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2,159 results on '"Hôpital Bretonneau"'

1. First-Dose Coronavirus 2019 Vaccination Coverage among the Residents of Long-Term Care Facilities in France

Author: Carmelo Lafuente-Lafuente, Patrick Hidoux, Pierre Lutzler, Olivier Drunat, Joël Belmin, CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Embrun (CH Embrun), Fédération Hospitalière de France, EHPAD l'Edelweiss, Gap, France, Hôpital Bretonneau, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bretonneau, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Tapia, Claudia
Subjects: Vaccine coverage, Aging, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, Coronavirus-19, medicine.disease_cause, Asymptomatic, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Serology, Long-term care facility, Vaccination, Long-term care, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Vaccination coverage, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical Section: Brief Report, Geriatrics and Gerontology, medicine.symptom, business, Demography, Coronavirus
Abstract: Background: Long-term care facilities (LTCFs) experienced severe burden from the Coronavirus 2019 (COVID-19), and vaccination against SARS-CoV-2 is a major issue for their residents. Objective: The objective of this study was to estimate the vaccination coverage rate among the residents of French LTCFs. Method: Participants and settings: 53 medical coordinators surveyed 73 LTCFs during the first-dose vaccination campaign using the BNT162b2 vaccine, conducted by health authorities in January and early February 2021. Measurements: in all the residents being in the LTCF at the beginning of the campaign, investigators recorded age, sex, history of clinical or asymptomatic COVID-19, serology for SARS-CoV-2 or severe allergy, current end-of-life situation, infectious or acute disease, refusal of vaccination by the resident or by the representative person of vaccine, and the final status, vaccinated or not. Results: Among the 4,808 residents, the average coverage rate for COVID-19 vaccination was 69%, and 46% of the LTCFs had a coverage rate p < 0.001), a history of severe allergy (3.7 vs. 0.1%, p < 0.001), end-of-life situation (4.9 vs. 0.3%, p < 0.001), current infectious or acute illness (19.6 vs. 0.3%, p < 0.001), and refusal of vaccination by residents or representative persons (38.9 vs. 0.4%, p < 0.001). Conclusions: About 3 out of 10 residents remained unvaccinated, and half of the LTCFs had a coverage rate
Published: 2021

2. Hypertension in kidney transplantation: a consensus statement of the 'hypertension and the kidney' working group of the European Society of Hypertension

Author: Alexandre Persu, Davide Bolignano, Michel Burnier, Charles J. Ferro, Gérard M. London, Jean-Michel Halimi, Pantelis Sarafidis, Anna Pisano, Alberto Ortiz, Francesca Mallamaci, Nada Kanaan, John Boletis, Patrick Rossignol, Liffert Vogt, Bénédicte Sautenet, Carmine Zoccali, Grégoire Wuerzner, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), 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 ), Universidad Autónoma de Madrid (UAM), Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital, Azienda Ospedaliera Ospedali Civili Riuniti, Lausanne University Hospital, Institute of Clinical Physiology, CNR, Centre Hospitalier Manhès [Fleury-Mérogis], Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], 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), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), University Hospitals Birmingham [Birmingham, Royaume-Uni], Laiko General Hospital, University of Athens School of Medicine, National and Kapodistrian University of Athens (NKUA), Amsterdam UMC - Amsterdam University Medical Center, Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), AO research is supported by FIS/Fondos FEDER (PI17/00257, PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. LV is supported by Senior Kolff grant (18OKG12) of the Dutch Kidney Foundation.This work was planned as part of the activities of the « Kidney and Hypertension » working group of the European Society of Hypertension (ESH)., European Project: PI17/00257, European Project, BOZEC, Erwan, FEDER PI17/00257 - PI17/00257 - INCOMING, ISCIII-RETIC REDinREN RD016/0009 - INCOMING, FEDER PI18/01386 - INCOMING, FEDER PI19/00588 - INCOMING, FEDER PI19/00815 - INCOMING, FEDER DTS18/00032 - INCOMING, KIDNEY ATTACK AC18/00064 - INCOMING, PERSTIGAN AC18/00071 - INCOMING, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de pathologie cardiovasculaire, UCL - (SLuc) Service de néphrologie, Nephrology, ACS - Microcirculation, and APH - Health Behaviors & Chronic Diseases
Subjects: medicine.medical_specialty, Consensus, Ambulatory blood pressure, Physiology, Population, Kidney, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, Humans, education, Antihypertensive Agents, Kidney transplantation, education.field_of_study, business.industry, medicine.disease, Kidney Transplantation, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Transplantation, Masked Hypertension, medicine.anatomical_structure, Blood pressure, surgical procedures, operative, Hypertension, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract: International audience; Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.
Published: 2021

3. Inhaled bacteriophage therapy in a porcine model of pneumonia caused by <scp> Pseudomonas aeruginosa </scp> during mechanical ventilation

Author: Céline Barc, Mickaël Riou, Yonatan Perez, Antoine Guillon, Jeoffrey Pardessus, Laurent Mereghetti, Elsa Bodier-Montagutelli, Emilie Dalloneau, Camille Thorey, Nathalie Heuzé-Vourc'h, Sandrine Le Guellec, Laurent Vecellio, Maria Cabrera, Youenn Jouan, Guillaume L'Hostis, Cindy Fevre, 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), Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pherecydes Pharma, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DTF-Aerodrug, DTF, public grant overseen by the Direction Générale des Armées (DGA)-France - Project RAPID—Pneumophage grant, Chanteloup, Nathalie Katy, 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 Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Phage therapy, Swine, medicine.drug_class, medicine.medical_treatment, Antibiotics, medicine.disease_cause, pseudomonas aeruginosa, Microbiology, Bacteriophage, Mice, 03 medical and health sciences, 0302 clinical medicine, bacteriophage, In vivo, medicine, Animals, pneumonia, Bacteriophages, Pseudomonas Infections, Phage Therapy, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, Mechanical ventilation, inhalation, 0303 health sciences, ventilation-associated pneumonia, biology, 030306 microbiology, Pseudomonas aeruginosa, business.industry, biology.organism_classification, medicine.disease, Respiration, Artificial, 3. Good health, Pneumonia, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030228 respiratory system, Lytic cycle, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pseudomonas Phages, business
Abstract: International audience; Background and purpose: Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of pneumonia caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized-phage therapy.Experimental approach: (i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled-phage therapy was evaluated in pigs, which were anesthetized, mechanically ventilated and infected with P. aeruginosa.Key results: By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5 Log reduction, p
Published: 2021

4. Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) under managed care: a clinical and environmental investigation in a French zoological park

Author: Estelle Cateau, Antoine Leclerc, Noémie Cartier, Isabel Valsecchi, Éric Bailly, Ronan Le Senechal, Margaux Becerra, Brice Le Gallou, Rose-Anne Lavergne, Adélaïde Chesnay, Jean-Patrice Robin, Carolyn Cray, Nicolas Goddard, Milan Thorel, Jacques Guillot, Baptiste Mulot, Guillaume Desoubeaux, Service de Parasitologie - Mycologie - Médecine Tropicale, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ZooParc de Beauval, 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), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), 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), 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), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Miami Leonard M. Miller School of Medicine (UMMSM), and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Azoles, Antifungal Agents, MICs, microsatellite genotypin, Aspergillus fumigatus, Managed Care Programs, Microbial Sensitivity Tests, General Medicine, Spheniscidae, Fungal Proteins, Infectious Diseases, MESH: Spheniscidae, Drug Resistance, Fungal, birds, Mutation, [SDE]Environmental Sciences, Aspergillus nishimurae, cyp51A, Animals, Aspergillosis, Humans, MESH: Aspergillosis, azole-resistance, Humboldt penguins
Abstract: Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs. The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018–20: all isolates were counted and characterized by sequencing. When identified as Aspergillus fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for minimal inhibitory concentrations (MICs) determination. At the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains. Environmental investigations highlighted the substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and a large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains. Lay summary
Published: 2022

5. 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

6. Human dentin characteristics of patients with osteogenesis imperfecta: insights into collagen-based biomaterials

Author: Catherine Bosser, Pragnère S, Auregan Jc, Linglart A, Thierry Hoc, Morad Bensidhoum, Catherine Chaussain, Cécile Nouguier-Lehon, École Centrale de Lyon (ECL), Université de Lyon, Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), Pathologies, Imagerie et Biothérapies oro-faciales (EA 2496), Université Paris Descartes - Paris 5 (UPD5), Service d'Odontologie [Bretonneau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bretonneau, CCSD, Accord Elsevier, Biologie, Bioingénierie et Bioimagerie Ostéo-articulaires (B3OA (UMR_7052)), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne-Centre National de la Recherche Scientifique (CNRS), Hôpital Bretonneau, Laboratoires Pathologies, Imagerie et Biothérapies orofaciales, and Partenaires INRAE
Subjects: Pathology, medicine.medical_specialty, Bone disease, Dentinogenesis imperfecta, [SDV]Life Sciences [q-bio], 0206 medical engineering, Biomedical Engineering, Biocompatible Materials, 02 engineering and technology, Biochemistry, Raman microspectroscopy, Biomaterials, Hydroxyproline, chemistry.chemical_compound, stomatognathic system, Dentinogenesis Imperfecta, Hardness, Dentin, medicine, Deciduous teeth, Humans, Molecular Biology, business.industry, Genetic disorder, General Medicine, biomineralization, 021001 nanoscience & nanotechnology, medicine.disease, 020601 biomedical engineering, [SDV] Life Sciences [q-bio], stomatognathic diseases, medicine.anatomical_structure, chemistry, Osteogenesis imperfecta, Collagen, 0210 nano-technology, business, Type I collagen, Biotechnology
Abstract: International audience; Osteogenesis imperfecta (OI), also known as "brittle bone disease", is a rare genetic disorder of the skeleton, whose most benign form I corresponds to autosomal dominant mutations in the genes encoding type I collagen (COLA1, COLA2). Several associated skeletal manifestations are often observed but, surprisingly, while dentin defects often reflect genetic bone disorders, about half of OI patients have no obvious oral manifestations. Here, we investigated the collagen, mineral and mechanical properties of dentin from deciduous teeth collected from patients with mild form of OI and displaying no obvious clinical signs of dentinogenesis imperfecta. For the first time, an increase in the hardness of OI dentin associated with an increase in mineral content compared to healthy patients was reported. In addition, OI altered the tissue characteristics of the dentin-enamel junction but the interfacial gradient was preserved. The impact of changes in molecular structure due to mutations in OI was assessed by Raman microspectroscopy. Our results highlighted a change in the hydroxyproline-proline ratio in direct association with collagen mineralization. Our findings suggest that the evaluation of teeth could be an important aid for mild types of OI that are often difficult to diagnose clinically and provide experimental evidence that hydroxyproline content should be considered in future studies on collagen-based biomaterials.
Published: 2021

