physical Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Cellular Types, Research Article, Cord, Imaging Techniques, Permutation, Research and Analysis Methods, 03 medical and health sciences, Atrophy, Signs and Symptoms, Diagnostic Medicine, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, Discrete Mathematics, lcsh:R, Muscle weakness, Biology and Life Sciences, Spinal muscular atrophy, Cell Biology, Spinal cord, medicine.disease, Neuroanatomy, Skeletal Muscles, Combinatorics, Cellular Neuroscience, lcsh:Q, business, 030217 neurology & neurosurgery, Mathematics, Neuroscience
Abstract: International audience; PurposeThe mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness.Materials and MethodsEighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores.ResultsCSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores.ConclusionsSpinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients.
Published: 2016
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35. Pig as a large animal model for posterior fossa surgery in oto-neurosurgery: A cadaveric study

Author: Yann Nguyen, Mohamed Elsayed, Renato Torres, Daniele Bernardeschi, Olivier Sterkers, Gestionnaire, Hal Sorbonne Université, Réhabilitation Chirurgicale mini-Invasive et Robotisée de l'Audition, Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Unité d’Otologie, implants auditifs et chirurgie de la base du crâne [CHU Pitié-Salpêtrière], Service d'Oto-Rhino-Laryngologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Alexandria University [Alexandrie], Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-CHU Pitié-Salpêtrière [AP-HP], 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: Swine, [SDV]Life Sciences [q-bio], Otology, Nervous System, Neurosurgical Procedures, 0302 clinical medicine, Skeletal Joints, Pig Models, Temporal bone, Medicine and Health Sciences, Medicine, 030223 otorhinolaryngology, Musculoskeletal System, Multidisciplinary, Nerves, Dissection, Cranial nerves, Cranial Nerves, Soft tissue, Animal Models, Facial nerve, [SDV] Life Sciences [q-bio], Facial Nerve, Experimental Organism Systems, Anatomy, Research Article, medicine.medical_specialty, Science, education, Surgical and Invasive Medical Procedures, Research and Analysis Methods, 03 medical and health sciences, Cadaver, otorhinolaryngologic diseases, Animals, Humans, business.industry, Biology and Life Sciences, Cerebellopontine angle, Surgery, Disease Models, Animal, Otorhinolaryngology, Cranial Fossa, Posterior, Face, Ear, Inner, Animal Studies, business, Cadaveric spasm, Head, 030217 neurology & neurosurgery
Abstract: International audience; This study proposes a practical model for a new approach to the posterior fossa in common domestic pigs. Several surgical procedures can be simulated in the nonliving pig model, including soft tissue dissection, drilling of temporal bone, dural incision, access to the cerebellopontine angle, exposure of cranial nerves and drilling of the internal auditory canal. The pig model perfectly simulates standard otological and neurosurgical procedures, and we highlight the feasibility of our approach for further experiments in a living pig model with the possibility of reproducing the model for research on cranial nerves in pigs to study their electrophysiological behavior.
Published: 2019
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36. Monitoring quality of obstetric care from hospital discharge databases: A Delphi survey to propose a new set of indicators based on maternal health outcomes

Author: Coralie Chiesa-Dubruille, A A Chantry, H Keita, François Goffinet, Priscille Sauvegrain, Catherine Deneux-Tharaux, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie et Obstétrique [Groupe Hospitalier Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], École de sages-femmes Baudelocque (ESF Baudelocque), Université Paris Descartes - Paris 5 (UPD5), Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [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), Université Paris Descartes - École de sages-femmes Baudelocque (UPD ESF Baudelocque), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Episiotomy, Critical Care and Emergency Medicine, Delphi Technique, Maternal Health, medicine.medical_treatment, Delphi method, Pathology and Laboratory Medicine, computer.software_genre, Vascular Medicine, Labor and Delivery, 0302 clinical medicine, Obstetrics and gynaecology, Pregnancy, Anesthesiology, Medicine and Health Sciences, Quality of Care, Medicine, Anesthesia, 030212 general & internal medicine, media_common, Response rate (survey), 030219 obstetrics & reproductive medicine, Multidisciplinary, Database, Pharmaceutics, Mortality rate, Obstetrics and Gynecology, Severe Blood Loss, Patient Discharge, 3. Good health, Uterine rupture, Maternal Mortality, Systematic review, Female, France, Research Article, Postnatal Care, Death Rates, Science, Health Personnel, media_common.quotation_subject, Hemorrhage, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, Signs and Symptoms, Population Metrics, Drug Therapy, Diagnostic Medicine, Humans, Maternal Health Services, Quality (business), Quality Indicators, Health Care, Population Biology, business.industry, Postpartum Hemorrhage, Biology and Life Sciences, medicine.disease, Pregnancy Complications, Health Care, Birth, Women's Health, Health Statistics, Morbidity, business, computer, Systematic Reviews as Topic
Abstract: ObjectivesMost indicators proposed for assessing quality of care in obstetrics are process indicators and do not directly measure health effects, and cannot always be identified from routinely available databases. Our objective was to propose a set of indicators to assess the quality of hospital obstetric care from maternal morbidity outcomes identifiable in permanent hospital discharge databases.MethodsVarious maternal morbidity outcomes potentially reflecting quality of obstetric care were first selected from a systematic literature review. Then a three-round Delphi consensus survey was conducted online from 11/2016 through 02/2017 among a French panel of 37 expert obstetricians, anesthetists-critical-care specialists, midwives, quality-of-care researchers, and user representatives. For a given maternal outcome, several definitions could be proposed and the indicator (i.e. corresponding rate) could be applied to all women or restricted to specific subgroup(s).ResultsOf the 49 experts invited to participate, 37 agreed. The response rate was 92% in the second round and 97% in the third. Finally, a set of 13 indicators was selected to assess the quality of hospital obstetric care: rates of uterine rupture, postpartum hemorrhage, transfusion incident, severe perineal lacerations, episiotomy, cesarean, cesarean under general anesthesia, post-cesarean site infection, anesthesia-related complications, postpartum pulmonary embolism, maternal readmission and maternal mortality. Six were considered in specific subgroups, with, for example, the postpartum hemorrhage rate assessed among all women and also among women at low risk of PPH.ImplicationsThis Delphi process enabled us to define consensually a set of indicators to assess the quality of hospital obstetrics care from routine hospital data, based on maternal morbidity outcomes. Considering 6 of them in specific subgroups of women is especially interesting. These indicators, identifiable through codes used in international classifications, will be useful to monitor quality of care over time and across settings.
Published: 2019
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37. Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study

