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201. Multifaceted intervention to improve obstetric practices: The OPERA cluster-randomized controlled trial

Author: Antoine Duclos, Sandrine Touzet, Norbert Winer, Corinne Dupont, Muriel Rabilloud, René-Charles Rudigoz, Cyril Huissoud, Laurent Gaucher, Florent Boutitie, Jacques Lansac, Bernard Branger, Cyrille Colin, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service d'obstétrique-gynécologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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 Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Réseau Sécurité Naissance - Naître Ensemble, Nantes, Réseau périnatal PerinatCentre, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie et d'Obstétrique (CHU Lyon), Pôle Information Médicale Evaluation Recherche (IMER), Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut cellule souche et cerveau (SBRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Program evaluation, Pediatrics, medicine.medical_specialty, Psychologists, Disease cluster, Logistic regression, law.invention, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, Intervention (counseling), mental disorders, medicine, Humans, Cluster-randomized trial, 030212 general & internal medicine, Cluster randomised controlled trial, Professional practices, Perinatal Mortality, Quality of Health Care, Morbidity and mortality conferences, 030219 obstetrics & reproductive medicine, Perinatal morbidity and mortality, business.industry, Incidence (epidemiology), Infant, Newborn, Obstetrics and Gynecology, Quality Improvement, 3. Good health, Perinatal morbidity, Obstetrics, Reproductive Medicine, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objective Suboptimal care contributes to perinatal morbidity and mortality. We investigated the effects of a multifaceted program designed to improve obstetric practices and outcomes. Study design A cluster-randomized trial was conducted from October 2008 to November 2010 in 95 French maternity units randomized either to receive an information intervention about published guidelines or left to apply them freely. The intervention combined an outreach visit with a morbidity/mortality conference (MMC) to review perinatal morbidity/mortality cases. Within the intervention group, the units were randomized to have MMCs with or without clinical psychologists. The primary outcome was the rate of suboptimal care among perinatal morbidity/mortality cases. The secondary outcomes included the rate of suboptimal care among cases of morbidity, the rate of suboptimal care among cases of mortality, the rate of avoidable morbidity and/or mortality cases, and the incidence of, morbidity and/or mortality. A mixed logistic regression model with random intercept was used to quantify the effect of the intervention on the main outcome. Results The study reviewed 2459 cases of morbidity or mortality among 165,353 births. The rate of suboptimal care among morbidity plus mortality cases was not significantly lower in the intervention than in the control group (8.1% vs. 10.6%, OR [95% CI]: 0.75 [0.50-1.12], p = 0.15. However, the cases of suboptimal care among morbidity cases were significantly lower in the intervention group (7.6% vs. 11.5%, 0.62 [0.40-0.94], p = 0.02); the incidence of perinatal morbidity was also lower (7.0 vs. 8.1‰, p = 0.01). No differences were found between psychologist-backed and the other units. Conclusions The intervention reduced the rate of suboptimal care mainly in morbidity cases and the incidence of morbidity but did not succeed in improving morbidity plus mortality combined. More clear-cut results regarding mortality require a longer study period and the inclusion of structures that intervene before and after the delivery room. (ClinicalTrials.gov ID: NCT02584166)
Published: 2017
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202. MRI remission after therapeutic intervention is associated with more time spent in clinical corticosteroids-free remission and decreased risk of surgery in Crohn's disease

Author: Buisson, A., Hordonneau, C., Goutorbe, F., Allimant, C., Goutte, Marion, Reymond, M., Pereira, B., Bommelaer, G., 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), Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Radiologie (LYON - Radio), CHU Lyon, Centre Hospitalier de la Côte Basque (CHCB), Délégation à la Recherche Clinique et à l'Innovation (DRCI), 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: 2017

203. Definition of therapeutic response criteria using MRI in Crohn's disease patients treated with anti-TNF therapy: a multicenter prospective study (the IRMA study)

Author: Constance Hordonneau, Reimund, Cédric Duron, Bruno Pereira, Jean-Marie, Anne-Laure Boucher, Camille Sautel, Marion Goutte, Gilles Bommelaer, Guillaume Bouguen, Leila Messadeg, Michel Dapoigny, Julien Scanzi, Felix Goutorbe, Anthony Buisson, 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), Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Radiologie (LYON - Radio), CHU Lyon, CHU Pontchaillou [Rennes], Centre Hospitalier de la Côte Basque, Departement de Gastroentérologie, Hôpital de Hautepierre [Strasbourg], Hôpital d'Issoire, Partenaires INRAE, Hôpital de Montluçon, Délégation à la Recherche Clinique et à l'Innovation (DRCI), and Centre Hospitalier de la Côte Basque (CHCB)
Subjects: 0301 basic medicine, medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, Surgery, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Anti-TNF therapy, business, Prospective cohort study, Response criteria, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

204. Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization

Author: Ali Dalloul, Yves Bertrand, Christine Bellanné-Chantelot, Julie Nguyen, Françoise Bachelerie, Sarah Beaussant-Cohen, Jean Donadieu, Marie-Laure Aknin, Fawzia Louache, Monika Wittner, Vincent Biajoux, Marion Espéli, Karl Balabanian, Françoise Gaudin, Vincent Rondeau, Christelle Freitas, Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inflammation, chimiokines et immunopathologie, Institut Paris-Saclay d’Innovation Thérapeutique (IPSIT), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut Gustave Roussy (IGR), Institut Paris Saclay d’Innovation Thérapeutique (IPSIT), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Service d’Hémato-Oncologie Pédiatrique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre français des neutropénies chroniques sévères, Centre de référence des déficits Immunitaires Héréditaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Balabanian, Karl, Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, medicine.medical_treatment, Cellular differentiation, [SDV]Life Sciences [q-bio], Gene Expression, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], CXCR4, 0302 clinical medicine, Homologous desensitization, Immunology and Allergy, Lymphocytes, Child, Research Articles, ComputingMilieux_MISCELLANEOUS, Bone Marrow Transplantation, Desensitization (medicine), Reverse Transcriptase Polymerase Chain Reaction, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Differentiation, Flow Cytometry, 3. Good health, Cell biology, Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Warts, Stem cell, Signal Transduction, Adult, Receptors, CXCR4, Cell Survival, Primary Immunodeficiency Diseases, Immunology, Bone Marrow Cells, Mice, Transgenic, Biology, Article, 03 medical and health sciences, medicine, Animals, Humans, Lymphocyte Count, Progenitor cell, Immunologic Deficiency Syndromes, Hematopoietic Stem Cells, 030104 developmental biology, Mutation, Bone marrow, Spleen
Abstract: Using a mouse model harboring a naturally occurring WHIM syndrome–linked gain-of-function Cxcr4 mutation, Freitas et al. show that Cxcr4 desensitization is critical for quiescence/cycling balance of murine short-term hematopoietic stem cells and their differentiation into multipotent and downstream lymphoid-biased progenitors., The CXCL12/CXCR4 signaling exerts a dominant role in promoting hematopoietic stem and progenitor cell (HSPC) retention and quiescence in bone marrow. Gain-of-function CXCR4 mutations that affect homologous desensitization of the receptor have been reported in the WHIM Syndrome (WS), a rare immunodeficiency characterized by lymphopenia. The mechanisms underpinning this remain obscure. Using a mouse model with a naturally occurring WS-linked gain-of-function Cxcr4 mutation, we explored the possibility that the lymphopenia in WS arises from defects at the HSPC level. We reported that Cxcr4 desensitization is required for quiescence/cycling balance of murine short-term hematopoietic stem cells and their differentiation into multipotent and downstream lymphoid-biased progenitors. Alteration in Cxcr4 desensitization resulted in decrease of circulating HSPCs in five patients with WS. This was also evidenced in WS mice and mirrored by accumulation of HSPCs in the spleen, where we observed enhanced extramedullary hematopoiesis. Therefore, efficient Cxcr4 desensitization is critical for lymphoid differentiation of HSPCs, and its impairment is a key mechanism underpinning the lymphopenia observed in mice and likely in WS patients.
Published: 2017
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205. Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features

Author: Adrian Ion-Mărgineanu, Gabriel Kocevar, Claudio Stamile, Diana M. Sima, Françoise Durand-Dubief, Sabine Van Huffel, Dominique Sappey-Marinier, 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), Department of Electrical Engineering [Leuven] (ESAT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), IMEC (IMEC), Icometrix [Leuven], Service de Neurologie [Lyon], CHU Lyon, 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: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Machine learning, computer.software_genre, multiple sclerosis, 030218 nuclear medicine & medical imaging, lcsh:RC321-571, Lesion, 03 medical and health sciences, 0302 clinical medicine, medicine, 10. No inequality, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, Clinically isolated syndrome, Expanded Disability Status Scale, medicine.diagnostic_test, SISTA, business.industry, General Neuroscience, Multiple sclerosis, Magnetic resonance spectroscopic imaging, McDonald criteria, Magnetic resonance imaging, longitudinal analysis, medicine.disease, Linear discriminant analysis, lesion load, 3. Good health, machine learning, magnetic resonance spectroscopic imaging, Artificial intelligence, EDSS, medicine.symptom, business, computer, 030217 neurology & neurosurgery, Neuroscience
Abstract: Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N-acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests. Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features. Conclusions: Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms. ispartof: Frontiers in Systems Neuroscience vol:11 issue:JUL ispartof: location:Switzerland status: published
Published: 2017
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206. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Author: Sylvain Manfredi, Eric Terrebonne, Gael Deplanque, Jean-Yves Scoazec, Anne-Laure Ran-Royo, Marc Ferec, Guillaume Cadiot, Eric Maringe, C. Desauw, Philippe Rougier, Thomas Aparicio, Castex, Guillaume Geslin, Jean-François Seitz, François Dewaele, Karine Bouhier-Leporrier, Vincent Hautefeuille, Anne Thirot-Bidault, Olivia Hentic, G. Roquin, David Tougeron, Olivier Dubreuil, C. Rebischung, Laetitia Dahan, Ivan Borbath, Jean-Louis Legoux, Laurent Bedenne, Sandrine Lavau denes, Catherine Ligeza, Mathieu Baconnier, K. Le Malicot, Laurent Cany, Côme Lepage, Thierry Lecomte, Céline Lepère, I. Bonnet, Valérie Rossi, Isabelle Wanicki Caron, Laetitia Stephanie, Cedric Lecaille, Eric Baudin, Thomas Walter, David Malka, Patricia Niccoli, Vincent Bourgeois, Etienne Suc, Joël Guigay, Romain Coriat, Rosine Guimbaud, Catherine Lombard-Bohas, Caroline Petorin, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Valenciennes, CHU Toulouse [Toulouse], Hôpital Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU de Lille, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital de la source, CHU Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], 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), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHU Amiens-Picardie, Hôpital Duchenne, CH Boulogne sur Mer, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Polyclinique Bordeaux Nord Aquitaine, Hôpital Michallon, CH du Haut Anjou (Château-Gontier), CH Annecy Genevois, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du pays de Morlaix, Hôpital Saint-Joseph, Assistance Publique-Hôpitaux de Paris, Cabinet privé des Dr Geslin Provost (Vannes), CHU Rouen, Normandie Université (NU), CHU Dupuytren, CHU Dijon, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Hospices Civils de Beaune [Centre hospitalier de Beaune], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Côte d'Azur (UCA)-UNICANCER
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Carboplatin, Cohort Studies, 03 medical and health sciences, Gastrointestinal cancer, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Neoplasm Metastasis, Prospective cohort study, Aged, Etoposide, Gastrointestinal Neoplasms, Univariate analysis, Performance status, business.industry, Large cell, Hazard ratio, Ki67 index, medicine.disease, Prognosis, 3. Good health, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Treatment, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Female, Cisplatin, business, Cohort study
Abstract: IF 6.029; International audience; BackgroundDiagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.Patients and methodsAll patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.Results253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).ConclusionsWe report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.
Published: 2017
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207. Measles virus infection of human keratinocytes: Possible link between measles and atopic dermatitis

Author: Geraldine Gourru-Lesimple, Sophie Grande, Cyrille Mathieu, Louis Marie Bloyet, Cindy G. Boer, Catherine Goujon, Katarzyna Tomczak, Céline Giraud, Catherine Cornu, Jean François Jégou, Branka Horvat, Vanessa Guillaume-Vasselin, Thomas Thevenet, Immunobiologie des infections virales – Immunobiology of Viral Infections (IbIV), 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), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, hospices civils de Lyon, 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), 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: 0301 basic medicine, Keratinocytes, Male, Biopsy, Dermatitis, Biochemistry, 0302 clinical medicine, Multiplicity of infection, Chlorocebus aethiops, Medicine, Prospective Studies, Skin, biology, Vaccination, Atopic dermatitis, Middle Aged, CC, Rash, 3. Good health, Chemokines, CC, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Chemokines, Adult, Thymic stromal lymphopoietin, Dermatology, Measles, Atopic, Dermatitis, Atopic, Cell Line, Cercopithecus aethiops, Measles virus, 03 medical and health sciences, Thymic Stromal Lymphopoietin, Double-Blind Method, Humans, Animals, Immune response, Molecular Biology, Vero Cells, business.industry, Chemokine CCL26, biology.organism_classification, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, Immune System, Immunology, Measles vaccine, business, 030215 immunology
Abstract: International audience; BACKGROUND: Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. OBJECTIVE: We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. METHODS: We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. RESULTS: We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. CONCLUSIONS: Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease.
Published: 2017
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208. Intérêt de l’analyse de résidus de toilettes sèches collectés lors d’un festival de musique électronique pour le suivi de consommation de drogues récréatives

Author: Bottinelli, Charline, Boucher, Alexandra, Airieau, Antinéa, Bayard, R., Bévalot, Fabien, Laboratoire Lat Lumtox, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Déchets Eaux Environnement Pollutions (DEEP), Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)
Subjects: Street drug analysis Designer drugs analysis Toilet facilities Waste water analysis, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [SDE]Environmental Sciences, Stupéfiants Nouveaux produits de synthèse Toilettes sèches Eaux usées, [CHIM]Chemical Sciences
Abstract: International audience; SummaryObjectiveAnalyses of substances seized by police or customs reveal dozens of different recreational drugs on the French market each year. It is difficult to assess the actual consumption of these substances, as only a few are found on analysis of biological samples. The objective of the present study was to assess the contribution of analyzing dry-toilet samples taken at a rave party as a means of monitoring recreational substances consumption.MethodEleven dry-toilet residue samples were analyzed. After liquid-phase extraction and derivatization (acetylation), GC-MS General Unknown Screening and targeted GC-MS/MS screening for 21 molecules were performed.ResultsEighteen substances including medical drugs and metabolites were identified. The highest concentration was for 3,4-methylenedioxymethamphetamine (MDMA), followed by amphetamine, benzoylecgonine and ketamine. The only designer drug found at this event was 1-(3-chlorophenyl)-piperazine (mCPP).DiscussionAlthough only one designer drug was detected, due perhaps to limitations in analytic technique, specificities of consumption at the particular event or rapid metabolism of certain molecules, dry-toilet residue analysis is a useful means of monitoring recreational substances consumption.; RésuméObjectifLes analyses de saisies douanières ou policières mettent en évidence la circulation sur le territoire français de plusieurs dizaines de substances récréatives différentes chaque année. Il est complexe de caractériser la consommation réelle de ces substances puisque seules quelques-unes sont retrouvées lors d’analyses de prélèvements biologiques. La présente étude avait pour objectif d’évaluer l’intérêt de l’analyse de résidus de toilettes sèches, issus d’un festival de musique électronique, comme outil de suivi de consommation de substances récréatives.MéthodeOnze échantillons de résidus de toilettes sèches ont été analysés. Après extraction en phase liquide et dérivation (acétylation), un dépistage large (screening) par chromatographie en phase gazeuse couplée à la spectrométrie de masse (GC-MS) ainsi qu’un criblage de 21 molécules par chromatographie gazeuse couplée à la spectrométrie de masse en tandem (GC-MS/MS) ont été réalisés.RésultatsDix-huit substances dont des médicaments et des métabolites ont été identifiés. La molécule la plus concentrée était la 3,4-méthylènedioxyméthamphétamine (MDMA) puis l’amphétamine, la benzoylecgonine et la kétamine. En termes de nouveaux produits de synthèse (NPS), seule de la 1-(3-chlorophenyl)-pipérazine (mCPP) a été détectée sur le festival ciblé.DiscussionMalgré le faible nombre de NPS détecté, pouvant être dû aux limites de la technique analytique, l’absence de consommation sur cet évènement ou la forte métabolisation de ces molécules, l’analyse des résidus de toilettes sèches est un outil intéressant pour le suivi de la consommation de substances récréatives.
Published: 2017
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209. dUTPase ( DUT ) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure

