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1. Consensus statement by the French Society of Endocrinology (SFE) and French Society of Pediatric Endocrinology & Diabetology (SFEDP) on diagnosis of Cushing's syndrome

Author: Antoine Tabarin, Guillaume Assié, Pascal Barat, Fidéline Bonnet, Jean François Bonneville, Françoise Borson-Chazot, Jérôme Bouligand, Anne Boulin, Thierry Brue, Philippe Caron, Frédéric Castinetti, Olivier Chabre, Philippe Chanson, Jean Benoit Corcuff, Christine Cortet, Régis Coutant, Anthony Dohan, Delphine Drui, Stéphanie Espiard, Delphine Gaye, Solenge Grunenwald, Laurence Guignat, Elif Hindie, Frédéric Illouz, Peter Kamenicky, Hervé Lefebvre, Agnès Linglart, Laetitia Martinerie, Marie Odile North, Marie Laure Raffin-Samson, Isabelle Raingeard, Gérald Raverot, Véronique Raverot, Yves Reznik, David Taieb, Delphine Vezzosi, Jacques Young, Jérôme Bertherat, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Endocrinologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], 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), Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM], Aix Marseille Université (AMU), Institut Marseille Maladies Rares (MarMaRa), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service Endocrinologie, diabétologie, maladies métaboliques et nutrition (LILLE - Endocrino), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Endocrinologie pédiatrique[CHU 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), Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), 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 hospitalier universitaire de Nantes (CHU Nantes), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Service de médecine nucléaire [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), AP-HP. Université Paris Saclay, Hôpital Bicêtre, Hôpital Robert Debré, Service d’endocrinologie et nutrition [AP-HP Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Lapeyronie [Montpellier] (CHU), Groupement Hospitalier Lyon-Est (GHE), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Suppression, Endocrinology, Genetic, Cushing’s syndrome, Pregnancy, Endocrinology, Diabetes and Metabolism, Hypercortisolism, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Cushing’s disease, ACTH
Abstract: International audience; Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.
Published: 2022
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2. Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer

Author: Thomas Bachelot, Paul Cottu, Sylvie Chabaud, Florence Dalenc, Djelila Allouache, Suzette Delaloge, Jean-Philippe Jacquin, Julien Grenier, Laurence Venat Bouvet, Apurna Jegannathen, Mario Campone, Francesco Del Piano, Marc Debled, Anne-Claire Hardy-Bessard, Sylvie Giacchetti, Marie-Ange Mouret-Reynier, Philippe Barthelemy, Laure Kaluzinski, Audrey Mailliez, Eric Legouffe, Matthew Sephton, Judith Bliss, Jean-Luc Canon, Frederique Penault-Llorca, Jerome Lemonnier, David Cameron, Fabrice Andre, Rhodia Opérations, RHODIA, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Léon Bérard [Lyon], Department of Medical Oncology, Institut Curie, Paris 75248, France, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Oncologie Médicale [Saint Priest en Jarez], Institut de Cancérologie Lucien Neuwirth [Saint Priest en Jarez], Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Bergonié [Bordeaux], Centre Armoricain de Radiothérapie, d'Imagerie médicale et d'Oncologie [Plérin, Saint-Brieuc] (CARIO), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), ChemBioPharm, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Qingdao Agricultural University Qingdao, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CRLCC Paul Papin, Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), École des Hautes Études en Santé Publique [EHESP] (EHESP), Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Veille Sanitaire (INVS)
Subjects: Cancer Research, MESH: Xenograft Model Antitumor Assays, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], H3K27me3, JMJD3, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Everolimus, Disease-Free Survival, AR status, GSK-J4, Double-Blind Method, Antineoplastic Combined Chemotherapy Protocols, Humans, asymptomatic, MESH: Double-Blind Method, Everolimus, epidrugs, COVID, Prostate cancer, MESH: Humans, epigenetics, Cancer patients, MESH: Receptor, ErbB-2, MESH: Antineoplastic Combined Chemotherapy Protocols, xenografts, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH: Pyrimidines, MESH: Disease-Free Survival, Female, MESH: Female, MESH: Breast Neoplasms
Abstract: PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS In this randomized double-blind phase III study, women with high-risk, hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271 ). RESULTS Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting.
Published: 2022
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3. A ROD–CONE DYSTROPHY IS SYSTEMATICALLY ASSOCIATED TO THE RTN4IP1 RECESSIVE OPTIC ATROPHY

Author: Patrizia Amati-Bonneau, Xavier Zanlonghi, Claire-Marie Dhaenens, Gaël Manes, Béatrice Bocquet, Agathe Roubertie, Isabelle Meunier, Guy Lenaers, Majida Charif, 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), Université Mohamed 1 Oujda MAROC, UF Génopathies - Laboratoire de Biochimie et Biologie Moléculaire [Lille] (LBBM), Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Biochimie et Génétique [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), Clinique Jules-Vernes [Nantes], MitoVasc - 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), and LENAERS, Guy
Subjects: Male, Visual acuity, genetic structures, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Visual Acuity, inherited optic neuropathy, RTN4IP1, Original Study, Fluorescein Angiography, Child, rod–cone dystrophy, medicine.diagnostic_test, General Medicine, Middle Aged, Pedigree, [SDV] Life Sciences [q-bio], Phenotype, Mitochondrial respiratory chain, Female, medicine.symptom, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Adolescent, Fundus Oculi, Retinal ganglion, Mitochondrial Proteins, Young Adult, Atrophy, Ophthalmology, Electroretinography, medicine, Rod-cone dystrophy, Humans, Retrospective Studies, Cerebellar ataxia, business.industry, recessive disease, Dystrophy, DNA, medicine.disease, eye diseases, Mutation, sense organs, Visual Fields, Carrier Proteins, business, Cone-Rod Dystrophies
Abstract: Although RTN4IP1 has been firmly associated to recessive optic atrophies, we identified by systematic examination of the 55° fundus autofluorescence frames and the peripheral spectral-domain optical coherence tomographic images, a progressive rod–cone dystrophy in all individuals with biallelic RTN4IP1 mutations., Purpose: RTN4IP1 biallelic mutations cause a recessive optic atrophy, sometimes associated to more severe neurological syndromes, but so far, no retinal phenotype has been reported in RTN4IP1 patients, justifying their reappraisal. Methods: Seven patients from four families carrying biallelic RTN4IP1 variants were retrospectively reviewed, with emphasis on their age of onset, visual acuity, multimodal imaging including color and autofluorescence frames, spectral-domain optical coherence tomography with RNFL and macular analyses. Results: Seven patients from four RTN4IP1 families developed in their first decade of life a bilateral recessive optic atrophy with severe central visual loss, and primary nystagmus developed in 5 of 7 patients. Six patients were legally blind. In a second stage, the seven individuals developed a rod–cone dystrophy, sparing the macular zone and the far periphery. This retinal damage was identified by 55° field fundus autofluorescence frames and also by spectral-domain optical coherence tomography scans of the temporal part of the macular zone in five of the seven patients. Full-field electroretinography measurements disclosed reduced b-wave amplitude of the rod responses in all patients but two. Family 4 with the p.R103H and c.601A > T (p.K201*) truncating mutation had further combined neurological signs with cerebellar ataxia, seizures, and intellectual disability. Conclusion: RTN4IP1 recessive optic atrophy is systematically associated to a rod–cone dystrophy, which suggests that both the retinal ganglion cells and the rods are affected as a result of a deficit in the mitochondrial respiratory chain. Thus, systematic widefield autofluorescence frames and temporal macular scans are recommended for the evaluation of patients with optic neuropathies.
Published: 2020
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4. Age-related alterations on the capacities to navigate on a bike: use of a simulator and entropy measures

Author: Cédric Annweiler, Anne Humeau-Heurtier, Antoine Jamin, Pierre Abraham, Guillaume T. Duval, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
Subjects: irregularity, multiscale cross-entropy, Computer science, Computer Applications, Biomedical Engineering, Human physiology, Virtual reality, 01 natural sciences, 010305 fluids & plasmas, Computer Science Applications, age, 13. Climate action, Age related, 0103 physical sciences, time series, complexity, 010306 general physics, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Simulation
Abstract: International audience; Studying the impact of age is important to understand the phenomenon of aging and the disorders that are associated. In this work, we analyze age-related alterations on the capacities to navigate on a bike. For this purpose, we use CycléoONE, a bike simulator, and entropy measures. We thus record navigation data (handlebar angle and speed) during the ride. They are processed with two cross-distribution entropy methods (time-shift multiscale cross-distribution entropy and multiscale cross-distribution entropy). We also analyze the time series with a detrended cross-correlation analysis to determine which method can the best underline age-related alterations. Our results show that methods based on cross-distribution entropy may be efficient to stress the decrease in navigation capacities with age. The results are very encouraging for our future goal of adding medical benefits to a leisure equipment. They also show the value of using virtual reality to study the impact of age.
Published: 2020
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5. Agents Involved and Severity of Acute Ocular Exposure Reported at a Poison Control Center

Author: Adrien Buisset, E. Puskarczyk, Alexis Descatha, Gaël Le Roux, Philippe Gohier, Stéphanie Leruez, Centre Antipoison et Toxicovigilance du Grand Ouest (Angers) (CAPTV Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'ophtalmologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Centre de Recherche Clinique [GH Saint-Joseph, Paris], Université Paris Descartes - Paris 5 (UPD5)-GH Saint-Joseph, Centre antipoison et de toxicovigilance (Nancy) (CAPTV Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut de recherche en santé, environnement et travail (Irset), 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 ), Centres antipoison et de toxicovigilance (CAPTV Angers), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), and Bodin, Julie
Subjects: Adult, medicine.medical_specialty, Poison Control Centers, Adolescent, Injury control, Epidemiology, Accident prevention, household products, Poison control, macromolecular substances, Suicide prevention, poison center, Occupational safety and health, Young Adult, 03 medical and health sciences, 0302 clinical medicine, detergent, Injury prevention, medicine, Humans, childhood accident, 030212 general & internal medicine, Child, Retrospective Studies, business.industry, chemical eye burns, Human factors and ergonomics, occupational injuries, Middle Aged, Poison control center, [STAT] Statistics [stat], 3. Good health, [STAT]Statistics [stat], Ophthalmology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency medicine, 030221 ophthalmology & optometry, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Purpose - The aim was to identify severity factors useful in the initial management of patients with acute ocular exposure while considering both categories of products involved and circumstances of exposure. Methods - A retrospective study over a one-year period that included patients who benefited from the poison center services for eye exposure to a chemical substance. Results - Within a year, 1582 patients were identified. The sex ratio (M/F) was 0.8. The mean age was 28.5 ± 20.3 years. Among children, those under 4 years represented the most significant age category (n = 277; 50.1%). Exposure to chemicals were mild (n = 1342, 84.8%). Adults over 65 years appeared to be more likely to have severe ocular damage (OR: 4.75; [2.26; 9.98]). Unintentional exposures were the most frequent (n = 1548; 97.8%). Ocular exposure primarily occurred at home (n = 937; 59.2%), and at the workplace (n = 396; 25%) which was associated with a higher risk of severe injury (OR: 2.93 [2.16; 3.97]). Cleaning products accounted for 31.2% of exposure cases (n = 457). Exposure to disinfectants is a risk factor of more severe injuries (OR: 1.48 [1.002; 2.19] = .0472) whereas pH and severity of injuries were not statistically significant. Conclusions - Our study showed the very wide variety of products involved in ocular exposures. Clinicians should pay attention to factors associated with severe injury, including young and old age, work-related injury, substances such as disinfectants, in addition to previously known factors such as acids and bases.
Published: 2020
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6. Vitamin D concentration and focal brain atrophy in older adults: a voxel‐based morphometric study

Author: Pauline Ali, Matthieu Labriffe, Nastassia Navasiolava, Marc‐Antoine Custaud, Mickaël Dinomais, Cédric Annweiler, the SAM group, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Service de médecine interne et gérontologie clinique [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), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Aging, [SDV]Life Sciences [q-bio], Physiology, Neurosciences. Biological psychiatry. Neuropsychiatry, Brief Communication, computer.software_genre, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Voxel, Intracranial volume, medicine, Vitamin D and neurology, Humans, Gray Matter, Vitamin D, Left calcarine sulcus, RC346-429, Aged, business.industry, General Neuroscience, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Calcarine sulcus, 030104 developmental biology, Brain size, Female, Neurology (clinical), Neurology. Diseases of the nervous system, Brief Communications, business, computer, 030217 neurology & neurosurgery, RC321-571
Abstract: International audience; Vitamin D is involved in brain health and function. Our objective was to determine whether lower 25-hydroxyvitamin D (25OHD) concentration was associated with focal brain volume reduction in older adults. Serum 25OHD concentration was measured among 53 older adults (72 ± 5 years; 38% female; mean 25OHD = 67.3 ± 20.8 nmol/L). Gray matter volume (GMV) was automatically segmented using voxel-based morphometry with CAT12 software. Covariables were age, gender, education, total intracranial volume, and season. Serum 25OHD was positively associated with GMV in left calcarine sulcus (P < 0.05, TFCE, FWE-corrected). We found atrophy of the calcarine sulcus with lower 25OHD concentrations in older adults.© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
Published: 2020
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7. Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association study

Author: Eric Trépo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Eric Letouzé, Nathalie Ganne-Carrié, Christophe Moreno, Abderrahim Oussalah, Cyrille Féray, Jean Frédéric Blanc, Bruno Clément, Patrick Hillon, Jérôme Boursier, Valérie Paradis, Julien Calderaro, Viviane Gnemmi, Jean-Charles Nault, Jean-Louis Guéant, Jacques Devière, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean-Pierre Bronowicki, Thierry Gustot, Angela Sutton, Marianne Ziol, Pierre Nahon, Jessica Zucman-Rossi, Clément Meiller, Qian Cao, Théo Z. Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, Université libre de Bruxelles (ULB), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), People's Hospital of Peking University (PKUPH), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Paul Brousse, CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre de Ressources Biologiques Santé (CRB Santé), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Beaujon [AP-HP], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpitaux Universitaires Paris Seine-Saint-Denis [Sevran] (HUP2SD), 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), BB-0033-00027, H2020 Marie Skłodowska-Curie Actions, MSCA, University Hospitals, UH: NCT03311152, Bpifrance, Agence Nationale de la Recherche, ANR: ANR-11-LABX-0021, Institut National de la Santé et de la Recherche Médicale, Inserm, Assistance Publique - Hôpitaux de Paris, AP-HP, Ligue Contre le Cancer, Fondation de France, Institut National Du Cancer, INCa, Université Libre de Bruxelles, Conseil régional de Bourgogne-Franche-Comté, Korean Association for the Study of the Liver, KASL, GENTHEP Consortium: Clément Meiller, Qian Cao, Théo Z Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet, ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), École pratique des hautes études (EPHE), Jonchère, Laurent, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-CRLCC Eugène Marquis (CRLCC), Faculté de Médecine [Bruxelles] [ULB], Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)], Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Institut National de la Santé et de la Recherche Médicale [INSERM], Centre Hépato-Biliaire [Hôpital Paul Brousse] [CHB], Bordeaux Research In Translational Oncology [Bordeaux] [BaRITOn], Lipides - Nutrition - Cancer [Dijon - U1231] [LNC], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon], Centre Hospitalier Universitaire d'Angers [CHU Angers], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques [HIFIH], Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12], Institut Mondor de Recherche Biomédicale [IMRB], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux [NGERE], Nutrition, Métabolismes et Cancer [NuMeCan], Laboratoire de Recherche Vasculaire Translationnelle [LVTS (UMR_S_1148 / U1148)], Hôpital Européen Georges Pompidou [APHP] [HEGP], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], and Equipe EPICAD (LNC - U1231)
Subjects: Adult, Male, Carcinoma, Hepatocellular, Genotype, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Wnt3A Protein, Humans, Genetic Predisposition to Disease, Aged, Aged, 80 and over, Liver Neoplasms, Genetic Variation, Middle Aged, Wnt Proteins, [SDV] Life Sciences [q-bio], Oncology, Case-Control Studies, Phospholipases A2, Calcium-Independent, Female, Alcohol-Related Disorders, Acyltransferases, Genome-Wide Association Study
Abstract: International audience; Background: Hepatocellular carcinoma is a frequent consequence of alcohol-related liver disease, with variable incidence among heavy drinkers. We did a genome-wide association study (GWAS) to identify common genetic variants for alcohol-related hepatocellular carcinoma. Methods: We conducted a two-stage case-control GWAS in a discovery cohort of 2107 unrelated European patients with alcohol-related liver disease aged 20–92 years recruited between Oct 22, 1993, and March 12, 2017. Cases were patients with alcohol-related hepatocellular carcinoma diagnosed by imaging or histology. Controls were patients with alcohol-related liver disease without hepatocellular carcinoma. We used an additive logistic regression model adjusted for the first ten principal components to assess genetic variants associated with alcohol-related hepatocellular carcinoma. We did another analysis with adjustment for age, sex, and liver fibrosis. New candidate associations (pandlt;1 × 10−6) and variants previously associated with alcohol-related hepatocellular carcinoma were evaluated in a validation cohort of 1933 patients with alcohol-related liver disease aged 29–92 years recruited between July 21, 1995, and May 2, 2019. We did a meta-analysis of the two case–control cohorts. Findings: The discovery cohort included 775 cases and 1332 controls. Of 7 962 325 variants assessed, we identified WNT3A-WNT9A (rs708113; p=1·11 × 10−8) and found support for previously reported regions associated with alcohol-related hepatocellular carcinoma risk at TM6SF2 (rs58542926; p=6·02 × 10−10), PNPLA3 (rs738409; p=9·29 × 10−7), and HSD17B13 (rs72613567; p=2·49 × 10−4). The validation cohort included 874 cases and 1059 controls and three variants were replicated: WNT3A-WNT9A (rs708113; p=1·17 × 10−3), TM6SF2 (rs58542926; p=4·06 × 10−5), and PNPLA3 (rs738409; p=1·17 × 10−4). All three variants reached GWAS significance in the meta-analysis: WNT3A-WNT9A (odds ratio 0·73, 95% CI 0·66–0·81; p=3·93 × 10−10), TM6SF2 (1·77, 1·52–2·07; p=3·84×10−13), PNPLA3 (1·34, 1·22–1·47; p=7·30 × 10−10). Adjustment for clinical covariates yielded similar results. We observed an additive effect of at-risk alleles on alcohol-related hepatocellular carcinoma. WNT3A-WNT9A rs708113 was not associated with liver fibrosis. Interpretation: WNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma, suggesting an early role of the Wnt–β-catenin pathway in alcohol-related hepatocellular carcinoma carcinogenesis.
Published: 2022
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8. Humoral response to a third injection of BNT162b2 vaccine in patients on maintenance haemodialysis