7. 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

8. COVID-19 Outbreaks in Nursing Homes Despite Full Vaccination with BNT162b2 of a Majority of Residents

Author: Lafuente, Carmelo, Rainone, Antonio, Guérin, Olivier, Drunat, Olivier, Jeandel, Claude, Hanon, Olivier, Belmin, Joël, 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), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Côte d'Azur (UCA), Hôpital Bretonneau, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bretonneau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe hospitalier Broca, Sorbonne Université (SU), and Lafuente, Carmelo
Subjects: Male, Aging, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, outbreak, SARS-CoV-2, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, COVID-19, vaccination, Disease Outbreaks, Nursing Homes, nursing home, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Female, Geriatrics and Gerontology, BNT162 Vaccine, older adults, Aged
Abstract: Background: It is not known if widespread vaccination can prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subpopulations at high risk, like older adults in nursing homes (NH). Objective: The objective of the study was to know if coronavirus disease 2019 (COVID-19) outbreaks can occur in NH with high vaccination coverage among its residents. Methods: We identified, using national professional networks, NH that suffered COVID-19 outbreaks despite having completed a vaccination campaign, and asked them to send data, using predefined collecting forms, on the number of residents exposed, their vaccination status and the number, characteristics, and evolution of patients infected. The main outcome was to identify outbreaks occurring in NH with high vaccine coverage. Secondary outcomes were residents’ risk of being infected, developing severe disease, or dying from COVID-19 during the outbreak. SARS-CoV-2 infection was defined by a positive reverse transcriptase-polymerase chain reaction. All residents were serially tested whenever cases appeared in a facility. Unadjusted secondary attack rates, relative risks, and vaccine effectiveness during the outbreak were estimated. Results: We identified 31 NH suffering an outbreak during March–April 2021, of which 27 sent data, cumulating 1,768 residents (mean age 88.4, 73.4% women, 78.2% fully vaccinated). BNT162b2 was the vaccine employed in all NH. There were 365 cases of SARS-CoV-2 infection. Median secondary attack rates were 20.0% (IQR 4.4%–50.0%) among unvaccinated residents and 16.7% (IQR 9.5%–29.2%) among fully vaccinated ones. Severe cases developed in 42 of 80 (52.5%) unvaccinated patients, compared with 56 of 248 (22.6%) fully vaccinated ones (relative risks [RR] 4.17, 95% CI: 2.43–7.17). Twenty of the unvaccinated patients (25.0%) and 16 of fully vaccinated ones (6.5%) died from COVID-19 (RR 5.11, 95% CI: 2.49–10.5). Estimated vaccine effectiveness during the outbreak was 34.5% (95% CI: 18.5–47.3) for preventing SARS-CoV-2 infection, 71.8% (58.8–80.7) for preventing severe disease, and 83.1% (67.8–91.1) for preventing death. Conclusions: Outbreaks of COVID-19, including severe cases and deaths, can still occur in NH despite full vaccination of a majority of residents. Vaccine remains highly effective, however, for preventing severe disease and death. Prevention and control measures for SARS-CoV-2 should be maintained in NH at periods of high incidence in the community.
Published: 2022

9. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

Author: Le Meur, Yannick, Badet, Lionel, Essig, Marie, Thierry, Antoine, Büchler, Matthias, Drouin, Sarah, Deruelle, Charles, Morelon, Emmanuel, Pesteil, Francis, Delpech, Pierre-Olivier, Boutin, Jean-Michel, Renard, Felix, Barrou, Benoit, Delpech, Pierre‐Olivier, Boutin, Jean‐Michel, 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), Service d'urologie [Hôpital Edouard-Herriot, CHU-HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU de Brest, service de chirurgie urologique et de la transplantation reinale (CHU - BREST - Urologie), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service d'urologie [CHU de Poitiers], Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [Poitiers], 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, delayed graft function (DGF), Organ Preservation Solutions, 030232 urology & nephrology, Ischemia, Urology, Cold storage, Renal function, kidney transplantation/nephrology, 030230 surgery, Kidney, clinical research/practice, Cold Ischemia Time, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, organ transplantation in general, Pharmacology (medical), Adverse effect, Transplantation, Machine perfusion, business.industry, Graft Survival, clinical trial, Organ Preservation, medicine.disease, Kidney Transplantation, Thrombosis, Tissue Donors, 3. Good health, Oxygen, Perfusion, ischemia reperfusion injury (IRI), [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.
Published: 2020

10. 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

11. Ein Prototyp der transienten Hochfrequenz-Elastografie zur Beurteilung der Haut (Dermis) -Fibrose: Eine diagnostische Studie bei Patienten mit venöser Insuffizienz und Kontrollprobanden

Author: Emilie Vierron, Laurent Machet, Thibault Kervarrec, Frédéric Ossant, Frédéric Patat, Geoffroy Faleweei, Caroline Chartier, Paul-Armand Dujardin, Gabriela Georgescou, Valérie Gissot, Marie-Christine Machet, Valerie Tauveront, Yassine Mofid, Annabel Maruani, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie (TOURS - Radio), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de dermatologie (CHRU de 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), Service de Pathologie [CHRU Tours], Infectiologie et Santé Publique (UMR ISP), Université de Tours-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), 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 Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Liver Cirrhosis, Skin score, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Physical examination, chronic venous disorders - high frequency transient elastography - skin fibrosis - dermis thickness - young’s Modulus, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Dermis, Fibrosis, Humans, Medicine, Radiology, Nuclear Medicine and imaging, In patient, Skin, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Ultrasound, medicine.disease, medicine.anatomical_structure, ROC Curve, Venous Insufficiency, Elasticity Imaging Techniques, Radiology, business, Transient elastography, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: High-frequency transient elastography (HF-TE) is a noninvasive technique for assessing shear-wave speed and finally elasticity in thin tissue such as the skin. It has never been validated for monitoring fibrotic skin diseases. The purpose was to evaluate the potential of HF-TE to assess skin fibrosis in patients with chronic venous disorders (CVD). This clinical study enrolled 48 patients at various stages of CVD and 48 paired healthy volunteers. Subjects underwent a clinical examination with an evaluation of Rodnan's fibrosis skin score. We studied the dermis thickness measured using ultrasound (US) and elasticity measurements using cutometer and HF-TE studied according to 3 cutaneous zones positioned on the leg. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnosis performance for a combined parameter (PRL) based on a logistic regression model using both elasticity and dermal thickness. Patients with CVD had significantly higher values of skin elasticity than healthy subjects, 134.5 kPa and 132.1 kPa vs. 91.3 kPa, respectively. The dermis thickness also increased with escalation in CVD stage for all studied zones. The PRL parameter had an AUC value of 0.79 for all zones and stages of CVD clustered. The discriminating power of PRL increased with escalation of the CVD stage; with an AUC value of up to 0.89 for evolved stages, and a sensitivity and specificity of 0.79 and 0.89, respectively. HF-TE, coupled with a US measurement of dermis thickness, made it possible to propose a new biomarker, which proved to be a good diagnostic tool for skin fibrosis.ZIEL: Die transiente Hochfrequenz-Elastografie (HF-TE), eine nichtinvasive Technik zur Beurteilung der Scherwellengeschwindigkeit und nicht zuletzt der Elastizität von dünnem Gewebe wie der Haut, wurde noch nie für das Monitoring fibrotischer Hautkrankheiten validiert. Ziel war es, die Leistungsfähigkeit der HF-TE bei der Beurteilung der Hautfibrose bei Patienten mit chronisch-venöser Insuffizienz (CVI) zu untersuchen. Für diese klinische Studie wurden 48 Patienten mit CVI in verschiedenen Stadien zusammen mit 48 gesunden Probanden gepaart aufgenommen. Bei allen wurde eine klinische Untersuchung mit dem Rodnan-Fibrose-Hautscore durchgeführt. Wir untersuchten die Dermisdicke mittels Ultraschalls (US) und führten Elastizitätsbestimmungen mit dem Cutometer und der HF-TE an 3 Hautbereichen am Bein durch. Die Fläche unter der ROC-Kurve (AUC) wurde berechnet, um die diagnostische Leistung für einen kombinierten Parameter (PRL) zu bewerten, der auf einem logistischen Regressionsmodell unter Einbeziehung sowohl der Elastizität als auch der Hautdicke basierte. Patienten mit CVI hatten signifikant höhere Werte der Hautelastizität mit 134,5 kPa und 132,1 kPa gegenüber gesunden Probanden mit 91,3 kPa. Die Dermisdicke nahm mit dem Anstieg der CVI-Stadien in allen untersuchten Bereichen zu. Der PRL hatte einen AUC-Wert von 0,79 für alle Bereiche und Stadien des CVI-Clusters. Die Trennschärfe des PRL nahm mit dem Anstieg der CVI-Stadien zu; mit einem AUC-Wert von bis zu 0,89 für fortgeschrittene Stadien sowie einer Sensitivität von 0,79 und einer Spezifität von 0,89. Die HF-TE zusammen mit der US-Bestimmung der Dermisdicke erwies sich als gutes Diagnosewerkzeug bei Hautfibrose und kann als möglicher neuer Biomarker dienen.
Published: 2020