Author: Lorella Marselli, Sophie Romero, Cécile Julier, Baz Baz, Jean-François Gautier, Anne Philippi, Céline Besse, Sarah Ivanoff, Reinaldo Sousa Dos Santos, Piero Marchetti, Marc Nicolino, Decio L. Eizirik, Gérard Socié, Julien Masliah-Planchon, Delphine Bacq, Mathilde Daures, Laura Marroquí, Jean Soulier, Valérie Senée, Université libre de Bruxelles (ULB), UMR958 Protozoaires Entéricoles des Volailles, INRA/ENVL, Islet Cell Laboratory, University of Pisa - Università di Pisa, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie pédiatrique [CHU Lyon-Hospices Civils de Lyon], Hospices Civils de Lyon (HCL), Hôpital Saint-Louis, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université Libre de Bruxelles [Bruxelles] (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Computer Science Department [Bruxelles] (ULB), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Genetics, Mutation, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Bone marrow failure, Consanguinity, Bone Marrow Aplasia, Biology, medicine.disease, medicine.disease_cause, 3. Good health, 03 medical and health sciences, Diabetes mellitus genetics, 030104 developmental biology, Internal Medicine, medicine, Missense mutation, Exome, Gene, ComputingMilieux_MISCELLANEOUS
Abstract: We describe a new syndrome characterized by early-onset diabetes associated with bone marrow failure, affecting mostly the erythrocytic lineage. Using whole-exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (National Center for Biotechnology Information Gene ID 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, whereas none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation. This replicated observation probability was highly significant, thus confirming the role of this DUT mutation in this syndrome. DUT is a key enzyme for maintaining DNA integrity by preventing misincorporation of uracil into DNA, which results in DNA toxicity and cell death. We showed that DUT silencing in human and rat pancreatic β-cells results in apoptosis via the intrinsic cell death pathway. Our findings support the importance of tight control of DNA metabolism for β-cell integrity and warrant close metabolic monitoring of patients treated by drugs affecting dUTP balance.
Published: 2017
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210. App, psen1, and psen2 mutations in early-onset alzheimer disease:a genetic screening study of familial and sporadic cases

Author: Lanoiselée, Hélène-Marie, Nicolas, Gaël, Wallon, David, Rovelet-Lecrux, Anne, Lacour, Morgane, Rousseau, Stéphane, Richard, Anne-Claire, Pasquier, Florence, Rollin-Sillaire, Adeline, Martinaud, Olivier, Quillard-Muraine, Muriel, De La Sayette, Vincent, Boutoleau-Bretonnière, Claire, Etcharry-Bouyx, Frédérique, Chauviré, Valérie, Sarazin, Marie, Le Ber, Isabelle, Epelbaum, Stéphane, Jonveaux, Thérèse, Rouaud, Olivier, Ceccaldi, Mathieu, Felician, Olivier, Godefroy, Olivier, Formaglio, Maite, Croisile, Bernard, Auriacombe, Sophie, Chamard, Ludivine, Vincent, Jean-Louis, Sauvee, Mathilde, Marelli-Tosi, Cecilia, Gabelle, Audrey, Ozsancak, Canan, Pariente, Jérémie, Paquet, Claire, Hannequin, Didier, Campion, Dominique, CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional d'Orléans (CHRO), Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de neurologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie [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 neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sainte Anne [Paris], 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), Service de Neurologie [Lyon], CHU Lyon, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Département de neurologie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), CHU Toulouse [Toulouse], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université 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 Hospitalier Régional d'Orléans (CHR), Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, Heredity, Physiology, Substitution mutation, Gene Identification and Analysis, Research and Analysis Methods, Biochemistry, Nervous System, Amyloid beta-Protein Precursor, Database and Informatics Methods, Alzheimer Disease, Presenilin-2, Mental Health and Psychiatry, Presenilin-1, Genetics, Medicine and Health Sciences, Humans, Genetic Testing, Age of Onset, Cerebrospinal Fluid, Mutation databases, Biology and Life Sciences, Neurodegenerative Diseases, Genetic screens, Middle Aged, Alzheimer's disease, Body Fluids, Mutation detection, Biological Databases, Neurology, Mutation, Female, Dementia, France, Anatomy, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: Background Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. Methods and findings We report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Conclusions Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only. Among the 90 distinct mutations found in the whole sample of families and isolated cases, definite pathogenicity is currently established for only 77%, emphasizing the need to pursue the effort to classify variants., In a cohort including patients with familial Alzheimer disease as well as sporadic cases of early-onset Alzheimer disease, Dominique Campion and colleagues identify previously unreported mutations to PSEN1 and PSEN2., Author summary Why was this study done? Mutations in the amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes are a known cause of familial, early-onset Alzheimer disease (EOAD) (onset below age 65). However, in order to improve genetic counseling, it is necessary to report mutational screening from large cohorts of patients. What did the researchers do and find? In the present study, we performed sequencing of the APP, PSEN1, and PSEN2 genes in EOAD families and in 129 sporadic cases. Mutations were identified in 170 EOAD families and in 18 sporadic cases. In 10 sporadic cases, we showed that the mutation was absent in the parents, indicating that it occurred “de novo.” What do these findings mean? Sufficient evidence of pathogenicity is reached for 77% of the 90 distinct mutations identified in this sample, allowing their use in genetic counseling. Our results suggest a potential benefit to screening nonfamilial Alzheimer disease (AD) cases with onset before 50 y for APP, PSEN1, and PSEN2 mutations.
Published: 2017
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211. In situ analysis by SEM-EDX spectroscopy of 10 sarcoidosis cases from MINASARC study

Author: Catherine Cavalin, Nathalie Freymond, Olivia Freynet, Michel Vincent, C. Chemarin, Paul-André Rosental, F. Arbib, Ana-Maria Sfarghiu, Marianne Kambouchner, Christophe Pison, Jean-François Mornex, Mickaël Catinon, Françoise Thivolet, Jean-François Bernaudin, Dominique Valeyre, 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]), 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), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Institut National de la Recherche Agronomique (INRA)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), 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), Clinique de pneumologie, CHU Grenoble, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Rétrovirus et Pathologie Comparée (RPC), 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-Ecole Nationale Vétérinaire de Lyon (ENVL), Études sociales et politiques des populations de la protection sociale et de la santé, Centre d'études européennes et de politique comparée (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre de Mise en Forme des Matériaux (CEMEF), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Physiopathologie des maladies génétiques d'expression pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris Dauphine-PSL, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po), Centre National de la Recherche Scientifique (CNRS)-PSL Research University (PSL)-MINES ParisTech - École nationale supérieure des mines de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Paris Dauphine-PSL-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: medicine.diagnostic_test, Scanning electron microscope, business.industry, Energy-dispersive X-ray spectroscopy, inorganic exposome, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, [SPI]Engineering Sciences [physics], Tissue sections, medicine.anatomical_structure, In situ analysis, Biopsy, medicine, Sarcoidosis, Lymph, sarcoidosis, Nuclear medicine, business, MINARSAC, Lymph node, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction: MINASARC is a case-control study designed to assess the inorganic “exposome” by a specific questionnaire concomitantly with the mineralogical analysis (MA) of Broncho-Alveolar Lavage (BAL) by transmission electron microscopy (MA-TEM) and paraffin embedded biopsy by scanning electron microscopy (MA-SEM). We report the results obtained by MA-SEM from 10 sarcoidosis cases. Objectives: To compare the results of MA-SEM and MA-TEM. Methods: 5 mediastinal lymph nodes obtained by endobronchial ultrasound trans-bronchial needle aspiration (EBUS/TBNA) and 5 bronchial biopsies (BB) were studied by SEM-EDX. Results: * + to ++++: level of particles load Discussion and conclusion: MA-SEM on tissue sections is feasible and may give potential interesting results. In one manicurist (n°4), it identified silica particles in the lymph node and a high level in BAL. In a fire safety worker (n°10), it identified steel particles associated to a steel overload in the BAL. However, we have to be cautious for interpretation of EBUS/TBNA collected samples, as we identified FeCrNi and TiNi particles compatible with metal particles release from needles used for TBNA, as already reported [Gounant et al., Chest 2010]. MA-SEM on paraffin embedded biopsies allows to determine the chemical composition of particles observed in the preserved structures of tissues. It offers additional information on the patient9s exposure to inorganic dusts.
Published: 2017
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212. Magnetic resonance index of activity (MaRIA) and Clermont score are two MRI indices which are highly and equally effective in detecting mucosal healing in Crohn's disease

Author: C. Allimant, Constance Hordonneau, Anthony Buisson, Gilles Bommelaer, Maud Reymond, Bruno Pereira, Marion Goutte, 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), Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Délégation à la Recherche Clinique et à l'Innovation (DRCI), Département de Radiologie (LYON - Radio), and CHU Lyon
Subjects: Crohn's disease, medicine.medical_specialty, Pathology, Index (economics), Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Magnetic resonance imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, mucosal healing, 03 medical and health sciences, 0302 clinical medicine, crohn’s disease, 030220 oncology & carcinogenesis, Mucosal healing, Internal medicine, clermont score, MRI remission, medicine, 030211 gastroenterology & hepatology, business
Abstract: International audience; BACKGROUND: Magnetic resonance index of activity (MaRIA) and Clermont score are currently the two main MRI indices that have been validated compared to endoscopy in Crohn's disease (CD). AIMS: To compare the accuracy of MaRIA and Clermont score in assessing CD mucosal healing. METHODS: Fourty-four CD patients underwent prospectively and consecutively MRI and colonoscopy. RESULTS: Considering 207 segments, MaRIA>7 and Clermont score>8.4 demonstrated substantial accuracy to detect endoscopic ulcerations (73.9% and 74.0%, respectively) and presented with high specificity (82.1% and 81.3%) and high negative predictive value (NPV) (82.1% and 82.4%) for MaRIA and Clermont score, respectively. The sensitivity for detecting deep ulcerations was 90.9% for both MaRIA>11 and Clermont score>12.5, with a specificity of 82.0% and 80.0%, respectively. Among 44 patients, deep MRI remission predicted mucosal healing with specificity=85.3% and NPV=85.3% according to Barcelona criteria (no segmental MaRIA>7), and specificity=88.2% and NPV=85.7% according to Clermont criteria (no segmental Clermont score>8.4). In addition, MRI remission predicted mucosal healing with specificity=76.5% and NPV=86.7% according to Barcelona criteria (no segmental MaRIA>11), and specificity=79.4% and NPV=84.4% according to Clermont criteria (no segmental Clermont score>12.5). CONCLUSION: MaRIA and Clermont score are equally effective in detecting CD endoscopic ulcerations supporting their use as therapeutic endpoints.
Published: 2017

213. Characteristics in limbic encephalitis with anti–adenylate kinase 5 autoantibodies

Author: Sabine Brugière, Christine Lebrun-Frenay, Eve Chanson, Bastien Joubert, Véronique Rogemond, Le-Duy Do, Thomas de Brouker, François Ducray, Maïté Formaglio, François Tison, Jonathan Curot, Virginie Desestret, Yohann Couté, Jean-Yves Delattre, J. Honnorat, Catherine Thomas-Antérion, Laura Borrega, Jean-Christophe Antoine, Brice Laurens, Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Neurologie [Lyon], CHU Lyon, French Reference Center on Paraneoplastic Neurological Syndrome, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de neurologie, Hôpital Bellevue, Université de Bordeaux (UB), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Toulouse [Toulouse], Department of Neurology, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], 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 Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Neurologie [CHU de Saint-Étienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre Sclérose Latérale Amyotrophique et maladies du motoneurone [CHU Saint-Etienne]
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Anterograde amnesia, [SDV]Life Sciences [q-bio], Tau protein, Hippocampal formation, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Limbic Encephalitis, medicine, Humans, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Aged, Autoantibodies, Retrospective Studies, Aged, 80 and over, Neurons, biology, business.industry, Adenylate Kinase, Limbic encephalitis, Autoantibody, Brain, Middle Aged, medicine.disease, 3. Good health, HEK293 Cells, Treatment Outcome, 030104 developmental biology, biology.protein, Immunohistochemistry, Female, Immunotherapy, Neurology (clinical), medicine.symptom, Antibody, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Objective:To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs).Methods:We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay.Results:AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57–80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances. Anterograde amnesia can be isolated, but some patients also complained of prosopagnosia, paroxysmal anxiety, or abnormal behavior. No associated cancer was observed. All 10 patients had bilateral hippocampal hypersignal on a brain MRI. CSF analysis generally showed a mild pleiocytosis with elevated immunoglobulin G index and oligoclonal bands, as well as high levels of tau protein with normal concentration of Aβ42 and phospho-tau, suggesting a process of neuronal death. Except for one patient, clinical response to immunotherapy was unfavorable, with persistence of severe anterograde amnesia. Two patients evolved to severe cognitive decline. Hippocampal atrophy was observed on control brain MRI. Using in vitro tests on hippocampal neurons, we did not identify clues suggesting a direct pathogenic role of AK5-Abs.Conclusions:AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage.
Published: 2017
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214. Auditory steady state responses and cochlear implants: Modeling the artifact-response mixture in the perspective of denoising

Author: Faten, Mina, Virginie, Attina, Yvan, Duroc, Evelyne, Veuillet, Eric, Truy, Hung, Thai-Van, Feart, Catherine, 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), Service d'audiologie et d'explorations otoneurologiques [Hôpital Edouard Herriot, Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département ENT [HCL Hospices Civils de Lyon], This study is part of a larger project that is supported by funding from the French Fonds Unique Interministériel (FUI) (Neurosyllabic). The funding was acquired and received by Prof. Hung Thai-Van., 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), CHU Lyon, and Université de Lyon
Subjects: Auditory Pathways, Physiology, lcsh:Medicine, Electrode Recording, Medicine and Health Sciences, Electrochemistry, lcsh:Science, Membrane Electrophysiology, Evoked Potentials, ComputingMilieux_MISCELLANEOUS, Clinical Neurophysiology, Brain Mapping, Applied Mathematics, Simulation and Modeling, Electroencephalography, Cochlear Implantation, Electrophysiology, Chemistry, Bioassays and Physiological Analysis, Brain Electrophysiology, Physical Sciences, Evoked Potentials, Auditory, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, Artifacts, Algorithms, Research Article, Imaging Techniques, Models, Neurological, Neurophysiology, Neuroimaging, Surgical and Invasive Medical Procedures, Research and Analysis Methods, Membrane Potential, Humans, Computer Simulation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hearing Loss, Auditory Cortex, Analysis of Variance, Scalp, Functional Electrical Stimulation, Electrode Potentials, [SCCO.NEUR]Cognitive science/Neuroscience, Electrophysiological Techniques, lcsh:R, Computational Biology, Biology and Life Sciences, Cochlear Implants, Acoustic Stimulation, lcsh:Q, Clinical Medicine, Head, Mathematics, Neuroscience
Abstract: International audience; Auditory steady state responses (ASSRs) in cochlear implant (CI) patients are contaminated by the spread of a continuous CI electrical stimulation artifact. The aim of this work was to model the electrophysiological mixture of the CI artifact and the corresponding evoked potentials on scalp electrodes in order to evaluate the performance of denoising algorithms in eliminating the CI artifact in a controlled environment. The basis of the proposed computational framework is a neural mass model representing the nodes of the auditory pathways. Six main contributors to auditory evoked potentials from the cochlear level and up to the auditory cortex were taken into consideration. The simulated dynamics were then projected into a 3-layer realistic head model. 32-channel scalp recordings of the CI artifact-response were then generated by solving the electromagnetic forward problem. As an application, the framework's simulated 32-channel datasets were used to compare the performance of 4 commonly used Independent Component Analysis (ICA) algorithms: info-max, extended infomax, jade and fastICA in eliminating the CI artifact. As expected, two major components were detectable in the simulated datasets, a low frequency component at the modulation frequency and a pulsatile high frequency component related to the stimulation frequency. The first can be attributed to the phase-locked ASSR and the second to the stimulation artifact. Among the ICA algorithms tested, simulations showed that infomax was the most efficient and reliable in denoising the CI artifact-response mixture. Denoising algorithms can induce undesirable deformation of the signal of interest in real CI patient recordings. The proposed framework is a valuable tool for evaluating these algorithms in a controllable environment ahead of experimental or clinical applications.
Published: 2017
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215. Predictors of responses to immune checkpoint blockade in advanced melanoma