Author: Cécile Goujard, Patrick Miailhes, Firouzé Bani-Sadr, Laure Esterle, Anne Simon, Daniel Vittecoq, Karine Lacombe, Dominique Salmon, Gilles Pialoux, Lionel Piroth, Didier Neau, François Dabis, Linda Wittkop, Claudine Duvivier, François Raffi, Philippe Morlat, Caroline Lascoux-Combe, Stéphanie Dominguez, Isabelle Poizot-Martin, Olivier Bouchaud, Victor de Ledinghen, Anne Gervais-Hasenknoff, Laurent Alric, Marc-Antoine Valantin, Philippe Sogni, David Zucman, Eric Rosenthal, Daniel Garipuy, Hugues Aumaitre, Sarah Shili-Masmoudi, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital l'Archet, CHU Saint-Antoine [AP-HP], 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 Tenon [AP-HP], Service de maladies infectieuses et tropicales [CHU Avicenne], Hôpital Avicenne [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire d'Immunologie [AP-HP Hôpital Kremlin-Bicêtre] (GHU Paris-Sud), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Tenon], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Maladies infectieuses et tropicales [CHU Tenon], and HAL AMU, Administrateur
Subjects: Male, RNA viruses, Sustained Virologic Response, Metabolic disorders, Social Sciences, HIV Infections, Hepacivirus, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, Immunodeficiency Viruses, Risk Factors, Psychology, Alcohol consumption, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pathology and laboratory medicine, Multidisciplinary, Death rates, Coinfection, Hepatitis C virus, Mortality rate, Hazard ratio, virus diseases, Hepatitis C, Middle Aged, Medical microbiology, Addicts, 3. Good health, Liver, Drug users, Viruses, Cohort, Elasticity Imaging Techniques, Medicine, Female, 030211 gastroenterology & hepatology, France, Pathogens, Research Article, Cohort study, Adult, medicine.medical_specialty, Science, Liver fibrosis, Addiction, Gastroenterology and Hepatology, Antiviral Agents, Microbiology, 03 medical and health sciences, Population Metrics, Internal medicine, Retroviruses, medicine, Humans, Mortality, Liver diseases, Proportional Hazards Models, Nutrition, Medicine and health sciences, Biology and life sciences, Flaviviruses, Population Biology, business.industry, Proportional hazards model, Lentivirus, Organisms, Viral pathogens, HIV, Hepatitis C, Chronic, medicine.disease, Hepatitis viruses, Microbial pathogens, Diet, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. Methods HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. Results 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.
Published: 2019
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38. Derivation and internal validation of a mortality risk index for aged people living with HIV: The Dat'AIDS score

