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1. ETP par application mobile auprès d'adolescent.es diabétiques : perceptions des professionnel.les de santé des effets sur la relation soignant.e-adolescent.e

Author: Charles, Anne-Elodie, Vansimaeys, Camille, Balagué, Christine, Colmel, Corinne, Le Tallec, Claire, Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université de Paris (UP), Laboratoire en Innovation, Technologies, Economie et Management (EA 7363) (LITEM), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Institut Mines-Télécom Business School (IMT-BS), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Consommateur Connecté dans la Société Numérique (CONNECT), Département Droit, Economie et Finances (DEFI), Télécom Ecole de Management (TEM)-Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom Business School (IMT-BS), Institut Mines-Télécom [Paris] (IMT)-Télécom Ecole de Management (TEM)-Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom Business School (IMT-BS), Institut Mines-Télécom [Paris] (IMT)-Département Management, Marketing et Stratégie (MMS), Institut Mines-Télécom [Paris] (IMT), Département Management, Marketing et Stratégie (MMS), Enfance Adolescence & Diabète, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], LITEM-NPR, balague, Christine, Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Paris Cité (UPCité), Département Droit, Economie et Finances (IMT-BS - DEFI), Institut Mines-Télécom [Paris] (IMT)-Département Management, Marketing et Stratégie (IMT-BS - MMS), Département Management, Marketing et Stratégie (IMT-BS - MMS), Association Enfance Adolescence & Diabète [Toulouse], Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme 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), Association Francophone de Psychologie de la Santé (AFPSA), and CHU Toulouse [Toulouse]
Subjects: Professionnel de santé, [STAT.AP]Statistics [stat]/Applications [stat.AP], [STAT.ME] Statistics [stat]/Methodology [stat.ME], Mhealth, Recherche qualitative, Diabète de type 1, [SHS]Humanities and Social Sciences, Relation soignant-soigné, [STAT.AP] Statistics [stat]/Applications [stat.AP], [SHS.GESTION]Humanities and Social Sciences/Business administration, [SHS] Humanities and Social Sciences, [SHS.GESTION] Humanities and Social Sciences/Business administration, application, [STAT.ME]Statistics [stat]/Methodology [stat.ME]
Abstract: International audience; Contexte : Il est peu abordé dans la littérature l’impact des technologies mobiles et applicatives sur la relation soignant.e-soigné.e, et la perception des professionnel.les de santé travaillant avec des adolescent.es vivant avec un de diabète de type 1. L’objectif de cette étude est de présenter le point de vue des professionnel.les de santé concernant les effets sur la relation soignant.e-soigné.e de l’usage d’une application mobile d’ETP auprès d’adolescents diabétiques. Méthode : Nous avons eu recours à un design d’étude qualitative afin de réaliser des entretiens semi-directifs auprès de 14 professionnel.les de santé (médecins, infirmières, diététiciennes, psychologue). Ces entretiens ont été enregistrés et retranscrits ad verbatim, puis analysés selon une méthode inductive. Résultats : L’analyse des entretiens fait ressortir trois thèmes : 1) les applications favorisent la construction et le renforcement de la relation soignant.e-soigné.e, 2) la conscience et la prise en compte du risque que peut engendrer la digitalisation sur la relation, 3) la démarche importante d’intégration du numérique tout en préservant la relation. Discussion : Les résultats viennent nourrir une réflexion plus générale au sujet du risque de déshumanisation du soin lié à la digitalisation des pratiques de soin et des prises en charge. La perspective des professionnel.les de santé, converge avec celle des patient.es décrite dans la littérature, notamment en ce qui concerne l’amélioration de la communication et la prise de décision partagée. Par conséquent, la digitalisation de l’ETP par l’usage d’application mobile semble compatible avec la préservation de la relation humaine essentielle au soin.
Published: 2021

2. Orosensory Perception of Fat/Sweet Stimuli and Appetite-Regulating Peptides before and after Sleeve Gastrectomy or Gastric Bypass in Adult Women with Obesity

Author: Arnaud Bernard, Nathalie Casanova, Johanne Le Beyec-Le Bihan, Xavier Collet, Cindy Le Bourgot, Muriel Coupaye, Cédric Le May, Pascaline Delaby, Séverine Ledoux, Ouidad Sami, Philippe Besnard, Loredana Radoi, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Lesieur Groupe Avril, Tereos, AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Beaujon [AP-HP], Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU 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 de référence du syndrome de Prader-Willi et autres syndromes avec troubles du comportement alimentaire (CRMR PRADOR), Centre de Référence du Syndrome de Prader-Willi, 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)-Hôpital Marin d'Hendaye-CHU Pitié-Salpêtrière [AP-HP], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Tereos R&D, Radoï, Loredana, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, Taste, Sucrose, obesity, medicine.medical_treatment, Appetite, Gastroenterology, 0302 clinical medicine, Surveys and Questionnaires, Postoperative Period, media_common, Nutrition and Dietetics, digestive, oral, and skin physiology, Taste Perception, health, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Postprandial Period, Obesity, Morbid, Treatment Outcome, Female, lcsh:Nutrition. Foods and food supply, Adult, Sleeve gastrectomy, medicine.medical_specialty, media_common.quotation_subject, bariatric surgery, Gastric bypass, Gastric Bypass, 030209 endocrinology & metabolism, lcsh:TX341-641, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Article, Gastrointestinal Hormones, Linoleic Acid, 03 medical and health sciences, Food Preferences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Gastrectomy, Internal medicine, Perception, sweet taste, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, 030109 nutrition & dietetics, business.industry, Sweet taste, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, appetite-regulating hormones, Obesity, fat taste, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Hormone
Abstract: The aim of this study was to explore the impact of bariatric surgery on fat and sweet taste perceptions and to determine the possible correlations with gut appetite-regulating peptides and subjective food sensations. Women suffering from severe obesity (BMI &gt, 35 kg/m2) were studied 2 weeks before and 6 months after a vertical sleeve gastrectomy (VSG, n = 32) or a Roux-en-Y gastric bypass (RYGB, n = 12). Linoleic acid (LA) and sucrose perception thresholds were determined using the three-alternative forced-choice procedure, gut hormones were assayed before and after a test meal and subjective changes in oral food sensations were self-reported using a standardized questionnaire. Despite a global positive effect of both surgeries on the reported gustatory sensations, a change in the taste sensitivity was only found after RYGB for LA. However, the fat and sweet taste perceptions were not homogenous between patients who underwent the same surgery procedure, suggesting the existence of two subgroups: patients with and without taste improvement. These gustatory changes were not correlated to the surgery-mediated modifications of the main gut appetite-regulating hormones. Collectively these data highlight the complexity of relationships between bariatric surgery and taste sensitivity and suggest that VSG and RYGB might impact the fatty taste perception differently.
Published: 2021
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3. Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis

Author: Pineau, Fanny, Caimmi, Davide, Magalhães, Milena, Fremy, Enora, Mohamed, Abdillah, Mely, Laurent, Leroy, Sylvie, Murris, Marlene, Claustres, Mireille, Chiron, Raphaël, De Sario, Albertina, 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), 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, 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, Centre de Ressources et de Compétences en Mucoviscidose [Toulouse] (CRCM [Toulouse]), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), DE SARIO, Albertina, 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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Cystic Fibrosis, Pulmonology, [SDV]Life Sciences [q-bio], Cystic Fibrosis Transmembrane Conductance Regulator, Pulmonary Function, Gene Expression, Comorbidity, Pathology and Laboratory Medicine, White Blood Cells, Endocrinology, Animal Cells, Medicine and Health Sciences, Lung, Gene Ontologies, Pseudomonas Aeruginosa, Genomics, Bacterial Pathogens, [SDV] Life Sciences [q-bio], Genetic Diseases, Medical Microbiology, Medicine, Female, Pathogens, Cellular Types, Research Article, Adult, Cell Binding, Cell Physiology, Endocrine Disorders, Science, Immune Cells, Immunology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Microbiology, Autosomal Recessive Diseases, Pseudomonas, Diabetes Mellitus, Genetics, Humans, Pseudomonas Infections, Microbial Pathogens, Clinical Genetics, Genes, Modifier, Blood Cells, Bacteria, Organisms, Biology and Life Sciences, Computational Biology, Cell Biology, Genome Analysis, Fibrosis, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Metabolic Disorders, Mutation, Transcriptome, Developmental Biology
Abstract: International audience; Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze-omic datasets in rare genetic diseases as patient cohorts are inevitably small.
Published: 2020
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4. Dynamic changes of DNA methylation and lung disease in cystic fibrosis: lessons from a monogenic disease

Author: Nathan Alary, Laurent Mely, Florence Busato, Milena Magalhães, Sylvie Leroy, Fanny Pineau, Isabelle Rivals, Raphaël Chiron, Albertina De Sario, Jörg Tost, Davide Caimmi, M. Murris, Mireille Claustres, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Epigénétique et d'Environnement [Evry] (CNG - CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de Genotypage-Institut de Génomique [Evry], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), 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 National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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 Hospitalier Universitaire de Nice (CHU Nice), 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, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Gene Expression, Nose, Biology, Cystic fibrosis, cystic fibrosis, 03 medical and health sciences, Immune system, Genetics, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Enhancer, Gene, ComputingMilieux_MISCELLANEOUS, epigenetics and disease, DNA methylation, Lung, Epithelial Cells, medicine.disease, Phenotype, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, CpG site, Cancer research, CpG Islands, Female
Abstract: Aim: To assess whether DNA methylation levels account for the noninherited phenotypic variations observed among cystic fibrosis (CF) patients. Patients & methods: Using the 450 K BeadChip, we profiled DNA methylation in nasal epithelial cells collected from 32 CF patients and 16 controls. Results: We detected substantial DNA methylation differences up to 55% (median β change 0.13; IQR: 0.15–0.11) between CF patients and controls. DNA methylation levels differed between mild and severe CF patients and correlated with lung function at 50 CpG sites. Conclusion: In CF samples, dynamic changes of DNA methylation occurred in genes responsible for the integrity of the epithelium and the inflammatory and immune responses, were prominent in transcriptionally active genomic regions and were over-represented in enhancers active in lung tissues. ( Clinicaltrials.gov NCT02884622).
Published: 2018
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5. Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis

Author: Pierre-Régis Burgel, Anne Munck, Isabelle Durieu, Raphaël Chiron, Laurent Mely, Anne Prevotat, Marlene Murris-Espin, Michele Porzio, Michel Abely, Philippe Reix, Christophe Marguet, Julie Macey, Isabelle Sermet-Gaudelus, Harriet Corvol, Stéphanie Bui, Lydie Lemonnier, Clémence Dehillotte, Jennifer Da Silva, Jean-Louis Paillasseur, Dominique Hubert, Julie Mounard, Claire Poulet, Cinthia Rames, Christine Person, Françoise Troussier, Thierry Urban, Marie-Laure Dalphin, Jean-Claude Dalphin, Didier Pernet, Bénédicte Richaud-Thiriez, Mickael Fayon, Julie Macey-Caro, Karine Campbell, Muriel Laurans, Corinne Borderon, Marie-Christine Heraud, André Labbé, Sylvie Montcouquiol, Laurence Bassinet, Natascha Remus, Annlyse Fanton, Anne Houzel-Charavel, Frédéric Huet, Stéphanie Perez-Martin, Amale Boldron-Ghaddar, Manuela Scalbert, Boubou Camara, Catherine Llerena, Isabelle Pin, Sébastien Quétant, Aurélie Cottereau, Antoine Deschildre, Alice Gicquello, Thierry Perez, Lidwine Stervinou-Wemeau, Caroline Thumerelle, Benoit Wallaert, Nathalie Wizla, Jane Languepin, Céline Ménétrey, Magalie Dupuy-Grasset, Lucie Bazus, Clelia Buchs, Virginie Jubin, Marie-Christine Werck-Gallois, Catherine Mainguy, Thomas Perrin, Agnès Toutain-Rigolet, Stéphane Durupt, Quitterie Reynaud, Raphaele Nove-Josserand, Melisande Baravalle-Einaudi, Bérangère Coltey, Nadine Dufeu, Jean-Christophe Dubus, Nathalie Stremler, Davide Caimmi, Yves Billon, Jocelyne Derelle, Sébastien Kieffer, Anne-Sophie Pichon, Cyril Schweitzer, Aurélie Tatopoulos, Sarah Abbes, Tiphaine Bihouée, Isabelle Danner-Boucher, Valérie David, Alain Haloun, Adrien Tissot, Sylvie Leroy, Carole Bailly-Piccini, Annick Clément, Aline Tamalet, Isabelle Honoré, Reem Kanaan, Clémence Martin, Cécile Bailly, Frédérique Chédevergne, Jacques De Blic, Brigitte Fauroux, Murielle Le Bourgeois, Bertrand Delaisi, Michèle Gérardin, Michel Abély, Bruno Ravoninjatovo, Chantal Belleguic, Benoit Desrues, Graziella Brinchault, Michel Dagorne, Eric Deneuville, Sylvaine Lefeuvre, Anne Dirou, Jean Le Bihan, Sophie Ramel, Stéphane Dominique, Annabelle Payet, Romain Kessler, Vincent Rosner, Laurence Weiss, Sandra de Miranda, Dominique Grenet, Abdoul Hamid, Clément Picard, François Brémont, Alain Didier, Géraldine Labouret, Marie Mittaine, Marlène Murris-Espin, Laurent Têtu, Laure Cosson, Charlotte Giraut, Anne-Cécile Henriet, Julie Mankikian, Sophie Marchand, Sandrine Hugé, Véronique Storni, Emmanuelle Coirier-Duet, CHU Cochin [AP-HP], Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Ressources et de Compétences en Mucoviscidose [Lyon] (CRCM [Lyon]), Hospices Civils de Lyon (HCL)-CHU Lyon-Hôpital Renée Sabran [CHU - HCL], Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse], 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), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de recherche Croissance et signalisation (UMR_S 845), 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 pneumologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Association Vaincre La Mucoviscidose, Institut Cochin (IC UM3 (UMR 8104 / U1016)), EFFI-STAT, CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), CHU Trousseau [APHP], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca-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) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe hospitalier Broca-Université Paris Descartes - Paris 5 (UPD5)-Hôtel-Dieu-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Cystic Fibrosis, Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], Aminopyridines, Quinolones, Critical Care and Intensive Care Medicine, Logistic regression, Aminophenols, Cystic fibrosis, Body Mass Index, Ivacaftor, chemistry.chemical_compound, 0302 clinical medicine, Deprescriptions, Forced Expiratory Volume, Medicine, 030212 general & internal medicine, Fatigue, 2. Zero hunger, biology, Lumacaftor, Headache, lumacaftor–ivacaftor, Cystic fibrosis transmembrane conductance regulator, 3. Good health, Anti-Bacterial Agents, Drug Combinations, Treatment Outcome, Administration, Intravenous, Female, France, medicine.drug, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Metrorrhagia, Adolescent, Nutritional Status, 03 medical and health sciences, Young Adult, Internal medicine, Product Surveillance, Postmarketing, Humans, Benzodioxoles, Adverse effect, Bronchial Spasm, business.industry, Editorials, Myalgia, medicine.disease, Discontinuation, Dyspnea, Logistic Models, 030228 respiratory system, chemistry, Cough, Multivariate Analysis, biology.protein, postmarketing study, business, Body mass index
Abstract: International audience; Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting.Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations.Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses.Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.
Published: 2019
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6. Intestinal Inflammation in Children with Cystic Fibrosis Is Associated with Crohn's-Like Microbiota Disturbances

Author: Patrick Berger, Thomas Bazin, Thierry Lamireau, Christophe Hubert, Michael Fayon, Thomas Barnetche, Thierry Schaeverbeke, Laurence Delhaes, H. Clouzeau, Katarzyna B. Hooks, Aurélien Barré, Philippe Lehours, Cécile Bébéar, Stéphanie Bui, Macha Nikolski, Raphaël Enaud, Marie Massot, 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), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), CHU Bordeaux [Bordeaux], Laboratoire Hubert Curien [Saint Etienne] (LHC), Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS), Biodiversité, Gènes & Communautés (BioGeCo), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), USC EA 3671, infections humaines à mycoplasmes et chlamydiae, Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Pneumologie Pédiatrique [Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Centre d'Investigation Clinique (CIC 0005), Infection à helicobacter, inflammation et cancer, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], Service de Parasitologie et de Mycologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), 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 Hooks, Katarzyna
Subjects: 0301 basic medicine, dysbiosis index, Faecalibacterium prausnitzii, lcsh:Medicine, Inflammation, Gut flora, Cystic fibrosis, digestive system, Article, cystic fibrosis, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, fluids and secretions, intestinal inflammation, Medicine, Veillonella dispar, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, gut microbiota, business.industry, fecal calprotectin, lcsh:R, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, stomatognathic diseases, 030104 developmental biology, Immunology, 030211 gastroenterology & hepatology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacteroides, medicine.symptom, Calprotectin, business, Dysbiosis
Abstract: Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut inflammation and microbiota dysbiosis is still poorly understood. The main objective of this study was to assess gut microbiota composition in CF children depending on their intestinal inflammation. We collected fecal samples from 20 children with CF. Fecal calprotectin levels were measured and fecal microbiota was analyzed by 16S rRNA sequencing. We observed intestinal inflammation was associated with microbiota disturbances characterized mainly by increased abundances of Staphylococcus, Streptococcus, and Veillonella dispar, along with decreased abundances of Bacteroides, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Those changes exhibited similarities with that of Crohn&rsquo, s disease (CD), as evidenced by the elevated CD Microbial-Dysbiosis index that we applied for the first time in CF. Furthermore, the significant over-representation of Streptococcus in children with intestinal inflammation appears to be specific to CF and raises the issue of gut&ndash, lung axis involvement. Taken together, our results provide new arguments to link gut microbiota and intestinal inflammation in CF and suggest the key role of the gut&ndash, lung axis in the CF evolution.
Published: 2019
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7. Carriage of a Single Strain of Nontoxigenic Corynebacterium diphtheriae bv. Belfanti ( Corynebacterium belfantii ) in Four Patients with Cystic Fibrosis