Author: Brigitte Dréno, Caroline Flament, Nicolas Jacquelot, B. Balme, Yaron Meirow, Mitchell P. Levesque, Jeffrey S. Weber, Christophe Borg, Lawrence Fong, Amir Khammari, Guido Kroemer, Sylvie Rusakiewicz, Morten Hartvig Hansen, Ignacio Melero, Gorana Tomasic, Henrik Schmidt, Meriem Messaoudene, Andrea Cavalcanti, Maria Paula Roberti, Sarah Jegou, Yoshinobu Koguchi, Stefan Michiels, Moshe Sade-Feldman, Michal Baniyash, Ana C. Anderson, Byoung S. Kwon, Lieping Chen, Aurélien Marabelle, David Enot, Arun Burra, Inge Marie Svane, Stéphane Dalle, A.M. Di Giacomo, Dirk Schadendorf, Nils Ternès, Laurence Zitvogel, Reinhard Dummer, Andressa L. Sodre, Serena S. Kwek, O Beatrix, Vijay K. Kuchroo, Alexander M.M. Eggermont, David M. Woods, Benjamin Weide, Mark J. Smyth, Michele Maio, Maha Ayyoub, François Aubin, Connie P.M. Duong, Michal Lotem, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Institut Gustave Roussy (IGR), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Microorganismes et physiopathologie intestinale (ERL INSERM U1157 - CNRS UMR 7203), Laboratoire des biomolécules (LBM UMR 7203), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laura & Isaac Perlmutter Cancer Center [New York, NY, USA], New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU)-NYU System (NYU), Department of Hematology and Oncology [Herlev, Denmark], Copenhagen University Hospital, The Lautenberg Center for General and Tumor Immunology [Jerusalem, Israel], The Hebrew University Hadassah Medical School -BioMedical Research institute Israel Canada of the Faculty of Medicine [Jerusalem, Israel], Division of Hematology-Oncology [San Francisco, CA, USA] (Department of Medicine), University of California [San Francisco] (UCSF), University of California-University of California, Department of Immunobiology [New Haven, CT, USA] (Yale School of Medicine), Yale University [New Haven], Eutilex Co., Ltd [Seoul, Korea], Section of Clinical Immunology, Allergy, and Rheumatology [New Orleans, LA, USA] (Department of Medicine), Tulane University Health Sciences Center [New Orleans, LA, USA], Evergrande Center for Immunologic Diseases [Boston, MA, USA] (Ann Romney Center for Neurologic Diseases), Brigham & Women's Hospital, Harvard Medical School, Department of Dermatology [Tubingen, Germany], University Medical Center [Tubingen, Germany], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Oncologie Médicale [CHRU Besançon], Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Lyon-Sud - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de biologie et pathologie médicales [Gustave Roussy], Division of Medical Oncology and Immunotherapy [Siena, Italy], University Hospital of Siena, Department of Dermatology [Heidelberg, Germany], University Duisburg-Essen [Germany]-University Hospital [Heidelberg, Germany]-Germany & German Cancer Consortium - DKTZ [Heidelberg, Germany], Division of Hepatology and Gene Therapy (CIMA), Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV)-Universidad de Navarra [Pamplona] (UNAV), Oncology Department [Pamplona, Spain], University Clinic of Navarra - CUN [Pamplona, Spain], Centro de Investigación Biomedica en Red de Oncologia [Pamplona, Spain] (CIBERO), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Department of Dermatology [Zürich, Switzerland], Universität Zürich [Zürich] = University of Zurich (UZH)-University hospital of Zurich [Zurich], Earle A. Chiles Research Institute [Portland, OR, USA], Providence Portland Medical Center-Robert W. Franz Cancer Research Center, Sharett Institute of Oncology [Jerusalem, Israel], Hadassah Medical Organization [Jerusalem, Israel], Department of Oncology [Aarhus, Denmark], Aarhus University Hospital, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Sorbonne Paris Cité (USPC), Pôle de biologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Département de chirurgie générale [Gustave Roussy], Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Immunology in Cancer and Infection Laboratory [Herston, QLD, Australia], QIMR Berghofer Medical Research Institute, School of Medicine [Herston, QLD, Australia], University of Southern Queensland (USQ), This work was supported by Institut National du Cancer INCa, ANR, Ligue contre le cancer (équipe labellisée de L.Z.) and Swiss Bridge Foundation, ISREC Foundation, LABEX OncoImmunology, la direction générale de l’offre de soins (DGOS), Université Paris-Sud, SIRIC SOCRATE (INCa/DGOS/INSERM 6043), PACRI network and PIA2 TORINO-LUMIERE. N.J. received a fellowship from Cancéropole Idf. M.J.S. was supported by a National Health and Medical Research Council of Australia Senior Principal Research Fellowship., Bernardo, Elizabeth, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), 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]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), 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), Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-University Hospital [Heidelberg, Germany]-Germany & German Cancer Consortium - DKTZ [Heidelberg, Germany], Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: 0301 basic medicine, Oncology, medicine.medical_treatment, Medizin, General Physics and Astronomy, 0302 clinical medicine, METASTATIC MELANOMA, TUMOR-INFILTRATING LYMPHOCYTES, lcsh:Science, Cancer, screening and diagnosis, Multidisciplinary, CD137, 3. Good health, Detection, 030220 oncology & carcinogenesis, Patient Safety, BREAST-CANCER PATIENTS, Nivolumab, Adjuvant, CIRCULATING SOLUBLE FAS, medicine.drug, medicine.medical_specialty, CELL LUNG-CANCER, Science, PROGNOSTIC IMPACT, Clinical Trials and Supportive Activities, Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Clinical Research, Internal medicine, Journal Article, STAGE-III MELANOMA, medicine, CLINICAL-SIGNIFICANCE, business.industry, UNTREATED MELANOMA, General Chemistry, Immune checkpoint, Blockade, 4.1 Discovery and preclinical testing of markers and technologies, 030104 developmental biology, COMBINED NIVOLUMAB, Immunology, lcsh:Q, business, CD8
Abstract: Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel., The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
Published: 2017
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216. Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease

Author: Nicolas Decorte, Bernard Wuyam, Jean-Marc Vallier, Samuel Verges, Sébastien Quétant, Boubou Camara, Mathieu Gruet, Laurent Mely, Université de Toulon (UTLN), Laboratoire Motricité Humaine Expertise Sport Santé (LAMHESS), Université Côte d'Azur (UCA)-Université de Toulon (UTLN)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE 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 Côte d'Azur (UCA)-Université de Toulon (UTLN)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), 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), Centre de Recherche et d'Innovation en Kinésiologie, Kinésiopathologie et Kinésithérapie (CRIK3), CHU Grenoble, 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), and 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)
Subjects: Adult, Lung Diseases, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Cystic Fibrosis, Anabolism, Limb muscle, Statistics as Topic, Cystic fibrosis, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Power output, Muscle, Skeletal, ComputingMilieux_MISCELLANEOUS, Exercise Tolerance, business.industry, Patient Acuity, Skeletal muscle, Metabolism, medicine.disease, medicine.anatomical_structure, Endocrinology, Lower Extremity, 030228 respiratory system, Calf muscle, Lung disease, Pediatrics, Perinatology and Child Health, Exercise Test, Female, Energy Metabolism, business, 030217 neurology & neurosurgery
Abstract: Background Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. Aims and objectives We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. Methods Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by 31 P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. Results Maximal cycling test revealed lower exercise capacities in CF (VO 2peak 2.44±0.11 vs. 3.44±0.23L·Min −1 , P =0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls ( P >0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P =0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF −33±7%, controls −34±6%, P =0.44), while PCr degradation at identical absolute workload was greater in CF patients ( P =0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm 2 ; P =0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. Conclusion Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF.
Published: 2017
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217. Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability

Author: Isabelle Marey, Anne Faudet, Sandra Chantot-Bastaraud, Caroline Rooryck, Annick Toutain, Damien Haye, Vincent des Portes, Corinne Mach, Laurence Olivier-Faivre, Thierry Billette de Villemeur, Sandra Whalen, Eric Fonteneau, Marie-Laure Moutard, Delphine Héron, Alice Masurel-Paulet, D Sanlaville, Sophie Naudion, Christel Depienne, Cyril Mignot, Cédric Le Caignec, Christel Thauvin-Robinet, Didier Lacombe, Caroline Nava, Dorothée Ville, Aurélia Jacquette, Boris Keren, Jean-Pierre Siffroi, Fabien Lesne, Solveig Heide, Elodie Lejeune, université de Bourgogne, LNC, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme [ CHU Pitié-Salpêtrière AP-HP] (GRC : DIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de génétique, cytogénétique, embryologie [CHU Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des Sciences cognitives Marc Jeannerod - Laboratoire sur le langage, le cerveau et la cognition (L2C2), 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 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 Lyon, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de génétique et embryologie médicales [CHU Trousseau], Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Service de génétique, cytogénétique, embryologie [Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), 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 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), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Candidate gene, Cell Cycle Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Corpus callosum, Bioinformatics, corpus callosum, chromosomal microarray, Chromosome Duplication, Intellectual disability, Gene duplication, Basic Helix-Loop-Helix Transcription Factors, Prospective Studies, Copy-number variation, Child, Genetics, TCF4, agenesis of corpus callosum, Child, Preschool, Female, Chromosomes, Human, Pair 3, Chromosome Deletion, SNP array, Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 8, Adult, Adolescent, DNA Copy Number Variations, CNV, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, Intellectual Disability, mental disorders, medicine, Humans, SNP, Hedgehog Proteins, dysgenesis of corpus callosum, [SDV.GEN]Life Sciences [q-bio]/Genetics, Chromosomes, Human, Pair 10, business.industry, Zinc Finger E-box-Binding Homeobox 1, Microarray Analysis, medicine.disease, 030104 developmental biology, Pediatrics, Perinatology and Child Health, business, Chromosomes, Human, Pair 19
Abstract: International audience; OBJECTIVE:To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays.RESULTS:In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes.CONCLUSIONS:Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.Copyright © 2017 Elsevier Inc. All rights reserved.
Published: 2017
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218. What score should be used for evaluation of Crohn's disease severity using magnetic resonance imaging?

Author: Constance Hordonneau, Marion Goutte, Gilles Bommelaer, Anthony Buisson, Département de Gastroentérologie, Hôpital Européen [Fondation Ambroise Paré - Marseille], 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), Département de Radiologie (LYON - Radio), CHU Lyon, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), and Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)
Subjects: imagerie par résonance magnétique, medicine.medical_specialty, macromolecular substances, 03 medical and health sciences, 0302 clinical medicine, Disease severity, Ileum, Surgical oncology, Internal medicine, Humans, Medicine, gravité, Crohn's disease, medicine.diagnostic_test, business.industry, Crohn disease, Gastroenterology, Magnetic resonance imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, maladie de crohn, Hepatology, crohn disease, medicine.disease, equipment and supplies, Magnetic Resonance Imaging, Colorectal surgery, digestive system diseases, gravity, nervous system, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Radiology, business, human activities, Abdominal surgery
Abstract: What score should be used for evaluation of Crohn's disease severity using magnetic resonance imaging?
Published: 2017
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219. Clinical nutrition guidelines of the French Speaking Society of Clinical Nutrition and Metabolism (SFNEP): Summary of recommendations for adults undergoing non-surgical anticancer treatment

Author: Françoise May-Levin, Patrick Bachmann, René-Jean Bensadoun, Jocelyne Meuric, Paule Latino-Martel, Xavier Hébuterne, François Goldwasser, Corinne Bouteloup, Isabelle Bourdel-Marchasson, Olivier Guérin, Marie-Paule Vasson, Isabelle Besnard, Pierre Senesse, Mauricette Michallet, Pascal Crenn, Centre Léon Bérard [Lyon], Université Montpellier 2 - Sciences et Techniques (UM2), Université Montpellier 1 (UM1), Radiation Oncology Department, SanPau Hospital, CHU, Université de Bordeaux Ségalen [Bordeaux 2], Pôle de Gérontologie Clinique, CHU Bordeaux [Bordeaux]-Hôpital Xavier Arnozan, Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre de Recherche en Nutrition Humaine, CHU Clermont-Ferrand, Groupe de Recherche Clinique et Technologique sur le Handicap (GRCTH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Anticanc Ctr Curie, Paris, France, Partenaires INRAE, French League Canc, Paris, France, CHU Lyon Sud, Pierre Benite, France, Anticanc Ctr Jean Perrin, Clermont Ferrand, France, Univ Nice Sophia Antipolis, CHU Nice, F-06189 Nice, France, Aguettant, Baxter, Fresenius-Kabi, Nestl, Nutricia, Nestle, Fresenius-Kabi, Baxter, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Cachexia, 030309 nutrition & dietetics, bone-marrow transplantation, Clinical practice, Antioxidants, polyunsaturated fatty-acid, Nutrition Policy, neck-cancer patient, 0302 clinical medicine, Weight loss, Neoplasms, subjective global assessment, Nutritional care, stem-cell transplantation, 2. Zero hunger, 0303 health sciences, Gastroenterology, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Dietary Proteins, medicine.symptom, Adult, medicine.medical_specialty, Evidence-based practice, Directive Counseling, Nutritional Status, Clinical nutrition, percutaneous endoscopic gastrostomy, 03 medical and health sciences, total parenteral-nutrition, Quality of life (healthcare), medicine, Humans, locally advanced head, Intensive care medicine, Hepatology, business.industry, improves patient outcome, Cancer, Evidence-based medicine, medicine.disease, Malnutrition, Nutrition Assessment, quality-of-life, Dietary Supplements, Physical therapy, Energy Intake, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Evidence-based
Abstract: International audience; Up to 50% of patients with cancer suffer from weight loss and undernutrition (as called cachexia) even though it is rarely screened or properly handled. Patients' prognosis and quality of life could be greatly improved by simple and inexpensive means encompassing nutritional status assessment and effective nutritional care. These guidelines aim to give health professionals and patients practical and up-to-date advice to manage nutrition in the principal situations encountered during the cancer course according to the type of tumour and treatment (i.e. radio and/or chemotherapy). Specific suggestions are made for palliative and elderly patients because of specific risks of undernutrition and related comorbidities in this subset. Levels of evidence and grades of recommendations are detailed as stated by current literature and consensus opinion of clinical experts in each field.
Published: 2014
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220. Cadre nosologique et stratégie diagnostique de la myélite aiguë transverse longitudinalement étendue

Author: Bertrand Audoin, Hélène Zéphir, Groupe Nomadmus, Romain Marignier, David Brassat, Sandra Vukusic, François Cotton, Nicolas Collongues, F. Durand-Dubief, David-Axel Laplaud, C. Papeix, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), 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), Department of Neurology, CHU Lyon, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Nosology, medicine.medical_specialty, Neuromyelitis optica, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, business.industry, [SDV]Life Sciences [q-bio], Myelitis, medicine.disease, Transverse myelitis, Sagittal plane, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Acute Transverse Myelitis, medicine.anatomical_structure, Neurology, medicine, Etiology, 030212 general & internal medicine, Neurology (clinical), Radiology, business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery
Abstract: Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment.
Published: 2014
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221. Tolerance of methotrexate in a daily practice cohort of adults with atopic dermatitis

Author: Fanny Delcroix, Benjamine Delcasso, Audrey Nosbaum, Sophie Grande, Jean-François Nicolas, Frédéric Bérard, F. Hacard, Catherine Goujon, 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), 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: Adult, Male, Pediatrics, medicine.medical_specialty, Administration, Oral, Dermatology, Severity of Illness Index, Drug Administration Schedule, Dermatitis, Atopic, Cohort Studies, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Drug tolerance, Severity of illness, medicine, Humans, Young adult, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Dose-Response Relationship, Drug, business.industry, Retrospective cohort study, Drug Tolerance, Atopic dermatitis, Middle Aged, Prognosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Methotrexate, Treatment Outcome, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Cohort study, medicine.drug
Abstract: International audience
Published: 2018
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222. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study