Author: Moustapha Dramé, Maxime Hentzien, Marc-Antoine Valantin, Pascal Pugliese, Clotilde Allavena, Firouzé Bani-Sadr, David Rey, Lise Cuzin, Christine Jacomet, André Cabié, Cyrille Delpierre, Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses [Nice], Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service des maladies infectieuses et tropicales [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 Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France]-Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Maladies infectieuses et tropicales dans la Caraïbe (MAITC EA 4537), CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-CHU de la Martinique [Fort de France], Coordination régionale de la lutte contre le virus de l’immunodéficience humaine ( COREVIH [Toulouse]), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), 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), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Université des Antilles (UA), and Centre d'Investigation Clinique Antilles Guyane, Inserm CIC1424
Subjects: Male, RNA viruses, 0301 basic medicine, Viral Diseases, Epidemiology, lcsh:Medicine, HIV Infections, Comorbidity, Cardiovascular Medicine, Pathology and Laboratory Medicine, Cohort Studies, 0302 clinical medicine, Immunodeficiency Viruses, Risk Factors, Medicine and Health Sciences, Prospective Studies, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, 2. Zero hunger, education.field_of_study, Multidisciplinary, Liver Diseases, Anemia, Epidemiology of Aging, Hematology, Middle Aged, Viral Load, Prognosis, 3. Good health, AIDS, Infectious Diseases, Cirrhosis, Medical Microbiology, Cardiovascular Diseases, Viral Pathogens, Viruses, Cohort, Female, France, Pathogens, Risk assessment, Viral load, Research Article, Cohort study, medicine.medical_specialty, Prognostic variable, Population, Gastroenterology and Hepatology, Microbiology, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, Retroviruses, medicine, Humans, education, Microbial Pathogens, Aged, Proportional Hazards Models, business.industry, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, medicine.disease, 030112 virology, CD4 Lymphocyte Count, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Co-Infections, Multivariate Analysis, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, business, Viral Transmission and Infection
Abstract: International audience; OBJECTIVE:The objective was to develop a multivariable prognostic index for overall mortality over a five-year span integrating classical HIV biomarkers and comorbidities in people living with HIV (PLHIV) aged 60 or older.DESIGN:Prospective multicenter cohort study from the French Dat'AIDS cohort.METHODS:All HIV-1 infected patients aged 60 years or older on 1st January 2008 were included. Sociodemographic data, CD4 cell count, CD4 nadir, HIV viral load, history of comorbidities, hepatitis co-infections and laboratory parameters at baseline were considered as potential prognostic variables. Primary outcome was all-cause mortality.RESULTS:Among 1415 patients included, we derived a score comprising the following predictors: Age (65-74: 1 point; ≥75: 8 points), CD4 cell count (200-349: 3 points
Published: 2018
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39. Early Left Parietal Activity Elicited by Direct Gaze: A High-Density EEG Study

Author: Nathalie George, Nicolas Burra, Dirk Kerzel, HAL-UPMC, Gestionnaire, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Faculté de Psychologie et des Sciences de l’Education, Université de Genève = University of Geneva (UNIGE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), and Université de Genève (UNIGE)
Subjects: Male, genetic structures, Photic Stimulation, Physiology, Vision, Social Sciences, Event-Related Potentials, lcsh:Medicine, Electroencephalography, Orienting response, 0302 clinical medicine, Parietal Lobe, Medicine and Health Sciences, Psychology, Attention, Evoked potential, lcsh:Science, Evoked Potentials, media_common, Clinical Neurophysiology, Cerebral Cortex, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, 05 social sciences, Brain, Electrophysiology, Bioassays and Physiological Analysis, Brain Electrophysiology, Female, Sensory Perception, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, Research Article, Adult, Social contact, Imaging Techniques, media_common.quotation_subject, Neurophysiology, Neuroimaging, Research and Analysis Methods, 050105 experimental psychology, 03 medical and health sciences, Young Adult, Diagnostic Medicine, Ocular System, Perception, medicine, Humans, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Behavior, Scalp, Electrophysiological Techniques, lcsh:R, Cognitive Psychology, Biology and Life Sciences, Inferior parietal lobule, Gaze, Face, Cognitive Science, Eyes, lcsh:Q, Neuroscience, Head, 030217 neurology & neurosurgery
Abstract: International audience; Gaze is one of the most important cues for human communication and social interaction. In particular, gaze contact is the most primary form of social contact and it is thought to capture attention. A very early-differentiated brain response to direct versus averted gaze has been hypothesized. Here, we used high-density electroencephalography to test this hypothesis. Topographical analysis allowed us to uncover a very early topographic modulation (40–80 ms) of event-related responses to faces with direct as compared to averted gaze. This modulation was obtained only in the condition where intact broadband faces–as opposed to high-pass or low-pas filtered faces–were presented. Source estimation indicated that this early modulation involved the posterior parietal region, encompassing the left precuneus and inferior parietal lobule. This supports the idea that it reflected an early orienting response to direct versus averted gaze. Accordingly, in a follow-up behavioural experiment, we found faster response times to the direct gaze than to the averted gaze broadband faces. In addition, classical evoked potential analysis showed that the N170 peak amplitude was larger for averted gaze than for direct gaze. Taken together, these results suggest that direct gaze may be detected at a very early processing stage, involving a parallel route to the ventral occipito-temporal route of face perceptual analysis.
Published: 2016
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40. Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations

Author: Marzolf, Guillaume, Sabou, Marcela, Lannes, Béatrice, Cotton, François, Meyronet, David, Galanaud, Damien, Cottier, Jean-Philippe, Grand, Sylvie, Desal, Hubert, Kreutz, Julie, Schenck, Maleka, Meyer, Nicolas, Schneider, Francis, Dietemann, Jean-Louis, Koob, Meriam, Herbrecht, Raoul, Kremer, Stéphane, Zhang, Heye, Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Parasitologie et de Mycologie Médicale [Strasbourg], Service de pathologie [CHU Strasbourg], CHU Strasbourg, Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie [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), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neuroradiologie [St Herblain], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Radiologie [Liège], Centre Hospitalier Universitaire de Liège (CHU-Liège), Service de Réanimation Médicale [Strasbourg], Laboratoire de biostatistique, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie et Hématologie [Strasbourg], Université Lumière - Lyon 2 (UL2), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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 National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Inria de Paris, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: 0301 basic medicine, Male, Pathology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cerebral arteries, lcsh:Medicine, Corpus callosum, Aspergillosis, Pathology and Laboratory Medicine, Vascular Medicine, Diagnostic Radiology, 0302 clinical medicine, Paranasal Sinuses, Medicine and Health Sciences, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Neuroaspergillosis, Fungal Pathogens, Brain Diseases, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Radiology and Imaging, Fungal Diseases, Arteries, Middle Aged, Prognosis, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Infectious Diseases, Aspergillus, Aspergillus Fumigatus, Medical Microbiology, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Radiology, medicine.symptom, Anatomy, Pathogens, Aneurysms, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Research Article, Adult, medicine.medical_specialty, Imaging Techniques, Brain Morphometry, 030106 microbiology, Neuroimaging, Mycology, Research and Analysis Methods, Microbiology, Lesion, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Vascular Diseases, Pathological, Microbial Pathogens, Aged, Retrospective Studies, business.industry, Diffusion Weighted Imaging, lcsh:R, Organisms, Fungi, Biology and Life Sciences, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Magnetic resonance imaging, Cerebral Arteries, medicine.disease, Molds (Fungi), Abscesses, Paranasal sinuses, Lesions, Cardiovascular Anatomy, Blood Vessels, lcsh:Q, business, 030217 neurology & neurosurgery, Diffusion MRI, Neuroscience
Abstract: Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.
Published: 2016
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41. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence

Author: Philippe Bernard, Jean-Charles Bizot, Alain Puech, Fabrice Trovero, Sabrina David, Jean-Pol Tassin, Key-Obs, Greenpharma S.A.S., Service de pharmacologie médicale [CHU Pitié-Salpêtrière], 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), Expression des Gènes et comportement adaptatifs = Molecular Genetics, Neurophysiology and Behavior (NPS-15), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), and HAL UPMC, Gestionnaire
Subjects: Male, 0301 basic medicine, Sensory Receptors, Physiology, Social Sciences, lcsh:Medicine, Pharmacology, Cyproheptadine, Drug Abuse, Mice, chemistry.chemical_compound, Mathematical and Statistical Techniques, 0302 clinical medicine, Piperidines, Medicine and Health Sciences, Serotonin 5-HT2 Receptor Antagonists, Psychology, Public and Occupational Health, Biomechanics, Receptor, Serotonin, 5-HT2A, lcsh:Science, Mammals, Alcohol Consumption, Multidisciplinary, Behavior, Animal, Pharmaceutics, 3. Good health, Alcoholism, Mice, Inbred DBA, Vertebrates, Physical Sciences, Sensory Perception, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Statistics (Mathematics), Research Article, Signal Transduction, medicine.drug, Substance-Related Disorders, Addiction, Research and Analysis Methods, Rodents, 03 medical and health sciences, Drug Therapy, Mental Health and Psychiatry, Prazosin, medicine, Ifenprodil, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Statistical Methods, Amphetamine, 5-HT receptor, Nutrition, Behavior, Analysis of Variance, Ethanol, Biological Locomotion, business.industry, Alcohol dependence, lcsh:R, Organisms, Biology and Life Sciences, Cell Biology, Diet, Mice, Inbred C57BL, 030104 developmental biology, chemistry, Adrenergic alpha-1 Receptor Antagonists, lcsh:Q, Serotonin, business, Mathematics, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg) and cyproheptadine (1 mg/kg) (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively) blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v) and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France) and cyproheptadine (1 mg/kg) could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.
Published: 2016
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42. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project)

Author: Sofie Compernolle, Ketevan Glonti, Greet Cardon, Harry Rutter, Ilse De Bourdeaudhuij, Katrien De Cocker, Jean-Michel Oppert, Helga Bárdos, Jeroen Lakerveld, Joreintje D. Mackenbach, Célina Roda, Universiteit Gent = Ghent University (UGENT), Research Foundation - Flanders [Brussel] (FWO), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-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)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), London School of Hygiene and Tropical Medicine (LSHTM), University of Debrecen Egyetem [Debrecen], Seventh Framework Programme (CORDIS FP7) of the European Commission, HEALTH (FP7-HEALTH-two-stage), Maciej Buchowski, European Project: 278186,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,SPOTLIGHT(2012), HAL UPMC, Gestionnaire, Sustainable prevention of obesity through integrated strategies - SPOTLIGHT - - EC:FP7:HEALTH2012-03-01 - 2016-02-29 - 278186 - VALID, De Bourdeaudhuij, Ilse, Ghent University [Belgium] (UGENT), Research Foundation - Flanders, Institute of Development Policy and Management, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Debrecen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Universiteit Gent = Ghent University [Belgium] (UGENT), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), 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), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], 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: Questionnaires, Male, Urban Population, Physiology, NEIGHBORHOOD WALKABILITY, VIRTUAL AUDIT, Social Sciences, lcsh:Medicine, Destinations, Surveys, Body Mass Index, 0302 clinical medicine, DESIGN, Sociology, Residence Characteristics, Surveys and Questionnaires, 11. Sustainability, SITTING TIME, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, lcsh:Science, Neighbourhood (mathematics), Built environment, media_common, OBESOGENIC CHARACTERISTICS, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, Socioeconomic Aspects of Health, Europe, Physiological Parameters, Research Design, OBESITY, CONCEPTUAL-FRAMEWORK, Female, HEALTH, Psychology, Research Article, Public park, Adult, media_common.quotation_subject, education, Motor Activity, Research and Analysis Methods, Education, 03 medical and health sciences, Perception, Environmental health, medicine, Adults, Humans, Obesity, Recreation, Educational Attainment, Aged, Behavior, Survey Research, Body Weight, lcsh:R, Biology and Life Sciences, ADULTS, 030229 sport sciences, Physical Activity, medicine.disease, Educational attainment, Health Care, BUILT ENVIRONMENT, Cross-Sectional Studies, Socioeconomic Factors, Age Groups, People and Places, Population Groupings, lcsh:Q, Self Report, Sedentary Behavior, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: WP3 SPOTLIGHT group; International audience; BackgroundThe relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level.MethodsIn 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables.ResultsLower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours.ConclusionPreliminary evidence was found for associations between neighbourhood environmental factors and domain-specific sedentary behaviours among adults. However, these associations varied according to objective or subjective environmental measures. More research is needed to confirm and clarify the associations.
Published: 2016
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43. The Brain Network of Naming: A Lesson from Primary Progressive Aphasia