Author: Frédéric Huet, K. Astruc, Marion Benouachkou, Catherine Neuwirth, Diane Pivot, Annlyse Fanton, Alexis Criscuolo, Serge Aho, Julie Toubiana, Edgar Badell-Ocando, Lucie Amoureux, Sylvain Brisse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported financially by Dijon University Hospital, Institut Pasteur, and Public Health France., We acknowledge the help of Melody Dazas and Annick Carmi-Leroy for the microbiological characterization of the isolates. We thank the 'Plateforme de Microbiologie Mutualisée' from Institut Pasteur for genomic sequencing, Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), MESH: Cystic Fibrosis, Biovar, [SDV]Life Sciences [q-bio], Corynebacterium, MESH: Asymptomatic Infections, Cystic fibrosis, Microbiology, cystic fibrosis, 03 medical and health sciences, MESH: Corynebacterium diphtheriae, MESH: Anti-Bacterial Agents, medicine, Colonization, MESH: Diphtheria, 030304 developmental biology, Corynebacterium diphtheriae, 0303 health sciences, Corynebacterium diphtheriae bv. belfanti, MESH: Humans, biology, 030306 microbiology, business.industry, transmission, MESH: Adult, Antimicrobial, biology.organism_classification, medicine.disease, colonization, MESH: Male, 3. Good health, MESH: France, Carriage, genomic sequencing, epidemiology, business, MESH: Whole Genome Sequencing, MESH: Female
Abstract: International audience; Cystic fibrosis (CF) patients are commonly colonized by bacterial pathogens, which can induce persistent lung inflammation and may contribute to clinical deterioration. Colonization of CF patients and cross-transmission by Corynebacterium diphtheriae have not been reported so far. The aim of this article was to investigate the possibility of a cross-transmission of C. diphtheriae biovar Belfanti between four patients of a CF center. C. diphtheriae biovar Belfanti (now formally called C. belfantii) isolates were collected from four patients in a single CF care center over a period of 6 years and analyzed by microbiological methods and whole-genome sequencing. Epidemiological links among patients were investigated. Ten isolates were collected from 4 patients. Whole-genome sequencing of one isolate from each patient showed that a single strain was shared among them. In addition, one patient was found to have the same strain in two consecutive samplings performed 9 months apart. The strain was nontoxigenic and was susceptible to most antimicrobial agents. Ciprofloxacin resistance was observed in one patient. The idea of transmission of the strain among patients was supported by the occurrence of same-day visits to the CF center. This study demonstrated colonization of CF patients by C. diphtheriae biovar Belfanti (C. belfantii), and the data suggest persistence and transmission of a unique strain during at least 6 years in a single CF patient care center.
Published: 2019
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8. Moving the Dial on Airway Inflammation in Response to Trikafta in Adolescents with Cystic Fibrosis

Author: Agathe, Lepissier, Anne Sophie, Bonnel, Nathalie, Wizla, Laurence, Weiss, Marie, Mittaine, Katia, Bessaci, Eitan, Kerem, Véronique, Houdouin, Philippe, Reix, Christophe, Marguet, Isabelle, Sermet-Gaudelus, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Référence Maladies Rares, Mucoviscidose et maladies apparentées (CRMR2MA / CHU Necker - Enfants Malades [AP-HP]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de Hautepierre [Strasbourg], 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), Service de pédiatrie générale et spécialisée [CHU de Reims - American Memorial Hospital] (SPGS), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Reims), Hadassah Hebrew University Medical Center [Jerusalem], Centre de ressources et de compétences pour la mucoviscidose [Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Cité (UPCité), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche sur le Handicap Ventilatoire (GRHV), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Goethe-University Frankfurt am Main, and dormoy, valerian
Subjects: [SDV] Life Sciences [q-bio], Pulmonary and Respiratory Medicine, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Biomarker, Inflammation, Critical Care and Intensive Care Medicine, CFTR modulator
Abstract: International audience; No abstract available
Published: 2023
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9. 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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10. Developmental dyslexia, developmental coordination disorder and comorbidity discrimination using multimodal structural and functional neuroimaging

Author: Federico Nemmi, Fabien Cignetti, Marianne Vaugoyeau, Christine Assaiante, Yves Chaix, Patrice Péran, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Santé, Plasticité, Motricité (TIMC-SPM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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 (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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 (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Pédiatrie générale et infectiologie [CHU Toulouse], Pôle Enfants [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Neuropsychology and Physiological Psychology, Cognitive Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, Experimental and Cognitive Psychology
Abstract: International audience
Published: 2023
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11. Amygdala hyperactivation relates to eating behavior: a potential indicator of food addiction in Prader-Willi syndrome

Author: Strelnikov, Kuzma, Debladis, Jimmy, Salles, Juliette, Valette, Marion, Cortadellas, Julie, Tauber, Maithé, Barone, Pascal, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and BARONE, Pascal
Subjects: [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, addiction, amygdala, Prader-Willi syndrome, eating behavior
Abstract: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder involving nutritional, endocrine /metabolic, emotional and behavior dimensions. There is evidence for impaired hypothalamic development and function in PWS, involving oxytocin and ghrelin, which can account for the typical PWS phenotype. Hyperphagia with addiction-like behavior is one of the common features of PWS and is a consequence of the hypothalamic dysfunction. In this study, we hypothesized that brain regions associated with compulsive eating behavior would be abnormally activated by food-related odors in PWS, as these can stimulate the appetite and induce hunger-related behavior.MethodsWe used a classic olfactory discrimination test to verify that olfaction was normal in patients with PWS. In an fMRI scanner, we presented two odors, a tulip and a caramel odor, which have a different hedonic valence and a different capacity to arouse hunger-related behavior.ResultsThere was a five-fold higher activation in the right amygdala for the caramel odor compared with the tulip odor in patients with PWS (n=14). No such hyperactivation was found in age-matched controls (n=11). Cluster analysis of clinical hyperphagia scores in patients with PWS revealed a link with the right amygdala hyperactivation.ConclusionsOur study provides evidence for functional alteration of the right amygdala in PWS, which is part of the brain reward network involved in food addiction. This finding may relate to dysfunction of the ghrelin and oxytocin systems in PWS, as these are involved in addictive behavior, appetite, and olfactory bulb regulation.
Published: 2022
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12. SNORD116 and growth hormone therapy impact IGFBP7 in Prader–Willi syndrome

Author: Lisa Cole Burnett, Françoise Conte Auriol, Eric Bieth, Jean Pierre Salles, Juliette Salles, Maithé Tauber, Gwenaelle Diene, Catherine Molinas, Rudolph L. Leibel, Boris V. Skryabin, Isabelle Gennero, Timofey S. Rozhdestvensky, Sanaa Eddiry, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Service Psychiatrie et psychologie médicale [CHU Toulouse], Pôle Psychiatrie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Illinois [Chicago] (UIC), University of Illinois System, Columbia University [New York], and Pistre, Karine
Subjects: 0301 basic medicine, MESH: Prader-Willi Syndrome* / genetics, medicine.medical_specialty, MESH: RNA, Small Nucleolar, congenital, hereditary, and neonatal diseases and abnormalities, IGFBP7, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, MESH: Neurons, MESH: Induced Pluripotent Stem Cells, Article, MESH: Prader-Willi Syndrome* / drug therapy, 03 medical and health sciences, Mice, 0302 clinical medicine, Neurodevelopmental disorder, Downregulation and upregulation, Internal medicine, medicine, Animals, Humans, RNA, Small Nucleolar, MESH: Animals, MESH: Mice, Genetics (clinical), Neurons, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Dopaminergic, nutritional and metabolic diseases, medicine.disease, Phenotype, Pathophysiology, nervous system diseases, [SDV] Life Sciences [q-bio], 030104 developmental biology, Endocrinology, MESH: Growth Hormone, Growth Hormone, Knockout mouse, business, Genomic imprinting, Prader-Willi Syndrome, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS.Methods: We collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness.Results: We found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1.Conclusion: SNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.
Published: 2021
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13. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

Author: Aleksander Edelman, Philippe Reix, Stéphanie Bui, E. Deneuville, F. Huet, Gérard Lenoir, Delphine Roussel, Gabriel Bellon, Isabelle Sermet-Gaudelus, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Régulation des systèmes de transport dans les épithéliums (UMR_S467), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre de Ressources et de Compétences de la Mucoviscidose, hôpital Sud, Hôpital d'Enfants du Bocage, Centre de Ressources et de compétences de la mucoviscidose (CRCM), Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Supported by Assistance Publique des Hôpitaux de Paris, Vaincre La Mucoviscidose and ABCF Protéines Associations., Edelman, Aleksander, Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, and Hospices Civils de Lyon (HCL) - Hospices Civils de Lyon (HCL)
Subjects: Male, Pathology, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Mucous membrane of nose, MESH : Equipment Design, MESH : Child, Preschool, MESH: Catheterization, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Gastroenterology, MESH: Amiloride, Amiloride, Study Protocol, MESH : Catheterization, MESH: Genetic Screening, Subcutaneous Tissue, 0302 clinical medicine, MESH : Electric Conductivity, Reference Values, MESH : Chlorides, MESH : Female, 030212 general & internal medicine, Sympathomimetics, Sweat, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, Mutation, biology, medicine.diagnostic_test, lcsh:RJ1-570, MESH : Infant, Equipment Design, MESH: Infant, Cystic fibrosis transmembrane conductance regulator, Electrodes, Implanted, 3. Good health, Perfusion, Research Design, Child, Preschool, Chloride channel, Female, France, Sodium Channel Blockers, MESH: Infant, Newbo, medicine.medical_specialty, MESH : Electrodes, Implanted, MESH: Cystic Fibrosis, MESH: Electric Conductivity, Sensitivity and Specificity, Catheterization, 03 medical and health sciences, MESH : Amiloride, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neonatal Screening, Chlorides, Predictive Value of Tests, MESH : Cystic Fibrosis, 030225 pediatrics, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunoreactive trypsinogen, Pediatrics, Perinatology, and Child Health, Genetic Testing, MESH: Chlorides, MESH : France, Genetic testing, MESH : Genetic Screening, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Newborn screening, MESH: Humans, Ion Transport, business.industry, MESH : Cystic Fibrosis Transmembrane Conductance Regulator, MESH : Humans, MESH: Child, Preschool, Sodium, Electric Conductivity, Infant, Newborn, Isoproterenol, Infant, lcsh:Pediatrics, medicine.disease, MESH: France, Nasal Mucosa, MESH : Infant, Newbo, Pediatrics, Perinatology and Child Health, biology.protein, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Electrodes, Implanted, business, MESH: Female, MESH: Equipment Design
Abstract: Background Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. Methods/Design We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na+) transport in response to the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl-) secretion in response to isoproterenol, a β-agonist in a Cl- free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. Discussion A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.
Published: 2006
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14. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real‐life French multi‐centre adult cohort

Author: Laurent Guilleminault, Lise Rosencher, A. Proust, Arnaud Bourdin, Clairelyne Dupin, S. Fry, Drifa Belhadi, Cécile Chenivesse, Patrick Berger, Frédéric de Blay, Alain Didier, Anne‐Sophie Gamez, Camille Couffignal, Philippe Bonniaud, Gilles Garcia, Camille Taillé, Pierre-Olivier Girodet, Chantal Raherison, Christophe Leroyer, Geneviève Le Bourdellès, Guillaume Mahay, MORNET, Dominique, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), CHU Strasbourg, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université européenne de Bretagne - European University of Brittany (UEB), CHU Rouen, Normandie Université (NU), Université de Bordeaux (UB), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Hôpital Bicêtre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Investigation Clinique – Épidémiologie Clinique [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Service de pneumologie et allergologie pédiatrique [CHU Toulouse]
Subjects: Male, 0301 basic medicine, Hypereosinophilia, Severity of Illness Index, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Prednisone, Interquartile range, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, oral steroid, MESH: Antibodies, Monoclonal, Humanized / adverse effects, MESH: Middle Aged, EPICENE, MESH: Follow-Up Studies, Middle Aged, Dupilumab, 3. Good health, Cohort, Female, France, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.symptom, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Immunology, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, T2 inflammation, MESH: Severity of Illness Index, Internal medicine, side‐effect, medicine, Humans, MESH: Asthma / physiopathology, hypereosinophilia, MESH: Antibodies, Monoclonal, Humanized / administration & dosage, Retrospective Studies, Asthma, MESH: Humans, business.industry, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, MESH: Asthma / drug therapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, asthma, medicine.disease, MESH: Male, MESH: France, 030104 developmental biology, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Asthma / blood, business, MESH: Female, Follow-Up Studies
Abstract: International audience; Background: Dupilumab is a monoclonal anti‐IL‐4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side‐effects and/or life‐threatening exacerbations.Objective: To assess changes in asthma control between baseline and 12 months of treatment.Methods: Multi‐centre (n = 13) retrospective real‐life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447).Results: Overall, 64 patients with SA (median age 51, interquartile range [44‐61]; 53% females) received dupilumab as add‐on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7‐16] to 22 [17‐24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47‐75] to 68% [58‐88] (P = .001); and daily prednisone dose was reduced from 20 [10‐30] to 5 [0‐7] mg/d (P < .001). Annual exacerbations decreased from 4 [2‐7] to 1 [0‐2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow‐up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection‐site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators.Conclusion & clinical relevance: In this first real‐life cohort study of predominantly steroid‐dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long‐term prognosis of sustained dupilumab‐induced hypereosinophilia.
Published: 2020
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15. A defect of amphiregulin release predicted longer survival independently of YAP expression in patients with pleural mesothelioma in the IFCT ‐0701 MAPS phase 3 trial

Author: Maille, Elodie, Levallet, Jérôme, Dubois, Fatéméh, Antoine, Martine, Danel, Claire, Creveuil, Christian, Mazieres, Julien, Margery, Jacques, Greillier, Laurent, Gounant, Valérie, Moro‐sibilot, Denis, Molinier, Olivier, Léna, Hervé, Monnet, Isabelle, Bergot, Emmanuel, Langlais, Alexandra, Morin, Franck, Sherpereel, Arnaud, Zalcman, Gérard, Levallet, Guénaëlle, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Toulouse (CHU 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), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Le Mans (CH Le Mans), Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Brunaud, Carole, Service d'Anatomie et cytologie pathologiques [CHU Tenon], 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] Life Sciences [q-bio], Mesothelioma, Lung Neoplasms, Cell Line, Tumor, Pleural Neoplasms, [SDV]Life Sciences [q-bio], Mesothelioma, Malignant, Humans, malignant pleural mesothelioma, amphiregulin, YAP
Abstract: CERVOXY; International audience; The Hippo pathway effector YAP is dysregulated in malignant pleural mesothelioma (MPM). YAP’s target genes include the secreted growth factor amphiregulin (AREG), which is overexpressed in a wide range of epithelial cancers and plays an elusive role in MPM. We assayed the expression of YAP and AREG in MPM pathology samples and that of AREG additionally in plasma samples of patients from the randomized phase 3 IFCT-0701 Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) using immunohistochemistry and ELISA assays, respectively. MPM patients frequently presented high levels of tumor AREG (64.3%), a high cytosolic AREG expression being predictive of a better prognosis with longer median overall and progression-free survival. Surprisingly, tumor AREG cytosolic expression was not correlated with secreted plasma AREG. By investigating the AREG metabolism and function in MPM cell lines H2452, H2052, MSTO-211H, and H28, in comparison with the T47D ER+ breast cancer cell line used as a positive control, we confirm that AREG is important for cell invasion, growth without anchorage, proliferation, and apoptosis in mesothelioma cells. Yet, most of these MPM cell lines failed to correctly execute AREG post-translational processing by metalloprotease ADAM17/tumor necrosis factor-alpha-converting enzyme (TACE) and extra-cell secretion. The favorable prognostic value of high cytosolic AREG expression in MPM patients could therefore be sustained by default AREG post-translational processing and release. Thus, the determination of mesothelioma cell AREG content could be further investigated as a prognostic marker for MPM patients and used as a stratification factor in future clinical trials.
Published: 2022
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16. Avis de l'Anses relatif à la Pertinence de la ré-évaluation de la VTR chronique par voie orale pour les ions perchlorate