Author: Marine Dekervel, Marine Asfar, Sophie Blanchi, Virginie Besson, Anne-Sophie Garnier, Giorgina Barbara Piccoli, Lise-Marie Pouteau, Jean-François Augusto, Massimo Torreggiani, Chloé Mellaza, Alexandra Ducancelle, Jean-Paul Imiela, Amaury Dujardin, Nicolas Henry, Axelle Paquin, Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Laval (CH Laval), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie-Dialyse-Transplantation [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), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
Subjects: medicine.medical_specialty, SARS-Cov-2, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, immunogenicity, Immunoglobulin G, Serology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Seroconversion, education, AcademicSubjects/MED00340, 030203 arthritis & rheumatology, Transplantation, education.field_of_study, BNT162b2 vaccine, biology, business.industry, Immunogenicity, COVID-19, 3. Good health, Vaccination, haemodialysis, Nephrology, Cohort, biology.protein, Original Article, Antibody, business
Abstract: Background Humoral response against sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after two doses of BNT162b2 (Pfizer-BioNTech) has been proven to be less intense in maintenance dialysis patients as compared with healthy subjects, leading the French authorities to recommend a third injection in this population. Here we investigated the response to the third injection in two cohorts of haemodialysis (HD) patients. Methods Data from two prospective observational cohorts were collected. In the first (‘systematic’) cohort, patients from two HD centres (n = 66) received a third injection of BNT162b2, regardless of the response after two injections. In the second (‘conditional’) cohort, the injection was only prescribed to patients (n = 34) with no or low response to the previous two doses. In both cohorts, the third dose was injected 1–2 months after the second dose. Serology was performed after the second and third doses to assess anti-Spike immunoglobulin G (S IgG) antibody titre. Results In the systematic cohort, anti-S IgG was found in 83.3 and 92.4% of patients after the second and third doses of BNT162b2, respectively. In this cohort, 6/11 (54.5%) and 20/21 (95.2%) patients switched from non-responder to low responder and from low responder to high responder, respectively. In low and high responders to two doses, 50/55 (90.9%) at least doubled their anti-S IgG titre. Similar trends were observed in the conditional cohort. Conclusions In maintenance HD patients, humoral response against SARS-CoV-2 was boosted after a third dose of BNT162b2, allowing seroconversion in more than half of non-responders. These data may support an intensified vaccination protocol with a third dose of BNT162b2 in dialysis patients., Graphical Abstract Graphical Abstract
Published: 2021
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9. Lessons from a large nationwide cohort of 350 children with ovarian mature teratoma: A study in favor of ovarian-sparing surgery

Author: Hortense Alliot, Sabine Irtan, Fanny Delehaye, Jérémie Rouger, Julien Rod, Claude Borionne, Anne Croue, Guillaume Podevin, Cécile Faure-Conter, Aurélien Scalabre, Agnès Wacrenier, Matthieu Peycelon, Solène Joseph, Quentin Ballouhey, Yann Chaussy, Louise Galmiche, Camille Duchesne, Frederic Lavrand, Jean-Jacques Parienti, Estelle Aubry, Sabine Sarnacki, Frédéric Hameury, Daniel Orbach, Isabelle Pommepuy, Marie Pierre Guibal, Alaa Cheikhelard, Florent Guérin, E. Habonimana, Elodie Haraux, Anne Dariel, Frédérique Dijoud, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Necker - Enfants Malades [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 Paris Cité (UPCité), Service de pédiatrie, adolescents, jeunes adultes [Institut Curie], Institut Curie [Paris], Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'hémato-immuno-oncologie pédiatrique [Rouen], CHU Rouen, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Environnement périnatal et croissance - EA 4489 (EPS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Pathologie [CHU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département de Pathologie Cellulaire et Tissulaire [CHU Angers] (Laboratoire d’Histopathologie-Cytopathologie), 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), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service de Pédiatrie médicale [CHU Limoges], Service de chirurgie pédiatrique [CHU Bordeaux], Hôpital des Enfants - Groupe hospitalier Pellegrin - CHU de Bordeaux, Service de Chirurgie Viscerale et Urologie Pediatriques, Hôpital Robert Debré, Université Sorbonne Paris Cité (USPC), Maladies Endocriniennes Rares de la Croissance (CRMERC), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Riley Children's Hospital at Indiana University Health, Indiana University School of Medicine, Indiana University System, Université Paris Diderot - Paris 7 (UPD7), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pédiatrie Médicale [Caen], and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: medicine.medical_specialty, conservative surgery, Adolescent, media_common.quotation_subject, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ovariectomy, Fertility, Ovarian tumor, children, Laparotomy, medicine, Humans, mature teratoma, germ cell tumors, Laparoscopy, Child, media_common, Retrospective Studies, Ovarian Neoplasms, medicine.diagnostic_test, business.industry, Teratoma, Oophorectomy, Hematology, Perioperative, medicine.disease, Surgery, Oncology, Pediatrics, Perinatology and Child Health, Cohort, Female, Germ cell tumors, ovarian tumors, business
Abstract: International audience; Background Ovarian mature teratoma (OMT) is a common ovarian tumor found in the pediatric population. In 10%-20% of cases, OMT occurs as multiple synchronous or metachronous lesions on ipsi- or contralateral ovaries. Ovarian-sparing surgery (OSS) is recommended to preserve fertility, but total oophorectomy (TO) is still performed. Design This study reviews the clinical data of patients with OMT, and analyzes risk factors for second events. A national retrospective review of girls under 18 years of age with OMTs was performed. Data on clinical features, imaging, laboratory studies, surgical reports, second events and their management were retrieved. Results Overall, 350 children were included. Eighteen patients (5%) presented with a synchronous bilateral form at diagnosis. Surgery was performed by laparotomy (85%) and laparoscopy (15%). OSS and TO were performed in 59% and 41% of cases, respectively. Perioperative tumor rupture occurred in 23 cases, independently of the surgical approach. Twenty-nine second events occurred (8.3%) in a median time of 30.5 months from diagnosis (ipsilateral: eight cases including one malignant tumor; contralateral: 18 cases; both ovaries: three cases). A large palpable mass, bilateral forms, at diagnosis and perioperative rupture had a statistical impact on the risk of second event, whereas the type of surgery or approach did not. Conclusion This study is a plea in favor of OSS as the first-choice treatment of OMT when possible. Close follow-up during the first 5 years is mandatory considering the risk of 8.3% of second events, especially in cases with risk factors.
Published: 2021
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10. Impact of aging on phenotype and prognosis in IgA vasculitis

Author: Stanislas Faguer, Noémie Le Gouellec, François Maurier, Bertrand Lioger, Patrice Cacoub, Noémie Jourde-Chiche, Sébastien Sanges, Christian Lavigne, Benjamin Terrier, Julie Goutte, Geoffrey Urbanski, Zahir Amoura, Aurélie Hummel, Evangeline Pillebout, Sophie Deriaz, Loic Raffray, Alban Deroux, Alexandra Audemard-Verger, Elisabeth Diot, Guillaume Moulis, Nicole Feirreira-Maldent, Johan Chanal, François Maillot, A. Baldolli, Loïc Guillevin, Jean-François Augusto, Eric Thervet, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LUNAM Université [Nantes Angers Le Mans], 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), PRES Université Nantes Angers Le Mans (UNAM), 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), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), 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 Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), 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), Hôpital Ambroise Paré [AP-HP], Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), MitoVasc - 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Plateforme Histologie, Immunomarquage et Microdissection laser [Institut Cochin] (HistIM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Immunoglobulin A, Adult, Male, Vasculitis, medicine.medical_specialty, Aging, Henoch-Schonlein purpura, Disease, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Aged, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Age Factors, Retrospective cohort study, Middle Aged, medicine.disease, renal involvement, Purpura, 030104 developmental biology, Phenotype, Quartile, age, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology.protein, outcome, Kidney Failure, Chronic, Female, prognosis, medicine.symptom, business, Henoch–Schönlein purpura
Abstract: Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
Published: 2021
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11. Risk of infection according to the gamma globulin level in the 100 days following allogeneic stem cell transplantations

Author: Aline Schmidt, Aurelien Giltat, Jean-Baptiste Robin, Jérémie Riou, Valentin Lacombe, Mathilde Hunault, Valérie Ugo, Pierre Abgueguen, Christopher Nunes Gomes, Sylvie François, Sylvain Thepot, Valérie Daniel, Corentin Orvain, Xavier Dieu, Laurane Cottin, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Service d'hématologie [Angers], Service des maladies infectieuses et tropicales [CHU Angers], Département de Pharmacie [CHU d'Angers], Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Male, Transplantation Conditioning, Lymphoma, medicine.medical_treatment, Graft vs Host Disease, gamma-globulins, Hematopoietic stem cell transplantation, Gastroenterology, Hypogammaglobulinemia, 0302 clinical medicine, Leukemia, biology, Risk of infection, Immunoglobulins, Intravenous, Gamma globulin, Bacterial Infections, Hematology, General Medicine, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, hematopoietic stem cell transplantation, Cyclosporine, Female, Antibody, Stem cell, Immunosuppressive Agents, allografts, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Opportunistic Infections, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, business.industry, infections, Immunologic Deficiency Syndromes, Mycophenolic Acid, Myeloablative Agonists, medicine.disease, Increased risk, Mycoses, ROC Curve, Myelodysplastic Syndromes, biology.protein, Virus Activation, business, 030215 immunology
Abstract: International audience; Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.Results: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level
Published: 2021
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12. Warburg-like effect is a hallmark of complex I assembly defects

Author: Naïg Gueguen, Anaïs Lebert, Guy Lenaers, Patrizia Amati-Bonneau, Magalie Barth, Mariame Selma Kane, Cédric Gadras, Pascal Reynier, David Goudenège, Dominique Bonneau, Valérie Desquiret-Dumas, Stéphanie Leruez, Stéphanie Chupin, Daniel Henrion, Morgane Le Mao, Céline Wetterwald, Vincent Procaccio, Salim Khiati, Géraldine Leman, Guillaume Geffroy, Lydie Tessier, Arnaud Chevrollier, 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), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), ARN : régulations naturelle et artificielle, Université Bordeaux Segalen - Bordeaux 2-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biochimie et Génétique [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), Réseau Maladies Métaboliques, Hôpitaux Universitaires du Grand Ouest, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie et thérapie des déficits sensoriels et moteurs, and Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Mitochondrial Diseases, [SDV]Life Sciences [q-bio], Citric Acid Cycle, Regulator, 03 medical and health sciences, 0302 clinical medicine, Humans, Glycolysis, RNA, Small Interfering, Overproduction, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Principal Component Analysis, Reactive oxygen species, Electron Transport Complex I, ATP synthase, biology, Catabolism, NADH Dehydrogenase, Fibroblasts, Pyruvate dehydrogenase complex, Warburg effect, Mitochondria, Cell biology, 030104 developmental biology, Metabolic Engineering, chemistry, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, RNA Interference, Reactive Oxygen Species
Abstract: Due to its pivotal role in NADH oxidation and ATP synthesis, mitochondrial complex I (CI) emerged as a crucial regulator of cellular metabolism. A functional CI relies on the sequential assembly of nuclear- and mtDNA-encoded subunits; however, whether CI assembly status is involved in the metabolic adaptations in CI deficiency still remains largely unknown. Here, we investigated the relationship between CI functions, its structure and the cellular metabolism in 29 patient fibroblasts representative of most CI mitochondrial diseases. Our results show that, contrary to the generally accepted view, a complex I deficiency does not necessarily lead to a glycolytic switch, i.e. the so-called Warburg effect, but that this particular metabolic adaptation is a feature of CI assembly defect. By contrast, a CI functional defect without disassembly induces a higher catabolism to sustain the oxidative metabolism. Mechanistically, we demonstrate that reactive oxygen species overproduction by CI assembly intermediates and subsequent AMPK-dependent Pyruvate Dehydrogenase inactivation are key players of this metabolic reprogramming. Thus, this study provides a two-way-model of metabolic responses to CI deficiencies that are central not only in defining therapeutic strategies for mitochondrial diseases, but also in all pathophysiological conditions involving a CI deficiency.
Published: 2019
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13. 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
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14. Impact de l’extension de la vaccination obligatoire sur les couvertures vaccinales du nourrisson : des premiers résultats prometteurs

Author: Robert M. Cohen, L. Longfier, Alain Martinot, H. Lepetit, P. Pujol, B. Leboucher, Jean-Paul Stahl, Damien Subtil, Joël Gaudelus, F. Denis, Service de Néonatologie [CHI Créteil], Centre Hospitalier Intercommunal de Créteil (CHIC), Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Centre Hospitalier Universitaire d'Angers [CHU Angers], Université Grenoble Alpes [2016-2019] [UGA [2016-2019]], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Vaccination Coverage, Mothers, Pilot Projects, Mandatory Programs, Mandatory vaccination, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Vaccination obligatoire, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Internet, 0303 health sciences, 030306 microbiology, business.industry, Public health, Vaccination, Vaccination coverage, Infant, Newborn, Infant, Couverture vaccinale, Hepatitis B, medicine.disease, 3. Good health, Infectious Diseases, Vaccination policy, Family medicine, Female, France, Public Health, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, Attitude to Health
Abstract: International audience; OBJECTIVE: In France infant vaccines protecting against 11 diseases have changed from a recommended to a mandatory status for all children born on or after January 1, 2018. Using the Vaccinoscopie survey, we measured the impact of this new vaccination policy on vaccine coverage rates (VCRs) and on mothers' perception of vaccination.METHODS: Online survey with 1000 mothers of 0- to 11-month-old infants.RESULTS: VCRs for at least one dose at the age of 6 months strongly progressed for diseases that previously did not meet Public Health objectives (+8 points for Hepatitis B and +31 points for meningococcal C vaccines). Mothers were more favorable to mandatory vaccination and better informed in 2018 than in 2017.CONCLUSIONS: These first results showed a positive impact of the extension of mandatory vaccination on mothers' opinion regarding vaccination and on infant VCRs.; Objectifs: En France, pour les enfants nés depuis le 1er janvier 2018, les vaccins du nourrisson protégeant contre 11 maladies, auparavant recommandés, sont devenus obligatoires. L’enquête Vaccinoscopie permet de mesurer l’impact de cette nouvelle politique vaccinale sur les couvertures vaccinales (CV) et l’opinion des mères sur la vaccination.Méthodes: Étude réalisée sur Internet par questionnaire auto-administré auprès de 1000 mères de nourrissons âgés de 0–11 mois.Résultats: Les CV pour au moins une dose à l’âge de 6 mois ont fortement progressé pour les valences qui n’atteignaient pas les objectifs de santé publique (+8 points pour l’hépatite B et +31 points pour le méningocoque C). Les mères étaient plus favorables à la vaccination obligatoire et mieux informées en 2018 qu’en 2017.Conclusion: Ces premiers résultats montrent un impact positif de l’extension de la vaccination obligatoire sur les CV du nourrisson et sur l’opinion des mères quant à la vaccination.
Published: 2019
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15. Large International Validation of ABSIS and PDAI Pemphigus Severity Scores