Author: Sophie Ferrieux, Romain Valabregue, Bruno Dubois, Claire Boutet, Marie Nogues, Richard Levy, Didier Dormont, Marc Teichmann, Raffaella Migliaccio, Stéphane Lehéricy, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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)-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 Neuroradiologie [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), Laboratoire d'imagerie fonctionnelle [CHU Pitié-Salpétriêre] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Service de Neurologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], HAL UPMC, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Neuro-Imagerie de Recherche (CENIR), 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), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], Laboratoire d'imagerie fonctionnelle [Paris] (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de neurologie, APHP St Antoine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], 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: Male, Central Nervous System, Word processing, Social Sciences, lcsh:Medicine, Pathology and Laboratory Medicine, Nervous System, Brain mapping, Diagnostic Radiology, Primary progressive aphasia, Cognition, 0302 clinical medicine, Overlap zone, Medicine and Health Sciences, Psychology, Gray Matter, lcsh:Science, Language, Brain Mapping, Multidisciplinary, Radiology and Imaging, 05 social sciences, Organ Size, Conceptual semantics, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Semantics, Female, Anatomy, Comprehension, Research Article, Cognitive psychology, Imaging Techniques, Brain Morphometry, Neuroimaging, Phonology, Research and Analysis Methods, 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Terminology as Topic, medicine, Humans, Speech, 0501 psychology and cognitive sciences, Aged, Analysis of Variance, Morphometry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, lcsh:R, Cognitive Psychology, Biology and Life Sciences, Linguistics, medicine.disease, Aphasia, Primary Progressive, Cognitive Science, lcsh:Q, Atrophy, Nerve Net, Conceptual Semantics, Voxel-Based Morphometry, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; ObjectiveWord finding depends on the processing of semantic and lexical information, and it involves an intermediate level for mapping semantic-to-lexical information which also subserves lexical-to-semantic mapping during word comprehension. However, the brain regions implementing these components are still controversial and have not been clarified via a comprehensive lesion model encompassing the whole range of language-related cortices. Primary progressive aphasia (PPA), for which anomia is thought to be the most common sign, provides such a model, but the exploration of cortical areas impacting naming in its three main variants and the underlying processing mechanisms is still lacking.MethodsWe addressed this double issue, related to language structure and PPA, with thirty patients (11 semantic, 12 logopenic, 7 agrammatic variant) using a picture-naming task and voxel-based morphometry for anatomo-functional correlation. First, we analyzed correlations for each of the three variants to identify the regions impacting naming in PPA and to disentangle the core regions of word finding. We then combined the three variants and correlation analyses for naming (semantic-to-lexical mapping) and single-word comprehension (lexical-to-semantic mapping), predicting an overlap zone corresponding to a bidirectional lexical-semantic hub.Results and ConclusionsOur results showed that superior portions of the left temporal pole and left posterior temporal cortices impact semantic and lexical naming mechanisms in semantic and logopenic PPA, respectively. In agrammatic PPA naming deficits were rare, and did not correlate with any cortical region. Combined analyses revealed a cortical overlap zone in superior/middle mid-temporal cortices, distinct from the two former regions, impacting bidirectional binding of lexical and semantic information. Altogether, our findings indicate that lexical/semantic word processing depends on an anterior-posterior axis within lateral-temporal cortices, including an anatomically intermediate hub dedicated to lexical-semantic integration. Within this axis our data reveal the underpinnings of anomia in the PPA variants, which is of relevance for both diagnosis and future therapy strategies.
Published: 2016
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44. Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status