Author: Chevalier, Nicolas, Bodin, Laurent, Fini, Jean Baptiste, Garnier, Robert, Joyeux, Michel, Laurentie, Michel, Mortamais, Marion, Oliver Petit, Isabelle, Roudot, Alain-Claude, Viguié, Catherine, Wemeau, Jean-Louis, Angeli, Karine, Farion, Nicolas, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Retraité, Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille - Direction de la recherche et de l’innovation, Centre Hospitalier Universitaire de Lille (CHU de Lille), Direction de l'Evaluation des Risques (DER), and Anses
Subjects: Perchlorates, Toxicological reference values, Benchmark doses, [SDV]Life Sciences [q-bio], ions, valeur toxicologique de référence
Abstract: Since 2011, ANSES has been asked on several occasions to examine the health risks associated with perchlorate (ClO4-) in DW following the identification of situations in which resources used for DW production were contaminated. In 2011, the Agency had recommended a guideline value (GV) for perchlorate in DW of 15 µg.L-1 for adult consumers, derived from the TRV of 0.7 µg.kg bw-1.d-1(ANSES, 2011), based on the inhibition of iodine uptake by the thyroid gland. ANSES had also advised against using water contaminated by perchlorate when preparing feeding bottles for infants aged up to 6 months, pending a national survey on perchlorate contamination of food, in particular to clarify the concentrations found in the powdered infant formula used for bottle preparation.In 2012, in its opinion concerning epidemiological studies on associations between exposure to perchlorate in DW and thyroid function in specific populations, the Agency had concluded that: "the results from the evaluated epidemiological studies do not enable conclusions to be drawn concerning the possible association between thyroid-stimulating hormone (TSH) levels and perchlorate concentrations in drinking water in pregnant women and newborns [...]. The absence of information concerning the iodine status of the studied populations makes it difficult to interpret the published epidemiological data." (ANSES, 2012).In its opinion of 8 April 2014 on the presence of perchlorate in infant formula and in DW, the Agency had noted the same limitations relating to the available epidemiological studies and insisted on the need to take account of the iodine status of the study population for assessing the health impact of human exposure to perchlorate and for interpreting the published epidemiological data.In its opinion of 26 December 2018, the Agency had concluded that recent epidemiological studies, including the one by the French Institute for Public Health Surveillance1(InVS) published in 2016, did not provide any additional conclusive evidence on the biological or clinical effects of perchlorate versus those taken into account in the previous ANSES opinions (ANSES 2011, 2012, 2014). The data examined in this opinion did not call into question the conclusions of the previous ANSES opinions concerning the hazard characterisation and the RV proposed by the Agency in 2011.However, with regard to the assessment of exposure to perchlorate, new data made it possible to estimate the average oral exposure of the adult population to perchlorate. This estimate was based firstly on data on perchlorate contamination of food collected by the Directorate General for Competition Policy, Consumer Affairs and Fraud Control (DGCCRF) as part of its national surveys, and secondly on data on DW contamination for the period 2014-2017 produced by the Regional Health Agencies (ARSs) and available in the SISE-Eaux database. On this basis, ANSES estimated that exposure via DW consumption accounted for about 25% of ingestion exposure. As this estimate was in line with the data in the literature and was close to the 20% default percentage defined by the World Health Organization (WHO) in 2016, the Agency felt it necessary to lower to 20% the share of exposure via water (which had previously been set at 60%) used for calculating the GV of perchlorate in DW for adults. As a result, the proposed GV was lowered to 5 µg.L-1 for the adult population.ANSES also emphasised that the existing data on food contamination were too incomplete to characterise the distribution of the general population's exposure to perchlorate by the oral route and to assess the health risk. It therefore recommended that perchlorate be included in the third French Total Diet Study (TDS3).In the absence of new data on the contamination of infant formula with perchlorate since the 2014 expert appraisal, the Agency also reiterated the conclusions of this earlier expert appraisal: "daily intakes of perchlorate, calculated on the basis of perchlorate levels in infant formulas available on the French market, do not exceed the TRV of 0.7 µg.kg bw-1.d-1for 95% of the population of children aged under 6 months consuming infant formula based on an average concentration of perchlorate of 1 µg.L-1in DW for reconstituting infant bottles" (ANSES, 2018).Lastly, ANSES indicated in this same 2018 opinion, in Section 3.2.8 concerning the conclusions on the choice of the TRV, that the Working Group on "Assessment of the health risks associated with chemical parameters in drinking water" (ERS EDCH) and the Expert Committee (CES) on "Water" considered that in any future assessment of the health risks associated with the ingestion of perchlorate, following publication of the work under way by the US EPA, it would be necessary to re-examine the method for determining the critical dose and establishing the TRV for perchlorate."All the agencies establishing chronic oral TRVs for perchlorate have chosen inhibition of iodine uptake by the thyroid as the critical effect (Table 1 on page 8).In 2019, the US EPA adopted a different approach based on toxicokinetic-toxicodynamic modelling to assess the impact of perchlorate exposure on thyroid hormone (TH) production and the effect of a reduction in maternal plasma free thyroxine (fT4) concentrations during the first trimester of pregnancy on the child's neurodevelopment, as measured by a decrease in intelligence quotient. The US EPA suggested adopting a TRV of 2.2 µg.kg bw-1.d-1, resulting in a maximum contaminant level of 56 µg.L-1 perchlorate in DW.As mentioned previously, and in view of the management difficulties encountered, the DGS had formally asked ANSES to analyse the US EPA's work on assessing the health risks associated with the presence of perchlorate in DW, in order to provide the ARSs with appropriate and proportionate guidance on the health risk.In view of this, ANSES was asked to re-examine the assessment of the health risks associated with the ingestion of perchlorate, in light of the US EPA's work. The first deliverable of this formal request therefore had the ultimate objective of determining whether the ANSES TRV of 0.7 µg.kg bw1.d-1 should be maintained. This first deliverable concluded that this TRV should not be called into question in light of the US EPA's work, mainly because of major uncertainties about the predictive ability of the model used. The Agency therefore decided to retain its chronic oral TRV established in 2011, based on the no-effect level observed in the study by Greer et al. (2002). However, all the TRVs established since that date are based on a Benchmark Dose (BMD) approach, so the Agency therefore issued an internal request to assess the relevance of this approach, based in particular on recent publications (Weterings et al. 2016, Bruce et al. 2018, Haber et al. 2021).; Depuis 2011, l’Anses a été saisie à plusieurs reprises sur les risques sanitaires liés aux ions perchlorate (ClO4-) dans les eaux destinées à la consommation humaine (EDCH), suite à la mise en évidence de situations de contamination de ressources utilisées pour la production d’EDCH. En 2011, l’Agence avait préconisé une valeur guide (VG) pour les ions perchlorate dans les EDCH de 15 µg.L-1 pour le consommateur adulte, définie à partir de la VTR de 0,7 µg.kg p.c.-1.j-1(Anses, 2011), fondée sur l’inhibition du captage de l’iode par la thyroïde. L’Anses avait également conseillé de ne pas utiliser une eau contaminée par les ions perchlorate pour la préparation des biberons des nourrissons jusqu’à 6 mois, dans l'attente de la réalisation d’une enquête nationale sur la contamination des aliments en perchlorates, en particulier pour préciser les concentrations retrouvées dans les formulations de lait maternisé en poudre utilisées pour la préparation des biberons.En 2012, dans son avis relatif aux études épidémiologiques portant sur les associations entre une exposition aux ions perchlorate dans les EDCH et la fonction thyroïdienne dans des populations spécifiques, l’Agence concluait : « les résultats des études épidémiologiques examinées par les experts ne permettent pas de conclure quant à l’existence ou à l’absence d’une association chez les femmes enceintes ou les nouveau-nés entre les niveaux de thyréostimuline (TSH, thyroid stimulating hormone) et des concentrations en ions perchlorate dans les eaux de boisson […]. L’absence d’information concernant le statut en iode des populations étudiées rend difficile l’interprétation des données épidémiologiques publiées. »(Anses, 2012).Dans son avis du 8 avril 2014 relatif à la présence d’ions perchlorate dans le lait infantile et dans les EDCH, l’Agence relevait les mêmes limites relatives aux études épidémiologiques disponibles et insistait sur la nécessité de prendre en compte le statut en iode de la population étudiée pour l’évaluation de l’impact sanitaire de l’exposition aux ions perchlorate chez l’Homme et pour l’interprétation des données épidémiologiques publiées.Dans son avis du 26 décembre 2018, l’Agence concluait que les études épidémiologiques récentes, y compris celle de de l’Institut de veille sanitaire1(InVS) publiée en 2016, n’apportaient pas d’éléments conclusifs supplémentaires sur les effets biologiques ou cliniques des ions perchlorate par rapport à celles prises en compte dans les précédents avis de l’Anses (Anses 2011, 2012, 2014). Les données examinées dans cet avis n’étaient pas de nature à remettre en cause les conclusions des avis précédents de l’Anses, concernant la caractérisation des dangers et la VTR proposée en 2011 par l’Agence.Cependant, s’agissant de l’évaluation de l’exposition aux ions perchlorate, de nouvelles données ont permis d’estimer l’exposition moyenne de la population adulte aux ions perchlorate par voie orale. Cette estimation se fondait d’une part sur les données de contamination des aliments par les ions perchlorate, recueillies par la Direction générale de la concurrence, de la consommation et de la répression des fraudes (DGCCRF) dans le cadre de ses enquêtes nationales et d’autre part sur les données de contamination des EDCH pour la période 2014-2017, produites par les Agences régionales de santé (ARS) et disponibles dans la base de données SISE-Eaux. Sur cette base, l’Anses estimait que la contribution de ’exposition liée à la consommation d’EDCH représente environ 25% de l’exposition par ingestion. Cette estimation concordant avec les données de la littérature et se rapprochant du pourcentage de 20% défini par défaut par l’Organisation Mondiale de la Santé (OMS) en 2016, l’Agence considérait nécessaire d’abaisser à 20% la part de l’exposition hydrique pour le calcul de la VG des ions perchlorate dans les EDCH pour les adultes, antérieurement fixée à 60%. En conséquence, la VG proposée avait été abaissée à 5 µg.L-1 pour la population adulte. L’Anses soulignait, par ailleurs, que les données existantes de contamination des aliments étaient trop parcellaires pour caractériser la distribution de l’exposition de la population générale aux ions perchlorate par voie orale et évaluer le risque sanitaire. En conséquence, elle recommandait de prendre en compte les ions perchlorate lors de l’étude de l’alimentation totale (EAT) 3.En l’absence de nouvelles données de contamination des laits infantiles par les ions perchlorate depuis l’expertise de 2014, l’Agence rappelait également les conclusions de ce précédent avis : « les apports journaliers en ions perchlorate, calculés sur la base des teneurs en ions perchlorate des laits infantiles disponibles sur le marché français, ne dépassent pas la VTR de 0,7 µg.kg p.c.-1.j-1 pour 95% de la population des enfants âgés de moins de 6 mois consommateurs de laits infantiles sur la base d’une concentration moyenne en ions perchlorate dans l’EDCH de 1 µg.L-1 pour la reconstitution des biberons » (Anses, 2018).Enfin, l’Anses indiquait dans ce même avis publié en 2018, au paragraphe 3.2.8 relatif aux conclusions sur le choix de la VTR : « le groupe de travail « Évaluation des risques sanitaires associés aux paramètres chimiques des eaux destinées à la consommation humaine) » (ERS EDCH) et le comité d’experts spécialisés (CES) « Eaux » estiment qu’en cas de future évaluation des risques sanitaires liés à l’ingestion d’ions perchlorate postérieure à la publication des travaux en cours de l’US EPA, il sera nécessaire de réexaminer le mode de détermination de la dose critique et de construction de la VTR des ions perchlorate. »L’ensemble des organismes établissant une VTR chronique par voie orale pour les ions perchlorate ont retenu comme effet critique l'inhibition du captage de l'iode au niveau thyroïdien (Tableau 1 en page 8). En 2019, l'US EPA a adopté une approche différente reposant d'une part sur une modélisation toxicocinétique-toxicodynamique permettant d'évaluer l'impact d'une exposition aux ions perchlorate sur la production d'hormones thyroïdiennes (HT) et d'autre part d'évaluer l'effet d’une diminution des concentrations plasmatiques de thyroxine libre (fT4) maternelles lors du premier trimestre de grossesse sur le neurodéveloppement de l’enfant, objectivé par une baisse du quotient intellectuel. L’US EPA suggérait de retenir une VTR de 2,2 µg.kg p.c.-1.j-1, aboutissant à une valeur de gestion de 56 µg.L-1 en ions perchlorate dans les EDCH.Comme mentionné précédemment et au regard des difficultés de gestion rencontrées, la DGS avait saisi l’Anses pour analyser les travaux de l’US EPA relatifs à l’évaluation des risques sanitaires liés à la présence d’ions perchlorate dans l’EDCH, afin de donner aux ARS des orientations adaptées et proportionnées au risque sanitaire.Compte tenu de ces éléments, l’Anses avait donc été sollicitée pour examiner à nouveau l’évaluation des risques sanitaires liés à l’ingestion d’ions perchlorate, à la lumière des travaux de l’US EPA. Le premier livrable de cette saisine a eu, par conséquent, pour objectif final de déterminer si la VTR de l’Anses à 0,7 µg.kg p.c.-1.j-1 devait être maintenue. La conclusion de ce premier livrable fut de ne pas remettre en cause cette VTR à la lumière des travaux de l’US EPA, du fait notamment d’incertitudes majeures sur la capacité prédictive du modèle utilisé.L’Agence a donc décidé de conserver sa VTR chronique par voie orale établie en 2011, fondée sur la dose sans effet observée dans l’étude de Greer et al. (2002). Cependant, toutes les VTR établies depuis cette date s’appuient sur une approche Benchmark Dose (BMD), de sorte que l’Agence s’est auto-saisie pour évaluer la pertinence de cette approche, en s’appuyant notamment sur les publications récentes (Weterings et al. 2016, Bruce et al. 2018, Haber et al. 2021).[Saisines liées : 1-SA-0336 ; 2012-SA-0119 ; 2016-SA-0155 et 2017-SA-0170]
Published: 2022

17. Can antidepressants unlock prescription of rimonabant in the fight against COVID-19?

Author: Hugues Chap, Fabienne Briand-Mésange, Stephanie Trudel, Jérôme Ausseil, Jean-Pierre Salles, Juliette Salles, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Benson-Rumiz, Alicia
Subjects: MESH: Prescriptions, 2019-20 coronavirus outbreak, Cell biology, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MESH: Rimonabant / therapeutic use, Bioinformatics, Biochemistry, Cellular and Molecular Neuroscience, Rimonabant, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Antidepressive Agents / therapeutic use, Correspondence, medicine, MESH: COVID-19, MESH: SARS-CoV-2, Medical prescription, Molecular Biology, Depression (differential diagnoses), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Depression, Drug discovery, Psychiatry and Mental health, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; We read with real enthusiasm the paper by Hoertel et al. showing an “association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19”. Their observation reinforces preliminary data of a double-blind, randomized clinical trial showing significant reduction of COVID-19 worsening in outpatients treated with fluvoxamine. By the time those promising results should obviously stimulate organization of large randomized clinical trials on the use of antidepressants in the fight against COVID-19, we want to plead for introducing rimonabant combined to an antidepressant in some of those trials as well as in preclinical studies.
Published: 2021
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18. Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients

Author: Gwenaelle Diene, Fabien Mourre, Alice Clerc, Graziella Pinto, Maithé Tauber, Christine Poitou, Héléna Mosbah, Virginie Laurier, Muriel Coupaye, Christine Merrien, Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Marin d'Hendaye, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, HAL Sorbonne Université 5, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, endocrine system diseases, type 2 diabetes mellitus, Population, 030209 endocrinology & metabolism, Overweight, Article, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Family history, education, 030304 developmental biology, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Blood glucose monitoring, 0303 health sciences, education.field_of_study, medicine.diagnostic_test, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Obesity, 3. Good health, nervous system diseases, Cohort, Medicine, medicine.symptom, Prader-Willi syndrome, syndromic obesity, business
Abstract: Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7, 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11–24) and the median BMI was 39 kg/m2 [34.6, 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period.
Published: 2021
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19. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?

Author: Frédérick Barreau, Emmanuel Mas, Alexis Cassard, Vickie Lacroix, CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DGOS (Reference Center of Rare Digestive Diseases of Toulouse University Hospital), the patient association François Aupetit, Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and SEGUIN, Nathalie
Subjects: Crohn’s disease, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Review, Disease, Gut flora, Bioinformatics, Inflammatory bowel disease, 0302 clinical medicine, A, E, Precision Medicine, Biology (General), Phylogeny, Spectroscopy, 0303 health sciences, Crohn's disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Microbiota, General Medicine, Ulcerative colitis, 3. Good health, Computer Science Applications, Chemistry, Mas, Disease Progression, 030211 gastroenterology & hepatology, F. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, QH301-705.5, Omics, digestive system, eulcerative colitis, Catalysis, Inorganic Chemistry, 03 medical and health sciences, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Barreau, 030304 developmental biology, Bacteria, business.industry, V, Organic Chemistry, Cassard, Lacroix, Inflammatory Bowel Diseases, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, digestive system diseases, Prognostic inflammatory bowel disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Gastrointestinal Microbiome, Crohn's diseas, Metagenomics, Personalized medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Dysbiosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Inflammatory bowel diseases (IBDs), which include Crohn’s disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new ‘omics’ techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by “omics” and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
Published: 2021
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20. Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study

Author: Arnaud Petit, Carine Domenech, Marion Strullu, Brigitte Nelken, Jacqueline Clavel, Audrey Bonaventure, Gérard Michel, Ghinaj Chandab, Roula Ajrouche, Geneviève Plat, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lebanese University [Beirut] (LU), 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), Hôpital Robert Debré, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), and Bonaventure, Audrey
Subjects: medicine.medical_specialty, Inverse Association, Childhood leukemia, aetiology, Population, Context (language use), Polymorphism, Single Nucleotide, lymphoblastic leukaemia, Th2 Cells, Internal medicine, Hypersensitivity, medicine, Humans, genetics, Medical history, Child, education, Childhood Acute Lymphoblastic Leukemia, gene-gene interaction, education.field_of_study, Interleukin-13, business.industry, Interleukins, case-control studies, Childhood leukaemia, Case-control study, Hematology, Odds ratio, Precursor Cell Lymphoblastic Leukemia-Lymphoma, allergy, medicine.disease, cytokines, gene-environment interaction, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Interleukin-4, business
Abstract: International audience; Context A negative association between a history of allergy and childhood acute lymphoblastic leukaemia (ALL) has been reported in previous studies, but remains debated. This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (IL4, IL10, IL13 and IL4-receptor (IL4R)). Methods Analyses were based on the French case-control study ESTELLE (2010-2011). The complete sample included 629 ALL cases and 1,421 population-based controls frequency-matched on age and gender. The child's medical history was collected through standardised maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. Results In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR=0.65 [0.42-0.98]; p= 0.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in IL4 and IL4R (pinteraction=0.003), as well as a gene-environment interaction between IL4R-rs1801275 and a reported history of asthma (IOR=0.23; pint=0.008) and eczema (IOR= 0.47; pint=0.06). We observed no interaction with the candidate polymorphisms in IL4 and IL13. Conclusion These results suggest that the association between allergic symptoms and childhood ALL could be modified by IL4R-rs1801275, and that this variant could also interact with a functional variant in IL4 gene. While they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.
Published: 2021
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21. Patients with PWS and related syndromes display differentially methylated regions involved in neurodevelopmental and nutritional trajectory

Author: Catherine Molinas, Maithé Tauber, Jean-Pierre Salles, Juliette Salles, Emmanuelle Lacassagne, Sanaa Eddiry, Nicolas Franchitto, Eric Bieth, Virginie Laurier, Benson-Rumiz, Alicia, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Marin d'Hendaye, Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Gene Expression, Genome-wide association study, Biology, Genome-wide methylation analysis, Frameshift mutation, Epigenesis, Genetic, MAGEL2, Young Adult, Neurodevelopmental disorder, SNORD116, Genetics, medicine, Humans, Epigenetics, Child, Molecular Biology, Genetics (clinical), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Research, Age Factors, nutritional and metabolic diseases, Infant, Prader–Willi, DNA Methylation, medicine.disease, Human genetics, nervous system diseases, Nutrition Disorders, Differentially methylated regions, Neurodevelopmental Disorders, Chromosomal region, Female, Prader-Willi, Genomic imprinting, Prader-Willi Syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology, Genome-Wide Association Study
Abstract: Background Prader–Willi syndrome is a rare genetic neurodevelopmental disorder caused by a paternal deficiency of maternally imprinted gene expression located in the chromosome 15q11–q13 region. Previous studies have demonstrated that several classes of neurodevelopmental disorders can be attributed to either over- or under-expression of specific genes that may lead to impairments in neuronal generation, differentiation, maturation and growth. Epigenetic changes that modify gene expression have been highlighted in these disorders. One recent study focused on epigenetic analysis and compared patients with PWS with patients with other imprinting disorders. No study, however, has yet focused on epigenetics in patients with PWS specifically by comparing the mutations associated with this syndrome. Objective This study investigated the epigenetic modifications in patients with PWS and patients with PWS-related disorders caused by inactivation of two genes of the PWS chromosomal region, SNORD116 and MAGEL2. Our approach also aimed to compare the epigenetic modifications in PWS and PWS-related disorders. Methods We compared genome-wide methylation analysis (GWAS) in seven blood samples from patients with PWS phenotype (five with deletions of the PWS locus, one with a microdeletion of SNORD116 and one with a frameshift mutation of MAGEL2 presenting with Schaaf–Yang syndrome), as well as two control patients. Controls were infants that had been studied for suspicion of genetic diseases that was not confirmed by the genetic analysis and the clinical follow-up. Results The analysis identified 29,234 differentially methylated cytosines, corresponding to 5,308 differentially methylated regions (DMRs), which matched with 2,280 genes. The DMRs in patients with PWS were associated with neurodevelopmental pathways, endocrine dysfunction and social and addictive processes consistent with the key features of the PWS phenotype. In addition, the separate analysis for the SNORD116 and MAGEL2 deletions revealed that the DMRs associated with the SNORD116 microdeletion were found in genes implicated in metabolic pathways and nervous system development, whereas MAGEL2 mutations mostly concerned genes involved in macromolecule biosynthesis. Conclusion The PWS is associated with epigenetic modifications with differences in SNORD116 and MAGEL2 mutations, which seem to be relevant to the different associated phenotypes.
Published: 2021
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22. Hypertension in Children and Adolescents

Author: Bouhanick, Béatrice, Sosner, Philippe, Brochard, Karine, Mounier-Véhier, Claire, Plu-Bureau, Geneviève, Hascoet, Sébastien, Ranchin, Bruno, Pietrement, Christine, Martinerie, Laetitia, Boivin, Jean Marc, Fauvel, Jean Pierre, Bacchetta, Justine, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire 'Mobilité, Vieillissement, Exercice' (MOVE) (MOVE), Université de Poitiers, Centre médico-sportif Mon Stade [Paris], Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Gynécologie Médicale, AP-HP, Hôpital Port-Royal, Université de Paris, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Centre de Référence des Maladies Rénales Rares, Hospices Civil de Lyon, Filières Maladies Rares ORKID et ERK-Net, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Néphrologie Hospices Civils - hta - dialyse, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and 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)
Subjects: hypertension, children, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, French position statement, adolescents, high blood pressure
Abstract: International audience; Hypertension is much less common in children than in adults. The group of experts decided to perform a review of the literature to draw up a position statement that could be used in everyday practice. The group rated recommendations using the GRADE approach. All children over the age of 3 years should have their blood pressure measured annually. Due to the lack of data on cardiovascular morbidity and mortality associated with blood pressure values, the definition of hypertension in children is a statistical value based on the normal distribution of blood pressure in the paediatric population, and children and adolescents are considered as having hypertension when their blood pressure is greater than or equal to the 95th percentile. Nevertheless, it is recommended to use normative blood pressure tables developed according to age, height and gender, to define hypertension. Measuring blood pressure in children can be technically challenging and several measurement methods are listed here. Regardless of the age of the child, it is recommended to carefully check for a secondary cause of hypertension as in 2/3 of cases it has a renal or cardiac origin. The care pathway and principles of the therapeutic strategy are described here.
Published: 2021
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23. How Can a Polymeric Formula Induce Remission in Crohn’s Disease Patients ?