Author: Hébert, Vivien, Boulard, Claire, Houivet, Estelle, Lehembre, Sophie, Borradori, Luca, Della, Rocco, Feliciani, Claudio, Fania, Luca, Zambruno, Giovanna, Camaioni, Diana, Didona, Biago, Marinovic, Branka, Schmidt, Enno, Schumacher, Nina, Hü Nefeld 10, Christian, Schanz, Stefan, Kern, Johannes, Hofmann, Silke, Bouyeure, Anne, Picard-Dahan, Catherine, Prost-Squarcioni, Catherine, Caux, Frederic, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Bagot, Martine, Tancrede-Bohin, Emmanuelle, David Bouaziz, Jean, Franck, Nathalie, Vabres, Pierre, Labeille, Bruno, Richard, Marie, Delaporte, Emmanuel, Dupuy, Alain, D'Incan, Michel, Quereux, Gaelle, Skowro, François, Paul, Carle, Livideanu, Cristina, Beylot-Barry, Marie, Doutre, Marie, Avenel-Audran, Martine, Bedane, Christophe, Bernard, Philippe, Machet, Laurent, Maillard, Hervé, Jullien, Denis, Debarbieux, Sebastien, Sassolas, Bruno, Misery, Laurent, Abasq, Claire, Dereure, Olivier, Lagoutte, Philippe, Ferranti, Vincent, Werth, Victoria, Murrell, Dedee, Hertl, Michael, Benichou, Jacques, Joly, Pascal, Duvert Lehembre, Sophie, Della Torre, Rocco, Hünefeld, Christian, Kern, Johannes Steffen, Bouyeure, Anne Charlotte, Bouaziz, Jean David, Richard, Marie Aleth, D’Incan, Michel, Livideanu, Cristina Bulai, Doutre, Marie Sylvie, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Universität Bern [Bern], Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de dermatologie [Avicenne], Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13), CHU Henri Mondor, Service de Dermatologie [AP-HP Hôpital Saint Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital Saint-Louis, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Hospital of St-Etienne, Department of Dermatology, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes (UGA), Service de dermatologie (CHRU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie [CHU Limoges], CHU Limoges, Club Rhumatismes et Inflammation, Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Seventh Framework Programme, French Society of Dermatology, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), CHU Rouen, Normandie Université (NU), Service de dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Unité de biostatistiques [Rouen], Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), L'Oréal recherche et innovation, L'Oréal, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie, Hôtel-Dieu, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Toulouse III - Paul Sabatier (UPS), Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), INSERM U1234, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Dermatologie [Rennes] = Dermatology [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Universität Bern [Bern] (UNIBE), IDI-IRCCS [Roma, Italy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Henri Mondor [Créteil], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université de Toulouse (UT), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Autoimmune Bullous Skin Disorder Intensity Score, Intraclass correlation, [SDV]Life Sciences [q-bio], intraclass correlation coefficient, Autoimmunity, PV, Validation Studies as Topic, Severity of Illness Index, Biochemistry, PDAI, 0302 clinical medicine, Medicine, DLQI, Pemphigus foliaceus, Skin, integumentary system, Desmoglein 1, PGA, CI, 3. Good health, ABSIS, month, 030220 oncology & carcinogenesis, PF, medicine.medical_specialty, pemphigus vulgaris, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, 03 medical and health sciences, Dermatology Quality of Life Index, Internal medicine, Severity of illness, Humans, In patient, pemphigus foliaceus, Molecular Biology, Autoantibodies, Pemphigus severity scores, ICC, business.industry, Pemphigus vulgaris, Cell Biology, medicine.disease, Confidence interval, Moderate extent, Pemphigus Disease Area Index, Pemphigus, 030104 developmental biology, confidence interval, Physician Global Assessment, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IF 6.448 (2017); International audience; The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.
Published: 2019
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16. Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation

Author: Karine Duroure, Estelle Colin, Thomas Edouard, Ludovic Martin, Linda Grimaud, Lyndon Gallacher, George McGillivray, Guy Lenaers, Valérie Desquiret-Dumas, Clarisse Billon, Anne Breton, Mohammed Zarhrate, Emmanuel Mas, Dominique Bonneau, Lynn Pais, Daniel Henrion, Thomas Haaf, Reza Maroofian, Marianna Parlato, Frank M. Ruemmele, Anne-Laure Guihot, Anaïs Philippe, Ehsan Ghayoor Karimiani, Pauline E. Schneeberger, Stanislas Lyonnet, Bernadette Bègue, Bruno Moulin, Rémi Duclaux-Loras, Nicolas Cagnard, Michael Frank, Laurence Faivre, Ruben Attali, Yves Alembik, Filippo Del Bene, Kerstin Kutsche, Céline Revenu, Fabienne Charbit-Henrion, Katta M. Girisha, Aboulfazl Rad, Eyal Reinstein, Shalini S. Nayak, Barbara Vona, Nadine Cerf-Bensussan, Caroline Lekszas, Shay Tzur, Alban Ziegler, Susan M. White, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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), Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ingénierie Radioprotection Sûreté Démantèlement (IRSD), Centre National de la Recherche Scientifique (CNRS), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Embryology and genetics of human malformation, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de Hautepierre [Strasbourg], Nouvel Hôpital Civil de Strasbourg, Tel Aviv University (TAU), Emedgene Technologies [Tel Aviv], Murdoch Children's Research Institute (MCRI), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Kasturba Medical College, Manipal, Massachusetts Institute of Technology (MIT), University College of London [London] (UCL), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, St George's, University of London, University of Würzburg = Universität Würzburg, Fondation Princesse Grace, Fondation Maladies Rares, Harbig Family Foundation, Royal Children's Hospital Foundation, University of Tubingen (2545-1-0), Federal Ministry of Education and Research (01DQ17003 to K.K.), Indian Council of Medical Research (file no. 5/7/1508/2016 to K.M.G), National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung, and Blood Institute grant UM1 HG008900, National Human Genome Research Institute grant R01 HG009141, Victorian Government's Operational Infrastructure Support Program, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018), European Project: 661527,H2020,H2020-MSCA-IF-2014,NMJALS(2015), European Project: 339407,EC:FP7:ERC,ERC-2013-ADG,IMMUNOBIOTA(2014), Service de génétique [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), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Embryology and genetics of human malformation (Equipe Inserm U1163), SEGUIN, Nathalie, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Enabling Vision Restoration - - FOReSIGHT2018 - ANR-18-IAHU-0001 - IAHU - VALID, In vivo analysis of neuromuscular junction stability in zebrafish models of amyotrophic lateral sclerosis - NMJALS - - H20202015-11-16 - 2017-11-15 - 661527 - VALID, Host-microbiota interactions across the gut immune system:lessons from early onset inflammatory bowel diseases and from gnotobiotic mice - IMMUNOBIOTA - - EC:FP7:ERC2014-03-01 - 2019-02-28 - 339407 - VALID, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Connective Tissue Disorder, Loss of Heterozygosity, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, IPO8, TGF-β signaling, Pathogenesis, 0302 clinical medicine, Loss of Function Mutation, Transforming Growth Factor beta, connective tissue disorder, Child, Connective Tissue Diseases, Zebrafish, Genetics (clinical), Karyopherin, chemistry.chemical_classification, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunity, Cellular, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, beta Karyopherins, Pedigree, arterial dilatation, Cell biology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phenotype, medicine.anatomical_structure, Cardiovascular Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Bone Diseases, Signal Transduction, Adult, Adolescent, Connective tissue, Biology, Importin 8, Young Adult, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Report, Genetics, medicine, Animals, Humans, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Infant, Immune dysregulation, Loeys-Dietz syndrome, biology.organism_classification, joint hyperlaxity, chemistry, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Transforming growth factor
Abstract: International audience; Dysregulated transforming growth factor TGF-beta signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-beta-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-beta signaling, ipo8(-/-) zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8(-/-) zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-beta signaling during development and reinforces the existing link between TGF-beta signaling and connective tissue defects.
Published: 2021
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17. Clinical guidelines and care pathway for management of low back pain with or without radicular pain

Author: Thomas Le Vraux, Gilles Vuides, Florian Bailly, Catherine Sebire, Sabrina Dadoun, Jean-Baptiste Fassier, Rogatien Faguer, Sylvie Rozenberg, MichÃ le Koleck, FranÃ Ois Rannou, Karine Petitprez, Alexandra Roren, Sandrine Bercier, Liesse Brigitte, Louis Lassalle, Aline Ramond-Roquin, Anne-Priscille Trouvin, Jean-Philippe Deneuville, Petit Audrey, Jean-FranÃ Ois Renard, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinique Geoffroy Saint-Hilaire, Institut Pprime (PPRIME), Université de Poitiers-ENSMA-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hospices Civils de Lyon (HCL), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Haute Autorité de Santé [Saint-Denis La Plaine] (HAS), Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), 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)-Institut de Veille Sanitaire (INVS), Épidémiologie en Santé au Travail et Ergonomie (IRSET-ESTER), Institut de recherche en santé, environnement et travail (Irset), 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 )-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 rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], Admin, Oskar, Service de Rhumatologie [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 rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Bordeaux (UB), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 )-Université d'Angers (UA)-Université de Rennes 1 (UR1), and 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 )
Subjects: medicine.medical_specialty, Consensus, Guidelines, Recommendations, Academic institution, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Musculoskeletal Pain, Multidisciplinary approach, medicine, Care pathway, Humans, Low back pain, 030212 general & internal medicine, 030203 arthritis & rheumatology, business.industry, Guideline, medicine.disease, 3. Good health, Systematic review, Radicular pain, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, Critical Pathways, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Patient representatives, medicine.symptom, business, Systematic Reviews as Topic
Abstract: International audience; OBJECTIVE: To develop guidelines for low back pain management according to previous international guidelines and the updated literature. METHODS: A report was compiled from a review of systematic reviews of guidelines published between 2013 and 2018 and meta-analysis of the management of low back pain published between 2015 and 2018. This report summarized the state-of-the-art scientific knowledge for each predefined area of the guidelines from a critical review of selected literature. A multidisciplinary panel of experts including 17 health professionals involved in low back pain management and 2 patient representatives formulated preliminary guidelines based on the compilation report and a care pathway. The compilation report and preliminary guidelines were submitted to 25 academic institutions and stakeholders for the consultation phase. From responses of academic institutions and stakeholders, the final guidelines were developed. For each area of the guidelines, agreement between experts was assessed by the RAND/UCLA method. RESULTS: The expert panel drafted 32 preliminary recommendations including a care pathway, which was amended after academic institution and stakeholder consultation. The consensus of the multidisciplinary expert panel was assessed for each final guideline: 32 recommendations were assessed as appropriate; none was assessed as uncertain or inappropriate. Strong approval was obtained for 27 recommendations and weak for 5. CONCLUSION: These new guidelines introduce several concepts, including the need to early identify low back pain at risk of chronicity to provide quicker intensive and multidisciplinary management if necessary.
Published: 2021
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18. What effects does awake craniotomy have on functional and survival outcomes for glioblastoma patients?

Author: Philippe Menei, Anne Clavreul, Aram Ter Minassian, Ghislaine Aubin, Matthieu Delion, Jean-Michel Lemée, Département de neurochirurgie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Centre de Rééducation et Réadaptation Fonctionnelle Adulte et Pédiatrique [CHU Angers] (Les Capucins), Département d'Anesthésie-Réanimation [CHU Angers], Clavreul, Anne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Male, Cancer Research, medicine.medical_specialty, Neurology, Survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, Asymptomatic, Complete resection, Neurosurgical Procedures, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Monitoring, Intraoperative, medicine, Humans, Wakefulness, Aged, Retrospective Studies, Surgical approach, Brain Neoplasms, business.industry, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Functional outcomes, Surgery, Survival Rate, Awake craniotomy, Regimen, Oncology, 030220 oncology & carcinogenesis, Female, Neurology (clinical), medicine.symptom, business, Glioblastoma, Craniotomy, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; Purpose Neurosurgeons adopt several different surgical approaches to deal with glioblastomas (GB) located in or near eloquent areas. Some attempt maximal safe resection by awake craniotomy (AC), but doubts persist concerning the real benefits of this type of surgery in this situation. We performed a retrospective study to evaluate the extent of resection (EOR), functional and survival outcomes after AC of patients with GB in critical locations. Methods Forty-six patients with primary GB treated with the Stupp regimen between 2004 and 2019, for whom brain mapping was feasible, were included. We assessed EOR, postoperative language and/or motor deficits three months after AC, progression-free survival (PFS) and overall survival (OS). Results Complete resection was achieved in 61% of the 46 GB patients. The median PFS was 6.8 months (CI 6.1; 9.7) and the median OS was 17.6 months (CI 14.8; 34.1). Three months after AC, more than half the patients asymptomatic before surgery remained asymptomatic, and one third of patients with symptoms before surgery experienced improvements in language, but not motor functions. The risk of postoperative deficits was higher in patients with preoperative deficits or incomplete resection. Furthermore, the presence of postoperative deficits was an independent predictive factor for shorter PFS. Conclusion AC is an option for the resection of GB in critical locations. The observed survival outcomes are typical for GB patients in the Stupp era. However, the success of AC in terms of the recovery or preservation of language and/or motor functions cannot be guaranteed, given the aggressiveness of the tumor.
Published: 2021
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19. STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain

Author: Codron, P., Letournel, F., Marty, S., Renaud, L., Bodin, A., Duchesne, M., Verny, C., Duyckäerts, C., Julien, J.‐P., Cassereau, J., Chevrollier, A., Lenaers, Guy, Bonneau, Dominique, Delneste, Yves, Papon, Nicolas, 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), Département de Pathologie Cellulaire et Tissulaire, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Gérontologie (BICETRE - Géronto), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Neurologie et thérapeutique expérimentale, IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Lewy Body Disease, Male, 0301 basic medicine, Histology, [SDV]Life Sciences [q-bio], Central nervous system, STORM, tau Proteins, Context (language use), Neuropathology, Biology, Pathology and Forensic Medicine, White matter, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, amyloid‐β, Physiology (medical), medicine, Humans, Dementia, tau, ComputingMilieux_MISCELLANEOUS, Inclusion Bodies, Neurons, Microscopy, neuropathology, Neocortex, α‐synuclein, Lewy body, Brain, Parkinson Disease, Original Articles, Human brain, medicine.disease, TDP‐43, 030104 developmental biology, medicine.anatomical_structure, Neurology, alpha-Synuclein, Lewy Bodies, Original Article, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery
Abstract: Aims Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high‐resolution imaging approaches is a current challenge in neuroscience. Methods To this end, we used a recent super‐resolution imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyse human brain sections. We combined STORM cell imaging protocols with neuropathological techniques to image cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. Results This approach allowed us to perform 2D‐, 3D‐ and two‐colour‐STORM in neocortex, white matter and brainstem samples. STORM proved to be particularly effective at visualizing the organization of dense protein inclusions and we imaged with a
Published: 2020
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20. Impact of Driver Mutations on the Evolution of Isolated Metachronous Lung Metastasis of Pancreatic Ductal adenocarcinoma

Author: Carole Vitellius, Aurélien Venara, Nathalie Baize, Philippe Guardiola, Océane Griveaux, Eloise Dincuff, Estelle Pedrono, Benjamin Morvant, Olivier Ingster, François-Xavier Caroli-Bosc, Marie-Christine Rousselet, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique [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), and Département de Pathologie Cellulaire et Tissulaire
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Lung Neoplasms, [SDV]Life Sciences [q-bio], Gene mutation, Adenocarcinoma, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genetics, Carcinoma, medicine, Biomarkers, Tumor, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Smad4 Protein, Pharmacology, Aged, 80 and over, Lung, business.industry, Incidence (epidemiology), Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Prognosis, Primary tumor, digestive system diseases, 3. Good health, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, Molecular Medicine, Female, KRAS, Neoplasm Recurrence, Local, business, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract: The incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing sharply. The survival of patients with metastases is usually about a year. However, the occurrence of isolated lung metastases after resection of the primary tumor, although rare, seems to indicate a better prognosis, with an average survival ranging from 40 to 80 months. KRAS, TP53, CDK2NA, and SMAD4 are the most common driver genes in pancreatic adenocarcinoma. Our objectives were to determine whether a link exists between survival and mutations of driver genes in patients with isolated pulmonary metastases. All patients who underwent curative surgery in our institution between 2010 and 2018 were included in the study. From these, we identified patients for whom recurrence was only pulmonary and those with metastases at other sites. KRAS, TP53, CDK2NA, and SMAD4 were analyzed on the primary tumor of patients with pulmonary metastases. Among 233 patients diagnosed with PDAC in our institution over 8 years, 41 (17.5%) underwent curative surgery. Of these, seven (3%) developed isolated pulmonary metastases, 32 developed other metastases, and two did not recur. Median survival was 59 months for patients with isolated lung metastases and 25.3 months for patients with metastases at other sites. An absence of mutations of two driver genes in primary tumors (CDK2NA and SMAD4) was observed in patients with isolated pulmonary metastases. The absence of mutations in the CDK2NA and SMAD4 tumor-suppressor genes in patients with isolated pulmonary metastases contrasts with the commonly observed high rates of driver gene mutations and suggests a link with overall survival.
Published: 2020
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21. Nuclear Activation Function 2 Estrogen Receptor α Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice

Author: Guivarc'h, Emmanuel, Favre, Julie, Guihot, Anne‐Laure, Vessières, Emilie, Proux, Coralyne, Rivron, Jordan, Barbelivien, Agnès, Fassot, Céline, Briet, Marie, Lenfant, Françoise, Fontaine, Coralie, Loufrani, Laurent, Arnal, Jean‐François, Henrion, Daniel, 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), MITOVASC institute and CARFI facility, UMR CNRS 6015, INSERM U1083, University of Angers, Angers, France., Laboratoire de Pharmacologie, CHU d'Angers, Laboratoire de Pharmacologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020
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22. A Plasma Metabolomic Profiling of Exudative Age-Related Macular Degeneration Showing Carnosine and Mitochondrial Deficiencies

Author: Delphine Mirebeau-Prunier, Vincent Procaccio, Stéphanie Leruez, Adrien Buisset, Jeanne Muller, Lydie Tessier, Guy Lenaers, Dan Milea, Odile Blanchet, Pascal Reynier, Marc Ferré, Juan Manuel Chao de la Barca, Gilles Simard, Laurie Moureauzeau, Stéphanie Chupin, Thibaut Macé, Philippe Gohier, Barnabé Rondet-Courbis, Guillaume Plubeau, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Biochimie et Génétique [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), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Stress Oxydant et Pathologies Métaboliques (SOPAM), Rigshospitalet [Copenhagen], and Copenhagen University Hospital
Subjects: medicine.medical_specialty, genetic structures, [SDV]Life Sciences [q-bio], lcsh:Medicine, Carnosine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Metabolomics, Valine, Internal medicine, Lipidomics, medicine, Carnitine, Proline, age-related macular degeneration, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, metabolomics, 2. Zero hunger, 0303 health sciences, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, lcsh:R, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Macular degeneration, medicine.disease, eye diseases, 3. Good health, Endocrinology, chemistry, 030221 ophthalmology & optometry, lipidomics, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, medicine.drug
Abstract: To determine the plasma metabolomic profile of exudative age-related macular degeneration (AMD), we performed a targeted metabolomics study on the plasma from patients (n = 40, mean age = 81.1) compared to an age- and sex-matched control group (n = 40, mean age = 81.8). All included patients had documented exudative AMD, causing significant visual loss (mean logMAR visual acuity = 0.63), compared to the control group. Patients and controls did not differ in terms of body mass index and co-morbidities. Among the 188 metabolites analyzed, 150 (79.8%) were accurately measured. The concentrations of 18 metabolites were significantly modified in the AMD group, but only six of them remained significantly different after Benjamini&ndash, Hochberg correction. Valine, lysine, carnitine, valerylcarnitine and proline were increased, while carnosine, a dipeptide disclosing anti-oxidant and anti-glycating properties, was, on average, reduced by 50% in AMD compared to controls. Moreover, carnosine was undetectable for 49% of AMD patients compared to 18% in the control group (p-value = 0.0035). Carnitine is involved in the transfer of fatty acids within the mitochondria, proline, lysine and valerylcarnitine are substrates for mitochondrial electrons transferring flavoproteins, and proline is one of the main metabolites supplying energy to the retina. Overall, our results reveal six new metabolites involved in the plasma metabolomic profile of exudative AMD, suggesting mitochondrial energetic impairments and carnosine deficiency.
Published: 2020
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23. Clinical identification of older adults with hypovitaminosis D: Feasibility, acceptability and accuracy of the ‘Vitamin D Status Diagnosticator’ in primary care

Author: Spyridon N. Karras, Jean-Michel Le Moigno, Gaëlle Annweiler, Cédric Annweiler, Jérémie Riou, David J. Llewellyn, Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et gérontologie clinique [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), CCSD, Accord Elsevier, Faculté de Médecine d'Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche sur l'Autonomie et la Longévité [CHU Angers] (CeRAL [CHU Angers]), Aristotle University of Thessaloniki, University of Exeter Medical School, University of Exeter, Robarts Research Institute [Canada], and University of Western Ontario (UWO)
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Acceptance rate, Clinical Biochemistry, Recurrent falls, Primary care, Biochemistry, vitamin D deficiency, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Hypovitaminosis, Prevalence, Vitamin D and neurology, Humans, Medicine, Blood test, Vitamin D, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Osteomalacia, Vitamin D deficiency, Primary Health Care, medicine.diagnostic_test, business.industry, Vitamins, Cell Biology, Patient Acceptance of Health Care, medicine.disease, [STAT] Statistics [stat], 3. Good health, [STAT]Statistics [stat], 030104 developmental biology, Older adults, 030220 oncology & carcinogenesis, Screening, Feasibility Studies, Molecular Medicine, Female, France, business
Abstract: International audience; The 16-item Vitamin D Status Diagnosticator (VDSD) tool was built to diagnose, without resorting to a blood test, hypovitaminosis D among healthy seniors living at home. The objective of this study was to determine the feasibility of the VDSD by general practitioners (GPs), the acceptability to outpatients, and the diagnostic accuracy of the VDSD in primary care. Ten French GPs were asked from March to May 2015 to perform the VDSD in 30 consecutive outpatients aged ≥70years, living at home, presenting with a history of recurrent falls and/or osteomalacia, and taking no vitamin D supplements. Feasibility was defined as a proportion >70% of VDSD forms fully completed. Completing time, acceptance rate and, when applicable, the reasons for non-completing were assessed, together with the metrological properties of the VDSD to identify hypovitaminosis D ≤75nmol/L, or ≤50nmol/L or ≤25nmol/L. Of the 242 enrolled patients, 218 (mean, 79 ± 6years; 46.3% women) received a VDSD, i.e. completing rate of 90.1%, with an average completing time of 1 min and 48s. The acceptance rate by the patients was 98.8%, and all GPs were satisfied with the tool. The VDSD identified hypovitaminosis D≤75nmol/L with an accuracy of 84.7%, hypovitaminosis D≤50nmol/L with accuracy 75.4%, and hypovitaminosis D≤25nmol/L with accuracy 71.0% (n = 183 assays). The 16-item VDSD can be considered as feasible, acceptable and accurate for diagnosing hypovitaminosis D among older outpatients in primary care without resorting to an expensive blood test.
Published: 2020
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24. The cytokine profile of follicular fluid changes during ovarian ageing

Author: Lisa Boucret, Simon Blanchard, Véronique Ferré-L’Hotellier, Pierre-Emmanuel Bouet, Juan Manuel Chao de la Barca, Pascale May-Panloup, Pascale Jeannin, Philippe Descamps, Pascal Reynier, Vincent Procaccio, Thomas Boueilh, Service de médecine reproductive [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), Unité de Biologie reproductive [CHU Angers], Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, PRES Université Nantes Angers Le Mans (UNAM), This study was supported by the University Hospital of Angers, and the University of Angers, France without specific funding., Bernardo, Elizabeth, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Adult, Infertility, Aging, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ovarian Disorder, Physiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fertilization in Vitro, 03 medical and health sciences, 0302 clinical medicine, Ovarian Follicle, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Ovarian Reserve, Ovarian reserve, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, Assisted reproductive technology, In vitro fertilisation, business.industry, Ovary, Obstetrics and Gynecology, Proto-Oncogene Proteins c-sis, medicine.disease, Follicular fluid, Follicular Fluid, 3. Good health, Cross-Sectional Studies, Cytokine, Reproductive Medicine, 030220 oncology & carcinogenesis, Cytokines, Female, Folliculogenesis, business, Infertility, Female
Abstract: International audience; Objective: Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing. Material and methods: Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls. Results: With univariate analysis, the cytokine profile was found to differ significantly between the two groups. After adjustment of the p-values, platelet-derived growth factor-BB (PDGF-BB) was the only cytokine with a significantly lower concentration in the DOR group (7.34 AE 16.11 pg/mL) than in the NOR group (24.39 AE 41.38 pg/mL) (p = 0.005), independently of chronological age. Conclusion: Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress.
Published: 2020
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25. Complement alternative pathway in ANCA-associated vasculitis: Two decades from bench to bedside

Author: Pascale Jeannin, Benoit Brilland, Alain Chevailler, Jean-François Subra, Jean-François Augusto, Anne-Sophie Garnier, Bernardo, Elizabeth, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie-Dialyse-Transplantation [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), Laboratoire d'Immunologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 0301 basic medicine, Neutrophils, Immunology, Complement Pathway, Alternative, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Pathogenesis, 03 medical and health sciences, Mice, 0302 clinical medicine, Glomerulonephritis, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, Immunology and Allergy, Medicine, Animals, Humans, Complement Activation, C5aR, 030203 arthritis & rheumatology, business.industry, Avacopan, Autoantibody, Complement alternative pathway, Chemotaxis, Complement System Proteins, Immune complex, 3. Good health, Complement system, 030104 developmental biology, Alternative complement pathway, business, ANCA-associated vasculitis
Abstract: International audience; Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAVs) are small vessel vasculitides involving predominantly ear-nose-throat, kidneys, lungs and nerves. AAVs are life-threatening diseases, especially in their most severe forms such as necrotizing crescentic glomerulonephritis (GN) and/or intra-alveolar hemorrhage. Unlike immune complex GN or anti-glomerular basement membrane GN, AAVs are classified as pauci-immune GN. However, based on recent insights from animal models, the view of AAVs as a complement-unrelated disease has been challenged. Indeed, complement activation, and especially complement alternative pathway (cAP) activation, has been shown to be determinant in AAV pathogenesis through C5a generation, a potent chemoattractant for neutrophils with priming capacities. Here, we review in vitro and in vivo data supporting the role of cAP in murine models and in human AAVs. These findings, together with the need to eradicate glucocorticoid toxicity, led to the development of an anti-C5aR molecule, CCX168, also known as avacopan. Its development and future opportunities are also discussed.
Published: 2020
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26. Metabolomics reveals highly regional specificity of cerebral sexual dimorphism in mice

Author: Franck Letournel, Dominique Bonneau, Floris Chabrun, Pascal Reynier, Stéphanie Chupin, Guy Lenaers, Xavier Dieu, Delphine Mirebeau-Prunier, Juan Manuel Chao de la Barca, Vincent Procaccio, Guillaume Rousseau, Gilles Simard, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Biochimie et Génétique [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), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, Cerebellum, Sex dimorphism, Frontal cortex, [SDV]Life Sciences [q-bio], Physiology, Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Murine brain, Neuroimaging, medicine, Animals, ComputingMilieux_MISCELLANEOUS, Sex Characteristics, General Neuroscience, Brain, Omics, Frontal Lobe, 3. Good health, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Sexual dimorphism, 030104 developmental biology, medicine.anatomical_structure, Female, Sphingomyelin, Neuroscience, 030217 neurology & neurosurgery, Brain Stem
Abstract: International audience; The development of personalized medicine according to gender calls for the integration of sexual dimorphism in pre-clinical models of diseases. Although sexual dimorphism in the brain of the mouse has been the subject of several behavioral, neuroimaging and experimental studies, very few have characterized the bases of sexual dimorphism in the brain on the omics scale. In particular, physiological variations in metabolomic and lipidomic terms related to gender have not been mapped in the brain. We carried out a metabolomic analysis, targeting 188 metabolites representative of various cellular structures and metabolisms, in three brain regions: frontal cortex, brain stem and cerebellum, in 3-month-old C57BL-6 J male (n = 20) vs. female (n = 20) mice. Our results demonstrate the existence of sexual dimorphism in the whole brain as well as in separate brain regions. Half of the 129 accurately measured metabolites were involved in the sexual dimorphism of the murine brain, but only 8% of those (hydroxyproline, creatinine, hexoses, tryptophan, threonine and lysoPC.a.C18.2) were involved in common in the three cerebral regions, while 71%, including phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, acylcarnitines, amino acids, biogenic amines, and polyamines, were specific to only one region of the brain, underscoring the highly regional specificity of cerebral sexual dimorphism in mice.
Published: 2020
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27. Lung- and Diaphragm-Protective Ventilation

Author: Robinder G. Khemani, Eddy Fan, Samir Jaber, Giacomo Grasselli, Alexandre Demoule, Sarina K. Sahetya, Jose Dianti, Dimitrios Georgopoulos, Francesco Mojoli, Tommaso Mauri, Laurent Brochard, Katerina Vaporidi, Claude Guérin, Coen A.C. Ottenheijm, Jeremy R. Beitler, Tom Schepens, Savino Spadaro, Takeshi Yoshida, Antonio Pesenti, Franco Laghi, Marcelo B. P. Amato, Ewan C. Goligher, Alain Mercat, Domenico Luca Grieco, Giacomo Bellani, L.M.A. Heunks, Irene Telias, Niall D. Ferguson, Martin Dres, Jordi Mancebo, Bhakti K. Patel, Physiology, ACS - Pulmonary hypertension & thrombosis, Intensive care medicine, University Health Network, Toronto General Hospital Research Institute [Canada] (TGHRI), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), 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), University of Chicago, Johns Hopkins University (JHU), Columbia University [New York], St. Michael's Hospital, Osaka University, University of Crete [Heraklion] (UOC), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Antwerp University Hospital [Edegem] (UZA), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Ferrara = University of Ferrara (UniFE), Italian Hospital of Buenos Aires, Universidade de São Paulo = University of São Paulo (USP), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of Toronto, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), 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), Children’s Hospital Los Angeles [Los Angeles], University of Southern California (USC), Loyola University [Chicago], Endocrinologie pédiatrique[CHU 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), Università degli Studi di Pavia = University of Pavia (UNIPV), Amsterdam UMC - Amsterdam University Medical Center, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hospital de la Santa Creu i Sant Pau, dres, martin, Interdepartmental Division of Critical Care Medicine, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), VU University Medical Center [Amsterdam], European Soc Intensive Care Med, Goligher, E, Dres, M, Patel, B, Sahetya, S, Beitler, J, Telias, I, Yoshida, T, Vaporidi, K, Grieco, D, Schepens, T, Grasselli, G, Spadaro, S, Dianti, J, Amato, M, Bellani, G, Demoule, A, Fan, E, Ferguson, N, Georgopoulos, D, Guérin, C, Khemani, R, Laghi, F, Mercat, A, Mojoli, F, Ottenheijm, C, Jaber, S, Heunks, L, Mancebo, J, Mauri, T, Pesenti, A, Brochard, L, Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The University of Chicago Medicine [Chicago], Johns Hopkins University School of Medicine [Baltimore], Columbia University College of Physicians and Surgeons, Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Graduate School of Medicine [Osaka], Osaka University [Osaka], Department of Physiopatology and Transplantation, University of Milan (DEPT), Universidade de São Paulo Medical School (FMUSP), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Stritch School of Medicine, Edward Hines, Jr. VA Hospital, and Fondazione IRCCS Policlinico San Matteo [Pavia]
Subjects: Pulmonary and Respiratory Medicine, Artificial ventilation, medicine.medical_specialty, Consensus, Critical Care, Ventilator-Induced Lung Injury, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Diaphragm, Electric Stimulation Therapy, Lung injury, Critical Care and Intensive Care Medicine, Artificial respiration, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, NO, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Mechanical ventilation, Intensive care, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Extracorporeal membrane oxygenation, Humans, Myotrauma, 030212 general & internal medicine, Intensive care medicine, business.industry, Decision Support Systems, Clinical, Respiration, Artificial, 3. Good health, Diaphragm (structural system), Phrenic Nerve, [SDV] Life Sciences [q-bio], Muscular Atrophy, 030228 respiratory system, Breathing, Human medicine, business, Critical Care Perspective
Abstract: International audience; Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient–ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
Published: 2020
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28. Oxidative stress contributes differentially to the pathophysiology of Charcot-Marie-Tooth disease type 2K

