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151. A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas

Author: Shai Rosenberg, Franck Bielle, Iva Simeonova, Isabelle Le Roux, Vincent Gleize, Marine Giry, Marie-Hélène Aubriot-Lorton, Emmanuelle Huillard, Bertille Bance, Michel Kalamarides, Anna Lasorella, Sophie Paris, Marc Sanson, Chiara Villa, Alexandre Vasiljevic, Dominique Figarella-Branger, Mailys Daniau, Antonio Iavarone, Emmanuèle Lechapt-Zalcman, Stefano Maria Pagnotta, Ariane Sharif, Karima Mokhtari, Marc Polivka, Maite Verreault, Aravindan Arun Nadaradjane, Yannick Marie, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sharett Institute of Oncology [Jerusalem, Israel], Hadassah Medical Organization [Jerusalem, Israel], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), OncoNeuroTek [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, 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, Herbert Irving Comprehensive Cancer Center, Columbia University [New York], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], 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, University of California-University of California-University of California [Los Angeles] (UCLA), University of California-University of California, Service de neurologie 2 [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), ONERA, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], 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, and program 'Investissements d'avenir' ANR-10-IAIHU-06,program 'Investissements d'avenir' ANR-10-IAIHU-06
Subjects: 0301 basic medicine, Adult, Male, Protein Kinase C-alpha, Science, [SDV]Life Sciences [q-bio], Mutant, function predictions, General Physics and Astronomy, medicine.disease_cause, Isozyme, General Biochemistry, Genetics and Molecular Biology, Cell membrane, 03 medical and health sciences, medicine, Humans, Point Mutation, lcsh:Science, Cancer genetics, Protein kinase C, Cells, Cultured, Aged, Cell Proliferation, eIF2, Multidisciplinary, Chemistry, Cell growth, Point mutation, General Chemistry, Glioma, Middle Aged, Molecular biology, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, OncogenesProtein, Female, lcsh:Q, Carcinogenesis, Cerebral Ventricle Neoplasms
Abstract: Chordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA D463H mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot PRKCA D463H mutation was not described in other tumors. PRKCA D463H is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKCαD463H mRNA levels are more abundant than wild-type PKCα transcripts, while PKCαD463H is less stable than the PCKαWT protein. Compared to PCKαWT, the PKCαD463H protein is depleted from the cell membrane. The PKCαD463H mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis.
Published: 2018
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152. Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with focal epilepsy: A systematic review and meta-analysis

Author: Michel Cucherat, Sylvain Rheims, Karine Ostrowsky-Coste, Jean Isnard, Hélène Catenoix, Marc Guénot, Pierre Bourdillon, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie fonctionnelle et d'épileptologie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Service de neurochirurgie fonctionnelle [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Cucherat, Michel
Subjects: medicine.medical_specialty, medicine.medical_treatment, Neurosurgical Procedures, Stereoelectroencephalography, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Radiofrequency thermocoagulation, Internal medicine, Electrocoagulation, medicine, Humans, 030212 general & internal medicine, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Electroencephalography, Retrospective cohort study, medicine.disease, Confidence interval, 3. Good health, Study heterogeneity, Treatment Outcome, Surgery, Computer-Assisted, Neurology, Meta-analysis, Epilepsies, Partial, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective Despite the increasing number of studies reporting results of stereo-electroencephalography (SEEG)-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) in the treatment of patients with drug-resistant focal epilepsy, the exact efficacy of this approach remains unclear. The seizure-freedom rate varies greatly across studies and the factors associated with efficacy have not been formally investigated. Methods All prospective or retrospective studies reporting efficacy and/or safety of SEEG-guided RF-TC in patients with drug-resistant focal epilepsy were included. The primary outcome was the seizure-free rate 1 year after the procedure. Secondary outcomes were (1) the responder rate 1 year after the procedure and (2) the proportion of patients with permanent neurologic deficit 1 year after the procedure. Each outcome was assessed in all patients and in 4 groups of patients defined by the etiology of epilepsy. Each outcome was pooled using inverse variance weighting, logit transformation of proportion, and a random-effects model. Results No prospective study was identified and a total of 6 retrospective studies, reporting efficacy and safety data of 296 patients, were included. The pooled rate of permanent neurologic deficit was 2.5% (95% confidence interval [CI] 1.2%-5.3%), without heterogeneity across studies. In contrast, both the seizure-free and responder rates varied greatly across studies, and statistical heterogeneity was high. The pooled seizure-free and responder rates were 23% (95% CI 8%-50%) and 58% (95% CI 36%-77%), respectively. Both for the seizure-free and responder rates, the greatest efficacy was observed in patients with periventricular nodular heterotopia and the lowest in patients with normal magnetic resonance imaging (MRI) findings. Significance SEEG-guided RF-TC is a safe procedure with low risk of complications. In contrast, the level of evidence regarding its efficacy remains low. Better identification of factors associated with seizure outcome are needed.
Published: 2018
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153. Functional assessment of newly identified SFTPA1 and SFTPA2 mutations in patients with idiopathic interstitial pneumonia (IIP) and lung cancer28th International Congress of the European-Respiratory-Society (ERS)

Author: Nathan, Nadia, Legendre, Marie, Filhol-Blin, Emilie, Borie, Raphael, Bouvry, Diane, Kannengiesser, Caroline, Kais, Ahmad, Albuisson, Juliette, Nathalie, Allou, Borensztajn, Keren, Afifaa, Butt, Copin, Bruno, Cottin, Vincent, Crestani, Bruno, Dalphin, Jean Charles, Dastot-Le Moal, Florence, Delacourt, Christophe, De Vuyst, Paul, Duquesnoy, Philippe, Giraud, Violaine, Gomez, Carine, Gouya, Laurent, Naud, Valérie, Nunes, Hilario, Picard, Clement, Prevot, Gregoire, Reix, Philippe, Reynaud-Gaubert, Martine, Traclet, Julie, L'Hermine-Coulomb, Aurore, Clement, Annick, Amselem, Serge, Service de Pneumologie Pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Sorbonne Université (SU), Université Sorbonne Nouvelle - Paris 3, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU de la Réunion, Saint-Denis, France., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Génétique et d'Embryologie Médicales [CHU Trousseau], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de pneumologie pédiatrique CHU de Besançon, CHU Trousseau [APHP], Erasme Hospital, Brussels, Service de Pneumologie [AP-HP Hôpital Ambroise Paré, Boulogne-Billancourt], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-AP-HP Hôpital Ambroise-Paré [Boulogne-Billancourt], Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Département de Génétique et Centre de Référence Maladies Rares Syndrome de Marfan et pathologies apparentées (AP HP, hôpital Bichat), AP-HP Hôpital Foch - Suresnes, Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Ambroise Paré [AP-HP], Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Foch [Suresnes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique et embryologie médicales [CHU Trousseau], Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], and CHU Toulouse [Toulouse]
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018
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154. Laser spectroscopy for in situ elemental imaging of lung tissue: a promising technology

Author: Lucie Sancey, Françoise Thivolet, Jean François Bernaudin, S. Moncayo, Benoit Busser, Vincent Bonneterre, Michel Vincent, Marianne Kambouchner, Vincent Motto Ros, Mickaël Catinon, UF Cancérologie biologique et biothérapie, CHU Grenoble, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Laboratoire d'Ecologie Alpine (LECA ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Radiopharmaceutiques biocliniques, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR130, Service d’Anatomie et de Cytologie Pathologiques [Louis Pradel - CHU Lyon], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’anatomie pathologique, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de Spectrométrie Physique (LSP), and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)
Subjects: In situ, Elemental imaging, business.industry, [SDV]Life Sciences [q-bio], Medicine, Lung tissue, business, Spectroscopy, ComputingMilieux_MISCELLANEOUS, Biomedical engineering
Abstract: International audience
Published: 2018
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155. Overall and differentiated sensory responses to cardiopulmonary exercise test in patients with cystic fibrosis: kinetics and ability to predict peak oxygen uptake

Author: Laurent Mely, Jean-Marc Vallier, Mathieu Gruet, Université de Toulon (UTLN), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), 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 de Toulon (UTLN)-Université Côte d'Azur (UCA), Laboratoire Motricité Humaine Expertise Sport Santé/Equipe de recherche de Toulon (LAMHESS-Toulon), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), and Institut national du sport, de l'expertise et de la performance (INSEP)
Subjects: Adult, Male, medicine.medical_specialty, Cystic Fibrosis, Sports medicine, Physiology, Physical Exertion, Exercise intolerance, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Physiology (medical), Cardiopulmonary exercise test, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Medicine, Orthopedics and Sports Medicine, In patient, Exercise, ComputingMilieux_MISCELLANEOUS, Rating of perceived exertion, business.industry, Public Health, Environmental and Occupational Health, VO2 max, 030229 sport sciences, General Medicine, medicine.disease, Oxygen, Kinetics, 030228 respiratory system, Exercise Test, Cardiology, Exercise intensity, Female, sense organs, medicine.symptom, business
Abstract: We evaluated the validity of predicting peak oxygen uptake ( $$\dot {V}$$ O2peak) from submaximal ratings of perceived exertion (RPE) during incremental cardiopulmonary exercise test (CPET) in patients with cystic fibrosis (CF) and compared the predictive accuracy between overall and differentiated RPE scores. Thirty-five adults with CF (FEV1 = 58 ± 23%) performed a CPET on cycle ergometer with gas exchange measurements. Leg, chest and overall RPE were collected every minute throughout the test. Linear regressions between $$\dot {V}$$ O2 and RPE ≤ 15 were extrapolated to maximal theoretical RPE (i.e. RPE18 and RPE19) to predict $$\dot {V}$$ O2peak. Agreements between measured and all predicted $$\dot {V}$$ O2peak were tested using Bland–Altman Plots, for the whole group and for subjects presenting significant exercise intolerance (n = 24). Leg, chest and overall RPE increased similarly with exercise intensity. No differences were found between predicted $$\dot {V}$$ O2peak and measured $$\dot {V}$$ O2peak with RPE18 as maximal RPE, for both overall and differentiated RPE (P range 0.94–0.98). Ranges for Pearson correlations and limits of agreements were 0.88–0.91 and 380–461 mL min−1 for the whole group and 0.92–0.94 and 269–365 mL min−1 for subjects with significant exercise intolerance. The greatest association and narrowest limits of agreements were obtained from chest RPE scores. Submaximal RPE scores obtained during CPET can provide acceptable estimate of $$\dot {V}$$ O2peak in adults with CF, particularly in those having significant exercise intolerance. Future studies should assess whether the prediction can be improved, particularly by encouraging the regular use of RPE scales during physical activities/exercise rehabilitations sessions.
Published: 2018
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156. Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study

Author: Noémie Resseguier, Natacha Rosso-Delsemme, Any Beltran Anzola, Karine Baumstarck, Vanessa Milien, Laurent Ardillon, Sophie Bayart, Claire Berger, Marie-Anne Bertrand, Christine Biron-Andreani, Annie Borel-Derlon, Sabine Castet, Pierre Chamouni, Ségolène Claeyssens Donadel, Emmanuelle De Raucourt, Dominique Desprez, Céline Falaise, Birgit Frotscher, Valérie Gay, Jenny Goudemand, Yves Gruel, Benoît Guillet, Annie Harroche, Abel Hassoun, Yoann Huguenin, Thierry Lambert, Aurélien Lebreton, Anne Lienhart, Michèle Martin, Sandrine Meunier, Fabrice Monpoux, Guillaume Mourey, Claude Negrier, Philippe Nguyen, Placide Nyombe, Caroline Oudot, Brigitte Pan-Petesch, Benoît Polack, Anne Rafowicz, Antoine Rauch, Delphine Rivaud, Pascale Schneider, Alexandra Spiegel, Cecile Stoven, Brigitte Tardy, Marc Trossaërt, Jean-Baptiste Valentin, Stéphane Vanderbecken, Fabienne Volot, Annelise Voyer-Ebrard, Bénédicte Wibaut, Tanguy Leroy, Thomas Sannie, Hervé Chambost, Pascal Auquier, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hématogoie pédiatrique, hôpital Sud, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Hématologie Biologique [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), Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Versailles André Mignot (CHV), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre Hospitalier Chambéry, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), 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 ), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Hôpital Morvan [Brest], 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), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hémato-immuno-oncologie pédiatrique [Rouen], Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque (GRT), Université Jean Monnet - Saint-Étienne (UJM), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Santé Publique, Université de la Méditerranée - Aix-Marseille 2, Ministère des Affaires Sociales et de la Santé, Filière MHEMO, Université Aix-Marseille, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Sud, Centre hospitalier de Versailles André-Mignot, 177, rue de Versailles, 78150 Le Chesnay, France, parent, Université de Tours, 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 ), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU de Nancy - Hôpitaux de Brabois, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Activities of daily living, Cross-sectional study, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Academic Performance, Protocol, Early childhood, adherence, adolescents, Young adult, ComputingMilieux_MISCELLANEOUS, Qualitative Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, transition, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Patient Satisfaction, Female, Family Relations, France, Psychosocial, Attitude to Health, Haematology (Incl Blood Transfusion), Adult, young adults, medicine.medical_specialty, Transition to Adult Care, Adolescent, haemophilia, Haemophilia, Hemophilia A, 03 medical and health sciences, Young Adult, Quality of life (healthcare), 030225 pediatrics, medicine, Humans, business.industry, Protective Factors, medicine.disease, Treatment Adherence and Compliance, Cross-Sectional Studies, Social Class, Family medicine, Quality of Life, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration numberNCT02866526; Pre-results.
Published: 2018
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157. Objective Evaluation of Multiple Sclerosis Lesion Segmentation using a Data Management and Processing Infrastructure