12. Immunopathological manifestations in Kabuki syndrome: a registry study of 177 individuals

Author: Margot, Henri, Boursier, Guilaine, Duflos, Claire, Sanchez, Elodie, Amiel, Jeanne, Andrau, Jean-Christophe, Arpin, Stéphanie, Brischoux-Boucher, Elise, Boute, Odile, Burglen, Lydie, Caille, Charlotte, Capri, Yline, Collignon, Patrick, Conrad, Solène, CORMIER-DAIRE, Valerie, Delplancq, Geoffroy, Dieterich, Klaus, Dollfus, Hélène, Fradin, Mélanie, Faivre, Laurence, Fernandes, Helder, Francannet, Christine, Gatinois, Vincent, Gérard, Marion, Goldenberg, Alice, Ghoumid, Jamal, Grotto, Sarah, Guerrot, Anne-Marie, Guichet, Agnès, Isidor, Bertrand, Jacquemont, Marie-Line, Julia, Sophie, Philip, K, Legendre, Marine, Le Quan Sang, K., Leheup, Bruno, Lyonnet, Stanislas, Magry, Virginie, Manouvrier, Sylvie, Martin, Dominique, Morel, Godelieve, Munnich, Arnold, Naudion, Sophie, Odent, Sylvie, Perrin, Laurence, Petit, Florence, Philip, Nicole, Rio, Marlène, Robbe, Julie, Rossi, Massimiliano, Sarrazin, Elisabeth, Toutain, Annick, Van Gils, Julien, Vera, Gabriella, Verloes, Alain, Weber, Sacha, Whalen, Sandra, Sanlaville, Damien, Lacombe, Didier, Aladjidi, Nathalie, Geneviève, David, Khau Van Kien, Philippe, Van Gils, Julie, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de Génétique Médicale, Hôpital intercommunal de Font-Pré, Centre hospitalier universitaire de Nantes (CHU Nantes), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muscle et Pathologies, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de génétique clinique, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des Maladies Rénales Héréditaires, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de génétique médicale et cytogénétique [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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 de référence car i b é en des maladies rares neuromusculaires et neurologiques adultes et enfant (CERCA), Hôpital Pierre Zobda Quitman-CHU Fort-de-France, U 1211 Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (MRGM), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire régional de télédétection, Institut de Recherche pour le Développement (IRD), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), AOM 07-090, Ministère de la Santé et des Services sociaux, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), gerard, marion, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, [SDV.GEN] Life Sciences [q-bio]/Genetics, Vitiligo, Severity of Illness Index, Hypogammaglobulinemia, 0302 clinical medicine, Prevalence, Medicine, KDM6A, Registries, Child, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Immunodeficiency, Histone Demethylases, 0303 health sciences, Genetic disorder, KMT2D, Middle Aged, Thrombocytopenic purpura, Neoplasm Proteins, 3. Good health, DNA-Binding Proteins, Vestibular Diseases, Child, Preschool, Female, Autoimmune hemolytic anemia, Adult, medicine.medical_specialty, Adolescent, Primary Immunodeficiency Diseases, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Autoimmune Diseases, Young Adult, 03 medical and health sciences, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Humans, Abnormalities, Multiple, Genetic Association Studies, Aged, 030304 developmental biology, Autoimmune disease, [SDV.GEN]Life Sciences [q-bio]/Genetics, Kabuki syndrome, business.industry, Infant, Newborn, Infant, medicine.disease, Hematologic Diseases, immunity, Dermatology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Face, Mutation, business, 030217 neurology & neurosurgery
Abstract: Kabuki syndrome (KS) (OMIM 147920 and 300867) is a rare genetic disorder characterized by specific facial features, intellectual disability, and various malformations. Immunopathological manifestations seem prevalent and increase the morbimortality. To assess the frequency and severity of the manifestations, we measured the prevalence of immunopathological manifestations as well as genotype–phenotype correlations in KS individuals from a registry. Data were for 177 KS individuals with KDM6A or KMT2D pathogenic variants. Questionnaires to clinicians were used to assess the presence of immunodeficiency and autoimmune diseases both on a clinical and biological basis. Overall, 44.1% (78/177) and 58.2% (46/79) of KS individuals exhibited infection susceptibility and hypogammaglobulinemia, respectively; 13.6% (24/177) had autoimmune disease (AID; 25.6% [11/43] in adults), 5.6% (10/177) with ≥2 AID manifestations. The most frequent AID manifestations were immune thrombocytopenic purpura (7.3% [13/177]) and autoimmune hemolytic anemia (4.0% [7/177]). Among nonhematological manifestations, vitiligo was frequent. Immune thrombocytopenic purpura was frequent with missense versus other types of variants (p = 0.027). The high prevalence of immunopathological manifestations in KS demonstrates the importance of systematic screening and efficient preventive management of these treatable and sometimes life-threatening conditions.
Published: 2020

13. The Influence of Underlying Disease on Rituximab Pharmacokinetics May be Explained by Target-Mediated Drug Disposition

Author: Emmanuel Gyan, Divi Cornec, Olivier Casasnovas, Gilles Paintaud, Denis Mulleman, Thierry Lamy, Céline Desvignes, Stéphane Leprêtre, David Ternant, Amina Bensalem, Ulrich Specks, Guillaume Cartron, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Mayo Clinic [Rochester], 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), 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), 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), CHU Pontchaillou [Rennes], 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), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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 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 ), 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), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau, Université de Rennes 1 (UR1), and 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 )
Subjects: Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Follicular lymphoma, 030226 pharmacology & pharmacy, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Elimination rate constant, Antigen, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Pharmacology (medical), Lymphoma, Follicular, Pharmacology, CD20, biology, business.industry, Antigens, CD20, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Lymphoma, 030220 oncology & carcinogenesis, Rheumatoid arthritis, biology.protein, Cancer research, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug
Abstract: International audience; BACKGROUND AND OBJECTIVES: Rituximab is an anti-CD20 monoclonal antibody approved in several diseases, including chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), rheumatoid arthritis (RA), and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The influence of underlying disease on rituximab pharmacokinetics has never been investigated for several cancer and non-cancer diseases simultaneously. This study aimed at assessing this influence using an integrated semi-mechanistic model accounting for target-mediated elimination of rituximab. METHODS: Rituximab concentration-time data from five studies previously published in patients with CLL, DLBCL, FL, RA, and AAV were described using a two-compartment model with irreversible binding of rituximab to its target antigen. Both underlying disease and target antigen measurements were assessed as covariates. RESULTS: Central volume of distribution was [95% confidence interval] 1.7-fold [1.6-1.9] higher in DLBCL than in RA, FL, and CLL, and it was 1.8-fold [1.6-2.1] higher in RA, FL, and CLL than in AAV. First-order elimination rate constants were 1.8-fold [1.7-2.0] and 1.3-fold [1.2-1.5] higher in RA, DLBCL, and FL than in CLL and AAV, respectively. Baseline latent antigen level (L(0)) was 54-fold [30-94], 20-fold [11-36], and 29-fold [14-64] higher in CLL, DLBCL, and FL, respectively, than in RA and AAV. In lymphoma, L(0) increased with baseline total metabolic tumor volume (p = 6.10(-7)). In CLL, the second-order target-mediated elimination rate constant (k(deg)) increased with baseline CD20 count on circulating B cells (CD20(cir), p = 0.0081). CONCLUSIONS: Our results show for the first time that rituximab pharmacokinetics is strongly influenced by underlying disease and disease activity. Notably, neoplasms are associated with higher antigen amounts that result in decreased exposure to rituximab compared to inflammatory diseases. Our model might be used to estimate unbound target amounts in upcoming studies.
Published: 2021

14. 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

15. 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

16. 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

17. Multiple erythema migrans and carditis-related atrial fibrillation: exceptional manifestations of early disseminated Lyme disease

Author: Sarah Ventéjou, Lisa Baldinger, Philippe Lanotte, Thibaud Genet, Louis Bernard, Mahtab Samimi, S. Leducq, Cédric Lenormand, Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de cardiologie, Centre National de référence des Borrelia (CNR), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Médecine Interne et Maladies Infectieuses [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de dermatologie [Strasbourg], CHU Strasbourg, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, business.industry, MEDLINE, Carditis, Atrial fibrillation, Dermatology, Early Disseminated Lyme Disease, medicine.disease, 3. Good health, medicine, Erythema migrans, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2021