Author: Nicolas Dufour, Matthew A. Croxen, Jérôme Tourret, B. Brett Finlay, Sara Dion, Erick Denamur, Benjamin P. Willing, Sarah Wachtel, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie [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), Université Pierre et Marie Curie - Paris 6 (UPMC), University of British Columbia (UBC), University of Alberta, British Columbia Centre for Disease Control [Vancouver] (BCCDC), Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris], Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Northwestern University Feinberg School of Medicine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Pasteur [Paris] (IP)
Subjects: Bacterial Diseases, 0301 basic medicine, Physiology, lcsh:Medicine, Pathology and Laboratory Medicine, medicine.disease_cause, Mice, Immune Physiology, Intestine, Small, Medicine and Health Sciences, Uropathogenic Escherichia coli, lcsh:Science, Immune Response, Escherichia coli Infections, Innate Immune System, Gastrointestinal tract, Multidisciplinary, Virulence, Enterobacteriaceae Infections, Bacterial Pathogens, 3. Good health, Interleukin-10, Infectious Diseases, medicine.anatomical_structure, Medical Microbiology, Urinary Tract Infections, Cytokines, Anatomy, Pathogens, Research Article, Virulence Factors, Immunology, 030106 microbiology, Biology, Microbiology, 03 medical and health sciences, Signs and Symptoms, Enterobacteriaceae, Ileum, Diagnostic Medicine, Immunity, Escherichia coli, medicine, Animals, Humans, Microbial Pathogens, Inflammation, Innate immune system, Bacteria, Interleukin-6, Tumor Necrosis Factor-alpha, lcsh:R, Organisms, Biology and Life Sciences, Molecular Development, Pathogenicity island, Small intestine, Immunity, Innate, Gastrointestinal Tract, Mice, Inbred C57BL, 030104 developmental biology, Immune System, lcsh:Q, Cytokine secretion, Digestive System, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract: International audience; Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated. Intestinal colonization was measured, and cytokine expression was determined in various organs recovered from mice after oral challenge. UPEC strain 536 efficiently colonized the mouse digestive tract, and prior Enterobacteriaceae colonization was found to impact strain 536 colonization efficiency. An innate immune response, detected as the production of TNFα, IL-6 and IL-10 cytokines, was activated in the ileum 48 hours after oral challenge with strain 536, and returned to baseline within 8 days, without a drop in fecal pathogen load. Although inflammation was detected in the ileum, histology was normal at the time of cytokine peak. Comparison of cytokine secretion 48h after oral gavage with E. coli strain 536, CFT073, MG1655 or ΔPAI-536 showed that inflammation was more pronounced with UPECs than with non-pathogenic or attenuated strains. Pathogenicity islands also seemed to be involved in host detection, as IL-6 intestinal secretion was increased after administration of E. coli strain 536, but not after administration of ΔPAI-536. In conclusion, UPEC colonization of the mouse digestive tract activates acute phase inflammatory cytokine secretion but does not trigger any pathological changes, illustrating the opportunistic nature of UPECs. This digestive tract colonization model will be useful for studying the factors controlling the switch from commensalism to pathogenicity.
Published: 2015
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45. A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases

Author: Sylvie Radenne, François Durand, Paul Amouyal, Laure Jamot, Christian Trautwein, Gilles Amouyal, Philippe Ichai, Nicolas Moniaux, Michael P. Manns, Christian Bréchot, Philippe Mathurin, Christophe Duvoux, Guido Gerken, Vincent Leroy, Didier Samuel, Bertrand Nalpas, Dominique Larrey, Nicolas Carbonell, Jacques Bernuau, Marika Rudler, Jamila Faivre, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie [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 d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Duisburg-Essen [Essen], Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School [Hannover] (MHH), Medical Department III, University Hospital Aachen, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Paul Brousse, Agence Universitaire de la Francophonie (AUF), and Service d'Hépato-gastro-entérologie [CHU Saint-Antoine]
Subjects: 0301 basic medicine, Male, Viral Diseases, Etiology, medicine.medical_treatment, Medizin, lcsh:Medicine, Pancreatitis-Associated Proteins, Liver transplantation, medicine.disease_cause, Pathology and Laboratory Medicine, Gastroenterology, Biochemistry, Antioxidants, law.invention, Hepatitis, Placebos, 0302 clinical medicine, Randomized controlled trial, law, Medicine and Health Sciences, lcsh:Science, Multidisciplinary, Pharmaceutics, Liver Diseases, Hepatitis A, Proteases, Middle Aged, Prognosis, Recombinant Proteins, 3. Good health, Extracellular Matrix, Enzymes, Infectious Diseases, Research Design, Area Under Curve, Acute Disease, 030211 gastroenterology & hepatology, Female, Research Article, Adult, medicine.medical_specialty, Clinical Research Design, Acute Liver Failure, Surgical and Invasive Medical Procedures, Gastroenterology and Hepatology, Placebo, Research and Analysis Methods, 03 medical and health sciences, Digestive System Procedures, Double-Blind Method, Drug Therapy, Antigens, Neoplasm, Internal medicine, medicine, Biomarkers, Tumor, Humans, Lectins, C-Type, Survival rate, Hepatitis B virus, Transplantation, Intention-to-treat analysis, business.industry, lcsh:R, Biology and Life Sciences, Proteins, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Organ Transplantation, medicine.disease, Liver Transplantation, 030104 developmental biology, Immunology, Enzymology, lcsh:Q, Adverse Events, Serine Proteases, business
Abstract: Objective No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. Design double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. Results 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). Conclusion ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. Trial Registration ClinicalTrials.gov NCT01318525
Published: 2015
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46. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

