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148 results on '"Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours"'

1. Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting

Author: Lixin Xie, Meilien Tu, Armèle Dornelas de Andrade, Jie Li, Lingyue Gong, Lei Yang, Stephan Ehrmann, James B Fink, Chris Burtin, Guoqiang Jing, Rush University [Chicago], Chang Gung University, Binzhou Medical University (MBBS), Partenaires INRAE, Universiteit Hasselt (UHasselt), Federal University of Pernambuco [Recife], Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRICS-TRIGGERSEP, Li, Jie/0000-0003-0121-1291, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, pulmonary aerosol delivery, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030226 pharmacology & pharmacy, transnasal pulmonary aerosol delivery, Hypoxemia, Aerosol therapy, 03 medical and health sciences, 0302 clinical medicine, Oxygen therapy, Administration, Inhalation, medicine, Cannula, Humans, survey, Mouthpiece, Original Research, Aerosols, hypoxemia, business.industry, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, General Medicine, High-flow nasal cannula, aerosol therapy, transnasal, Bronchodilator Agents, 3. Good health, Clinical Practice, Intensive Care Units, Nebulizer, Concomitant, Emergency medicine, medicine.symptom, business, Nasal cannula
Abstract: BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients. METHODS: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included. RESULTS: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40–50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC (a method shown to reduce inhaled dose), whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier. CONCLUSIONS: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.
Published: 2021

2. Chronic Hepatitis C Virus Infection After Kidney Transplantation With or Without Direct-Acting Antivirals in a Real-Life Setting: A French Multicenter Experience

Author: Nicolas Bouvier, Yannick Le Meur, Cyril Garrouste, Dominique Bertrand, Johnny Sayegh, Eloi Chevallier, Matthias Büchler, Sophie Caillard, Joseph Rivalan, Antoine Thierry, Lionel Rostaing, Philippe Gatault, Charlotte Colosio, Jean-Philippe Rerolle, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratory of Immunology, CHRU de Tours, Tours, France, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Nephrology, Reims University Hospital, Reims, France, Centre Hospitalier Universitaire de Rennes (CHU Rennes), Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Male, Ledipasvir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, 030232 urology & nephrology, Antiviral Agents, Gastroenterology, Group A, Virus, Group B, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Kidney transplantation, Retrospective Studies, Fluorenes, Transplantation, business.industry, Imidazoles, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Benzimidazoles, Female, 030211 gastroenterology & hepatology, Surgery, Carbamates, France, business, Viral hepatitis, medicine.drug
Abstract: Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.
Published: 2020

3. Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double‐blind, controlled study

Author: P. Bernard, Sophie Leducq, F. Boralevi, A. Le Gouge, Loïc Vaillant, F. Pascal, Camille Francès, Jean-Christophe Fricain, S. Agbo-Godeau, Mahtab Samimi, T. Passeron, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [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), French Ministry of Social Affairs and Health (French National Programme of Clinical Research [PHRC]), 2005, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Food intake, medicine.medical_specialty, Administration, Topical, [SDV]Life Sciences [q-bio], Betamethasone dipropionate, Dermatology, Betamethasone, Ointments, Double blind, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, medicine, Humans, Psoriasis, Adverse effect, Sirolimus, business.industry, 030206 dentistry, Odds ratio, 3. Good health, Treatment Outcome, Infectious Diseases, Clinical recurrence, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, After treatment, Lichen Planus, Oral, medicine.drug
Abstract: International audience; Background Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series.Objectives To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial.Methods Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase(R) or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events.Results During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis).Conclusion Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.
Published: 2020

4. It's never too early to beat your low-density lipoprotein cholesterol

Author: Gilles Barone-Rochette, François Mach, Denis Angoulvant, Cyrille Bergerot, Nathan Mewton, Gilles Lemesle, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials (FACT), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Département de cardiologie [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Geneva University Hospital (HUG), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Prévention sécondaire, Low density lipoprotein cholesterol, 030204 cardiovascular system & hematology, Risk Assessment, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Traitements hypolipémiants, Internal medicine, medicine, Humans, Healthy Lifestyle, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Dyslipidemias, Ldl cholesterol, Secondary prevention, business.industry, Anticholesteremic Agents, Cholesterol, LDL, General Medicine, Lipid-lowering therapies, medicine.disease, [SDV] Life Sciences [q-bio], Maladie coronaire, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, LDL cholesterol, Cardiology, Cardiology and Cardiovascular Medicine, business, Risk Reduction Behavior, Beat (music), Biomarkers, LDL cholestérol
Abstract: International audience
Published: 2021

5. Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD): a protocol for establishing a core outcome set for adults with chronic kidney disease who do not require kidney replacement therapy

Author: Andrew S. Levey, Armando Teixeira-Pinto, Samuel Fung, Nicole Scholes-Robertson, Gloria Ashuntantang, Laura Cortés Sanabria, Samaya Anumudu, Amelie Bernier-Jean, Martin Howell, Louese Dunn, Tim Usherwood, Eduardo Lorca, Martin Wilkie, Andrea Matus Gonzalez, Magdalena Madero, Ikechi G. Okpechi, Daniel Gallego, Jonathan C. Craig, Adeera Levin, Allison Tong, Patrick Rossignol, Katherine Widders, Yeoungjee Cho, Ian H. de Boer, Andrea K. Viecelli, David C. Wheeler, Nicole Evangelidis, Bénédicte Sautenet, Laura Sola, Chandana Guha, The University of Sydney, Westmead Hospital [Sydney], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Instituto Nacional de Cardiologia Ignacio Chavez, Université de Yaoundé I, Hospital Universitario de Guadalajara, Department of Medicine, Kidney Research Institute, University of Washington, Kidney Research Institute [Seattle] (KRI), Princess Margaret Hospital, Hong Kong, Federacion Nacional ALCER (Spanish Kidney Patient's Federation), Tufts University School of Medicine [Boston], University of British Columbia (UBC), Hospital Salvador, University of Cape Town, University of Alberta, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Dialysis Unit, CASMU-IAMPP, Montevideo, University of New South Wales [Sydney] (UNSW), Centre for Nephrology, UCL Medical School, Translational Research Institute, University College of London [London] (UCL), University of Queensland [Brisbane], Princess Alexandra Hospital, Brisbane, Baylor College of Medecine, Sheffield Children's NHS Foundation Trust, Flinders University [Adelaide, Australia], This project is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. NE is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. AT is supported by The University of Sydney Robinson Fellowship. YC is supported by the NHMRC Early Career Fellowship 1126256. AV is supported by a Jacquot Research Establishment Fellowship. The funding bodies do not have a role in the design, collection, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication., Division of Nephrology and Hypertension, Faculty of Health Sciences, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, and BOZEC, Erwan
Subjects: Nephrology, Medicine (General), Delphi Technique, 030232 urology & nephrology, Medicine (miscellaneous), urologic and male genital diseases, MESH: Delphi Technique, law.invention, Study Protocol, Clinical trials, 0302 clinical medicine, Randomized controlled trial, law, Chronic kidney disease, Outcome Assessment, Health Care, Pharmacology (medical), 030212 general & internal medicine, MESH: Treatment Outcome, MESH: Research Design, MESH: Nephrology, female genital diseases and pregnancy complications, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Renal Replacement Therapy, Treatment Outcome, Research Design, Outcomes research, Adult, medicine.medical_specialty, MESH: Renal Insufficiency, Chronic, 03 medical and health sciences, R5-920, Quality of life (healthcare), [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, MESH: Outcome Assessment, Health Care, Intensive care medicine, MESH: Humans, business.industry, Core outcome set, MESH: Quality of Life, MESH: Adult, medicine.disease, Transplantation, Clinical trial, Quality of Life, MESH: Renal Replacement Therapy, Patient-centred outcomes, MESH: Systematic Reviews as Topic, business, Systematic Reviews as Topic, Kidney disease, Qualitative research
Abstract: Background Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials. Methods SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD. Discussion Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD. Trial registration Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653.
Published: 2021

6. Early versus differed arterial catheterisation in critically ill patients with acute circulatory failure: a multicentre, open-label, pragmatic, randomised, non-inferiority controlled trial: the EVERDAC protocol

Author: Toufik Kamel, Damien Contou, Jean-Pierre Quenot, Alexandra Monnier, Thierry Boulain, Jean-Claude Lacherade, Maelle Martin, Sylvie Vimeux, Elsa Tavernier, Grégoire Muller, Solène Brunet Houdard, Florence Boissier, Stephan Ehrmann, Centre Hospitalier Régional d'Orléans (CHRO), Réseau CRICS-TRIGGERSEP [CHRU Tours] (F-CRIN research network), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier Argenteuil (CH Argenteuil), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Centre hospitalier de Montauban (CH Montauban), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and Malbec, Odile
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Informed consent, law, Medicine, health economics, 030212 general & internal medicine, adult intensive & critical care, Protocol (science), clinical trials, business.industry, 030208 emergency & critical care medicine, General Medicine, Arterial catheter, medicine.disease, Intensive care unit, Thrombosis, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Shock (circulatory), Emergency medicine, medicine.symptom, business
Abstract: IntroductionThe use of peripheral indwelling arterial catheter for haemodynamic monitoring is widespread in the intensive care unit and is recommended in patients with shock. However, there is no evidence that the arterial catheter could improve patient’s outcome, whereas the burden of morbidity generated is significant (pain, thrombosis, infections). We hypothesise that patients with shock may be managed without an arterial catheter.Methods and analysisThe EVERDAC study is an investigator-initiated, pragmatic, multicentre, randomised, controlled, open-label, non-inferiority clinical trial, comparing a less invasive intervention (ie, no arterial catheter insertion until felt absolutely needed, according to predefined safety criteria) or usual care (ie, systematic arterial catheter insertion in the early hours of shock). 1010 patients will be randomised with a 1:1 ratio in two groups according to the strategy. The primary outcome is all-cause mortality by 28 days after inclusion. A health economic analysis will be carried out.Ethics and disseminationThe study has been approved by the Ethics Committee (Comité de Protection des Personnes Île de France V, registration number 61606 CAT 2, 19 july 2018) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03680963.
Published: 2021

7. Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation

Author: Cécile Vigneau, Louis Bernard, Emmanuel Gyan, Florent von Tokarski, Philippe Gatault, Véronique Frémeaux-Bacchi, Guillaume Bayer, Jean-Michel Halimi, B. Thoreau, Elodie Merieau, Christelle Barbet, Fadi Fakhouri, Bénédicte Sautenet, Emmanuel Rusch, Sylvie Cloarec, Adeline Bauvois, François Maillot, Franck Perrotin, Denis Garot, Sébastien Lachot, Claire Pouplard, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), 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), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Adult, Male, medicine.medical_specialty, Thrombotic microangiopathy, Epidemiology, [SDV]Life Sciences [q-bio], Congenital cytomegalovirus infection, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Thrombotic Microangiopathies, Humans, In patient, infections, cytomegalovirus, Retrospective Studies, Transplantation, business.industry, Acute kidney injury, Retrospective cohort study, Original Articles, clinical epidemiology, Middle Aged, medicine.disease, clinical nephrology, 3. Good health, acute kidney injury, Nephrology, 030220 oncology & carcinogenesis, hemolytic uremic syndrome, Female, thrombotic microangiopathies, Presentation (obstetrics), business, epidemiology and outcomes
Abstract: BACKGROUND AND OBJECTIVES: In contrast to shigatoxin-associated Escherichia coli (STEC) causing hemolytic uremic syndrome, STEC-unrelated infections associated with thrombotic microangiopathy are less characterized. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective study in a four-hospital institution of 530 consecutive patients with adjudicated thrombotic microangiopathies during the 2009–2016 period studied STEC-unrelated infections’ epidemiology and major outcomes (death, acute dialysis, and major cardiovascular events). RESULTS: STEC-unrelated infection was present in 145 of 530 (27%) patients, thrombotic microangiopathies without infection were present in 350 of 530 (66%) patients, and STEC causing hemolytic and uremic syndrome was present in 35 of 530 (7%) patients. They (versus thrombotic microangiopathy without infection) were associated with age >60 years (36% versus 18%), men (53% versus 27%), altered consciousness (32% versus 11%), mean BP
Published: 2021

8. Intracluster correlation measures in cluster randomized trials with binary outcomes

Author: Mbekwe Yepnang, Ariane, Caille, Agnès, Eldridge, Sandra, Giraudeau, Bruno, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Queen Mary University of London (QMUL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Puel, Stephanie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, prevalence, cluster, variance partition coefficient, Intraclass correlation coefficient, binary outcome, median odds ratio, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, tetrachoric correlation coefficient
Abstract: International audience; In cluster randomized trials, a measure of intracluster correlation such as the intraclass correlation coefficient (ICC) should be reported for each primary outcome. Providing intracluster correlation estimates may help in calculating sample size of future cluster randomized trials and also in interpreting the results of the trial from which they are derived. For a binary outcome, the ICC is known to be associated with its prevalence, which raises at least two issues. First, it questions the use of ICC estimates obtained on a binary outcome in a trial for sample size calculations in a subsequent trial in which the same binary outcome is expected to have a different prevalence. Second, it challenges the interpretation of ICC estimates because they do not solely depend on clustering level. Other intracluster correlation measures have been proposed for clustered binary data settings including the variance partition coefficient, the median odds ratio and the tetrachoric correlation coefficient. Under certain assumptions, the theoretical maximum possible value for an ICC associated with a binary outcome can be derived and we propose to consider the relative deviation of an ICC estimate to this maximum value, as another measure of the intracluster correlation. We conducted a simulation study to explore the dependence of these intracluster correlation measures on outcome prevalence and found that all these measures are associated with prevalence. Even if some were slightly less dependent than the ICC in some scenarios, in general, none differs from the ICC regarding the dependence on prevalence.
Published: 2021