Author: kawthar Boumessid, Frédérick Barreau, Emmanuel Mas, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Raynaud, Christelle
Subjects: 0301 basic medicine, Crohn’s disease, medicine.medical_specialty, Crohn&#8217, Polymers, Lipid composition, Disease, Review, Inflammatory bowel disease, Gastroenterology, Models, Biological, Catalysis, Inorganic Chemistry, lcsh:Chemistry, s disease, mucosal healing, 03 medical and health sciences, Transforming Growth Factor beta2, 0302 clinical medicine, Crohn Disease, inflammatory bowel disease, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dietary therapy, Palatability, Physical and Theoretical Chemistry, Intestinal Mucosa, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Crohn's disease, business.industry, exclusive enteral nutrition, Organic Chemistry, Remission Induction, General Medicine, medicine.disease, 3. Good health, Computer Science Applications, 030104 developmental biology, Parenteral nutrition, lcsh:Biology (General), lcsh:QD1-999, Mucosal healing, 030211 gastroenterology & hepatology, business
Abstract: International audience; Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, dietary therapy with exclusive enteral nutrition is recommended as a first-line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content, but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.
Published: 2021
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24. Avis de l'Anses relatif à la pertinence de la ré-évaluation des risques sanitaires liés à la présence d'ions perchlorate dans les eaux destinées à la consommation humaine à la lumière des travaux de l'US EPA publiés le 23 mai 2019

Author: Chevalier, Nicolas, Bodin, Laurent, Brochot, Céline, Fini, Jean Baptiste, Garnier, Robert, Laurentie, Michel, Mhaouty-Kodja, Sakina, Mortamais, Marion, Oliver Petit, Isabelle, Wémeau, Jean-Louis, Angeli, Karine, Farion, Nicolas, Centre Hospitalier Universitaire de Nice (CHU Nice), Association EURATOM-CEA (CEA/DSM/DRFC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de l'Environnement Industriel et des Risques (INERIS), Musée National d'Histoire Naturelle de Luxembourg (MNHN), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Direction de l'Evaluation des Risques (DER), and Anses
Subjects: Perchlorates, toxicological reference value, [SDV]Life Sciences [q-bio], drinking water, ions, health risks, valeur toxicologique de référence, eaux destinées à la consommation humaine (EDCH), risques sanitaires
Abstract: Citation suggérée : Anses. (2021). Avis de l’Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail relatif à la « Pertinence de la ré-évaluation des risques sanitaires liés à la présence d’ions perchlorate dans les eaux destinées à la consommation humaine à la lumière des travaux de l’US EPA publiés le 23 mai 2019 ». (Saisine 2019-SA-0116). Maisons-Alfort : Anses, 82 p.; Depuis 2011, l’Anses a été saisie à plusieurs reprises sur les risques sanitaires liés aux ions perchlorate dans les eaux destinées à la consommation humaine (EDCH) suite à la mise en évidence de situations de contamination de ressources utilisées pour la production d’EDCH.En 2011, l’Agence avait préconisé une valeur guide (VG) pour les ions perchlorate dans les EDCH de 15 μg.L-1 pour le consommateur adulte, définie à partir de la valeur toxicologique de référence (VTR) de 0,7 μg.kg p.c.-1.j-1,fondée sur l’inhibition de la capture de l’iode par la thyroïde et conseillé de ne pas utiliser une eau contaminée par les ions perchlorate pour la préparation des biberons des nourrissons jusqu’à 6 mois.En 2012, dans son avis relatif aux études épidémiologiques portant sur les associations entre une exposition aux ions perchlorate dans les EDCH et la fonction thyroïdienne dans des populations spécifiques, l’Agence concluait que « les résultats des études épidémiologiques examinées par les experts ne permettent pas de conclure quant à l’existence ou à l’absence d’une association chez les femmes enceintes ou les nouveau-nés entre les niveaux de thyréostimuline (TSH, thyroid stimulating hormone) et des concentrations en ions perchlorate dans les eaux de boisson [...]. L’absence d’information concernant le statut en iode des populations étudiées rend difficile l’interprétation des données épidémiologiques publiées. »Dans son avis du 8 avril 2014 relatif à la présence d’ions perchlorate dans le lait infantile et dans les EDCH, l’Agence relevait les mêmes limites relatives aux études épidémiologiques disponibles et insistait sur la nécessité de prendre en compte le statut en iode de la population étudiée pour l’évaluation de l’impact sanitaire des ions perchlorate chez l’Homme et pourl’interprétation des données épidémiologiques publiées.Dans son dernier avis du 26 décembre 2018, l’Agence concluait que les études épidémiologiques récentes, y compris celle de de l’Institut de veille sanitaire (InVS) publiée en 2016, n’apportaient pas d’éléments conclusifs supplémentaires sur les effets biologiques ou cliniques des ions perchlorate par rapport à celles prises en compte dans les précédents avis de l’Anses (Anses 2011, 2012, 2014). Les données examinées dans cet avis n’étaient pas de nature à remettre en cause les conclusions des avis précédents de l’Anses, concernant la caractérisation des dangers et la VTR proposée en 2011 par l’Agence.Cependant, s’agissant de l’évaluation de l’exposition aux ions perchlorate, de nouvelles données ont permis d’estimer l’exposition moyenne de la population adulte aux ions perchlorate par voie orale. Cette estimation se fondait sur les données de contamination des aliments par les ions perchlorate (recueillies par la Direction générale de la concurrence, de la consommation et de la répression des fraudes (DGCCRF), dans le cadre de ses enquêtes nationales) et sur les données de contamination des EDCH pour la période 2014-2017 (produites par les Agences régionales de santé (ARS) et disponibles dans la base de données SISE-Eaux). Sur cette base, l’Anses estimait que la contribution de l’exposition liée à laconsommation d’EDCH représente environ 25% de l’exposition par ingestion. Cette estimation concordant avec les données de la littérature et se rapprochant du pourcentage de 20% défini par défaut par l’OMS en 2016, l’Agence considérait nécessaire d’abaisser la part de l’exposition hydrique alors fixée à 60%, pour le calcul de la VG des ions perchlorate dans lesEDCH pour les adultes. En conséquence, la VG proposée avait été abaissée à 5 μg.L-1 pour la population adulte.[Saisines liées 2011-SA-0024 ; 2011-SA-0208 ; 2011-SA-0336 ; 2012-SA-0119 ; 2016-SA-0155 et 2017-SA-0170]
Published: 2021

25. Impact of a Transition Education Program on the Quality of Life in Pediatric Patients with Congenital Heart Disease: Study Design for a Randomised Controlled Trial

Author: Oscar werner, Charlene Bredy, Kathleen LAVASTRE, Sophie Guillaumont, Gregoire De LA VILLEON, Marie Vincenti, Cristelle gerl, Yves DULAC, Nathalie Souletie, Philippe ACAR, Laurence Pages, Marie christine a PICOT, Gerard Bourrel, Agnes OUDE ENGBERINK, Elodie Millon, ABASSI Hamouda, Pascal Amedro, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Service pédiatrie-cardiologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Université de Montpellier (UM), MORNET, Dominique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], 3. Good health
Abstract: Background: Recent advances in the field of congenital heart disease (CHD) led to an improved prognosis of the patients and in consequence the growth of a new population: the grown up with congenital heart disease. Until recently, more than 50% of these patients were lost to follow up because of the lack of specialized structures. The critical moment is the transition between paediatric and adult unit. Therapeutic education is crucial to solve this issue by helping patient to become independent and responsible. The TRANSITION randomized trial aims to assess the impact of a transition education program on the quality of life (QoL) of adolescents and young adults with CHD. Methods: multicentre, randomised, controlled, parallel arm study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (Education program vs. no intervention). The primary outcome is the change in self-reported QoL between baseline and 12-month follow-up. A total of 100 patients in each group is required to observe a significant increase of the overall QoL score of 7±13.5 points (on 100) with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VO2max,VE/VCO2 slope), level of knowledge, physical and psychological status.Discussion: As the current research is opening on patient related outcomes, and as the level of proof in therapeutic education still low, we sought to assess the efficacy of a therapeutic education program on the QoL of CHD patients with a randomized trial.Trial registration: This study was approved by the National Ethics Committee (South-Mediterranean IV 2016-A01681-50) and was registered on Clinicaltrials.gov (NCT03005626) on 29th December 2016
Published: 2021

26. Hypertension in Children and Adolescents: A Position Statement From a Panel of Multidisciplinary Experts Coordinated by the French Society of Hypertension

Author: Béatrice Bouhanick, Philippe Sosner, Karine Brochard, Claire Mounier-Véhier, Geneviève Plu-Bureau, Sébastien Hascoet, Bruno Ranchin, Christine Pietrement, Laetitia Martinerie, Jean Marc Boivin, Jean Pierre Fauvel, Justine Bacchetta, BOZEC, Erwan, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire 'Mobilité, Vieillissement, Exercice' (MOVE) (MOVE), Université de Poitiers, Centre médico-sportif Mon Stade [Paris], Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Gynécologie Médicale, AP-HP, Hôpital Port-Royal, Université de Paris, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Centre de Référence des Maladies Rénales Rares, Hospices Civil de Lyon, Filières Maladies Rares ORKID et ERK-Net, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Néphrologie Hospices Civils - hta - dialyse, 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), Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de Néphrologie Médecine Interne Pédiatrique, Hôpital des Enfants, CHU Toulouse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université de Paris (UP), and 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)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Position statement, Percentile, medicine.medical_specialty, hypertension, 030204 cardiovascular system & hematology, Pediatrics, RJ1-570, 03 medical and health sciences, 0302 clinical medicine, children, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Multidisciplinary approach, 030225 pediatrics, Medicine, adolescents, Therapeutic strategy, Measurement method, business.industry, French position statement, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Blood pressure, Family medicine, Pediatrics, Perinatology and Child Health, Normative, Systematic Review, business, Paediatric population, high blood pressure
Abstract: International audience; Hypertension is much less common in children than in adults. The group of experts decided to perform a review of the literature to draw up a position statement that could be used in everyday practice. The group rated recommendations using the GRADE approach. All children over the age of 3 years should have their blood pressure measured annually. Due to the lack of data on cardiovascular morbidity and mortality associated with blood pressure values, the definition of hypertension in children is a statistical value based on the normal distribution of blood pressure in the paediatric population, and children and adolescents are considered as having hypertension when their blood pressure is greater than or equal to the 95th percentile. Nevertheless, it is recommended to use normative blood pressure tables developed according to age, height and gender, to define hypertension. Measuring blood pressure in children can be technically challenging and several measurement methods are listed here. Regardless of the age of the child, it is recommended to carefully check for a secondary cause of hypertension as in 2/3 of cases it has a renal or cardiac origin. The care pathway and principles of the therapeutic strategy are described here.
Published: 2021
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27. The RDoC approach for translational psychiatry

Author: Salles, Juliette, Lacassagne, Emmanuelle, Benvegnu, Grégoire, Berthoumieu, Sophie Çabal, Franchitto, Nicolas, Tauber, Maithé, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées, and PINIER, CHRISTINE
Subjects: MESH: Prader-Willi Syndrome* / genetics, MESH: Humans, MESH: Psychiatry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Research Design, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Addiction, MESH: Brain / diagnostic imaging, Clinical genetics, MESH: Mental Disorders* / genetics
Abstract: International audience; The Research Domain Criteria project (RDoc) proposes a new classification system based on information from several fields in order to encourage translational perspectives. Nevertheless, integrating genetic markers into this classification has remained difficult because of the lack of powerful associations between targeted genes and RDoC domains. We hypothesized that genetic diseases with psychiatric manifestations would be good models for RDoC gene investigations and would thereby extend the translational approach to involve targeted gene pathways. To explore this possibility, we reviewed the current knowledge on Prader–Willi syndrome, a genetic disorder caused by the absence of expression of some of the genes of the chromosome 15q11–13 region inherited from the father. Indeed, we found that the associations between genes of the PW locus and the modification identified in the relevant behavioral, physiological, and brain imaging studies followed the structure of the RDoC matrix and its six domains (positive valence, negative valence, social processing, cognitive systems, arousal/regulatory systems, and sensorimotor systems).
Published: 2020
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28. Saliva sampling for diagnosing SARS-CoV-2 infections in symptomatic patients and asymptomatic carriers

Author: Jacques Izopet, Pierre Delobel, Catherine Mengelle, Jean-Michel Mansuy, Marion Migueres, M. Alvarez, Alain Didier, Chloé Dimeglio, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie et allergologie pédiatrique [CHU Toulouse], Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), and PINIER, CHRISTINE
Subjects: MESH: Coronavirus, Saliva, medicine.disease_cause, 0302 clinical medicine, COVID-19 Testing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19, Medicine, Sampling (medicine), 030212 general & internal medicine, Coronavirus, 0303 health sciences, biology, 3. Good health, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Betacoronavirus, Coronavirus Infections, MESH: Pneumonia, Viral / epidemiology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Article, 03 medical and health sciences, Betacoronavirus, MESH: Coronavirus Infections / diagnosis, Virology, Internal medicine, Humans, MESH: SARS-CoV-2, MESH: Saliva, MESH: Coronavirus Infections / epidemiology, Pandemics, MESH: Clinical Laboratory Techniques, MESH: Humans, 030306 microbiology, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, MESH: COVID-19 Testing, COVID-19, medicine.disease, biology.organism_classification, Pneumonia, MESH: Pandemics, business, Asymptomatic carrier
Abstract: International audience; In a recent review of laboratory tests for diagnosing SARS-CoV-2 infection, Zheng et al. concluded that the detection rate of real-time quantitative PCR was lower than that of computed tomography [1]. But the authors did not discuss the possibility of using saliva sampling. Nasopharyngeal (NP) swabs are the preferred collection vehicles in France and many other countries and several studies have indicated that this method is more sensitive than sampling other sites [2–4]. Saliva sampling is less invasive for patients, less hazardous for health care workers, requires fewer experimented staff and is less expensive for mass testing. However, little is known about any differences in the sensitivities of saliva and NP sampling or how any differences vary with presence or absence of clinical symptoms
Published: 2020
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29. SRF-FOXO1 and SRF-NCOA1 Fusion Genes Delineate a Distinctive Subset of Well-differentiated Rhabdomyosarcoma

Author: Nadège Corradini, Jean-Yves Blay, Adeline Duc-Gallet, Marie-Pierre Castex, Franck Tirode, Véronique Minard, Daniel Pissaloux, François Le Loarer, Carole Chevenet, Anne Gomez-Brouchet, Carla Fernandez, Marie Karanian, TIRODE, Franck, 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 d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Service d'Anatomie Pathologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie pédiatrique [CHU Toulouse], and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Serum Response Factor, Paraspinal Muscles, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pathology and Forensic Medicine, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, Nuclear Receptor Coactivator 1, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neck Muscles, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Rhabdomyosarcoma, medicine, Adjuvant therapy, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Nuclear atypia, In Situ Hybridization, Fluorescence, Comparative Genomic Hybridization, Forkhead Box Protein O1, Sequence Analysis, RNA, Infant, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Differentiation, medicine.disease, Phenotype, 3. Good health, 030104 developmental biology, Treatment Outcome, PTCH1, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Child, Preschool, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Surgery, Female, Anatomy, Gene Fusion, Comparative genomic hybridization
Abstract: International audience; Rhabdomyosarcoma (RMS) encompasses a heterogenous collection of tumors in which new groups have recently been identified that improved the World Health Organization (WHO) classification. While performing RNA-sequencing in our routine practice, we identified 3 cases of well-differentiated RMS harboring new fusion genes. We also analyzed these tumors through array-comparative genomic hybridization. Clinically, these tumors were deep paraspinal tumors, occurring in neo-nat and young children. The patients underwent resection and adjuvant therapy. At the time of last follow-up (ranging from 12 to 108 mo), they were alive without disease. Histologically, these tumors consisted of well-differentiated rhabdomyoblastic proliferations with nuclear atypia, infiltrative borders, and a specific growth pattern. These tumors harbored new fusion genes involving SRF and either FOXO1 or NCOA1. We compared the expression profiles of these 3 tumors to the expression data of a series of 33 skeletal muscle tumors including embryonal RMSs, alveolar rhandomyosarcomas, RMSs with VGLL2 fusions, RMSs with the myoD1 mutation, EWSR1/FUS-TFCP2 epithelioid and spindle cell RMSs of the bone, and rhabdomyomas with PTCH1 loss. According to clustering analyses, the 3 SRF-fused tumors formed a distinct group with a specific expression profile different from that of the other types of skeletal muscle tumors. Array-comparative genomic hybridization showed a recurrent gain of chromosome 11. These 3 tumors define a new group of RMS associated with a fusion of the SRF gene. FOXO1 rearrangements, usually used to confirm the diagnosis of alveolar RMS and identify poor-outcome RMSs, were identified in a nonalveolar RMS for the first time.
Published: 2020
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30. A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation

Author: Benjamin Bonhomme, Cleofe Romagosa, Gaëlle Pierron, Anne Moreau, Jean Michel Coindre, Arjen H.G. Cleven, Irma Ramos-Oliver, François Le Loarer, Sophie Le Guellec, Corinne Bouvier, Sébastien Salas, Anne Gomez-Brouchet, Virginie Audard, Marie Pierre Castex, Frédérique Larousserie, Anand Sherwood, Anne-Marie Cleton-Jansen, Dilara C. Savci-Heijink, Camille Laurent, Franck Tirode, Judith V.M.G. Bovée, Daniel Pissaloux, Jessica Baud, Antoine Giraud, Herman M. Kroon, Institut Bergonié [Bordeaux], UNICANCER, Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Leiden University Medical Center (LUMC), Département de pathologie [CHU La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Vall d'Hebron University Hospital [Barcelona], Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Léon Bérard [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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biologie des Tumeurs, Institut Curie [Paris], Department of Conservative Dentistry and Endodontics [CSI College of Dental Sciences, Madurai, India], Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and TIRODE, Franck
Subjects: Male, 0301 basic medicine, Pathology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fusion gene, 0302 clinical medicine, CDKN2A, Rhabdomyosarcoma, Anaplastic Lymphoma Kinase, Prospective Studies, Child, Exome, Aged, 80 and over, medicine.diagnostic_test, Epithelioid Cells, Soft tissue, Middle Aged, Prognosis, Immunohistochemistry, Up-Regulation, 3. Good health, DNA-Binding Proteins, Phenotype, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Sarcoma, Gene Fusion, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Craniofacial, Retrospective Studies, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, 030104 developmental biology, Transcription Factors, Fluorescence in situ hybridization
Abstract: International audience; Rhabdomyosarcomas with TFCP2 fusions represent an emerging subtype of tumors, initially discovered by RNA-sequencing. We report herein the clinicopathological, transcriptional, and genomic features of a series of 14 cases. Cases were retrospectively and prospectively recruited and studied by immunohistochemistry (MYF4, MYOD1, S100, AE1/E3, ALK), fluorescence in situ hybridization with TFCP2 break-apart probe (n = 10/14), array-comparative genomic hybridization (Agilent), whole RNA-sequencing (Truseq Exome, Illumina), or anchored multiplex PCR-based targeted next-generation sequencing (Archer® FusionPlex® Sarcoma kit). Patient's age ranged between 11 and 86 years, including 5 pediatric cases. Tumors were located in the bone (n = 12/14) and soft tissue (n = 2/14). Most bone tumors invaded surrounding soft tissue. Craniofacial bones were over-represented (n = 8/12). Median survival was 8 months and five patients are currently alive with a median follow-up of 20 months. Most tumors displayed a mixed spindle cell and epithelioid pattern with frequent vesicular nuclei. All tumors expressed keratins and showed a rhabdomyogenic phenotype (defined as expression of MYF4 and/or MYOD1). ALK was overexpressed in all but three cases without underlying ALK fusion on break-apart FISH (n = 5) nor next-generation sequencing (n = 14). ALK upregulation was frequently associated with an internal deletion at genomic level. TFCP2 was fused in 5' either to EWSR1 (n = 6) or FUS (n = 8). EWSR1 was involved in both soft tissue cases. FISH with TFCP2 break-apart probe was positive in all tested cases (n = 8), including one case with unbalanced signal. On array-CGH, all tested tumors displayed complex genetic profiles with genomic indexes ranging from 13 to 107.55 and recurrent CDKN2A deletions. FET-TFCP2 rhabdomyosarcomas clustered together and distinctly from other rhabdomyosarcomas subgroups. Altogether, our data confirm and expand the spectrum of the new family of FET-TFCP2 rhabdomyosarcomas, which are associated with a predilection for the craniofacial bones, an aggressive course, and recurrent pathological features. Their association with ALK overexpression might represent a therapeutic vulnerability.
Published: 2020
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31. Defining the risk of first intravenous immunoglobulin unresponsiveness in non-Asian patients with Kawasaki disease

Author: Fouad Madhi, Isabelle Koné-Paut, Stéphanie Tellier, Martha Darce Bello, Ulrich Meinzer, Maryam Piram, Franck Boralevi, Rolando Cimaz, Celine Piedvache, Sylvie Di Filippo, Pediatric Rheumatology [Le Kremlin-Bicêtre], Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre] (CeRéMAIA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Paediatric Rheumatology, Nephrology and Internal medicine [Toulouse], Centre Hospitalier Régional Universitaire de Toulouse (CHRU Toulouse), Hospices Civils de Lyon (HCL), Dermatology [Bordeaux], CHU Bordeaux [Bordeaux], Paediatrics [Créteil], Centre Hospitalier Intercommunal de Créteil (CHIC), Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Milan, Clinical Research Unit [Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, The sponsor was Assistance Publique-Hôpitaux de Paris (Département de la Recherche Clinique et du Développement). The study was funded by a grant from Programme Hospitalier de Recherche Clinique-PHRC 2009 (French Ministry of Health) and the French Society of Rheumatology (SFR)., Bodescot, Myriam, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Università degli Studi di Milano = University of Milan (UNIMI)
Subjects: Male, Multivariate analysis, Vasculitis syndromes, Drug Resistance, lcsh:Medicine, Drug resistance, 030204 cardiovascular system & hematology, Pediatrics, Severity of Illness Index, 0302 clinical medicine, Risk Factors, Ethnicity, Medicine, Prospective Studies, Prospective cohort study, lcsh:Science, Child, education.field_of_study, Paediatric rheumatic diseases, Multidisciplinary, Immunoglobulins, Intravenous, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Child, Preschool, Female, France, Risk assessment, medicine.medical_specialty, Population, Mucocutaneous Lymph Node Syndrome, Risk Assessment, Sensitivity and Specificity, Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030225 pediatrics, Internal medicine, Severity of illness, Humans, education, Retrospective Studies, business.industry, lcsh:R, Infant, Reproducibility of Results, Retrospective cohort study, medicine.disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, Kawasaki disease, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: About 10–20% of patients with Kawasaki disease (KD) are unresponsive to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations. We investigated the accuracy of 3 Japanese scoring systems and studied factors associated with IVIg unresponsiveness in a large multiethnic French population of children with KD to build a new scoring system. Children admitted for KD between 2011–2014 in 65 centers were enrolled. Factors associated with second line-treatment; i.e. unresponsiveness to initial IVIg treatment, were analyzed by multivariate regression analysis. The performance of our score and the Kobayashi, Egami and Sano scores were compared in our population and in ethnic subgroups. Overall, 465 children were reported by 84 physicians; 425 were classified with KD (55% European Caucasian, 12% North African/Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 14–61%). On multivariate regression analysis, predictors of secondary treatment after initial IVIG were hepatomegaly, ALT level ≥30 IU/L, lymphocyte count 3 and time to treatment
Published: 2020
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32. Palliative Care in SMA Type 1: A Prospective Multicenter French Study Based on Parents' Reports

Author: Marie Hully, Christine Barnerias, Delphine Chabalier, Sophie Le Guen, Virginie Germa, Elodie Deladriere, Catherine Vanhulle, Jean-Marie Cuisset, Brigitte Chabrol, Claude Cances, Carole Vuillerot, Caroline Espil, Michele Mayer, Marie-Christine Nougues, Pascal Sabouraud, Jeremie Lefranc, Vincent Laugel, Francois Rivier, Ulrike Walther Louvier, Julien Durigneux, Sylvia Napuri, Catherine Sarret, Michel Renouil, Alice Masurel, Marcel-Louis Viallard, Isabelle Desguerre, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Clinical Research Department, Necker–Enfants Malades Hospital, APHP, Paris, France, Physical Rehabilitation Department, Necker–Enfants Malades Hospital, APHP, Paris , France, Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Maladies Neuromusculaires de l'Enfant, Hôpital Roger Salengro [Lille], Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Service de neuropédiatrie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), American Memorial Hospital (Reims), CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital de Hautepierre [Strasbourg], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pediatric Neurology Department, University Hospital, Ang ers, France, Service de pédiatrie, hôpital Sud, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), 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), Palliative Care Team, Necker–Enfants Malades Hospital, AP HP, Paris, France, Éthique, recherches, translations = Ethics, research, translations [CRC] (ETRES), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service de neurométabolisme, Pediatric Neurology Department, Necker–Enfants Malades H ospital, APHP, Paris, France, MORNET, Dominique, Service de neurologie pédiatriques et maladies du dévéloppement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuropédiatrie [CHU Trousseau], 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), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Département de Pédiatrie, CHU Toulouse [Toulouse], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), and Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN)
Subjects: Pediatrics, medicine.medical_specialty, caregivers, Palliative care, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, 030225 pediatrics, medicine, SMA, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Original Research, palliative care, business.industry, lcsh:RJ1-570, lcsh:Pediatrics, Gastrostomy, Intensive care unit, ethics, 3. Good health, Natural history, [SDV] Life Sciences [q-bio], Clinical research, Parenteral nutrition, standard of care, Pediatrics, Perinatology and Child Health, Nusinersen, business
Abstract: International audience; Spinal muscular atrophy type 1 (SMA-1) is a severe neurodegenerative disorder, which in the absence of curative treatment, leads to death before 1 year of age in most cases. Caring for these short-lived and severely impaired infants requires palliative management. New drugs (nusinersen) have recently been developed that may modify SMA-1 natural history and thus raise ethical concerns about the appropriate level of care for patients. The national Hospital Clinical Research Program (PHRC) called "Assessment of clinical practices of palliative care in children with Spinal Muscular Atrophy Type 1 (SMA-1)" was a multicenter prospective study conducted in France between 2012 and 2016 to report palliative practices in SMA-1 in real life through prospective caregivers' reports about their infants' management. Thirty-nine patients were included in the prospective PHRC (17 centers). We also studied retrospective data regarding management of 43 other SMA-1 patients (18 centers) over the same period, including seven treated with nusinersen, in comparison with historical data from 222 patients previously published over two periods of 10 years (1989-2009). In the latest period studied, median age at diagnosis was 3 months [0.6-10.4]. Seventy-seven patients died at a median 6 months of age[1-27]: 32% at home and 8% in an intensive care unit. Eighty-five percent of patients received enteral nutrition, some through a gastrostomy (6%). Sixteen percent had a non-invasive ventilation (NIV). Seventy-seven percent received sedative treatment at the time of death. Over time, palliative management occurred more frequently at home with increased levels of technical supportive care (enteral nutrition, oxygenotherapy, and analgesic and sedative treatments). No statistical difference was found between the prospective and retrospective patients for the last period. However, significant differences were found between patients treated with nusinersen vs. those untreated. Our data confirm that palliative care is essential in management of SMA-1 patients and that parents are extensively involved in everyday patient care. Our data suggest that nusinersen treatment was accompanied by significantly more invasive supportive care, indicating that a re-examination of standard clinical practices should explicitly consider what treatment pathways are in infants' and caregivers' best interest. This study was registered on clinicaltrials.gov under the reference NCT01862042 (https://clinicaltrials.gov/ct2/show/study/NCT01862042?cond=SMA1&rank=8).
Published: 2020
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33. Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study

Author: Pascal Chanez, Alain Didier, Patrick Berger, Christophe Brousse, Cécile Chenivesse, Maeva Zysman, Chantal Raherison, Francis Couturaud, Nicolas Roche, Pierre-Régis Burgel, Gilles Devouassoux, Carey M. Suehs, Y. Martinat, Gaëtan Deslée, Romain Kessler, Philippe Devillier, Thierry Chinet, Arnaud Bourdin, Olivier Le Rouzic, Mathieu Molimard, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Hôpital Foch [Suresnes], Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Strasbourg, 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), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, MORNET, Dominique, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CRP Clinique du Parc, Castelnau-Le-Lez, Service de pneumologie et allergologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], CM PAROT, Lyon, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Delphi Technique, Exacerbation, medicine.medical_treatment, lcsh:Medicine, Therapeutics, Respiratory medicine (see thoracic medicine), [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Likert scale, Leukocyte Count, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Surveys and Questionnaires, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Intubation, Chronic airways disease, 030212 general & internal medicine, Intensive care medicine, Respiratory Medicine, PharmacoEpi-Drugs, Mechanical ventilation, Protocol (science), COPD, business.industry, lcsh:R, EPICENE, General Medicine, medicine.disease, 3. Good health, Eosinophils, Hospitalization, Pneumonia, Pulmonology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business
Abstract: ObjectivesPresently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes.DesignA modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results.SettingCOPD exacerbation management in France.Participants34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds.Results105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation.ConclusionsThis Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients.Study registrationThe eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.
Published: 2020
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34. How can we minimise the use of regular oral corticosteroids in asthma?

Author: Pierre Val, Y. Martinat, Philippe Chanson, Ian M. Adcock, Pascal Chanez, Cécile Chenivesse, Antoine Deschildre, Arnaud Bourdin, Antoine Magnan, Gilles Devouassoux, Nicolas Roche, Camille Taillé, Alain Didier, Thierry Perez, Philippe Bonniaud, Gilles Garcia, Patrick Berger, Jacques de Blic, Philippe Devillier, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Imperial College London, 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), Service des maladies respiratoires [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Physiologie et physiopathologie endocriniennes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Pneumologie, Immunologie et Allergologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille 2 - Faculté de Médecine, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie, Hôpital Foch [Suresnes], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de pneumologie et allergologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Hôpital Bicêtre, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Cochin [AP-HP], Service de Pneumologie A [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie endocriniennes (PHYSENDO), Faculté de Médecine Henri Warembourg - Université de Lille, 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), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Commission of the European Communities, Thoracic Medicine, Imperial College London, London, UK., Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CHU Bordeaux [Bordeaux], Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Lille-II, Laboratory of Pharmacology, Hôpital Foch, Suresnes, Fran, Service de Pneumologie, Hôpital Larrey, Centre Hospitalier Universitaire de Toulouse, Université de Toulouse III, Toulouse, France., Institut du Thorax, Nantes, France, Cabinet de Pneumologie, Lyon, France., Respiratory, Hopital Calmette, CHRU Lille, Lille, France., Lung function, Hôpital Calmette, CHRU Lille, Lille, France., Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), UMR 6293, Clermont Ferrand, France, Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Marseille, Marseille, France, Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), and MORNET, Dominique
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Endotype, Time Factors, Referral, [SDV]Life Sciences [q-bio], Severe asthma, Respiratory System, MEDLINE, Administration, Oral, Risk Assessment, Severity of Illness Index, Tertiary care, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, medicine, Humans, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Intensive care medicine, Lung, Asthma, lcsh:RC705-779, Evidence-Based Medicine, business.industry, lcsh:Diseases of the respiratory system, medicine.disease, 3. Good health, Treatment Outcome, 030228 respiratory system, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 1116 Medical Physiology, Disease Progression, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Research questions, Patient Safety, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: Options to achieve oral corticosteroid (OCS)-sparing have been triggering increasing interest since the 1970s because of the side-effects of OCSs, and this has now become achievable with biologics. The Société de Pneumologie de Langue Française workshop on OCSs aimed to conduct a comprehensive review of the basics for OCS use in asthma and issue key research questions. Pharmacology and definition of regular use were reviewed by the first working group (WG1). WG2 examined whether regular OCS use is associated with T2 endotype. WG3 reported on the specificities of the paediatric area. Key “research statement proposals” were suggested by WG4. It was found that the benefits of regular OCS use in asthma outside episodes of exacerbations are poorly supported by the existing evidence. However, complete OCS elimination couldn’t be achieved in any available studies for all patients and the panel felt that it was too early to conclude that regular OCS use could be declared criminal. Repeated or prolonged need for OCS beyond 1 g·year−1 should indicate the need for referral to secondary/tertiary care. A strategic sequential plan aiming at reducing overall exposure to OCS in severe asthma was then held as a conclusion of the workshop.
Published: 2020
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35. Congenital disorders of intestinal digestion and absorption (sugars, proteins, lipids, ions)

Author: Team1 Carmen, Carmen Lab, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CarMeN, laboratoire
Subjects: Ions, Chloride diarrhea, Maltase-glucoamylase, [SDV]Life Sciences [q-bio], Gastroenterology, Chylomicron retention disease, Hypobetalipoprotenemia, Fructose, Congenital diarrhea, Lipids, Abetalipoproteinemia, Intestines, Saccharase-isomaltase, [SDV] Life Sciences [q-bio], Pregnancy, Glucose-galactose, Humans, Digestion, Female, Sugars, Hypocholesterolemia, Sodium diarrhea, Lactase
Abstract: International audience; Congenital diarrhea may result from 2 main different mechanisms: 1) osmotic diarrhea is caused by the non-digestion-absorption of nutrients leading to the non-absorbed nutrients going into the lumen, increasing the osmotic force and driving fluids; 2) secretory diarrhea induced by the inhibition of intestinal absorption of electrolytes, increasing electrolyte and water flux towards the intestinal lumen. The malabsorption of macronutrients (carbohydrates, proteins and lipids) induces energy deficiency with symptoms depending on the macronutrient: carbohydrates with watery acidic diarrhea; protein with rapid malnutrition, edema, and hypoalbuminemia; and lipids with malnutrition, steatorrhea and hypocholesterolemia. Ionic malabsorption (Cl and Na) is responsible for severe and rapid dehydration sometimes with prenatal abnormalities (polyhydramnios and bowel dilatation).
Published: 2022
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36. Screening of esophageal varices in children using esophageal capsule endoscopy: a multicenter prospective study