Author: Franca Wagner, Sorina Camarasu-Pop, Hélène Urien, Isabelle Bloch, Xavier Tomas-Fernandez, Jeremy Beaumont, John Muschelli, Chunliang Wang, Baptiste Laurent, Charles R.G. Guttmann, Tristan Glatard, Michael Kain, Mathieu Simon, Michel Dojat, April Khademi, Martin Styner, Pascal Girard, Thomas Tourdias, Michel M. dos Santos, Wellington Pinheiro dos Santos, Sergi Valverde, Richard McKinley, Abel G. Silva-Filho, Jesse Knight, Eloy Roura, Sandra Vukusic, Francisco Javier Vera-Olmos, François Cotton, Xavier Lladó, Elizabeth M. Sweeney, Senan Doyle, Anne Kerbrat, Olivier Commowick, Mariano Cabezas, Florent Leray, Amirreza Mahbod, Norberto Malpica, Gilles Edan, Roxana Ameli, Christian Barillot, Frederic Cervenansky, Florence Forbes, Simon K. Warfield, Audrey Istace, Jean-Christophe Ferré, Vision, Action et Gestion d'informations en Santé ( VisAGeS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE ( IRISA_D5 ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Université de Bretagne Sud ( UBS ) -École normale supérieure - Rennes ( ENS Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Traitement de l'Information Medicale ( LaTIM ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Mines-Télécom [Paris], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de neurochirurgie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de neurologie [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Concordia University [Montreal], Pixyl Medical [Grenoble], Modelling and Inference of Complex and Structured Stochastic Systems ( MISTIS ), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Institut National Polytechnique de Grenoble ( INPG ), University of Guelph, Department of Electrical and Computer Engineering [TORONTO] ( ECE ), University of Toronto, Royal Institute of Technology [Stockholm] ( KTH ), University of Bern, Johns Hopkins Bloomberg School of Public Health [Baltimore, MD, USA], Visio per computador I robotica ( VICOROB ), Universitat de Girona ( UdG ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Computational Radiology Laboratory [Boston] ( CRL ), Brigham and Women's Hospital [Boston]-Children's Hospital, Laboratoire Traitement et Communication de l'Information ( LTCI ), Télécom ParisTech-Institut Mines-Télécom [Paris]-Université Paris-Saclay, Universidad Rey Juan Carlos [Madrid] ( URJC ), Brigham and Women's Hospital [Boston], Service de Neurologie, CHU Pontchaillou, Rennes, Grenoble Institut des Neurosciences ( GIN ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Computer Science ( North Carolina State University ), North Carolina State University [Raleigh] ( NCSU ), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Radiologie [CHU de Rennes], Université de Rennes (UR), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS ), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Ryerson University [Toronto], Royal Institute of Technology [Stockholm] (KTH ), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Research institute of Computer Vision and Robotics [Girona] (VICOROB), Universitat de Girona (UdG), Universidade Federal de Pernambuco [Recife] (UFPE), Computational Radiology Laboratory [Boston] (CRL), Brigham and Women's Hospital [Boston]-Boston Children's Hospital, Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Universidad Rey Juan Carlos [Madrid] (URJC), Service de Neurologie [Lyon], CHU Lyon, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), This work was partly funded by France Life Imaging (grant ANR-11-INBS-0006 from the French 'Investissements d’Avenir' program) for funding and sponsoring the challenge. This work has also been partly supported by a grant (OFSEP) provided by the French State and handled by the 'Agence nationale de la recherche', within the framework of the 'Investissements d’Avenir' program, under the reference ANR-10-COHO-002. We also thank the French national cohort OFSEP (a French 'Investissements d’Avenir' program), and particularly the imaging group inside this cohort consortium for their constant support, fruitful discussions on the challenge and providing the MR images., ANR-11-INBS-0006,FLI,France Life Imaging(2011), ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut National Polytechnique de Grenoble (INPG), Boston Children's Hospital-Brigham and Women's Hospital [Boston], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-INBS-0006/11-INBS-0006,FLI,France In vivo Imaging(2011), ANR-10-COHO-002-01/10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Images et Modèles, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Informatique et développements, Department of Electrical and Computer Engineering [University of Toronto] (ECE), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT), Service de Neurologie [CHU Rennes], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Computer Science (North Carolina State University), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), RMN et optique : De la mesure au biomarqueur, Edan, Gilles, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Cohortes - Observatoire Français de la Sclérose en Plaques - - OFSEP2010 - ANR-10-COHO-0002 - COHO - VALID, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Computer science, Data management, MESH: Parenchymal Tissue, lcsh:Medicine, Esclerosi múltiple, computer.software_genre, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Machine Learning, 0302 clinical medicine, open science, Image Processing, Computer-Assisted, Segmentation, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Image processing -- Digital techniques, lcsh:Science, 610 Medicine & health, Multiple sclerosis lesion, image segmentation, MESH: Machine Learning, Magnetic Resonance Imaging, MESH: Image Processing, Computer-Assisted, Random forest, performance evaluation, MESH: Neural Networks, Computer, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Objective evaluation, Algorithms, MESH: Algorithms, Machine learning, Article, Multiple sclerosis, 03 medical and health sciences, Imatges -- Processament -- Tècniques digitals, distributed computing, Image Interpretation, Computer-Assisted, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Parenchymal Tissue, Retrospective Studies, MESH: Humans, business.industry, Deep learning, Imatge -- Segmentació, lcsh:R, MESH: Retrospective Studies, MESH: Multiple Sclerosis, MESH: Male, Imaging segmentation, computing infrastructure, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Q, Neural Networks, Computer, Artificial intelligence, business, computer, MESH: Female, MESH: Image Interpretation, Computer-Assisted, 030217 neurology & neurosurgery
Abstract: We present a study of multiple sclerosis segmentation algorithms conducted at the international MICCAI 2016 challenge. This challenge was operated using a new open-science computing infrastructure. This allowed for the automatic and independent evaluation of a large range of algorithms in a fair and completely automatic manner. This computing infrastructure was used to evaluate thirteen methods of MS lesions segmentation, exploring a broad range of state-of-theart algorithms, against a high-quality database of 53 MS cases coming from four centers following a common definition of the acquisition protocol. Each case was annotated manually by an unprecedented number of seven different experts. Results of the challenge highlighted that automatic algorithms, including the recent machine learning methods (random forests, deep learning, …), are still trailing human expertise on both detection and delineation criteria. In addition, we demonstrate that computing a statistically robust consensus of the algorithms performs closer to human expertise on one score (segmentation) although still trailing on detection scores This work was partly funded by France Life Imaging (grant ANR-11-INBS-0006 from the French “Investissements d’Avenir” program) for funding and sponsoring the challenge. This work has also been partly supported by a grant (OFSEP) provided by the French State and handled by the “Agence nationale de la recherche”, within the framework of the “Investissements d’Avenir” program, under the reference ANR-10-COHO-002. We also thank the French national cohort OFSEP (a French “Investissements d’Avenir” program), and particularly the imaging group inside this cohort consortium for their constant support, fruitful discussions on the challenge and providing the MR images
Published: 2018
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158. Enhance quality care performance: Determination of the variables for establishing a common database in French paediatric critical care units

Author: RECHER, Morgan, BERTRAC, Caroline, Guillot, Camille, BAUDELET, Jean Benoit, KARACA-ALTINTAS, Yasemin, HUBERT, Hervé, Leclerc, Francis, Leteurtre, Stéphane, DEVICTOR, Denis, Chevret, Laurent, Javouhey, Etienne, VANEL, Blandine, Valla, Frédéric, Cambonie, Gilles, Milesi, Christophe, LIET, JeanMichel, Joram, Nicolas, HUBERT, Philippe, DUPIC, Laurent, Ozanne, Bruno, Tirel, Olivier, Dauger, Stéphane, Desprez, Philippe, CHANTREUIL, Julie, Réanimation Pédiatrique, CHU Lille, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), CHU Lyon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), NeckerEnfant Malades, parent, CHU Rennes, CHU Strasbourg, CHU Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Databases, Factual, Delphi Technique, DATABASE, [SDV]Life Sciences [q-bio], Australia, Original Articles, Intensive Care Units, Pediatric, Quality Improvement, United States, critical care, paediatrics, Humans, Original Article, France, Registries, Child, Quality of Health Care
Abstract: Selected variables for the French Paediatric Intensive Care registry. Rationale, aims, and objectives Providing quality care requires follow‐up in regard to clinical and economic activities. Over the past decade, medical databases and patient registries have expanded considerably, particularly in paediatric critical care medicine (eg, the Paediatric Intensive Care Audit Network (PICANet) in the UK, the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry in Australia and New Zealand, and the Virtual Paediatric Intensive Care Unit Performance System (VPS) in the USA). Such a registry is not yet available in France. The aim of this study was to determine variables that ought to be included in a French paediatric critical care registry. Methods Variables, items, and subitems from 3 foreign registries and 2 French local databases were used. Items described each variable, and subitems described items. The Delphi method was used to evaluate and rate 65 variables, 90 items, and 17 subitems taking into account importance or relevance based on input from 28 French physicians affiliated with the French Paediatric Critical Care Group. Two ratings were used between January and May 2013. Results Fifteen files from 10 paediatric intensive care units were included. Out of 65 potential variables, 48 (74%) were considered to be indispensable, 16 (25%) were considered to be optional, and 1 (2%) was considered to be irrelevant. Out of 90 potential items, 62 (69%) were considered to be relevant, 23 (26%) were considered to be of little relevance, and 5 (6%) were considered to be irrelevant. Out of 17 potential subitems, 9 (53%) were considered to be relevant, 6 (35%) were considered to be of little relevance, and 2 (12%) were considered to be irrelevant. Conclusions The necessary variables that ought to be included in a French paediatric critical care registry were identified. The challenge now is to develop the French registry for paediatric intensive care units.
Published: 2018
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159. Adrenocortical development: Lessons from mouse models

Author: T. Dumontet, Pierre Val, Nathanaëlle Montanier, Antoine Martinez, Isabelle Sahut-Barnola, Anne Marie Lefrançois-Martinez, David T. Breault, Ingrid Plotton, Amandine Septier, Jean Christophe Pointud, Véronique Ducros, Mohamad Zubair, Florence Roucher-Boulez, Ken Ichirou Morohashi, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’endocrinologie diabétologie et maladies métaboliques, CHU Clermont-Ferrand, Hospices Civils de Lyon (HCL), CHU Lyon, Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, 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), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Sexual Maturation, MESH: Mice, Knockout, Cushing syndrome, Mice, 0302 clinical medicine, Endocrinology, Adrenal Glands, PKA, MESH: Animals, Sexual Maturation, MESH: Adrenal Glands, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Adrenal cortex, Wnt signaling pathway, Cell Differentiation, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.anatomical_structure, Zone réticulée, MESH: Models, Animal, Models, Animal, Zona reticularis, Female, MESH: Cell Differentiation, medicine.medical_specialty, Modèle animal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Zona fasciculata, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, Involution (medicine), Animal model, MESH: Mice, Fetus, Syndrome de Cushing, Cortex surrénalien, MESH: Humans, Adrenarche, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, MESH: Male, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Adrenal Cortex, MESH: Adrenal Cortex, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; The adrenocortical gland undergoes structural and functional remodelling in the fetal and postnatal periods. After birth, the fetal zone of the gland undergoes rapid involution in favor of the definitive cortex, which reaches maturity with the emergence of the zona reticularis(zR) at the adrenarche. The mechanisms underlying the adrenarche, the process leading to pre-puberty elevation of plasma androgens in higher primates, remain unknown, largely due to lack of any experimental model. By following up fetal and definitive cortex cell lines in mice, we showed that activation of protein kinase A (PKA) signaling mainly impacts the adult cortex by stimulating centripetal regeneration, with differentiation and then conversion of the zona fasciculata into a functional zR. Animals developed Cushing syndrome associated with primary hyperaldosteronism, suggesting possible coexistence of these hypersecretions in certain patients. Remarkably, all of these traits were sex-dependent: testicular androgens promoted WNT signaling antagonism on PKA, slowing cortical renewal and delaying onset of Cushing syndrome and the establishment of the zR in male mice, this being corrected by orchidectomy. In conclusion, zR derives from centripetal conversion of the zona fasciculata under cellular renewal induced by PKA signaling, determining the size of the adult cortex. Finally, we demonstrated that this PKA-dependent mobilization of cortical progenitors is sexually dimorphic and could, if confirmed in humans, account for female preponderance in adrenocortical pathologies.
Published: 2018
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160. Further delineation of the MECP2 duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features

Author: Sophie Scheidecker, Françoise Devillard, Gaetan Lesca, Maryline Carneiro, Christèle Dubourg, Ganaëlle Remerand, Catherine Badens, Odile Boespflug-Tanguy, Nathalie Marle, Serge Romana, Nadia Bahi-Buisson, Jean-Paul Bonnefont, Hubert Journel, Bénédicte Duban-Bedu, Brigitte Gilbert-Dussardier, Mathilde Nizon, Nathalie Perreton, Sophie Julia, Cyril Goizet, Delphine Héron, Véronique Satre, Marguerite Miguet, Joris Andrieux, Pierre-Simon Jouk, Laurence Perrin, Renaud Touraine, Ghislaine Plessis, Dominique Martin-Coignard, Caroline Rooryck, Catherine Vincent-Delorme, Laurence Faivre, Salima El Chehadeh, Thierry Bienvenu, Jean-Luc Alessandri, Anne-Claude Tabet, Laurent Pasquier, Martine Raynaud, Réseau AChro-Puce, Marjolaine Willems, Bruno Leheup, Marianne Till, Jeanne Amiel, Jacqueline Vigneron, Nicole Philip, Valérie Kremer, Massimiliano Rossi, Boris Keren, Annick Toutain, Fabienne Prieur, Bertrand Isidor, Séverine Drunat, Marilyn Lackmy-Port-Lis, Albert David, Christel Thauvin-Robinet, Damien Sanlaville, Laetitia Lambert, Lydie Burglen, Klaus Dieterich, Catherine Sarret, Anne Moncla, Didier Lacombe, Fanny Laffargue, Kim Maincent, Marlène Rio, Clarisse Baumann, Mathilde Lefebvre, Sabine Sigaudy, Laurent Guibaud, Adeline Vigouroux, Valérie Malan, Patrick Callier, Chantal Missirian, Christophe Philippe, Christine Francannet, Anne-Laure Mosca-Boidron, Valérie Cormier-Daire, Cédric Le Caignec, Vincent des Portes, Charles Coutton, Alexandra Afenjar, Sandrine Chantot-Bastaraud, Julien Thevenon, Mylène Béri-Dexheimer, Hilde Van Esch, Bernard Echenne, Jean-Marie Cuisset, Jean-Michel Pedespan, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Service de Génétique Médicale [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Clinique (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Génétique Clinique [CHU Rennes] (Réseau de Génétique et Génomique Médicale), Hôpitaux Universitaires du Grand Ouest, Laboratoire de Génétique Moléculaire & Génomique [CHU Rennes], CHU Pontchaillou [Rennes], Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Image Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne - Clermont-Ferrand I (UdA), Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Génétique Médicale (CHU de Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de neuro-pédiatrie (CHRU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Médicale, Hopital Jeanne de Flandre, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Radiologie [Hôpital Femme Mère Enfant - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de génétique clinique [CHU Necker], Département de neurologie pédiatrique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Service de génétique clinique [Debré], Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies (TIMC-IMAG-DyCTiM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Maladies rares, génétique et métabolisme / Rare Diseases, Genetics and Metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-École de sage femme - Groupe hospitalier Pellegrin - CHU de Bordeaux, Service de Génétique Médicale du CHU de Bordeaux, 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), Laboratoire de génétique chromosomique [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Biologie Moléculaire (MARSEILLE - Biolo Moléculaire), Assistance Publique - Hôpitaux de Marseille (APHM), CIC 1407, Hospices Civils de Lyon (HCL), Service de neurologie pédiatrique [CHU de Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul], GHICL-Hôpital Saint Vincent de Paul, Service de Neuropédiatrie [CHU Necker - Enfants Malades], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Laboratoire de génétique médicale et cytogénétique [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de Génétique [HCL Groupement Hospitalier Est], Groupement hospitalier Lyon-Est, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Moléculaire [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), 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)-Université Bretagne Loire (UBL), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Service de Neurologie Pédiatrique [CHU Lyon], Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre for Human Genetics, University Hospitals Leuven [Leuven], Institut des Sciences cognitives Marc Jeannerod - Laboratoire sur le langage, le cerveau et la cognition (L2C2), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de référence des déficiences intellectuelles de causes rares (Hospices Civils de Lyon), Hospices civils de Lyon (HCL), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Dynamiques Cellulaire et Tissulaire - Interdisciplinarité, Modélisation & Microscopie (TIMC-IMAG-DyCTiM2), Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Groupement Hospitalier Lyon-Est (GHE), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-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), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, MECP2 duplication syndrome, MECP2gene, Scoliosis, MECP2duplication syndrome, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Gene duplication, Genetics, medicine, Spasticity, Genetics (clinical), X-linked, Vasomotor, business.industry, facial dysmorphism, medicine.disease, Gait, Hypotonia, 3. Good health, 030104 developmental biology, Xq28 duplication, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, medicine.symptom, business, 030217 neurology & neurosurgery, genetic counselling
Abstract: The Xq28 duplication involving theMECP2gene (MECP2duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitialMECP2duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype ofMECP2duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.
Published: 2018
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161. Epidermolysis bullosa simplex generalized severe induces a Th17 response and is improved by Apremilast treatment