Author: Lucile Musset, Makoto Miyara, Alexis Mathian, Jehane Fadlallah, Laetitia Claër, Romain Jouenne, Fleur Cohen-Aubart, Julien Haroche, Guy Gorochov, Driss Chader, Zahir Amoura, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immunologie [CHU Pitié-Salpétrière], Service de médecine interne [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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Regulatory T cell, lcsh:Medicine, Arthritis, Peripheral blood mononuclear cell, Methylprednisolone, T-Lymphocytes, Regulatory, Young Adult, Prednisone, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Young adult, lcsh:Science, Infusions, Intravenous, Multidisciplinary, Lupus erythematosus, Dose-Response Relationship, Drug, business.industry, lcsh:R, Middle Aged, medicine.disease, Dose–response relationship, Endocrinology, medicine.anatomical_structure, Treatment Outcome, lcsh:Q, Female, business, medicine.drug, Follow-Up Studies, Research Article
Abstract: International audience; Background/PurposeA slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.MethodsWe prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.ResultsSeventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.ConclusionIV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.
Published: 2015
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47. Later cART Initiation in Migrant Men from Sub-Saharan Africa without Advanced HIV Disease in France

Author: Laure-Amélie de Monteynard, Rosemary Dray-Spira, Pierre de Truchis, Sophie Grabar, Odile Launay, Jean-Luc Meynard, Marie-Aude Khuong-Josses, Jacques Gilquin, David Rey, Anne Simon, Juliette Pavie, Aba Mahamat, Sophie Matheron, Dominique Costagliola, Sophie Abgrall, French Hospital Database on HIV, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine Aiguë Spécialisée, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5), Unité de biostatistique et épidémiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Services des Maladies Infectieuses et Tropicales [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 des maladies infectieuses et tropicales, Hôpital Delafontaine, Unité d'immunoinfectiologie, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de soins de l'infection par le VIH, Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Immunologie Clinique, Hôpital Européen Georges Pompidou, Paris, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Avicenne [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches]-Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], CHU Cochin [AP-HP], Service des maladies infectieuses et tropicales [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Département de médecine interne, CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and AP-HP Groupe Hospitalier Avicenne
Subjects: Cart, Adult, Male, Adolescent, Anti-HIV Agents, lcsh:Medicine, HIV Infections, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Men who have sex with men, Time-to-Treatment, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Medicine, Humans, lcsh:Science, Africa South of the Sahara, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Transients and Migrants, Multidisciplinary, business.industry, Coinfection, Hazard ratio, lcsh:R, virus diseases, Hepatitis C, Viral Load, medicine.disease, Hepatitis B, CD4 Lymphocyte Count, Immunology, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Patient Compliance, lcsh:Q, Female, France, business, Viral load, Demography, Research Article
Abstract: International audience; ObjectiveTo compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care.MethodsAntiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002–2010, with CD4 cell counts >200/μL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200–349, 350-499, ≥500/μL), we examined the crude time until cART initiation within three years after enrolment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrolment period, region of care, plasma viral load, and HBV/HBC coinfection.ResultsAmong 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1–28) and 20% (95%CI, 2–38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM.ConclusionSSA/NFW migrant men living in France with CD4 >350/μL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.
Published: 2015
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48. ANKS3 Co-Localises with ANKS6 in Mouse Renal Cilia and Is Associated with Vasopressin Signaling and Apoptosis In Vivo in Mice

Author: Delestré, Laure, Bakey, Zeineb, Prado, Cécilia, Hoffmann, Sigrid, Bihoreau, Marie-Thérèse, Lelongt, Brigitte, Gauguier, Dominique, 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), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Heidelberg University Hospital [Heidelberg], National Genotyping Centre (CeGen), Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (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 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), 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), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -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 ), INSERM UMR_S1155, CHU Tenon [APHP], CNIO, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and HAL UPMC, Gestionnaire
Subjects: Polycystic Kidney Diseases, [ SDV ] Life Sciences [q-bio], Vasopressins, [SDV]Life Sciences [q-bio], Amino Acid Motifs, lcsh:R, Down-Regulation, lcsh:Medicine, Apoptosis, Kidney, Ankyrin Repeat, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Mice, Mutation, Animals, lcsh:Q, Cilia, Carrier Proteins, lcsh:Science, Cell Proliferation, Protein Binding, Signal Transduction, Research Article
Abstract: International audience; Mutations in Ankyrin repeat and sterile alpha motif domain containing 6 (ANKS6) play a causative role in renal cyst formation in the PKD/Mhm(cy/+) rat model of polycystic kidney disease and in nephronophthisis in humans. A network of protein partners of ANKS6 is emerging and their functional characterization provides important clues to understand the role of ANKS6 in renal biology and in mechanisms involved in the formation of renal cysts. Following experimental confirmation of interaction between ANKS6and ANKS3 using a Yeast two hybrid system, we demonstrated that binding between the two proteins occurs through their sterile alpha motif (SAM) and that the amino acid 823 in rat ANSK6 is key for this interaction. We further showed their interaction by co-immunoprecipitation and showed in vivo in mice that ANKS3 is present in renal cilia. Downregulated expression of Anks3 in vivo in mice by Locked Nucleic Acid (LNA) modified antisense oligonucleotides was associated with increased transcription of vasopressin-induced genes, suggesting changes in renal water permeability, and altered transcription of genes encoding proteins involved in cilium structure, apoptosis and cell proliferation. These data provide experimental evidence of ANKS3-ANKS6 direct interaction through their SAM domain and co-localisation in mouse renal cilia, and shed light on molecular mechanisms indirectly mediated by ANKS6 in the mouse kidney, that may be affected by altered ANKS3-ANKS6 interaction. Our results contribute to improved knowledge of the structure and function of the network of proteins interacting with ANKS6, which may represent therapeutic targets in cystic diseases.
Published: 2015
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49. Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