9. Gender imbalance in intensive care: High time for action and evaluation!

Author: Hauw-Berlemont, Caroline, Salmon Gandonnière, Charlotte, Boissier, Florence, Aissaoui, Nadia, Bodet-Contentin, Laetitia, Fartoukh, Muriel, Jourdain, Mercedes, Le Marec, Julien, Tamion, Fabienne, Hamzaoui, Olfa, Aubron, Cécile, Group For The French Intensive Care Society, The Femmir (femme Médecins En Médecine Intensive Réanimation), Gestionnaire, Hal Sorbonne Université, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), The FEMMIR (Femme Médecins en Médecine Intensive Réanimation) Group for the French Intensive Care Society : Caroline Hauw-Berlemont, Charlotte Salmon Gandonnière, Florence Boissier, Nadia Aissaoui, Laetitia Bodet-Contentin, Muriel Sarah Fartoukh, Mercedes Jourdain, Julien Le Marec, Fabienne Tamion, Olfa Hamzaoui & Cécile Aubron, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and 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: Critical Care, business.industry, RC86-88.9, [SDV]Life Sciences [q-bio], Research, Sexism, MEDLINE, 030208 emergency & critical care medicine, Medical emergencies. Critical care. Intensive care. First aid, Critical Care and Intensive Care Medicine, medicine.disease, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Editorial, 030228 respiratory system, Action (philosophy), Intensive care, Medicine, Humans, Medical emergency, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

10. Ivermectin as a potential treatment for COVID-19?

Author: Didier Guillemot, Hervé Bourhy, Olivier Chosidow, Marc Lecuit, Charlotte Bernigaud, Bruno Giraudeau, Anne Lespine, Zahir Amoura, Jean-Pierre Changeux, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Neuroscience - Department of Neuroscience, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP), Biologie des Infections - Biology of Infection, Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, HAL Sorbonne Université 5, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre d'Immunologie et de Maladies Infectieuses (CIMI)
Subjects: RNA viruses, Viral Diseases, Coronaviruses, Epidemiology, Ectoparasitic Infections, RC955-962, law.invention, Scabies, 0302 clinical medicine, Ivermectin, Medical Conditions, Randomized controlled trial, law, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Materials, Pathology and laboratory medicine, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Mammals, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Eukaryota, Medical microbiology, Vaccination and Immunization, Solutions, Infectious Diseases, Viruses, Vertebrates, Physical Sciences, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hamsters, SARS CoV 2, Pathogens, Public aspects of medicine, RA1-1270, medicine.drug, Neglected Tropical Diseases, 2019-20 coronavirus outbreak, Drug Research and Development, Coronavirus disease 2019 (COVID-19), SARS coronavirus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Materials Science, Sexually Transmitted Diseases, Research and Analysis Methods, Microbiology, Rodents, Formal Comment, 03 medical and health sciences, Vaccine Development, medicine, Parasitic Diseases, Humans, Animals, Clinical Trials, 030304 developmental biology, Pharmacology, Biology and life sciences, business.industry, SARS-CoV-2, Public Health, Environmental and Occupational Health, Organisms, Viral pathogens, Covid 19, medicine.disease, Tropical Diseases, Virology, Randomized Controlled Trials, COVID-19 Drug Treatment, Microbial pathogens, Medical Risk Factors, Mixtures, Amniotes, Preventive Medicine, Clinical Medicine, business, Zoology
Abstract: International audience
Published: 2021

11. Continuous enteral nutrition compared with a maximal gastric vacuity strategy at the time of extubation in the intensive care unit: protocol for a non-inferiority cluster randomised trial (the Ambroisie Project)

Author: Stephan Ehrmann, Anne Rebion, Jean Reignier, Johann Auchabie, Bruno Giraudeau, Mai-Anh Nay, Arnaud W. Thille, Elsa Tavernier, Noemie Hubert, Alain Robert, Mickael Landais, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Régional d'Orléans (CHRO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, intensive & critical care, medicine.medical_specialty, Critical Illness, [SDV]Life Sciences [q-bio], nutritional support, Disease cluster, law.invention, 03 medical and health sciences, 0302 clinical medicine, Non inferiority, Enteral Nutrition, Informed consent, law, medicine, Intubation, Intratracheal, Humans, 030212 general & internal medicine, adult intensive & critical care, Randomized Controlled Trials as Topic, Protocol (science), Critically ill, business.industry, Intensive Care, General Medicine, Intensive care unit, 3. Good health, Intensive Care Units, Parenteral nutrition, 030228 respiratory system, Concomitant, Emergency medicine, Airway Extubation, Medicine, business
Abstract: IntroductionFasting is frequently imposed to patients before extubation in the intensive care unit based on scheduled surgery guidelines. This practice has never been evaluated among critically ill patients and may delay extubation, increase nursing workload and reduce caloric intake. We are hypothesising that continuous enteral nutrition until extubation represents a safe alternative compared with fasting prior to extubation in the intensive care unit.Methods and analysisAdult patients ventilated more than 48 hours and receiving pre-pyloric enteral nutrition for more than 24 hours are included in this open-label cluster randomised parallel group non-inferiority trial. The participating centres are randomised allocated to continued enteral nutrition until extubation or 6-hour fasting (with concomitant gastric suctioning when feasible) prior to extubation. The primary outcome is extubation failure (ie, reintubation within 7 days following extubation).Ethics and disseminationThis study has been approved by the national ethics review board (comité de protection, des personnes Sud Mediterranée III No 2017.10.02 bis) and patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberClinicalTrials.gov Registry (NCT03335345).
Published: 2021

12. Splenectomy for haemophagocytic lymphohistiocytosis of unknown origin: risks and benefits in 21 patients

Author: Guillemette Fouquet, G. Urbanski, Claire Larroche, Fabrice Bonnet, Nanthara Sritharan, Charlotte Salmon Gandonnière, Coralie Bloch-Queyrat, Estibaliz Lazaro, Benjamin Carpentier, Antoinette Perlat, Olivier Hermine, Carole Lacout, François Lifermann, Louis Terriou, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier de Dax, Centre Hospitalier de Saint-Denis [Ile-de-France], 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), CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Admin, Oskar, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Splenectomy, Hemophagocytic lymphohistiocytosis, Risk Assessment, Lymphohistiocytosis, Hemophagocytic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Diagnosis, medicine, Humans, Risks and benefits, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: International audience; No abstract available
Published: 2021

13. Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

Author: Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, 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), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract: International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
Published: 2019

14. Lack of impact of iodinated contrast media on kidney cell-cycle arrest biomarkers in critically ill patients

Author: Stephan Ehrmann, Emmanuelle Rouve, Youenn Jouan, Laetitia Bodet-Contentin, Karim Lakhal, Charlotte Salmon Gandonnière, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ehrmann, Stephan
Subjects: Male, Nephrology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Contrast Media, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Prospective Studies, 030212 general & internal medicine, Kidney, Acute kidney injury, Middle Aged, medicine.anatomical_structure, Iodinated contrast media, Female, Research Article, medicine.drug, medicine.medical_specialty, Critical Illness, Urinary system, Iohexol, Urology, 03 medical and health sciences, TIMP-2, Internal medicine, medicine, Humans, Aged, Tissue Inhibitor of Metalloproteinase-2, Creatinine, business.industry, Iopromide, Iobitridol, 030208 emergency & critical care medicine, Cell Cycle Checkpoints, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, IGFBP-7, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, Tomography, X-Ray Computed, business, Biomarkers, Kidney disease
Abstract: International audience; Background: Iodinated contrast media may contribute to acute kidney injury. However, several recent works suggest that this toxicity is minimal in the clinical setting. Recently, urinary G1 cell-cycle arrest proteins tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin like growth factor binding protein 7 (IGFBP-7) were identified as highly sensitive and specific biomarkers for early detection of kidney aggression. The impact of contrast administration on those biomarkers has not been specifically evaluated but could provide clues about the toxicity of contrast media. This study aimed at measuring changes in TIMP-2 and IGFBP-7 urinary concentrations before and after a contrast-enhanced computed tomography in critically ill patients.Methods: 77 patients were included in a prospective observational cohort study. Urinary [TIMP -2]·[IGFBP-7] was measured before, 6 and 24 h after contrast infusion. Urine output and serum creatinine were followed 3 days.Results: Median [TIMP-2]·[IGFBP-7] was 0.06 [interquartile range 0.04;0.26], 0.07 [0.03;0.34] and 0.10 [0.04;0.37] (ng/mL)2/1000 respectively before, 6 and 24 h after contrast infusion. Individual changes from baseline were − 0.01 [− 0.11;0.11] and 0.00 [− 0.10;0.09] (ng/ml)2/1000 at 6 and 24 h. These changes were not higher among the patients increasing their Kidney Disease Improving Global Outcome (KDIGO) classification within 3 days after contrast infusion (n = 14 [18%] based on creatinine criterion only, n = 42 [55%] based on creatinine and urine output).Conclusions: Changes in [TIMP-2]·[IGFBP-7] urinary concentration after contrast-enhanced computed tomography were insignificant, suggesting minimal kidney aggression by modern iodinated contrast media.
Published: 2018

15. Inter-hospital transport of critically ill patients to manage the intensive care unit surge during the COVID-19 pandemic in France

Author: Painvin, Benoit, Messet, Hélène, Rodriguez, Maeva, Lebouvier, Thomas, Chatellier, Delphine, Soulat, Louis, Ehrmann, Stephane, Thille, Arnaud W., Gacouin, Arnaud, Tadie, Jean-Marc, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University Hospital of Rennes, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], Mechanical ventilation, Research, [SDV]Life Sciences [q-bio], lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, ARDS, Intensive care unit, lcsh:RC86-88.9, Mortality, Hospital transport
Abstract: International audience; BACKGROUND: The COVID-19 pandemic led authorities to evacuate via various travel modalities critically ill ventilated patients into less crowded units. However, it is not known if interhospital transport impacts COVID-19 patient’s mortality in intensive care units (ICUs). A cohort from three French University Hospitals was analysed in ICUs between 15th of March and the 15th of April 2020. Patients admitted to ICU with positive COVID-19 test and mechanically ventilated were recruited. RESULTS: Among the 133 patients included in the study, 95 (71%) were male patients and median age was 63 years old (interquartile range: 54-71). Overall ICU mortality was 11%. Mode of transport included train (48 patients), ambulance (6 patients), and plane plus helicopter (14 patients). During their ICU stay, 7 (10%) transferred patients and 8 (12%) non-transferred patients died (p = 0.71). Median SAPS II score at admission was 33 (interquartile range: 25-46) for the transferred group and 35 (27-42) for non-transferred patients (p = 0.53). SOFA score at admission was 4 (3-6) for the transferred group versus 3 (2-5) for the non-transferred group (p = 0.25). In the transferred group, median PaO(2)/FiO(2) ratio (P/F) value in the 24 h before departure was 197 mmHg (160-250) and remained 166 mmHg (125-222) in the first 24 h post arrival (p = 0.13). During the evacuation 46 (68%) and 21 (31%) of the patients, respectively, benefited from neuromuscular blocking agents and from vasopressors. Transferred and non-transferred patients had similar rate of nosocomial infections, 37/68 (54%) versus 34/65 (52%), respectively (p = 0.80). Median length of mechanical ventilation was significantly increased in the transferred group compared to the non-transferred group, 18 days (11-24) and 14 days (8-20), respectively (p = 0.007). Finally, ICU and hospital length of stay did not differ between groups. CONCLUSIONS: In France, inter-hospital evacuation of COVID-19 ventilated ICU patients did not appear to increase mortality and therefore could be proposed to manage ICU surges in the future.
Published: 2021

16. Is randomized trial design adapted to population health intervention research?

Author: Corinne Alberti, Bruno Giraudeau, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Puel, Stephanie
Subjects: medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Population Health, business.industry, Gold standard, Public Health, Environmental and Occupational Health, Population health, 030204 cardiovascular system & hematology, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, Clinical research, Randomized controlled trial, law, Research Design, Intervention research, Physical therapy, Medicine, Humans, 030212 general & internal medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Randomized Controlled Trials as Topic
Abstract: International audience; Randomized trials are frequently used in clinical research and considered the gold standard, but they are less common in population health intervention research (PHIR). We discuss issues that are sometimes shared and sometimes distinct between PHIR and clinical research, notably the randomization unit, design, standardization of the intervention, outcome(s) and ethical issues. In the end, both PHIR and clinical research share the common aim of assessing interventions, and randomized trials should be more widely used in PHIR, provided that how they are planned and conducted is adapted to the PHIR context.
Published: 2021

17. Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial

Author: Raoul Desbriere, Olivier Parant, Caroline Diguisto, Chloé Arthuis, Norbert Winer, Bruno Giraudeau, Patrick Rozenberg, Gael Beucher, Guillaume Ducarme, Christophe Poncelet, Cyrille Faraguet, René Gabriel, Jacob Hannigsberg, Denis Gallot, Franck Perrotin, Céline Chauleur, Amélie Le Gouge, Helene Isly, Lallemant, Christopher, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris 13 (UP13), Centre Hospitalier René Dubos [Pontoise], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU - BREST - Service de Gynécologie-Obstétrique et Chirurgie, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), 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), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Saint-Joseph [Marseille], Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gynécologie Obstétrique, Centre hospitalier de Chartres (Chartres), Hôpitaux de Chartres [Chartres], Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CHU Pontchaillou [Rennes], Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie-Obstétrique [CHRU Tours], 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), CHU Toulouse [Toulouse], Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service de gynécologie-obstétrique [Tours], CIC Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Ingénierie et Santé (CIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Service de Gynécologie et Obstétrique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Maternal Health, Peptide Hormones, Silicones, Cardiovascular Medicine, Oxytocin, Biochemistry, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, Heart Rate, Oxytocics, Medicine and Health Sciences, Pregnancy, Prolonged, 030212 general & internal medicine, 030219 obstetrics & reproductive medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Vaginal delivery, Obstetrics, Compilcation, Obstetrics and Gynecology, food and beverages, Ripening, Neurochemistry, General Medicine, 3. Good health, Chemistry, medicine.anatomical_structure, Obstetric Procedures, Physical Sciences, Gestation, Engineering and Technology, Medicine, Female, France, Neurochemicals, Research Article, Biotechnology, Pessary, Adult, medicine.medical_specialty, Catheters, Bishop score, Cardiology, Bioengineering, Surgical and Invasive Medical Procedures, Guidelines, Dinoprostone, Cardiovascular Pharmacology, 03 medical and health sciences, medicine, Humans, Labor, Induced, Cervix, Pharmacology, business.industry, Cesarean Section, Chemical Compounds, Biology and Life Sciences, Pessaries, medicine.disease, Delivery, Obstetric, Hormones, Health Care, Women's Health, Medical Devices and Equipment, Health Statistics, Morbidity, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cervical Ripening, Neuroscience
Abstract: Background Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2). Methods and findings This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks’ gestation, a Bishop score, In this trial, Caroline Diguisto and colleagues compare two methods for addressing non-reassuring fetal status in caesarian deliveries., Author summary Why was this study done? Induction of labour may be necessary when pregnancies reach 41 weeks of gestation. Ripening methods include mechanical and pharmacological options and both are currently used in pregnancies that reach 41 weeks of gestation. Mechanical cervical ripening leads to less uterine tachysystole and less fetal heart rate anomalies than pharmacological methods. Whether mechanical methods are associated with reduced perinatal morbidity in prolonged pregnancies in comparison with pharmacological methods needed to be investigated by a sufficiently powered randomised trial. What did the researchers do and find? We conducted a trial to compare cervical ripening with a silicone double-balloon catheter (mechanical method) to cervical ripening with a vaginal dinoprostone slow-release system (pharmacological method) among women with prolonged pregnancies. We did not find that cervical ripening with a silicone double-balloon catheter was superior to cervical ripening with a vaginal dinoprostone slow-release system to reduce the rate of cesarean for nonreassuring fetal heart rate and overall maternal and neonatal morbidity. What do these findings mean? There is no evidence to justify preferring mechanical cervical ripening over pharmacological cervical ripening in pregnancies that have reached 41 weeks.
Published: 2021

18. Perceived inequity, professional and personal fulfillment by women intensivists in France

Author: Caroline Hauw-Berlemont, Cécile Aubron, Nadia Aissaoui, Laetitia Bodet-Contentin, Florence Boissier, Muriel Sarah Fartoukh, Mercedes Jourdain, Julien Le Marec, Julia Pestel, Charlotte Salmon Gandonnière, Fabienne Tamion, Olfa Hamzaoui, FEMMIR Group for the SRLF Trial Group, HAL-SU, Gestionnaire, Service de Pneumologie et Soins Intensifs [CHU HEGHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Anesthésie réanimation [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], CHU Rouen, Normandie Université (NU), AP-HP - Hôpital Antoine Béclère [Clamart], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Quality of life, medicine.medical_specialty, [SHS.SOCIO] Humanities and Social Sciences/Sociology, education, Intensivist, Personal life, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), 5. Gender equality, Intensive care, Medicine, 030212 general & internal medicine, Mailing list, Work–life balance, 10. No inequality, Work-life balance, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SHS.SOCIO]Humanities and Social Sciences/Sociology, business.industry, RC86-88.9, 030208 emergency & critical care medicine, Medical emergencies. Critical care. Intensive care. First aid, 16. Peace & justice, [SHS.GENRE] Humanities and Social Sciences/Gender studies, Family medicine, Workforce, Harassment, Women in medicine, business, [SHS.GENRE]Humanities and Social Sciences/Gender studies, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Women intensivists
Abstract: Background The medical workforce has been feminized for the last two decades worldwide. Nonetheless, women remain under-represented among intensivists. We conducted a survey among French women intensivists to assess their professional and personal quality of life and their perception of potential gender discrimination at work. Methods We conducted an observational descriptive study by sending a survey, designed by the group FEMMIR (FEmmes Médecins en Médecine Intensive Réanimation), to women intensivists in France, using primarily the Société de Réanimation de Langue Française (SRLF) mailing list. The questionnaire was also available online between September 2019 and January 2020 and women intensivists were encouraged to answer through email reminders. It pertained to five main domains, including demographic characteristics, work position, workload and clinical/research activities, self-fulfillment scale, perceived discrimination at work and suggested measures to implement. Results Three hundred and seventy-one women responded to the questionnaire, among whom 16% had an academic position. Being a woman intensivist and pregnancy were both considered to increase difficulties in careers’ advancement by 31% and 73% of the respondents, respectively. Almost half of the respondents (46%) quoted their quality of life equal to or lower than 6 on a scale varying from 1 (very bad quality of life) to 10 (excellent quality of life). They were 52% to feel an imbalance between their personal and professional life at the cost of their personal life. Gender discrimination has been experienced by 55% of the respondents while 37% confided having already been subject of bullying or harassment. Opportunities to adjust their work timetable including part-time work, better considerations for pregnant women including increasing the number of intensivists and the systematic replacement during maternity leave, and the respect of the law regarding the paternity leave were suggested as key measures to enable better professional and personal accomplishment by women intensivists. Conclusion In this first large French survey in women intensivists, we pointed out issues felt by women intensivists that included an imbalance between professional and personal life, a perceived loss of opportunity due to the fact of being a woman, frequent reported bullying or harassment and a lack of consideration of the needs related to pregnancy and motherhood.
Published: 2021

19. Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study

Author: Damien Contou, Gwenhaël Colin, Brendan Travert, Sébastien Jochmans, Marie Conrad, Jean-Baptiste Lascarrou, Benoit Painvin, Alexis Ferré, David Schnell, Béatrice La Combe, Rémi Coudroy, Stephan Ehrmann, Jérôme Rambaud, Arnaud Wiedemann, Pierre Asfar, Pierre Kalfon, Emmanuel Guérot, Sébastien Préau, Laurent Argaud, Florence Daviet, Jean Dellamonica, Audrey Dupont, Muriel Fartoukh, Toufik Kamel, Gaetan Beduneau, Florence Canouï-Poitrine, Emmanuelle Boutin, Gérard Lina, Armand Mekontso Dessap, Anne Tristan, Nicolas de Prost, French m-TSS Study Group, Centre Hospitalier Victor Dupouy, CH Départemental Vendée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Melun (CHM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Laboratoire Lasers, Plasmas et Procédés photoniques (LP3), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Angoulême (CH Angoulême), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation polyvalente [Chartres], Hôpital Louis Pasteur [Chartres], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation (ORLEANS - Réa), Centre Hospitalier Régional d'Orléans (CHRO), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), 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 Henri Mondor, CarMeN, laboratoire, Centre Hospitalier de Melun, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, 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 Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Staphylococcus aureus, medicine.medical_specialty, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Disease, law.invention, Sepsis, Menstruation, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Intensive care, medicine, Humans, 030212 general & internal medicine, Child, menstrual toxic shock syndrome, Retrospective Studies, Superantigens, Critically ill, business.industry, Medical record, Tracheal intubation, Toxic shock syndrome, Retrospective cohort study, Staphylococcal Infections, tampon, bacterial infections and mycoses, Institutional review board, medicine.disease, Shock, Septic, Intensive care unit, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Infectious Diseases, Icu, Female, Observational study, menstruation, business
Abstract: Background Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. Methods This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. Results In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. Conclusions In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.
Published: 2021

20. Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL

Author: Gaël Piton, Arnaud W. Thille, Damien Contou, Laura Federici, Bertrand Guidet, Jean Reignier, Julie Badin, Erwan I'her, Dalila Benzekri-Llefevre, Pascal Beuret, Riad Chelha, Suela Demiri, Christophe Vinsonneau, Michel Djibré, Juliette Masse, Nicolas Terzi, Francois Thouy, Juliette Audibert, Olivier Lesieur, Stephan Ehrmann, Hassene Rahmani, Alexandre Boyer, Saad Nseir, Denis Frasca, Christophe Girault, Jean-Pierre Frat, René Robert, Martial Thyrault, Jean-Pierre Quenot, Laurent Argaud, Christophe Guitton, Didier Thevenin, Nadia Aissaoui, Khaldoune Kuteifan, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier de Blois (CH Blois), CHU Rouen, Normandie Université (NU), Centre Hospitalier Le Mans (CH Le Mans), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Roanne (CH Roanne), CH de Roanne, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional d'Orléans (CHRO), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Strasbourg (UNISTRA), CHU Strasbourg, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Saint-Louis de La Rochelle (CH La Rochelle), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Lens, Centre Hospitalier Victor Dupouy, CHU Grenoble, Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Hospitalier Nord Essonne [Longjumeau], Centre Hospitalier de Béthune Beuvry (CH Béthune Beuvry), Hôpital Louis Pasteur [Chartres], Université catholique de Lille (UCL), Groupe hospitalier Pellegrin, CHU Saint-Antoine [AP-HP], Centre Hospitalier Privé Claude Galien - Ramsay Santé, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Blois (CHB), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life, law, Informed consent, Oxygen therapy, medicine, Humans, respiratory medicine (see thoracic medicine), 030212 general & internal medicine, Prospective Studies, Prospective cohort study, adult intensive & critical care, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, Intensive Care, General Medicine, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Oxygen, Intensive Care Units, 030228 respiratory system, medical ethics, Propensity score matching, Emergency medicine, Quality of Life, Observational study, business, Respiratory Insufficiency, Cohort study
Abstract: IntroductionA palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.Methods and analysisThis is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.Ethics and disseminationThe study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03673631
Published: 2021

21. Childhood Trauma increases suicidal behaviour in a treatment-resistant depression population: a FACE-DR report

Author: Antoine Yrondi, Guillaume Vaiva, Michel Walter, Thierry D Amato, Frank Bellivier, Djamila Bennabi, Thierry Bougerol, Vincent Camus, Olivier Doumy, Jean-Baptiste Genty, Emmanuel Haffen, Jérôme Holtzmann, Mathilde Horn, Christophe Lançon, Marion Leboyer, Pierre-Michel Llorca, Julia Maruani, Rémi Moirand, Fanny Molière, Jean Petrucci, Raphaelle Richieri, Ludovic Samalin, Laurent Schmitt, Florian Stephan, Philippe Courtet, Wissam El-Hage, Bruno Aouizerate, B. Aouizerate, D. Bennabi, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, H. Laouamri, Karmene Souryis, L. Mallet, L. Yon, J. Petrucci, J.B. Genty, A. Yrondi, D. Pierre, L. Schmitt, M. Sarrail, I. Ryff, E. Beuchet, G. Tio, C. Cappe, E. Clerc, M. Garnier, R.M. Honciuc, E. Allauze, O. Blanc, F. Bellivier, N. Allaili, I. Nieto, J. Meheust, Y. Sunthavy, J. Maruani, T. Bougerol, M. Polosan, P. Courvoisier, J. Holtzmann, B. Fredembach, S. Foubert-Andreani, V. Camus, W. El Hage, T. D’Amato, F. Haesebaert, C. Dubien, M. Lefebvre, A. Meznad, J. Brunelin, R. Moirand, O. Doumy, C. Lancon, R. Richieri, P. Peri, M. Faugere, C. Faget-Agius, P. Courtet, J.P. Boulenger, F. Moliere, F. Stephan, M. Walter, C. Mesmeur, G. Vaiva, M. Horn, Fondation FondaMental [Créteil], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital de Bohars - CHRU Brest (CHU - BREST ), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Henri Mondor, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Charles Perrens [Bordeaux], CHU Henri Mondor [Créteil], CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Depressive disorders, MESH: Depression, MESH: Violence, Population, Poison control, Violence, Suicide prevention, Childhood trauma, MESH: Depressive Disorder, Treatment-Resistant, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Rating scale, Surveys and Questionnaires, Humans, Medicine, MESH: Surveys and Questionnaires, Risk factor, education, Suicidal ideation, Childhood neglect, Biological Psychiatry, education.field_of_study, MESH: Humans, MESH: Suicidal Ideation, Depression, business.industry, Childhood abuse, CTQ tree, 3. Good health, 030227 psychiatry, Suicide, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Treatment-resistant depression, medicine.symptom, Columbia Suicide Severity Rating Scale, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.
Published: 2021

22. Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial

Author: Olivier Casasnovas, Thierry Lamy, Catherine Thieblemont, Pierre Feugier, Clementine Joubert, Steven Le Gouill, Kamal Bouadballah, Remy Gressin, Hervé Tilly, Anne Moreau, Emmanuel Gyan, Gandhi Damaj, Hervé Maisonneuve, Olivier Hermine, Benoit Tessoulin, François Lemonnier, Lucie Oberic, David Chiron, Hacene Zerazhi, Vincent Ribrag, Eric Van Den Neste, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de gastro-entérologie, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], CHU Grenoble, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Henri Duffaut (Avignon), Hôpital Henri Mondor, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Cliniques Universitaires Saint-Luc [Bruxelles], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Chard-Hutchinson, Xavier
Subjects: Oncology, Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Lymphoma, Mantle-Cell, Transplantation, Autologous, Disease-Free Survival, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Autologous transplantation, Humans, Prospective Studies, Transplantation, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Oxaliplatin, [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, Mantle cell lymphoma, Rituximab, Cisplatin, business, 030215 immunology, medicine.drug
Abstract: National audience; LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.
Published: 2021