Author: E. Castela, Christine Chiaverini, Frédéric Bérard, Fanny Morice-Picard, J.-P. Lacour, Didier Bessis, Jean-François Nicolas, Aurore Rozières, Meri K. Tulic, D. Baty, Jean Kanitakis, Pierre Vabres, J. Mazereeuw, Thierry Passeron, Emmanuelle Bourrat, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de dermatologie [CHU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Ninewells Hospital and Medical School [Dundee], Centre de Référence des Epidermolyses Bulleuses Héréditaires [Nice] (CREBHN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), CHU Necker - Enfants Malades [AP-HP]-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Toulouse [Toulouse], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Inflammation, Pilot Projects, Dermatology, Pathogenesis, 030207 dermatology & venereal diseases, 03 medical and health sciences, Epidermolysis bullosa simplex, Young Adult, 0302 clinical medicine, medicine, CXCL10, Humans, Child, Retrospective Studies, Skin, integumentary system, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Infant, Newborn, Keratin-14, Infant, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Thalidomide, Treatment Outcome, Child, Preschool, Epidermolysis Bullosa Simplex, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, CXCL9, Keratin-5, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Apremilast, medicine.symptom, business, Infiltration (medical), Immunostaining, medicine.drug
Abstract: International audience; BACKGROUND: Epidermolysis bullosa simplex generalized severe is a genetic disorder caused by mutation in KRT5 or KRT14 genes. Usually considered as a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: The aim of this study was to assess the inflammation in the skin of patients with EBS. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 EBS-gen sev patients. A second multicenter prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemistry analysis and quantitative real time PCR. Cytokine expression was analyzed in blister fluid and compared with controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocytes infiltrate in skin biopsies of blister (n=17) as well as in rubbed skin (n=5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases and an increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of Th17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast with a dramatic improvement of skin blistering and good tolerance. CONCLUSION: Our study demonstrates the importance of inflammation in EBS-gen sev patients and underlines the key role for Th17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder. This article is protected by copyright. All rights reserved.
Published: 2018
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162. Emergency drugs, health geography interest to study spatial accessibility: application for clotting factor concentrates

Author: Leroy, Vincent, Freyssenge, Julie, Florent, Renard, Tazarourte, Karim, Negrier, Claude, Chamouard, Valerie, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Urgences Médicales, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Université de Lyon, Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), and Freyssenge, Julie
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

163. T-bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

Author: Sébastien Viel, Jiang Zhang, Anne-Laure Mathieu, Marie Marotel, Sébastien Fauteux-Daniel, Thierry Walzer, Antoine Marçais, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Shanghai Key Laboratory of Regulatory Biology (Institute of Biomedical Sciences and School of Life Sciences, Shanghai), East China Normal University [Shangaï] (ECNU), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE15-0008,GAMBLER,Etude du mécanisme d'action des facteurs de transcription de type(2016)
Subjects: 0301 basic medicine, Immunology, Eomes, ILCs, Biology, T-bet, Communicable Diseases, 03 medical and health sciences, Mice, Neoplasms, medicine, Immunology and Allergy, Cytotoxic T cell, Animals, Humans, Transcription factor, Gene knockout, Zinc Finger E-box Binding Homeobox 2, Transcriptional activity, Innate lymphoid cell, Cancer, Cell Differentiation, medicine.disease, Phenotype, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lymphocyte Subsets, Cell biology, DNA-Binding Proteins, Killer Cells, Natural, 030104 developmental biology, NK cell differentiation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, T-Box Domain Proteins, T-box transcription factors, Function (biology)
Abstract: International audience; T-bet and Eomes are T-box transcription factors that drive the differentiation and function of cytotoxic lymphocytes such as NK cells. Their DNA-binding domains are highly similar, suggesting redundant transcriptional activity. However, while these transcription factors have different patterns of expression, the phenotype of loss-of-function mouse models suggests that they play distinct roles in the development of NK cells and other innate lymphoid cells (ILCs). Recent technological advances using reporter mice and conditional knockouts were fundamental in defining the regulation and function of these factors at steady state and during pathological conditions such as various types of cancer or infection. Here, we review these recent developments, focusing on NK cells as prototypical cytotoxic lymphocytes and their development, and also discuss parallels between NK cells and T cells. We also examine the role of T-bet and Eomes in human NK cells and ILC1s. Considering divergent findings on mouse and human ILC1s, we propose that NK cells are defined by coexpression of T-bet and Eomes, while ILC1s express only one of these factors, either T-bet or Eomes, depending on the tissue or the species.
Published: 2018
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164. L’endurance des muscles respiratoires dans la mucoviscidose : évaluation et impact clinique

Author: Laurent Mely, Julie Larribaut, Mathieu Gruet, Jean-Marc Vallier, Boubou Camara, Samuel Verges, Université de Toulon (UTLN), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), 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 de Toulon (UTLN)-Université Côte d'Azur (UCA), Laboratoire Motricité Humaine Expertise Sport Santé/Equipe de recherche de Toulon (LAMHESS-Toulon), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Hypoxie et physiopathologies cardiovasculaire et respiratoire, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], 030209 endocrinology & metabolism, Orthopedics and Sports Medicine, 030229 sport sciences, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction Dans son histoire respiratoire la mucoviscidose (MV) majore la sollicitation des muscles respiratoires (MR). De nombreux travaux ont etudie la force des MR du patient MV mais peu de donnees sont disponibles sur leur endurance (RME) [1] . Cette etude souhaite comparer deux tests d’endurance des muscles respiratoires et preciser leur role dans l’intolerance a l’effort de ces patients. Materiel et methode Vingt-cinq adultes MV (VEMS = 57,2 ± 19,4 %) ont ete inclus. RME a ete mesure par deux methodologies : un test d’endurance inspiratoire contre resistance (IRB) et un test d’endurance de type hyperpnee-isocapnique (IHE). Les criteres retenus etaient : le temps d’exercice, la pression inspiratoire maximale ou la ventilation minute maximale. La force maximale inspiratoire (MIP), la fonction pulmonaire et les reponses maximales au test a l’effort sur ergocycle (ex. VO2pic, VEpic) ont aussi ete mesures. Resultats Aucune correlation n’a ete trouvee entre IHE et IRB pour le temps d’endurance, la pression inspiratoire maximale ou la ventilation minute maximale (p > 0,05). La ventilation maximale (L.min−1) pendant l’IHE et la pression inspiratoire absolue maximale pendant l’IRB etaient toutes deux correlees avec MIP (r = 0,41 et 0,74), CVF (r = 0,68 et r = 0,59), VEMS (r = 0,64 et 0,50), VEpic (r = 0,73 et r = 0,56) et VO2pic (r = 0,45 et r = 0,42) pendant l’exercice (tous p Conclusion Ces resultats soulignent la signification clinique de la mesure de RME dans la MV. Transpose a la pratique clinique des APA, l’entrainement des MR est un outil qui merite consideration dans cette population. Favoriser l’engagement des MR lors des prises en charge par l’exercice, avec par exemple la methode Pilate, pourraient presenter un interet majeur en raison du potentiel impact clinique positif pour les patients.
Published: 2018
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165. A Meta-Analysis of Outcomes After In Situ Reconstructions for Aortic Graft Infection

Author: Michel Batt, Matthieu Revest, Frederic Laurent, Christian Chidiac, Amandine Coffy, Jocelyne Caillon, Jean Pierre Daures, Brigitte Calvet, Patrick Feugier, Eric Senneville, Fabrice Camou, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Unité de Chirurgie Vasculaire, CHU Lyon, Hôpital Saint-André, Département des Maladies Infectieuses [CH Tourcoing] (Hôpital Gustave Dron), Centre Hospitalier de Tourcoing-Centre Hospitalier Gustave Dron [Tourcoing], Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Béziers, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Gustave Dron [Tourcoing]-Centre Hospitalier de Tourcoing, Centre International de Recherche en Infectiologie (CIRI), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), 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), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Reoperation, medicine.medical_specialty, Prosthesis-Related Infections, reconstruction, [SDV]Life Sciences [q-bio], Treatment outcome, 030204 cardiovascular system & hematology, Prosthesis Design, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, 0302 clinical medicine, Blood vessel prosthesis, Humans, Medicine, Prosthesis design, 030212 general & internal medicine, Prosthesis-Related Infection, Aortic graft, business.industry, in situ, infection, Blood Vessel Prosthesis, 3. Good health, Surgery, Treatment Outcome, surgical procedures, operative, graft, cardiovascular system, Cardiology and Cardiovascular Medicine, business, aortic
Abstract: Objective: To confirm the advantage of in situ reconstruction (ISR) over extra-anatomic reconstruction (EAR) for aortic graft infection and determine the most appropriate conduit including autogenous veins, cryopreserved allografts, and synthetic prosthesis (standard, rifampicin of silver polyesters). Methods: A meta-analysis was conducted with rate of mortality, graft occlusion, amputation, and reinfection. A meta-regression was performed with 4 factors: patients’ age, presence of prosthetic-duodenal fistula (PDF), virulent organisms, or nonvirulent organisms. Results: In situ reconstruction over EAR seems to favor all events. For the 5 conduits used for ISR, according to operative mortality, age of the patients looks to have a positive correlation only for silver polyester and no conduit present any advantage in the presence of PDF. Reinfection seems to be not significantly different for the 5 conduits, and only autogenous veins appear to have a positive correlation with infecting organisms. Conclusion: In situ reconstruction may be considered as first-line treatment. Our results suggest that silver polyesters appear to be most appropriate for older patients, and in order to limit reinfection, autogenous veins are probably the most suitable conduit.
Published: 2018
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166. Comparison of five one-step reconstruction algorithms for spectral CT

Author: Salim Si-Mohamed, Bruno Sixou, Simon Rit, Cyril Mory, Loic Boussel, 4 - Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Service de Radiologie et IRM [CHU Lyon], Hospices Civils de Lyon ( HCL ), This work was performed within the framework of the EU’s H2020 research and innovation program under the grant agreement No. 633937, the SIRIC LYric Grant INCa-DGOS-4664, and the LABEX PRIMES (ANR-11-LABX-0063) of Université de Lyon, within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the ANR., ANR-11-IDEX-0007-02/11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation ( 2011 ), ANR-11-IDEX-0007-02/11-IDEX-0007,Avenir L.S.E.,Avenir L.S.E. ( 2011 ), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2012), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Photons, Tomographic reconstruction, Radiological and Ultrasound Technology, Phantoms, Imaging, Computer science, Bayes Theorem, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Photon counting, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Quadratic equation, 030220 oncology & carcinogenesis, Image Processing, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [ SPI ] Engineering Sciences [physics], Humans, Radiology, Nuclear Medicine and imaging, Tomography, X-Ray Computed, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithm, Algorithms
Abstract: Over the last decade, dual-energy CT scanners have gone from prototypes to clinically available machines, and spectral photon counting CT scanners are following. They require a specific reconstruction process, consisting of two steps: material decomposition and tomographic reconstruction. Image-based methods perform reconstruction, then decomposition, while projection-based methods perform decomposition first, and then reconstruction. As an alternative, 'one-step inversion' methods have been proposed, which perform decomposition and reconstruction simultaneously. Unfortunately, one-step methods are typically slower than their two-step counterparts, and in most CT applications, reconstruction time is critical. This paper therefore proposes to compare the convergence speeds of five one-step algorithms. We adapted all these algorithms to solve the same problem: spectral photon-counting CT reconstruction from five energy bins, using a three materials decomposition basis and spatial regularization. The paper compares a Bayesian method which uses non-linear conjugate gradient for minimization (Cai et al 2013 Med. Phys. 40 111916-31), three methods based on quadratic surrogates (Long and Fessler 2014 IEEE Trans. Med. Imaging 33 1614-26, Weidinger et al 2016 Int. J. Biomed. Imaging 2016 1-15, Mechlem et al 2018 IEEE Trans. Med. Imaging 37 68-80), and a primal-dual method based on MOCCA, a modified Chambolle-Pock algorithm (Barber et al 2016 Phys. Med. Biol. 61 3784). Some of these methods have been accelerated by using μ-preconditioning, i.e. by performing all internal computations not with the actual materials the object is made of, but with carefully chosen linear combinations of those. In this paper, we also evaluated the impact of three different μ-preconditioners on convergence speed. Our experiments on simulated data revealed vast differences in the number of iterations required to reach a common image quality objective: Mechlem et al (2018 IEEE Trans. Med. Imaging 37 68-80) needed ten iterations, Cai et al (2013 Med. Phys. 40 111916-31), Long and Fessler (2014 IEEE Trans. Med. Imaging 33 1614-26) and Weidinger et al (2016 Int. J. Biomed. Imaging 2016 1-15) several hundreds, and Barber et al (2016 Phys. Med. Biol. 61 3784) several thousands. We also sum up other practical aspects, like memory footprint and the need to tune extra parameters.
Published: 2018
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167. Vaccination post-allogeneic hematopoietic stem cell transplantation: what is feasible?