Author: Cécile Talbotec, Marc Bellaiche, Jacques Cardey, Catherine Le Gall, Laure Bridoux-Henno, Thierry Lamireau, Jérôme Viala, Alain Dabadie, Emmanuel Mas, Alain Lachaux, Lioara Restier-Miron, Laurent Michaud, Centre Technique Interprofessionnel des Oléagineux, des Protéagineux et du Chanvre (CETIOM), CHU Pontchaillou [Rennes], CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Aix Marseille Université (AMU), Département de pédiatrie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Necker, Terres Inovia, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Robert Debré, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospices Civils de Lyon (HCL), 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), 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), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Adolescent, [SDV]Life Sciences [q-bio], Esophageal and Gastric Varices, Capsule Endoscopy, Sensitivity and Specificity, Gastroenterology, Esophageal capsule endoscopy, 03 medical and health sciences, 0302 clinical medicine, Esophageal varices, Internal medicine, Hypertension, Portal, medicine, Humans, Endoscopy, Digestive System, Child, Prospective cohort study, business.industry, Reproducibility of Results, Gastric varices, medicine.disease, Predictive value, 3. Good health, 030220 oncology & carcinogenesis, Portal hypertension, Female, 030211 gastroenterology & hepatology, France, business, Varices
Abstract: Background Esophagogastroduodenoscopy (EGD) is the standard method for diagnosis of esophageal and gastric varices in children. In this prospective study we evaluated the use of PillCam esophageal capsule endoscopy (ECE) in pediatric patients. Methods Patients aged 7 to 18 years presenting with portal hypertension and/or cirrhosis underwent ECE (PillCam ESO 2, Given Imaging Ltd.) followed by EGD. Results 102 patients were screened, 81 (52 boys; mean age 13.96 ± 0.25 years) were included and 21 were excluded (16 for “candy test” failure). Esophageal varices were identified by EGD in 62 patients (77 %) and by ECE in 57 patients (70 %) using the de Franchis classification (DFC). The sensitivity of ECE for esophageal varices was 92 % and the specificity was 100 % using DFC. Based upon 57/81 patients with small, medium, and large varices on both ECE and EGD, using DFC, the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 55 %, 92 %, 89 %, and 63 %, respectively, giving a total overall accuracy of 72 %. To improve sensitivity and specificity in classification of esophageal varices, we propose using a modified score. This score detected esophageal varices with 100 % sensitivity, 93 % specificity, 94 % PPV, and 100 % NPV, giving a total overall accuracy of 97 %. All patients preferred ECE over EGD. No capsule retention was recorded. Conclusions ECE is a well-tolerated and safe procedure in children. Using the modified score, the sensitivity of ECE is currently sufficient to detect esophageal varices and replace EGD in infants with suspicion of esophageal varices or when EGD is refused.
Published: 2018
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37. Parental smoking, maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies

Author: Arnaud Petit, Stéphane Ducassou, Anne-Sophie Defachelles, Christophe Bergeron, Gudrun Schleiermacher, Gambart Marion, Paula Rios, Caroline Munzer, Jacqueline Clavel, Dominique Valteau-Couanet, Claire Poulalhon, Helen D. Bailey, Laurent Orsi, Brigitte Lacour, Nicolas Sirvent, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-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)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Western Australia (UWA), Hôpital Paul Brousse, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Curie [Paris], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Service d'hématologie-immunologie-oncologie 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU de Bordeaux Pellegrin [Bordeaux], Unité d’Hémato-Immuno-Oncologie pédiatrique [CHU Toulouse] (Pôle Pédiatrique), CHU Toulouse [Toulouse], 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), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Cancéropôle du Grand Est, Registre National des Cancers de l'Enfant - National Registry of Childhood Cancers [Villejuif & CHU Nancy] (RNCE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [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), Université de Lille-UNICANCER, Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse]
Subjects: Male, Cancer Research, medicine.medical_specialty, Alcohol Drinking, case-control study, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Logistic regression, tobacco, 03 medical and health sciences, Neuroblastoma, 0302 clinical medicine, MESH: Alcohol Drinking / epidemiology, Pregnancy, Odds Ratio, Tobacco Smoking, medicine, Humans, childhood cancer, risk factors, Registries, education, Socioeconomic status, education.field_of_study, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Obstetrics, business.industry, alcohol, Case-control study, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Odds ratio, medicine.disease, Confidence interval, 3. Good health, Logistic Models, Oncology, Maternal Exposure, Case-Control Studies, Child, Preschool, 030220 oncology & carcinogenesis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Paternal Exposure, Etiology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; Neuroblastoma (NB) is the most common extra-cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population-based case-control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life-style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta-analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9-1.7]; summary OR from meta-analysis 1.1 [95% CI 1.0-1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9-1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1-2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8-1.4], summary OR from meta-analysis 1.0 [95% CI 0.9-1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy.
Published: 2019
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38. Newly diagnosed and growing subependymal giant cell astrocytoma in adults with tuberous sclerosis complex: results from the international TOSCA study

Author: Jansen, Anna C., Belousova, Elena, Benedik, Mirjana P., Carter, Tom, Cottin, Vincent, Curatolo, Paolo, d'Amato, Lisa, d'Augeres, Guillaume Beaure, Vries, Petrus J., Ferreira, Jose C., Feucht, Martha, Fladrowski, Carla, Hertzberg, Christoph, Jozwiak, Sergiusz, Lawson, John A., Macaya, Alfons, Marques, Ruben, Nabbout, Rima, O'Callaghan, Finbar, Qin, Jiong, Sander, Valentin, Sauter, Matthias, Shah, Seema, Takahashi, Yukitoshi, Touraine, Renaud, Youroukos, Sotiris, Zonnenberg, Bernard, Fattal-Valevski, Aviva, Papathanasopoulos, Panagiotis, Papavasiliou, Antigone Syrigou, Giannakodimos, Stylianos, Gatzonis, Stylianos, Pavlou, Evangelos, Tzoufi, Meropi, Vergeer, A. M. H., Dhooghe, Marc, Verhelst, Helene, Roelens, Filip, Nassogne, Marie Cecile, Defresne, Pierre, de Waele, Liesbeth, Leroy, Patricia, Demonceau, Nathalie, Legros, Benjamin, van Bogaert, Patrick, Ceulemans, Berten, Dom, Lina, Castelnau, Pierre, Martin, Anne de Saint, Riquet, Audrey, Milh, Mathieu, Cances, Claude, Pedespan, Jean-Michel, Ville, Dorothée, Roubertie, Agathe, Auvin, Stephane, Berquin, Patrick, Richelme, Christian, Allaire, Catherine, Gueden, Sophie, Tich, Sylvie Nguyen The, Godet, Bertrand, Falco Rojas, Maria Luz Ruiz, Campistol Planas, Jaume, Martinez Bermejo, Antonio, Smeyers Dura, Patricia, Roldan Aparicio, Susana, Martinez Gonzalez, Maria Jesus, Lopez Pison, Javier, Blanco Barca, Manuel Oscar, Lopez Laso, Eduardo, Alonso Luengo, Olga, Aguirre Rodriguez, Francisco Javier, Malaga Dieguez, Ignacio, Camacho Salas, Ana, Marti Carrera, Itxaso, Martinez Salcedo, Eduardo, Yoldi Petri, Maria Eugenia, Cancho Candela, Ramon, Carrilho, Ines da Conceicao, Vieira, Jose Pedro, Silva Oliveira Monteiro, Jose Paulo, Oliveira Ferreira Leao, Miguel Jorge Santos, Marceano Ribeiro Luis, Catarina Sofia, Mendonca, Carla Pires, Endziniene, Milda, Strautmanis, Jurgis, Talvik, Inga, Canevini, Maria Paola, Gambardella, Antonio, Pruna, Dario, Buono, Salvatore, Fontana, Elena, Dalla Bernardina, Bernardo, Burloiu, Carmen, Cosma, Iuliu Stefan Bacos, Vintan, Mihaela Adela, Popescu, Laura, Zitterbart, Karel, Payerova, Jaroslava, Bratsky, Ladislav, Zilinska, Zuzana, Gruber-Sedlmayr, Ursula, Baumann, Matthias, Haberlandt, Edda, Rostasy, Kevin, Pataraia, Ekaterina, Elmslie, Frances, Johnston, Clare Ann, Crawford, Pamela, Uldall, Peter, Dahlin, Maria, Uvebrant, Paul, Rask, Olof, Bjoernvold, Marit, Brodtkorb, Eylert, Sloerdahl, Andreas, Solhoff, Ragnar, Jaatun, Martine Sofie Gilje, Mandera, Marek, Radzikowska, Elzbieta Janina, Wysocki, Mariusz, Fischereder, Michael, Kurlemann, Gerhard, Wilken, Bernd, Wiemer-Kruel, Adelheid, Budde, Klemens, Marquard, Klaus, Knuf, Markus, Hahn, Andreas, Hartmann, Hans, Merkenschlager, Andreas, Trollmann, Regina, [Jansen AC] Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel VUB, Brussels, Belgium. [Belousova E] Research and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia. [Benedik MP] Child Neurology Department, SPS Pediatriêna Klinika, Ljubljana, Slovenia. [Carter T] Tuberous Sclerosis Association, Nottingham, United Kingdom. [Cottin V] Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France. [Curatolo P] Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University Hospital, Rome, Italy. [Macaya A] Neurologia pediàtrica, Hospital Universitari Vall d’Hebron, Barcelona, Spain, Departament de Salut, Moscow Regional Research Clinical Institute (MONICA), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Association Sclérose Tubéreuse de Bourneville (Gradignan), Universitat Autònoma de Barcelona (UAB), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Génétique Clinique Chromosomique et Moléculaire, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), University Medical Center [Utrecht], Department of Neurology, University Hospital Patras, University Hospitals Leuven [Leuven], CHU de Liège, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), University of Antwerp (UA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Neuro-pédiatrie[Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de neurologie pédiatrique [CHU de Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), AP-HP Hôpital universitaire Robert-Debré [Paris], Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Neurologie [Chateaulin], Centre Toul-arC'hoat, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [CHU Limoges], CHU Limoges, Lithuanian University of Health Sciences [Kaunas, Lithuania], Regional Epilepsy Center, Reggio Calabria, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Witten/Herdecke University, St. George's Hospital, Danish Epilepsy Centre, Denmark and Aarhus University, Aarhus, Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University [Toruń], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], The International TOSCA Study, De Waele, L, and Neurogenetics
Subjects: 0301 basic medicine, Pediatrics, Neurology, [SDV]Life Sciences [q-bio], Nervous System Diseases::Nervous System Diseases::Nervous System Diseases::Neurodegenerative Diseases::Heredodegenerative Disorders, Nervous System::Tuberous Sclerosis [DISEASES], tuberous sclerosis complex, 030105 genetics & heredity, registry, SEGA, lcsh:RC346-429, RECOMMENDATIONS, Tuberous sclerosis, 0302 clinical medicine, Medicine and Health Sciences, Original Research, Esclerosi tuberosa, TUMORS, 3. Good health, mTOR, medicine.symptom, Life Sciences & Biomedicine, Astrocitomes, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Persons::Age Groups::Adult [NAMED GROUPS], Clinical Neurology, Newly diagnosed, Asymptomatic, 03 medical and health sciences, medicine, MANAGEMENT, Adults, In patient, lcsh:Neurology. Diseases of the nervous system, TOSCA, personas::Grupos de Edad::adulto [DENOMINACIONES DE GRUPOS], Science & Technology, Subependymal giant cell astrocytoma, business.industry, Neurosciences, enfermedades del sistema nervioso::enfermedades del sistema nervioso::enfermedades del sistema nervioso::enfermedades neurodegenerativas::trastornos heredodegenerativos del sistema nervioso::esclerosis tuberosa [ENFERMEDADES], neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma::astrocitoma [ENFERMEDADES], medicine.disease, Clinical neurology, nervous system diseases, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::Astrocytoma [DISEASES], REGISTRY, Neurosciences & Neurology, Neurology (clinical), TSC2, business, 030217 neurology & neurosurgery
Abstract: SEGA; TOSCA; Tuberous sclerosis complex SEGA; TOSCA; Complex d’esclerosi tuberosa SEGA; TOSCA; Complejo de esclerosis tuberosa The onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2. The study was funded by Novartis Pharma AG.
Published: 2019
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39. Clinical Characteristics of Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis Complex

Author: Karas, Antonina, Jiang, yuwu, Zou, Liping, Xu, Kaifeng, Zhang, yushi, Luan, Guoming, Zhang, yuqin, Wang, yi, Jin, Meiling, ye, Dingwei, Liao, Weiping, Zhou, Liemin, Liu, Jie, Liao, Jianxiang, yan, Bo, Deng, yanchun, Jiang, Li, Liu, Zhisheng, Huang, Shaoping, Li, Hua, Kim, Kijoong, Chen, Pei-Lung, Lee, Hsiu-Fen, Tsai, Jeng-Dau, Chi, Ching-Shiang, Huang, Chao-Ching, Riney, Kate, yates, Deborah, Kwan, Patrick, Likasitwattanakul, Surachai, Nabangchang, Charcrin, Chomtho, Lunliya Thampratankul Krisnachai, Katanyuwong, Kamornwan, Sriudomkajorn, Somjit, Wilmshurst, Jo, Segel, Reeval, Gilboa, Tal, Tzadok, Michal, Fattal-Valevski, Aviva, Papathanasopoulos, Panagiotis, Papavasiliou, Antigone Syrigou, Giannakodimos, Stylianos, Gatz, Stylianos, Pavlou, Evangelos, Tzoufi, Meropi, Vergeer, A. M. H., Dhooghe, Marc, Verhelst, Helene, Roelens, Filip, Nassogne, Marie Cecile, Defresne, Pierre, de Waele, Liesbeth, Leroy, Patricia, Demonceau, Nathalie, Legros, Benjamin, van Bogaert, Patrick, Ceulemans, Berten, Dom, Lina, Castelnau, Pierre, Martin, Anne de St, Riquet, Audrey, Milh, Mathieu, Cances, Claude, Pedespan, Jean-Michel, Ville, Dorothee, Roubertie, Agathe, Auvin, Stephane, Berquin, Patrick, Richelme, Christian, Allaire, Catherine, Gueden, Sophie, Tich, Sylvie Nguyen The, Godet, Bertrand, Rojas, Maria Luz Ruiz Falco, Planas, Jaume Campistol, Bermejo, Antonio Martinez, Dura, Patricia Smeyers, Aparicio, Susana Roldan, Gonzalez, Maria Jesus Martinez, Pison, Javier Lopez, Barca, Manuel Oscar Blanco, Laso, Eduardo Lopez, Luengo, Olga Alonso, Rodriguez, Francisco Javier Aguirre, Dieguez, Ignacio Malaga, Salas, Ana Camacho, Carrera, Itxaso Marti, Salcedo, Eduardo Martinez, Petri, Maria Eugenia yoldi, Candela, Ramon Cancho, Carrilho, Ines da Conceicao, Vieira, Jose Pedro, Monteiro, Jose Paulo da Silva Oliveira, Leao, Miguel Jorge Santos de Oliveira Ferreira, Luis, Catarina Sofia Marceano Ribeiro, Mendonca, Carla Pires, Endziniene, Milda, Strautmanis, Jurgis, Talvik, Inga, Canevini, Maria Paola, Gambardella, Antonio, Pruna, Dario, Buono, Salvatore, Fontana, Elena, Dalla Bernardina, Bernardo, Burloiu, Carmen, Cosma, Iuliu Stefan Bacos, Vintan, Mihaela Adela, Popescu, Laura, Zitterbart, Karel, Payerova, Jaroslava, Bratsky, Ladislav, Zilinska, Zuzana, Gruber-Sedlmayr, Ursula, Baumann, Matthias, Haberland, Edda, Rostasy, Kevin, Pataraia, Ekaterina, Elmslie, Frances, Johnston, Clare Ann, Crawford, Pamela, Uldall, Peter, Uvebrant, Paul, Rask, Olof, Bjoernvold, Marit, Brodtkorb, Eylert, Sloerdahl, Andreas, Solhoff, Ragnar, Jaatun, Martine Sofie Gilje, Mandera, Marek, Radzikowska, Elzbieta Janina, Wysocki, Mariusz, Fischereder, Michael, Kurlemann, Gerhard, Wilken, Bernd, Wiemer-Kruel, Adelheid, Budde, Klemens, Marquard, Klaus, Knuf, Markus, Hahn, Andreas, Hartmann, Hans, Merkenschlager, Andreas, Trollmann, Regina, Jansen, Anna C., Belousova, Elena, Benedik, Mirjana P., Carter, Tom, Cottin, Vincent, Curatolo, Paolo, Dahlin, Maria, d'Amato, Lisa, d'Augeres, Guillaume Beaure, Vries, Petrus J., Ferreira, Jose C., Feucht, Martha, Fladrowski, Carla, Hertzberg, Christoph, Jozwiak, Sergiusz, Lawson, John A., Macaya, Alfons, Marques, Ruben, Nabbout, Rima, O'Callaghan, Finbar, Qin, Jiong, Sander, Valentin, Sauter, Matthias, Shah, Seema, Takahashi, yukitoshi, Touraine, Renaud, youroukos, Sotiris, Zonnenberg, Bernard, Kingswood, John C., Shinohara, Nobuo, Horie, Shigeo, Kubota, Masaya, Tohyama, Jun, Imai, Katsumi, Kaneda, Mari, Kaneko, Hideo, Uchida, yasushi, Kirino, Tomoko, Endo, Shoichi, Inoue, yoshikazu, Uruno, Katsuhisa, Serdaroglu, Ayse, yapici, Zuhal, Anlar, Banu, Altunbasak, Sakir, Lvova, Olga, Belyaev, Oleg Valeryevich, Agranovich, Oleg, Levitina, Elena Vladislavovna, Maksimova, yulia Vladimirovna, Johns Hopkins University (JHU), Fudan University [Shanghai], EED, University of California [Los Angeles] (UCLA), University of California-University of California, Chimie pour la Reconnaissance et l’Etude d’Assemblages Biologiques (CREAB), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), College of Computing (GATECH), Georgia Institute of Technology [Atlanta], Institute for Human Genetics, Safra Children's Hospital, Department of Neurology, University Hospital Patras, University Hospitals Leuven [Leuven], CHU de Liège, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), University of Antwerp (UA), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Neuro-pédiatrie[Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pédiatrie [CHU Toulouse], CHU Toulouse [Toulouse], Service de neurologie pédiatrique [CHU de Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Neurologie [Chateaulin], Centre Toul-arC'hoat, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [CHU Limoges], CHU Limoges, Lithuanian University of Health Sciences [Kaunas, Lithuania], Regional Epilepsy Center, Reggio Calabria, Innsbruck Medical University [Austria] (IMU), Witten/Herdecke University, St. George's Hospital, Danish Epilepsy Centre, Denmark and Aarhus University, Aarhus, Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University [Toruń], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Moscow Regional Research Clinical Institute (MONICA), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Universitat Autònoma de Barcelona (UAB), CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Department of Clinical Genetics, Physiotherapy, Human Physiology and Anatomy, Pediatrics, Public Health Sciences, Mental Health and Wellbeing research group, Neurogenetics, De Waele, L, University of California (UC)-University of California (UC), UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), [Jansen AC] Pediatric Neurology Unit, Department of Pediatrics, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium. [Belousova E] Research and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia. [Benedik MP] Child Neurology Department, SPS Pediatriêna Klinika, Ljubljana, Slovenia. [Carter T] Tuberous Sclerosis Association, Nottingham, United Kingdom. [Cottin V] Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France. [Curatolo P] Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University Hospital, Rome, Italy. [Macaya A] Neurologia pediàtrica, Hospital Universitari Vall d’Hebron, Barcelona, Spain., and Vall d'Hebron Barcelona Hospital Campus
Subjects: Quinases, Pediatrics, enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-serina-treonina cinasas::TOR serina-treonina cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Angiomyolipoma, Neurology, [SDV]Life Sciences [q-bio], CHILDREN, tuberous sclerosis complex, registry, Neoplasms::Neoplasms by Histologic Type::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Neoplasms, Neuroepithelial::Glioma::Neoplasms::Neoplasms by Histologic Type::Astrocytoma [DISEASES], SEGA, RECOMMENDATIONS, DISEASE, lcsh:RC346-429, Tuberous sclerosis, DOUBLE-BLIND, 0302 clinical medicine, EVEROLIMUS, neoplasias::hamartoma::esclerosis tuberosa [ENFERMEDADES], Medicine and Health Sciences, 030212 general & internal medicine, Original Research, Intracranial pressure, Esclerosi tuberosa, 3. Good health, medicine.anatomical_structure, mTOR, Astrocitomes, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Clinical Neurology, DIAGNOSIS, 03 medical and health sciences, medicine, MANAGEMENT, TOSCA, lcsh:Neurology. Diseases of the nervous system, Everolimus, Science & Technology, Subependymal giant cell astrocytoma, business.industry, ANGIOMYOLIPOMA, neoplasias::neoplasias por tipo histológico::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::neoplasias neuroepiteliales::glioma::neoplasias::neoplasias por tipo histológico::astrocitoma [ENFERMEDADES], Neurosciences, medicine.disease, SEVERITY, Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinases [CHEMICALS AND DRUGS], Neurology (clinical), TSC1, Neurosciences & Neurology, TSC2, business, 030217 neurology & neurosurgery, Neoplasms::Hamartoma::Tuberous Sclerosis [DISEASES]
Abstract: SEGA; TOSCA; Tuberous sclerosis complex SEGA; TOSCA; Complejo de esclerosis tuberosa SEGA; TOSCA; Complex d'esclerosi tuberosa Background: This study evaluated the characteristics of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC) entered into the TuberOus SClerosis registry to increase disease Awareness (TOSCA). Methods: The study was conducted at 170 sites across 31 countries. Data from patients of any age with a documented clinical visit for TSC in the 12 months preceding enrollment or those newly diagnosed with TSC were entered. Results: SEGA were reported in 554 of 2,216 patients (25%). Median age at diagnosis of SEGA was 8 years (range, 18 years. SEGA were symptomatic in 42.1% of patients. Symptoms included increased seizure frequency (15.8%), behavioural disturbance (11.9%), and regression/loss of cognitive skills (9.9%), in addition to those typically associated with increased intracranial pressure. SEGA were significantly more frequent in patients with TSC2 compared to TSC1 variants (33.7 vs. 13.2 %, p < 0.0001). Main treatment modalities included surgery (59.6%) and mammalian target of rapamycin (mTOR) inhibitors (49%). Conclusions: Although SEGA diagnosis and growth typically occurs during childhood, SEGA can occur and grow in both infants and adults. The study was funded by Novartis Pharma AG. Novartis has contributed to the study design, data analysis, and the decision to publish. Novartis authors reviewed the draft for submission.
Published: 2019
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40. Clinical study of 19 patients with SCN 8A ‐related epilepsy: Two modes of onset regarding EEG and seizures