23. T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX)

Author: Jean-Paul Mira, Jeremy Bourenne, Agathe Delbove, René Robert, Gaetan Beduneau, Jean-Pierre Frat, Jérôme Devaquet, Arnaud Gacouin, Laurence Dangers, Nicolas Terzi, Stéphanie Ragot, Guylaine Labro, Antoine Romen, Gael Pradel, Christophe Leroy, Jean Reignier, Laurent Argaud, Rémi Coudroy, Quentin Levrat, Stephan Ehrmann, Jean-Pierre Quenot, Emmanuel Vivier, Guillaume Lacave, Christophe Guitton, Marie-Ange Azais, Alexandre Lautrette, Mai-Anh Nay, Anahita Rouzé, Damien Contou, Martin Dres, Gwenaël Prat, Jean Dellamonica, Arnaud W. Thille, Nicholas Sedillot, Béatrice Lacombe, Université de Lille, CNRS, Centre hospitalier universitaire de Poitiers [CHU Poitiers], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], Centre Hospitalier Victor Dupouy, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier de Pau, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Versailles André Mignot [CHV], CHU Dijon, CIC - CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] [CHU], CHRU Brest - Service de Réanimation Médicale [CHU - BREST - Réa Med], Centre Hospitalier Emile Muller [Mulhouse] [CH E.Muller Mulhouse], Centre hospitalier universitaire de Nantes [CHU Nantes], Service d'anesthésie et réanimation chirurgicale [Nantes], Service de réanimation médicale [CHU Rouen], Centre Hospitalier Universitaire de Nice [CHU Nice], Centre Hospitalier Régional d'Orléans [CHRO], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre hospitalier Bretagne Atlantique (Morbihan) [CHBA], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Hôpital Edouard Herriot [CHU - HCL], Hôpital Foch [Suresnes], Centre hospitalier Saint Joseph - Saint Luc [Lyon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon [CHD Vendée], Centre Hospitalier Emile Roux [AP-HP], INSERM CIC 0802 [INSERM - CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Félix-Guyon [Saint-Denis, La Réunion, France], Centre Hospitalier de Versailles André Mignot (CHV), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Henri Mondor d'Aurillac, Unité de soins intensifs médicaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHRU Brest - Service de Réanimation Médicale (CHU - BREST - Réa Med), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Fleyriat [Bourg en Bresse], Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hospices Civils de Lyon (HCL), Centre Hospitalier de La Rochelle (CHR), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, 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), REVA research network, CarMeN, laboratoire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), 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 Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pressure support ventilation, law.invention, Spontaneous breathing trial, Positive-Pressure Respiration, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, medicine, respiratory medicine (see thoracic medicine), Humans, 030212 general & internal medicine, adult intensive & critical care, respiratory physiology, Mechanical ventilation, business.industry, Intensive Care, General Medicine, Intensive care unit, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], 030228 respiratory system, Anesthesia, Breathing, Airway Extubation, Medicine, France, business, Ventilator Weaning
Abstract: IntroductionIn intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90.Ethics and disseminationThe study has been approved by the central ethics committee ‘Ile de France V’ (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04227639.
Published: 2020

24. The minimal perceived change: a formal model of the responder definition according to the patient's meaning of change for patient-reported outcome data analysis and interpretation

Author: Antoine Vanier, Véronique Sébille, Myriam Blanchin, Jean-Benoit Hardouin, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Malbec, Odile, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Data Analysis, Medicine (General), Patient-Reported Outcomes, Psychometrics, [SDV]Life Sciences [q-bio], Emotions, Minimal Clinically Important Difference, Clinical research, Minimal Important Difference, [SDV] Life Sciences [q-bio], R5-920, Health-Related Quality of Life, Surveys and Questionnaires, Quality of Life, Responder Definition, Humans, Theory, sense organs, Patient Reported Outcome Measures, skin and connective tissue diseases, Estimation, Research Article, Model
Abstract: International audience; Background: Patient-Reported Outcomes (PROs) are standardized questionnaires used to measure subjective outcomes such as quality of life in healthcare. They are considered paramount to assess the results of therapeutic interventions. However, because their calibration is relative to internal standards in people's mind, changes in PRO scores are difficult to interpret. Knowing the smallest value in the score that the patient perceives as change can help. An estimator linking the answers to a Patient Global Rating of Change (PGRC: a question measuring the overall feeling of change) with change in PRO scores is frequently used to obtain this value. In the last 30 years, a plethora of methods have been used to obtain these estimates, but there is no consensus on the appropriate method and no formal definition of this value. Methods: We propose a model to explain changes in PRO scores and PGRC answers. Results: A PGRC measures a construct called the Perceived Change (PC), whose determinants are elicited. Answering a PGRC requires discretizing a continuous PC into a category using threshold values that are random variables. Therefore, the populational value of the Minimal Perceived Change (MPC) is the location parameter value of the threshold on the PC continuum defining the switch from the absence of change to change. Conclusions: We show how this model can help to hypothesize what are the appropriate methods to estimate the MPC and its potential to be a rigorous theoretical basis for future work on the interpretation of change in PRO scores.
Published: 2020

25. 4C3 Human Monoclonal Antibody: A Proof of Concept for Non-pathogenic Proteinase 3 Anti-neutrophil Cytoplasmic Antibodies in Granulomatosis With Polyangiitis

Author: Granel, Jérôme, Lemoine, Roxane, Morello, Eric, Gallais, Yann, Mariot, Julie, Drapeau, Marion, Musnier, Astrid, Poupon, Anne, Pugnière, Martine, Seren, Seda, Nouar, Dalila, Gouilleux-Gruart, Valérie, Watier, Herve, Korkmaz, Brice, Hoarau, Cyrille, EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours, Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MAbSilico SAS, Dynamiques de populations multi-échelles pour des systèmes physiologiques (MUSCA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Region Centre-Val-de-Loire (program Ambition Research and Development 'Biopharmaceuticals'), University of Tours, ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010), Université de Tours (UT), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Glycosylation, human neutrophils, biologie computationnelle, [SDV]Life Sciences [q-bio], Myeloblastin, Immunology, Antibody Affinity, Proof of Concept Study, Neutrophil Activation, Antibodies, Antineutrophil Cytoplasmic, Cell Line, Epitopes, immune system diseases, Antibody Specificity, Humans, Immunology and Allergy, cardiovascular diseases, skin and connective tissue diseases, Aged, Original Research, B-Lymphocytes, epitope, granulomatosis with polyangiitis, Antibodies, Monoclonal, Middle Aged, respiratory tract diseases, proteinase 3, Case-Control Studies, anti-neutrophil cytoplasmic antibodies, Female, Binding Sites, Antibody, Biomarkers, Epitope Mapping
Abstract: International audience; Granulomatosis with polyangiitis (GPA) is a severe autoimmune vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) mainly targeting proteinase 3 (PR3), a neutrophilic serine proteinase.PR3-ANCA binding to membrane-bound PR3 on neutrophils induce their auto-immune activation responsible for vascular lesions. However, the correlation between PR3-ANCA level and disease activity remains inconsistent, suggesting the existence of non-pathogenic PR3-ANCA. In order to prove their existence, we immortalized B lymphocytes from blood samples of GPA patients in remission having persistent PR3-ANCA to isolate non-activating PR3-ANCA. We obtained for the first time a non-activating human IgG1κanti-PR3 monoclonal antibody (mAb) named 4C3. This new mAb binds soluble PR3 with a high affinity and membrane-bound PR3 on an epitope close to the PR3 hydrophobic patch and in the vicinity of the active site. 4C3 is able to bind FcγRIIA and FcγRIIIB and has a G2F glycosylation profile on asparagine 297. 4C3 did not induce activation of neutrophils and could inhibit human polyclonal PR3-ANCA-induced activation suggesting that 4C3 is non-pathogenic This characteristic relies on the recognized epitope on PR3 rather than to the Fc portion properties. The existence of non-pathogenic PR3-ANCA, which do not activate neutrophils, could explain the persistence of high PR3-ANCA levels in some GPA patients in remission and why PR3-ANCA would not predict relapse. Finally, these results offer promising perspectives particularly regarding the understanding of PR3-ANCA pathogenicity and the development of new diagnostic and therapeutic strategies in GPA
Published: 2020
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26. Expert consensus-based clinical practice guidelines management of intravascular catheters in the intensive care unit

Author: Alain Lepape, Michel Slama, Louis Bernard, Virginie Maxime, Michael Darmon, Jean-Pierre Quenot, Olivier Leroy, Matthieu Schmidt, Marc Leone, Walter Zingg, Zied Merchaoui, Antoine Roch, Jean-François Timsit, Eric Desruennes, Bertrand Souweine, Jean-Christophe Lucet, Julien Baleine, Benoit Misset, Jean-Jacques Parienti, Silvia Calvino-Gunther, Laetitia Bodet-Contentin, Jean Dellamonica, Jean-Ralph Zahar, Olivier Mimoz, Gestionnaire, Hal Sorbonne Université, Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Nord [CHU - APHM], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Liège, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Lille Nord de France (COMUE)-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Bacteremia, Review, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Sepsis, Intensive care, Medicine, 030212 general & internal medicine, Critically ill, Vein, Brachiocephalic vein, Dialysis, ddc:616, Catheter, 0303 health sciences, 030306 microbiology, business.industry, Prevention, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, Arterial catheter, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Clinical Practice, medicine.anatomical_structure, Emergency medicine, Infection, business
Abstract: The French Society of Intensive Care Medicine (SRLF), jointly with the French-Speaking Group of Paediatric Emergency Rooms and Intensive Care Units (GFRUP) and the French-Speaking Association of Paediatric Surgical Intensivists (ADARPEF), worked out guidelines for the management of central venous catheters (CVC), arterial catheters and dialysis catheters in intensive care unit. For adult patients: Using GRADE methodology, 36 recommendations for an improved catheter management were produced by the 22 experts. Recommendations regarding catheter-related infections’ prevention included the preferential use of subclavian central vein (GRADE 1), a one-step skin disinfection(GRADE 1) using 2% chlorhexidine (CHG)-alcohol (GRADE 1), and the implementation of a quality of care improvement program. Antiseptic- or antibiotic-impregnated CVC should likely not be used (GRADE 2, for children and adults). Catheter dressings should likely not be changed before the 7th day, except when the dressing gets detached, soiled or impregnated with blood (GRADE 2− adults). CHG dressings should likely be used (GRADE 2+). For adults and children, ultrasound guidance should be used to reduce mechanical complications in case of internal jugular access (GRADE 1), subclavian access (Grade 2) and femoral venous, arterial radial and femoral access (Expert opinion). For children, an ultrasound-guided supraclavicular approach of the brachiocephalic vein was recommended to reduce the number of attempts for cannulation and mechanical complications. Based on scarce publications on diagnostic and therapeutic strategies and on their experience (expert opinion), the panel proposed definitions, and therapeutic strategies.
Published: 2020

27. Seven Years Leptospirosis Follow-Up in a Critical Care Unit of a French Metropolitan Hospital; Role of Real Time PCR for a Quick and Acute Diagnosis

Author: Stephan Ehrmann, Olivier Bahuaud, Adeline Pastuszka, Cécile Le Brun, Philippe Lanotte, Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, and Chanteloup, Nathalie Katy
Subjects: medicine.medical_specialty, Diagnostic methods, diagnosis, [SDV]Life Sciences [q-bio], polymerase chain reaction, 030231 tropical medicine, lcsh:Medicine, Disease, intensive care unit, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Antibiotic therapy, medicine, leptospirosis, Sampling (medicine), 0303 health sciences, 030306 microbiology, business.industry, lcsh:R, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Leptospirosis, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Real-time polymerase chain reaction, Emergency medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: International audience; (1) Background: Leptospirosis infection can lead to multiple organ failure, requiring hospitalization in an intensive care unit for supportive care, along with initiation of an adapted antibiotic therapy. Achieving a quick diagnosis is decisive in the management of these patients. (2) Methods: We present here a review of leptospirosis cases diagnosed in the intensive care unit of our hospital over seven years. Clinical and biological data were gathered, and we compared the differences in terms of diagnostic method. (3) Results: Molecular biology method by Polymerase Chain Reaction (PCR) allowed quick and reliable diagnosis when performed in the first days after the symptoms began. Moreover, we identified that sampling blood and urine for PCR was more efficient than performing PCR on only one type of biological sample. (4) Conclusions: Our results confirm the efficiency of PCR for the quick diagnosis of leptospirosis and suggest that testing both blood and urine early in the disease might improve diagnosis.
Published: 2020