Author: Florence Ader, Florent Valour, Anne Conrad, Vincent Alcazer, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hématologie clinique, CHU Lyon, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), 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), 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: Adult, chronic graft-versus-host disease, medicine.medical_treatment, Immunology, Graft vs Host Disease, chemical and pharmacologic phenomena, Hematopoietic stem cell transplantation, immune response, 03 medical and health sciences, 0302 clinical medicine, Immune system, Drug Discovery, hyposplenism, Humans, Medicine, Immunization Schedule, Pharmacology, Vaccines, business.industry, Vaccination, vaccine-preventable infection, immune reconstitution, Pneumococcus, Hematologic Diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Influenza, 3. Good health, Hematological Diseases, surgical procedures, operative, Curative treatment, Hematologic Neoplasms, 030220 oncology & carcinogenesis, hematopoietic stem cell transplantation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract: International audience; INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is a major curative treatment option for malignant and non-malignant hematological diseases, but is associated with an increased risk for infections, of which some are preventable by vaccination. Vaccination guidelines recommend repeated doses of most inactivated vaccines to achieve long-lasting immune responses. However, the efficacy of immunization is often hampered by graft-versus-host disease or severe opportunistic infections. Areas covered: This review summarizes the vaccine recommendations for adult allogeneic HSCT recipients and discusses the challenges and future directions regarding vaccine immunization in these patients. Expert commentary: Vaccination is a well-tolerated therapeutic intervention to prevent infections after allogeneic HSCT. Allogeneic HSCT recipients could benefit from experience regarding vaccine efficacy capitalized through specific data registries. An individualized immunization approach, modulating inception and intensity of vaccination schedule according to transplant characteristics, transplant-related complications and immune recovery status, might help to improve vaccine efficacy in this specific population. Identification of surrogate markers of the immune status and of vaccine efficacy, beyond antibody testing, as well as development of new vaccines are exciting fields of future research.
Published: 2018
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168. Prognostic Value of the Persistence of C1q-Binding Anti-HLA Antibodies in Acute Antibody-Mediated Rejection in Kidney Transplantation

Author: Valérie Chabot, Gilles Blancho, Raj Purgus, A. Parissiadis, Barbara Proust, Christiane Mousson, Moglie Le Quintrec, Philippe Grimbert, Matthias Büchler, Philippe Gatault, Paolo Malvezzi, Johnny Sayegh, Vincent Vuiblet, Valérie Chatelet, Yvon Lebranchu, Gwendaline Guidicelli, Isabelle Top, Frédéric Dehaut, Dany Anglicheau, Jérôme Tourret, Emmanuel Morelon, Elodie Bailly, Pierre François Westeel, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Service de Néphrologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Marseille, CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Graft Rejection, Male, Time Factors, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030230 surgery, Gastroenterology, 0302 clinical medicine, HLA Antigens, Isoantibodies, Risk Factors, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Plasma Exchange, biology, Graft Survival, Immunoglobulins, Intravenous, Middle Aged, 3. Good health, Treatment Outcome, Predictive value of tests, Female, Rituximab, France, Antibody, Immunosuppressive Agents, Protein Binding, medicine.drug, Adult, medicine.medical_specialty, Placebo, 03 medical and health sciences, Predictive Value of Tests, Glomerulopathy, Internal medicine, Complement C4b, medicine, Humans, Aged, Transplantation, business.industry, Complement C1q, Transplant glomerulopathy, medicine.disease, Kidney Transplantation, Peptide Fragments, biology.protein, business
Abstract: International audience; Background: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs helps in better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown.Methods: We included patients from the French multicenter RITUX ERAH study diagnosed with acute ABMR within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange). We centrally analyzed serum samples at the time of ABMR, 3 and 6 months after ABMR, with anti-HLA DSAs specificities and C1q-binding capacity assessment.Results: Twenty-five patients were included: 68% had C1q-binding DSAs at the time of ABMR. The presence of C1q-binding DSAs was associated with a poorer evolution of chronic glomerulopathy at 6 months (P = 0.036). The persistence of C1q-binding DSAs at 3 and/or 6 months after ABMR was associated with more severe chronic glomerulopathy (P = 0.006), greater C4d score deposition score at 6 months after ABMR (P = 0.008), and graft loss 5 years after ABMR (P = 0.029). C1q-binding capacity was associated with the DSA MFI but 5 C1q-binding DSAs in 4 patients had low MFI values without a prozone effect.Conclusion: The presence and persistence of anti-HLA C1q-binding DSAs after ABMR is a detrimental marker, leading to transplant glomerulopathy and graft loss. Assessment of the complement-binding capacities of DSAs could help decide treatment intensification.
Published: 2018
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169. Quelle utilisation des traitements de fond chez des patients ayant une SEP rémittente en France sur la période 1990–2017 ? Éléments de réponse à partir des données de l’Ofsep

Author: Romain Casey, David Laplaud, Jonathan Roux, Emmanuelle Leray, Fabien Rollot, Jérôme De Seze, Sandra Vukusic, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, 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), Service de Neurologie [Lyon], CHU Lyon, 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)
Subjects: 03 medical and health sciences, 0302 clinical medicine, Étude observationnelle, Neurology, Traitements de fond, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Neurology (clinical), 030217 neurology & neurosurgery, Sclérose en plaques
Abstract: Introduction Depuis l’arrivee en 1996 des interferons, l’arsenal therapeutique a disposition des neurologues pour la prise en charge des patients avec une sclerose en plaques (SEP) remittente a fortement change. Objectifs Decrire l’utilisation des traitements de fond chez les patients ayant une SEP remittente en France entre 1990 et 2017 : quels traitements ? A quel moment ? Combien de temps ? Quels switchs ? Methodes Tous les patients de la cohorte Ofsep, ayant une SEP remittente, vivants au 1er janvier 1996 ont ete inclus, soit au total 41 305 patients. Tous les traitements de fond, y compris utilises hors AMM, ont ete pris en compte, sans duree minimale. Seule la phase remittente de la maladie a ete consideree. Les donnees ont ete analysees globalement et separement dans les 4 periodes suivantes
Published: 2018
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170. Wells' syndrome-like reaction following Argas reflexus bites

Author: Aurore Rozières, Clemmie Martin, Sébastien Debarbieux, Frédéric Bérard, Christiane Hilger, Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Infection and Immunity [Luxembourg City], Luxembourg Institute of Health (LIH), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Département d'allergie et d'immunologie clinique [CHU Lyon Sud], 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), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, Argas, Dermatology, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Eosinophilia, medicine, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Tick Bites, business.industry, Biopsy, Needle, Cellulitis, Argas reflexus, Immunohistochemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, 030228 respiratory system, Wells syndrome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business
Abstract: International audience
Published: 2018
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171. Occupational immediate contact allergy to hydrolysed wheat protein after cosmetic exposure

Author: Delaunay, Juliette, Hacard, Florence, Denery-Papini, Sandra, Garnier, Lorna, Bérard, Frédéric, Nicolas, Jean-François, Nosbaum, Audrey, Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], 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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Adult, Allergic Contact, Croatia, Gloves, Dermatitis, Cosmetics, Wheat Hypersensitivity, Risk Assessment, Occupational Exposure, Industry, Humans, case report, ComputingMilieux_MISCELLANEOUS, immediate hypersensitivity, Patch Tests, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Occupational, Protective, Dermatitis, Occupational, hydrolysed wheat protein, Dermatitis, Allergic Contact, occupational disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, contact allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Gloves, Protective
Abstract: International audience
Published: 2018
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172. Fluxomic assay-assisted diagnosis orientation in a cohort of 11 patients with myopathic form of CPT2 deficiency

Author: Caroline Espil-Taris, Roland Jaussaud, Guilhem Solé, Christine Vianey-Saban, Karine Mention-Mulliez, Audrey Boutron, Cécile Acquaviva, Isabelle Kim, Dries Dobbelaere, Manuel Schiff, Wim Wuyts, Anne-Frédérique Dessein, Marie Joncquel-Chevalier Curt, Joseph Vamecq, Dominique Roland, Monique Fontaine, Claire Douillard, Centre de référence des maladies rares neuromusculaires Aquitaine-Grand Sud Ouest, CHU Bordeaux [Bordeaux], Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Groupement Hospitalier Est-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Palmitic Acid, Mitochondrial fatty acid oxidation, Compound heterozygosity, Biochemistry, Gastroenterology, Deuterated acylcarnitines, Rhabdomyolysis, 0302 clinical medicine, Endocrinology, Known and new CPT2 variants, Missense mutation, Child, Genetics & Heredity, Deuterated palmitate, beta-oxidation disorders, Research & Experimental, acid oxidation disorders, deficiency, Middle Aged, Prognosis, 3. Good health, carnitine palmitoyltransferase, Child, Preschool, intermembrane space pool of carnitine, Medicine, Female, medicine.symptom, Oxidation-Reduction, medicine.drug, Acylcarnitines, Adult, medicine.medical_specialty, Adolescent, ii deficiency, beta-oxidation, Frameshift mutation, 03 medical and health sciences, Young Adult, Endocrinology & Metabolism, Muscular Diseases, Internal medicine, Genetics, medicine, Humans, Carnitine, Fluxomic study, Myopathy, gene, Molecular Biology, Retrospective Studies, mitochondrial-membrane, CPT1, Carnitine O-Palmitoyltransferase, business.industry, CPT2, Carnitine palmitoyltransferase type 2, Infant, Retrospective cohort study, Diagnosis orientation, medicine.disease, Metabolic Flux Analysis, Late presentation, 030104 developmental biology, Human medicine, mutation, business, Acute rhabdomyolysis, metabolism, 030217 neurology & neurosurgery, Biomarkers, Metabolism, Inborn Errors, Follow-Up Studies
Abstract: International audience; Carnitine palmitoyltransferase type 2 (CPT2) deficiency, a mitochondrial fatty acid oxidation disorder (MFAOD), is a cause of myopathy in its late clinical presentation. As for other MFAODs, its diagnosis may be evocated when blood acylcarnitine profile is abnormal. However, a lack of abnormalities or specificity in this profile is not exclusive of CPT2 deficiency. Our retrospective study reports clinical and biological data in a cohort of 11 patients with circulating acylcamitine profile unconclusive enough for a specific diagnosis orientation. In these patients, CPT2 gene studies was prompted by prior fluxomic explorations of mitochondrial beta-oxidation on intact whole blood cells incubated with pentadeuterated ([16-H-2(3), 15-H-2(2)])-palmitate. Clinical indication for fluxomic explorations was at least one acute rhabdomyolysis episode complicated, in 5 of 11 patients, by acute renal failure. Major trigger of rhabdomyolysis was febrile infection. In all patients, fluxomic data indicated deficient CPT2 function showing normal deuterated palmitoylcarnitine (C16-Cn) formation rates associated with increased ratios between generated C16-Cn and downstream deuterated metabolites (Sigma deuterated C2-Cn to C14-Cn). Subsequent gene studies showed in all patients pathogenic gene variants in either homozygous or compound heterozygous forms. Consistent with literature data, allelic frequency of the c.338C \textgreater T[p.Ser113Leu] mutation amounted to 68.2% in our cohort. Other missense mutations included c.149C \textgreater A[p.Pro50His] (9%), c.200C \textgreater G[p.A1a200Gly] (4.5%) and previously unreported c.1171A \textgreater G[p.ser391Gly] (4.5%) and c.1420G \textgreater C[p.Ala474Pro] (4.5%) mutations. Frameshift c.1666-1667delTT[p.Leu556val*16] mutation (9%) was observed in two patients unknown to be related.
Published: 2018
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173. Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Author: Marc Bonnin, Nathalie Bendriss-Vermare, Ludovic Aillot, Sarah Maadadi, Caroline Scholtes, David Durantel, Isabel Najera, Fabien Zoulim, Julie Lucifora, Miroslava Subic, Malika Ait-Goughoulte, Laura Dimier, 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), Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], Département d'Hématologie [CHU Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Développement Cancer et Thérapies Ciblées / Cancer Development and Targeted Therapies (DEVweCAN LabEx), Université de Lyon - UDL, This work was supported by grants from ANRS (French national agency for research on AIDS and viral hepatitis), FINOVI (Foundation for innovation in infectiology), and INSERM. Besides academic funding, this work was mainly supported by Hoffmann-La Roche via its RPF (Roche Postdoc Fellowship) program, M. Bonnin was the recipient of this program under the supervision of D. Durantel (academic side) and M. Ait-Goughoulte/I. Najera (Roche scientist leaders)., ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Durantel, David, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, and PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID
Subjects: 0301 basic medicine, Agonist, entry inhibition, HBsAg, CpG Oligodeoxynucleotide, medicine.drug_class, [SDV]Life Sciences [q-bio], Alpha interferon, chemical and pharmacologic phenomena, medicine.disease_cause, Antiviral Agents, Cell Line, 03 medical and health sciences, immune system diseases, parasitic diseases, medicine, Humans, Pharmacology (medical), Receptor, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, agonist, Pharmacology, Hepatitis B virus, plasmacytoid cells, Chemistry, Virion, TLR9, Interferon-alpha, hemic and immune systems, Toll-like receptor 9, Dendritic Cells, Molecular biology, digestive system diseases, 3. Good health, Toll-Like Receptor 9, Toll-like receptors, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oligodeoxyribonucleotides, plasmacytoid dendritic cells, hepatocytes, hepatitis B virus
Abstract: International audience; We previously reported that Toll-like receptor 9 (TLR9)-CpG oligonucleo-tides could inhibit the establishment of hepatitis B virus (HBV) infections in hepato-cytes. Our aim was to uncover the underlying mechanisms of this inhibition. HepaRG cells, RPMI-B lymphoblastoma cells, and primary plasmacytoid dendritic cells (pDCs) exposed to HBV and TLR9 ligands/agonists in various configurations were used. We observed an inhibition of HBV infection upon TLR9 stimulations only when agonist was applied during inoculation. This inhibition was independent of interleukin-6 (IL-6)/interferon-inducible protein 10 (IP-10) production as well as of TLR9 expression in hepatocytes. We further demonstrated an entry inhibition mechanism by showing a noncovalent binding of TLR9 agonist to HBV particles. Besides inhibiting HBV entry into hepatocytes, this biophysical interaction between HBV virions and TLR9 agonist was responsible for a reduction of alpha interferon (IFN-) expression by pDCs. Interestingly , subviral particles composed of only HBsAg were able to genuinely inhibit the TLR9 pathway, without titrating TLR9 ligands. To conclude, our data suggest that synthetic TLR9-CpG oligonucleotides can strongly inhibit HBV entry by " coating " HBV virions and thereby preventing their interaction with cellular receptor. This titration effect of TLR9 agonist is also artifactually responsible for the inhibition of TLR9 engagement in pDCs, whereas a genuine inhibition of this innate pathway was confirmed with HBsAg subviral particles. H epatitis B virus (HBV) chronically infects 240 million people worldwide and represents one of the major etiologies for cirrhosis and hepatocellular carcinoma (1, 2). The progression rate of chronicity is tightly linked with the maturity of the immune system, since 90 to 95% of infected newborns become chronic carriers, whereas only 5 to 10% of adults do (3). As HBV long-term persistence is characterized by subversion of both innate and adaptive immunity (4, 5), a better understanding of the underlying cellular and molecular mechanisms of this escape should help in defining new therapeutic strategies to reactivate the host immune system and control viral replication. Current front-line therapies include the use of nucleoside analogues to specifically inhibit viral reverse transcription and/or pegylated interferon alpha 2a or 2b (Peg-IFN
Published: 2018
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174. High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Author: Nicolas Mansencal, Erwan Donal, Didier Klug, Estelle Gandjbakhch, Dagmar I. Keller, Alexis Hermida, Pierre Cosnay, Jean-Claude Deharo, Vincent Probst, Véronique Fressart, Philippe Chevalier, Etienne Delacrétaz, Fabrice Extramiana, Patrice Scanu, Françoise Hidden-Lucet, Philippe Charron, Stephanie Rouanet, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Service de Cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, CHU Pontchaillou [Rennes], 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)-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), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Marseille, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], Hôpital de l'Ile, Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), AP-HP - Hôpital Bichat - Claude Bernard [Paris], University hospital of Zurich [Zurich], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Unité de recherche de l'institut du thorax (ITX-lab)
Subjects: Proband, Adult, Male, medicine.medical_specialty, Heterozygote, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Desmoglein-2, 030204 cardiovascular system & hematology, Right ventricular cardiomyopathy, 03 medical and health sciences, Electrocardiography, Young Adult, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Arrhythmogenic Right Ventricular Dysplasia, Retrospective Studies, Heart Failure, Plakophilin-2, Desmoglein 2, business.industry, DNA, Middle Aged, medicine.disease, Arrhythmogenic right ventricular cardiomyopathy/dysplasia, 3. Good health, Pedigree, Transplantation, Phenotype, Dysplasia, Heart failure, Cohort, Mutation (genetic algorithm), Mutation, Cardiology, Ventricular arrhythmia, Cardiac transplantation, Female, Cardiology and Cardiovascular Medicine, business, Plakophilins, Follow-Up Studies
Abstract: International audience; BACKGROUND:Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene.METHODS AND RESULTS:Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005).CONCLUSIONS:In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.
Published: 2018
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175. A double-blind placebo-controlled randomised trial of omega-3 supplementation in children with moderate ADHD symptoms