Author: Svetlana Gataullina, Cécile Mignon-Ravix, Julien Denis, Frédéric Villega, Cecilia Altuzarra, Melanie Martin, Magalie Barth, Jean-Michel Pedespan, Sophie Julia, Alexandra Afenjar, Laurent Villard, Nathalie Villeneuve, Laurence Lion-François, Sophie Gueden, Diane Doummar, Jeremie Lefranc, Mathieu Milh, Pierre Cacciagli, Caroline Lacoste, Claude Cances, Lena Damaj, Cyril Mignot, Sébastien Moutton, Hubert Journel, Bruria Ben Zeev, Olivier Dulac, Sylvia Napuri, Gaetan Lesca, Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Epilepsie et ischémie cérébrale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de pédiatrie, hôpital Sud, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], CHU Bordeaux [Bordeaux], Service de Génétique Médicale du CHU de Bordeaux, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pédiatrie [CHU Toulouse], CHU Toulouse [Toulouse], Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Pediatrics, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Tel Aviv University [Tel Aviv], Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Sud, CHU Pitié-Salpêtrière [APHP], Service de neuropédiatrie [Trousseau], Centre Hospitalier Bretagne Atlantique [Vannes], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Tel Aviv University (TAU)
Subjects: Male, 0301 basic medicine, Pediatrics, Delayed Diagnosis, Movement disorders, [SDV]Life Sciences [q-bio], Electroencephalography, Epilepsy, 0302 clinical medicine, Pregnancy, Prospective Studies, Age of Onset, Fetal Movement, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Seizure types, Normal interictal EEG, 3. Good health, Epileptic spasms, Phenotype, Neurology, Cohort, Anticonvulsants, Female, medicine.symptom, Sodium Channel Blockers, medicine.medical_specialty, Myoclonic Jerk, Mutation, Missense, 03 medical and health sciences, Munc18 Proteins, Seizures, medicine, Humans, KCNQ2 Potassium Channel, business.industry, Infant, Newborn, Infant, medicine.disease, Early Diagnosis, 030104 developmental biology, Amino Acid Substitution, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, NAV1.6 Voltage-Gated Sodium Channel, Neurology (clinical), business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. Methods We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types. We made genotypic/phenotypic correlation based on epilepsy-associated missense variant localization over the protein. Results We found 19 patients carrying a de novo mutation of SCN8A, representing 3% of our cohort, with 9 mutations being novel. Age at onset of epilepsy was 1 day to 16 months. We found two modes of onset: 12 patients had slowly emerging onset with rare and/or subtle seizures and normal interictal EEG (group 1). The first event was either acute generalized tonic-clonic seizure (GTCS; Group 1a, n = 6) or episodes of myoclonic jerks that were often mistaken for sleep-related movements or other movement disorders (Group 1b, n = 6). Seven patients had a sudden onset of frequent tonic seizures or epileptic spasms with abnormal interictal EEG leading to rapid diagnosis of epileptic encephalopathy. Sodium channel blockers were effective or nonaggravating in most cases. Significance SCN8A is the third most prevalent early onset epileptic encephalopathy gene and is associated with two modes of onset of epilepsy.
Published: 2019
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41. A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management

Author: Hubert Journel, Sylvie Ragot-Mandry, Delphine Héron, Brigitte Chabrol, S. Peudenier, Jean-Marie Cuisset, Guillaume Bassez, Pascal Sabouraud, Catherine Sarret, Claude Cances, Mélanie Fradin, Agnès Jacquin-Piques, Julie Perrier-Boeswillald, Isabelle Desguerre, Michèle Mayer, Susana Quijano-Roy, Arnaud Isapof, Vincent Laugel, Marie De Antonio, Frédérique Audic, Nathalie Bach, Emmanuelle Lagrue, C. Espil, Rémi Bellance, Catherine Vanhulle, Armelle Magot, Hervé Testard, Julien Durigneux, Yann Péréon, Cécile Laroche-Raynaud, Romain K. Gherardi, Christine Barnerias, Céline Dogan, Véronique Manel, François Rivier, Dalil Hamroun, Ulrike Walther-Louvier, Christian Richelme, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Département de Pédiatrie [CHU Toulouse], CHU Toulouse [Toulouse], Service de Neurologie Pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de Référence des Maladies Héréditaires du Métabolisme, Service de neurométabolisme, Service de neuropédiatrie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique clinique [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Groupe de recherche clinique 'déficience intellectuelle et autisme', Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neuropédiatrie [CHU Trousseau], 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), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Hôpital de Hautepierre [Strasbourg], Laboratoire d'Explorations Fonctionnelles, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de neurologie pédiatriques et maladies du dévéloppement, 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), Atlantic Gene Therapies, Service de Pédiatrie, Rééducation et Réanimation Neurorespiratoire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service de pédiatrie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), American Memorial Hospital (Reims), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'histologie-Hôpital Henri Mondor, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP, Paris-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service de neuropédiatrie [Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), École Pratique des Hautes Études (EPHE), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Foot Deformities, Male, Pediatrics, medicine.medical_specialty, Adolescent, Myotonic dystrophy, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Genotype-phenotype distinction, Cataracts, Severity of illness, medicine, Humans, Myotonic Dystrophy, Registries, Child, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Evidence-Based Medicine, Muscle Weakness, business.industry, Infant, Newborn, Evidence-based management, Infant, Cardiorespiratory fitness, Arrhythmias, Cardiac, Evidence-based medicine, medicine.disease, 3. Good health, 030104 developmental biology, Multicenter study, Child, Preschool, Cohort, Autism, Female, Neurology (clinical), France, business, Respiratory Insufficiency, Trinucleotide Repeat Expansion, 030217 neurology & neurosurgery
Abstract: ObjectiveTo genotypically and phenotypically characterize a large pediatric myotonic dystrophy type 1 (DM1) cohort to provide a solid frame of data for future evidence-based health management.MethodsAmong the 2,697 patients with genetically confirmed DM1 included in the French DM-Scope registry, children were enrolled between January 2010 and February 2016 from 24 centers. Comprehensive cross-sectional analysis of most relevant qualitative and quantitative variables was performed.ResultsWe studied 314 children (52% females, with 55% congenital, 31% infantile, 14% juvenile form). The age at inclusion was inversely correlated with the CTG repeat length. The paternal transmission rate was higher than expected, especially in the congenital form (13%). A continuum of highly prevalent neurodevelopmental alterations was observed, including cognitive slowing (83%), attention deficit (64%), written language (64%), and spoken language (63%) disorders. Five percent exhibited autism spectrum disorders. Overall, musculoskeletal impairment was mild. Despite low prevalence, cardiorespiratory impairment could be life-threatening, and frequently occurred early in the first decade (25.9%). Gastrointestinal symptoms (27%) and cataracts (7%) were more frequent than expected, while endocrine or metabolic disorders were scarce.ConclusionsThe pedDM-Scope study details the main genotype and phenotype characteristics of the 3 DM1 pediatric subgroups. It highlights striking profiles that could be useful in health care management (including transition into adulthood) and health policy planning.
Published: 2019
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42. NOD2 Expression in Intestinal Epithelial Cells Protects Toward the Development of Inflammation and Associated Carcinogenesis

Author: Ferrand, Audrey, Al Nabhani, Ziad, Sola Tapias, Nùria, Mas, Emmanuel, Hugot, Jean-Pierre, Barreau, Frederick, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), CRI UMR 1149, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP Hôpital universitaire Robert-Debré [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Ferrand, Audrey
Subjects: Carcinogenesis, NOD2, nucleotide-binding oligomerization domain 2, TNBS, trinitrobenzene sulfonic acid, [SDV]Life Sciences [q-bio], Nod2 Signaling Adaptor Protein, NF-κB, nuclear factor-κB, Review, Epithelial cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MDP, muramyl dipeptide, Models, Biological, Nod2, Cancer, Colitis, Gut, HD, human defensin, CD, Crohn’s disease, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, IFN, interferon, AMP, antimicrobial peptide, MLCK, myosin light-chain kinase, IRF4, interferon regulatory factor 4, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Physiologie, Inflammation, PP, Peyer’s patch, TNF, tumor necrosis factor, KO, knockout, Muc, mucin, WT, wild-type, mRNA, messenger RNA, digestive system diseases, [SDV] Life Sciences [q-bio], Intestines, CEC, colonic epithelial cells, CARD, caspase activation and recruitment domain, CRC, colorectal cancer, physiology, MAPK, mitogen-activated protein kinase, TLR, Toll-like receptor
Abstract: Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan-conserved motifs in cytosol and stimulates host immune response including epithelial and immune cells. The association of NOD2 mutations with a number of inflammatory pathologies including Crohn’s disease (CD), graft-versus-host diseases, or Blau syndrome, highlights its pivotal role in inflammatory response and the associated-carcinogenesis development. Since its identification in 2001 and its association with CD, the role of NOD2 in epithelial cells and immune cells has been investigated extensively but the precise mechanism by which NOD2 mutations lead to CD and the associated carcinogenesis development is largely unknown. In this review, we present and discuss recent developments about the role of NOD2 inside epithelial cells on the control of the inflammatory process and its linked carcinogenesis development., Graphical abstract
Published: 2019
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43. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

Author: Nizar Mahlaoui, Capucine Picard, Perrine Bach, Laurence Costes, Virginie Courteille, Anja Ranohavimparany, Alexandre Alcaïs, Jean-Philippe Jais, Alain Fischer, Christine Bellanné-Chantelot, Jacinta Bustamante, Sylvie Chollet-Martin, Christian Drouet, Véronique Fremeaux-Bacchi, Caroline Kannengiesser, Virginie Girardin, Nathalie Lambert, Valérie Proulle, Jérémie Rosain, Marie José Stasia, Dominique Stoppa Lyonnet, Ioannis Theodorou, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Emilie Catherinot, Nathalie Cheikh, Sarah Cohen-Beaussant, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Geneviève de Saint Basile, Catherine Devoldere, Anne Deville, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, David Launay, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Dalila Nouar, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, IFR Necker-Enfants Malades (IRNEM), 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)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Service de Biostatistique et Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), the Study Center of Primary Immunodeficiencies, CHU Necker - Enfants Malades [AP-HP], Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Tronche, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hématogoie pédiatrique, hôpital Sud, SIGNAL-IMAGE-COMMUNICATION (SIC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], 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), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [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), Hôpital Foch [Suresnes], Service de pédiatrie (CHU de Dijon), Developpement Normal et Pathologique du Système Immunitaire, 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 Universitaire de Nice (CHU Nice), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Claude Huriez [Lille], CHU Lille, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, cellules dendritiques et greffes (JE 2448), Université de Tours (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne, maladies infectieuses, immunologie clinique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Hémato-Oncologie Pédiatrique, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Internal Medicine, Paris, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Clermont-Ferrand, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], American Memorial Hospital, American Memory Hospital, Department of Clinical Immunology, 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 Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Hématologie Infantile, CHU Amiens-Picardie, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Clinical Haematology, CHU Hôtel-Dieu, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], French Ministry of Health, LFB, GlaxoSmithKlineGlaxoSmithKline, CSL BehringCSL Behring, ShireShire, Octapharma, Binding Site, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Chaire Médecine expérimentale (A. Fischer), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], 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), 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]), 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), 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 ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie pédiatrique, CHU Toulouse [Toulouse], CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de médecine de l'enfant et de l'adolescent, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), 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)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (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), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Service de médecine interne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours, 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 National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], McGill University, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Amiens (CHU), centre hospitalier universitaire amiens, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Joseph Fourier - Grenoble 1 (UJF)-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 Joseph Fourier - Grenoble 1 (UJF)-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), and 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)
Subjects: 0301 basic medicine, Primary Immunodeficiency Diseases, medicine.medical_treatment, Genetic counseling, Immunology, Genomics, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Genotype, Humans, Immunology and Allergy, Medicine, Genetic Testing, Registries, Retrospective Studies, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Common variable immunodeficiency, Retrospective cohort study, medicine.disease, Phenotype, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Identification (biology), France, business, 030215 immunology
Abstract: International audience; To the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...]
Published: 2019
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44. EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity

Author: Anne-Isabelle Bertozzi, Emmanuelle Uro-Coste, Claude-Alain Maurage, Sarah Péricart, Sergio Boetto, Yvan Nicaise, Sophie Le Guellec, Camille Franchet, Alix Delrieu, Matthieu Vinchon, David Grand, Frédéric Escudié, David T.W. Jones, Valérie Rigau, Anne Gomez-Brouchet, Aurore Siegfried, Jean-Christophe Sol, Audrey Rousseau, Franck-Emmanuel Roux, Dominique Figarella-Branger, Département de Pathologie [CHU Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Pathologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Pathologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Claudius-Regaud [IUCT, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Département de Neurochirurgie [CHU Toulouse], Département de Neurochirurgie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Département de Pathologie [Centre Médical Universitaire Montpellier], Centre Médical Universitaire Montpellier - CMUM, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncopédiatrie [CHU Toulouse], Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Division of Pediatric Neurooncology [Heidelberg, Germany], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-German Cancer Consortium [Heidelberg] (DKTK), Département de Pathologie [CHU Marseille], CHU Marseille, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), D. Jones is supported by funding for the Everest Centre for Paediatric Low- Grade Brain Tumour Research through the Brain Tumour Charity (UK). We are grateful to Karen Silva for her help in handling tumor samples from the different pathological departments. Samples from Marseille were retrieved from the AP-HM tumor bank AC 2017:1786. Samples from Toulouse were retrieved from the CHU de Toulouse tumor bank BB-0033-00014., Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), Service Neurochirurgie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Bernardo, Elizabeth, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA - Département NOHMAD - Equipe 17), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopp Children's Cancer Center at the NCT Heidelberg - KiTZ [Heidelber, Germany]g, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Design and Application of Innovative Local Treatments in Glioblastoma ( CRCINA - Département NOHMAD - Equipe 17 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -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 ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre hospitalier universitaire d'Angers ( CHU Angers ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Institut pour la Recherche sur le Cancer de Lille ( U837 INSERM - IRCL ), Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Institut de pharmacologie et de biologie structurale ( IPBS ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Universitaire du Cancer Toulouse - Oncopôle ( IUCT ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Toulouse Neuro Imaging Center ( ToNIC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse-Université Toulouse III - Paul Sabatier, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), German Cancer Research Center ( DKFZ ) -German Cancer Consortium - DKTK [Heidelberg, Germany], Institut de neurophysiopathologie ( INP ), and Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Adult, Male, DNA Copy Number Variations, Kruppel-Like Transcription Factors, Locus (genetics), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Ganglioglioma, Fusion gene, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, medicine, Biomarkers, Tumor, Humans, Copy-number variation, Child, In Situ Hybridization, Fluorescence, Research Articles, Sanger sequencing, Brain Neoplasms, General Neuroscience, Methylation, DNA Methylation, medicine.disease, Neoplasms, Neuroepithelial, 3. Good health, Repressor Proteins, 030104 developmental biology, Fusion transcript, Cancer research, symbols, Female, Neurology (clinical), Gene Fusion, RNA-Binding Protein EWS, 030217 neurology & neurosurgery
Abstract: International audience; We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N terminal transcriptional activation domain of EWSR1 gene and the C terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB-ZF (broad-complex, tramtrack and bric-à-brac -zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1-PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAF[V600E] negative ganglioglioma, the second a BRAF[V600E] negative glioneuronal tumor, not otherwise specified, and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAF[V600E] negative gangliogliomas were screened by FISH using EWSR1 break-apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well-defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1-PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.
Published: 2019
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45. Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells

Author: Raoudha Mezghani-Jarraya, Cynthia Girardi, Rachid Chawech, Nicolas Fabre, Imen Nasri, Audrey Ferrand, Emmanuel Mas, Nathalie Vergnolle, Claire Racaud-Sultan, Université de Sfax, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Racaud-Sultan, Claire, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: 0301 basic medicine, Magnetic Resonance Spectroscopy, Flavonols, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, glycogène synthase kinase3, Pharmaceutical Science, 0302 clinical medicine, Tandem Mass Spectrometry, GSK-3, Drug Discovery, Glycosides, Receptor, Chromatography, High Pressure Liquid, chemistry.chemical_classification, biology, medicine.diagnostic_test, cytotoxicité, food and beverages, General Medicine, Glycogen synthase kinase 3b, glycogen synthase kinase 3β, Biochemistry, 030220 oncology & carcinogenesis, Colonic Neoplasms, Molecular Medicine, medicine.symptom, Signal Transduction, Research Article, Cell Survival, medicine.drug_class, Inflammation, Flowers, diplotaxis, Anti-inflammatory, 03 medical and health sciences, Western blot, medicine, Humans, cancer, Flavonoids, Intestine, Cancer, activité anti-inflammatoire, Protein Kinase Inhibitors, intestine, Pharmacology, Glycogen Synthase Kinase 3 beta, Plants, Medicinal, Plant Extracts, Methanol, lcsh:RM1-950, Glycoside, Brassicaceae, Inflammatory Bowel Diseases, biology.organism_classification, Antineoplastic Agents, Phytogenic, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, Complementary and alternative medicine, chemistry, inflammation, Cell culture, Solvents, cellule épithéliale intestinale, flavonoïde, Caco-2 Cells, inflammation de l'intestin, Phytotherapy
Abstract: International audience; Context and objective: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 b (GSK3b) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3b and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3b. Materials and methods: Methanol extracts from D. harra flowers were prepared and the bio-guided fractionation of their active compounds was performed using inflammatory [protease-activated receptor 2 (PAR2)-stimulated IEC6 cells] and cancer (human Caco-2 cell line) intestinal cells. 50–100 lg/mL of fractions or compounds purified by HPLC were incubated with cells whose inhibited form of GSK3b (Pser9 GSK3b) and survival were analyzed by Western blot at 1 h and colorimetric assay at 24 h, respectively. LC-UV-MS profiles and MS-MS spectra were used for the characterization of extracts and flavonoids-enriched fractions, and the identification of pure flavonoids was achieved by MS and NMR analysis. Results: The methanol extract from D. harra flowers and its flavonoid-enriched fraction inhibit GSK3b in PAR2-stimulated IEC6 cells. GSK3b inhibition by the flavonoid-enriched D. harra fraction was dependent on PKC activation. The flavonoid-enriched D. harra fraction and its purified compound isorhamnetin-3,7- di-O-glucoside induced a 20% decrease of PAR2-stimulated IEC6 and Caco-2 cell survival. Importantly, normal cells (non-stimulated IEC6 cells) were spared by these treatments. Conclusion: This work indicates that flavonoids from D. harra display cytotoxic activity against inflammatory and cancer intestinal cells which could depend on GSK3b inhibition.
Published: 2016
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46. Associations between cognitive performance and the rehabilitation, medical care and social support provided to French children with Prader-Willi syndrome

Author: Natacha Lehman, Didier Lacombe, Delphine Héron, Frédérique Debomy, Sylvie Manouvrier, Frédéric Huet, Patrick Edery, Laurence Faivre, Sylvie Odent, Myriam Mikaty, Jennifer Gallard, Sophie Chancenotte, Sandrine Vinault, Maïté Tauber, David Geneviève, Coralie Rastel, Nicole Philip, Christine Binquet, Mathieu Bordes, Alain Verloes, Jamal Ghoumid, Elodie Gautier, Christel Thauvin-Robinet, Emilie Schmitt, Jenny Cornaton, Marie Bournez, Nolwenn Jean, Catherine Lejeune, Delphine Minot, Alice Masurel, Pierre-Henri Roux-Levy, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence du Syndrome de Prader-Willi, CHU Toulouse [Toulouse], Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), CHU Dijon, Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, medicine.medical_treatment, Intellectual disability, MESH: Cognition, CBCL, 030105 genetics & heredity, Cognition, Multidisciplinary approach, MESH: Child, Medicine, Child, Genetics (clinical), Rehabilitation, MESH: Hormone Replacement Therapy, Neurological Rehabilitation, Neuropsychology, Wechsler Adult Intelligence Scale, General Medicine, 3. Good health, MESH: Young Adult, Child, Preschool, Education, Special, Female, France, Prader-Willi Syndrome, Occupational therapy, medicine.medical_specialty, Adolescent, Hormone Replacement Therapy, MESH: Social Support, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Young Adult, 03 medical and health sciences, Social support, MESH: Neurological Rehabilitation, Genetics, Humans, Psychiatry, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Social Support, medicine.disease, MESH: Male, MESH: France, Patient care management, 030104 developmental biology, MESH: Education, Special, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Prader-Willi Syndrome, business, MESH: Female
Abstract: International audience; Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with a characteristic behavioural phenotype. A multidisciplinary approach to care is required to prevent multiple medical complications in individuals affected by PWS. The aim of this study was to describe the rehabilitation, medical care, educational and social support provided to school-aged French PWS patients with varying neuropsychological profiles. Data were obtained from a French multicentre study that included patients aged 4-20 years with diverse genetic syndromes. Nineteen PWS subjects with a mean age of 9.2 years were included. The mean full-scale intellectual quotient (IQ) was 58 (Wechsler scale). There were frequent dissociations between verbal and performance IQ that were not associated with a specific profile. We also observed lower autonomy and communication scores (5.3 years and 5.9 years equivalent, respectively, Vineland scale), the absence of hyperactivity (Conners scale), and the presence of behavioural abnormalities (CBCL scale). Multidisciplinary medical supervision was generally coordinated by the paediatric endocrinologist and did not always include follow-up with all of the recommended specialists, in particular with a paediatric psychiatrist. Analysis of multidisciplinary rehabilitation conducted in public and private-sector establishment revealed failings in psychological support, occupational therapy and dietary follow-up. Regarding education, most children younger than 10 years were in normal schools, while older individuals were often cared for in medico-social institutions. In conclusion, children and adolescents with PWS generally received appropriate care. Though there have been considerable improvements in the management of children with PWS, reference centres should continue reinforcing the coordination of multidisciplinary supervision.
Published: 2020
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47. Factors influencing the participation of adolescents and young adults with a congenital heart disease in a transition education program: A prospective multicentre controlled study

Author: Kathleen Lavastre, Hamouda Abassi, Marie-Christine Picot, Philippe Acar, Oscar Werner, Nathalie Souletie, Chris Serrand, Pascal Amedro, Sophie Guillaumont, Charlene Bredy, Yves Dulac, Service de cardiologie Pédiatrique [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Medical Information, La Colombière Hospital, Montpellier, France, Service pédiatrie-cardiologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and MORNET, Dominique
Subjects: Gerontology, Adult, Heart Defects, Congenital, Male, Health Knowledge, Attitudes, Practice, Transition to Adult Care, Heart disease, Adolescent, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Cardiology, Disease, 03 medical and health sciences, Body piercing, Congenital, Young Adult, 0302 clinical medicine, Quality of life, Deconditioning, Patient Education as Topic, medicine, Health knowledge, Humans, 030212 general & internal medicine, Prospective Studies, Young adult, Risk factor, media_common, Practice, business.industry, 030503 health policy & services, interests, digestive, oral, and skin physiology, General Medicine, Continuity of Patient Care, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Attitudes, Quality of Life, Heart defects, Female, Patient Participation, 0305 other medical science, business, interests.hobby, Autonomy
Abstract: Objective Transition education programs dedicated to adolescents and young adults with congenital heart disease (CHD) aim to facilitate transfer to adult cardiology and bring more autonomy to teenagers. This prospective controlled multicentre study analysed the factors influencing the participation in a transition education program. Methods CHD patients aged 13–25 y were offered to participate in the transition program. A multiple linear regression identified the explanatory factors for participation in the program. Results A total of 123 patients (mean age 19.6 ± 3.4 y) were included in the study, with 57 participants and 66 non-participants. Both groups showed similar socio-demographic and quality of life characteristics, low level of physical activity with muscular deconditioning and high exposure to risk behaviours (71% patients with ≥1 risk factor). Patients with complex CHD (OR = 4.1, P = 0.03), poor disease knowledge (OR = 0.3, P = 0.02), risk behaviours (body piercing, OR = 5.53, P = 0.01; alcohol, OR = 3.12, P = 0.06), and aged Conclusion Many risk factors influencing the participation of adolescents and young adults with CHD in transition education programs are controllable. Practice implication Further randomized studies are necessary to evaluate the impact of transition education program on quality of life, successful transfer to adult centre and, ultimately, prognosis.
Published: 2018
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48. Impact of a centre and home-based cardiac rehabilitation program on the quality of life of teenagers and young adults with congenital heart disease: The QUALI-REHAB study rationale, design and methods

Author: Laurent Poirette, Frederique Sidney, Claire Dauphin, Fanny Bajolle, Loïc Macé, Magalie Ladouceur, Nicolas Combes, Laurence Cohen, Oxana-Anca Neagu, Arthur Gavotto, Philippe Brosset, Antoine Legendre, Pascal Amedro, Camille Soullier, Stefan Matecki, Yves Dulac, Hélène Bouvaist, Gilles Bosser, Jean-Benoit Thambo, Sébastien Hascoët, Caroline Ovaert, Sophie Guillaumont, Xavier Iriart, Damien Bonnet, Sonia Corone, Manon Ladeveze, Sarah Cohen, Gregoire De La Villeon, Charlene Bredy, D'Arcy Vandenberghe, Kathleen Lavastre, Marie-Christine Picot, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Institut Régional de Médecine Physique et de Réadaptation Louis Pierquin [Nancy] (IRR Louis Pierquin), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Centre de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre médical de Bligny, Centre hospitalier de Bligny, 91640 Briis-sous-Forges, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Service pédiatrie-cardiologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille, Centre réhabilitation Cardiaque de Beaumont de Lomagne, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Leon Berard Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service cardiologie pédiatrique [Bordeaux], CHU Bordeaux [Bordeaux], Clinique Pasteur [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche Magellan, Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MORNET, Dominique
Subjects: Adult, Heart Defects, Congenital, Male, medicine.medical_specialty, Heart disease, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Deconditioning, Quality of life, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Young adult, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, Rehabilitation, Cardiac Rehabilitation, Exercise Tolerance, business.industry, VO2 max, medicine.disease, Home Care Services, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Physical therapy, Quality of Life, Health education, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Background Advances in congenital heart disease (CHD) have transferred the mortality from childhood to adulthood. Exercise capacity in young patients with CHD remains lower than in the general population, resulting in deconditioning and impaired quality of life. Evidence based-medicine in cardiac rehabilitation in this age group with CHD remains limited. We present the QUALI-REHAB study rationale, design and methods. Methods The QUALI-REHAB trial is a nationwide, multicentre, randomised, controlled study, aiming to assess the impact of a combined centre and home-based cardiac rehabilitation program on the quality of life of adolescents and young adults (13 to 25 years old) with CHD. Patients with a maximum oxygen uptake (VO2max) Conclusion After focusing on the survival in CHD, current research is opening on secondary prevention and patient-related outcomes. The QUALI-REHAB trial intends to assess if a combined centre and home-based rehabilitation program, could improve the quality of life and the exercise capacity in youth with CHD. Trial registration: Clinicaltrials.gov ( NCT03690518 ).
Published: 2018
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49. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond–like syndrome

Author: Aline Schmidt, Felipe Suarez, Eric Oksenhendler, Barbara Schmaltz-Panneau, Philippe Bensaid, Jean Donadieu, Gérard Pierron, Yves Bertrand, Aurélie Docet, Blandine Beaupain, Vincent Barlogis, Frédéric Bauduer, Séverine Clauin, Christine Bellanné-Chantelot, Isabelle Plo, Isabelle Callebaut, Nathalie Aladjidi, Françoise Mazingue, Sylvie Souquere, Iléana Antony-Debré, Cécile Stoven, Thuan Chong Quah, Isabelle Pellier, Caroline Marty, Hubert Journel, Thierry Leblanc, Marie Ouachee, Gandhi-Laurent Damaj, Liana Carausu, Claire Fieschi, Odile Fenneteau, Véronique Saada, Claire Galambrun, Odile Boespflug-Tanguy, Marlène Pasquet, Brigitte Nelken, William Vainchenker, Claire Berger, 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Hematology, Centre Hospitalier Universitaire (CHU), Faculté de Médecine, University of Normandie Caen, Department of Pediatric Hematology and Immunology, Robert Debré Hospital, AP-HP, Paris, Department of Pediatric Hematology, Immunology and Oncology, CHU, Angers, Department of Pediatrics, CHU La Réunion, Groupe Hospitalier Sud Réunion, Physiologie et physiopathologie des rétrovirus endogènes et infectieux (RETRO-ENDO), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Unit of Pediatric Hematology, Centre d'Investigation Clinique 1401INSERM Centre d'Investigation Clinique Plurithématique, CHU Bordeaux, 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 Côte Basque, Bayonne, Department of Pediatrics, Centre Hospitalier Argenteuil, Argenteuil, Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Department of Pediatric Hematology and Oncology, CHU, Saint-Etienne, Pediatric Hematology and Oncology Institute, Lyon, Department of Pediatric Hematology and Oncology, CHU Brest, Department of Clinical Immunology, Saint-Louis Hospital, AP-HP, Paris, Service d'Hématologie pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Hematology, CHU, Angers, 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), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatric Hematology and Oncology, CHRU, Lille, Department of Pediatrics, National University Hospital, Singapore, Service d'hématologie-oncologie adultes, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Institut of Pediatric Hematology and Oncology, Lyon, Hématologie pédiatrique, CHU Toulouse [Toulouse], Laboratory of Hematology, Gustave Roussy, Villejuif, Department of Hematology, Necker-Enfants Malades University Hospital, AP-HP, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Paris Descartes, CNRS UMR9196, Gustave Roussy, Villejuif, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Département de biologie et pathologie médicales [Gustave Roussy], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Paris Descartes - Paris 5 (UPD5), Rétrovirus endogènes et éléments rétroïdes des eucaryotes supérieurs (UMR 9196), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de la Côte Basque (CHCB), National University of Singapore (NUS), Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Gene knockdown, Shwachman–Diamond syndrome, Mutation, business.industry, [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Neutropenia, medicine.disease, medicine.disease_cause, Biochemistry, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Membrane protein, Unfolded protein response, medicine, Cancer research, Congenital Neutropenia, business, Exocrine pancreatic insufficiency, ComputingMilieux_MISCELLANEOUS
Abstract: Congenital neutropenias (CNs) are rare heterogeneous genetic disorders, with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and 1 autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with 7 distinct germ line SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases. In nearly all patients, neutropenia was chronic and profound with promyelocytic maturation arrest, occurring within the first months of life, and required long-term granulocyte colony-stimulating factor therapy with a poor response. Neutropenia was sometimes associated with a severe neurodevelopmental delay (n = 5) and/or an exocrine pancreatic insufficiency requiring enzyme supplementation (n = 3). The SRP54 protein is a key component of the ribonucleoprotein complex that mediates the co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). We showed that SRP54 was specifically upregulated during the in vitro granulocytic differentiation, and that SRP54 mutations or knockdown led to a drastically reduced proliferation of granulocytic cells associated with an enhanced P53-dependent apoptosis. Bone marrow examination of SRP54-mutated patients revealed a major dysgranulopoiesis and features of cellular ER stress and autophagy that were confirmed using SRP54-mutated primary cells and SRP54 knockdown cells. In conclusion, we characterized a pathological pathway, which represents the second most common cause of CN with maturation arrest in the French CN registry.
Published: 2018
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50. Feasibility, Safety and Accuracy of Echocardiography-Fluoroscopy Imaging Fusion During Percutaneous Atrial Septal Defect Closure in Children

Author: Clément Karsenty, Alain Fraisse, Khaled Hadeed, Francoise Auriol, Nicolas Combes, Philippe Acar, François Heitz, Gerald Chausseray, Xavier Alacoque, Yves Dulac, Pascal Amedro, Sébastien Hascoët, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Service pédiatrie-cardiologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Clinique Pasteur [Toulouse], CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aix Marseille Université (AMU), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse]
Subjects: Male, Cardiac Catheterization, Percutaneous, Adolescent, Septal Occluder Device, Pediatric cardiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], education, Echocardiography, Three-Dimensional, 030204 cardiovascular system & hematology, Multimodal Imaging, Heart Septal Defects, Atrial, Congenital heart diseases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, Fluoroscopy, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Prospective Studies, Cardiac Surgical Procedures, Child, Fluoroscopic imaging, Cardiac catheterization, 3D echocardiography, medicine.diagnostic_test, business.industry, Imaging guidance, Reproducibility of Results, Atrial septal defect closure, Echocardiography, Doppler, Color, Treatment Outcome, Surgery, Computer-Assisted, Child, Preschool, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, Fluoroscopic image, business, Nuclear medicine, EchoNavigator, Echocardiography, Transesophageal, Imaging fusion
Abstract: Imaging fusion between echocardiography and fluoroscopy was recently developed. The aim of this study was to assess its feasibility and accuracy during pediatric cardiac catheterization.Thirty-one patients (median weight, 26 kg; interquartile range [IQR], 21-37 kg) who underwent percutaneous atrial septal defect closure were prospectively included. The feasibility and accuracy of various imaging fusion modalities (live two-dimensional, live color two-dimensional, live three-dimensional and markers) with EchoNavigator software were assessed. To assess the accuracy of spatial registration of the echocardiogram on the fluoroscopic image, the occluder screw, an object that appeared on each image, was used as a reference tool, and the distance between the two when fused was measured. A distance was measured on the fusion screen between a marker positioned on the screw from the echocardiography screen and from the fluoroscopy screen (distance 1). Another distance was measured on the fusion screen between the screw visualized by three-dimensional echocardiography and by fluoroscopy (distance 2). The two distances were measured on four C-arm orientations in end-systolic and end-diastolic frames.Fusion and marker positioning were feasible in real time in all cases. On the fusion screen, median systolic and diastolic distance 1 were 0.5 mm (IQR, 0.3-1 mm) and 2 mm (IQR, 1.5-2.5 mm; P .0001), respectively. The marker positioned from the echocardiography screen was fixed on the fusion screen and did not follow the movement of the screw. Median systolic and diastolic distance 2 were 0.5 mm (IQR, 0-0.5 mm) and 2 mm (IQR, 1.5-2.5 mm; P .0001), respectively.Echocardiographic fluoroscopic imaging fusion is feasible, safe, and accurate in children weighting20 kg. This technique offers a new method of imaging guidance in the catheterization laboratory for complex procedures and training.
Published: 2018
Full Text: View/download PDF

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