28. Ribavirin for Hepatitis E Virus Infection After Organ Transplantation

Author: Kamar, Nassim, Legrand-Abravanel, Florence, Behrendt, Patrick, Hofmann, Jörg, Pageaux, Georges Phillippe, Barbet, Christelle, Moal, Valerie, Couzi, Lionel, Horvatits, Thomas, de Man, Robert, Cassuto, Elisabeth, Elsharkawy, Ahmed, Riezebos-Brilman, Annelies, Scemla, Anne, Hillaire, Sophie, Donnelly, Mhairi, Radenne, Sylvie, Sayegh, Johnny, Garrouste, Cyril, Dumortier, Jérôme, Glowaki, François, Matignon, Marie, Coilly, Audrey, Figueres, Lucile, Mousson, Christiane, Minello, Anne, Dharancy, Sébastien, Rerolle, Jean Philippe, Lebray, Pascal, Etienne, Isabelle, Perrin, Peggy, Choi, Mira, Olivier, Marion, Izopet, Jacques, Bellière, J, Cointault, O., del Bello, Arnaud, Espostio, L, Hebral, A, Lavayssière, L, Lhomme, S, Mansuy, J, Wedemeyer, H, Nickel, P, Bismuth, M., Stefic, K, Buchler, M., D’alteroche, L, Colson, P., Bufton, S, Ramière, C, Trimoulet, P., Pischke, S, Todesco, E, Sberro Soussan, R, Legendre, C, Mallet, V., Johannessen, I, Simpson, K, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Bordeaux [Bordeaux], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Universitaire de Nice (CHU Nice), University Hospitals Birmingham [Birmingham, Royaume-Uni], University Medical Center Groningen [Groningen] (UMCG), Réseau CENTAURE, Hôpital Foch [Suresnes], Royal Infirmary of Edinburgh, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Paul Brousse, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Hôpital Claude Huriez [Lille], CHU Lille, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service d'Hépato-Gastro-Entérologie [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 Rouen, Normandie Université (NU), CHU Strasbourg, Département de Néphrologie et Transplantation d'organes [Toulouse], Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Gastroenterology & Hepatology, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Université de Montpellier (UM)-CHU Saint-Eloi, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de néphrologie et immunologie clinique, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: 0301 basic medicine, MESH: Antiviral Agents / therapeutic use, Sofosbuvir, viruses, medicine.disease_cause, Gastroenterology, THERAPY, Organ transplantation, Hepatitis E virus / genetics, Hepatitis E / drug therapy, Humans, chemistry.chemical_compound, 0302 clinical medicine, Hepatitis E virus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, MUTATION, MESH: Hepatitis E* / drug therapy, POLYMERASE, organ transplantation, virus diseases, MESH: Ribavirin / therapeutic use, Anemia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Hepatitis E, anemia, 3. Good health, PREDICTS, Sustained virological response, Infectious Diseases, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, 030211 gastroenterology & hepatology, sustained virological response, medicine.drug, Microbiology (medical), medicine.medical_specialty, ribavirin, MESH: Organ Transplantation / adverse effects, RNA, Viral Retrospective Studies, Ribavirin / therapeutic use, Alpha interferon, MESH: Organ Transplantation* / adverse effects, hepatitis E virus, Antiviral Agents, Virus, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Ribavirin, Retrospective Studies, MESH: Hepatitis E virus* / genetics, MESH: Humans, business.industry, Retrospective cohort study, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, IN-VITRO, medicine.disease, digestive system diseases, 030104 developmental biology, chemistry, SOFOSBUVIR, HEV, REPLICATION, INTERFERON-ALPHA, business
Abstract: Background Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response. Methods Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months. Results After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event. Conclusions This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance. This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.
Published: 2020

29. Left amygdala volume and brain tissue pulsatility are associated with neuroticism: an MRI and ultrasound study

Author: Robert Courtois, Valérie Gissot, Wissam El-Hage, Vincent Camus, Jean-Pierre Remenieras, Jean-Philippe Cottier, Bruno Brizard, Frédéric Patat, Marta Andrea Siragusa, Thomas Desmidt, Paul-Armand Dujardin, Frédéric Andersson, Thomas Rufin, Catherine Belzung, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Qualité de vie et Santé psychologique [Tours] (QualiPsy - E.E. 1901), Université de Tours (UT), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Psychiatrique Universitaire [Tours], Université Francois Rabelais [Tours], UMR930, Imagerie et cerveau, Laboratoire Ultrasons Signaux et Instrumentation (LUSI), Laboratoire Ultrasons Signaux et Instrumentation (LUSSI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Courtois, Robert
Subjects: medicine.medical_specialty, Cognitive Neuroscience, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SHS.PSY]Humanities and Social Sciences/Psychology, Brain tissue pulsatility, Amygdala volume, 050105 experimental psychology, [SHS.PSY] Humanities and Social Sciences/Psychology, 03 medical and health sciences, Behavioral Neuroscience, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Risk factor, ComputingMilieux_MISCELLANEOUS, Depression (differential diagnoses), Neuroradiology, 2. Zero hunger, Neuroticism, Tissue pulsatility imaging, medicine.diagnostic_test, business.industry, 05 social sciences, Neuropsychology, Brain, Magnetic resonance imaging, Middle Aged, Amygdala, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Neurology, Cerebral blood flow, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cerebrovascular Circulation, Brain size, Cardiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Brain changes associated with the personality trait of neuroticism have been partly elucidated. While subcortical brain volume changes, especially a larger amygdala, appear consistent in high neuroticism, functional changes, such as cerebral blood flow (CBF) differences, have shown conflicting results, possibly because of the limitations in methods of CBF measurement. In our study, we investigated changes in amygdala volume and CBF-related function associated with neuroticism in healthy and depressed subjects using both conventional magnetic resonance imaging (MRI) measures of brain volume and the innovative technique of ultrasound Tissue Pulsatility Imaging (TPI), which has a high level of detection in measuring brain tissue pulsatility (BTP). Middle-aged females with depression (n = 25) and without depression (n = 25) underwent clinical examination, magnetic resonance imaging (MRI) and ultrasound assessment (TPI). Neuroticism was positively associated with left amygdala volume and mean BTP in individuals without depression, in both simple and multiple regressions that included potential confounding factors such as age and body mass index. No association was found in the depressed group. We confirmed the role of the left amygdala in the brain physiology of neuroticism in nondepressed individuals. Moreover, we identified a novel mechanism associated with high neuroticism, namely BTP, that may reflect greater CBF and account for the increased risk of cerebrovascular disease in individuals with high neuroticism. Because neuroticism is considered a risk factor for depression, our paper provides potential objective biomarkers for the identification of subjects at risk for depression.
Published: 2020

30. Les directives anticipées chez des patients en hémodialyse chronique : étude de faisabilité

Author: Pauline D’Halluin, Maud François, Bénédicte Sautenet, Béatrice Birmelé, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Service de néphrologie et immunologie clinique [CHRU Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)
Subjects: Medical knowledge, education.field_of_study, business.industry, media_common.quotation_subject, [SDV]Life Sciences [q-bio], education, Population, 030232 urology & nephrology, medicine.disease, 3. Good health, 03 medical and health sciences, Patient support, 0302 clinical medicine, Nephrology, Ambulatory, Medicine, Anxiety, Medical emergency, medicine.symptom, business, Autonomy, media_common
Abstract: Respect of patient's autonomy is essential. So that patients are able to write their advance directives in case of a situation where they are unable to make decisions for themselves. Currently, few people have written advance directives. We studied the feasibility of a systematic implementation of advance directives in haemodialysis patients. This prospective, single-center study was conducted in an ambulatory hemodialysis center. There were 4 steps: caregivers survey about advance directives; selection of patients and information about advance directives; writing advance directives with the interested patients; and finally, non-participation causes assessment of the other informed patients. Caregivers are not comfortable with advance directives, and have reluctances: the patient's lack of medical knowledge; the anxiety generated by end-of-life talk. Fifty-six patients (51.6%) were included and received the information. Nine of them wanted to write their advance directives on a suitable form. Eight finalised them (7.4% of the initial population). The majority wanted a therapeutic limitation. Twenty-nine patients, who have received the information about advance directives, didn't want to write them, the main reason was that they felt healthy or that they thought that their relatives would take the right decisions. Eighteen patients left the centre during the study. The development of advance directives requires information and training of caregivers and patient support. Few patients went to the end of the process. The limit of the patient's ability to decide for himself is difficult to define. The role of the doctor is central to accompany the patient during this process.
Published: 2020

31. Research Techniques Made Simple: Randomized~Controlled Trials for Topical Drugs in~Dermatology: When~and How Should We Use a~Within-Person Design?

Author: Agnès Caille, Bruno Giraudeau, Laurence Le Cleach, Annabel Maruani, Mahtab Samimi, Elsa Tavernier, Sophie Leducq, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bruere, Gérard, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Research design, medicine.medical_specialty, Randomization, Administration, Topical, [SDV]Life Sciences [q-bio], Psychological intervention, MEDLINE, Dermatology, Biochemistry, Skin Diseases, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Humans, Medical physics, Molecular Biology, Completely randomized design, Randomized Controlled Trials as Topic, Observer Variation, Cross-Over Studies, business.industry, Cell Biology, Crossover study, 3. Good health, ArtThese, [SDV] Life Sciences [q-bio], 030104 developmental biology, Sample size determination, Research Design, 030220 oncology & carcinogenesis, Sample Size, Dermatologic Agents, business
Abstract: International audience; Topical drugs are often used as first-line treatment for dermatological conditions. Depending on the disease and the drug, three main designs can be used for randomized controlled trials assessing topical drugs: the classical individual parallel design, the cluster randomized design, and designs allowing within-individual comparisons, including the cross-over design (in which patients are randomized to a sequence of interventions) and the within-person design (also called the split-body design). Within-person design can be used to compare different drugs concomitantly in the same patient. Randomization does not concern patients but rather lesions or body sites within patients, and the drugs to be compared are applied to the different lesions (or sites). This design considerably reduces interobservation variability, and thus, the number of patients to be included in the trial (sample size). However, this design has major methodological constraints, especially the need to resolve the problem of a possible carry-across effect. First, we describe the specificities of randomized controlled trials evaluating a topical drug. Second, we present the different designs available and discuss the methodological points that should be considered, especially for a within-person design. Finally, we compare the relevance of the within-person design with that of other trial designs by considering three different scenarios.
Published: 2020

32. The Presence of Renal IgG Deposits in Necrotizing Crescentic Glomerulonephritis Associated with ANCA Is Not Related to Worse Renal Clinical Outcomes

Author: Cécile Vigneau, Matthias Büchler, Nolwenn Rabot, Marie-Christine Machet, Vianney Charpy, Jean-François Augusto, Jean-Michel Halimi, Christelle Barbet, Fadi Fakhouri, Caroline Dudreuilh, Philippe Gatault, Marion Chapal, Department of Nephrology [Le Kremlin-Bicêtre], Institut francilien de recherche en néphrologie et transplantation [Le Kremlin-Bicêtre] (IFRNT), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), CHU Pontchaillou [Rennes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de néphrologie, Le Bihan, Sylvie, Service de néphrologie et immunologie clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Service néphrologie et immunologie clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de Néphrologie, Immunologie clinique, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: medicine.medical_specialty, ANCA - associated vasculitis, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Gastroenterology, Immunoglobulin G, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Necrotizing RPGN, 030212 general & internal medicine, Acute tubular necrosis, Anti-neutrophil cytoplasmic antibody, Kidney, biology, business.industry, Autoantibody, Glomerulonephritis, GPA, medicine.disease, dual antibody-positive disease, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, biology.protein, Anti-GBM disease, business, Vasculitis, Systemic vasculitis, Research Article
Abstract: International audience; Introduction:Diagnosing the etiology of a rapidly progressive glomerulonephritis is of vital importance to guide appropriate therapeutic management. This case highlights the complexity involved in establishing diagnosis when presentation is atypical. In certain cases diagnosis cannot be established based on clinical presentation or biopsy findings alone, and critical analysis of biopsy findings in context of clinical presentation is crucial to guide the clinical decision-making process.Case presentation: A 47-year-old Hispanic male with history of granulomatosis with polyangiitis (GPA) in remission on azathioprine, presented with fatigue and lethargy. Physical examination was unremarkable. Laboratory data revealed elevated creatinine and otherwise normal electrolytes. Urinalysis showed numerous dysmorphic red blood cells with few red cell casts. His serologic results were all negative except anti-proteinase-3 antibody at very low titers. Kidney biopsy showed necrotizing crescentic glomerulonephritis with linear immunoglobulin G staining along the basement membrane.Conclusion: This case presented conflicting serologic and histopathologic findings. The presence of anti-proteinase-3 antibody supported diagnosis of recurrence of GPA. However, linear staining of immunoglobulin G (IgG) on immunofluorescence (IF) staining of renal biopsy supported anti-glomerular basement membrane (GBM) disease. The treatment of anti-GBM disease and GPA both involve immunosuppression with prednisone and cyclophosphamide. However, patients with anti-GBM disease are also treated with plasmapheresis early in the disease presentation to prevent further damage. The patient with GPA, on the other hand, was shown to benefit from plasmapheresis only in the case of severe renal disease (serum creatinine level more than 5 mg/dL) or pulmonary hemorrhage. In this case, since the patient did not have detectable circulating anti-GBM antibody, the decision was made not to proceed with plasmapheresis. The patient was treated with a standard immunosuppressive regimen consisting of prednisone and cyclophosphamide with partial renal recovery at 2 months.
Published: 2020

33. [Tricks and misuses of rapid diagnostic testing for malaria diagnosis]