Author: Catherine Cornu, Sandrine Masson, Marie-France Le Heuzey, Valérie Laudy, Julie Mouchet, H. Desombre, Tiphanie Ginhoux, Patrick Berquin, Behrouz Kassai, Olivier Revol, Nathalie Franc, Patrice Nony, Catherine Mercier, Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Biostatistique des Hospices Civils de Lyon, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Centre d'investigation clinique, Service de neuropédiatrie, CHU Amiens-Picardie, Service de psychopathologie de l'enfant et de l'adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), CHU Hôpital Nord Amiens, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, Pediatrics, medicine.medical_specialty, Adolescent, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Rating scale, Fatty Acids, Omega-3, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Humans, Child, Adverse effect, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, business.industry, General Medicine, 030227 psychiatry, 3. Good health, Clinical trial, Psychiatry and Mental health, Treatment Outcome, Attention Deficit Disorder with Hyperactivity, Pediatrics, Perinatology and Child Health, Physical therapy, Anxiety, Female, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Clinical trials and inconclusive meta-analyses have investigated the effects of omega-3 supplements in children with Attention-Deficit Hyperactivity Disorder (ADHD). We performed a randomised placebo-controlled trial to evaluate the efficacy of omega-3 fatty acids. Children aged 6–15 years with established diagnosis of ADHD were randomised 1:1 to receive either supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or a placebo for 3 months. Psychotropic or omega-3-containing treatments were not authorised during the study. The primary outcome was the change in the Attention-Deficit Hyperactivity Disorder Rating Scale version 4 (ADHD-RS-IV). Other outcomes included safety, lexical level (Alouette test), attention (Test of Attentional Performance for Children—KiTAP), anxiety (48-item Conners Parent Rating Scale-Revised—CPRS-R), and depression (Children’s Depression Inventory—CDI). Between 2009 and 2011, 162 children were included in five French child psychiatry centres. The mean age was 9.90 (SD 2.62) years and 78.4% were boys. The inclusion ADHD-RS-IV at was 37.31 (SD 8.40). The total ADHD-RS-IV score reduction was greater in the placebo group than in the DHA–EPA group: −19 (−26, −12) % and −9.7 (−16.6, −2.9) %, respectively, p = 0.039. The other components of the Conners score had a similar variation but the differences between groups were not significant. Two patients in the DHA–EPA group and none in the placebo group experienced a severe adverse event (hospitalisation for worsening ADHD symptoms). This study did not show any beneficial effect of omega-3 supplement in children with mild ADHD symptoms.
Published: 2018
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176. Weekly follow up of acute lesions in three early multiple sclerosis patients using MR spectroscopy and diffusion

Author: Salem Hannoun, Françoise Durand-Dubief, Gabriel Kocevar, Claudio Stamile, François Cotton, Jean-Amédée Roch, Dominique Sappey-Marinier, Sandra Vukusic, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Lyon], CHU Lyon, Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Adult, In vivo magnetic resonance spectroscopy, Pathology, medicine.medical_specialty, Magnetic Resonance Spectroscopy, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Contrast Media, Signal-To-Noise Ratio, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Fractional anisotropy, Image Processing, Computer-Assisted, Organometallic Compounds, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Remyelination, ComputingMilieux_MISCELLANEOUS, Brain Chemistry, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, medicine.disease, Hyperintensity, 3. Good health, Diffusion Tensor Imaging, medicine.anatomical_structure, Anisotropy, Female, Neurology (clinical), medicine.symptom, Nuclear medicine, business, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Object Pathophysiological mechanisms underlying multiple sclerosis (MS) lesion formation, including inflammation, demyelination/remyelination and axonal damage, and their temporal evolution are still not clearly understood. To this end, three acute white matter lesions were monitored using a weekly multimodal magnetic resonance (MR) protocol. Materials and methods Three untreated patients with early relapsing-remitting MS and one healthy control subject were followed weekly for two months. MR protocol included conventional MR imaging (MRI), diffusion tensor imaging (DTI), and localized MR spectroscopy (MRS), performed on the largest gadolinium-enhancing lesion, selected at the first exam. Results Mean diffusivity increased and fractional anisotropy decreased in lesions compared to healthy control. Cho/Cr ratios remained elevated in lesions throughout the follow-up. In contrast, temporal profiles of mI/Cr ratios varied between patients’ lesions. For patient 1, mI/Cr ratios were already elevated at the beginning of the follow-up. Patients 2 and 3 ratios increase was delayed by two and five weeks. Blood-brain barrier (BBB) recovery occurred after three weeks. Conclusion This multimodal MR follow-up highlighted the complementary role of DTI and MRS in identifying temporal relationships between BBB disruption, inflammation, and demyelination. Diffusion metrics showed high sensitivity to detect inflammatory processes. The different temporal profiles of mI suggested a potential better specificity to monitor pathological mechanisms occurring after lesion formation, such as glial proliferation and remyelination.
Published: 2018
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177. Effect of desipramine on patients with breathing disorders in RETT syndrome

Author: Mancini, Josette, Dubus, Jean-Christophe, Jouve, Elisabeth, Roux, Jean-Christophe, Franco, Patricia, Lagrue, Emmanuelle, Castelnau, Pierre, Cances, Claude, Chaix, Yves, Rougeot-Jung, Christelle, Cornu, Catherine, Desportes, Vincent, Vallée, Louis, Bahi-Buisson, Nadia, Truillet, Romain, Attolini, Laurence, Villard, Laurent, Blin, Olivier, Micallef, Joëlle, Hôpital de la Timone [CHU - APHM] (TIMONE), Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Physiologie integrée du système d'éveil, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR19-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pédiatrie, CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neuropédiatrie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Clinical Investigation Centre (CIC-UPCET) and Department of Clinical Pharmacology, Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM)-Assistance Publique - Hôpitaux de Marseille (APHM), Euromov (EuroMov), Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Roux, Jean-Christophe, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: [SDV] Life Sciences [q-bio], [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Abstract: International audience; Objective: Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipra-mine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2-deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT. Methods: The trial was a 6-month, multicenter, randomized, double-blind, placebo-controlled study registered with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to clinical examination and confirmed by genotyping were randomly assigned in a 1:1:1 ratio to receive 2–3 mg/kg Desipramine per day (high Desi-pramine), 1–2 mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome was the change of apnea hypopnea index (AHI), defined by the number of apnea and hypopnea events per hour, assessed at 6 months from baseline. Intention-to-treat analysis was applied. Results: The median change in AHI from baseline to 6 months was À31 (IQR: À37 to À11) for the high Desipramine, À17.5 (IQR: À31 to 13) for the low Desipramine, and À13 (IQR:À31 to 0) for the placebo group. We did not find any significant difference in these changes between the groups (P = 0.781). A significant inverse correlation between Desipramine plasma concentration and AHI (r = À0.44; P = 0.0002) was underlined. Interpretation: This first clinical trial of desipra-mine did not show clinical efficacy. Although required further studies, the significant correlation between Desipramine concentrations and improvement of AHI provided additional and relevant reasons to test the noradrenergic pathway in RTT. 118
Published: 2018
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178. Benign and malignant enlarged chest nodes staging by diffusion-weighted MRI: an alternative to mediastinoscopy?

Author: Pia Akl, Caroline Mesmann, Salim Si-Mohamed, Loic Boussel, Philippe Douek, Monica Sigovan, François Tronc, Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de chirurgie thoracique (HCL, Hôpital Louis Pradel, Bron), Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Radiologie et IRM [CHU Lyon], and Hôpital Cardiovasculaire Louis Pradel (HCLP)
Subjects: Adult, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Mediastinoscopy, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Effective diffusion coefficient, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, Aged, 80 and over, medicine.diagnostic_test, Receiver operating characteristic, Full Paper, business.industry, Mediastinum, General Medicine, Middle Aged, medicine.anatomical_structure, Diffusion Magnetic Resonance Imaging, 030220 oncology & carcinogenesis, Predictive value of tests, Lymphatic Metastasis, Background suppression, Radiology, Lymph Nodes, business, Diffusion MRI
Abstract: International audience; Objective:To evaluate the accuracy of diffusion-weighted MRI with background suppression (DWIBS) in differentiating between malignant and benign mediastinal lymph-nodes.Methods:Consecutive patients with enlarged mediastinal lymph-nodes underwent MRI DWIBS within 10 days prior to mediastinoscopy. Relative contrast ratios (RCRs) were computed on b800 and apparent diffusion coefficient (ADC) maps by dividing the node signal with the chest muscle signal, using manually drawn regions of interest (ROIs) by radiologists, blinded to pathology. Unpaired Student's t-tests were used to compare RCR-b800 and ADC between malignant and benign nodes. Receiver operating characteristic curves analyses were also performed.Results:Six patients were excluded for poor image quality. Analysis was performed for 54 patients. Mean ADC values were significantly higher for benign (1740 ± 401 × 10−6 mm2 s–1) compared with malignant nodes (1266 ± 403 × 10−6 mm2 s–1, p = 0.0001). Mean RCR-b800 values were significantly lower for benign (2.64 ± 1.07) compared with malignant nodes (6.44 ± 3.47, p < 0.0001).Receiver operating characteristic analysis for RCR-b800 (cut-off of 3.6), showed a sensitivity of 90.9%, a specificity 83% and an accuracy 85% for differentiating benign from malignant nodes. For ADC (cut-off of 1285), the sensitivity was 68.2%, the specificity 84.6% and the accuracy 80.4%.Conclusion:DWIBS can accurately differentiate malignant from benign states in enlarged mediastinal lymph-nodes and represents an alternative method in aetiological work-up of mediastinal lymphadenopathies.Advances in knowledge:DWIBS may represent a useful adjunctive imaging modality, particularly for diagnosis of benign mediastinal lymph node, and thus may reduce the frequency of futile mediastinoscopy, which remains an invasive procedure.
Published: 2018
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179. PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

Author: Dumontet, Typhanie, Sahut-Barnola, Isabelle, Septier, Amandine, Montanier, Nathanaëlle, Plotton, Ingrid, Roucher-Boulez, Florence, Ducros, Véronique, Martinez, Anne-Marie, Pointud, Jean-Christophe, Zubair, Mohamad, Morohashi, Ken-Ichirou, Breault, David, Val, Pierre, Martinez, Antoine, Lefrançois-Martinez, Anne-Marie, 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), Interactions génétiques et cellulaires au cours de la différenciation, Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), CHU Lyon, Service de Biochimie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, Reproduction et Développement (GReD), 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), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Development, Mouse models, Mice, Endocrinology, Protein kinases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Adrenarche, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Sex Characteristics, Adrenal cortex, Age Factors, Cell Differentiation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Embryo, Mammalian, Zona Reticularis, Cell biology, Sexual dimorphism, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Models, Animal, Androgens, Pka signaling, Female, Zona Fasciculata, Signal Transduction, Research Article, Genetic diseases
Abstract: International audience; The adrenal cortex undergoes remodeling during fetal and postnatal life. How zona reticularis emerges in the postnatal gland to support adrenarche, a process whereby higher primates increase prepubertal androgen secretion, is unknown. Using cell-fate mapping and gene deletion studies in mice, we show that activation of PKA has no effect on the fetal cortex, while it accelerates regeneration of the adult cortex, triggers zona fasciculata differentiation that is subsequently converted into a functional reticularis-like zone, and drives hypersecretion syndromes. Remarkably, PKA effects are influenced by sex. Indeed, testicular androgens increase WNT signaling that antagonizes PKA, leading to slower adrenocortical cell turnover and delayed phenotype whereas gonadectomy sensitizes males to hypercorticism and reticularis-like formation. Thus, reticularis results from ultimate centripetal conversion of adult cortex under the combined effects of PKA and cell turnover that dictate organ size. We show that PKA-induced progenitor recruitment is sexually dimorphic and may provide a paradigm for overrepresentation of women in adrenal diseases.
Published: 2018
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180. Performances et critères de qualité de l’IRM, du colo-scanner, de l’entéro IRM/CT pour le diagnostic d’endométriose pelvienne, RPC Endométriose CNGOF-HAS