Author: Arnaud Chevrollier, Philippe Codron, Cyril Goizet, Naïg Gueguen, Guy Lenaers, Pascal Reynier, Dominique Bonneau, Vincent Procaccio, Julien Cassereau, Christophe Verny, 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), 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), Service de Génétique Médicale du CHU de Bordeaux, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Nerve Tissue Proteins, Mitochondrion, Resveratrol, medicine.disease_cause, Antioxidants, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Developmental Neuroscience, Charcot-Marie-Tooth Disease, medicine, Humans, NRF1, Fibroblast, ComputingMilieux_MISCELLANEOUS, Mutation, Electron Transport Complex I, biology, Sirtuin 1, Glutathione, Fibroblasts, Mitochondria, 3. Good health, Cell biology, Oxidative Stress, 030104 developmental biology, medicine.anatomical_structure, Neurology, chemistry, biology.protein, 030217 neurology & neurosurgery, Oxidative stress
Abstract: Charcot-Marie-Tooth (CMT) disease is a common inherited peripheral neuropathy. The CMT2K axonal form is associated with GDAP1 dominant mutations, which according to the affected domain cause a gradient of severity. Indeed, the p.C240Y mutation, located within GDAP1 glutathione S-transferase (GST) domain and associated to a mitochondrial complex I defect, is related to a faster disease progression, compared to other mutations, such as the p.R120W located outside the GST domain. Here, we analysed the pathophysiology of six CMT2K fibroblast cell lines, carrying either the p.C240Y or p.R120W mutations. We show that complex I deficiency leads to a redox potential alteration and a significant reduction of sirtuin 1 (SIRT1) expression, a major deacetylase sensitive to the cellular redox state, and NRF1 the downstream target of SIRT1. In addition, we disclosed that the p.C240Y mutation is associated with a greater mitochondrial oxidative stress than the p.R120W mutation. Moreover, complex I activity is further restored in CMT2K mutant cell lines exposed to resveratrol. Together, these results suggest that the reduction of oxidative stress may constitute a promising therapeutic strategy for CMT2K.
Published: 2020
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29. Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma

Author: Philippe Moreau, Laurent Garderet, Bertrand Arnulf, Sabrina Maheo, Lotfi Benboubker, Mamoun Dib, Sabine Brechignac, Nelly Robillard, Mohamad Mohty, Margaret Macro, Brigitte Pegourie, Thierry Facon, Brigitte Kolb, Karim Belhadj, Nikhil C. Munshi, Bruno Royer, Olivier Decaux, Arnaud Jaccard, Valérie Lauwers-Cances, Marie-Lorraine Chretien, Anne-Marie Stoppa, Hervé Avet-Loiseau, Xavier Leleu, Kenneth C. Anderson, Jean-Richard Eveillard, Martin Moorhead, Chantal Doyen, Cecile Fohrer, Lionel Karlin, Jill Corre, Victoria Carlton, Paul G. Richardson, Malek Faham, Jean-Luc Harousseau, Michel Attal, Nathalie Meuleman, Thomas D. Willis, Aurore Perrot, Cyrille Hulin, Thomas Dejoie, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Dpt hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Biochimie [Nantes], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire de Bobigny, Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Universitaire de Caen, Department of Energy / Joint Genome Institute (DOE), Los Alamos National Laboratory (LANL), Département d'Hématologie Clinique [CHU Nantes], Département d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département d'Hématologie [CHU Nantes], Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hématologie [IUCT Oncopole, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Département d'hématologie [CHU Saint-Antoine, AP-HP], AP-HP - Hôpital Saint-Antoine, Institut Jules Bordet, Service hématologie (CHU d'Amiens), Département d'Hématologie Clinique [CHU Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service d'Hématologie [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Oncology, Neoplasm, Residual, Biochemistry, Dexamethasone, Bortezomib, Observations Lymphoid Neoplasia, 0302 clinical medicine, Maintenance therapy, Bone Marrow, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Lenalidomide, Multiple myeloma, Lymphoid Neoplasia, Hazard ratio, High-Throughput Nucleotide Sequencing, Hematology, Minimal Residual Disease Negativity, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, medicine.drug, medicine.medical_specialty, Plasma Cells, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Humans, Clinical Trials, Survival rate, Aged, business.industry, Cell Biology, medicine.disease, Minimal residual disease, Transplantation, 030104 developmental biology, business, Follow-Up Studies
Abstract: IF 15.132 (2017); International audience; The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (
Published: 2018
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30. Factors influencing physiotherapists’ attitudes and beliefs toward chronic low back pain: Impact of a care network belonging

Author: Audrey Petit, Cyril Bègue, Isabelle Richard, Yves Roquelaure, PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire d'Angers (CHU Angers), Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), 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)-Institut de Veille Sanitaire (INVS), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA)-Institut de Veille Sanitaire (INVS)
Subjects: Adult, Male, musculoskeletal diseases, Biopsychosocial model, Health Knowledge, Attitudes, Practice, 030506 rehabilitation, medicine.medical_specialty, Attitude of Health Personnel, Physical Therapy, Sports Therapy and Rehabilitation, biopsychosocial, 03 medical and health sciences, Professional Role, 0302 clinical medicine, Surveys and Questionnaires, health services administration, Humans, Pain Management, Physiotherapist, Medicine, biomechanical, Patient Care Team, Delivery of Health Care, Integrated, business.industry, Chronic low back pain, Physical Therapists, Cross-Sectional Studies, chronic low back pain, Physical therapy, beliefs, Female, Interdisciplinary Communication, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Chronic Pain, 0305 other medical science, business, Low Back Pain, 030217 neurology & neurosurgery
Abstract: International audience; Objectives - To assess the attitudes and beliefs of physiotherapists (PTs) regarding the management of chronic LBP and to investigate the factors which influence them. Methods - A cross-sectional study conducted in the French Loire Valley region by a questionnaire sent to the private PTs between June and September 2014. Demographic data and modalities of practices were collected in association with the Pain Attitudes and Beliefs Scale (PABS) which is a specific self-administered questionnaire designed to assess the "biomedical" or "behavioral" (i.e., biopsychosocial) management orientation of PTs toward chronic LBP. Results - One hundred and sixty-eight of the 704 PTs entirely completed the questionnaire (63% of men, 58% >40 years of age) of whom 15 were involved in a LBP care network. A higher biomechanical score was observed with a higher age and lower with full-time employment, less than 20 years of length of practice and a recent LBP-specific training (p
Published: 2018
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31. Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study

Author: Caroline Neulier, Alexandra Lomont, J. Merrer, B. Grandbastien, J.C. Lucet, Jean-Ralph Zahar, Delphine Hilliquin, V. Thepot Seegers, Didier Lepelletier, R. Le Guern, Anne-Marie Rogues, C. Legeay, V. Marie, CHU Lille, Université de Lille, Centre Hospitalier Universitaire d'Angers [CHU Angers], Recherche translationnelle : relations hôte-pathogènes - EA 7366, Recherche translationelle relations hôte-pathogènes, Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO], AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU de Bordeaux Pellegrin [Bordeaux], Centre hospitalier universitaire de Nantes [CHU Nantes], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, Multivariate analysis, [SDV]Life Sciences [q-bio], Mesh:Adult, 0302 clinical medicine, Mesh:Risk Factors, Mesh:Case-Control Studies, 030212 general & internal medicine, Mesh:Aged, Mesh:Klebsiella pneumoniae/enzymology, OXA-48, Aged, 80 and over, Mesh:Klebsiella Infections/microbiology, Univariate analysis, Screening, Contact patients, Carbapenemases, Carbapenemase-producing, Risk factors, Enterobacteriaceae, General Medicine, Middle Aged, 3. Good health, Klebsiella pneumoniae, Infectious Diseases, Mesh:Klebsiella Infections/epidemiology, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Mesh:Young Adult, beta-Lactamases, Young Adult, 03 medical and health sciences, Mesh:Retrospective Studies, Mesh:Klebsiella pneumoniae/isolation & purification, Mesh:Middle Aged, Internal medicine, Mesh:80 and over, medicine, Humans, Aged, Retrospective Studies, business.industry, Case-control study, Retrospective cohort study, Odds ratio, medicine.disease, Confidence interval, Klebsiella Infections, Mesh:beta-Lactamases/analysis, Surgery, Mesh:Humans, Case-Control Studies, Concomitant, Klebsiella pneumonia, business
Abstract: International audience; BACKGROUND: Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading.OBJECTIVE: To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations.METHODS: A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times.RESULTS: Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P
Published: 2018
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32. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study

Author: GuÃ©rin, C., Beuret, P., Constantin, J. M., Bellani, G., Garcia-Olivares, P., Roca, O., Meertens, J. H., Maia, P. Azevedo, Becher, T., Peterson, J., Larsson, A., Gurjar, M., Hajjej, Z., Kovari, F., Assiri, A. H., Mainas, E., Hasan, M. S., Morocho-Tutillo, D. R., Baboi, L., ChrÃ©tien, J. M., FranÃ§ois, G., Ayzac, L., Chen, L., Brochard, L., Mercat, A., Hajjej, Zied, Sellami, Walid, Ferjani, M., Gurjar, Mohan, Assiri, Amer, Al Bshabshe, Ali, Almekhlafi, Ghaleb, Mandourah, Yasser, Hasan, Mohd Shahnaz, Rai, Vineya, Marzida, M., Corcoles Gonzalez, Virgilio, Sanchez Iniesta, Rafael, Garcia, Pablo, Garcia-Montesinos de la PeÃ±a, Manuel, Garcia Herrera, Adriana, Roca, Oriol, Garcia-de-Acilu, Marina, Masclans Enviz, Joan Ramon, Mancebo, Jordi, Heili, Sarah, Artigas Raventos, Antonio, Blanch Torra, LluÃs, Roche-Campo, Ferran, Rialp, Gemma, Forteza, Catalina, Berrazueta, Ana, Martinez, Esther, Penuelas, Oscar, Jara-Rubio, Ruben, Mallat, Jihad, Thevenin, D., Zogheib, Elie, Mercat, Alain, Levrat, Albrice, Porot, Veronique, Bedock, B., Grech, Ludovic, Plantefeve, Gaetan, Badie, Julio, Besch, Guillaume, Pili-Floury, SÃ©bastien, Guisset, Olivier, Robine, Adrien, Prat, Gwenael, Doise, Jean-Marc, Badet, Michel, Thouret, J. M., Just, Bernard, Perbet, SÃ©bastien, Lautrette, Alexandre, Souweine, B., Chabanne, Russell, Danguy des DÃ©serts, Marc, Rigaud, Jean-Philippe, Marchalot, Antoine, Rigaud, J. P., Bele, Nicolas, Beague, SÃ©bastien, Hours, Sandrine, Marque, Sophie, Durand, Michel, Payen, J. F., Stoclin, Annabelle, Gaffinel, Alain, Winer, Arnaud, Chudeau, Nicolas, Tirot, Patrice, Thyrault, Martial, Paulet, RÃ©mi, Thyrault, M., Aubrun, Frederic, Guerin, Claude, Floccard, Bernard, Rimmele, T., Argaud, Laurent, Hernu, Romain, Crozon Clauzel, Jullien, Wey, Pierre-FranÃ§ois, Bourdin, Gael, Pommier, C., Cueuille, NadÃge, de Varax, null, Marchi, Elisa, Papazian, L., Jochmans, Sebastien, Monchi, M., Jaber, Samir, de Jong, Audrey, Moulaire, Valerie, Capron, Matthieu, Jarrige, L., Barberet, Guillaume, Lakhal, Karim, Rozec, B., Dellamonica, Jean, Robert, Alexandre, Bernardin, G., Danin, Pierre-Eric, Raucoules, M., Runge, Isabelle, Foucrier, Arnaud, Hamada, Sophie, Tesniere, Antoine, Fromentin, MÃ©lanie, Samama, C. M., Mira, Jean-Paul, Diehl, Jean-Luc, Mekontso Dessap, Armand, Arbelot, Charlotte, Demoule, Alexandre, Roche, Anne, Similowski, T., Ricard, Jean-Damien, Gaudry, StÃ©phane, Dreyfuss, D., de Montmolin, Etienne, da Silva, Daniel, Verdiere, B., Ardisson, Fanny, Lemiale, Virginie, Azoulay, Elie, Bruel, CÃ©dric, Tiercelet, Kelly, Fartoukh, Muriel, Voiriot, Guillaume, Hoffmann, Clement, Leclerc, T., Thille, Arnaud, Robert, RÃ©nÃ©, Beuret, Pascal, Beduneau, GaÃ«tan, Beuzelin, Marion, Tamion, F., Morel, JÃ©rÃ´me, Tremblay, Aymeric, Molliex, S., Amal, Jean-Michel, Meaudre, Eric, Goutorbe, Philippe, Laffon, Marc, Gros, Antoine, Nica, Alexandru, Barjon, Genevieve, Dahyot-Fizelier, Claire, Imzi, Nadia, Gally, Josette, Real, null, Sauneuf, Bertrand, Souloy, Xavier, Girbes, Armand, Tuinman, Pieter Roel, Schultz, Marcus, Winters, Tineke, Mijzen, Lisa, Roekaerts, P. M. H. J., Vermeijden, Wytze, Beishuizen, Albertus, Trof, R., Corsten, Stijn, Kesecioglu, Jozef, Meertens, John, Dieperink, Wim, Pickers, Peter, Roovers, Noortje, Maia, Paulo, Duque, Melanie, Rua, Fernando, Pereira de Figueired, AntÃ³nio Manuel, Ramos, Armindo, Fragoso, Elsa, Azevedo, Pilar, Gouveia, Joao, Costa E. Silva, ZÃ©lia, Silva, Goncalo, Chaves, Susana, Nobrega, J. J., Lopes, LuÃs, Valerio, Bernardino, Araujo, Ana Carolina, de Freitas, Paulo Telles, Bouw, Maria Jose, Melao, Maria, Granja, C., Marcal, Paulo, Fernandes, Antero, Joao, GonÃ§alves Pereira, Maia, DionÃsio Faria, Spadaro, Savino, Volta, Carlo Alberto, Bellani, Giacomo, Citerio, G., Mauri, Tommaso, Alban, Laura, Pesenti, A., Mistraletti, Giovanni, Formenti, Paolo, Tommasino, C., Tardini, Francesca, Fumagalli, R., Colombo, Riccardo, Fossali, Tommaso, Catena, E., Todeschini, Manuel, Gnesin, Paolo, Cracchiolo, Andrea Neville, Palma, Daniela, Tetamo, R., Albiero, Daniela, Costantini, Elena, Raimondi, F., Coppadoro, Andrea, Vascotto, Ettore, Lusenti, F., Becher, Tobias, SchÃ¤dler, Dirk, Weiler, N., Karagiannidis, Christian, Petersson, Johan, Konrad, D., Kawati, Rafael, Wessbergh, Joanna, Valtysson, J., Rockstroh, Matthias, Borgstrom, Sten, Larsson, Niklas, Thunberg, J., Camsooksai, Julie, Briggs, null, Kovari, Ferenc, Cuesta, J., Anwar, Sibs, Oâ€™Brien, B., Barberis, Luigi, Sturman, J., Mainas, Efstratios, Karatzas, S., Piza, Petr, Sottiaux, Thierry, Adam, J. F., Gawda, Ryszard, Gawor, Maen, Alqdah, M., Cohen, D., Brochard, Laurent, Baker, A., Ã‘amendys-Silva, Silvio Antonio, Garcia-Guillen, Francisco Javier, Morocho Tutillo, Diego Rolando, Jibaja Vega, Manuel, Zakalik, Graciela, Pagella, Gonzalo, Marengo, J., KARLI, Mélanie, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Lyon, 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), 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 [2017-2020] (UCA [2017-2020]), Hospital General Universitario 'Gregorio Marañón' [Madrid], Vall d'Hebron University Hospital [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), University Medical Center Groningen [Groningen] (UMCG), Centro Hospitalar do Porto, Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Uppsala University, University of Malaya [Kuala Lumpur, Malaisie], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Université d'Angers - Faculté de médecine (UA UFR Médecine), 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), Other departments, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Critical Care, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), Guã©rin, C, Beuret, P, Constantin, J, Bellani, G, Garcia-Olivares, P, Roca, O, Meertens, J, Maia, P, Becher, T, Peterson, J, Larsson, A, Gurjar, M, Hajjej, Z, Kovari, F, Assiri, A, Mainas, E, Hasan, M, Morocho-Tutillo, D, Baboi, L, Chrã©tien, J, Franã§ois, G, Ayzac, L, Chen, L, Brochard, L, Mercat, A, Sellami, W, Ferjani, M, Al Bshabshe, A, Almekhlafi, G, Mandourah, Y, Rai, V, Marzida, M, Corcoles Gonzalez, V, Sanchez Iniesta, R, Garcia, P, Garcia-Montesinos de la PeÃ±a, M, Garcia Herrera, A, Garcia-de-Acilu, M, Masclans Enviz, J, Mancebo, J, Heili, S, Artigas Raventos, A, Blanch Torra, L, Roche-Campo, F, Rialp, G, Forteza, C, Berrazueta, A, Martinez, E, Penuelas, O, Jara-Rubio, R, Mallat, J, Thevenin, D, Zogheib, E, Levrat, A, Porot, V, Bedock, B, Grech, L, Plantefeve, G, Badie, J, Besch, G, Pili-Floury, S, Guisset, O, Robine, A, Prat, G, Doise, J, Badet, M, Thouret, J, Just, B, Perbet, S, Lautrette, A, Souweine, B, Chabanne, R, Danguy des DÃ©serts, M, Rigaud, J, Marchalot, A, Bele, N, Beague, S, Hours, S, Marque, S, Durand, M, Payen, J, Stoclin, A, Gaffinel, A, Winer, A, Chudeau, N, Tirot, P, Thyrault, M, Paulet, R, Aubrun, F, Guerin, C, Floccard, B, Rimmele, T, Argaud, L, Hernu, R, Crozon Clauzel, J, Wey, P, Bourdin, G, Pommier, C, Cueuille, N, de Varax, N, Marchi, E, Papazian, L, Jochmans, S, Monchi, M, Jaber, S, de Jong, A, Moulaire, V, Capron, M, Jarrige, L, Barberet, G, Lakhal, K, Rozec, B, Dellamonica, J, Robert, A, Bernardin, G, Danin, P, Raucoules, M, Runge, I, Foucrier, A, Hamada, S, Tesniere, A, Fromentin, M, Samama, C, Mira, J, Diehl, J, Mekontso Dessap, A, Arbelot, C, Demoule, A, Roche, A, Similowski, T, Ricard, J, Gaudry, S, Dreyfuss, D, de Montmolin, E, da Silva, D, Verdiere, B, Ardisson, F, Lemiale, V, Azoulay, E, Bruel, C, Tiercelet, K, Fartoukh, M, Voiriot, G, Hoffmann, C, Leclerc, T, Thille, A, Robert, R, Beduneau, G, Beuzelin, M, Tamion, F, Morel, J, Tremblay, A, Molliex, S, Amal, J, Meaudre, E, Goutorbe, P, Laffon, M, Gros, A, Nica, A, Barjon, G, Dahyot-Fizelier, C, Imzi, N, Gally, J, Real, N, Sauneuf, B, Souloy, X, Girbes, A, Tuinman, P, Schultz, M, Winters, T, Mijzen, L, Roekaerts, P, Vermeijden, W, Beishuizen, A, Trof, R, Corsten, S, Kesecioglu, J, Dieperink, W, Pickers, P, Roovers, N, Duque, M, Rua, F, Pereira de Figueired, A, Ramos, A, Fragoso, E, Azevedo, P, Gouveia, J, Costa E. Silva, Z, Silva, G, Chaves, S, Nobrega, J, Lopes, L, Valerio, B, Araujo, A, de Freitas, P, Bouw, M, Melao, M, Granja, C, Marcal, P, Fernandes, A, Joao, G, Maia, D, Spadaro, S, Volta, C, Citerio, G, Mauri, T, Alban, L, Pesenti, A, Mistraletti, G, Formenti, P, Tommasino, C, Tardini, F, Fumagalli, R, Colombo, R, Fossali, T, Catena, E, Todeschini, M, Gnesin, P, Cracchiolo, A, Palma, D, Tetamo, R, Albiero, D, Costantini, E, Raimondi, F, Coppadoro, A, Vascotto, E, Lusenti, F, Schã¤dler, D, Weiler, N, Karagiannidis, C, Petersson, J, Konrad, D, Kawati, R, Wessbergh, J, Valtysson, J, Rockstroh, M, Borgstrom, S, Larsson, N, Thunberg, J, Camsooksai, J, Briggs, N, Cuesta, J, Anwar, S, Oâ€™Brien, B, Barberis, L, Sturman, J, Karatzas, S, Piza, P, Sottiaux, T, Adam, J, Gawda, R, Gawor, M, Alqdah, M, Cohen, D, Baker, A, Ã‘amendys-Silva, S, Garcia-Guillen, F, Morocho Tutillo, D, Jibaja Vega, M, Zakalik, G, Pagella, G, and Marengo, J
Subjects: ARDS, RECEIVING MECHANICAL VENTILATION, Epidemiology, medicine.medical_treatment, cross-sectional studies, RESPIRATORY-DISTRESS-SYNDROME, vrouwelijk, buikligging, Critical Care and Intensive Care Medicine, respiratory distress syndrome, adult/therapy, law.invention, Positive-Pressure Respiration, Prone position, 0302 clinical medicine, Mechanical ventilation, prospectieve studies, Randomized controlled trial, law, middle aged, Medicine, FAILURE, adult/therapy, humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, RANDOMIZED CONTROLLED-TRIAL, respiratory distress syndrome, 3. Good health, cross-sectionele studies, ademnoodsyndroom, aged, female, SURVIVAL, middelbare leeftijd, medicine.medical_specialty, Pain medicine, positieve druk uitademing, NO, 03 medical and health sciences, male, mensen, Anesthesiology, ouderen, METAANALYSIS, business.industry, MORTALITY, 030208 emergency & critical care medicine, mannelijk, CARE, medicine.disease, prospective studies, EVOLUTION, body regions, 030228 respiratory system, Emergency medicine, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: While prone positioning (PP) has been shown to improve patient survival in moderate to severe acute respiratory distress syndrome (ARDS) patients, the rate of application of PP in clinical practice still appears low.Aim: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).Methods: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).Results: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH(2)O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH(2)O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).Conclusions: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.
Published: 2018
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33. Pulmonary embolism rule-out criteria (PERC) rule in European patients with low implicit clinical probability (PERCEPIC): a multicentre, prospective, observational study