Author: Corinne Vigouroux, Jean-Philippe Bastard, Laurence Meyer, Laurence Gérard, Jacqueline Capeau, Soraya Fellahi, Mathilde Ghislain, Anne Simon, Thierry May, Cécile Goujard, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de santé publique et d'épidémiologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Lipopolysaccharide Receptors, lcsh:Medicine, Systemic inflammation, Zidovudine, Insulin resistance, Internal medicine, Diabetes mellitus, Humans, Receptors, Tumor Necrosis Factor, Type II, Medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Prospective Studies, Prospective cohort study, lcsh:Science, Immunodeficiency, Inflammation, Acquired Immunodeficiency Syndrome, Multidisciplinary, biology, Interleukin-6, business.industry, Insulin, C-reactive protein, lcsh:R, Middle Aged, medicine.disease, CD4 Lymphocyte Count, 3. Good health, C-Reactive Protein, Endocrinology, Anti-Retroviral Agents, HIV-1, biology.protein, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, lcsh:Q, medicine.symptom, business, Biomarkers, Research Article, medicine.drug
Abstract: International audience; ObjectivesHIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation.MethodsImmunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142).ResultsMedian CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07).ConclusionAfter three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.
Published: 2015
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50. Antiretroviral therapy as a risk factor for chronic kidney disease: Results from traditional regression modeling and causal approach in a large observational study

Author: Cuzin, Lise, Pugliese, Pascal, Allavena, Clotilde, Rey, David, Chirouze, Catherine, Bani-Sadr, Firouze, Cabié, André, Huleux, Thomas, Poizot-Martin, Isabelle, Cotte, Laurent, Isnard Bagnis, Corinne, Flandre, Philippe, De Socio, Giuseppe Vittorio, Service de Maladies Infectieuses et Tropicales, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Ingénierie Circulation Transport (LICIT), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École Nationale des Travaux Publics de l'État (ENTPE)-Université de Lyon, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Unité des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France]-Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Service Universitaire des Maladies Infectieuses et du Voyageur [Tourcoing], Centre Hospitalier Tourcoing, Service d'immuno-hématologie clinique (CISIH), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Equipe 16, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Neuroradiologie [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), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Chrono-environnement (UMR 6249) (LCE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: RNA viruses, Male, Oncology, [SDV]Life Sciences [q-bio], lcsh:Medicine, HIV Infections, Pathology and Laboratory Medicine, Biochemistry, 01 natural sciences, 010104 statistics & probability, Endocrinology, 0302 clinical medicine, Immunodeficiency Viruses, Chronic Kidney Disease, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Reverse-transcriptase inhibitor, Antimicrobials, Drugs, Antiretrovirals, Viral Load, Middle Aged, Antivirals, Vaccination and Immunization, 3. Good health, Nephrology, Medical Microbiology, Viral Pathogens, Creatinine, Viruses, Regression Analysis, Reverse Transcriptase Inhibitors, Female, France, Pathogens, Research Article, medicine.drug, Adult, medicine.medical_specialty, Endocrine Disorders, Anti-HIV Agents, Immunology, Antiretroviral Therapy, Renal function, Microbiology, 03 medical and health sciences, Antiviral Therapy, Virology, Microbial Control, Internal medicine, Retroviruses, Diabetes Mellitus, medicine, Humans, 0101 mathematics, Risk factor, Microbial Pathogens, Pharmacology, business.industry, Proportional hazards model, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, Models, Theoretical, medicine.disease, Regimen, Metabolic Disorders, HIV-1, Kidney Failure, Chronic, lcsh:Q, Ritonavir, Preventive Medicine, business, Viral Transmission and Infection, Biomarkers, Kidney disease
Abstract: Objective We investigated whether patients receiving selected antiretroviral combinations had a higher risk of chronic kidney disease (CKD) using traditional regression modeling and a causal approach in a large prospective cohort. Patients and methods For the purpose of this study, we selected 6301 patients who (i) started their first antiretroviral regimen after 1st January 2004, (ii) had at least one serum creatinine measurement within 6 months before ART initiation (study entry), and (iii) had at least two measurements after study entry. Baseline eGFR was defined from the last serum creatinine measurement before study entry. All eGFR values were calculated using the Modification of Diet and Renal Disease (MDRD) equation. Both traditional Cox proportional hazards model and Cox marginal structural models were applied. Distinct coding for antiretroviral therapy exposure were investigated as well as double robust estimators. Results Overall we showed that patients receiving tenofovir (TDF) with a ritonavir boosted protease inhibitor (rbPI) exhibited a higher risk of CKD compared with patients who received TDF with a non-nucleosidic reverse transcriptase inhibitor (NNRTI). Such an increased risk was observed considering both initial and current regimens. Our analysis revealed a clinician-driven switch away from TDF among persons experiencing a decline in renal function while receiving this drug. Conclusion Our results show that combination of TDF and boosted protease inhibitor is associated with a higher CKD risk than TDF and a NNRTI.
Published: 2017
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