Author: Thomassin-Naggara, Isabelle, Bendifallah, Sofiane, Rousset, Pascal, Bazot, Marc, Ballester, Marcos, Daraï, Emile, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Diagnostic Imaging, Endométriose, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Coloscan, Entéro-IRM, Endometriosis, Rectum, Genitalia, Female, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Pelvis, IRM pelvienne, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Entero-MRI, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Diagnosis, Entéro-CT, Coloscanner, Humans, Female, Pelvic MRI, Diagnostic
Abstract: Diagnostic performance of MR imaging for the diagnosis of pelvic endometriosis are good. Even if some differences of performances exists according the location considered, the risk of misdiagnosis is lower than 10% for trained teams (NP2). The performance of pelvic MR imaging and surgery are quite similar to diagnose endometrioma (sensitivity and specificity>90%). A negative pelvic MR imaging allows to exclude deep pelvic endometriosis with a performance similar to surgery but a positive MR imaging is less accurate than surgery because of a high number of false positives (23%). Pelvic MR imaging is more sensitive and less specific than ultrasonography for the diagnosis of uterosacral ligament, vagina or recto vaginal septum (NP2). Pelvic ultrasonography is more sensitive than pelvic MR imaging for the diagnosis of colorectal location (NP3). Pelvic MR imaging is a reproducible technique for the diagnosis of pelvic endometriosis (NP3). Regarding, quality criteria of pelvic MR imaging, no data are enough to recommend a specific MR unit, digestive preparation, or a specific moment during the menstrual cycle to realize the examination. Vaginal and/or rectal opacification are options. Most of studies are based a protocol including 3D T2W and 3DT1W sequences. Gadolinium injection is useful to characterize a complex adnexal mass. In clinical routine, slices crossing the kidneys are useful to evaluate the presence of pyelo calic distension. ColoCT is an accurate technique to diagnose pelvic digestive endometriosis (rectosigmoide and iléocaecal) (NP3)., Les performances de l’IRM pelvienne pour le diagnostic d’endométriose sont bonnes. Même si des différences existent entre les différentes localisations, le risque de classement à tort est égal ou inférieur à 10 % pour les équipes entraînées (NP2). L’IRM pelvienne peut être considérée comme une technique diagnostique proche de la chirurgie pour le diagnostic d’endométriome ovarien (sensibilité et spécificité supérieures à 90 %). Une IRM pelvienne négative permet d’exclure des lésions d’endométriose pelvienne profonde avec une performance proche de la chirurgie alors qu’une IRM pelvienne positive est moins performante que la chirurgie en raison du nombre de faux positifs d’environ 23 % (NP1). L’IRM pelvienne est plus sensible et moins spécifique que l’échographie endovaginale pour le diagnostic des ligaments utérosacrés, du vagin, et de la cloison rectovaginale (NP2). L’échographie pelvienne est plus sensible que l’IRM pelvienne pour le diagnostic de l’endométriose du rectosigmoide (NP3). L’IRM pelvienne est une technique reproductible pour le diagnostic d’endométriose pelvienne (NP3). Concernant les critères de qualité de l’IRM pelvienne, aucune donnée suffisante dans la littérature ne permet de recommander une machine spécifique, une préparation préalable ou des conditions de réalisation spécifique au cours du cycle. L’opacification du vagin et/ou du rectum est une option. La plupart des études se basent sur des séquences multi planaires en T2 et T1 pour faire le diagnostic d’endométriose pelvienne. L’injection de gadolinium est utile pour caractériser une masse annexielle complexe. Les recommandations de bonne pratique sont de disposer de coupes passant par les reins et de faire une acquisition à vessie semi pleine pour ne pas gêner l’interprétation (accord d’expert). Le ColoCT est une technique performante pour le diagnostic d’endométriose pelvienne digestive du rectosigmoide et iléocaecale (NP3).
Published: 2018
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181. Treatment of chronic spontaneous urticaria: Immunomodulatory approaches

Author: Laurence de Montjoye, Marie Baeck, Anne Herman, Jean-François Nicolas, Cheval, Christelle, Department of Dermatology [Brussels, Belgium], Université Catholique de Louvain = Catholic University of Louvain (UCL)-Saint-Luc University Hospital [Brussels, Belgium], Institute of Experimental and Clinical Research [Brussels, Belgium] (Pole of Pneumology, ENT and Dermatology), Université Catholique de Louvain = Catholic University of Louvain (UCL), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de dermatologie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Urticaria, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Immunology, Complex disease, Disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, B-lymphocytes, Humans, Immunology and Allergy, T-lymphocytes, Autoantibodies, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, Autoantibody, Chronic spontaneous urticaria, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Pathophysiology, Basophils, 3. Good health, Treatment, 030228 respiratory system, chemistry, Chronic Disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Histamine H1 Antagonists, Mast cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antihistamine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Histamine
Abstract: International audience; This paper summarizes and reviews the mechanisms of action and data concerning efficacy of recommended treatments as well as other treatments that have been tested, independently of the outcomes, in the management of chronic spontaneous urticaria. Due to the central role of mast cells, basophils and histamine in the pathophysiology of this disease, H1-antihistamines remain the first-line treatment. However, current knowledge about this complex disease, also recognizes an important role for T lymphocytes, B lymphocytes, and autoantibodies. Implications of these others mediators thus provide further targets for treatment. Indeed, agents previously used to treat other autoimmune and inflammatory diseases, have demonstrated efficacy in chronic spontaneous urticaria and are therefore potential therapeutic alternatives for antihistamine unresponsive patients.
Published: 2018
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182. Accessibility to drugs in the context of a rare bleeding disorder: analysis of a cohort of haemophiliac in a French region

Author: Leroy, Vincent, Freyssenge, Julie, Florent, Renard, Tazarourte, Karim, Negrier, Claude, Chamouard, Valerie, Freyssenge, Julie, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Urgences Médicales, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Université de Lyon, Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

183. Pediatric renal transplantation: A retrospective single-center study on epidemiology and morbidity due to EBV

Author: Behrouz Kassai, Bruno Lina, Pascal Roy, Audrey Laurent, Pierre Cochat, Amna Klich, J. Bacchetta, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Service de Biostatistique des Hospices Civils de Lyon, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), 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), Institut des Agents Infectieux [Lyon] (IAI), EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Service de Biostatistiques [Lyon], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Epstein-Barr Virus Infections, PLTD, Adolescent, 030232 urology & nephrology, Kaplan-Meier Estimate, 030230 surgery, Single Center, 03 medical and health sciences, Outcome Assessment (Health Care), 0302 clinical medicine, Postoperative Complications, EBV, Risk Factors, Internal medicine, hemic and lymphatic diseases, Epidemiology, Outcome Assessment, Health Care, medicine, Humans, Risk factor, Child, Preschool, Kidney transplantation, Proportional Hazards Models, Retrospective Studies, Transplantation, Proportional hazards model, business.industry, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Newborn, EBV nuclear antigen, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, pediatric renal transplantation, business, Viral load, Follow-Up Studies
Abstract: International audience; Pediatric R-Tx patients are at high risk of developing EBV primary infection. Although high DNA replication is a risk factor for PTLD, some patients develop PTLD with low viral load. In this retrospective single-center study including all pediatric patients having received R-Tx (2003-2012 period), we aimed to identify risk factors for uncontrolled reactions to EBV (defined as the presence of a viral load \textgreater10~000~copies/mL or PTLD). A Cox proportional hazard model was performed. A total of 117 patients underwent R-Tx at a mean age of 9.7~\textpm~5.3~years, 46 of them being seronegative for EBV at the time of R-Tx. During follow-up, 54 patients displayed positive EBV viral load, 22 of whom presenting with primary infection. An uncontrolled reaction to EBV was observed in 24 patients, whilst 4 patients developed PTLD. Univariate and multivariate analyses suggested the following risk factors for an uncontrolled reaction: age below 5~years, graft from a deceased donor, >=5 HLA mismatches, EBV-seronegative status at the time of R-Tx, and a secondary post-Tx loss of anti-EBNA. Monitoring anti-EBNA after R-Tx may contribute to the early identification of patients at risk for uncontrolled reaction.
Published: 2018
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184. A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis

Author: Olson, Heather, Jean-Marçais, Nolwenn, Yang, Edward, Héron, Delphine, Tatton-Brown, Katrina, van der Zwaag, Paul, Bijlsma, Emilia, Krock, Bryan, Backer, E., Kamsteeg, Erik-Jan, Sinnema, Margje, Reijnders, Margot R.F., Bearden, David, Begtrup, Amber, Telegrafi, Aida, Lunsing, Roelineke, Burglen, Lydie, Lesca, Gaetan, Cho, Megan, Smith, Lacey, Sheidley, Beth, Moufawad El Achkar, Christelle, Pearl, Phillip, Poduri, Annapurna, Skraban, Cara, Tarpinian, Jennifer, Nesbitt, Addie, Fransen van de Putte, Dietje, Ruivenkamp, Claudia A.L., Rump, Patrick, Chatron, Nicolas, Sabatier, Isabelle, De Bellescize, Julitta, Guibaud, Laurent, Sweetser, David, Waxler, Jessica, Wierenga, Klaas, DDD Study,, Donadieu, Jean, Narayanan, Vinodh, Ramsey, Keri, C4RCD Research Group,, Nava, Caroline, Rivière, Jean-Baptiste, Vitobello, Antonio, Tran Mau-Them, Frederic, Philippe, Christophe, Bruel, Ange-Line, Duffourd, Yannis, Thomas, Laurel, Lelieveld, Stefan, Schuurs-Hoeijmakers, Janneke, Brunner, Han, Keren, Boris, Thevenon, Julien, Faivre, Laurence, Thomas, Gary, Thauvin-Robinet, Christel, Department of Neurology, Children's Hospital [Boston], Boston Children's Hospital, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Medical Center Groningen [Groningen] (UMCG), Department of Clinical Genetics (Leiden University Medical Center), Leiden University Medical Center (LUMC), Children’s Hospital of Philadelphia (CHOP ), GeneDx [Gaithersburg, MD, USA], Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GRC ConCer-LD, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Génétique [HCL Groupement Hospitalier Est], Groupement hospitalier Lyon-Est, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology and Laboratory Medicine [Philadelphia, PA, USA], University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], Department of Clinical Genetics [Leiden, the Netherlands], Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département d'Epilepsie, Sommeil et Neurophysiologie Pédiatrique [HCL, Lyon], Hospices Civils de Lyon (HCL), Service de Radiologie [Hôpital Femme Mère Enfant - HCL], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Department ofMicrobiology and Molecular Genetics ( University of Pittsburgh), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Pittsburgh Cancer Institute, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, and MUMC+: DA Klinische Genetica (5)
Subjects: Male, 0301 basic medicine, Pathology, PACS-2, Vesicular Transport Proteins, PHENOTYPE, Bioinformatics, DISEASE, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Epilepsy, 0302 clinical medicine, Missense mutation, Global developmental delay, Age of Onset, Child, Genetics (clinical), Epileptic encephalopathy, APOPTOSIS, 3. Good health, cerebellar dysgenesis, Mutation, Missense/genetics, intellectual disability, Child, Preschool, Epilepsy, Generalized, Female, PACS2, CLINICAL EPILEPSY, medicine.medical_specialty, Heterozygote, Generalized/genetics, PROTEINS, Genetic counseling, Mutation, Missense, Missense/genetics, Neonatal onset, Biology, DIAGNOSIS, Vesicular Transport Proteins/genetics, Facial dysmorphism, 03 medical and health sciences, Dysgenesis, All institutes and research themes of the Radboud University Medical Center, Cerebellar Diseases, Report, MENDELIAN DISORDERS, Genetics, medicine, Humans, Generalized epilepsy, Preschool, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Cerebellar Diseases/genetics, business.industry, MUTATIONS, Infant, Newborn, Correction, Infant, Facies, Newborn, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, epilepsy, Autism, business, Epilepsy, Generalized/genetics, 030217 neurology & neurosurgery
Abstract: International audience; Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.). Whole-exome sequencing and intensive data sharing identified a recurrent de novo PACS2 heterozygous missense variant in 14 unrelated individuals. Their phenotype was characterized by epilepsy, global developmental delay with or without autism, common cerebellar dysgenesis, and facial dysmorphism. Mixed focal and generalized epilepsy occurred in the neonatal period, controlled with difficulty in the first year, but many improved in early childhood. PACS2 is an important PACS1 paralog and encodes a multifunctional sorting protein involved in nuclear gene expression and pathway traffic regulation. Both proteins harbor cargo(furin)-binding regions (FBRs) that bind cargo proteins, sorting adaptors, and cellular kinase. Compared to the defined PACS1 recurrent variant series, individuals with PACS2 variant have more consistently neonatal/early-infantile-onset epilepsy that can be challenging to control. Cerebellar abnormalities may be similar but PACS2 individuals exhibit a pattern of clear dysgenesis ranging from mild to severe. Functional studies demonstrated that the PACS2 recurrent variant reduces the ability of the predicted autoregulatory domain to modulate the interaction between the PACS2 FBR and client proteins, which may disturb cellular function. These findings support the causality of this recurrent de novo PACS2 heterozygous missense in DEEs with facial dysmorphim and cerebellar dysgenesis.
Published: 2018
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185. Multiple Micronutrient Plasma Level Changes Are Related to Oxidative Stress Intensity in Critically Ill Children

Author: Charlotte Cuerq, Marion Pitance, Etienne Javouhey, Emilie Blond, Amandine Bellon, Tiphanie Ginhoux, Sylvain Roche, Aurélie Portefaix, Jenna Ridout, Carole Ford-Chessel, Muriel Bost, René Ecochard, Frédéric V. Valla, Hospices Civils de Lyon (HCL), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Division of Pediatric Intensive Care, Hôpital Femme Mère Enfant, Laboratoire de Mécanique des Systèmes et des Procédés (LMSP), Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC)-Barcelona Institute of Science and Technology (BIST), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Department of Biochemistry, Lyon Sud Hospital, Laboratoire d'Analyse de Traces et Métaux Toxiques, hospices civils de Lyon, Service de Biostatistique, Université de Lyon, Paediatric Intensive Care Unit, Addensbrooke's Hospital, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Department of Pediatric Anestesiology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Service diététique, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université de Lyon-Université de Lyon-Université Gustave Eiffel (UNIV GUSTAVE EIFFEL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and Université de Lyon-Université de Lyon-Université Gustave Eiffel
Subjects: Male, Micronutrient deficiency, medicine.medical_treatment, [SDV]Life Sciences [q-bio], vitamin C, vitamin E, Critical Care and Intensive Care Medicine, medicine.disease_cause, Severity of Illness Index, Pediatrics, clinical-trial, chemistry.chemical_compound, 0302 clinical medicine, SANTE, 030212 general & internal medicine, Micronutrients, Prospective Studies, Child, selenium, 2. Zero hunger, chemistry.chemical_classification, pediatric critical illness, Glutathione peroxidase, zinc, Micronutrient, 3. Good health, Child, Preschool, controlled-trial, Female, Vitamin, medicine.medical_specialty, EPIDEMIOLOGIE, Adolescent, Critical Illness, critical-care medicine, antioxidant status, CAROTENE, 03 medical and health sciences, support therapy, Internal medicine, General & Internal Medicine, medicine, Humans, enteral nutrition, carotene, Vitamin C, business.industry, Vitamin E, Infant, 030208 emergency & critical care medicine, medicine.disease, Malnutrition, Oxidative Stress, Cross-Sectional Studies, american, society, chemistry, Case-Control Studies, copper, Pediatrics, Perinatology and Child Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, inflammatory response syndrome, patient society, business, Oxidative stress, Biomarkers
Abstract: Objectives: Micronutrient supplementation in critically ill adults remains controversial. In the pediatric setting, the impact of oxidative stress on the overall micronutrient status has been poorly explored, due to the limited number of studies and to confounding factors (i.e., malnutrition or extra losses). In order to better understand this phenomenon, we aim to describe micronutrient status, focusing on seven micronutrients, in well-nourished critically ill children presenting with severe oxidative stress. Design: Prospective, transversal, observational, single-center study. Setting: PICU, and anesthesiology department, Lyon, France. Patients: Three groups of patients were clinically defined: severe oxidative stress PICU group (at least two organ dysfunctions), moderate oxidative stress PICU group (single organ dysfunction), and healthy control group (prior to elective surgery); oxidative stress intensity was controlled by measuring plasma levels of glutathione peroxidase and glutathione. Children presenting any former condition leading to micronutrient deficiency were excluded (malnutrition, external losses). Interventions: Plasma levels of selenium, zinc, copper, vitamin A, vitamin E, vitamin C, and -carotene were measured in PICU oxidative stress conditions and compared with those of healthy children. Measurements and Main Results: Two hundred one patients were enrolled (51, 48, and 102 in severe, moderate, and healthy control groups, respectively). Median age was 7.1 years (interquartile range, 2.1-13.8 yr). There was a significant trend (p \textless 0.02) toward plasma level decrease of six micronutrients (selenium, zinc, copper, vitamin E, vitamin C, and -carotene) while oxidative stress intensity increased. Biological markers of oxidative stress (glutathione peroxidase and glutathione) were in accordance with the clinical definition of the three groups. Conclusions: A multiple micronutrient deficiency or redistribution occurs in critically ill children presenting with severe oxidative stress. These findings will help to better identify children who might benefit from micronutrient supplementation and to design adapted supplementation trials in this particular setting.
Published: 2018
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186. Severe liver failure rather than cirrhosis is associated with mortality in patients with infectious endocarditis: a retrospective case-control study