Author: Andrea Penaloza, Quentin Delmez, Olivier Sanchez, N. Delvau, Nicolas Marjanovic, Alexandre Ghuysen, Jeannot Schmidt, Thomas Moumneh, Farès Moustafa, Christian Brice, Philippe Girard, Guy Meyer, Grégoire Le Gal, Béatrice Gable, Jacques Bouget, Lionel Imsaad, Caroline Soulie, Pierre-Marie Roy, Catherine Le Gall, A Trinh-Duc, Dominique El Kouri, Jean-Marie Chretien, Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Modélisation Conceptuelle des Connaissances Biomédicales, Université de Rennes (UR), Département des Urgences, CHU Clermont-Ferrand, Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Victor Dupouy, Délégation à la recherche clinique et innovation, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), 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)-Université de Brest (UBO), Centre de Recherche Clinique (CRC Angers), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Adult, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, White People, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, medicine, Clinical endpoint, Humans, Prospective Studies, 030212 general & internal medicine, education, Prospective cohort study, False Negative Reactions, Case report form, ComputingMilieux_MISCELLANEOUS, Aged, Ultrasonography, education.field_of_study, Intention-to-treat analysis, business.industry, Angiography, Anticoagulants, Hematology, Emergency department, Middle Aged, medicine.disease, 3. Good health, Pulmonary embolism, Treatment Outcome, Observational study, Emergency Service, Hospital, Pulmonary Embolism, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Summary Background The ability of the pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism without further testing remains debated outside the USA, especially in the population with suspected pulmonary embolism who have a high prevalence of the condition. Our main objective was to prospectively assess the predictive value of negative PERC to rule out pulmonary embolism among European patients with low implicit clinical probability. Methods We did a multicentre, prospective, observational study in 12 emergency departments in France and Belgium. We included consecutive patients aged 18 years or older with suspected pulmonary embolism. Patients were excluded if they had already been hospitalised for more than 2 days, had curative anticoagulant therapy in progress for more than 48 h, or had a diagnosis of thromboembolic disease documented before admission to emergency department. Physicians completed a standardised case report form comprising implicit clinical probability assessment (low, moderate, or high) and a list of risk factors including criteria of the PERC rule. They were asked to follow international recommendations for diagnostic strategy, masked to PERC assessment. The primary endpoint was the proportion of patients with low implicit clinical probability and negative PERC who had venous thromboembolic events, diagnosed during initial diagnostic work-up or during 3-month follow-up, as externally adjudicated by an independent committee masked to the PERC and clinical probability assessment. The upper limit of the 95% CI around the 3-month thromboembolic risk was set at 3%. We did all analyses by intention to treat, including all patients with complete follow-up. This trial is registered with ClinicalTrials.gov, number NCT02360540. Findings Between May 1, 2015, and April 30, 2016, 1773 consecutive patients with suspected pulmonary embolism were prospectively assessed for inclusion, of whom 1757 were included. 1052 (60%) patients were classed as having low clinical probability, 49 (4·7%, 95% CI 3·5–6·1) of whom had a venous thromboembolic event. In patients with a low implicit clinical probability, 337 (32%) patients had negative PERC, of whom four (1·2%; 95% CI 0·4–2·9) went on to have a pulmonary embolism. Interpretation In European patients with low implicit clinical probability, PERC can exclude pulmonary embolism with a low percentage of false-negative results. The results of our prospective, observational study allow and justify an implementation study of the PERC rule in Europe. Funding French Ministry of Health.
Published: 2017
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34. Risk factors for episodic neck pain in workers: a 5-year prospective study of a general working population

Author: Alexis Descatha, Natacha Fouquet, Julie Bodin, Audrey Petit, Yves Roquelaure, Angélique Delarue, PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire d'Angers (CHU Angers), Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), 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)-Institut de Veille Sanitaire (INVS), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Santé publique France - French National Public Health Agency [Saint-Maurice, France], and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité)
Subjects: Adult, Male, medicine.medical_specialty, Physical Exertion, Posture, Individual, Workload, Logistic regression, Work related, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Risk factor, Prospective cohort study, Neck pain, Neck Pain, business.industry, Incidence, Incidence (epidemiology), Public health, Work-related, Public Health, Environmental and Occupational Health, Middle Aged, 030210 environmental & occupational health, Occupational Diseases, Etiology, Physical therapy, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Ergonomics, France, medicine.symptom, Neck disorder, business, Demography
Abstract: Development of neck pain (NP) in workers has a multifactorial etiology and depends on both individual and workplace factors. The aim of this study was to investigate risk factors for episodic NP in a large diverse sample of active workers. A prospective study based on the surveillance program implemented by the French Public Health Agency in the Loire Valley region. Between 2002 and 2005, 3710 workers were included. Between 2007 and 2010, 2332 workers responded to a follow-up questionnaire which assessed: (1) musculoskeletal symptoms (Nordic questionnaire) and (2) individual and work-related risk factors. Associations between episodic NP in 2007 (i.e., free subjects at baseline and who suffered at least 8 days during the preceding 12 months) and individual and work-related risk factors at baseline were studied using logistic regression modeling, stratified by sex. Among the 1510 workers (914 men, 596 women) still active at follow-up, 10.4% (8.4–12.4) of men and 14.6% (11.8–17.4) of women declared episodic NP. Among men, work pace dependence of guests or permanent hierarchical controls were risk factors of NP [OR = 1.8 (1.1–2.8) and OR = 2.1 (1.3–3.3), respectively]. Among women, the combination of sustained/repeated arm abduction with high physical perceived exertion was the strongest risk factor for NP [OR = 3.5 (1.7–7.2)]; age and paced work were also predictors for NP in women. NP results from complex relationships between individual and work-related variables. High physical workload, awkward postures, and poor organizational environment together with age differently predicted episodic NP according to the sex.
Published: 2017
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35. Exophiala dermatitidis Revealing Cystic Fibrosis in Adult Patients with Chronic Pulmonary Disease

Author: Bénédicte Richaud-Thiriez, Marie Gainet-Brun, Jean-Philippe Bouchara, B. Cimon, Heloise Pana-Katatali, Marie-Claire Malinge, Frédéric Grenouillet, Yohann Le Govic, Christine Person, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département de Biochimie et Génétique [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), Astellas, Pfizer, and MSD
Subjects: 0301 basic medicine, food.ingredient, Veterinary (miscellaneous), 030106 microbiology, Applied Microbiology and Biotechnology, Microbiology, Cystic fibrosis, 03 medical and health sciences, Elderly, food, Exophiala, Humans, Medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Aged, 80 and over, Bronchiectasis, Lung Diseases, Fungal, biology, business.industry, Respiratory disease, biology.organism_classification, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Late diagnosis, 3. Good health, Exophiala dermatitidis, Phaeohyphomycosis, medicine.anatomical_structure, Immunology, biology.protein, Female, business, Agronomy and Crop Science, Dimorphic fungus, Rasamsonia, Respiratory tract
Abstract: International audience; Cystic fibrosis (CF) is a genetic inherited disease due to mutations in the gene cystic fibrosis transmembrane conductance regulator (CFTR). Because of the huge diversity of CFTR mutations, the CF phenotypes are highly heterogeneous, varying from typical to mild form of CF, also called atypical CF. These atypical features are more frequently diagnosed at adolescence or adulthood, and among clinical signs and symptoms leading to suspect a mild form of CF, colonization or infection of the respiratory tract due to well-known CF pathogens should be a warning signal. Exophiala dermatitidis is a melanized dimorphic fungus commonly detected in respiratory specimens from CF patients, but only very rarely from respiratory specimens from non-CF patients. We described here two cases of chronic colonization of the airways by E. dermatitidis, with recurrent pneumonia and hemoptysis in one patient, which led clinicians to diagnose mild forms of CF in these elderly patients who were 68- and 87-year-old. These cases of late CF diagnosis suggest that airway colonization or respiratory infections due to E. dermatitidis in patients with bronchiectasis should led to search for a mild form of CF, regardless of the age and associated symptoms. On a broader level, in patients with chronic respiratory disease and recurrent pulmonary infections, an allergic bronchopulmonary mycosis or an airway colonization by CF-related fungi like E. dermatitidis or some Aspergillus, Scedosporium or Rasamsonia species, should be considered as potential markers of atypical CF and should led clinicians to conduct investigations for CF diagnosis.
Published: 2017
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36. Inhibition of effector antigen-specific T cells by intradermal administration of heme oxygenase-1 inducers

Author: Julien Pogu, Philippe Blancou, Maud Maquigneau, Frédéric Brau, Séverine Remy, Thomas Simon, Ignacio Anegon, Sylvie Pogu, Jean-François Fonteneau, Gilles Blancho, Eliane Piaggio, Nicolas Poirier, Bernard Vanhove, Centre de Recherche en Transplantation et Immunologie ( U1064 Inserm - CRTI - CHU Nantes ), Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Center for Vascular and Inflammatory Diseases [Baltimore, USA], University of Maryland School of Medicine [Baltimore], Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] ( IECM ), Université de Nantes ( UN ) -Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique ( ONIRIS ) -Institut National de la Recherche Agronomique ( INRA ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, OSE Immunotherapeutics [Nantes], Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), ANR-10-IBHU-0005/10-IBHU-0005,CESTI (TSI-IHU),CESTI (TSI-IHU) ( 2010 ), ANR-11-LABX-0016/11-LABX-0016,IGO,Immunothérapies Grand Ouest ( 2011 ), ANR-10-IDEX-0001-02/10-IDEX-0001,PSL,PSL ( 2010 ), ANR-10-IDEX-0001-02/11-LABX-0043,DCBIOL,Biologie des cellules dendritiques ( 2010 ), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-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), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Progreffe, JDRF [5-2010-640], IMBIO network, Region Pays de la Loire, IHU-Cesti project, Investissements d'Avenir French, ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-IBHU-0005/10-IBHU-0005,CESTI (TSI-IHU),CESTI (TSI-IHU)(2010), ANR-11-LABX-0016/11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-10-IDEX-0001-02/10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-IDEX-0001-02/11-LABX-0043,DCBIOL,Biologie des cellules dendritiques(2010), Bernardo, Elizabeth, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: CD4-Positive T-Lymphocytes, 0301 basic medicine, T-lymphocyte, Chemokine, T-Lymphocytes, T cell, Immunology, Antigen-Presenting Cells, Mice, Transgenic, T-Cell Antigen Receptor Specificity, [SDV.CAN]Life Sciences [q-bio]/Cancer, Autoimmunity, Autoantigens, Autoimmune Diseases, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, medicine, Animals, Humans, Immunology and Allergy, Hypersensitivity, Delayed, Intradermal injection, Antigens, Migration, biology, Effector, Diabetes, Dendritic cell, Papio anubis, Auto-immune encephalomyelitis, Delayed type hypersensitivity, 3. Good health, Heme oxygenase, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Heme oxygenase-1, biology.protein, Cytokines, Immunization, Myelin-Oligodendrocyte Glycoprotein, Tolerance, Monocyte-derived dendritic cells, CD8, T-Lymphocytes, Cytotoxic
Abstract: International audience; Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice. This phenomenon was observed in both a CD8 þ T cell-mediated model of T1D and in a CD4 þ T cell-dependent MS model. Intradermal injection of HO-1 in-ducers induced the recruitment of HO-1 þ monocyte-derived dendritic cell (MoDCs) exclusively to the lymph nodes (LN) draining the site of intradermal injection. After encountering HO-1 þ MoDCs, effector T-cells exhibited a lower velocity and a reduced ability to migrate towards chemokine gradients resulting in impaired accumulation to the inflamed organ. Intradermal co-injection of a clinically approved HO-1 inducer and a specific antigen to non-human primates also induced HO-1 þ MoDCs to accumulate in dermal draining LN and to suppress delayed-type hypersensitivity. Therefore, in both mice and non-human primates, HO-1 inducers delivered locally inhibited effector T-cells in an antigen-specific manner, paving the way for repositioning these drugs for the treatment of immune-mediated diseases.
Published: 2017
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37. Different Impact of the Number of Organ Failures and Graft-Versus-Host Disease on the Outcome of Allogeneic Stem Cell Transplantation Recipients Requiring Intensive Care