18. 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

19. 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

20. CRISPR typing increases the discriminatory power of Streptococcus agalactiae typing methods

Author: Clémence Beauruelle, Ludovic Treluyer, Adeline Pastuszka, Thierry Cochard, Clément Lier, Laurent Mereghetti, Philippe Glaser, Claire Poyart, Philippe Lanotte, Service de Bactériologie-Virologie, Hygiène Hospitalière et Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Brest (CHRU 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service de Bactériologie [CHU Cochin, AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-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), and Chanteloup, Nathalie Katy
Subjects: 0301 basic medicine, Microbiology (medical), group B Streptococcus, 030106 microbiology, Locus (genetics), Computational biology, Biology, medicine.disease_cause, Microbiology, Streptococcus agalactiae, 03 medical and health sciences, molecular subtyping, medicine, Direct repeat, CRISPR, Typing, CRISPR-Cas, Genotyping, Original Research, typing, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, 030104 developmental biology, Multilocus sequence typing, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mobile genetic elements
Abstract: matériel supplémentaire : https://www.frontiersin.org/articles/10.3389/fmicb.2021.675597/full#supplementary-material; International audience; We explored the relevance of a Clustered regularly interspaced short palindromic repeats (CRISPR)-based genotyping tool for Streptococcus agalactiae typing and we compared this method to current molecular methods [multi locus sequence typing (MLST) and capsular typing]. To this effect, we developed two CRISPR marker schemes (using 94 or 25 markers, respectively). Among the 255 S. agalactiae isolates tested, 229 CRISPR profiles were obtained. The 94 and 25 markers made it possible to efficiently separate isolates with a high diversity index (0.9947 and 0.9267, respectively), highlighting a high discriminatory power, superior to that of both capsular typing and MLST (diversity index of 0.9017 for MLST). This method has the advantage of being correlated with MLST [through analysis of the terminal direct repeat (TDR) and ancestral spacers] and to possess a high discriminatory power (through analysis of the leader-end spacers recently acquired, which are the witnesses of genetic mobile elements encountered by the bacteria). Furthermore, this “one-shot” approach presents the benefit of much-reduced time and cost in comparison with MLST. On the basis of these data, we propose that this method could become a reference method for group B Streptococcus (GBS) typing.
Published: 2021

21. Awake prone positioning in non-intubated patients with acute hypoxemic respiratory failure due to COVID-19: A systematic review of proportional outcomes comparing observational studies with and without awake prone positioning in the setting of COVID-19

Author: Pavlov, Ivan, He, Hangyong, Mcnicholas, Bairbre, Perez, Yonatan, Tavernier, Elsa, Trump, Matthew, Jackson, Julie, Zhang, Wei, Rubin, Daniel, Spiegel, Thomas, Hung, Anthony, Estrada, Miguel Ángel Ibarra, Roca, Oriol, Vines, David, Cosgrave, David, Mirza, Sara, Laffey, John, Rice, Todd, Ehrmann, Stephan, Li, Jie, Department of Emergency Medicine [Montréal, Canada], Hôpital du Sacré-Coeur de Montréal, Capital University of Medical Sciences [Beijing] (CUMS), University Hospital Galway, 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 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), CRICS-TRIGGERSEP, Centre Hospitalier Régional Universitaire de Tours (CHRU 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), Second Military Medical University [Shanghai], University of Chicago, Universidad de Guadalajara, Instituto de Salud Carlos III [Madrid] (ISC), Rush University Medical Center [Chicago], National University of Ireland [Galway] (NUI Galway), Vanderbilt University School of Medicine [Nashville], 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), 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 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 de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and 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)
Subjects: Acute respiratory failure (ARF), Coronavirus disease 2019 (COVID-19), High-flow nasal cannula (HFNC), Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), Acute hypoxemic respiratory failure (AHRF), Acute respiratory distress syndrome (ARDS), Non-invasive ventilation (NIV), Continuous positive airway pressure (CPAP), Awake prone positioning (APP), [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; Background Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubations of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP.Methods: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care.Results: A total of 46 published and 4 unpublished observational studies that included 2994 patients were included, of which 921 patients were managed with APP, and 870 patients were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 patients treated with APP, and 852 patients treated with usual care), the intubation rate was 27%(95%CI, 19 to 37%), as compared to 30%(95%CI, 20 to 42%)(p=0.71), even when duration of application, use of adjunctive respiratory assist device (high flow nasal cannula or non-invasive ventilation) and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when treated with APP was compared with usual care (11% v.s. 22%), which was not statistically significant.Conclusions: APP was associated with improvement of oxygenation but did not reduce the intubation rate in patients with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation and mortality rate in these patients.
Published: 2021

22. 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

23. Novel missense mutations in PTCHD1 alter its plasma membrane subcellular localization and cause intellectual disability and autism spectrum disorder

Author: Sylviane Marouillat, Marie-Laure Vuillaume, Thomas Smol, Rose-Anne Thépault, Lyse Ruaud, Sarah Grotto, Jamal Ghoumid, Nicolas Chatron, Annick Toutain, Marianne Till, Alain Verloes, Manon Dixneuf, Valérie Chune, Gaetan Lesca, Frédéric Laumonnier, Nathalie Couque, Bénédicte Gérard, Martine Raynaud, Judith Halewa, Dévina C. Ung, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), 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), Les Hôpitaux Universitaires de Strasbourg (HUS), Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Robert Debré, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, ANR-20-CE17-0006,ASDecode,Approches translationnelles pour la caractérisation de la voie PTCHD1 impliquée dans les troubles neurodéveloppementaux(2020), Laumonnier, Frédéric, Approches translationnelles pour la caractérisation de la voie PTCHD1 impliquée dans les troubles neurodéveloppementaux - - ASDecode2020 - ANR-20-CE17-0006 - AAPG2020 - VALID, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, [SDV]Life Sciences [q-bio], Mutation, Missense, autism spectrum disorder, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, functional analyses, PTCHD1 (patched domain containing 1) gene, 03 medical and health sciences, Mice, in vitro cellular models, subcellular localization, Genetics, medicine, Missense mutation, Animals, Humans, Gene, Genetics (clinical), Research Articles, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Endoplasmic reticulum, 030305 genetics & heredity, Cell Membrane, Membrane Proteins, Subcellular localization, medicine.disease, In vitro, Transmembrane protein, Amino acid, [SDV] Life Sciences [q-bio], chemistry, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism spectrum disorder, intellectual disability, missense variants, Research Article
Abstract: The X‐linked PTCHD1 gene, encoding a synaptic membrane protein, has been involved in neurodevelopmental disorders with the description of deleterious genomic microdeletions or truncating coding mutations. Missense variants were also identified, however, without any functional evidence supporting their pathogenicity level. We investigated 13 missense variants of PTCHD1, including eight previously described (c.152G>A,p.(Ser51Asn); c.217C>T,p.(Leu73Phe); c.517A>G,p.(Ile173Val); c.542A>C,p.(Lys181Thr); c.583G>A,p.(Val195Ile); c.1076A>G,p.(His359Arg); c.1409C>A,p.(Ala470Asp); c.1436A>G,p.(Glu479Gly)), and five novel ones (c.95C>T,p.(Pro32Leu); c.95C>G,p.(Pro32Arg); c.638A>G,p.(Tyr213Cys); c.898G>C,p.(Gly300Arg); c.928G>C,p.(Ala310Pro)) identified in male patients with intellectual disability (ID) and/or autism spectrum disorder (ASD). Interestingly, several of these variants involve amino acids localized in structural domains such as transmembrane segments. To evaluate their potentially deleterious impact on PTCHD1 protein function, we performed in vitro overexpression experiments of the wild‐type and mutated forms of PTCHD1‐GFP in HEK 293T and in Neuro‐2a cell lines as well as in mouse hippocampal primary neuronal cultures. We found that six variants impaired the expression level of the PTCHD1 protein, and were retained in the endoplasmic reticulum suggesting abnormal protein folding. Our functional analyses thus provided evidence of the pathogenic impact of missense variants in PTCHD1, which reinforces the involvement of the PTCHD1 gene in ID and in ASD., Thirteen missense variants in the PTCHD1 gene associated with X‐linked neurodevelopmental disorder were investigated to address their potentially deleterious impact. Their overexpression in various cell lines (HEK293T, Neuro‐2a) and in primary neuronal cultures revealed abnormal protein stability and impaired subcellular localization, thus providing further evidence for the significant impact of PTCHD1 genetic alterations in intellectual disability and in autism spectrum disorder.
Published: 2021

24. Modeling Hepatitis E infection in immunocompromised patients using a new pig model

Author: León janampa, Nancy, Barc, Céline, Darrouzain, François, Gatault, Philippe, Riou, Mickaël, Pinard, Anne, Pezant, Jérémy, Caballero-Posadas, Ignacio, Rossignol, Christelle, Gaudy-Graffin, Catherine, Brand, Denys, Marlet, Julien, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de Pharmacologie Médicale [CHRU Tours], 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)-Université de Tours-Hôpital Bretonneau, Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-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], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Hepatite E virus, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, animal model, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

25. 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

26. Le syndrome post-réanimation

Author: C. Salmon Gandonnière, Youenn Jouan, Stephan Ehrmann, J. Le Marec, 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), 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-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)-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), and 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)
Subjects: medicine.medical_specialty, media_common.quotation_subject, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), law, Intensive care, Health care, Internal Medicine, medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, media_common, business.industry, Respiratory dysfunction, Gastroenterology, 030208 emergency & critical care medicine, Cognition, Intensive care unit, Post-intensive care syndrome, 3. Good health, 030228 respiratory system, business, Autonomy
Abstract: Post-intensive care syndrome is an entity defined in 2010 and covering any sequelae following an extended hospitalization in intensive care unit. It comprises psychological, cognitive and physical disorders (neuromyopathy, respiratory dysfunction, joint stiffness, among others). These sequelae have important consequences on autonomy and quality of life of these patients, as well as on their healthcare consumption and on mortality. Psychological sequelae can also be seen in hospitalized patients' relatives. Screening and management of these disorders is more and more frequent but no method has formally proven effective. The number of patients surviving an intensive care unit hospitalization is increasing, and management of post-intensive care syndrome is a major issue. It seems important that the internist be aware of this syndrome, given his pivotal role in global management of patients and frequent implication into care after the intensive care unit.
Published: 2021