Author: Christophe Bureau, Je Combining Acute Accent Rôme Dumortier, Anis Sfaxi, Manon Allaire, Laurent Spahr, Jacques Denis, Vincent Di Martino, Gilles Macaigne, Jean-Pierre Bronowicki, Jean-Didier Grangé, Vincent Jouannaud, Salah Zerkly, Teresa Antonini, Isabelle Ollivier-Hourmand, Alexandre Pariente, Alexandre Louvet, He Combining Acute Accent le Combining Grave Accent Ne Blasco-Perrin, Pierre Iaria, Karine Dupont, Jean-Baptiste Nousbaum, Carine Chagneau-Derrode, Agne Combining Grave Accent S Pe Combining Acute Accent Laquier, Patrice Cacoub, Thierry Thevenot, Je Combining Acute Accent Rome Gournay, Jean-François Cadranel, Thong Dao, Ryme Chentouh, Christine Silvain, Isabelle Rosa-He Combining Acute Accent Zode, Nathalie Ganne-Carrie Combining Acute Accent, Xavier Causse, Marc Bourlie Combining Grave Accent Re, Laurent Alric, Armand Garioud, Hortensia Lison, Pagès, Nathalie, 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), Lab Excellence Inflamex (CRI INSERM U1149 - Bichat Medical Faculty), Université Paris Diderot - Paris 7 (UPD7), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier de Pau, Centre Hospitalier de Montélimar, CH Montélimar, Centre Hospitalier Universitaire Marseille, CHU Marseille, Centre Hospitalier Régional d'Orléans (CHRO), CHU Brest - Service hépato-gastro-entérologie (CHU de Brest) (CHU Brest - Service hépato-gastro-entérologie), CHU Lyon Croix-Rousse, Hospices civils de Lyon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre hospitalier universitaire de Bondy, CHU Bondy, Service de Cardiologie, Centre Hospitalier Lagny-Marne la Vallée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de chirurgie digestive et viscérale [Corbeil-Essonnes], Centre Hospitalier Sud Francilien, CH Evry-Corbeil-CH Evry-Corbeil, and Group Hospitalier public Sud Oise GHPSO (Creil)
Subjects: Liver Cirrhosis, Male, Cirrhosis, [SDV]Life Sciences [q-bio], Severity of Illness Index, Bacterial / drug therapy, 0302 clinical medicine, Risk Factors, Liver Cirrhosis / complications, Hospital Mortality, Liver Failure / mortality, Heart Diseases / epidemiology, Endocarditis, Gastroenterology, Bacterial / mortality, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Liver Failure / physiopathology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Switzerland, medicine.medical_specialty, Heart Diseases, MEDLINE, Switzerland / epidemiology, 03 medical and health sciences, France / epidemiology, Internal medicine, Severity of illness, medicine, Humans, In patient, Cardiac Surgical Procedures, Aged, Retrospective Studies, Hepatology, business.industry, Case-control study, Liver failure, Retrospective cohort study, Endocarditis, Bacterial, medicine.disease, Bacterial / complications, Liver Cirrhosis / mortality, Case-Control Studies, business, Liver Failure
Abstract: International audience; Background: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC.Patients and methods: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013.Results: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P
Published: 2018

187. Diagnostic performance of MR imaging, coloscan and MRI/CT enterography for the diagnosis of pelvic endometriosis: CNGOF-HAS Endometriosis Guidelines

Author: Marcos Ballester, Pascal Rousset, Isabelle Thomassin-Naggara, Marc Bazot, E Daraï, Sofiane Bendifallah, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Gynécologie-obstétrique et médecine de la reproduction - Maternité [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Endométriose, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Coloscan, Uterosacral ligament, Entéro-IRM, Endometriosis, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Adnexal mass, 030218 nuclear medicine & medical imaging, IRM pelvienne, 03 medical and health sciences, 0302 clinical medicine, Diagnosis, Entéro-CT, medicine, Pelvic MRI, Diagnostic, 030219 obstetrics & reproductive medicine, Pelvic endometriosis, business.industry, Obstetrics and Gynecology, Clinical routine, medicine.disease, Mr imaging, 3. Good health, Entero-MRI, medicine.anatomical_structure, Reproductive Medicine, Vagina, Coloscanner, Ultrasonography, business, Nuclear medicine
Abstract: International audience; Diagnostic performance of MR imaging for the diagnosis of pelvic endometriosis are good. Even if some differences of performances exists according the location considered, the risk of misdiagnosis is lower than 10% for trained teams (NP2). The performance of pelvic MR imaging and surgery are quite similar to diagnose endometrioma (sensitivity and specificity>90%). A negative pelvic MR imaging allows to exclude deep pelvic endometriosis with a performance similar to surgery but a positive MR imaging is less accurate than surgery because of a high number of false positives (23%). Pelvic MR imaging is more sensitive and less specific than ultrasonography for the diagnosis of uterosacral ligament, vagina or recto vaginal septum (NP2). Pelvic ultrasonography is more sensitive than pelvic MR imaging for the diagnosis of colorectal location (NP3). Pelvic MR imaging is a reproducible technique for the diagnosis of pelvic endometriosis (NP3). Regarding, quality criteria of pelvic MR imaging, no data are enough to recommend a specific MR unit, digestive preparation, or a specific moment during the menstrual cycle to realize the examination. Vaginal and/or rectal opacification are options. Most of studies are based a protocol including 3D T2W and 3DT1W sequences. Gadolinium injection is useful to characterize a complex adnexal mass. In clinical routine, slices crossing the kidneys are useful to evaluate the presence of pyelo calic distension. ColoCT is an accurate technique to diagnose pelvic digestive endometriosis (rectosigmoide and iléocaecal) (NP3).; Les performances de l’IRM pelvienne pour le diagnostic d’endométriose sont bonnes. Même si des différences existent entre les différentes localisations, le risque de classement à tort est égal ou inférieur à 10 % pour les équipes entraînées (NP2). L’IRM pelvienne peut être considérée comme une technique diagnostique proche de la chirurgie pour le diagnostic d’endométriome ovarien (sensibilité et spécificité supérieures à 90 %). Une IRM pelvienne négative permet d’exclure des lésions d’endométriose pelvienne profonde avec une performance proche de la chirurgie alors qu’une IRM pelvienne positive est moins performante que la chirurgie en raison du nombre de faux positifs d’environ 23 % (NP1). L’IRM pelvienne est plus sensible et moins spécifique que l’échographie endovaginale pour le diagnostic des ligaments utérosacrés, du vagin, et de la cloison rectovaginale (NP2). L’échographie pelvienne est plus sensible que l’IRM pelvienne pour le diagnostic de l’endométriose du rectosigmoide (NP3). L’IRM pelvienne est une technique reproductible pour le diagnostic d’endométriose pelvienne (NP3). Concernant les critères de qualité de l’IRM pelvienne, aucune donnée suffisante dans la littérature ne permet de recommander une machine spécifique, une préparation préalable ou des conditions de réalisation spécifique au cours du cycle. L’opacification du vagin et/ou du rectum est une option. La plupart des études se basent sur des séquences multi planaires en T2 et T1 pour faire le diagnostic d’endométriose pelvienne. L’injection de gadolinium est utile pour caractériser une masse annexielle complexe. Les recommandations de bonne pratique sont de disposer de coupes passant par les reins et de faire une acquisition à vessie semi pleine pour ne pas gêner l’interprétation (accord d’expert). Le ColoCT est une technique performante pour le diagnostic d’endométriose pelvienne digestive du rectosigmoide et iléocaecale (NP3).
Published: 2018
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188. Where there is inflammation, treatment may reduce disability progression - No

Author: Sandra Vukusic, Gilles Edan, Jonchère, Laurent, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Empenn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Université de Rennes (UNIV-RENNES), Service de Neurologie [Lyon], CHU Lyon, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Multiple sclerosis, [SDV]Life Sciences [q-bio], Inflammation, medicine.disease, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Internal medicine, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Disability progression, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018
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189. Faecal calprotectin as surrogate marker of transmural healing assessed using MRI in patients with Crohn's disease

Author: Allimant, C., Messadeg, L., Quinard, R. Minet, Goutte, Marion, Bouvier, D., Goutorbe, F., Pereira, B., Bommelaer, G., Hordonneau, C., Buisson, A., Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Radiologie (LYON - Radio), CHU Lyon, Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier de la Côte Basque (CHCB), Unité de Biostatistique, CRLCC René Gauducheau, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Centre Hospitalier de la Côte Basque
Subjects: [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

190. A Perspective on the Interplay of Ultraviolet-Radiation, Skin Microbiome and Skin Resident Memory TCRαβ+ Cells

Author: VijayKumar Patra, Léo Laoubi, Jean-François Nicolas, Marc Vocanson, Peter Wolf, Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical University Graz, Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Human skin, Inflammation, Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Psoriasis, medicine, skin resident memory T cells, Microbiome, Tissue homeostasis, lcsh:R5-920, integumentary system, General Medicine, Atopic dermatitis, photomedicine, ultraviolet-radiation, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, inflammation, Perspective, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, skin microbiome, immune suppression, medicine.symptom, lcsh:Medicine (General), 030215 immunology, phototherapy
Abstract: International audience; The human skin is known to be inhabited by diverse microbes, including bacteria, fungi, viruses, archaea, and mites. This microbiome exerts a protective role against infections by promoting immune development and inhibiting pathogenic microbes to colonize skin. One of the factors having an intense effect on the skin and its resident microbes is ultraviolet-radiation (UV-R). UV-R can promote or inhibit the growth of microbes on the skin and modulate the immune system which can be either favorable or harmful. Among potential UV-R targets, skin resident memory T cells (TRM) stand as well positioned immune cells at the forefront within the skin. Both CD4+ or CD8+ αβ TRM cells residing permanently in peripheral tissues have been shown to play prominent roles in providing accelerated and long-lived specific immunity, tissue homeostasis, wound repair. Nevertheless, their response upon UV-R exposure or signals from microbiome are poorly understood compared to resident TCRγδ cells. Skin TRM survive for long periods of time and are exposed to innumerable antigens during lifetime. The interplay of TRM with skin residing microbes may be crucial in pathophysiology of various diseases including psoriasis, atopic dermatitis and polymorphic light eruption. In this article, we share our perspective about how UV-R may directly shape the persistence, phenotype, specificity, and function of skin TRM; and moreover, whether UV-R alters barrier function, leading to microbial-specific skin TRM, disrupting the healthy balance between skin microbiome and skin immune cells, and resulting in chronic inflammation and diseased skin.
Published: 2018
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191. Massive increase in monocyte HLA-DR expression can be used to discriminate between septic shock and hemophagocytic lymphohistiocytosis-induced shock

Author: Solenn Remy, Etienne Javouhey, Guillaume Monneret, Jack Hayman, Aurélie Portefaix, Fabienne Venet, Alexandre Belot, Morgane Gossez, Hospices Civils de Lyon, Paediatric Intensive Care Unit, Mother and Children University Hospital, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Rheumatism and autoimmune diseases (RAISE), Hospices Civils de Lyon, Immunology Laboratory, E. Herriot Hospital, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU-Lyon, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), and Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)
Subjects: BIOMARKER, EPIDEMIOLOGIE, Letter, Critical Care and Intensive Care Medicine, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, Lymphohistiocytosis, Hemophagocytic, Monocytes, 03 medical and health sciences, 0302 clinical medicine, Immune system, IMMUNE RESPONSE, SANTE, medicine, HLA-DR, Humans, Hemophagocytic lymphohistiocytosis, Septic shock, business.industry, Monocyte, Organ dysfunction, SEPTIC SHOCK, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Shock, HLA-DR Antigens, lcsh:RC86-88.9, medicine.disease, Shock, Septic, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Shock (circulatory), Immunology, Biomarker (medicine), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Biomarkers
Abstract: Clinical presentations of hemophagocytic lymphohistiocytosis (HLH) and septic shock share many similarities, including multiple organ dysfunction and overall clinical and biological symptoms. However, these life-threatening conditions require specific and opposing treatments. Currently, no single biomarker is available to differentiate septic shock from HLH at patient admission
Published: 2018
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192. Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study

Author: François Cotton, Jean-Amédée Roch, Boubakeur Belaroussi, Sandra Vukusic, Dominique Sappey-Marinier, Charles R.G. Guttmann, Françoise Durand-Dubief, Michele Cavallari, Matthieu Rousset, Muriel Rabilloud, Salem Hannoun, Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital [Boston], Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nehme and Therese Tohme Multiple Sclerosis Center, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon, Service de Neurologie [Lyon], CHU Lyon, Bioclinica SAS (B SAS), Bioclinica SAS, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, High resolution, relapsing–remitting, Lesion formation, Inversion recovery, Fluid-attenuated inversion recovery, multiple sclerosis, Lesion, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Magnetic resonance imaging, 0302 clinical medicine, T2 lesions, medicine, Humans, Longitudinal Studies, Multiple sclerosis lesion, medicine.diagnostic_test, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, 030104 developmental biology, Neurology, Disease Progression, Female, Neurology (clinical), Radiology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. Objective: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. Methods: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing–remitting MS (RRMS). Results: Active lesions ( n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. Conclusion: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an ‘inside-out’ genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response.
Published: 2015
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193. Adult-onset Still's disease

Author: Yvan Jamilloux, Mathieu Gerfaud-Valentin, Pascal Sève, Jean Iwaz, Service de Médecine Interne [Hôpital Croix Rousse, CHU Lyon], CHU Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry [Lausanne], Université de Lausanne = University of Lausanne (UNIL), Service de Biostatistique des Hospices Civils de Lyon, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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), and Université de Lausanne (UNIL)
Subjects: Adult, Adult-Onset, Immunology, Arthritis, Disease, Hemophagocytic lymphohistiocytosis, Adaptive Immunity, Adult-onset Still's disease, Proinflammatory cytokine, chemistry.chemical_compound, Tocilizumab, medicine, Immunology and Allergy, Humans, Innate, Genetic Predisposition to Disease, Anakinra, business.industry, Immunity, medicine.disease, Autoinflammatory Syndrome, Prognosis, Still's Disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, 3. Good health, Autoinflammatory disorder, chemistry, Macrophage activation syndrome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Hyperferritinemia, business, Still's Disease, Adult-Onset, medicine.drug
Abstract: International audience; First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (\textless20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD.
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194. Fewer complications after UKA than TKA in patients over 85 years of age: A case-control study