Author: Philippe Guardiola, Sylvie François, François Beloncle, Sylvain Thepot, Mathilde Hunault-Berger, Achille Kouatchet, Norbert Ifrah, Jean-François Hamel, Jonathan Farhi, Aline Tanguy-Schmidt, Alain Mercat, Mélanie Mercier, Corentin Orvain, Pierre Asfar, Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation Médicale et de Médecine Hyperbare [Angers], Centre de Recherche Clinique (CRC Angers), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Plateforme SNP, Transcriptome & Epigénomique, and Bernardo, Elizabeth
Subjects: Male, Time Factors, medicine.medical_treatment, Graft vs Host Disease, Kaplan-Meier Estimate, law.invention, Patient Admission, 0302 clinical medicine, Risk Factors, law, Odds Ratio, Hospital Mortality, Middle Aged, Intensive care unit, Patient Discharge, 3. Good health, Intensive Care Units, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, Critical Care, Multiple Organ Failure, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, medicine, Humans, Transplantation, Homologous, Renal replacement therapy, Proportional Hazards Models, Retrospective Studies, Mechanical ventilation, Transplantation, Chi-Square Distribution, business.industry, Retrospective cohort study, Odds ratio, medicine.disease, Surgery, Logistic Models, Graft-versus-host disease, Multivariate Analysis, business, Stem Cell Transplantation, 030215 immunology
Abstract: International audience; Background. Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial , especially when graft-versus-host disease (GVHD) is present. Methods. We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. Results. Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively , whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 μmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). Conclusions. Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.
Published: 2017
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38. Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain

Author: Olivier Beauchet, Cédric Annweiler, Gonzague Foucault, Mickael Dinomais, Romain Simon, Guillaume T. Duval, Laboratoire de Mathématiques de l'INSA de Rouen Normandie (LMI), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Département de Médecine Interne et Gérontologie clinique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), PRES Université Nantes Angers Le Mans (UNAM), Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Faculté de Médecine d'Angers, McGill University = Université McGill [Montréal, Canada], and University of Western Ontario (UWO)
Subjects: Vitamin, Cingulate cortex, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Renal function, Neuroimaging, vitamin D, Gyrus Cinguli, cingulate cortex, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Cortex (anatomy), medicine, Vitamin D and neurology, Blood test, Humans, magnetic resonance imaging, 030212 general & internal medicine, memory disorders, Anterior cingulate cortex, older adults, Aged, medicine.diagnostic_test, business.industry, Brain, Middle Aged, Vitamin D Deficiency, Endocrinology, medicine.anatomical_structure, Cross-Sectional Studies, Neurology, chemistry, Posterior cingulate, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults.OBJECTIVE: Our objective was to investigate in older adults whether vitamin D insufficiency
Published: 2019
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39. OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database

Author: Le Roux, Bastien, Lenaers, Guy, Zanlonghi, Xavier, Amati-Bonneau, Patrizia, Chabrun, Floris, Foulonneau, Thomas, Caignard, Angélique, Leruez, Stéphanie, Gohier, Philippe, Procaccio, Vincent, Milea, Dan, den Dunnen, Johan T., Reynier, Pascal, Ferré, Marc, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service Exploration Fonctionnelle de la Vision, Clinique Sourdille, Département de Biochimie et Génétique [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), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Singapore Eye Research Institute, Singapore National Eye Centre, Human Genetics, Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LENAERS, Guy, and MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC)
Subjects: endocrine system, Dominant optic atrophy, Research, [SDV]Life Sciences [q-bio], lcsh:R, lcsh:Medicine, Interoperability, OPA1, eye diseases, GTP Phosphohydrolases, Pedigree, Database, [SDV] Life Sciences [q-bio], Sequence variant, Phenotype, Mutation, Optic Atrophy, Autosomal Dominant, Humans, Genetic Association Studies, Neurological disorders, ComputingMilieux_MISCELLANEOUS
Abstract: Background The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for a large spectrum of neurological disorders, each of which includes optic neuropathy. The database dedicated to OPA1 (https://www.lovd.nl/OPA1), created in 2005, has now evolved towards a centralized and more reliable database using the Global Variome shared Leiden Open-source Variation Database (LOVD) installation. Results The updated OPA1 database, which registers all the patients from our center as well as those reported in the literature, now covers a total of 831 patients: 697 with isolated dominant optic atrophy (DOA), 47 with DOA “plus”, and 83 with asymptomatic or unclassified DOA. It comprises 516 unique OPA1 variants, of which more than 80% (414) are considered pathogenic. Full clinical data for 118 patients are documented using the Human Phenotype Ontology, a standard vocabulary for referencing phenotypic abnormalities. Contributors may now make online submissions of phenotypes related to OPA1 mutations, giving clinical and molecular descriptions together with detailed ophthalmological and neurological data, according to an international thesaurus. Conclusions The evolution of the OPA1 database towards the LOVD, using unified nomenclature, should ensure its interoperability with other databases and prove useful for molecular diagnoses based on gene-panel sequencing, large-scale mutation statistics, and genotype-phenotype correlations. Electronic supplementary material The online version of this article (10.1186/s13023-019-1187-1) contains supplementary material, which is available to authorized users.
Published: 2019
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40. Z oonotic tuberculosis in humans assessed by next-generation sequencing: an 18-month nationwide study in Lebanon

Author: Claire Pinçon, Cyril Gaudin, Marwan Osman, Philip Supply, Christine Demanche, Mohamad Bachar Ismail, Monzer Hamze, Rayane Rafei, Salam El Achkar, Stéphanie Duthoy, Frédérique De Matos, Hiam Yaacoub, Biodiversité et fonctionnement du sol (BIOSOL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Microbiologie Santé et Environnement - LMSE [Tripoli, Lebanon] (Faculté de Santé Publique), Université Libanaise-Ecole Doctorale des Sciences et de Technologie [Tripoli, Lebanon], Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Genoscreen, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre AZM pour la Recherche en Biotechnologie et ses Applications, Université Libanaise, 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)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), 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), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM)
Subjects: Pulmonary and Respiratory Medicine, 0303 health sciences, International call, Tuberculosis, 030306 microbiology, business.industry, 030231 tropical medicine, MEDLINE, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Environmental health, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Income country, Medicine, business, Bit (key), ComputingMilieux_MISCELLANEOUS
Abstract: International audience; The World Health Organization (WHO) and other international organisations, including the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health and the International Union Against Tuberculosis and Lung Disease recently called for formally assessing and (re)prioritising the burden of zoonotic tuberculosis (TB) in people, due to Mycobacterium bovis [1, 2]. Its global contribution to human TB, otherwise principally caused by Mycobacterium tuberculosis, might be underestimated [2]. Nationally representative prevalence data are virtually non-existent on continents with the highest presumed burdens, i.e. in Africa and Asia [3]. In addition to causing hard-to-diagnose extrapulmonary TB more frequently, M. bovis is naturally resistant to pyrazinamide [4], a crucial drug for the standard short-course anti-TB therapy. Due to reliability issues, phenotypic susceptibility to pyrazinamide is often not tested [5]. The most commonly used phenotypic and molecular diagnostics, including the WHO-endorsed GeneXpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA), do not differentiate M. bovis from M. tuberculosis [1]. Thus, M. bovis-infected patients may receive inadequate treatment, risking poorer outcomes [6]. Underdiagnosis in people also implies the existence of undetected animal and food sources and zoonotic risks escaping common TB control measures [1, 2]. In Europe, patients with M. bovis infection are often African-or southern Mediterranean-born, suggesting regional endemicity [6, 7]. We determined the prevalence of M. bovis-caused TB in a survey including all TB patients reported to the national TB programme over an 18-month period in Lebanon. In addition to its national population and >1.5 million Syrian and Palestinian refugees, this Mediterranean country hosts large numbers of migrant workers from Africa and Asia [8]. Many are from Ethiopia [8], where proportions of extrapulmonary TB and M. bovis-caused disease among TB patients apparently culminate, reaching ∼30% [9] and 15-30% (in focal studies; [10]), respectively. We used a novel targeted next-generation sequencing-based assay for extensive drug resistance detection, including resistance to pyrazinamide, and genotypic differentiation between M. bovis and M. tuberculosis [11]. This survey was approved by the Azm Center/Lebanese University ethical committee (document CE-EDST-3-2016). Clinical samples were collected from all 1104 different TB patients with presumption of pulmonary or extrapulmonary TB, based on the presence of symptoms and prior tuberculin skin testing or radiological examination in local hospitals for a number of patients, and reported to all national anti-TB centres between June 1, 2016 and November 31, 2017. All of these 1104 patients were tested by at least one of the following assays: solid (Lowenstein-Jensen) and/or liquid (BBL MGIT; Beckton Dickinson, Franklin Lakes, NJ, USA) culturing, GeneXpert MTB/RIF on sputum, and Anyplex MTB/NTM Real-time (Seegene, Seoul, Republic of Korea) on sputum or culture on solid or liquid medium. Out of these 1104, 417 were confirmed as TB positive by GeneXpert and/or Anyplex. Among these 417 patients, 354 were culture positive. Among the 354 corresponding patients, 325 were new TB patients, 22 had a previous TB history, while TB history information was unavailable for seven patients. Available DNA extracts, obtained from 348 out of 354 primary cultures by using MasterPure™ DNA Purification Kit (Epicentre, Illumina, Madison, WI, USA), were subjected to targeted sequencing, more @ERSpublications In response to recent international calls, this study reveals the nationally representative prevalence of zoonotic tuberculosis in people in a non-high income country, highlighting the need for appropriate diagnostics and treatment of these patients http://bit.ly/2l3ydDh
Published: 2019
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41. The 'Patient-centered coordination by a care team' questionnaire achieves satisfactory validity and reliability

Author: Bridget L. Ryan, Jonathan Sussman, Martin Fortin, Louisa Bestard-Denommé, Maude Richards, Tarek Bouhali, Aline Ramond-Roquin, Moira Stewart, Judith Belle Brown, Laboratoire d'Ergonomie et d'Épidémiologie en Santé au Travail (LEEST), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA)-Institut de Veille Sanitaire (INVS), Université de Sherbrooke (UdeS), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Veille Sanitaire (INVS)
Subjects: Adult, Male, medicine.medical_specialty, Psychometrics, Intraclass correlation, Interprofessional Relations, media_common.quotation_subject, Validity, patient-centered care, 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, Patient-Centered Care, Health care, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Reliability (statistics), Aged, media_common, Patient Care Team, Teamwork, Primary Health Care, 030504 nursing, business.industry, questionnaire, Reproducibility of Results, General Medicine, Middle Aged, Exploratory factor analysis, 3. Good health, [STAT]Statistics [stat], Cross-Sectional Studies, Telephone interview, Coordination of care, validation study, Health Care Surveys, Chronic Disease, care team, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, 0305 other medical science, business, Psychology
Abstract: Increasing prevalence of chronic conditions and multimorbidity challenges health care systems and calls for patient-centered coordination of care. Implementation and evaluation of health policies focusing on the development of patient-centered coordination of care needs valid instruments measuring this dimension of care. The aim of this validation study was to assess the psychometric properties of the French version of the 14-item Patient-Centered Coordination by a Care Team (PCCCT) questionnaire in a primary care setting. PCCCT provides a total score from 0 (worst coordination) to 42 (best coordination). 165 adult patients consulting in primary care with one or more chronic condition(s) completed questionnaires (including PCCCT) at recruitment. After three weeks, participants completed PCCCT again, either by mail (group A) or during a telephone interview (group B). At recruitment, the mean (SD) PCCCT score was 33.3 (7.7). Exploratory factor analysis revealed a 2-dimension structure, 8 items relating to patient involvement and 6 items relating to coordination (factors loadings ranging from 0.34 to 0.88). PCCCT score correlated significantly with subscales of Haggerty's continuity questionnaire, Spearman correlation coefficients (95% confidence interval) ranging from 0.40 (0.22-0.57) to 0.52 (0.38-0.63). Internal consistency was excellent: Cronbach alpha 0.90 (0.79-0.92). Reliability was good, with an intraclass correlation coefficient of 0.68 (0.55-0.78) for test-retest reliability (group A) and of 0.65 (0.46-0.79) for reliability between the self-administered and the interviewer-administered versions of the questionnaire (group B,). The PCCCT questionnaire presents satisfactory validity and reliability; it can be used for the evaluation of health organizations involving team work in primary care.
Published: 2019
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42. Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake and in vivo biodistribution improvements

Author: Resnier, Pauline, Lepeltier, Elise, Emina, Anthea, Galopin, Natacha, Bejaud, Jérôme, David, Stéphanie, Ballet, Caroline, Benvegnu, Thierry, Pecorari, Frédéric, Chourpa, Igor, Benoit, Jean-Pierre, Passirani, Catherine, Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Nanomédicaments et Nanosondes, EA 6295 (NMNS), Université de Tours, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), R12164NN, Ligue Contre le Cancer, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Tours (UT), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oncologie nucléaire (CRCINA - Département NOHMAD - Equipe 13), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), 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 de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-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 de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, technology, industry, and agriculture, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Malignant melanoma is an aggressive tumor, associated with the presence of local and/or distant metastases. The development of gene therapy by the use of small interfering RNA (siRNA) represents a promising new treatment. However, the protection of this biomolecule is necessary in order for it to be intravenously administrated, for example via its incorporation into nanomedicines. In parallel to the passive targeting usually obtained by pegylation, various studies have aimed at developing "smart" nanomedicines to efficiently deliver the drug to tumor sites. In this work, siRNA loaded lipid nanocapsules (LNCs) were modified with DSPE-polyethylene glycol (DSPE-PEG), tetraether-PEG (TE-PEG) and/or with an Affitin model, to assay multiple targeting strategies. The uptake of fluorescently labelled LNCs, nanocarrier integrity and siRNA release into human SK-Mel28 melanoma cells were studied by flow cytometry, conventional confocal microscopy and by confocal spectral imaging in a Förster Resonance Energy Transfer (FRET) mode. Surface modified siRNA LNCs were followed after human plasma incubation and after intravenous injection, in order to compare the stealth properties. Finally, the biodistribution of the different siRNA LNCs in healthy and melanoma tumor bearing mice models was assessed by in vivo biofluorescence imaging (BFI), to evaluate the potential tumor targeting ability. The post-insertion of DSPE-PEG induced a strong decrease of the internalization into melanoma cells compared to TE-PEG modification. Both PEG polymer decorations induced a great plasma protection of siRNA but only DSPE-PEG led to stealth properties, even at low concentration (5 mM). The Affitin grafting by thiolation of DSPE-PEG was validated on siRNA LNCs. DSPE-PEG-Affitin LNCs were not detected in this melanoma tumor model but did not show unspecific accumulation in organs. DSPE-PEG and TE-PEG LNCs induced a significant intratumoral accumulation of modified LNCs.
Published: 2019
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43. Metabo-lipidomics of Fibroblasts and Mitochondrial-Endoplasmic Reticulum Extracts from ALS Patients Shows Alterations in Purine, Pyrimidine, Energetic, and Phospholipid Metabolisms