Author: Victor Mercier, Guillaume Desoubeaux, Éric Bailly, Louis Bernard, Eloi Chevallier, Nathalie Van Langendonck, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Service de néphrologie et immunologie clinique [CHRU Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)
Subjects: 030213 general clinical medicine, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Disease, Rapid diagnostic test, Health Services Misuse, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, LAMP, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Limit of Detection, parasitic diseases, Medicine, Humans, Diagnostic Errors, Malaria, Falciparum, Intensive care medicine, business.industry, Diagnostic Tests, Routine, Diagnostic test, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, medicine.disease, MESH: Humans, Malaria, Falciparum / diagnosis, 3. Good health, Malaria, Diagnosis of malaria, PCR, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Female, business, MESH: Diagnostic Errors, Diagnostic Tests, Routine / methods, Diagnostic Tests, Routine / standards
Abstract: International audience; Molecular biology or immunochromatographic tests are conventionally offered as aids in the routine diagnosis of malaria. However, the interpretation of their results requires a precise knowledge of their limits, both by the biologist and the physician. It is in particular conditioned by thorough interview of the patient in order to seek a history of recent or even older malaria disease. We discuss herein the different usages and how to interpret such diagnostics, through a concrete example of a malaria case which was particularly tough to investigate.; Des tests de biologie moléculaire ou de détection d’antigènes par immunochromatographie (tests de diagnostic rapide ou TDR) sont classiquement proposés comme aides au diagnostic du paludisme en routine. Cependant, l’interprétation de leurs résultats nécessite une connaissance précise de leurs limites, aussi bien par le biologiste que par le clinicien. Elle est en particulier conditionnée par un interrogatoire méticuleux du patient afin de ne pas méconnaître un antécédent d’accès palustre récent ou même plus ancien. Nous discutons ici des différents usages et de l’interprétation de ces outils diagnostiques, en prenant exemple d’un cas de paludisme particulièrement difficile à investiguer.
Published: 2020

34. Posterior Reversible Encephalopathy Syndrome in Clinical Toxicology: A Systematic Review of Published Case Reports

Author: Caroline Victorri-Vigneau, Stephan Ehrmann, Bérenger Largeau, Charlotte Salmon Gandonnière, Clara Cohen, David Boels, Service de Pharmacologie Clinique [CHU Nantes] (SPC), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Pharmacovigilance [Nantes] (CRP), Unité de Toxicologie Clinique et Toxico-surveillance Médicamenteuse [CHU Nantes] (SPC), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d'Évaluation et d'Information sur la Pharmacodépendance et d'Addictovigilance [Nantes] (SPC), Service de Neuroradiologie Diagnostique et Interventionnelle [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), TRial Group for Global Evaluation and Research in SEPsis (TRIGGERSEP), CRICS-TRIGGERSEP, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ehrmann, Stephan
Subjects: Pediatrics, medicine.medical_specialty, Hypertensive encephalopathy, hypertensive encephalopathy, Context (language use), blood–brain barrier, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:RC346-429, leukoencephalopathy syndrome, 03 medical and health sciences, 0302 clinical medicine, Edema, medicine, substance abuse, 030212 general & internal medicine, Risk factor, lcsh:Neurology. Diseases of the nervous system, business.industry, alcohol, Posterior reversible encephalopathy syndrome, medicine.disease, Reversible cerebral vasoconstriction syndrome, 3. Good health, poisoning, Blood pressure, Neurology, Etiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Systematic Review, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical and radiological entity characterized by a typical brain edema. Although several case reports have described PRES in a context of poisoning, to our knowledge, a comprehensive assessment has not been performed. The aim of this systematic review was to raise awareness on poisoning-specific PRES features and to encourage consistent and detailed reporting of substance abuse-and drug overdose-associated PRES. Methods: Medline/PubMed, Web of Science, and PsycINFO were screened through May 31, 2019, to systematically identify case reports and case series describing PRES associated with poisoning (i.e., alcohol, drugs, illicit drugs, natural toxins, chemical substances) in accidental context, intentional overdose, and substance abuse. The methodological quality of eligible case reports/series was assessed. Patients and exposure characteristics were recorded; relevant toxicological, radiological, and clinical data were extracted. Results: Forty-one case reports and one case series reporting 42 unique cases were included. The median time to PRES onset from the start of exposure was 3 days (IQR 2-10). Acute high blood pressure, visual disturbance, and seizure were reported in 70, 55, and 50% of patients, respectively. The initial clinical presentation was alertness disorders in 64% of patients. Nine patients (21%) required mechanical ventilation. One-third of patients had at least one risk factor for PRES such as chronic hypertension (17%) or acute/chronic kidney failure (24%). The main imaging pattern (67%) was the combination of classical parieto-occipital edema with another anatomical region (e.g., frontal, basal ganglia, posterior fossa involvement). Vasogenic edema was found in 86% of patients. Intracranial hemorrhage occurred in 14% of patients. Both brain infarction and reversible cerebral vasoconstriction syndrome were diagnosed in 5% of patients. Three patients (12%, 3/25) had non-reversible lesions on follow-up magnetic resonance imaging. The median time required to hospital discharge was 14 days (IQR 7-18). Mortality and neurological recurrence rate were null. Conclusions: Comorbidities such as chronic hypertension and kidney failure were less frequent than in patients with other PRES etiologies. Imaging analysis did not highlight a specific pattern for poisoning-induced PRES. Although less described, PRES in the context of poisoning, which shares most of the clinical and radiological characteristics of other etiologies, is not to be ignored.
Published: 2020

35. Is the R Coefficient of Interest in Cluster Randomized Trials with a Binary Outcome?

Author: Bruno Giraudeau, Agnès Caille, Sandra Eldridge, Ariane M Mbekwe Yepnang, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Queen Mary University of London (QMUL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bruere, Gérard
Subjects: Statistics and Probability, Epidemiology, Intraclass correlation, [SDV]Life Sciences [q-bio], R coefficient, prevalence, Disease cluster, 01 natural sciences, binary outcome, law.invention, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Randomized controlled trial, law, Statistics, 030212 general & internal medicine, 0101 mathematics, Cluster analysis, cluster, ComputingMilieux_MISCELLANEOUS, Intraclass correlation coefficient, Mathematics, Binary outcome, Outcome (probability), ArtThese, [SDV] Life Sciences [q-bio]
Abstract: In cluster randomized trials, the intraclass correlation coefficient (ICC) is classically used to measure clustering. When the outcome is binary, the ICC is known to be associated with the prevalence of the outcome. This association challenges its interpretation and can be problematic for sample size calculation. To overcome these situations, Crespi et al. extended a coefficient named R, initially proposed by Rosner for ophthalmologic data, to cluster randomized trials. Crespi et al. asserted that R may be less influenced by the outcome prevalence than is the ICC, although the authors provided only empirical data to support their assertion. They also asserted that “the traditional ICC approach to sample size determination tends to overpower studies under many scenarios, calling for more clusters than truly required”, although they did not consider empirical power. The aim of this study was to investigate whether R could indeed be considered independent of the outcome prevalence. We also considered whether sample size calculation should be better based on the R coefficient or the ICC. Considering the particular case of 2 individuals per cluster, we theoretically demonstrated that R is not symmetrical around the 0.5 prevalence value. This in itself demonstrates the dependence of R on prevalence. We also conducted a simulation study to explore the case of both fixed and variable cluster sizes greater than 2. This simulation study demonstrated that R decreases when prevalence increases from 0 to 1. Both the analytical and simulation results demonstrate that R depends on the outcome prevalence. In terms of sample size calculation, we showed that an approach based on the ICC is preferable to an approach based on the R coefficient because with the former, the empirical power is closer to the nominal one. Hence, the R coefficient does not outperform the ICC for binary outcomes because it does not offer any advantage over the ICC.
Published: 2020

36. Efficacy and safety of methotrexate versus placebo as add-on therapy to H1 antihistamines for patients with difficult-to-treat chronic spontaneous urticaria: A randomized, controlled trial

Author: Mahtab Samimi, Angèle Soria, C. Bara, Olivier Chosidow, Hélène Bourgoin, Nathalie Raison-Peyron, Germaine Gabison, Emmanuelle Amsler, Delphine Staumont-Sallé, Sophie Leducq, Catherine Droitcourt, E. Wierzbicka-Hainaut, Nathalie Beneton, Laurent Machet, Anne Grange-Prunier, Emilie Brenaut, Bruno Giraudeau, Annabel Maruani, Hélène Cornillier, Claire Bernier, Agnès Caille, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital 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 Le Mans (CH Le Mans), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie, Centre Hospitalier Universitaire Henri Mondor, Service de Dermatologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Augustin Morvan, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, medicine.medical_treatment, MEDLINE, Dermatology, Placebo, law.invention, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Randomized controlled trial, Quality of life, law, Internal medicine, Medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, 3. Good health, Add on therapy, 030228 respiratory system, Methotrexate, Antihistamine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug
Abstract: International audience
Published: 2020

37. Merkel cell carcinoma of lymph nodes without a skin primary tumor: A potential metastatic neoplasia associated with a brisk immune response

Author: Mahtab Samimi, Guido Bens, Thibault Kervarrec, Gaëlle Fromont, Eva Hainaut-Wierzbicka, J. Zaragoza, David Schrama, Yannick Le Corre, Patrick Michenet, Agnès Caille, Patricia Berthon, François Aubin, Serge Guyétant, Hervé Maillard, Roland Houben, Pauline Gaboriaud, Antoine Touzé, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Département de dermatologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Nantes Université (Nantes Univ), Département de Dermatologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Department of Dermatology (CHU Besançon), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Le Mans (CH Le Mans), University Hospital of Würzburg, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service de dermatologie (CHRU de Tours), Université de Tours (UT), CCSD, Accord Elsevier, Service de Pathologie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Dermatologie, Service de Dermatologie, Department of Dermatology, Venerology and Allergology, Universitätsklinikum Würzburg, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique de Nantes (CIC Nantes), and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Skin Neoplasms, [SDV]Life Sciences [q-bio], Dermatology, epithelial–mesenchymal transition, Merkel cell carcinoma without primary, 030207 dermatology & venereal diseases, 03 medical and health sciences, Merkel cell carcinoma, 0302 clinical medicine, Immune system, medicine, Biomarkers, Tumor, ZEB1, metastasis, Humans, ComputingMilieux_MISCELLANEOUS, business.industry, CD8, lymph node, medicine.disease, Primary tumor, 3. Good health, [SDV] Life Sciences [q-bio], Carcinoma, Merkel Cell, Merkel cell polyomavirus, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Cancer research, Neoplasms, Unknown Primary, Lymph, Lymph Nodes, CD33, business
Abstract: International audience; No abstract available
Published: 2019

38. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol

Author: Jean-Pierre Quenot, Nicolas Grégoire, Stephan Ehrmann, Mai-Anh Nay, Benoit Veber, François Barbier, Jean-Claude Lacherade, Qin Lu, Grégoire Muller, Thierry Boulain, Julie Helms, Marie Leclerc, Pascal Andreu, Gaëtan Plantefève, Deborah Le Pennec, Renaud Respaud, Claire Dahyot-Fizelier, Elsa Tavernier, Martine Ferrandière, Gaetan Beduneau, Laurent Vecellio, Anne Veinstein, Philippe Seguin, Maria Cabrera, Hamid Merdji, David Schnell, Jean-Etienne Herbrecht, Damien Roux, Sigismond Lasocki, Ferhat Meziani, Philippe Lanotte, Mickael Landais, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Les Hôpitaux Universitaires de Strasbourg (HUS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Le Mans (CH Le Mans), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre Hospitalier d'Angoulême (CH Angoulême), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Victor Dupouy, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Départemental Vendée (CHDV), University Hospital of Tours, France, Programme Hospitalier de Recherche Clinique National 2015 of the French Ministry of Health (PHRC-15-260), Association pour la promotion à Tours de la Réanimation Médicale, HAL-SU, Gestionnaire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, medicine.medical_treatment, infectious diseases, Placebo, law.invention, respiratory infections, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Informed consent, law, Administration, Inhalation, medicine, Humans, Multicenter Studies as Topic, Amikacin, adult intensive & critical care, Randomized Controlled Trials as Topic, Mechanical ventilation, clinical trials, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Intensive Care, Ventilator-associated pneumonia, Pneumonia, Ventilator-Associated, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Respiration, Artificial, 3. Good health, Clinical trial, Pneumonia, Treatment Outcome, 030228 respiratory system, Emergency medicine, Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: IntroductionPre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia.Methods and analysisAcademic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee.Ethics and disseminationThe protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals.Trial registration numbersEudraCT 2016-001054-17 and NCT03149640.
Published: 2021

39. BAY 41-4109-mediated aggregation of assembled and misassembled HBV capsids in cells revealed by electron microscopy

Author: Jean-Christophe Meunier, Florian Seigneuret, Roxane Lemoine, Julien Burlaud-Gaillard, Hugues de Rocquigny, Clovis Tauber, Christophe Hourioux, Barbara Testoni, Virgile Rat, Fabien Zoulim, Philippe Roingeard, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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 Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Hepatitis B virus, Pyridines, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, Antiviral Agents, Cell Line, law.invention, Protein Aggregates, 03 medical and health sciences, Capsid, law, Confocal microscopy, Virology, medicine, Humans, Pharmacology, biology, Chemistry, Virus Assembly, virus diseases, Hepatitis B Core Antigens, digestive system diseases, 3. Good health, Microscopy, Electron, Pyrimidines, 030104 developmental biology, medicine.anatomical_structure, Transmission electron microscopy, Cytoplasm, Biophysics, Ultrastructure, biology.protein, Capsid Proteins, Electron microscope, Protein A, Nucleus
Abstract: HBc is a small protein essential for the formation of the icosahedral HBV capsid. Its multiple roles in the replication cycle make this protein a promising target for the development of antiviral molecules. Based on the structure of HBc, a series of HBV assembly inhibitors, also known as capsid assembly modulators, were identified. We investigated the effect of BAY 41–4109, a heteroaryldihydropyrimidine derivative that promotes the assembly of a non-capsid polymer. We showed, by confocal microscopy, that BAY 41–4109 mediated HBc aggregation, mostly in the cytoplasm of Huh7 cells. Image analysis revealed that aggregate size depended on BAY 41–4109 concentration and treatment duration. Large aggregates in the vicinity of the nucleus were enclosed by invaginations of the nuclear envelope. This deformation of the nuclear envelope was confirmed by transmission electron microscopy (TEM) and immuno-TEM. These two techniques also revealed that the HBc aggregates were accumulations of capsid-like shells with an electron-dense material consisting of HBV core fragments. These findings, shedding light on the ultrastructural organization of HBc aggregates, provide insight into the mechanisms of action of BAY 41–4109 against HBV and will serve as a basis for comparison with other HBV capsid assembly inhibitors.
Published: 2019