Author: Yannick Herry, Elvire Servien, Sébastien Lustig, Romain Gaillard, Quentin Ode, Philippe Neyret, Cécile Batailler, Service de chirurgie orthopédique, CHU Lyon Croix-Rousse, Hospices civils de Lyon, Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), and Centre Albert-Trillat
Subjects: musculoskeletal diseases, Male, medicine.medical_specialty, Knee Joint, medicine.medical_treatment, Population, Total knee arthroplasty, TOTAL KNEE ARTHROPLASTY, BIOMECANIQUE, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, UNICOMPARTMENTAL KNEE ARTHROPLASTY, Survivorship curve, Medicine, Humans, Orthopedics and Sports Medicine, In patient, Unicompartmental knee arthroplasty, education, Arthroplasty, Replacement, Knee, Retrospective Studies, Geriatrics, Aged, 80 and over, COMPLICATIONS, 030222 orthopedics, education.field_of_study, business.industry, Case-control study, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 030229 sport sciences, Osteoarthritis, Knee, 3. Good health, Surgery, Prosthesis Failure, Treatment Outcome, Patient Satisfaction, Case-Control Studies, GERIATRIC SURGERY, Female, Implant, GERIATRICS, business, Knee Prosthesis, Follow-Up Studies
Abstract: Introduction Implanting a knee prosthesis in patients aged over 85 years is not without risk. Unicompartmental knee arthroplasty (UKA) is reputed to show lower morbidity and mortality than total knee arthroplasty (TKA). Elderly patients with isolated unicompartmental osteoarthritis without specific contraindications are thus good candidates for this procedure. The present retrospective case-control study compared complications rates in elderly patients receiving UKA versus TKA. The study hypothesis was that UKA incurs fewer complications, with equivalent functional results. Material and methods Five hundred and forty-four UKAs were performed between 1987 and 2015; all patients aged 85 years or over (n = 30) were included, and age-matched at a rate of 1 UKA for 3 TKAs in our database of 4,216 TKA procedures. Mean age was 87.5 years (range, 85–92 years). The main endpoint was complications rate; secondary endpoints comprised satisfaction, IKS function and knee scores, and implant survival. Results Mean follow-up was 32 months (range, 12–118 months) for UKA and 34 months (range, 12–100 months) for TKA. The medical complications rate was significantly lower with UKA (6.7% versus 25.6%; P = 0.02), with no early mortality. IKS scores were identical between UKA and TKA groups at last follow-up: knee, 93.8 (95% CI [89.7–98.0]) versus 89.5 (95% CI [85.6–93.4]), P = 0.06; function, 63.8 (95% CI [53.1–74.5]) versus 67.0 (95% CI [61.3–72.7]), P = 0.62. Satisfaction rates were likewise identical: 96% and 97%, respectively (P = 0.77); and implant survivorship was identical (P = 0.54). Discussion Early medical complications were fewer after UKA than TKA in a population aged ≥ 85 years, with comparable clinical outcome. These results argue in favor of UKA in elderly patients with comorbidities. Level of evidence III, case-control study.
Published: 2017
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195. Cytomegalovirus infection in the first year after pediatric kidney transplantation

Author: Pascal Roy, Anita Duncan, Corentin Tanné, Pierre Cochat, Audrey Laurent, Émilie Frobert, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Service de Biostatistique des Hospices Civils de Lyon, Hospices Civils de Lyon (HCL), Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Lyon], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), 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), Service de Biostatistiques [Lyon], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Ganciclovir, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, 030232 urology & nephrology, Congenital cytomegalovirus infection, Asymptomatic, Cohort Studies, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Internal medicine, medicine, Valganciclovir, Viral prophylaxis, Humans, Child, Kidney transplantation, Retrospective Studies, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business.industry, Retrospective cohort study, Immunosuppression, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Kidney Transplantation, Transplant Recipients, 3. Good health, Transplantation, Nephrology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytomegalovirus Infections, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.symptom, Cytomegalovirus (CMV), business, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: International audience; Cytomegalovirus is common in adult recipients (prevalence of 40-90%). Children are typically seronegative but immunosuppression may prone to primary-infection or viral reactivation, with potentially severe consequences. CMV infection incidence in pediatric kidney transplant recipients has seldom been investigated. The aim of our study was to evaluate the incidence and timing of CMV infection during the first year after renal transplantation. We assembled a retrospective cohort of 136 children who had received a kidney transplant between 2003 and 2014 with a year follow-up. The patients were classified regarding CMV infection as high risk (D+/R-), intermediate risk (R+) or low risk (D-/R-). CMV infection was defined by the viral replication remaining asymptomatic whereas CMV disease concerned viral replication with clinical and/or biological symptoms. Oral valganciclovir was used as prophylaxis for high-risk recipients. A total of 38 patients (27.9%) developed CMV infection, 13 (40.6%) of the 32 D+/R-, 24 (45.3%) of the 53 R+ and 1 (2.0%) of the 51 D-/R-. Of these 38 infected patients, 10 developed tissue-invasive disease. During the first year after kidney transplantation, 27.9% of recipients developed CMV infection. This study confirms the influence of donor and recipient CMV status on infection propensity and highlights the importance of adequate follow-up for intermediate risk patients.
Published: 2017
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196. Hypothermic pulsatile preservation of kidneys from uncontrolled deceased donors after cardiac arrest - a retrospective study

Author: Vannary Meas Yedid, Thomas Rimmelé, Alexandre Faure, Palmina Petruzzo, Xavier Matillon, Lionel Badet, Emmanuel Morelon, Ricardo Codas, Olivier Thaunat, Maud Rabeyrin, Fabrice Danjou, William Hanf, Claire Delsuc, Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Saint Camille, Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Département de Pathologie [CHU Lyon-Sud - HCL], Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Alpes-Léman - CHAL, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Male, Time Factors, medicine.medical_treatment, 030232 urology & nephrology, Pulsatile flow, 030230 surgery, outcomes, Cohort Studies, 0302 clinical medicine, Warm Ischemia, Kidney transplantation, uncontrolled deceased donors, Graft Survival, Statistics, Organ Preservation, perfusion machine, Treatment Outcome, Anesthesia, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Perfusion, medicine.medical_specialty, Tissue and Organ Procurement, Risk Assessment, Statistics, Nonparametric, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, Resistance Index, Extracorporeal membrane oxygenation, medicine, Humans, Nonparametric, Cardiopulmonary resuscitation, Retrospective Studies, Transplantation, Inulin Clearance, business.industry, Retrospective cohort study, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Surgery, Heart Arrest, Linear Models, business, donor management, Follow-Up Studies
Abstract: Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 31.12.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with “in situ” cold perfusion or a normothermic regional perfusion. All kidneys were perfused on hypothermic (1-4°C) pulsatile perfusion machine (RM3, Waters Medical System) and discarded when RI≥0.5 mmHg/mL/min after 6 hours of perfusion. There was one (2.2%) primary non-function, while 37 recipients (84.1%) experienced delayed graft function. Graft survival was 97.6% at 1 and 3 post-transplantation years. Linear regression models showed that lower values of RI at the end of perfusion were associated to higher values of MDRD at 3 (p=0.049) and 6 months after transplantation (p=0.010) and to higher values of inulin clearance at 1 year (p=0.030). RI showed to be a useful tool to select uDCD kidneys allowing to achieve good clinical results. This article is protected by copyright. All rights reserved.
Published: 2017
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197. Functional mapping of factor VIII C2 domain

Author: Marc Delcourt, Jean-Luc Pellequer, Jean-Luc Plantier, Didier Saboulard, Claude Negrier, Shu-wen W. Chen, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-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), Service de Biochimie et Toxicologie Nucléaire (SBTN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), BIOMETHODES, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Mutant, MESH: Protein Structure, Secondary, 030204 cardiovascular system & hematology, Epitope, Protein Structure, Secondary, law.invention, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Structure-Activity Relationship, law, MESH: Chlorocebus aethiops, hemic and lymphatic diseases, Chlorocebus aethiops, MESH: Animals, MESH: von Willebrand Factor, C2 domain, Alanine, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Hematology, MESH: Factor VIII, MESH: COS Cells, MESH: Mutagenesis, Site-Directed, Biochemistry, MESH: Blood Coagulation, COS Cells, Recombinant DNA, Blood Coagulation Tests, Protein Binding, MESH: Mutation, MESH: Alanine, In silico, Cofactor, 03 medical and health sciences, Structure-Activity Relationship, Von Willebrand factor, von Willebrand Factor, Animals, Humans, MESH: Protein Binding, Blood Coagulation, Factor VIII, MESH: Humans, MESH: Blood Coagulation Tests, Protein Structure, Tertiary, 030104 developmental biology, Mutation, biology.protein, Mutagenesis, Site-Directed
Abstract: SummaryThe factor VIII (FVIII) is a cofactor of the coagulation cascade. The FVIII C2 domain is a critical domain that participates in the interactions with the von Willebrand factor and the phospholipidic surfaces. To assess the importance of each residue of this domain in the maintenance of the structure and the function of FVIII, a number (n=139) of mutants were generated by substituting the original residues, from Ser2173 to Gly2325, by an alanine. Mutants were built within a complete B domain- deleted FVIII and expressed in COS-1 cells. Mutant antigen levels and procoagulant activities were measured. Two in silico analyses, a sliding average procedure and an analysis of the mutation energy cost were conducted in parallel on the FVIII structure. Both results were in agreement with the functional data, and illustrated the benefit of using such strategies prior to targeting specific residues in the aim of generating active recombinant molecules. The functional assays identify the residues that are important to maintaining the structure of the C2 domain, mainly those forming β-sheet, and those that can afford substitution, establishing a detailed functional relation with the available crystallographic data. This study provided a comprehensive functional mapping of the FVIII C2 domain and discussed the implication of specific residues in respect to the maintenance in the activity and structure stability, the efficiency in secretion, the binding to phospholipids and the formation of epitope.
Published: 2017
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198. Accessibilité spatiale aux médicaments utilisés dans le traitement d’une pathologie rare : exemple de l’hémophilie

Author: Leroy, Vincent, Freyssenge, Julie, Florent, Renard, Tazarourte, Karim, Negrier, Claude, Chamouard, Valerie, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Urgences Médicales, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Université de Lyon, Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), and Freyssenge, Julie
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

199. Stereoelectroencephalography and surgical outcome in polymicrogyria-related epilepsy: A multicentric study

Author: Maillard, Louis Georges, Tassi, Laura, Bartolomei, Fabrice, Catenoix, Hélène, Dubeau, François, Szurhaj, William, Kahane, Philippe, Nica, Anca, Marusic, Petr, Mindruta, Ioana, Chassoux, Francine, Ramantani, Georgia, University of Zurich, Ramantani, Georgia, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre « Claudio-Munari » pour la chirurgie de l'épilepsie et du Parkinson, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Service de Neurophysiologie Clinique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Service de neurologie fonctionnelle et d'épileptologie, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de mathématiques [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Noyaux gris centraux, Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 2728 Neurology (clinical), [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Neurology, 10036 Medical Clinic, 2808 Neurology, Clinical Neurology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 610 Medicine & health
Abstract: International audience; OBJECTIVE: We aimed to (1) assess the concordance between various polymicrogyria (PMG) types and the associated epileptogenic zone (EZ), as defined by stereoelectroencephalography (SEEG), and (2) determine the postsurgical seizure outcome in PMG-related drug-resistant epilepsy. METHODS: We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy. RESULTS: Mean age at SEEG or surgery was 28.3 years (range, 2-50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%) patients additionally had schizencephaly, heterotopia, or focal cortical dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74%, and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but 1 PMG patient with corticectomy or hemispherotomy had a unilateral PMG. At last follow-up (mean, 4.6 years; range, 1-16), 28 (72%) patients remained seizure free. Shorter epilepsy duration to surgery was an independent predictor of seizure freedom. INTERPRETATION: PMG-related drug-resistant epilepsy warrants a comprehensive presurgical evaluation, including SEEG investigations in most cases, given that the EZ may only partially overlap with the PMG or include solely remote cortical areas. Seizure freedom is feasible in a large proportion of patients. PMG extent should not deter from exploring the possibility of epilepsy surgery. Our data support the early consideration of epilepsy surgery in this patient group. Ann Neurol 2017;82:781-794.
Published: 2017
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200. Association de radiothérapie externe et de curiethérapie pour les cancers de la prostate

Author: Gilles Créhange, Alberto Bossi, O. Chapet, S. Horn, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Service d’Oncologie Médicale [CHU Lyon Sud], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Ciblage thérapeutique en Oncologie ( EA3738 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy ( IGR ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Département de Radiation oncologie, CGFL, Laboratoire d'Electronique, d'Informatique et d'Image UMR CNRS 6306 ( Le2i ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Arts et Métiers ( ENSAM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, UNICANCER-UNICANCER, Laboratoire d'Electronique, d'Informatique et d'Image [EA 7508] (Le2i), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, and HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, medicine.medical_specialty, Standard of care, medicine.medical_treatment, Brachytherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Boost, Radiothérapie, Cancer, Gynecology, Radiotherapy, business.industry, Genitourinary system, medicine.disease, 3. Good health, Radiation therapy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Curiethérapie, Hormonal therapy, business
Abstract: International audience; Brachytherapy as sole treatment is standard of care for D’Amico classification low-risk prostate cancer. For intermediate and high-risk patients, brachytherapy can be associated to external beam radiation therapy to better take into account the risk of extracapsular effraction and/or seminal vesicle involvement. Three randomized studies have shown that this association increases freedom from relapse survival compared to exclusive external beam radiation therapy. This benefit is not shown for overall survival. The addition of a hormonal therapy to this association is most likely mandatory for high-risk patients, and needs to be confirmed for intermediate risk patients. Both high-dose rate and low-dose rate brachytherapy are suitable with similar biochemical disease free survival rates. High-dose rate brachytherapy seems to have a better genitourinary tolerance profile, while low-dose rate brachytherapy is an easier process and has a more widespread expertise.; La curiethérapie exclusive est un traitement standard des cancers de prostate de bas risque selon la classification de D’Amico. Pour les cancers de risque intermédiaire à haut risque, il est proposé de l’associer à une radiothérapie externe afin de mieux prendre en compte le risque d’effraction capsulaire et/ou d’atteinte des vésicules séminales. Trois études randomisées ont montré que cette association améliorait la probabilité de survie sans récidive, par rapport à une radiothérapie externe exclusive. Ce bénéfice n’a pas été retrouvé en termes de survie globale. L’association d’une hormonothérapie est certainement nécessaire pour les cancers à haut risque. Sa place reste clairement à définir pour les cancers de prostate de risque intermédiaire pris en charge par cette association de radiothérapie externe et de curiethérapie. Les techniques de curiethérapie de haut ou de bas débit de dose sont adaptées, avec des résultats similaires en termes de contrôle biochimique. Le haut débit semble avoir un profil de tolérance urinaire meilleur. Le bas débit a l’avantage de l’expertise d’un plus grand nombre de centres et de la simplicité.Abstract
Published: 2017
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