Author: Louis Maillard, Lisa M. Bateman, Meng Tan, Elson L. So, Hans Høgenhaven, Andrew Bleasel, Barbara A. Dworetzky, Sylvain Rheims, Arielle Crespel, Torbjörn Tomson, Andreas Schulze-Bonhage, Michael A. Nitsche, Holger Lerche, Philippe Ryvlin, Samden D. Lhatoo, Paul Boon, Bernard Sadzot, Lina Nashef, James X. Tao, Mark C. Spitz, Ekaterina Pataraia, Cécile Marchal, Jonathan M. Bird, Terje Rabben, Jagarlapudi M K Murthy, Michael P. Malter, Anna Szucs, Masud Seyal, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), 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), Service d'explorations neurologiques et épileptologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie Fonctionnelle et d'Épileptologie, Hospices Civils de Lyon (HCL), Institut des Epilepsies de l'Enfant et de l'Adolescent (IDEE), CHU Lyon, Epilepsy Centre, University Hospital Freiburg, Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), 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), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: Male, MESH: Heart Arrest, Neurology, Epilepsy, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, MESH: New Zealand, MESH: Child, MESH: Incidence, Israel, Young adult, Child, Cause of death, 0303 health sciences, MESH: Middle Aged, Incidence, Incidence (epidemiology), MESH: Israel, Middle Aged, MESH: Seizures, 3. Good health, Europe, MESH: Young Adult, MESH: Epilepsy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Hospital Units, Hospital Units, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Adult, medicine.medical_specialty, MESH: Australia, Young Adult, 03 medical and health sciences, Seizures, medicine, Humans, Intensive care medicine, Retrospective Studies, 030304 developmental biology, MESH: Humans, business.industry, Australia, Cardiac arrhythmia, MESH: Adult, MESH: Retrospective Studies, MESH: Death, Sudden, Cardiac, Retrospective cohort study, Cardiorespiratory fitness, medicine.disease, MESH: Male, Heart Arrest, Death, Sudden, Cardiac, Emergency medicine, MESH: Europe, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, New Zealand
Abstract: International audience; BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS: Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS: 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5*1 (95% CI 2*6-9*2) per 1000 patient-years, with a risk of 1*2 (0*6-2*1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION: SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING: Commission of European Affairs of the International League Against Epilepsy.
Published: 2013
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223. Depressing Mitochondria-Reticulum Interactions Protects Cardiomyocytes From Lethal Hypoxia-Reoxygenation Injury

Author: Alain Lacampagne, Emily Tubbs, Jennifer Rieusset, Claire Crola Da Silva, Geoffrey Teixeira, Jérémy Fauconnier, Michel Ovize, Melanie Paillard, Ludovic Gomez, Elise Belaidi, Annie Durand, Pierre-Alain Thiebaut, Maryline Abrial, Nathan Mewton, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Université Montpellier 2 - Sciences et Techniques (UM2), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Louis Pradel [CHU - HCL], CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Paillard, Mélanie
Subjects: Male, Patch-Clamp Techniques, [SDV]Life Sciences [q-bio], Myocardial Reperfusion Injury, In Vitro Techniques, Biology, Mitochondrion, Endoplasmic Reticulum, Mitochondria, Heart, Cell Line, Cyclophilins, Mice, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), medicine, Animals, Inositol 1,4,5-Trisphosphate Receptors, HSP70 Heat-Shock Proteins, Myocytes, Cardiac, Calcium Signaling, Patch clamp, Cells, Cultured, 030304 developmental biology, Calcium signaling, Mice, Knockout, 0303 health sciences, Voltage-Dependent Anion Channel 1, Endoplasmic reticulum, Membrane Proteins, Intracellular Membranes, medicine.disease, Cell Hypoxia, Rats, Cell biology, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Oxygen, Mitochondrial matrix, Multiprotein Complexes, 030220 oncology & carcinogenesis, Chaperone (protein), biology.protein, Cardiology and Cardiovascular Medicine, VDAC1, Reperfusion injury, Cyclophilin D
Abstract: Background— Under physiological conditions, Ca 2+ transfer from the endoplasmic reticulum (ER) to mitochondria might occur at least in part at contact points between the 2 organelles and involves the VDAC1/Grp75/IP3R1 complex. Accumulation of Ca 2+ into the mitochondrial matrix may activate the mitochondrial chaperone cyclophilin D (CypD) and trigger permeability transition pore opening, whose role in ischemia/reperfusion injury is well recognized. We questioned here whether the transfer of Ca 2+ from ER to mitochondria might play a role in cardiomyocyte death after hypoxia-reoxygenation. Methods and Results— We report that CypD interacts with the VDAC1/Grp75/IP3R1 complex in cardiomyocytes. Genetic or pharmacological inhibition of CypD in both H9c2 cardiomyoblasts and adult cardiomyocytes decreased the Ca 2+ transfer from ER to mitochondria through IP3R under normoxic conditions. During hypoxia-reoxygenation, the interaction between CypD and the IP3R1 Ca 2+ channeling complex increased concomitantly with mitochondrial Ca 2+ content. Inhibition of either CypD, IP3R1, or Grp75 decreased protein interaction within the complex, attenuated mitochondrial Ca 2+ overload, and protected cells from hypoxia-reoxygenation. Genetic or pharmacological inhibition of CypD provided a similar effect in adult mice cardiomyocytes. Disruption of ER-mitochondria interaction via the downregulation of Mfn2 similarly reduced the interaction between CypD and the IP3R1 complex and protected against hypoxia-reoxygenation injury. Conclusions— Our data (1) point to a new role of CypD at the ER-mitochondria interface and (2) suggest that decreasing ER-mitochondria interaction at reperfusion can protect cardiomyocytes against lethal reperfusion injury through the reduction of mitochondrial Ca 2+ overload via the CypD/VDAC1/Grp75/IP3R1 complex.
Published: 2013
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224. Prevalence of rare mitochondrial DNA mutations in mitochondrial disorders

Author: Laurence Jonard, Xiaowu Gai, Hongbo Xie, Valérie Desquiret-Dumas, Claude Jardel, Gaëlle Hardy, Patrizia Amati-Bonneau, Catherine Florentz, Marni J. Falk, Nadia Aoutil, Agnès Rötig, Marc Ferré, Isabelle Durand-Zaleski, Annabelle Chaussenot, Hassani Maoulida, Delphine Martinez, Sylvie Bannwarth, Claire Hoarau, Anne-Sophie Lebre, Brigitte Chabrol, Konstantina Fragaki, Abdelhamid Slama, Bénédicte Mousson de Camaret, Vincent Procaccio, Pauline Gaignard, Jennifer Ceresuela, Jean-Paul Bonnefont, Véronique Paquis-Flucklinger, Kim-Hanh Le Quan Sang, Mylène Gilleron, Pascal Reynier, Claire Marie Dhaenens, Christophe Rocher, Nathanaël Charrier, Aurore Devos, Sandrine Marlin, Caroline Espil-Taris, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), URCEco, Hôpital Hôtel-Dieu [Paris], Children’s Hospital of Philadelphia (CHOP ), Centre Hospitalier Universitaire [Grenoble] (CHU), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), CHU Lyon, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Physiopathologie mitochondriale, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Adult, Male, Mitochondrial DNA, Mitochondrial Diseases, Mutation Report, Adolescent, [SDV]Life Sciences [q-bio], Mitochondrial disease, Biology, medicine.disease_cause, DNA, Mitochondrial, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Rare mutations, Prevalence, Genetics, medicine, Humans, Patient cohort, Age of Onset, Child, Gene, Genetics (clinical), Aged, 030304 developmental biology, 0303 health sciences, Mutation, Homoplasmy, Infant, Newborn, Infant, Middle Aged, medicine.disease, Phenotype, Heteroplasmy, 3. Good health, Child, Preschool, Female, Age of onset, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Mitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. Patients are usually tested only for deletions and for common mutations of mtDNA which account for 5-40% of cases, depending on the study. However, the prevalence of rare mtDNA mutations is not known. METHODS: We analysed the whole mtDNA in a cohort of 743 patients suspected of manifesting a mitochondrial disease, after excluding deletions and common mutations. Both heteroplasmic and homoplasmic variants were identified using two complementary strategies (Surveyor and MitoChip). Multiple correspondence analyses followed by hierarchical ascendant cluster process were used to explore relationships between clinical spectrum, age at onset and localisation of mutations. RESULTS: 7.4% of deleterious mutations and 22.4% of novel putative mutations were identified. Pathogenic heteroplasmic mutations were more frequent than homoplasmic mutations (4.6% vs 2.8%). Patients carrying deleterious mutations showed symptoms before 16 years of age in 67% of cases. Early onset disease (16 years) were associated with mutations in tRNA genes. MTND5 and MTND6 genes were identified as 'hotspots' of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes. CONCLUSIONS: Rare mitochondrial DNA mutations probably account for more than 7.4% of patients with respiratory chain deficiency. This study shows that a comprehensive analysis of mtDNA is essential, and should include young children, for an accurate diagnosis that is now accessible with the development of next generation sequencing technology.
Published: 2013
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225. Quality of qualitative studies centred on patients in family practice: a systematic review

Author: Eschalier, Benedicte, DESCAMPS, Stéphane, Pereira, Bruno, Vaillant-Roussel, Hélène, Girard, Guillaume, BOISGARD, Stéphane, Coudeyre, Emmanuel, Nazarian, Ara, Rehman, M., Tudrej, B.V., Soustre, J., Buisson, M., Archambault, P., Pouchain, D., Gueyffier, François, Faillie, J.-L., Perault-Pochat, C., Cornu, C., Boussageon, R., Cambon, Benoit, Vorilhon, Philippe, Michel, Laurence, Cadwallader, Jean-Sébastien, Aubin-Auger, Isabelle, Vaillant Roussel, Hélène, Département de Médecine Générale, Faculté de Médecine, Université Clermont Auvergne, Service d’Orthopédie Traumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Biostatistiques, Inferential, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), médecine physique et de réadaptation, CHU Clermont-Ferrand, Center for Advanced Orthopaedic Studies, Harvard Medical School [Boston] (HMS), Service de cardiologie [CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut des Sciences de la MER de Rimouski (ISMER), Université du Québec à Rimouski (UQAR), Université de Tours (UT), 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 1407, Hospices Civils de Lyon (HCL), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Générale [Clermont-Ferrand], Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Sorbonne Paris Cité (USPC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Recherche Clinique ville-hôpital, Méthodologies et Société (REMES), Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), and Université de Tours
Subjects: Research design, medicine.medical_specialty, Biomedical Research, media_common.quotation_subject, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Quality (business), Confidentiality, 030212 general & internal medicine, Research question, Qualitative Research, ComputingMilieux_MISCELLANEOUS, media_common, Data collection, Impact factor, business.industry, 030503 health policy & services, Focus Groups, Focus group, 3. Good health, Research Design, Family medicine, 0305 other medical science, business, Family Practice, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Qualitative research
Abstract: BACKGROUND Qualitative research is often used in the field of general medicine. Our objective was to evaluate the quality of published qualitative studies conducted using individual interviews or focus groups centred on patients monitored in general practice. METHODS We have undertaken a review of the literature in the PubMed and Embase databases of articles up to February 2014. The selection criteria were qualitative studies conducted using individual interviews or focus groups, centred on patients monitored in general practice. The articles chosen were analysed and evaluated using a score established from the Relevance, Appropriateness, Transparency and Soundness (RATS) grid. RESULTS The average score of the 52 studies chosen was 28 out of 42. The criteria least often present were the description of the patients who chose not to participate in the study, the justification of the end of data collection, the discussion of the influence of the researchers and the discussion of the confidentiality of the data. The criteria most frequently described were an explicit research question, justified and in relation to existing knowledge, the agreement of the ethical committee and the presence of quotations. The number of studies and the score increased from year-to-year. The score was independent of the impact factor of the journal. CONCLUSIONS Even though the qualitative research was published in reviews with a low impact factor, our results suggest that this research responded to the quality criteria of the RATS grid. The evaluation scored using RATS could be useful for authors or reviewers and for literature reviews.
Published: 2016
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226. Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure

Author: Cecile Campos, Anne Dubois, Gilles Bommelaer, Constance Hordonneau, Céline Lambert, Bruno Pereira, Marion Goutte, Anthony Buisson, Michel Dapoigny, Antoine Perrey, Felix Goutorbe, Service Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire de Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie, Hospices Civils de Lyon (HCL), Unité Biostatistique, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service Chirurgie Digestive, MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Hospira, CHU Clermont-Ferrand, 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), Département Gastroentérologie, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département de Radiologie (LYON - Radio), CHU Lyon, Délégation à la Recherche Clinique et à l'Innovation (DRCI), Department of Digestive surgery, Centre Hospitalier de la Côte Basque, and Centre Hospitalier de la Côte Basque (CHCB)
Subjects: Male, Physiology, Fistula, Anti-Inflammatory Agents, Constriction, Pathologic, Anti-TNF, 0302 clinical medicine, Crohn Disease, Risk Factors, Treatment Failure, Crohn's disease, medicine.diagnostic_test, retrecissement, Hazard ratio, Gastroenterology, stenosis, Age Factors, Middle Aged, Magnetic Resonance Imaging, 3. Good health, crohn’s disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, Radiology, Immunosuppressive Agents, MRI, imagerie par résonance magnétique, Adult, medicine.medical_specialty, Abdominal Abscess, 03 medical and health sciences, Young Adult, Gastrointestinal Agents, Internal medicine, medicine, Intestinal Fistula, Humans, Cross-sectional imaging, Retrospective Studies, business.industry, Predictors, Tumor Necrosis Factor-alpha, Magnetic resonance imaging, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, maladie de crohn, Protective Factors, medicine.disease, Infliximab, Discontinuation, Stenosis, business, Tomography, X-Ray Computed, Stricture, thérapie, Follow-Up Studies
Abstract: International audience; BACKGROUND: Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. AIM: To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. METHODS: In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. CONCLUSION: Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.
Published: 2016
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227. Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173 -activating mutations in 3 children

Author: Frédéric Rieux-Laucat, Didier Bessis, Bruno Charbit, Anne Hulin, Guilhem Cros, Philippe Reix, Darragh Duffy, Thierry Walzer, Muriel Le Bourgeois, Eric Jeziorski, Alexandre Belot, Mathieu P Rodero, Monique Fabre, Christine Bodemer, Yanick J. Crow, Stéphane Blanche, Nihel Khoudour, Nadia Jeremiah, Laureline Berteloot, Bénédicte Neven, Consuelo Modesto Caballero, Gillian I. Rice, Despina Moshous, Alain Fischer, Brigitte Bader-Meunier, Marie-Louise Frémond, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, rhumatologie et dermatologie pédiatriques, Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), University of Manchester [Manchester], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, 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 Nephrology-Rheumatology-Dermatology Pediatric, Bron, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de dermatologie [CHU de Montpellier], Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), 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 Hospitalier Universitaire de Montpellier (CHU Montpellier ), Manchester Centre for Genomic Medicine (MCGM), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-St Mary's Hospital Manchester, CHU Henri Mondor, Chaire Médecine expérimentale (A. Fischer), and Davoine, Laure-Hélène
Subjects: 0301 basic medicine, Male, Ruxolitinib, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Pharmacology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Journal Article, Immunology and Allergy, Medicine, Humans, Child, Preschool, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030203 arthritis & rheumatology, Mutation, Janus kinase 2, biology, Janus kinase 1, business.industry, Membrane Proteins, Janus Kinase 1, Janus Kinase 2, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Membrane protein, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Pyrazoles, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, medicine.drug
Abstract: International audience
Published: 2016
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228. Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes

Author: Carole Tarpin, Sophie Paget-Bailly, Xavier Pivot, David Assouline, Maria Rios, Isabelle Tennevet, Gilles Romieu, Jean-Marc Ferrero, Céline Faure-Mercier, Pierre Fumoleau, Jean-François Deleuze, David G. Cox, Hélène Blanché, Marie-Christine Mathieu, Thierry Petit, Christelle Jouannaud, Hugues Bourgeois, Oana Cojocarasu, Thomas Bachelot, Elsa Curtit, Jérôme Meunier, Ariane Darut-Jouve, Delphine Bacq, Jean-Yves Pierga, Sandrine Lavau-Denes, Iris Pauporté, Valérie Delecroix, Christelle Levy, Patrick Soulié, Pierre Kerbrat, Véronique Trillet-Lenoir, Anne Boland, Hervé Bonnefoi, Mourad Sahbatou, Gilles Thomas, Jean-Philippe Jacquin, Julie Henriques, Céline Besse, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), 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]), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Institut Régional Fédératif du Cancer (IRFC)-Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Département de Cancérologie Médicale [Lyon], Centre Léon Bérard : Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes, Service Oncologie Médicale [Angers], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Service Oncologie Médicale [Reims], Institut Jean Godinot [Reims], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Service d’Oncologie Médicale [Strasbourg], Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service Oncologie Médicale [Grenoble], Institut Daniel Hollard [Grenoble], Pathologie mammaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service Oncologie Médicale [Saint Priest en Jarez], Institut de Cancérologie Lucien Neuwirth [Saint Priest en Jarez], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre d'oncologie et de radiothérapie du parc [Dijon], Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Département d’Oncologie Médicale [Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Oncologie Médicale [Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Oncologie Médicale [Saint-Nazaire] (Pôle Mutualiste), Centre Etienne Dolet [Saint-Nazaire], Service d’Oncologie Médicale [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’Onco-Hématologie et Médecine interne [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service d’Oncologie médicale [Orleans], Centre Hospitalier Régional d'Orléans (CHRO), Département d'Oncologie Médicale [Paris], Institut Curie [Paris], Service d'Oncologie Médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Direction de la Recherche [Boulogne-Billancourt], Institut National du Cancer [Boulogne Billancourt] (INC), Centre de Ressources Biologiques [Paris], Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Centre de Ressources Biologiques [Evry], Centre National du Génotypage [Evry], Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre 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), This work has fully been funded by the sponsor of the study, l’Institut National du Cancer, France (INCa)., Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service d'Oncologie Médicale [Besançon], Centre Hospitalier Régional Universitaire Hôpital Jean Minjoz [Besançon], Unité de Méthodologie et de Qualité de Vie en Cancérologie ( UMQVC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Pôle cancérologie (CHU Besançon), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut Régional Fédératif du Cancer ( IRFC ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Institut Bergonié - CRLCC Bordeaux, UNICANCER - Institut de cancérologie de l'Ouest - Paul Papin [Angers], Centre Jean Bernard [Le Mans], Clinique Victor Hugo [Le Mans], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Centre d’oncologie et de radiothérapie du Parc [Dijon], Clinique Drévon [Dijon], UNICANCER - Centre Antoine Lacassagne [Nice], Institut Paoli-Calmettes [Marseille], Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Service Oncologie Médicale [Saint-Nazaire] ( Pôle Mutualiste ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Le Mans, Centre Hospitalier Régional d'Orléans ( CHR ), Institut Curie (Paris), CRLCC Eugène Marquis ( CRLCC ), Institut National du Cancer [Boulogne Billancourt] ( INC ), Centre d’Etudes du Polymorphisme Humain [Paris], Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-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)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, BMC, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Polyclinique du Parc - Clinique Drevon [Dijon], Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 0301 basic medicine, Oncology, [SDV]Life Sciences [q-bio], Metastasis, Cohort Studies, 0302 clinical medicine, Breast cancer, Neoplasm Metastasis, Prospective cohort study, Estrogen Receptor Status, Genetic variant, Randomized Controlled Trials as Topic, Aged, 80 and over, Framingham Risk Score, Middle Aged, Prognosis, Tumor Burden, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, Female, Research Article, Adult, medicine.medical_specialty, Genotype, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Neoplasm Staging, [ SDV ] Life Sciences [q-bio], business.industry, Cancer, medicine.disease, Survival Analysis, Single nucleotide polymorphism, 030104 developmental biology, Clinical Trials, Phase III as Topic, Risk score, Neoplasm Grading, business
Abstract: Background Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. Methods A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. Results The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1–97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. Conclusions In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients’ outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. Trial registration PHARE cohort: NCT00381901, Sept. 26, 2006 – SIGNAL cohort: INCa RECF1098, Jan. 28, 2009 Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0888-4) contains supplementary material, which is available to authorized users.
Published: 2016
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229. Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy

Author: Catherine Nowak, Kamiar Mireskandari, Masano Amamoto, Jean-Baptiste Rivière, Amber Begtrup, Thibaud Jouan, Laurence Faivre, Aline Saunier, Nicolas Chatron, Noriko Miyake, Mitsuhiro Kato, Dorothée Ville, Jessica Douglas, Stéphane Auvin, Bertrand Isidor, Guylène Lemeur, Stylianos E. Antonarakis, Naomichi Matsumoto, Mathieu Milh, Philippe Jonveaux, Hanan Hamamy, Neal Sondheimer, Mirna Assoum, Paolo Milani, Mitsuko Nakashima, Amira Masri, Gaetan Lesca, Julien Thevenon, Yannis Duffourd, Laurence Perrin, Caroline Paris, Christel Thauvin-Robinet, Christophe Philippe, Periklis Makrythanasis, Génétique des Anomalies du Développement ( GAD ), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne ( UB ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP), University of Geneva, Division of Clinical and Metabolic Genetics [Toronto], The Hospital for sick children [Toronto] ( SickKids ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Boston Children's Hospital, 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 ), Université de Lyon, Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), GeneDx, Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service de Neurologie Pédiatrique, HFME, Bron, France, Service d'ophtalmologie [Nantes], Hôtel-Dieu, Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pediatric Emergency Centre, Kitakyushu Municipal Yahata Hospital, Yokohama City University School of Medecine ( YCUSM ), University School of Medecine, University of Amman, 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 ), Regional Council of Burgundy Dijon University Hospital Association Française du Syndrome de Rett, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre hospitalier universitaire de Nantes (CHU Nantes), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Hospital for sick children [Toronto] (SickKids), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), GeneDx [Gaithersburg, MD, USA], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Yokohama City University School of Medecine (YCUSM), Yokohama University School of Medecine, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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, Male, Microcephaly, Developmental Disabilities, Postnatal microcephaly, copper-metabolism, Epilepsy, 0302 clinical medicine, expansion, hermansky-pudlak-syndrome, ddc:576.5, Age of Onset, Child, disorders, Genetics (clinical), seizures, Genetics, MEDNIK syndrome, Syndrome, 3. Good health, Pedigree, intellectual disability, Child, Preschool, mednik syndrome, Female, Developmental regression, Adaptor Protein Complex 3, Genes, Recessive, Biology, AP3B1, 03 medical and health sciences, Atrophy, Report, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, Adaptor Protein Complex beta Subunits, mouse, disease, ap-4 deficiency, Infant, Newborn, Infant, medicine.disease, Optic Atrophy, 030104 developmental biology, Mutation, Hermansky–Pudlak syndrome, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five additional families with eight affected individuals through the Matchmaker Exchange initiative by matching autosomal- recessive mutations in AP3B2. Reverse phenotyping of 12 affected individuals from eight families revealed a homogeneous EOEE phenotype characterized by severe developmental delay, poor visual contact with optic atrophy, and postnatal microcephaly. No spasticity, albinism, or hematological symptoms were reported. AP3B2 encodes the neuron-specific subunit of the AP-3 complex. Autosomal-recessive variations of AP3B1, the ubiquitous isoform, cause Hermansky-Pudlak syndrome type 2. The only isoform for the delta subunit of the AP-3 complex is encoded by AP3D1. Autosomal-recessive mutations in AP3D1 cause a severe disorder cumulating the symptoms of the AP3B1 and AP3B2 defects.
Published: 2016
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230. Employment in French young adult survivors of childhood leukemia: an LEA study (for Leucemies de l'Enfant et de l'Adolescent-childhood and adolescent leukemia)

Author: André Baruchel, Marie-Dominique Tabone, Justyna Kanold, Marie-Pascale Lehucher-Michel, Pascal Chastagner, Dominique Plantaz, Floriane Garnier, Nicolas Sirvent, Julie Berbis, Gérard Michel, Yves Bertrand, Pascal Auquier, Celine Reggio, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie pédiatrique, CHU Clermont-Ferrand-CIC Inserm 501, Université de Montpellier (UM), Service Hématologie Infantile, CHU Grenoble, Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Adult, Employment, Male, medicine.medical_specialty, Childhood leukemia, Adolescent, Population, [SHS.PSY]Humanities and Social Sciences/Psychology, Logistic regression, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, medicine, Humans, 030212 general & internal medicine, Survivors, Young adult, education, Psychiatry, Response rate (survey), education.field_of_study, Leukemia, Oncology (nursing), business.industry, Public health, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 3. Good health, Oncology, quality, 030220 oncology & carcinogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, 8. Economic growth, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography, Follow-Up Studies
Abstract: International audience; Our principal aim was to assess the occupational outcomes of French ă survivors of childhood leukemia, compared to national population. The ă secondary objective was to identify determinants linked with employment ă stability after childhood leukemia. ă All survivors aged 15 and over enrolled in the French LEA Cohort ă (Childhood and Adolescent Leukemia) were included. Occupational data ă were self-reported. The occupational distributions expected in the ă cohort for each age range were established based on the distribution in ă France as reference, and comparisons between observed and expected ă distributions were performed. Logistic regression model was used to ă explore determinants of stability of survivors' employment. ă The questionnaire was completed by 845 eligible survivors (response rate ă 87.8 %), with a mean age of 22.3 +/- 5.4 years and a mean follow-up ă duration of 14.3 +/- 6.3 years. Among the 361 survivors currently in the ă labor market, 36 (10.0 %) were seeking a job, which is significantly ă lower than expected (19.3 %) compared to French population. Conversely, ă among those currently employed, the number of survivors in unstable ă employment (43.9 %) was significantly higher than expected (33.5 %). ă Younger age and higher number of late effects were risk factors for ă unstable employment. ă While the employment rate of the young French adult population of ă childhood leukemia survivors seems rather positive, access to a steady ă job appears to be compromised for some survivors. ă A strategy to better identify particular subgroups of survivors at ă greatest risk for difficulties in their professional achievement will ă help ensure the development of specific intervention strategies and ă support procedures.
Published: 2016
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231. Metabolic syndrome in long-term survivors of childhood acute leukemia ă treated without hematopoietic stem cell transplantation: an LEA study

Author: Yves Bertrand, Paul Saultier, André Baruchel, Gérard Michel, Virginie Gandemer, Camille Vercasson, Patrick Lutz, Justyna Kanold, Audrey Contet, Guy Leverger, Stéphane Ducassou, Jean-Hugues Dalle, Marie-Dominique Tabone, Hervé Chambost, Sandrine Thouvenin, Marilyne Poirée, Nicolas Sirvent, Dominique Plantaz, Pascal Auquier, Julie Berbis, Claire Oudin, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Transplantation Médullaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital d'enfants, Service Hématologie Infantile, Hôpital Pellegrin Tripode, CHU Clermont-Ferrand-CIC Inserm 501, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, medicine.medical_treatment, [SHS.PSY]Humanities and Social Sciences/Psychology, Hematopoietic stem cell transplantation, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, Cohort Studies, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Prevalence, Survivors, Child, Abdominal obesity, Metabolic Syndrome, 2. Zero hunger, education.field_of_study, Acute leukemia, Leukemia, Remission Induction, Age Factors, Articles, Hematology, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Combined Modality Therapy, 3. Good health, quality, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, medicine.symptom, Cohort study, Adult, medicine.medical_specialty, Adolescent, Immunology, Population, Lower risk, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Risk factor, education, National Cholesterol Education Program, Radiotherapy, business.industry, Cell Biology, medicine.disease, Surgery, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Metabolic syndrome, business, Body mass index, Follow-Up Studies
Abstract: INTRODUCTION Acute leukemia (AL) accounts for one third of childhood cancers. Cardiovascular conditions are serious long-term complications of childhood AL. However, few studies have investigated the risk of metabolic syndrome (MetS), a known predictor of cardiovascular disease, in patients treated without hematopoietic stem cell transplantation (HSCT). We describe the overall and age-specific prevalence, and risk factors for MetS and its components in the L.E.A. French cohort of childhood AL survivors treated without HSCT. METHODS L.E.A. is a long-term follow-up program involving all childhood AL survivors treated in the French participating centers since 1980 (clinicaltrials.gov identifier: NCT 01756599). MetS was defined according to the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATPIII) criteria revised in 2005. RESULTS The study included 650 adult patients. The mean age at evaluation was 24.2 years and the mean follow-up after leukemia diagnosis was 16.0 years. Central nervous system (CNS) irradiation was performed in 18.0% of patients (n=117). The prevalence of MetS was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively, as shown in the Figure. The prevalence of decreased HDL-cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. The risk factors significantly associated with metabolic syndrome in the multivariate analysis were male gender, older age at last evaluation and higher body mass index at diagnosis, as shown in the Table. Cumulative steroid dose was not a significant risk factor. CNS-irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. DISCUSSION Our study aimed to precisely describe the overall and age-specific prevalence, and risk factors of MetS in a large cohort of childhood AL survivors treated without HSCT. Notably, the subgroup treated with chemotherapy alone is one of the largest ever published, which is of particular interest as current protocols include very limited CNS irradiation indications. The prevalence of MetS was approximately two-fold higher than that observed in the adult French general population under 40 years of age. Moreover, the prevalence of MetS was found to increase markedly with age. An increased BMI at diagnosis was a risk factor for MetS. Children with an elevated BMI at diagnosis may have a genetic predisposition to metabolic disturbances or a socio-familial environment that renders them more vulnerable to metabolic complications. CNS irradiation was not found to be a risk factor for MetS. In the literature however, brain irradiation has been frequently reported as a risk factor for MetS. This variation with our study can probably be explained in part by the observation that our irradiated patients displayed a lower risk of elevated blood pressure along with a greater risk of increased abdominal circumference. The irradiated patients may therefore have a different metabolic risk profile compared with the non-irradiated patients, thereby suggesting varying mechanisms of pathogenesis. The results of our study confirm the need for early and prolonged follow-up of adult survivors of childhood AL even when treated without HSCT and without CNS irradiation. This prerequisite could enable both early detection of metabolic abnormalities and implementation of appropriate therapeutic procedures to reduce the morbidity and mortality associated with cardiovascular complications in such patients. Table. Multivariate analysis of potential risk factors for the metabolic syndrome OR: odds ratio; CI: confidence interval; BMI: body mass index; CNS: central nervous system; † OR per each additional year of follow-up; ‡ OR per each additional z-score unit; *significant values (p < 0.05) Table. Multivariate analysis of potential risk factors for the metabolic syndrome. / OR: odds ratio; CI: confidence interval; BMI: body mass index; CNS: central nervous system; † OR per each additional year of follow-up; ‡ OR per each additional z-score unit; *significant values (p < 0.05) Figure. Age-specific cumulative prevalence of the metabolic syndrome Figure. Age-specific cumulative prevalence of the metabolic syndrome Disclosures No relevant conflicts of interest to declare.
Published: 2016
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232. Comparative histological analysis of drug-induced maculopapular exanthema and DRESS

Author: Sylvia H. Kardaun, Audrey Nosbaum, B. Balme, Delphine Maucort-Boulch, B. Bensaid, L. Depaepe, J.-F. Nicolas, Michel D'Incan, François Skowron, Jean Kanitakis, Frédéric Bérard, Centre hospitalier de Valence, 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], Department of Dermatology, Hôpital Edouard Herriot [CHU - HCL], 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), 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), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, University Medical Center, University of Groningen, 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), Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, Drug, Male, medicine.medical_specialty, Pathology, Drug-Related Side Effects and Adverse Reactions, media_common.quotation_subject, Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Maculopapular exanthema, medicine, 80 and over, Eosinophilia, Humans, SYSTEMIC SYMPTOMS DRESS, media_common, Retrospective Studies, Aged, Aged, 80 and over, Atypical Lymphocyte, Dermal Involvement, EOSINOPHILIA, integumentary system, business.industry, Exanthema, Middle Aged, medicine.disease, equipment and supplies, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Infectious Diseases, ERUPTIONS, Initial phase, Drug Hypersensitivity Syndrome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Histopathology, Female, medicine.symptom, business, human activities, Spongiosis
Abstract: BackgroundCutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized.ObjectivesTo study the cutaneous histopathological changes associated with MPE, sMPE and DRESS.MethodsA retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013.ResultsThe number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS.LimitationsThis was a retrospective study.ConclusionsNumerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.
Published: 2016
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233. Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