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

Author: Mélanie Fradin, Nicolas Sadoul, Xavier Waintraub, Didier Klug, Albert Hagège, Pascal Sabouraud, Arnaud Isapof, Julien Durigneux, Olivier Lascols, Pascal Laforêt, Armelle Magot, Ivana Dabaj, Eloi Marijon, Camille Vatier, Pascal Cintas, Emmanuelle Salort, Bénédicte Gaborit, Antoine Muchir, Xavier Ferrer, Pascale Richard, Corinne Metay, Stéphane Boulé, Sarah Leonard-Louis, Philippe Mabo, V. Tiffreau, Caroline Stalens, Jitendra K. Vohra, Stéphane Schaeffer, Khadija Chikhaoui, Eric Bieth, Sandra Mercier, Pierre Ambrosi, Aleksandra Nadaj-Pakleza, Michèle Mayer, Katja Zeppenfeld, Gisèle Bonne, Véronique Manel, Jean-Marc Davy, Guilhem Sole, Ghassan Moubarak, Nicolas Lamblin, Klaus Dieterich, Christophe Meune, Abdallah Fayssoil, Arnaud Lazarus, Philippe Maury, Karim Wahbi, Philippe Petiot, Isabelle Jéru, Annick Toutain, Corinne Vigouroux, Ana Ferreiro, Maud Michaud, H.M. Bécane, Bruno Eymard, Thomas D. Gossios, Marie-Christine Vantyghem, Saurabh Kumar, Estelle Gandjbakhch, Yann Péréon, T. Thompson, Marie-Christine Minot-Myhié, Anthony Behin, Frédéric Sacher, Philippe Charron, Nicolas Combes, Julien Praline, Dominique Babuty, Emmanuelle Lagrue, Usha B. Tedrow, Jean-Marc Sellal, Florence Petit, Perry M. Elliott, Frédéric Anselme, Philippe Chevalier, Frederic Taithe, Christine Barnerias, Vincent Laugel, Andoni Echaniz-Laguna, Raphaël P. Martins, Alexander F.A. Androulakis, Rabah Ben Yaou, Franck Boccara, Ulrike Walther-Louvier, Tanya Stojkovic, Françoise Bouhour, Annachiara De Sandre-Giovannoli, Susana Quijano-Roy, Françoise Chapon, Jean-Noël Trochu, Céline Tard, Anne Rollin, Jean-Marie Cuisset, Denis Duboc, Raphaël Porcher, Catherine Sarret, Jonathan M. Kalman, Florence Demurger, Damien Bonnet, Christine Francannet, Neal K. Lakdawala, Romain Eschalier, Fabien Labombarda, Kostantinos Savvatis, Raul Juntas Morales, Isabelle Desguerre, Nicolas Lévy, Anne-Claire Brehin, Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), St Bartholomew's Hospital (London), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Association française contre les myopathies (AFM-Téléthon), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Ambroise Paré [AP-HP], William Harvey Research Institute, Barts and the London Medical School, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Filière Neuromusculaire (FILNEMUS), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Caen Normandie (UNICAEN), Laboratoire d'Informatique Scientifique et Industrielle (LISI), Université de Poitiers-Ecole Nationale Supérieure de Mécanique et d'Aérotechnique [Poitiers] (ISAE-ENSMA), Hôpital Raymond Poincaré [AP-HP], CHU Lille, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Aix Marseille Université (AMU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique Pasteur [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Royal Melbourne Hospital, Leiden University Medical Center (LUMC), Universiteit Leiden, Service de neurologie pédiatrique [CHU Necker], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Hôpital Privé Le Bois Ramsay Santé [Lille], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Bordeaux], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [APHP], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], Hôpital Cochin [AP-HP], Hospices Civils de Lyon (HCL), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Laboratoire d'étude de la motricité humaine - EA 3608 (LEMH), Université de Lille, Droit et Santé, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montréal (UdeM), Laboratoire Génie des procédés papetiers (LGP2 ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), The Heart Hospital [London], University College of London [London] (UCL), This study was funded by grants from the AFM-Téléthon (French Alliance against Myopathies), which was not involved in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. Some of this work was undertaken at University College London (United Kingdom) and St. Bartholomew’s Hospital (London, United Kingdom), which received a portion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP]-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Laboratoire d'Informatique Scientifique et Industrielle (LISI / ENSMA), LISI-ENSMA, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Unité de Cardiologie et Soins Intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpital neurologique, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service Neurologie Pédiatrique, Service de Neuropédiatrie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Département de Neurologie, Hôpital Civil de Strasbourg, Groupe Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, CHU - HÔTEL-DIEU Clermont-Ferrand, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Clinique Ambroise Paré, CHU Cochin [AP-HP], Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hopital Neurologique-Hôpital Femme Mère Enfant, Department of Medicine, Columbia University [New York]-College of Physicians and Surgeons, Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Hôpital de Rangueil, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'étude de la motricité humaine (LEMH EA3608), Université de Montréal - UdeM (CANADA), Laboratoire Génie des procédés papetiers (LGP2), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hôpital Purpan [Toulouse], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Tachycardia, medicine.medical_specialty, implantable, Accurate estimation, Ventricular Tachyarrhythmias, Validation Studies as Topic, 030204 cardiovascular system & hematology, tachycardia, Sudden death, LMNA, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, death, Physiology (medical), Internal medicine, defibrillators, medicine, Humans, In patient, 030212 general & internal medicine, sudden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Prediction score, business.industry, Defibrillators, Implantable, ventricular, Tachycardia, Ventricular, Cardiology, Female, medicine.symptom, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business
Abstract: Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator–treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0–7.2] and 5.1 [2.0–9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711–0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642–0.959), and the calibration slope was 1.082 (95% CI, 0.643–1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03058185.
Published: 2019

28. 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

29. Characterization, Prognosis, and Treatment of Patients With Metastatic Lung Carcinoid Tumors

Author: Michel Ducreux, Amandine Berdelou, Patrick Robelin, Valérie Hervieu, Pierre-Jean Valette, Sophie Leboulleux, Eric Baudin, Jean-Yves Scoazec, Julien Hadoux, David Planchard, Catherine Lombard-Bohas, Thomas Walter, Julien Forestier, Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'oncologie médicale, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut Gustave Roussy (IGR), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], Carcinoid tumors, Carcinoid Tumor, Neuroendocrine tumors, Scintigraphy, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Neoplasm Metastasis, Aged, Randomized Controlled Trials as Topic, Retrospective Studies, Aged, 80 and over, Performance status, medicine.diagnostic_test, business.industry, Hazard ratio, Middle Aged, Prognosis, medicine.disease, 3. Good health, Oxaliplatin, Survival Rate, 030104 developmental biology, Oncology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Radionuclide therapy, Female, business, medicine.drug
Abstract: Introduction Metastatic lung carcinoids (MLCs) remain poorly characterized and no prognostic stratification exists. Methods We conducted a retrospective study including patients with MLCs in two European expert centers. The aims were to characterize these cases and to identify prognostic factors of survival and effectiveness of their treatments. Results A total of 162 patients with MLC were included: 50% were women, and the median age was 61 years. Half of the patients had synchronous metastases, mainly located in the liver (75%), bone (42%), and lung (25%). According to WHO classification, MLCs were typical (28%), atypical (60%), or unspecified (12%). A functioning syndrome was observed in 43% of cases and an uptake at somatostatin receptor scintigraphy in 76% of cases. The 5-year overall survival rate was 60% and at 10 years this was 25%. In multivariate analysis, Eastern Cooperative Oncology Group performance status of 0-1 (hazard ratio [HR]: 5.81, 95% confidence interval [CI]: 2.10–16.11), uptake on SRS (HR: 0.38, 95% CI: 0.22–0.66), low serum chromogranin A (HR: 2.27, 95% CI: 1.36–3.81), and typical carcinoid (HR: 1.87, 95% CI: 1.26–2.78) were associated with better survival. According to Response Evaluation Criteria in Solid Tumors version 1.0, the highest objective response rates were obtained after radiofrequency ablation of metastases (86%), liver embolization (56%), peptide receptor radionuclide therapy (27%), and oxaliplatin-based chemotherapy (18%). Conclusions MLCs are characterized by a high frequency of atypical carcinoids, functioning syndrome, and liver/bone metastases. WHO classification, performance status, somatostatin receptor scintigraphy, and chromogranin A were associated with longer survival. Partial response was more frequent with locoregional therapies, peptide receptor radionuclide therapy, or oxaliplatin-based chemotherapy.
Published: 2019

30. Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions

Author: Thierry Vincent, A.-M. Guennoc, Pierre Labauge, Anne Kerbrat, François Cotton, Stéphane Kremer, Béatrice Carsin-Nicol, Mahmoud Charif, Sandra Vukusic, Thibaut Allou, Jérôme De Seze, Aurélie Ruet, Laurent Magy, Nicolas Menjot de Champfleur, Clarisse Carra-Dalliere, Guido Ahle, Eric Thouvenot, Françoise Durand-Dubief, Hélène Oesterle, Valérie Rigau, Denis Sablot, Romain Marignier, Nicolas Collongues, Gilles Edan, Mikael Cohen, Sonia Hebbadj, Benoit Lhermitte, Frederic Taithe, M. P. Boncoeur-Martel, Xavier Ayrignac, Grelier, Elisabeth, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Département d’Immunologie, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de radiologie [Strasbourg], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pierre Wertheimer, Département de Neurologie, Service de Neurologie [Lyon], CHU Lyon, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Pasteur [Nice] (CHU), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Service de neurologie [Rennes], Université de Rennes (UR), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Radiologie et Imagerie Médicale [CHU Limoges], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Atypical inflammatory demyelinating syndrome, medicine.medical_specialty, Pathology, Multiple Sclerosis, Histopathology, Context (language use), Immunopathology, Cohort Studies, Lesion, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Pathological, Aged, Retrospective Studies, Neuroradiology, Aquaporin 4, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain biopsy, Neuromyelitis Optica, food and beverages, Magnetic resonance imaging, Middle Aged, medicine.disease, Atypical demyelinating lesions, Magnetic Resonance Imaging, 3. Good health, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Acute Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), medicine.symptom, business, Aquaporin-4, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Balo-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
Published: 2019

31. Relationships between brain perfusion and early recanalization after intravenous thrombolysis for acute stroke with large vessel occlusion

Author: Cyril Dargazanli, Yves Berthezène, Sébastien Richard, Vincent Costalat, Serge Bracard, Pierre Seners, Séverine Debiais, Ana-Paula Narata, Caroline Arquizan, Canan Ozsancak, Christophe Magni, Jean-Philippe Cottier, Jean-Louis Mas, Benjamin Gory, Laurence Legrand, Stéphanie Lion, Guillaume Turc, Jean-Claude Baron, Catherine Oppenheim, Norbert Nighoghossian, Tae-Hee Cho, Olivier Naggara, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional d'Orléans (CHRO), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Département de Neuroradiologie[Montpellier], Service de neurologie [CHRU Nancy], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Martinez Rico, Clara, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, thrombolysis, medicine.medical_specialty, Mechanical Thrombolysis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Ischemia, Perfusion scanning, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Cerebral perfusion, Internal medicine, ischemic stroke, medicine, Humans, magnetic resonance imaging, Prospective Studies, Registries, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], cardiovascular diseases, Thrombus, Stroke, Aged, Retrospective Studies, Acute stroke, Aged, 80 and over, business.industry, Brain, Original Articles, Thrombolysis, Middle Aged, medicine.disease, Perfusion, [SDV] Life Sciences [q-bio], Diffusion Magnetic Resonance Imaging, Neurology, thrombectomy, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Magnetic Resonance Angiography, 030217 neurology & neurosurgery, Large vessel occlusion
Abstract: In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR ( P = 0.006), shorter thrombus on T2*-imaging ( P
Published: 2019

32. Experience implication in subjective surgical ergonomics comparison between laparoscopic and robot-assisted surgeries

Author: Aurélien Binet, Franck Bruyère, Hubert Lardy, Thomas Hebert, Jean-Michel Escoffre, Frédéric Marchal, Vanda Mendes, Henri Marret, Service de gynécologie-obstétrique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, 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 Chirurgie Pédiatrique [CHRU Tours], Service d'oncogénétique [Vandoeuvre-Lès-Nancy] (Institut de Cancérologie de Lorraine - CLCC Alexis Vautrin), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Escoffre, Jean-Michel, Service de Gynécologie-Obstétrique [CHRU Tours], Université de Tours, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Laparoscopic surgery, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Health Informatics, 03 medical and health sciences, 0302 clinical medicine, Robotic Surgical Procedures, Physical Ergonomics, Humans, Medicine, Musculoskeletal Diseases, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Human factors and ergonomics, Workload, Occupational Diseases, 030220 oncology & carcinogenesis, Surgical ergonomics, Physical therapy, Operative time, Laparoscopy, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Surgery, Ergonomics, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction Laparoscopic surgery (LS) may lead to musculoskeletal disorders (MSDs) and an increase in physical and mental workloads to the surgeon. Robot-assisted surgery (RAS) should improve the ergonomy of the surgeon. This study assesses the experience influence in surgical ergonomics between LS and RAS. Methods LS and RAS lasting more than 60 min of effective operative time were compared. During the surgical procedure, the physical discomfort was evaluated using the Borg scale. At the end, the mental workload was evaluated using the NASA-TLX index. After global analysis, the experienced and young surgeons were assessed. Results 88 RAS and 82 LS were evaluated. During LS, the physical discomfort was significantly higher in all segments, and the pain increased significantly during the procedure in all segments compared to that evaluated in the RAS (p < 0.05). Forearms and the back were the most painful. The young surgeons did not display any improvement in the physical ergonomics of the RAS compared to the LS. Concerning the mental ergonomics, the overall workload and performance were significantly greater during the LS compared to the RAS (p < 0.05). For the young surgeons, the overall workload, the effort, the mental and the physical demands were greater during LS (p < 0.05). For the experienced surgeons, the physical demand was lower during the RAS compared to the LS (p < 0.05). However, the experienced surgeons expressed a feeling of greater performance after the LS (p < 0.01). RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons. Conclusion RAS significantly reduces the onset of MSDs compared to LS, especially for the experienced surgeons.
Published: 2019

33. 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

34. 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

35. Rational and Design of the SIMULATOR Study: A Multicentre Randomized Study to Assess the Impact of SIMULation-bAsed Training on Transoesophageal echocardiOgraphy leaRning for Cardiology Residents

Author: Théo Pezel, Anne Bernard, Yoan Lavie Badie, Julien Dreyfus, Etienne Audureau, Yohann Bohbot, Damien Fard, Arnaud Hubert, Lee S. Nguyen, Cécile Monteil, Loïc Bière, Florent Le Ven, Marjorie Canu, Sophie Ribeyrolles, Baptiste Mion, Basile Mouhat, Baptiste Bazire, Charles Fauvel, Julien Ternacle, Jennifer Cautela, Théo Cambet, Thierry Le Tourneau, Erwan Donal, Stéphane Lafitte, Nicolas Mansencal, Augustin Coisne, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Johns Hopkins University (JHU), 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)-Université de Tours-Hôpital Bretonneau, Faculté de Médecine, Université de Tours, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre cardiologique du Nord (CCN), 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), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), 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, CHU 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), Service de néphrologie et immunologie clinique [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 Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Henri Mondor [Créteil], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: medicine.medical_specialty, Randomization, education, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Transoesophageal echocardiography, transesophageal echoardiography, law.invention, Likert scale, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Internal medicine, medicine, Methods, Diseases of the circulatory (Cardiovascular) system, Simulation based, Simulation, business.industry, 3. Good health, Test (assessment), Multicenter study, RC666-701, Cardiology, residents, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, medical education, Educational program, human activities, simulation-based, randomized study
Abstract: Introduction: Simulation-based training in transesophageal echocardiography (TEE) seems promising. However, data are limited to non-randomized or single-center studies. To assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology.Materials and Methods: Nationwide prospective randomized multicenter study involving 43 centers throughout France allowing for the inclusion of >70% of all French cardiology residents. All cardiology residents naive from TEE will be included. Randomization with stratification by center will allocate residents to either a control group receiving theoretical knowledge by e-learning only, or to an intervention group receiving two simulation-based training sessions on a TEE simulator in addition.Results: All residents will undergo both a theoretical test (0–100 points) and a practical test on a TEE simulator (0–100 points) before and 3 months after the training. Satisfaction will be assessed by a 5-points Likert scale. The primary outcomes will be to compare the scores in the final theoretical and practical tests between the two groups, 3 months after the completion of the training.Conclusion: Data regarding simulation-based learning in TEE are limited to non-randomized or single-center studies. The randomized multicenter SIMULATOR study will assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology, and whether such an educational program should be proposed in first line for TEE teaching.
Published: 2021

36. The impact of diabetes on heart failure development: the cardio-renal-metabolic connection

Author: Paul Valensi, Jean-Michel Halimi, Erwan Donal, Sara Pinto, Gaëtan Prévost, Jonchère, Laurent, Service d'endocrinologie diabétologie, nutrition (Hôpital Jean Verdier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, CHU Rouen, Normandie Université (NU), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], For this review paper the authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, 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), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, GLP1-receptor agonists, Endocrinology, Diabetes and Metabolism, Population, heart failure, 030209 endocrinology & metabolism, Type 2 diabetes, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Intensive care medicine, Contraindication, [SDV.IB] Life Sciences [q-bio]/Bioengineering, education.field_of_study, business.industry, Diabetes, General Medicine, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Natural history, Diabetes Mellitus, Type 2, Heart failure, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, SGLT2 inhibitors, chronic kidney disease, coronary artery disease, Kidney disease
Abstract: Heart failure (HF) and chronic kidney disease (CKD) are often associated in type 2 diabetes (T2D), aggravate each other and exert synergistic effects to increase the risk of cardiac and renal events. The risks of renal worsening in HF patients and HF in CKD patients need to be evaluated to tailor preventive therapy. The recent CV and renal trials enriched our knowledge about the natural history of HF and CKD in T2D and provided evidence for the benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in HF and renal decline prevention. SGLT-2is are the best choice in patients with HFrEF to improve CV prognosis and HF-related outcomes and also to prevent kidney-related outcomes, and in CKD patients to slow down renal failure and also reduce hospitalization for HF and CV death. In both situations the number of patients to treat in order to prevent such events in one patient is lower than in the general T2D population at high CV risk. GLP1-receptor agonists could be an alternative in a patient who is intolerant or has a contraindication to SGLT-2is. A tight collaboration between diabetologists, nephrologists and cardiologists should be encouraged for a holistic and effective strategy to reduce the burden of cardio-renal-metabolic interaction.
Published: 2021

37. Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

Author: Arthur Dujardin, Arnaud de La Blanchardière, Julia Dina, Karl Stefic, Christophe Ravel, Julie Bonhomme, Renaud Verdon, Anna Lucie Fournier, Unité de Maladies Infectieuses et Tropicales [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), Normandie Université (NU), Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Immunology, Case Report, Serology, pancytopenia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, visceral leishmaniasis, Medical history, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Hemophagocytic lymphohistiocytosis, bone marrow aspirate, business.industry, HIV, RC581-607, medicine.disease, Pancytopenia, 3. Good health, Visceral leishmaniasis, medicine.anatomical_structure, hemophagocytic lymphohistiocytosis, Chills, Bone marrow, medicine.symptom, Immunologic diseases. Allergy, business, Viral load
Abstract: We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.
Published: 2021

38. Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: a retrospective study

Author: Eric Estève, Brigitte Dréno, Mahtab Samimi, Hervé Maillard, Yannick Le Corre, Agnès Caille, Astrid Blom, Monica Dinulescu, Philippe Saiag, Thibault Kervarrec, E. Wierzbicka-Hainaut, Frédéric Jaouen, Université de Tours (UT), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pathologie [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), 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), 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), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Département de Dermatologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie Générale et Oncologique [AP-HP Hôpital Ambroise-Paré, Paris], Hôpital Ambroise Paré [AP-HP], Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, 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 Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and CCSD, Accord Elsevier
Subjects: Male, Wide Local Excision, Neoplasm, Residual, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cohort Studies, 030207 dermatology & venereal diseases, 0302 clinical medicine, Merkel cell carcinoma, Surgical margins, Wide local excision, Hazard ratio, Margins of Excision, Merkel Cell Carcinoma, Middle Aged, Prognosis, Combined Modality Therapy, Primary tumor, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Female, France, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Disease-Free Survival, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Mortality, General surgery, Survival rate, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, Retrospective cohort study, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Skin neoplasms, Survival Analysis, Surgery, Carcinoma, Merkel Cell, Radiation therapy, Multivariate Analysis, Radiotherapy, Adjuvant, Neoplasm Recurrence, Local, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Follow-Up Studies
Abstract: Wide local excision constitutes the standard of care for Merkel cell carcinoma, but the optimal margin width remains controversial.To assess whether narrow margins (0.5-1 cm) were associated with outcome.Patients were recruited from a retrospective French multicentric cohort and included if they had had excision of primary tumor with minimum lateral margins of 0.5 cm. Factors associated with mortality and recurrence were assessed by multivariate regression.Among the 214 patients included, 58 (27.1%) had undergone excision with narrow margins (0.5-1 cm) versus 156 (72.9%) with wide margins (1 cm). During a median follow-up of 50.7 months, cancer-specific survival did not differ between groups (5-year specific survival rate 76.8% [95% confidence interval 61.7%-91.9%] and 76.2% [95% confidence interval 68.8%-83.6%], respectively). Overall survival, any recurrence-free survival, and local recurrence-free survival did not significantly differ between groups. Cancer-specific mortality was associated with age, male sex, American Joint Committee on Cancer stage III, and presence of positive margins.Retrospective design, heterogenous baseline characteristics between groups.Excision with narrow margins was not associated with outcome in this cohort, in which most patients had clear margins and postoperative radiation therapy. Residual tumor, mostly found on deep surgical margins, was independently associated with prognosis.
Published: 2021

39. Bordetella hinzii : an Unusual Pathogen in Human Urinary Tract Infection

Author: Laurent Mereghetti, Charlotte Descours, Camille Petillon, Nived Collercandy, Maryam Abid, Marie-Frédérique Lartigue, Claudia Carvalho-Schneider, Service de bactériologie-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de bactériologie et d'hygiène hospitalière [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU 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), Service de Médecine Interne et Maladies Infectieuses [Tours], 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 Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Abdominal pain, Urinary system, [SDV]Life Sciences [q-bio], 030106 microbiology, Physical examination, Bordetella hinzii, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Medical history, 030212 general & internal medicine, Pathogen, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, biology, business.industry, lithiasis, Left flank, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Tenderness, pyelonephritis, urinary tract infections, medicine.symptom, business
Abstract: A 37-year-old man with no prior medical history except chronic alcohol and tobacco consumption was admitted for fever at 38.5°C and abdominal pain starting 2 days before admission. Physical examination confirmed tenderness of the left flank with no other abnormalities. Blood testing found increased
Published: 2021

40. Cochlear Implantation and Other Treatments in Single-Sided Deafness and Asymmetric Hearing Loss: Results of a National Multicenter Study Including a Randomized Controlled Trial

Author: Alain Uziel, Sébastien Schmerber, Bernard Fraysse, Daniele Bernardeschi, M. Marx, Nicolas-Xavier Bonne, Isabelle Mosnier, Frédéric Venail, David Bakhos, Michel Mondain, Christophe Vincent, Emmanuel Lescanne, Olivier Deguine, Yann Nguyen, Benoit Lepage, Olivier Sterkers, Benoit Godey, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d'Oto-Rhino-Laryngologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service ORL et chirurgie cervico-faciale [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Neurosciences de Montpellier (INM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Adult, Quality of life, medicine.medical_specialty, Physiology, Visual analogue scale, medicine.medical_treatment, Asymmetric hearing loss, Deafness, Audiology, Hearing Loss, Unilateral, law.invention, 03 medical and health sciences, Speech and Hearing, 0302 clinical medicine, Randomized controlled trial, law, Cochlear implant, Bone-anchored hearing system, medicine, otorhinolaryngologic diseases, Humans, Prospective Studies, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Hearing Loss, 030223 otorhinolaryngology, business.industry, Cochlear Implantation, Sensory Systems, Confidence interval, Treatment Outcome, Otorhinolaryngology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Speech Perception, Cochlear implants, Contralateral routing of the signal hearing Aids, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Tinnitus, Research Article, Cohort study
Abstract: Introduction: Cochlear implantation is a recent approach proposed to treat single-sided deafness (SSD) and asymmetric hearing loss (AHL). Several cohort studies showed its effectiveness on tinnitus and variable results on binaural hearing. The main objective of this study is to assess the outcomes of cochlear implantation and other treatment options in SSD/AHL on quality of life. Methods: This prospective multicenter study was conducted in 7 tertiary university hospitals and included an observational cohort study of SSD/AHL adult patients treated using contralateral routing of the signal (CROS) hearing aids or bone-anchored hearing systems (BAHSs) or who declined all treatments, and a randomized controlled trial in subjects treated by cochlear implantation, after failure of CROS and BAHS trials. In total, 155 subjects with SSD or AHL, with or without associated tinnitus, were enrolled. After 2 consecutive trials with CROS hearing aids and BAHSs on headband, all subjects chose any of the 4 treatment options (abstention, CROS, BAHS, or cochlear implant [CI]). The subjects who opted for a CI were randomized between 2 arms (CI vs. initial observation). Six months after the treatment choice, quality of life was assessed using both generic (EuroQoL-5D, EQ-5D) and auditory-specific quality-of-life indices (Nijmegen Cochlear implant Questionnaire [NCIQ] and Visual Analogue Scale [VAS] for tinnitus severity). Performances for speech-in-noise recognition and localization were measured as secondary outcomes. Results: CROS was chosen by 75 subjects, while 51 opted for cochlear implantation, 18 for BAHSs, and 11 for abstention. Six months after treatment, both EQ-5D VAS and auditory-specific quality-of-life indices were significantly better in the “CI” arm versus “observation” arm. The mean effect of the CI was particularly significant in subjects with associated severe tinnitus (mean improvement of 20.7 points ± 19.7 on EQ-5D VAS, 20.4 ± 12.4 on NCIQ, and 51.4 ± 35.4 on tinnitus). No significant effect of the CI was found on binaural hearing results. Before/after comparisons showed that the CROS and BAHS also improved significantly NCIQ scores (for CROS: +7.7, 95% confidence interval [95% CI] = [4.5; 10.8]; for the BAHS: +14.3, 95% CI = [7.9; 20.7]). Conclusion: Cochlear implantation leads to significant improvements in quality of life in SSD and AHL patients, particularly in subjects with associated severe tinnitus, who are thereby the best candidates to an extension of CI indications.
Published: 2021