Author: Patrick Vourc'h, Charlotte Veyrat-Durebex, Benoît Funalot, Philippe Couratier, Stéphanie Chupin, Cinzia Bocca, Philippe Codron, Céline Bris, Hélène Blasco, Julien Cassereau, Philippe Corcia, Christian R. Andres, Guy Lenaers, Rudolf Hergesheimer, Pascal Reynier, 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), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours, 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), Biomolécules Thérapies anti-tumorales (EA4021), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), 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 Neurologie [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Francois Rabelais [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), and Grelier, Elisabeth
Subjects: Male, 0301 basic medicine, Mitochondrial DNA, [SDV]Life Sciences [q-bio], Neuroscience (miscellaneous), Oxidative phosphorylation, Biology, Mitochondrion, Endoplasmic Reticulum, DNA, Mitochondrial, Oxidative Phosphorylation, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Metabolomics, Lipidomics, Metabolome, Humans, Phospholipids, ComputingMilieux_MISCELLANEOUS, Endoplasmic reticulum, Middle Aged, Fibroblasts, Lipidome, Lipid Metabolism, Amyotrophic lateral sclerosis, Mitochondria, Pyrimidines, 030104 developmental biology, Neurology, Biochemistry, Purines, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Oxidative stress, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Energy Metabolism, 030217 neurology & neurosurgery
Abstract: International audience; Amyotrophic lateral sclerosis (ALS) is characterized by a wide metabolic remodeling, as shown by recent metabolomics and lipidomics studies performed in samples from patient cohorts and experimental animal models. Here, we explored the metabolome and lipidome of fibroblasts from sporadic ALS patients (n = 13) comparatively to age- and sex-matched controls (n = 11), and the subcellular fraction containing the mitochondria and endoplasmic reticulum (mito-ER), given that mitochondrial dysfunctions and ER stress are important features of ALS patho-mechanisms. We also assessed the mitochondrial oxidative respiration and the mitochondrial genomic (mtDNA) sequence, although without yielding significant differences. Compared to controls, ALS fibroblasts did not exhibit a mitochondrial respiration defect nor an increased proportion of mitochondrial DNA mutations. In addition, non-targeted metabolomics and lipidomics analyses identified 124 and 127 metabolites, and 328 and 220 lipids in whole cells and the mito-ER fractions, respectively, along with partial least-squares-discriminant analysis (PLS-DA) models being systematically highly predictive of the disease. The most discriminant metabolomic features were the alteration of purine, pyrimidine, and energetic metabolisms, suggestive of oxidative stress and of pro-inflammatory status. The most important lipidomic feature in the mito-ER fraction was the disturbance of phosphatidylcholine PC (36:4p) levels, which we had previously reported in the cerebrospinal fluid of ALS patients and in the brain from an ALS mouse model. Thus, our results reveal that fibroblasts from sporadic ALS patients share common metabolic remodeling, consistent with other metabolic studies performed in ALS, opening perspectives for further exploration in this cellular model in ALS.
Published: 2019
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44. CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

Author: Lemerle, Marie, Garnier, Anne-Sophie, Planchais, Martin, Brilland, Benoit, Delneste, Yves, Subra, Jean-François, Blanchet, Odile, Blanchard, Simon, Croue, Anne, Duveau, Agnès, Augusto, Jean-François, 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), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'Immunologie et d'Allergologie [CHU Angers], Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), Département de Pathologie Cellulaire et Tissulaire [CHU Angers] (Laboratoire d’Histopathologie-Cytopathologie), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: medicine.medical_specialty, Lymphocyte, T cell, lcsh:Medicine, kidney transplantation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, 030230 surgery, lymphocyte, Gastroenterology, acute rejection, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, Internal medicine, Medicine, Cytotoxic T cell, Kidney transplantation, CD45RC, 030304 developmental biology, 0303 health sciences, business.industry, lcsh:R, General Medicine, medicine.disease, 3. Good health, body regions, Transplantation, medicine.anatomical_structure, business, CD8
Abstract: Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.
Published: 2019
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45. Nicotinamide Deficiency in Primary Open-Angle Glaucoma

Author: Kouassi Nzoughet, Judith, Chao de La Barca, Juan Manuel, Guehlouz, Khadidja, Coulbault, Laurent, Allouche, Stéphane, Bocca, Cinzia, Muller, Jeanne, Gohier, Philippe, Simard, Gilles, Milea, Dan, Desquiret-Dumas, Valérie, Leman, Géraldine, Wetterwald, Celine, Chupin, Stéphanie, Lebert, Anaïs, Khiati, Salim, Le Mao, Morgane, Geffroy, Guillaume, Kane, Mariame Selma, Chevrollier, Arnaud, Goudenège, David, Gadras, Cédric, Tessier, Lydie, Barth, Magalie, Leruez, Stéphanie, Amati-Bonneau, Patrizia, Henrion, Daniel, Bonneau, Dominique, Procaccio, Vincent, Reynier, Pascal, Lenaers, Guy, Gueguen, Naïg, 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), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de biochimie [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), Singapore Eye Research Institute, Singapore National Eye Centre, ARN : régulations naturelle et artificielle, Université Bordeaux Segalen - Bordeaux 2-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biochimie et Génétique [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), Réseau Maladies Métaboliques, Hôpitaux Universitaires du Grand Ouest, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)
Subjects: 0301 basic medicine, Adult, Male, Niacinamide, Intraocular pressure, Spectrometry, Mass, Electrospray Ionization, medicine.medical_specialty, Open angle glaucoma, [SDV]Life Sciences [q-bio], Urology, Glaucoma, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Intraocular Pressure, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Therapeutic strategy, Aged, 80 and over, 0303 health sciences, Nicotinamide, Case-control study, Nicotinamide deficiency, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, chemistry, Case-Control Studies, Plasma concentration, Cohort, 030221 ophthalmology & optometry, Female, 030217 neurology & neurosurgery, Glaucoma, Open-Angle, Cohort study, Chromatography, Liquid
Abstract: PurposeTo investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG).MethodsPlasma of 34 POAG individuals were compared to that of 30 age-and sex-matched controls using a semi-quantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls.ResultsUsing the semi-quantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 µM (median: 0.12 µM; range: 0.06-0.28 µM) in the POAG group (−30 %;p= 0.022), and 0.19 µM (median: 0.18 µM; range: 0.08-0.47 µM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (−33 %;p= 0.011) in the replicative cohort with mean concentrations of 0.14 µM (median: 0.14 µM; range: 0.09-0.25 µM) in the POAG group, and 0.19 µM (median: 0.21 µM; range: 0.09-0.26 µM) in the control group.ConclusionsGlaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.
Published: 2019
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46. Clinical study of 19 patients with SCN 8A ‐related epilepsy: Two modes of onset regarding EEG and seizures

Author: Svetlana Gataullina, Cécile Mignon-Ravix, Julien Denis, Frédéric Villega, Cecilia Altuzarra, Melanie Martin, Magalie Barth, Jean-Michel Pedespan, Sophie Julia, Alexandra Afenjar, Laurent Villard, Nathalie Villeneuve, Laurence Lion-François, Sophie Gueden, Diane Doummar, Jeremie Lefranc, Mathieu Milh, Pierre Cacciagli, Caroline Lacoste, Claude Cances, Lena Damaj, Cyril Mignot, Sébastien Moutton, Hubert Journel, Bruria Ben Zeev, Olivier Dulac, Sylvia Napuri, Gaetan Lesca, Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Epilepsie et ischémie cérébrale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de pédiatrie, hôpital Sud, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], CHU Bordeaux [Bordeaux], Service de Génétique Médicale du CHU de Bordeaux, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Département de Pédiatrie [CHU Toulouse], CHU Toulouse [Toulouse], Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Pediatrics, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Tel Aviv University [Tel Aviv], Service de génétique [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), Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Sud, CHU Pitié-Salpêtrière [APHP], Service de neuropédiatrie [Trousseau], Centre Hospitalier Bretagne Atlantique [Vannes], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Tel Aviv University (TAU)
Subjects: Male, 0301 basic medicine, Pediatrics, Delayed Diagnosis, Movement disorders, [SDV]Life Sciences [q-bio], Electroencephalography, Epilepsy, 0302 clinical medicine, Pregnancy, Prospective Studies, Age of Onset, Fetal Movement, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Seizure types, Normal interictal EEG, 3. Good health, Epileptic spasms, Phenotype, Neurology, Cohort, Anticonvulsants, Female, medicine.symptom, Sodium Channel Blockers, medicine.medical_specialty, Myoclonic Jerk, Mutation, Missense, 03 medical and health sciences, Munc18 Proteins, Seizures, medicine, Humans, KCNQ2 Potassium Channel, business.industry, Infant, Newborn, Infant, medicine.disease, Early Diagnosis, 030104 developmental biology, Amino Acid Substitution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, NAV1.6 Voltage-Gated Sodium Channel, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. Methods We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types. We made genotypic/phenotypic correlation based on epilepsy-associated missense variant localization over the protein. Results We found 19 patients carrying a de novo mutation of SCN8A, representing 3% of our cohort, with 9 mutations being novel. Age at onset of epilepsy was 1 day to 16 months. We found two modes of onset: 12 patients had slowly emerging onset with rare and/or subtle seizures and normal interictal EEG (group 1). The first event was either acute generalized tonic-clonic seizure (GTCS; Group 1a, n = 6) or episodes of myoclonic jerks that were often mistaken for sleep-related movements or other movement disorders (Group 1b, n = 6). Seven patients had a sudden onset of frequent tonic seizures or epileptic spasms with abnormal interictal EEG leading to rapid diagnosis of epileptic encephalopathy. Sodium channel blockers were effective or nonaggravating in most cases. Significance SCN8A is the third most prevalent early onset epileptic encephalopathy gene and is associated with two modes of onset of epilepsy.
Published: 2019
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47. Transfer RNA Maturation Defects Lead to Inhibition of ribosomal RNA Processing via Synthesis of pppGpp

Author: Trinquier, Aude, Ulmer, Jonathan, Gilet, Laetitia, Figaro, Sabine, Hammann, Philippe, Kuhn, Lauriane, Braun, Frédérique, Condon, Ciaran, Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Platforme Prote Strasbourg Esplanade, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de biologie physico-chimique (IBPC), Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), and PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes
Subjects: ppGpp, [SDV]Life Sciences [q-bio], ribosome biogenesis, RNA maturation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, stringent response, rRNA, tRNA, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019
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48. Second report of RING finger protein 113A (RNF113A) involvement in a Mendelian disorder

Author: Dominique Bonneau, Jean-Philippe Bault, Vincent Procaccio, Marine Tessarech, Stéphane Triau, Houria Salhi, Annie Laquerrière, Alban Ziegler, Agnès Guichet, Françoise Boussion, Céline Bris, B. Delorme, Pascal Reynier, Magali Gorce, Catherine Fallet-Bianco, Estelle Colin, Salim Khiaty, Majida Charif, Delphine Héron, Aurélia Jacquette, Service de gynécologie-obstétrique, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de foetopathologie, PRES Université Nantes Angers Le Mans (UNAM), Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Microcephaly, [SDV]Life Sciences [q-bio], Trichothiodystrophy, Biology, 03 medical and health sciences, 0302 clinical medicine, Genes, X-Linked, Intellectual Disability, Exome Sequencing, Genetics, medicine, Humans, Trichothiodystrophy Syndromes, Exome, Gene, Genetics (clinical), Exome sequencing, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Zinc finger, 0303 health sciences, Corpus Callosum Agenesis, Genetic Diseases, X-Linked, medicine.disease, Pedigree, RNF113A, DNA-Binding Proteins, RNA splicing, Female, Agenesis of Corpus Callosum, 030217 neurology & neurosurgery
Abstract: RING Finger Protein 113 A (RNF113A, MIM 300951) is a highly conserved gene located on chromosome Xq24-q25, encoding a protein containing two conserved zinc finger domains involved in DNA alkylation repair and premessenger RNA splicing. To date, only one pathogenic variant of RNF113A, namely c.901C>T; p.Gln301Ter, has been reported in humans by Tarpey et al. in 2009. Thereafter, Corbett et al. stated that this variant was responsible for an X-linked form of nonphotosensitive trichothiodystrophy associated with profound intellectual disability, microcephaly, partial corpus callosum agenesis, microphallus, and absent or rudimentary testes. This variant was then shown to alter DNA alkylation repair, providing an additional argument supporting its pathogenicity and important clues about the underlying pathophysiology of nonphotosensitive trichothiodystrophy. Using exome sequencing, we identified exactly the same RNF113A variant in two fetuses affected with abnormalities similar to those previously reported by Corbett et al. To our knowledge, this is the second report of a RNF113A pathogenic variant in humans.
Published: 2019
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49. Metabolomics signatures of a subset of RET variants according to their oncogenic risk level

Author: Nathalie Bouzamondo, Pascal Reynier, Delphine Prunier-Mirebeau, Anne Barlier, Xavier Dieu, Delphine Drui, Gilles Simard, Charlotte Veyrat-Durebex, Juan Manuel Chao de la Barca, Morgane Le Mao, Françoise Borson-Chazot, Céline Bris, Cédric Gadras, Lydie Tessier, 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), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biochimie et Génétique [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), Département d'Endocrinologie [CHU Nantes] (Institut du Thorax), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut du Thorax [Nantes], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Mitochondrie : Régulations et Pathologie, Service Biochimie et Génétique, MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Risk, Cancer Research, Ret gene, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Cell, Endogeny, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Proto-Oncogene Mas, Germline, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Metabolomics, medicine, Animals, Humans, Thyroid Neoplasms, Phosphorylation, Allele, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, 030304 developmental biology, Genetics, 0303 health sciences, Models, Statistical, [SDV.BA]Life Sciences [q-bio]/Animal biology, Proto-Oncogene Proteins c-ret, Genetic Variation, Medullary thyroid cancer, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Carcinoma, Neuroendocrine, 3. Good health, medicine.anatomical_structure, Oncology, Cell culture, 030220 oncology & carcinogenesis, Mutation, Metabolome, NIH 3T3 Cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Signal Transduction
Abstract: Thirty percent of medullary thyroid carcinomas (MTCs) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: ‘moderate’, ‘high’ and ‘highest’. The present study compares the metabolomics profiles of five pathogenic variants, whether already classified or not. We have generated six stable murine fibroblast cell lines (NIH3T3) expressing the WT allele or variants of the human RET gene, with different levels of pathogenicity, including the M918V variant that is yet to be accurately classified. We carried out a targeted metabolomics study of the cell extracts with a QTRAP mass spectrometer, using the Biocrates Absolute IDQ p180 kit, which allows the quantification of 188 endogenous molecules. The data were then subjected to multivariate statistical analysis. One hundred seventy three metabolites were accurately measured. The metabolic profiles of the cells expressing the RET variants were found to be correlated with their oncogenic risk. In addition, the statistical model we constructed for predicting the oncogenic risk attributed a moderate risk to the M918V variant. Our results indicate that metabolomics may be useful for characterizing the pathogenicity of the RET gene variants and their levels of aggressiveness.
Published: 2019
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50. Internal carotid artery hypoplasia A new clinical feature in pseudoxanthoma elasticum

Author: Pierre-Jean Mention, Maxence Laot, Jacques-Olivier Fortrat, Loukman Omarjee, Pedro Valdivielso, Guillaume Mahé, Olivier Vanakker, Juan Luis Carrillo Linares, Georges Leftheriotis, Gilles Kauffenstein, Nastassia Navasiolava, Estelle Le Pabic, Ludovic Martin, Antoine Larralde, 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 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), Centre de Consultation PXE [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 radiologie et imagerie médicale [Rennes] = Radiology [Rennes], CHU Pontchaillou [Rennes], Département de Biostatistique et de Méthodologie [CHU Rennes], Service de Médecine Nucléaire [CHU Angers] (Pôle Signal Image Stérilisation), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Internal Medicine Unit [Malaga, Spain] (IBIMA), Hospital Virgen de la Victoria [Malaga, Spain]-Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), Center for Medical Genetics [Ghent], Ghent University Hospital, Département de physiologie et d'investigations vasculaires [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Neurology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, DISEASE, Internal carotid artery hypoplasia, 03 medical and health sciences, AGENESIS, 0302 clinical medicine, Text mining, Medicine and Health Sciences, medicine, INTRACRANIAL ANEURYSM, Letter to the Editor, Stroke, ComputingMilieux_MISCELLANEOUS, business.industry, medicine.disease, Pseudoxanthoma elasticum, [SDV] Life Sciences [q-bio], lcsh:RC666-701, Feature (computer vision), Agenesis, Neurology (clinical), Radiology, Cardiology and Cardiovascular Medicine, business, STROKE, 030217 neurology & neurosurgery
Abstract: International audience
Published: 2019
Full Text: View/download PDF

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