Author: Jacques Cohen, Isabelle Guilhem, Gilbert Simonin, Françoise Labay, Brigitte Mignot, Chantal Stuckens, Anne-Marie Bertrand, Ariane Zelinsky-Gurung, Dominique Thevenieau, Corinne Fourmy Chatel, Régis Coutant, Vincent Gajdos, S. Le Fur, Marie-Emmanuelle Combes-Moukhovsky, Candace Ben Signor, Djamel Bendifallah, Florence Joubert, Anne Fargeot-Espaliat, Joachim Bassil, Agnès Tamboura, François Kurtz, Norbert Laisney, Agnès Guillou, Lucy Chaillous, Laetitia Pantalone, Sophie Valtat, Marie Laloi-Michelin, Chantal Stheneur, Emmanuelle Dubosclard, Anne Paoli, Véronique Kerlan, Yves Reznic, Sylvaine Clavel, Claudie Kerouedan, Philippe Talon, Armelle Pambou, Iva Gueorguieva, Daniel Dervaux, Hélène Bony-Trifunovic, Régis Piquemal, Pierre Gourdy, Brigitte Zymmermann, Hervé Dubourg, Rachel Desailloud, Stéphanie Jellimann, Pierre-Henri Ducluzeau, Bernard Le Luyer, Guy-André Loeuille, Jamil Khoury, Catherine Atlan, Elisabeth Baechler, Felix Balazard, Berthe Razafimahefa, Pierre Lecomte, Randa Salet, Marina Raoulx, Marie-Laure Pignol, Jean-François Gautier, Christine Vervel, Anne Lienhardt-Roussie, Françoise Popelard, P. Bougnères, Sylviane Fournier, Myriam Pepin-Donat, Mélanie Priou-Guesdon, Marc Nicolino, Sabine Baron, Vincent Rigalleau, Pierre-Yves Benhamou, Edwige Yollin, Marie-Claire Wielickzo, Jacques Weill, Pascal Barat, Déborah Ancelle, Jean-Pierre Brossier, Fabienne Dallavale, Laure Oilleau, Catherine Radet, Sylvie Nadalon, Chantal Metz, Etienne Larger, Céline Lukas, Sophie Caudrelier, Isabelle Guemas, Dominique Paris Bockel, Pierre Bougnères, Arnaud Monier, Estelle Marcoux, Alfred Penformis, Abdelkader Benmahammed, Daniel Terral, Philippe Jan, Marc De Kerdanet, Alain-Jacques Valleron, Catherine Boniface, Denis Dufillot, Frédérique Olivier, Jean-Pierre Cappoen, Anne Gourdin et Catherine Dumont, Guilhem Parlier, Bénédicte Guérin, Marie-Noëlle Bortoluzzi, Odile Richard, Service d'Endocrinologie (AMIENS - Endocrino), CHU Amiens-Picardie, Service Endocrinologie-Diabétologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Endocrinologie pédiatrique[CHU Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), Centre Hospitalier d’Arras, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Centre Gabriel Naudé, École pratique des hautes études (EPHE)-École nationale supérieure des sciences de l'information et des bibliothèques (ENSSIB), Université de Lyon-Université de Lyon, Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Pédiatrie-diabétologie, Hôpital Jeanne de Flandre [Lille], UMR1286 Nutrition et Biologie Intégrative, Institut National de la Recherche Agronomique (INRA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bichat, Service d'Endocrinologie (CHRU - Endocrino), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Pédiatrie Neonatalogie, Centre Hospitalier Général, Brive-la-Gaillarde, Brive-la-Gaillarde, France, Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania (UTAS), Eli Lilly UK, 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) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôtel-Dieu, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pédiatrie, Centre hospitalier Jean Monnet, Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CH Laval, CH Le Havre, Thérapie génique, Génomique et Epigénomique (U 1169), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Service d'endocrinologie pédiatrique [CHU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Service de Pédiatrie médicale [CHU Limoges], Laboratoire Identité Culturelle, Textes et Théâtralité (ICTT), Avignon Université (AU), Service d'endocrinologie pédiatrique [CHU Lyon-Hospices Civils de Lyon], Hospices Civils de Lyon (HCL), Institut d'Informatique et de Mathématiques Appliquées de Grenoble (IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes des Mondes Africains (CEMAf), Université Panthéon-Sorbonne (UP1)-Université de Provence - Aix-Marseille 1-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Clinique d'Endocrinologie, Maladies Métaboliques et Nutrition, Hôpital Laennec, Service d'Endocrinologie Pédiatrique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of diabetes, Chu (saint-Louis)/inserm, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Service de Diabétologie - Maladies Métaboliques - Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Geothalg, Université de Liège, Groupe Hospitalier Artois-Ternois Centre Hospitalier d’Arras, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), École nationale supérieure des sciences de l'information et des bibliothèques (ENSSIB), Université de Lyon-Université de Lyon-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, 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), Institute for Marine and Antarctic Studies [Hobart] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), 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), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de Laval (CH Laval), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris 1 Panthéon-Sorbonne (UP1)-Université de Provence - Aix-Marseille 1-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), Université de Lyon-Université de Lyon-École pratique des hautes études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Jeanne de Flandre [Lille], Université Paris 1 Panthéon-Sorbonne (UP1)-Université de Provence - Aix-Marseille 1-École pratique des hautes études (EPHE), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was sponsored by an ongoing institutional grant from NovoNordiskFrance, a specific Inserm support lasting from 2008 to 2014, the ProgrammeHospitalier de Recherche Clinique (PHRC ISIS-DIAB and ISIS-VIRUS), the AgenceNationale de la Recherche (ANR ENVIROGENEPIG), the Association pour laRecherche sur le Diabète (ARD)., The Isis diab collaborative group which is composed of the following physicians: Dominique Thevenieau, Corinne Fourmy Chatel, Rachel Desailloud, Hélène Bony-Trifunovic, Pierre-Henri Ducluzeau, Régis Coutant, Sophie Caudrelier, Armelle Pambou, Emmanuelle Dubosclard, Florence Joubert, Philippe Jan, Estelle Marcoux, Anne-Marie Bertrand, Dr Brigitte Mignot, Alfred Penformis, Chantal Stuckens, Régis Piquemal, Pascal Barat, Vincent Rigalleau, Chantal Stheneur, Sylviane Fournier, Véronique Kerlan, Chantal Metz, Anne Fargeot-Espaliat, Yves Reznic, Frédérique Olivier, Iva Gueorguieva, Arnaud Monier, Catherine Radet, Vincent Gajdos, Daniel Terral, Christine Vervel, Djamel Bendifallah, Candace Ben Signor, Daniel Dervaux, Abdelkader Benmahammed, Guy-André Loeuille, Françoise Popelard, Agnès Guillou, Pierre-Yves Benhamou, Jamil Khoury, Jean-Pierre Brossier, Joachim Bassil, Sylvaine Clavel, Bernard Le Luyer, Pierre Bougnères, Françoise Labay, Isabelle Guemas, Jacques Weill, Jean-Pierre Cappoen, Sylvie Nadalon, Anne Lienhardt-Roussie, Anne Paoli, Claudie Kerouedan, Edwige Yollin, Marc Nicolino, Gilbert Simonin, Jacques Cohen, Catherine Atlan, Agnès Tamboura, Hervé Dubourg, Marie-Laure Pignol, Philippe Talon, Stéphanie Jellimann, Lucy Chaillous, Sabine Baron, Marie-Noëlle Bortoluzzi, Elisabeth Baechler, Randa Salet, Ariane Zelinsky-Gurung, Fabienne Dallavale, Etienne Larger, Marie Laloi-Michelin, Jean-François Gautier, Bénédicte Guérin, Dr Laure Oilleau, Laetitia Pantalone, Céline Lukas, Isabelle Guilhem, Marc De Kerdanet, Marie-Claire Wielickzo, Mélanie Priou-Guesdon, Odile Richard, François Kurtz, Norbert Laisney, Déborah Ancelle, Guilhem Parlier, Catherine Boniface, Dominique Paris Bockel, Denis Dufillot, Berthe Razafimahefa,Pierre Gourdy, Pierre Lecomte, Myriam Pepin-Donat, Marie-Emmanuelle Combes-Moukhovsky, Brigitte Zymmermann, Marina Raoulx, Anne Gourdin et Catherine Dumont., ANR-10-BLAN-1113,HYPOCRYPT-ENVIROGENEPIG,Facteurs Environnementaux, Génétiques et Epigénétiques prédisposant à l'hypospadias et la cryptorchidie communs(2010), BMC, BMC, and BLANC - Facteurs Environnementaux, Génétiques et Epigénétiques prédisposant à l'hypospadias et la cryptorchidie communs - - HYPOCRYPT-ENVIROGENEPIG2010 - ANR-10-BLAN-1113 - BLANC - VALID
Subjects: Pediatrics, medicine.medical_specialty, endocrine system diseases, Epidemiology, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Correlation and dependence, Environment, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Type 1 diabetes, business.industry, Public health, lcsh:Public aspects of medicine, Incidence (epidemiology), Case-control study, Public Health, Environmental and Occupational Health, nutritional and metabolic diseases, lcsh:RA1-1270, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Bee stings, Data-driven, 3. Good health, [SDV] Life Sciences [q-bio], Cohort, Propensity score matching, Biostatistics, business, Case–control, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Environmental epidemiology
Abstract: BackgroundThe incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown.PurposeTo unravel environmental markers associated with T1D. Methods: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.ResultsWe found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.ConclusionsThe found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.
Published: 2016
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234. DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis

Author: Isabelle Rivals, Anne Bergougnoux, Mélodie Thomasset, Mireille Claustres, Sylvie Leroy, Davide Caimmi, Emmanuelle Beyne, M. Murris, Raphaël Chiron, Isabelle Vachier, Laurent Mely, Harriet Corvol, Jessica Varilh, Albertina De Sario, Milena Magalhães, Loïc Guillot, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Equipe de Statistique Appliquée (UMRS 1158) (ESA), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de 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), Centre de Ressources et de Compétences en Mucoviscidose [Nice] (CRCM [Nice]), Les Hôpitaux Pédiatriques de Nice CHU-Lenval, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Ressources et de Compétences en Mucoviscidose [Toulouse] (CRCM [Toulouse]), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, The project was funded by VLM, INSERM, and Montpellier Hospital. MM was supported by the Ciência Sem Fronteiras Program (CNPq, Brazil) and EB by CHU Montpellier. The FrGMC cohort was supported by INSERM, APHP, UPMC Univ Paris 06, ANR (R09186DS), DGS, VLM, and AICM., Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Pneumologie pédiatrique [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre de Ressources et de Compétences en Mucoviscidose [CHU Toulouse] (CRCM Toulouse), Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and BMC, BMC
Subjects: 0301 basic medicine, Epigenomics, Lung Diseases, Male, [SDV]Life Sciences [q-bio], Cystic Fibrosis Transmembrane Conductance Regulator, Cystic fibrosis, Severity of Illness Index, Nasal epithelial cells, Co-methylation, Genetics (clinical), Glutathione Transferase, Sequence Deletion, DNA methylation, biology, Pyrosequencing, Environmental exposure, Receptor, Endothelin A, Cystic fibrosis transmembrane conductance regulator, 3. Good health, [SDV] Life Sciences [q-bio], Female, Adult, Pulmonary function, Nose, 03 medical and health sciences, Young Adult, Genetics, medicine, Humans, Allele, Polymorphism, Molecular Biology, Gene, Modifier gene, Genes, Modifier, Research, Epigenome, Sequence Analysis, DNA, medicine.disease, Molecular biology, 030104 developmental biology, Cancer research, biology.protein, Next-generation sequencing, Heme Oxygenase-1, Developmental Biology
Abstract: Background Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients. Results We profiled DNA methylation at CFTR, the disease-causing gene, and at 13 lung modifier genes in nasal epithelial cells and whole blood samples from 48 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and ≥18-year-old were stratified according to the lung disease severity. DNA methylation was measured by bisulfite and next-generation sequencing. The DNA methylation profile allowed us to correctly classify 75% of the subjects, thus providing a CF-specific molecular signature. Moreover, in CF patients, DNA methylation at specific genes was highly correlated in the same tissue sample. We suggest that gene methylation in CF cells may be co-regulated by disease-specific trans-factors. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. Also, lower DNA methylation levels at GSTM3 were associated with the GSTM3*B allele, a polymorphic 3-bp deletion that has a protective effect in cystic fibrosis. Conclusions DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; other changes may result in small expression variations that collectively modulate the lung disease severity. Electronic supplementary material The online version of this article (doi:10.1186/s13148-016-0300-8) contains supplementary material, which is available to authorized users.
Published: 2016
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235. The 1-Minute Sit-to-Stand Test in Adults With Cystic Fibrosis: Correlations With Cardiopulmonary Exercise Test, 6-Minute Walk Test, and Quadriceps Strength

Author: Laurent Mely, Mathieu Gruet, Jean-Marc Vallier, Leonardo Alexandre Peyré-Tartaruga, 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], and Hospices Civils de Lyon (HCL)
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Cystic Fibrosis, Posture, Quadriceps strength, Walk Test, Critical Care and Intensive Care Medicine, Physical strength, Cystic fibrosis, Quadriceps Muscle, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Oxygen Consumption, Quality of life, Heart Rate, Cardiopulmonary exercise test, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, 030212 general & internal medicine, Muscle Strength, ComputingMilieux_MISCELLANEOUS, Exercise Tolerance, business.industry, VO2 max, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, Physical activity level, Test (assessment), 030228 respiratory system, Physical therapy, Exercise Test, Quality of Life, Female, business
Abstract: BACKGROUND: Exercise testing is part of the regular assessment of patients with cystic fibrosis (CF). We aimed to evaluate (1) the convergent validity of the 1-min sit-to-stand (STS) test in CF by investigating its relationships with peak oxygen uptake (peak VO2), quadriceps strength, and quality of life and (2) to compare these associations with those of the 6-min walk test (6MWT). METHODS: Twenty-five adults with CF (FEV1 = 59 ± 24%) performed the STS test, the 6MWT, quadriceps strength assessment, and cardiopulmonary exercise test (CPET). Physical activity level, quality of life, and self-esteem were assessed by questionnaires. RESULTS: STS repetitions, 6-min walk distance, quadriceps strength, and peak VO2 were, respectively, 71 ± 12, 90 ± 10, 93 ± 29, and 62 ± 16% of predicted. The STS test had moderate associations with peak VO2 (r = 0.56, P = .004), quadriceps strength (r = 0.52, P = .008), and some questionnaire items (eg, perceived physical strength, r = 0.67, P CONCLUSIONS: The STS test cannot be used as a replacement for CPET to accurately assess peak exercise capacity in CF. The STS test may have utility in detecting patients with CF who may exhibit a high level of oxygen desaturation during heavy exercise. Further studies should identify the factors contributing to STS performance to confirm the potential interest of STS repetitions × body weight outcome as a useful submaximal exercise parameter in CF.
Published: 2016
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236. Néphrectomie partielle vs ablation percutanée dans le traitement de tumeurs rénales en indication impérative

Author: M. Rouprêt, P. Gimel, V. Comat, Nicolas Grenier, F. Nougaud, Pierre Bigot, Y. Grassano, J-C. Bernhard, Idir Ouzaid, Q. Le Clerc, T. Bodin, Karim Bensalah, Gregory Verhoest, Christian Sengel, A. Mejean, François Cornelis, J.-L. Descotes, Nathalie Rioux-Leclercq, Philippe Paparel, L. Salomon, Alexandra Masson-Lecomte, Romain Boissier, Jean-Alexandre Long, Laurence Albiges, Jean-Baptiste Rigaud, C. Lanchon, Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), 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]), CHU Bordeaux [Bordeaux], Service d'Urologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Association Française d'Urologie, Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre d'Urologie Prado Louvain [Marseille], CHU Rouen, Normandie Université (NU), CHU Marseille, Centre de Médecine Générale Avicenne [Cabestany], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'urologie et de chirurgie de transplantation [CHU Nantes], Département de neurosciences (CHU Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cancer du rein : bases moléculaires de la tumorogenèse, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Urology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, medicine, business
Abstract: Objectifs Comparer la nephrectomie partielle (NP) et l’ablation percutanee (AP) dans le traitement des tumeurs renales en indication imperative. Methodes Entre 2000 et 2015, 297 patients consecutifs porteurs d’une tumeur du rein en indication imperative de traitement conservateur ont ete retrospectivement inclus dans une etude multicentrique. Cent soixante-dix-sept NP (ouverte [n = 151], laparoscopique [n = 9] ou robotique [n = 17]) et 120 ablations percutanees (radiofrequence [n = 112] ou cryoablation [n = 8]) ont ete realisees pour une tumeur sur rein unique (n = 144), une tumeur bilaterale (n = 77) ou une tumeur sur une insuffisance renale chronique (IRC) (n = 76). Resultats Il n’y avait pas de differences entre les deux groupes en ce qui concerne l’âge, le score Charlson (CCI), les raisons de l’indication imperative et le DFG preoperatoire. Les patients du groupe NP avaient des tumeurs plus grosses et un score RENAL superieur. La NP avait de moins bons resultats en termes de taux de transfusion, de duree du sejour et de complication. La survie sans recidive locale etait plus longue pour la NP mais la survie sans recidive metastatique etait similaire. Le DFG a long terme et le pourcentage de diminution du DFG etaient similaires dans les 2 groupes. En analyse multivariee, la NP etait un facteur predictif independant d’un meilleur DFG postoperatoire par rapport a l’ablation percutanee apres ajustement sur la complexite tumorale, le CCI et le DFG preoperatoire. Conclusion En indication imperative de traitement conservateur d’une tumeur du rein, la NP et l’AP sont possibles. La NP offre la possibilite de gerer des tumeurs plus complexes tout en offrant un meilleur controle local et une renale de fonction renale similaire. Cependant, elle est plus a risque de complications majeures.
Published: 2016
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237. Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study