41. 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

42. 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

43. Mental health and burnout of radiologists: Measurement tools, risk factors. Survey in the Center Val-de-Loire region

Author: Philibert, C., colombat, philippe, Coillot, H., Fouquereau, Evelyne, Cottier, J.P., Qualité de vie et Santé psychologique [Tours] (QualiPsy - E.E. 1901), Université de Tours, Hôpital Bretonneau, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bretonneau, and Université de Tours (UT)
Subjects: Santé mentale, Région Centre-Val-de-Loire, Burnout, Mental health, Radiology, Caregiver, Radiologie, [SHS]Humanities and Social Sciences
Abstract: International audience; The syndrome of professional exhaustion or burnout particularly affects physicians with very little data available on French radiology.The objective of this article is to present the characteristics of burnout and the commonly used rating scale (MBI scale) as well as the scale used to assess anxiety and depression (HADS scale). The results of a survey carried out among radiologists in the Center Val-de-Loire region, based on these scales by associating them with additional questions specific to radiological activity, shows very worrying and more pejorative mental health scores than for most other medical specialties.This article invites each radiologist to take stock of their mental health using the scales proposed and to engage in a dialogue within the teams on this inventory to propose solutions aimed at improving satisfaction and personal fulfillment at work. The combination of organizational changes and support for individuals provides an effective approach to reducing stress at work.; Le syndrome d’épuisement professionnel ou burnout touche tout particulièrement les médecins avec très peu de données disponibles concernant la radiologie française. Données récentes L’objectif de cet article est de présenter les caractéristiques du burnout,l’échelle d’évaluation habituellement utilisée (Échelle MBI) ainsi que l’échelle utilisée pour évaluer l’anxiété et la dépression (Échelle HADS). Les résultats d’une enquête effectuée auprès des radiologues de la région Centre Val-de-Loire, reposant sur ces échelles en y associant des questions complémentaires propres à l’activité radiologique, montre des scores de santé mentale très préoccupants et plus péjoratifs que pour la plupart des autres spécialités médicales. Conclusion Cet article invite chaque radiologue à faire le point sur sa santé mentale à l’aide des échelles proposées et à engager un dialogue au sein des équipes sur cet état des lieux pour proposer des solutions visant à améliorer la satisfaction et l’accomplissement personnel au travail. La combinaison des changements organisationnels et d’une aide apportée aux individus fournit une approche efficace pour réduire le stress au travail.
Published: 2021

44. DLG4-related synaptopathy: a new rare brain disorder

Author: Edgard Verdura, Alex MacKenzie, Rolph Pfundt, Tobias B. Haack, Ange Line Bruel, Paulino Gómez-Puertas, Anna C.E. Hurst, Bert B.A. de Vries, Stella A. de Man, Maria Johansson Soller, Bregje W.M. van Bon, Elisabeth Sarrazin, Agustí Rodríguez-Palmero, Stephan Waldmüller, Melanie O’Leary, Anne Sophie Denommé-Pichon, Bitten Schönewolf-Greulich, Joseph T. Shieh, V. A. Bjerregaard, Vahid Bahrambeigi, Malin Kvarnung, Agatha Schlüter, Anne Marie Bisgaard, Ingrid M.B.H. van de Laar, Elisa Giorgio, Lars Feuk, Mieke M. van Haelst, Thomas D. Challman, Ineke van de Burgt, Sulagna Kushary, Simone F. Reiter, David B. Everman, Zeynep Tümer, Giorgia Mandrile, Conny M. A. van Ravenswaaij-Arts, Charles Shaw-Smith, Juliane Hoyer, Chad R. Haldeman-Englert, Lotte Kleinendorst, Bryce A. Mendelsohn, Anna Lindstrand, Christine Coubes, Gea Beunders, Sixto García-Miñaur, Antonio Vitobello, Melissa Maria Boerrigter, Alysia Kern Lovgren, Anya Revah-Politi, Carlos E. Prada, Bertrand Isidor, Elena Repnikova, Stephanie Spranger, Esmée van Drie, Frédéric Tran Mau-Them, Zohra Shad, Ben Pode-Shakked, Aurora Pujol, Christiane Zweier, Bjørn Ivar Haukanes, David Gómez-Andrés, Kathleen A. Leppig, Marta Pacio-Míguez, Motti Shohat, Yuval Landau, Benjamin Cogné, Frances Elmslie, Kimberly A. Aldinger, Anita Rauch, Juliann M. Savatt, Nicolas Gruchy, Sharon Whiting, William B. Dobyns, Thomas J. Dye, Sebastien Moutton, Heidi Thiese, Setareh Moghadasi, Iñigo Marcos-Alcalde, Jenny Morton, Sumit Parikh, María Palomares-Bralo, Stéphanie Arpin, Tracy S. Gertler, Meredith J. Ross, Bernt Popp, Amelie J. Müller, Claudia A. L. Ruivenkamp, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Enfermedades Raras (CIBERER), Hospital Universitario Germans Trias I Pujol, Vall d'Hebron University Hospital [Barcelona], Center for Integrative Brain Research [Seattle, WA, USA], University of Washington [Seattle]-Seattle Children's Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Department of Molecular and Human Genetics (Baylor College of Medicine), Baylor College of Medecine, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinical Genetics, Human Genetics, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)
Subjects: 0301 basic medicine, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], 030105 genetics & heredity, Biology, 03 medical and health sciences, Intellectual Disability, Intellectual disability, medicine, Missense mutation, Humans, Global developmental delay, Exome, Genetics (clinical), Genetics, Brain Diseases, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Brain, medicine.disease, 030104 developmental biology, Phenotype, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Autism spectrum disorder, Neurodevelopmental Disorders, Synaptopathy, DLG4, Postsynaptic density, Disks Large Homolog 4 Protein
Abstract: Contains fulltext : 245031.pdf (Publisher’s version ) (Closed access) PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies. CONCLUSION: The present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
Published: 2021

45. 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

46. 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

47. Cumulative effects of therapies on disability in relapsing multiple sclerosis

Author: Romain Casey, Fabien Rollot, Gilles Edan, David-Axel Laplaud, Emmanuelle Leray, Sandra Vukusic, Sandrine Wiertlewski, Marc Debouverie, 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), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), CHU Pontchaillou [Rennes], 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), Agence Nationale de la Recherche, Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Eugène Devic EDMUS Foundation, 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), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-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 (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Adult, medicine.medical_specialty, Treatment response, [SDV]Life Sciences [q-bio], cumulative effect, Multiple sclerosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Cumulative effect, business.industry, Cumulative effects, treatment response, medicine.disease, 3. Good health, long-term observational study, Neurology, Female, Neurology (clinical), Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract: Background: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. Objective: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. Results: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). Conclusion: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.
Published: 2021

48. 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

49. 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

50. Identification of PITX3 mutations in individuals with various ocular developmental defects

Author: Caroline Michot, Julie Plaisancié, Marta Corton, Edouard Cottereau, Julian Delanne, Nicolas Chassaing, Nicola K. Ragge, Jacmine Pechmeja, Celia Zazo Seco, P Calvas, Tatiana Lupasco, Carmen Ayuso, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Génétique Médicale [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), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service d'Ophtalmologie [Hopital Purpan - Toulouse], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIBER de Enfermedades Raras (CIBERER), Oxford Brookes University, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, CARBILLET, Véronique, Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Ophtalmologie [CHU Toulouse], Pôle Céphalique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Male, genetic structures, MESH: Congenital Abnormalities / pathology, medicine.disease_cause, Microphthalmia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Peters anomaly, Microphthalmos, PITX3, Eye Abnormalities, Child, Genetics (clinical), MESH: Heterozygote, Genetics, Sanger sequencing, MESH: Aged, MESH: Microphthalmos / pathology, Mutation, MESH: Infant, Newborn, sclereocornea, MESH: Congenital Abnormalities / genetics, MESH: Infant, 3. Good health, Pedigree, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Congenital cataracts, symbols, Female, Heterozygote, MESH: Mutation, Adolescent, MESH: Pedigree, Biology, MESH: Transcription Factors / genetics, Cataract, Congenital Abnormalities, 03 medical and health sciences, symbols.namesake, Cataracts, Anterior segment mesenchymal disorder, medicine, Humans, MESH: Homeodomain Proteins / genetics, Aged, MESH: Adolescent, Homeodomain Proteins, Anophthalmia, MESH: Humans, Genetic heterogeneity, MESH: Child, Preschool, MESH: Microphthalmos / genetics, Infant, Newborn, MESH: Eye Abnormalities / pathology, Infant, MESH: Cataract / pathology, medicine.disease, MESH: Male, eye diseases, Ophthalmology, 030104 developmental biology, MESH: Cataract / genetics, MESH: Eye Abnormalities / genetics, Pediatrics, Perinatology and Child Health, Eye development, sense organs, MESH: Female, Transcription Factors
Abstract: Background: Congenital cataract displays large phenotypic (syndromic and isolated cataracts) and genetic heterogeneity. Mutations in several transcription factors involved in eye development, like PITX3, have been associated with congenital cataracts and anterior segment mesenchymal disorders. Materials and methods: Targeted sequencing of 187 genes involved in ocular development was performed in 96 patients with mainly anophthalmia and microphthalmia. Additionally, Sanger sequencing analysis of PITX3 was performed on a second cohort of 32 index cases with congenital cataract and Peters anomaly and/or sclereocornea. Results: We described five families with four different PITX3 mutations, two of which were novel. In Family 1, the heterozygous recurrent c.640_656dup (p.Gly220Profs*95) mutation cosegregated with eye anomalies ranging from congenital cataract to Peters anomaly. In Family 2, the novel c.669del [p.(Leu225Trpfs*84)] mutation cosegregated with dominantly inherited eye anomalies ranging from posterior embryotoxon to congenital cataract in heterozygous carriers and congenital sclereocornea and cataract in a patient homozygous for this mutation. In Family 3, we identified the recurrent heterozygous c.640_656dup (p.Gly220Profs*95) mutation segregating with congenital cataract. In Family 4, the de novo c.582del [p.(Ile194Metfs*115)] mutation was identified in a patient with congenital cataract, microphthalmia, developmental delay and autism. In Family 5, the c.38G>A (p.Ser13Asn) mutation segregated dominantly in a family with Peters anomaly, which is a novel phenotype associated with the c.38G>A variant compared with the previously reported isolated congenital cataract. Conclusions: Our study unveils different phenotypes associated with known and novel mutations in PITX3, which will improve the genetic counselling of patients and their families.
Published: 2021
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