40. Prognostic and Long-term Survival of Immune Thrombotic Thrombocytopenic Purpura in older patients

Author: Prevel, Renaud, Roubaud-Roubaud, Claire, Gourlain, Samuel, Jamme, Matthieu, Pérès, Karine, Benhamou, Ygal, Galicier, Lionel, Azoulay, Elie, Poullin, Pascale, Provôt, François, Maury, Eric, Presne, Claire, Hamidou, Mohamed, Saheb, Samir, Wynckel, Alain, Servais, Aude, Girault, Stéphane, Delmas, Yahsou, Châtelet, Valérie, Augusto, Jean-François, Mousson, Christiane, Perez, Pierre, Halimi, Jean-Michel, Kanouni, Tarik, Lautrette, Alexandre, Charvet Rumpler, Anne, Deligny, Christophe, Chauveau, Dominique, Veyradier, Agnès, Coppo, Paul, CHI Poissy-Saint-Germain, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d\'hémaphérèse, Hôpital de la Conception, APHM, Marseille, France, Service d'hémaphérèse, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Saint-Antoine [AP-HP], Laboratoire de Physico-Chimie Moléculaire (LPCM), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Limoges, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie, CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Unité de transplantation allogénique [CHU de Montpellier], Département d'Hématologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019

41. Nephrotoxic drug burden among 1001 critically ill patients: impact on acute kidney injury

Author: Laurent Martin-Lefevre, Bruno Giraudeau, Stephan Ehrmann, Dalila Benzekri-Lefevre, Jean-Claude Lacherade, Auguste Dargent, Julie Helms, Anne Bretagnol, Jean-Pierre Quenot, Arnaud Desachy, Ferhat Meziani, Elsa Tavernier, Pierre-François Dequin, René Robert, Jean-Etienne Herbrecht, Gaëtan Plantefève, Aurélie Joret, Frédéric Bellec, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), 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)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-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)-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 National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Université de La Réunion (UR), Service de réanimation et de surveillance continue [CH Mautauban], Centre hospitalier de Montauban, Centre Hospitalier Victor Dupouy, Service de Réanimation Polyvalente - CHR d’Orleans, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Soins Critiques [Bretonneau], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-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), Ehrmann, Stephan, Université Paris Diderot - Paris 7 (UPD7)-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 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), Centre hospitalier de Montauban (CH Montauban), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
Subjects: medicine.medical_specialty, Intensive-care units [MeSH], Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Vancomycin, 03 medical and health sciences, 0302 clinical medicine, MESH: Kidney tubular necrosis, Renal insufficiency [MeSH], Internal medicine, Anesthesiology, MESH: Renal insufficiency, medicine, MESH: Intensive-care units, Kidney tubular necrosis, MESH: Diuretics, 030212 general & internal medicine, Medical prescription, Simplified Acute Physiology Score, Prospective cohort study, MESH: Acute, business.industry, Research, Acute kidney injury, lcsh:Medical emergencies. Critical care. Intensive care. First aid, MESH: Aminoglycosides, 030208 emergency & critical care medicine, Odds ratio, lcsh:RC86-88.9, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Vancomycin [MeSH], [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Diuretics [MeSH], 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Contrast media [MeSH], Cohort, MESH: Contrast media, Aminoglycosides [MeSH], business, Acute [MeSH], Kidney disease
Abstract: Background Nephrotoxic drug prescription may contribute to acute kidney injury (AKI) occurrence and worsening among critically ill patients and thus to associated morbidity and mortality. The objectives of this study were to describe nephrotoxic drug prescription in a large intensive-care unit cohort and, through a case–control study nested in the prospective cohort, to evaluate the link of nephrotoxic prescription burden with AKI. Results Six hundred and seventeen patients (62%) received at least one nephrotoxic drug, among which 303 (30%) received two or more. AKI was observed in 609 patients (61%). A total of 351 patients were considered as cases developing or worsening AKI a given index day during the first week in the intensive-care unit. Three hundred and twenty-seven pairs of cases and controls (patients not developing or worsening AKI during the first week in the intensive-care unit, alive the case index day) matched on age, chronic kidney disease, and simplified acute physiology score 2 were analyzed. The nephrotoxic burden prior to the index day was measured in drug.days: each drug and each day of therapy increasing the burden by 1 drug.day. This represents a semi-quantitative evaluation of drug exposure, potentially easy to implement by clinicians. Nephrotoxic burden was significantly higher among cases than controls: odds ratio 1.20 and 95% confidence interval 1.04–1.38. Sensitivity analysis showed that this association between nephrotoxic drug prescription in the intensive-care unit and AKI was predominant among the patients with lower severity of disease (simplified acute physiology score 2 below 48). Conclusions The frequently observed prescription of nephrotoxic drugs to critically ill patients may be evaluated semi-quantitatively through computing drug.day nephrotoxic burden, an index significantly associated with subsequent AKI occurrence, and worsening among patients with lower severity of disease.
Published: 2019

42. The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use

Author: Sylvie Chalon, Johnny Vercouillie, Pierre Payoux, Jean-Bernard Deloye, Cécile Malherbe, Florence Le Jeune, Nicolas Arlicot, Anne-Sophie Salabert, Denis Guilloteau, Patrick Emond, Maria-Joao Ribeiro, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse], Zionexa [Paris, France], Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Université de Rennes (UNIV-RENNES), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR), Chalon, Sylvie, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Parkinson's disease, [SDV]Life Sciences [q-bio], Context (language use), Review, radiopharmaceutical, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, In vivo, dopaminergic neuron, Basal ganglia, Medicine, Dopamine transporter, lcsh:R5-920, medicine.diagnostic_test, biology, business.industry, Dopaminergic, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], PET, Positron emission tomography, basal ganglia, biology.protein, Differential diagnosis, business, lcsh:Medicine (General), Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease.
Published: 2019

43. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study

Author: Daniel Delgadillo, Carole Soussain, Bachir Aidaoui, Eileen M Boyle, Philippe Agapé, Vincent Delwail, Agusti Alentorn, Adrien Chauchet, Olivier Casasnovas, Hassen Douzane, Franck Morschhauser, Magali Le Garff-Tavernier, Marie Blonski, Olivier Chinot, Luc Taillandier, Matthieu Peyre, Myrto Costopoulos, Chantal Campello, Fabrice Jardin, Jerome Tamburini, Aurélie Kas, Alexandra Amiel, Frédéric Charlotte, Michel Fabbro, Karima Mokhtari, Emeline Tabouret, Caroline Houillier, Valérie Touitou, Agathe Waultier, Jacques-Olivier Bay, Gandhi Damaj, Nadine Martin-Duverneuil, Lucie Oberic, Julie Abraham, Roch Houot, Hervé Ghesquières, Marie-Pierre Moles-Moreau, Remy Gressin, Corinne Haioun, Adrian Tempescul, Diane Genet, Thierry Lamy, Safia Chebrek, Philippe Colin, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Jean-Pierre Marolleau, Guido Ahle, Loïc Feuvret, Luc-Matthieu Fornecker, Khê Hoang-Xuan, Emmanuel Gyan, Kamel Laribi, Bertrand Mathon, Caroline Serrier, Pierre Soubeyran, Nathalie Cassoux, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Palliative care, Adolescent, Databases, Factual, Lymphoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Article, Central Nervous System Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, hemic and lymphatic diseases, Outcome Assessment, Health Care, medicine, Humans, Progression-free survival, Young adult, education, Aged, Retrospective Studies, education.field_of_study, business.industry, Age Factors, Retrospective cohort study, Middle Aged, Combined Modality Therapy, Progression-Free Survival, 3. Good health, Transplantation, Clinical trial, Methotrexate, 030220 oncology & carcinogenesis, Rituximab, Neurology (clinical), France, Cranial Irradiation, business, 030217 neurology & neurosurgery, medicine.drug, Stem Cell Transplantation
Abstract: ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients 60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.
Published: 2019

44. Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome

Author: Karoui, Khalil, Boudhabhay, Idris, Petitprez, Florent, Vieira-Martins, Paula, Fakhouri, Fadi, Zuber, Julien, Aulagnon, Florence, Matignon, Marie, Rondeau, Eric, Mesnard, Laurent, Halimi, Jean-Michel, Frémeaux-Bacchi, Véronique, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire d’immunologie [Hôpital Européen Georges Pompidou - APHP], 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), Immunotherapy in Transplantation And Autoimmunity (Team 3 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie et transplantation rénale [Hôpital Necker Enfants Malades - APHP], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, This work was supported by grants from the SFNDT (société francophone de Néphrologie, Dialyse et Transplantation) (to KEK), from the Délégation Régionale à la Recherche Clinique, Assistance Publique – Hôpitaux de Paris (Programme Hospitalier de Recherche Clinique (AOM08198) (to VFB), by the EU FP7 Grant 2012-305608 (EURenOmics) (to VFB), the Fondation Du Rein (FRM, Prix 2012 FDR) (to VFB), the Association pour l’Information et la Recherche dans les maladies Rénales génétiques (AIRG France). FP is supported by a CARPEM (CAncer Research for PErsonalized Medicine) doctoral fellowship., Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de néphrologie et immunologie clinique [CHRU Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)
Subjects: Platelets, complement gene variant, hypertensive emergency, hemolytic uremic syndrome, Thrombotic Thrombocytopenic Purpura, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Atypical hemolytic uremic syndrome is a prototypic thrombotic microangiopathy attributable to complement dysregulation. Hypertensive emergency, characterized by elevation of systolic (>180mmHg) or diastolic (>120mmHg) blood pressure together with end-organ damage, can cause thrombotic microangiopathy which may mimic atypical hemolytic uremic syndrome. We sought to retrospectively evaluate the clinical, biological and complement genetic characteristics of 76 and 61 atypical hemolytic uremic syndrome patients with and without hypertensive emergency, respectively. Patients with hypertensive emergency-hemolytic uremic syndrome were more frequently males, with neurological involvement, and a slightly higher hemoglobin level. At least one complement rare variant was identified in 51.3% (39/76) and in 67% (41/61) patients with or without hypertensive emergency, respectively (p=0.06). In both group, renal prognosis was severe with 23% and 40% of patients reaching end stage renal disease after a 5-year follow-up (p=0.1). The 5-year renal survival was 77% in patients without hypertensive emergency nor complement variant, and below 25% in the three groups of patients with hypertensive emergency and/or complement variant (p=0.02). In patients without hypertensive emergency, 5-year renal survival was 100% vs 40% with or without Eculizumab, respectively (p
Published: 2019

45. Extensive exploration of a novel rat model of Parkinson's disease using partial 6-hydroxydopamine lesion of dopaminergic neurons suggests new therapeutic approaches

Author: Jean-Bernard Deloye, Gabrielle Chicheri, Lydie Nadal-Desbarats, Jackie Vergote, Sylvie Chalon, Sylvie Bodard, Patrick Emond, Claire Tronel, Steven Vetel, Frédéric Dollé, Johnny Vercouillie, Sophie Serrière, Antoine Lefèvre, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Zionexa [Paris, France], Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Médecine Nucléaire [Tours], 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), Chalon, Sylvie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, Tyrosine 3-Monooxygenase, [SDV]Life Sciences [q-bio], PET imaging, Nigrostriatal pathway, Striatum, Lesion, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroinflammation, medicine, Translocator protein, Animals, Rats, Wistar, Oxidopamine, dopamine transporter, 030304 developmental biology, Dopamine transporter, Dopamine Plasma Membrane Transport Proteins, 0303 health sciences, Tyrosine hydroxylase, biology, Chemistry, Dopaminergic Neurons, Dopaminergic, Parkinson Disease, Receptors, GABA-A, metabolomics, Corpus Striatum, Rats, [SDV] Life Sciences [q-bio], Disease Models, Animal, medicine.anatomical_structure, nervous system, Positron-Emission Tomography, Metabolome, biology.protein, Microglia, medicine.symptom, Carrier Proteins, Neuroscience, 030217 neurology & neurosurgery, TSPO
Abstract: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons constituting the nigrostriatal pathway. Neuroinflammation, related to microglial activation, plays an important role in this process. Exploration of animal models of PD using neuroimaging modalities allows to better understand the pathophysiology of the disease. Here, we fully explored a moderate lesion model in the rat in which 6-hydroxydopamine was unilaterally delivered in three sites along the striatum. The degenerative process was assessed through in vivo Positron Emission Tomography (PET) imaging and in vitro autoradiographic quantitation of the striatal dopamine transporter (DAT) and immunostaining of tyrosine hydroxylase (TH). The microglial activation was studied through in vitro autoradiographic quantitation of the 18 kDa translocator protein (TSPO) in the striatum and CD11b staining in the SN. In addition, a targeted metabolomics exploration was performed in both these structures using mass spectrometry coupled to HPLC. Our results showed a reproducible decrease in the striatal DAT density associated with a reduction in the number of TH-positive cells in the SN and striatum, reflecting a robust moderate degeneration of nigrostriatal DA neurons. In addition, we observed strong microglia activation in both the striatum and SN ipsilateral to the lesion, highlighting that this moderate degeneration of DA neurons was associated with a marked neuroinflammation. Our metabolomics studies revealed alterations of specific metabolites and metabolic pathways such as carnitine, arginine/proline, and histidine metabolisms. These results bring new insights in the PD mechanism knowledge and new potential targets for future therapeutic strategies.
Published: 2019