Author: P. Braquet, F. Alla, C. Cornu, F. Goehringer, L. Piroth, C. Chirouze, M. Revest, C. Lechiche, X. Duval, V. Le Moing, Catherine Chirouze, Elodie Curlier, Cécile Descottes-Genon, Bruno Hoen, Isabelle Patry, Lucie Vettoretti, Pascal Chavanet, Jean-Christophe Eicher, Marie-Christine Greusard, Catherine Neuwirth, André Péchinot, Lionel Piroth, Marie Célard, Catherine Cornu, François Delahaye, Malika Hadid, Pascale Rausch, Audrey Coma, Florence Galtier, Philippe Géraud, Hélène Jean-Pierre, Vincent Le Moing, Catherine Sportouch, Jacques Reynes, Nejla Aissa, Thanh Doco-Lecompte, François Goehringer, Nathalie Keil, Lorraine Letranchant, Hepher Malela, Thierry May, Christine Selton-Suty, Nathalie Bedos, Jean-Philippe Lavigne, Catherine Lechiche, Albert Sotto, Xavier Duval, Emila Ilic Habensus, Bernard Iung, Catherine Leport, Pascale Longuet, Raymond Ruimy, Eric Bellissant, Pierre-Yves Donnio, Fabienne Le Gac, Christian Michelet, Matthieu Revest, Pierre Tattevin, Elise Thebault, François Alla, Pierre Braquet, Marie-Line Erpelding, Laetitia Minary, Michèle Bès, Jérôme Etienne, Anne Tristan, François Vandenesch, Alex Van Belkum, Willem Vanwamel, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), 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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Fonction, structure et inactivation d'ARN bactériens, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERA CIC, Hôpital Bichat - Claude Bernard, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses ( TransVIHMI ), Université de Montpellier ( UM ) -Universtié Yaoundé 1 [Cameroun]-Université Cheikh Anta Diop ( UCAD ) -Université Montpellier 1 ( UM1 ) -Institut de Recherche pour le Développement ( IRD ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique - Innovation Technologique ( CIC-IT ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire Chrono-environnement - UFC (UMR 6249) ( LCE ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service des maladies infectieuses et réanimation médicale, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Centre d'Investigation Clinique - Innovation Technologique (CIC-IT), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), and Jonchère, Laurent
Subjects: 0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Staphylococcus aureus, medicine.drug_class, 030106 microbiology, Antibiotics, Bacteremia, Penicillins, Prognostic factors, Tertiary Care Centers, 03 medical and health sciences, Interquartile range, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Vancomycin, Internal medicine, Case fatality rate, medicine, Humans, Blood culture, Prospective Studies, Prospective cohort study, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Antistaphylococcal penicillins, Cross Infection, medicine.diagnostic_test, business.industry, Septic shock, General Medicine, Middle Aged, Staphylococcal Infections, medicine.disease, Prognosis, Survival Analysis, 3. Good health, Surgery, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Bacteraemia, Antistaphylococcal penicillin, Female, France, business, medicine.drug
Abstract: International audience; Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5–78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44–1.69), septic shock (OR 5.11; 95% CI 3.84–6.80), metastatic cancer (OR 4.28; 95% CI 2.88–6.38), and unknown primary focus (OR 2.62; 95% CI 2.02–3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17–0.95) and vancomycin (OR 0.37; 95% CI 0.17–0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia. © 2016 European Society of Clinical Microbiology and Infectious Diseases
Published: 2016
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238. The Impact of Donor Type on Long-Term Health Status and Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Leukemia: A Leucemie de l'Enfant et de L'Adolescent Study

Author: André Baruchel, Gérard Michel, Guy Leverger, Geneviève Plat, Charlotte Jubert, Marie-Dominique Tabone, Hervé Chambost, Justyna Kanold, Catherine Paillard, Jean-Hugues Dalle, Claire Galambrun, Virginie Gandemer, Yves Bertrand, Jacinthe Bonneau, Maryline Poiree, Claire Freycon, Virginie Villes, Isabelle Pellier, Sandrine Visentin, Julie Berbis, Claire Oudin, Cécile Pochon, Anne Sirvent, Pascal Auquier, Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Groupe hospitalier Pellegrin, Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hématogoie pédiatrique, hôpital Sud, Service d'oncologie médicale [CHU Strasbourg], CHU Strasbourg, Service d'hématologie pédiatrique, CHU Clermont-Ferrand-CIC Inserm 501, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Toulouse [Toulouse], Hôpital Robert Debré Paris, Hôpital Robert Debré, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), the French National Clinical Research Program (grant no. PHRC10-24-02), French National Cancer Institute (InCA), French National Research Agency (ANR) [2011-043], Canceropole PACA [2016-03], Regional Council PACA [2016-03], Herault and the Bouches-du-Rhone departmental comities of the Ligue Contre le Cancer, French Institute for Public Health Research (IRESP), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Pediatrics, Cord blood transplantation, MESH: Late effects, medicine.medical_treatment, Health Status, MESH: Quality of life, Hematopoietic stem cell transplantation, Childhood leukemia, 0302 clinical medicine, Quality of life, Child, MESH: Cord blood transplantation, Acute leukemia, Late effect, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Tissue Donors, 3. Good health, Leukemia, 030220 oncology & carcinogenesis, Child, Preschool, Female, Cord Blood Stem Cell Transplantation, medicine.symptom, Unrelated Donors, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Hematopoietic stem cell transplantation, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Childhood leukemia, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Transplantation, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Late effects, Infant, Odds ratio, medicine.disease, Surgery, business, 030215 immunology
Abstract: International audience; We compared the long-term impact of donor type (sibling donor [SD] versus matched unrelated donor [MUD] or umbilical cord blood [UCB]) on late side effects and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic stem cell transplantation. We included 314 patients who underwent transplantation from 1997 to 2012 and were enrolled in the multicenter French Leucemie de l'Enfant et de L'Adolescent ("Leukemia in Children and Adolescents") cohort. More than one-third of the patients were adults at last visit; mean follow-up duration was 6.2 years. At least 1 late effect was observed in 284 of 314 patients (90.4%). The average number of adverse late effects was 2.1 +/- 1, 2.4 +/- 2, and 2.4 +/- 2 after SD, MUD, and UCB transplantation, respectively. In a multivariate analysis, considering the SD group as the reference, we did not detect an impact of donor type for most sequelae, with the exception of increased risk of major growth failure after MUD transplantation (odds ratio [OR], 2.42) and elevated risk of osteonecrosis after UCB transplantation (OR, 4.15). The adults and children's parents reported comparable QoL among the 3 groups. Adult patient QoL scores were lower than age- and sex-matched French reference scores for almost all dimensions. We conclude that although these patients are heavily burdened by long-term complications, donor type had a very limited impact on their long-term health status and QoL.
Published: 2016
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239. Stereoselective determination of citalopram and desmethylcitalopram in human plasma and breast milk by liquid chromatography tandem mass spectrometry

Author: Chantal Csajka, Delphine Grosjean, Kim An Nguyen, Chin B. Eap, Etienne Weisskopf, Alice Panchaud, Jean-Michel Hascoet, Nicolas Ansermot, School of Pharmaceutical Sciences, University of Geneva [Switzerland], Service de Néonatalogie [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Pharmacologie Clinique (EPICIME), Hospices Civils de Lyon (HCL), 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), Service de Médecine Néonatale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Unit of Pharmacogenetics and Clinical Psychopharmacology [Lausanne], Centre for Psychiatric Neuroscience [Lausanne], Department of Psychiatry [Lausanne], Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Department of Psychiatry [Lausanne], and Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)
Subjects: Desmethylcitalopram, Spectrometry, Mass, Electrospray Ionization, Breast milk, Electrospray ionization, Clinical Biochemistry, Pharmaceutical Science, Citalopram, Tandem mass spectrometry, 030226 pharmacology & pharmacy, 01 natural sciences, High-performance liquid chromatography, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Plasma, 0302 clinical medicine, LC–MS/MS, Liquid chromatography–mass spectrometry, Tandem Mass Spectrometry, Quantification, Drug Discovery, Humans, Solid phase extraction, Spectroscopy, Chromatography, High Pressure Liquid, Chromatography, Reverse-Phase, Chromatography, Milk, Human, Enantiomer, 010401 analytical chemistry, Selected reaction monitoring, Solid Phase Extraction, Reproducibility of Results, Stereoisomerism, Reversed-phase chromatography, 0104 chemical sciences, chemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS) method was developed for the simultaneous, stereoselective quantification of the antidepressant citalopram and its active metabolite desmethylcitalopram in human plasma and breast milk. Sample preparation was performed by a two-step approach, including generic protein precipitation with acetonitrile followed by solid phase extraction. Enantiospecific separation of analytes was achieved on a Phenomenex® Lux Cellulose-2 column (4.6mm×150mm; 5μm), using reversed phase chromatography conditions characterized by a gradient elution of ammonium acetate buffer (pH 9.0; 20mM) and acetonitrile at a flow rate of 0.6ml/min. The compounds were detected by a tandem quadrupole mass spectrometer equipped with an electrospray ionization source and operating in multiple reaction monitoring mode. The method was fully validated in both biological fluids over a large concentration range of 0.1-100ng/ml for S-(+)- and R-(-)-citalopram, and 0.3-100ng/ml for S-(+)- and R-(-)-desmethylcitalopram. Trueness (90.0-113.3% and 97.1-103.6%), repeatability (0.9-15.9% and 0.9-8.4%) and intermediate precision (1.3-17.8% and 0.9-9.6%) in plasma and breast milk, respectively, meet international guidelines for method validation. Internal standard-normalized matrix effects ranged between 99 and 101% and 98-105%, respectively. The accuracy profiles (total error of trueness and precision) were mostly within the acceptance limits for biological samples defined as ±30%. The method was successfully applied to patient samples in a clinical trial setting.
Published: 2016
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240. Graph Theory-Based Brain Connectivity for Automatic Classification of Multiple Sclerosis Clinical Courses

Author: Gabriel Kocevar, Claudio Stamile, Salem Hannoun, François Cotton, Sandra Vukusic, Françoise Durand-Dubief, Dominique Sappey-Marinier, 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), Hospices Civils de Lyon (HCL), Service de Neurologie [Lyon], CHU Lyon, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), 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), 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 ), Nehme and Therese Tohme Multiple Sclerosis Center, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon, 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'Exploration et de Recherche Médicales par Émission de Positons ( CERMEP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -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 )
Subjects: 0301 basic medicine, MS Phenotype Classification Using Connectome, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, graph theory, SVM, Binary number, Machine learning, computer.software_genre, multiple sclerosis, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, medicine, structural connectivity, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, ComputingMilieux_MISCELLANEOUS, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Original Research, Kocevar et al, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, business.industry, General Neuroscience, Multiple sclerosis, Assortativity, Graph theory, medicine.disease, diffusion tensor imaging, Support vector machine, 030104 developmental biology, Binary classification, classification, Graph (abstract data type), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Diffusion MRI, Neuroscience, MRI
Abstract: Purpose: In this work, we introduce a method to classify Multiple Sclerosis (MS) patients into four clinical profiles using structural connectivity information. For the first time, we try to solve this question in a fully automated way using a computer-based method. The main goal is to show how the combination of graph-derived metrics with machine learning techniques constitutes a powerful tool for a better characterization and classification of MS clinical profiles. Materials and methods: Sixty-four MS patients (12 Clinical Isolated Syndrome (CIS), 24 Relapsing Remitting (RR), 24 Secondary Progressive (SP), and 17 Primary Progressive (PP)) along with 26 healthy controls (HC) underwent MR examination. T1 and diffusion tensor imaging (DTI) were used to obtain structural connectivity matrices for each subject. Global graph metrics, such as density and modularity, were estimated and compared between subjects’ groups. These metrics were further used to classify patients using tuned Support Vector Machine (SVM) combined with Radial Basic Function (RBF) kernel. Results: When comparing MS patients to HC subjects, a greater assortativity, transitivity and characteristic path length as well as a lower global efficiency were found. Using all graph metrics, the best F-Measures (91.8%, 91.8%, 75.6% and 70.6%) were obtained for binary (HC-CIS, CIS-RR, RR-PP) and multi-class (CIS-RR-SP) classification tasks, respectively. When using only one graph metric, the best F-Measures (83.6%, 88.9% and 70.7%) were achieved for modularity with previous binary classification tasks. Conclusion: Based on a simple DTI acquisition associated with structural brain connectivity analysis, this automatic method allowed an accurate classification of different MS patients’ clinical profiles.
Published: 2016
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241. Prognosis value of baseline total metabolic tumor volume (TMTV) in advanced Hodgkin lymphoma (HL) : Ancillary study of AHL2011 LYSA trial

Author: Kanoun, S., Berriolo-Riedinger, A., Tal, I., Edeline, V., Cottereau, A., Brice, P., Bouabdallah, R., Gilles Salles, Stamatoullas, A., Dupuis, J., Andre, M., Mounier, N., Ferme, C., Meignan, M., Casasnovas, R., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Beth Israel Deaconess Medical Center [Boston, USA], Harvard Medical School [Boston] ( HMS ), Institut Curie, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Lyon, Hospices Civils de Lyon ( HCL ), CRLCC Henri Becquerel, CHU Henri Mondor, Cliniques Universitaires UCL Mont-Godinne, Hôpital l'Archet, Institut Gustave Roussy ( IGR ), Sponsor(s):European Assoc Nucl Med, European-Association-of-Nuclear-Medicine (EANM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), 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, 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), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Harvard Medical School [Boston] (HMS), Institut Curie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Gustave Roussy (IGR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), université de Bourgogne, LE2I, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, ComputingMilieux_MISCELLANEOUS, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine
Abstract: International audience
Published: 2016

242. Tracking successive Wallerian degenerations in a relapsing-remitting multiple sclerosis patient

Author: Salem Hannoun, François Cotton, Françoise Durand-Dubief, Jean-Amédée Roch, Dominique Sappey-Marinier, Abu Haidar Neuroscience Institute, American University of Beirut, 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, 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), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), 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), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], and Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS)
Subjects: Pathology, medicine.medical_specialty, Wallerian degeneration, Radiological and Ultrasound Technology, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Multiple sclerosis, medicine.disease, 030218 nuclear medicine & medical imaging, 3. Good health, White matter, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Relapsing remitting, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, Diffusion MRI
Abstract: International audience
Published: 2016
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243. Giving meaning to illness: An investigation of self-defining memories in patients with relapsing-remitting multiple sclerosis patients

Author: Jérôme De Seze, Fabrice Berna, Virginie Voltzenlogel, David Brassat, Lilianne Manning, Alexandra Ernst, Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Service de Neurologie [Lyon], CHU Lyon, Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: Adult, Male, Psychotherapist, Multiple Sclerosis, media_common.quotation_subject, Memory, Episodic, [SHS.PSY]Humanities and Social Sciences/Psychology, Experimental and Cognitive Psychology, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Developmental and Educational Psychology, medicine, Meaning-making, Humans, 0501 psychology and cognitive sciences, In patient, Meaning (existential), media_common, Recall, Autobiographical memory, Multiple sclerosis, 05 social sciences, Cognition, medicine.disease, Self Concept, Personal identity, [SCCO.PSYC]Cognitive science/Psychology, Female, Psychology, Attitude to Health, 030217 neurology & neurosurgery, Clinical psychology
Abstract: International audience; Multiple sclerosis (MS) patients are often unable to adequately fulfill their established roles due to physical disabilities and cognitive changes, making this chronic illness particularly threatening to personal identity. Twenty-five MS patients and 25 healthy controls were asked to recall five self-defining memories (SDM). Overall characteristics of SDM did not differ between patients and controls; MS patients displayed preserved capacity to draw meaning upon past events. Moreover, almost two-thirds of MS patients mentioned at least one illness related SDM and about 25% of patients' SDM referred to MS. These memories were experienced as more negative and associated with more tension than other SDM but led toward more positive emotion and less negative emotion over time; they were also more central and more integrated to the personal identity. We concluded that self-challenging events due to MS may trigger both cognitive and emotional processes enabling the integration of illness in patients' self-representations.
Published: 2016
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244. NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects

Author: Gilles Blondin, Claudine Heinrichs, Sylvie Nivot, Maryline Ronze, Dominique Simon, Yves Morel, Pierre-François Souchon, Catherine Naud-Saudreau, Asmahane Ladjouze, Dinane Samara-Boustani, Christine Lefevre, Florence Roucher-Boulez, Laetitia Lemarchand, Laure Groisne, Houweyda Jilani, Delphine Mallet-Motak, Bruno Leheup, Xavier Bertagna, CHU Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Bab-el-Oued, Centre Hospitalier Universitaire de Bab-el-Oued, Alger, Algérie., American Memorial Hospital (Reims), Service d'Endocrinologie et Diabétologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, CHU Pontchaillou [Rennes], Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles (ULB), Université médicale de Vienne, Autriche, Centre hospitalier Lucien Hussel, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CH de Lorient, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pédiatrie, Hopital Saint-Louis, La Rochelle, Service de pédiatrie, Hopital Saint-Louis , La Rochelle, Université Claude Bernard Lyon 1 ( UCBL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université Libre de Bruxelles [Bruxelles] ( ULB ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Université Libre de Bruxelles [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Puberty, Precocious, Biology, Compound heterozygosity, Primary Adrenal Insufficiency, Young Adult, 03 medical and health sciences, Endocrinology, Hypothyroidism, nicotinamide nucleotide transhydrogenase, Internal medicine, primary adrenal insufficiency, NADP Transhydrogenases, medicine, Adrenal insufficiency, follow-up, Humans, Precocious puberty, oxidative stress, Child, Azoospermia, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV ] Life Sciences [q-bio], Homozygote, massive parallel sequencing, General Medicine, Middle Aged, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Congenital hypothyroidism, [SDV] Life Sciences [q-bio], 030104 developmental biology, Child, Preschool, Mutation, Etiology, Female, Thyroid function, Glucocorticoid, Adrenal Insufficiency, medicine.drug
Abstract: Objective Nicotinamide nucleotide transhydrogenase (NNT), one of the several genes recently discovered in familial glucocorticoid deficiencies (FGD), is involved in reactive oxygen species detoxification, suggesting that extra-adrenal manifestations may occur, due to the sensitivity to oxidative stress of other organs rich in mitochondria. Here, we sought to identify NNT mutations in a large cohort of patients with primary congenital adrenal insufficiency without molecular etiology and evaluate the degree of adrenal insufficiency and onset of extra-adrenal damages. Methods Sanger or massive parallel sequencing of NNT and patient monitoring. Results Homozygous or compound heterozygous NNT mutations occurred frequently (26%, 13 unrelated families, 18 patients) in our cohort. Seven new mutations were identified: p.Met337Val, p.Ala863Glu, c.3G>A (p.Met1?), p.Arg129*, p.Arg379*, p.Val665Profs*29 and p.Ala704Serfs*19. The most frequent mutation, p.Arg129*, was found recurrently in patients from Algeria. Most patients were diagnosed belatedly (8–18 months) after presenting severe hypoglycemia; others experiencing stress conditions were diagnosed earlier. Five patients also had mineralocorticoid deficiency at onset. One patient had congenital hypothyroidism and two cryptorchidism. In follow-up, we noticed gonadotropic and genitalia impairments (precocious puberty, testicular inclusions, interstitial Leydig cell adenoma, azoospermia), hypothyroidism and hypertrophic cardiomyopathy. Intrafamilial phenotype heterogeneity was also observed. Conclusions NNT should be sequenced, not only in FGD, but also in all primary adrenal insufficiencies for which the most frequent etiologies have been ruled out. As NNT is involved in oxidative stress, careful follow-up is needed to evaluate mineralocorticoid biosynthesis extent, and gonadal, heart and thyroid function.
Published: 2016
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245. 9th Hatter Biannual Meeting:position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection

Author: M. Ovize, Sean M. Davidson, John Walker, Andrew N. Redington, Hans Erik Bøtker, Raymond J. MacAllister, Robert M. Bell, Borja Ibanez, David P. Dutka, James M. Downey, Christian Stoppe, R. D. Carr, Gerd Heusch, Derek M. Yellon, 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), 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), British Health Foundation, Medical Research Council (Reino Unido), 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, CYCLOSPORINE-A, Physiology, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medizin, Injury, Apoptosis, ISCHEMIA-REPERFUSION INJURY, Review, 030204 cardiovascular system & hematology, Ischaemia, Ischaemic, Translational Research, Biomedical, Coronary artery disease, Clinical trials, 0302 clinical medicine, Mitochondrial transition pore, Myocardial infarction, SAFE pathway, CABG, p2y12, Cause of death, Cardioprotection, Beta blockers, RISK pathway, BYPASS GRAFT-SURGERY, Cardiac surgery, 3. Good health, Opiates, Infarction, Ischemic Preconditioning, Myocardial, Necroptosis, Cyclosporine, Cardiology, Cardiology and Cardiovascular Medicine, Metoprolol, ACUTE MYOCARDIAL-INFARCTION, medicine.medical_specialty, PERCUTANEOUS CORONARY INTERVENTION, EXPERIMENTAL-MODELS, SIGNAL-TRANSDUCTION, Myocardial Reperfusion Injury, Preconditioning, Asprin, Postconditioning, Necrosis, 03 medical and health sciences, Physiology (medical), Internal medicine, Autophagy, Pyroptosis, medicine, Animals, Humans, Intensive care medicine, Valve replacement, business.industry, Statins, SALVAGE KINASE, Percutaneous coronary intervention, DNA, medicine.disease, Clinical trial, MITOCHONDRIAL PERMEABILITY TRANSITION, 030104 developmental biology, Heart failure, Reperfusion, Pre-clinical, Basic research, business, Conditioning, CARDIAC-SURGERY
Abstract: International audience; In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.
Published: 2016
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246. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria

Author: Pierre Vacher, Marine Malleter, Yves Gouriou, Chi Li, L. Debure, Patrick Legembre, E. Lepvrier, Vanessa Delcroix, Amélie Fouqué, Mehdi Hammadi, Michel Ovize, Thomas Ducret, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, Hospices Civils de Lyon, Departement de Neurologie (HCL), 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 de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), ARC, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, CA106599, NIH, National Institutes of Health, CA175003, NIH, National Institutes of Health, GM106386, NIH, National Institutes of Health, 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), Institut Bergonié [Bordeaux], UNICANCER, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and TAN, Yossan-Var
Subjects: 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], bcl-X Protein, Down-Regulation, Apoptosis, Triple Negative Breast Neoplasms, Mitochondrion, Biology, Endoplasmic Reticulum, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Animals, Humans, Calcium Signaling, fas Receptor, Molecular Biology, PI3K/AKT/mTOR pathway, Calcium signaling, Mice, Knockout, Original Paper, Cell growth, Endoplasmic reticulum, Voltage-Dependent Anion Channel 1, Cell migration, Cell Biology, 3. Good health, Cell biology, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Mitochondrial Membranes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Calcium, Female, bcl-Associated Death Protein, Calcium Channels, Signal transduction, BH3 Interacting Domain Death Agonist Protein, Protein Binding
Abstract: International audience; Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca 2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca 2+ transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca 2+ uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs.
Published: 2016
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247. TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features

Author: Balestrini, Simona, Milh, Mathieu, Castiglioni, Claudia, Lüthy, Kevin, Finelli, Mattea J, Verstreken, Patrik, Cardon, Aaron, Stražišar, Barbara Gnidovec, Holder, J Lloyd, Lesca, Gaetan, Mancardi, Maria M, Poulat, Anne L, Repetto, Gabriela M, Banka, Siddharth, Bilo, Leonilda, Birkeland, Laura E, Bosch, Friedrich, Brockmann, Knut, Cross, J Helen, Doummar, Diane, Félix, Temis M, Giuliano, Fabienne, Hori, Mutsuki, Hüning, Irina, Kayserili, Hulia, Kini, Usha, Lees, Melissa M, Meenakshi, Girish, Mewasingh, Leena, Pagnamenta, Alistair T, Peluso, Silvio, Mey, Antje, Rice, Gregory M, Rosenfeld, Jill A, Taylor, Jenny C, Troester, Matthew M, Stanley, Christine M, Ville, Dorothee, Walkiewicz, Magdalena, Falace, Antonio, Fassio, Anna, Lemke, Johannes R, Biskup, Saskia, Tardif, Jessica, Ajeawung, Norbert F, Tolun, Aslihan, Corbett, Mark, Gecz, Jozef, Afawi, Zaid, Howell, Katherine B, Oliver, Karen L, Berkovic, Samuel F, Scheffer, Ingrid E, de Falco, Fabrizio A, Oliver, Peter L, Striano, Pasquale, Zara, Federico, Campeau, Phillipe M, Sisodiya, S M, Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Servicio di Neurologia, Clinica Las Condes, 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), Université de Lyon, Regional Genetic Service, St Mary's Hospital, Manchester, Department of Pediatrics and Neuropediatrics, Georg-August-University [Göttingen], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique médicale, Hôpital l'Archet, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Baylor College of Medicine (BCM), Baylor University, Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), University of Genova, Universita degli studi di Genova, Institute of Medical Genetics, Department of Neurodegenerative Diseases, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Molecular Biology and Genetics, Boaziçi University, University of Adelaide, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University = Georg-August-Universität Göttingen, Università degli studi di Genova = University of Genoa (UniGe), Balestrini, Simona, Milh, Mathieu, Castiglioni, Claudia, Lüthy, Kevin, Finelli, Mattea J, Verstreken, Patrik, Cardon, Aaron, Stražišar, Barbara Gnidovec, Holder, J. Lloyd, Lesca, Gaetan, Mancardi, Maria M, Poulat, Anne L, Repetto, Gabriela M, Banka, Siddharth, Bilo, Leonilda, Birkeland, Laura E, Bosch, Friedrich, Brockmann, Knut, Cross, J. Helen, Doummar, Diane, Félix, Temis M, Giuliano, Fabienne, Hori, Mutsuki, Hüning, Irina, Kayserili, Hulia, Kini, Usha, Lees, Melissa M, Meenakshi, Girish, Mewasingh, Leena, Pagnamenta, Alistair T, Peluso, Silvio, Mey, Antje, Rice, Gregory M, Rosenfeld, Jill A, Taylor, Jenny C, Troester, Matthew M, Stanley, Christine M, Ville, Dorothee, Walkiewicz, Magdalena, Falace, Antonio, Fassio, Anna, Lemke, Johannes R, Biskup, Saskia, Tardif, Jessica, Ajeawung, Norbert F, Tolun, Aslihan, Corbett, Mark, Gecz, Jozef, Afawi, Zaid, Howell, Katherine B, Oliver, Karen L, Berkovic, Samuel F, Scheffer, Ingrid E, de Falco, Fabrizio A, Oliver, Peter L, Striano, Pasquale, Zara, Federico, Campeau, Phillipe M, and Sisodiya, S. M.
Subjects: TBC1D24-related epilepsy syndromes, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Journal Article
Abstract: OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24.METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24).RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function.CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.
Published: 2016
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248. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome

Author: Hervé Avet-Loiseau, Sylvain Choquet, Murielle Roussel, Marie Lorraine Chretien, Annie Brion, Bertrand Arnulf, Lotfi Benboubker, Laurent Garderet, Bruno Royer, Margaret Macro, Mourad Tiab, Carine Chaleteix, Sabine Brechignac, Charles Dauriac, Sylvie Cailleres, Philippe Moreau, Lionel Karlin, Luc-Matthieu Forneker, Marc Wetterwald, Laurent Frenzel, Thierry Facon, Karim Belhadj, Jean Pierre Marolleau, Cyrille Hulin, Stephane Minvielle, Xavier Leleu, Momar Diouf, Jean Gabriel Fuzibet, CHU Amiens-Picardie, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse] (Pôle IUC - Oncopole), CHU Toulouse [Toulouse]-Oncopole de Toulouse, Centre Hospitalier Universitaire de Lyon (CHU Lyon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Général [Aix en Provence], Centre Hospitalier Régional Universitaire de Besançon - CHRU Besançon, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Général de Dunkerque, CHU Clermont-Ferrand, Hôpital Général de La Roche sur Yon, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Necker - Enfants Malades [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Hôpital L'Archet [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Bernardo, Elizabeth, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Pharmacology, Dexamethasone, Leukemia, Plasma Cell, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Transplantation, Homologous, Prospective Studies, Aged, Lenalidomide, Plasma cell leukemia, Chemotherapy, business.industry, Hematopoietic Stem Cell Transplantation, Middle Aged, medicine.disease, 3. Good health, Transplantation, Doxorubicin, 030220 oncology & carcinogenesis, Female, business, 030215 immunology, medicine.drug
Abstract: Purpose Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. Patients and Methods Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). Results Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). Conclusion In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.
Published: 2016
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249. The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators*

Author: Philippe Halimi, François Bidault, Guy Moulin, Aurore Caumont-Prim, Benoît Dupas, Anne-Paule Gimenez-Roqueplo, Guillaume Gravel, Françoise Borson-Chazot, Hervé Gouya, Anne Hernigou, Patricia Niccoli, Claude Marcus, Pascal Rousset, Vincent Rohmer, Anne Pasco-Papon, Jean Gabrillargues, Frédérique Dubrulle, Biochimie Endocrinienne et Métabolique [Marseille] (U38 Inserm - CHU Timone), Université de la Méditerranée - Aix-Marseille 2- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ingénierie des Réactions Biologiques, Bio-productions (IR2B), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Universitaire de Reims (CHU Reims), Therapies Interventionnelles Assistees Par l'Image et la Simulation - U 703 (Thiais), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR), Service de Radiologie, CHU Hôtel-Dieu, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de radiologie cardio-vasculaire [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Therapies Interventionnelles Assistees Par l'Image et la Simulation, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Adult, Male, medicine.medical_specialty, Heterozygote, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Sensitivity and Specificity, Magnetic resonance angiography, Paraganglioma, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, Medicine, Humans, Radiology, Nuclear Medicine and imaging, 10. No inequality, Head and neck, ComputingMilieux_MISCELLANEOUS, Neuroradiology, Retrospective Studies, Protocol (science), medicine.diagnostic_test, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, Interventional radiology, Retrospective cohort study, General Medicine, Gold standard (test), Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Magnetic Resonance Imaging, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Mutation, Female, Radiology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Magnetic Resonance Angiography
Abstract: To assess the performance of a simplified MRI protocol consisting of a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx mutation carriers. This retrospective sub-study is based on the multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the T1WIV images were read solely with knowledge of the clinical data but blind to the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified MRI protocol were compared to the full MRI protocol reading results and to the gold standard status obtained through the consensus of an expert committee. The sensitivity and specificity of the readings of the simplified MRI protocol were, respectively, 88.7 % (95 % CI = 78.1–95.3) and 93.7 % (95 % CI = 86.8–97.7) versus 80.7 % (95 % CI = 68.6–89.6) and 94.7 % (95 % CI = 88.1–98.3) for the readings of the full MRI protocol. The simplified post-contrast MRI with shorter duration (5 to 10 minutes) showed no performance difference compared to the lengthy standard full MRI and can be proposed for the detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. • Rapid angio-MRI protocol and the usual lengthy protocol show equal diagnostic performance. • The CE-MRA is the key sequence for the detection of HNPGLs. • The T1WIV sequence assists in localizing HNPGLs.
Published: 2016
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250. Late thyroid complications in survivors of childhood acute leukemia. An LEA study

Author: Gérard Michel, Marie-Dominique Tabone, Jean-Hugues Dalle, Dominique Plantaz, P Chastagner, Vincent Barlogis, Patrick Lutz, Pascal Auquier, Julie Berbis, Claire Oudin, Maryline Poiree, André Baruchel, Sandrine Thouvenin, Justyna Kanold, Yves Bertrand, Stéphane Ducassou, Virginie Villes, Guy Leverger, Anne Sirvent, Virginie Gandemer, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Hématologie et immunologie pédiatrique, Hospices Civils de Lyon (HCL)-CHU Lyon-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant (HFME), CHU Clermont-Ferrand-CIC Inserm 501, Service de Pédiatrie, Unité d'Oncologie et Hématologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Pellegrin Tripode, Service Hématologie Infantile, CHU Grenoble, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Robert Debré Paris, Hôpital Robert Debré, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Service de pédiatrie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), French National Clinical Research Program, French National Cancer Institute (InCA), French National Research Agency (ANR), Canceropole PACA, Regional Council PACA, Herault Departmental Comity of the Ligue Contre le Cancer, French Institute for Public Health Research (IRESP), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, MESH: Therapy/adverse effects, [SHS.PSY]Humanities and Social Sciences/Psychology, Gastroenterology, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Child, Prevalence, Cumulative incidence, Survivors, MESH: Incidence, Child, Thyroid cancer, MESH: Combined Modality, MESH: Survivors, Acute leukemia, Leukemia, MESH: Thyroid Diseases/diagnosis, MESH: France/epidemiology, Incidence, Thyroid, Hematology, MESH: Follow-Up Studies, Total body irradiation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Combined Modality Therapy, MESH: Leukemia/complications, 3. Good health, medicine.anatomical_structure, Child, Preschool, 030220 oncology & carcinogenesis, Acute Disease, MESH: Acute Disease, Female, France, Thyroid function, medicine.medical_specialty, MESH: Leukemia/epidemiology, MESH: Combined Modality Therapy/methods, MESH: Leukemia/therapy, MESH: Thyroid Diseases/epidemiology, Article, MESH: Multivariate Analysis, 03 medical and health sciences, Internal medicine, MESH: Thyroid Diseases/etiology, medicine, Humans, MESH: Prevalence, MESH: Humans, business.industry, MESH: Child, Preschool, medicine.disease, Thyroid Diseases, MESH: Male, Surgery, Transplantation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prophylactic cranial irradiation, business, MESH: Female, Follow-Up Studies, 030215 immunology
Abstract: International audience; Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599.
Published: 2016
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