46. Healthcare trajectories before and after critical illness: population-based insight on diverse patients clusters

Author: Leslie Grammatico-Guillon, Charlotte Salmon-Gandonnière, Claire Hassen-Khodja, Youenn Jouan, Stephan Ehrmann, Noémie Teixera, Antoine Guillon, Christophe Gaborit, Ehrmann, Stephan, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité d'Épidémiologie des données cliniques [Tours] (EpiDcliC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Accueil et d'Urgences, Service d'Information Médicale d'Epidemiologie et d'Economie de la Santé, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Laboratoire de Physico -& Toxico Chimie des systèmes naturels (LPTC), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Intensive Réanimation [Tours], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Post-intensive care syndrome, law.invention, 03 medical and health sciences, Healthcare trajectories, 0302 clinical medicine, Interquartile range, law, Anesthesiology, Septic shock, Health care, Medicine, education, Mechanical ventilation, education.field_of_study, Acute respiratory distress syndrome, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Intensive care unit, Long-term outcome, 3. Good health, 030228 respiratory system, Emergency medicine, Population study, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: Background The post intensive care syndrome (PICS) gathers various disabilities, associated with a substantial healthcare use. However, patients’ comorbidities and active medical conditions prior to intensive care unit (ICU) admission may partly drive healthcare use after ICU discharge. To better understand retative contribution of critical illness and PICS—compared to pre-existing comorbidities—as potential determinant of post-critical illness healthcare use, we conducted a population-based evaluation of patients’ healthcare use trajectories. Results Using discharge databases in a 2.5-million-people region in France, we retrieved, over 3 years, all adult patients admitted in ICU for septic shock or acute respiratory distress syndrome (ARDS), intubated at least 5 days and discharged alive from hospital: 882 patients were included. Median duration of mechanical ventilation was 11 days (interquartile ranges [IQR] 8;20), mean SAPS2 was 49, and median hospital length of stay was 42 days (IQR 29;64). Healthcare use (days spent in healthcare facilities) was analyzed 2 years before and 2 years after ICU admission. Prior to ICU admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. Healthcare trajectories were then explored at individual level, and patients were assembled according to their individual pre-ICU healthcare use trajectory by clusterization with the K-Means method. Interestingly, this revealed diverse trajectories, identifying patients with elevated and increasing healthcare use (n = 126), and two main groups with low (n = 476) or no (n = 251) pre-ICU healthcare use. In ICU, however, SAPS2, duration of mechanical ventilation and length of stay were not different across the groups. Analysis of post-ICU healthcare trajectories for each group revealed that patients with low or no pre-ICU healthcare (which represented 83% of the population) switched to a persistent and elevated healthcare use during the 2 years post-ICU. Conclusion For 83% of ARDS/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to ICU to a sustained higher healthcare recourse 2 years after ICU discharge. This underpins the hypothesis of long-term critical illness and PICS-related quantifiable consequences in healthcare use, measurable at a population level.
Published: 2019

47. Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): protocol for a randomised controlled trial

Author: Linda Lassel, Marion Boivin, Lucie Planche, Sébastien Barbarot, Vincent Dochez, Bertrand Kaeffer, Virginie Badon, Martine Tching-Sin, Clémentine Cabridain, Catherine Droitcourt, Marie Bodinier, Norbert Winer, Annabel Maruani, Franck Perrotin, David Riochet, Elodie Faurel-Paul, Hélène Aubert, Natasha K Rogers, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), University of Nottingham, UK (UON), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Agence Nationale de la RechercheAgence Nationale de la Recherche, Ministère des Affaires Sociales et de la SantéMinistère des Affaires Sociales et de la Santé, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CIC Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Jonchère, Laurent
Subjects: Male, Pediatrics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Psychological intervention, law.invention, 0302 clinical medicine, Randomized controlled trial, Quality of life, Pregnancy, law, Protocol, Multicenter Studies as Topic, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Prenatal Care, General Medicine, Atopic dermatitis, 3. Good health, [SDV] Life Sciences [q-bio], dermatology, Treatment Outcome, Alimentation et Nutrition, Gestation, eczema, paediatric dermatology, Female, medicine.medical_specialty, Médecine humaine et pathologie, Placebo, Dermatitis, Atopic, 03 medical and health sciences, Double-Blind Method, medicine, Humans, Food and Nutrition, business.industry, Prebiotic, Infant, Newborn, Infant, Maternal Nutritional Physiological Phenomena, medicine.disease, Clinical trial, Prebiotics, Dietary Supplements, Human health and pathology, Pregnant Women, business, 030217 neurology & neurosurgery
Abstract: IntroductionAtopic dermatitis (AD) is a chronic inflammatory disease affecting 10%–15% of children in Europe. There is a need for new primary preventive therapeutic strategies in at-risk populations. Recent research has indicated that atopic diseases are associated with a disrupted gut microbial ‘balance’ in early life raising the possibility that interventions which yield optimal patterns of microflora could improve host’s health. Prebiotics, sugars with immunomodulatory properties that stimulate the diversity of the digestive microbiota, are ideal candidates for such research. So far, most clinical trials have focused on improving infant gut colonisation postnatally. However, prenatal life is a crucial period during which different tolerance mechanisms are put in place. We aim to determine whether antenatal prebiotics supplementation prevents AD in high-risk children.Methods and analysisThis is a randomised, multicentre, double-blind, trial to evaluate the effectiveness of antenatal prebiotic maternal supplementation (galacto-oligosaccharide/inulin) in pregnant women versus placebo on the occurrence of AD at 1 year of age in at-risk children (defined as having a maternal history of atopic disease). Participating women will be randomised to daily ingestion of a prebiotics or placebo (maltodextrin) from 20 weeks’ gestation until delivery. The primary outcome is the prevalence of AD at 1 year of age, using the version of the UK Working Party Diagnostic Criteria optimised for preventive studies. Key secondary endpoints are AD severity, quality of life and prebiotics tolerance. The target sample size is 376 women (188 patients per group) which will provide 80% power to detect a 33% reduction of the risk of AD in the verum group (α=0.05). The primary analysis will be based on the intention-to-treat principle.Ethics and disseminationResults will be presented in peer-reviewed journals and at international conferences. Ethics approval for the study was obtained from the institutional ethical review board of ‘Comité de Protection des Personnes Sud Ouest—Outre-Mer III’ of the University Hospital Centre of Bordeaux (2017/13).Trial registration numberNCT03183440; Pre-results.
Published: 2019

48. A fluid dynamic model for quantitative contrast-enhanced ultrasound imaging: validation for the assessment of uteroplacental perfusion

Author: Denis de Senneville, Baudouin, Novell, Anthony, Arthuis, Chloé, Mendes, Vanda, Dujardin, Paul-Armand, Patat, Frédéric, Bouakaz, Ayache, Escoffre, Jean-Michel, Perrotin, Franck, University Medical Center [Utrecht], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Modélisation Mathématique pour l'Oncologie (MONC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

49. Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening

Author: Thomas Daix, Estelle Guerin, Elsa Tavernier, Emmanuelle Mercier, Valérie Gissot, Olivier Hérault, Jean-Paul Mira, Florence Dumas, Nicolas Chapuis, Christophe Guitton, Marie C. Béné, Jean-Pierre Quenot, Cindy Tissier, Julien Guy, Gaël Piton, Anne Roggy, Grégoire Muller, Éric Legac, Nicolas de Prost, Mehdi Khellaf, Orianne Wagner-Ballon, Rémi Coudroy, Elodie Dindinaud, Fabrice Uhel, Mikaël Roussel, Thomas Lafon, Robin Jeannet, Frédéric Vargas, Catherine Fleureau, Mickaël Roux, Kaoutar Allou, Philippe Vignon, Jean Feuillard, Bruno François, Adollës Di Vittorio, Sébastien Lachot, Marie-Thérèse Georget, Joelle Hanna, Cédric Bretonnière, Olivier Zambon, Laurent Nicolet, Noëlle Brule, Camille Debord, Yannick Le Bris, Nelly Robillard, Auguste Dargent, Anne Bretagnol, Armelle Mathonnet, Thierry Boulain, François Barbier, Dalila Benzekri, Isabelle Runge, Toufik Kamel, Jérôme Cecchini, Sabrina Bouyer, René Robert, Alexandre Ouattara, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CIC Tours, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Equipe LIPNESS (LNC - U1231) (LIPNESS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Réanimation Médicale [CHR d'Orléans], Centre Hospitalier Régional d'Orléans (CHR), Hématologie Biologique [CHR d'Orléans], Réanimation Médicale [CHU Henri Mondor - APHP] (DHU A-TVB), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Septiflux Trial Group : Di Vittorio A, Lachot S, Georget MT, Hanna J, Bretonnière C, Zambon O, Nicolet L, Brule N, Debord C, Le Bris Y, Robillard N, Dargent A, Bretagnol A, Mathonnet A, Boulain T, Barbier F, Benzekri D, Runge I, Kamel T, Cecchini J, Bouyer S, Robert R, Ouattara A., Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional d'Orléans (CHRO), CHU Henri Mondor-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Degauque, Nicolas, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and CHU Henri Mondor [Créteil]-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Organ Dysfunction Scores, medicine.medical_treatment, Inflammation, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, Prospective Studies, Simplified Acute Physiology Score, Aged, immunosuppression, Clinical Deterioration, Immature Granulocyte, business.industry, Septic shock, flow cytometry, Area under the curve, 030208 emergency & critical care medicine, Immunosuppression, medicine.disease, Survival Analysis, 3. Good health, Systemic inflammatory response syndrome, inflammation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, prognosis, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. Methods Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64pos granulocytes, CD16pos monocytes, CD16dim immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. Results Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 ± 48 years; Simplified Acute Physiology Score II, 36 ± 17; Sequential Organ Failure Assessment, 5 ± 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64pos granulocytes, CD16pos monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 ± 35.6 vs 43.5 ± 35.2, P =.07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P andlt;.01) and late (P andlt;.01) death. Conclusions Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration. Trial Registry ClinicalTrials.gov; No. NCT01995448; URL www.clinicaltrials.gov © 2018 American College of Chest Physicians
Published: 2018

50. Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

Author: Criogo Study Team, Pascale Bémer, Christophe Burucoa, Marie Kempf, Nathalie Stock, Laurent Bret, Geneviève Héry-Arnaud, Stéphane Corvec, Julie Léger, Didier Tandé, Chloé Plouzeau, Isabelle Quintin-Roue, Carole Lemarié, Anne Moreau, Gonzague de Pinieux, Serge Milin, Anne Sophie Valentin, Anne Jolivet-Gougeon, Marie-Christine Rousselet, Patrick Michenet, Centre Hospitalier Universiatire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service Bactériologie-Virologie, Hôpital Bretonneau-CHRU de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire d’anatomopathologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), UFR Santé [UNIV Angers], Université d'Angers (UA), Laboratoire de Bactériologie [CHU Angers], ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Trousseau, Laboratoire de Bactériologie, CHU de Poitiers, Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Prosthesis-Related Infections, Neutrophils, neutrophil threshold, Joint Prosthesis, [SDV]Life Sciences [q-bio], 030106 microbiology, Periprosthetic, Sensitivity and Specificity, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Bone-Implant Interface, Humans, Medicine, Prospective Studies, Prospective cohort study, Aged, periprosthetic interface membrane, Arthritis, Infectious, Bacteriological Techniques, business.industry, Histopathological analysis, Prosthetic joint infection, Bacteriology, Perioperative, prosthetic joint Infection, Predictive value, 3. Good health, Multicenter study, 030220 oncology & carcinogenesis, Female, Histopathology, business
Abstract: International audience; No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et al., Histopathology 54:847-853, 2009. https://doi.org/10.1111/j.1365-2559.2009.03313.x). We performed a multicenter prospective study, which compared both methods for the diagnosis of PJI. All suspicions of PJI ( = 264) between December 2010 and March 2012 in seven centers were prospectively included. Five perioperative specimens were collected per patient for cultures, and one was collected for histology. Diagnosis of PJI was made according to the Infectious Diseases Society of America (IDSA) guidelines. Histopathological analysis classified the patients according to the threshold of 23 neutrophils and according to the classification of Morawietz. Performances of both methods were compared by using clinical and/or bacteriological criteria as the gold standard. Among 264 patients with suspected PJI, a diagnosis of infection was confirmed in 215 and unconfirmed in 49 patients. Histopathological analysis was available for 150 confirmed PJI and 40 unconfirmed PJI cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.7%, 90.0%, 96.7%, 52.9%, and 81.1%, respectively, for the Morawietz classification, and 82.0%, 90.0%, 96.9%, 57.1%, and 83.7%, respectively, for the 23-neutrophil threshold. The new algorithm using a threshold of 23 neutrophils can be proposed as a new gold standard for the histopathological diagnosis of PJI.
Published: 2018

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