Author: "Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)" / Publisher: elsevier bv - Searchworks@Jio Institute Digital Library Search Results

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45 results on '"Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)"'

1. Rheology predicts sputum eosinophilia in patients with muco-obstructive lung diseases

Author: Mathilde Volpato, Jerome Vialaret, Christophe Hirtz, Aurélie Petit, Carey Suehs, Jérémy Patarin, Eric Matzner-Lober, Isabelle Vachier, Nicolas Molinari, Arnaud Bourdin, Jeremy Charriot, Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Rennes 2 (UR2), Hôpital de la Colombière, Institut Montpelliérain Alexander Grothendieck (IMAG), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Médecine de précision par intégration de données et inférence causale (PREMEDICAL), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Sputum, Biophysics, Cell Biology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Biochemistry, Asthma, Pulmonary Disease, Chronic Obstructive, Cross-Sectional Studies, Eosinophilia, Humans, Prospective Studies, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], Rheology, Molecular Biology
Abstract: International audience; Background: Mucus is known to play a pathogenic role in muco-obstructive lung diseases, but little is known about the determinants of mucus rheology. The purpose of this study is to determine which sputum components influence sputum rheology in patients with muco-obstructive lung diseases.Methods: We performed a cross sectional prospective cohort study. Spontaneous sputum was collected from consecutive patients with muco-obstructive lung diseases. Sputum rheology was assessed using the Rheomuco® rheometer (Rheonova, Grenoble); the elastic modulus G′, viscous modulus G″, and the critical stress threshold σc were recorded. Key quantitative and qualitative biological sputum components were determined by cytology, nucleic acid amplification tests and mass spectrometry.Results: 48 patients were included from January to August 2019. Among them, 10 had asthma, 14 COPD and 24 non-CF bronchiectasis (NCFB). The critical stress threshold σc predicted a sputum eosinophilia superior to 1.25% with 89.19% accuracy (AUC = 0.8762). G′ and G″ are positively correlated with MUC5AC protein concentration ((rho = 0.361; P = .013) and (rho = 0.335; P = .021), respectively). σc was positively correlated with sputum eosinophilia (rho = 0.394; P = .012), MUC5B (rho = 0.552; P < .001) and total protein (rho = 0.490; P < .001) concentrations. G′ and G″ were significantly higher in asthma patients (G’ = 14.49[7.18–25.26]Pa, G’‘ = 3.0[2.16–5.38]Pa) compared to COPD (G’ = 5.01[2.94–6.48]Pa, P = .010; G’‘ = 1.45[1.16–1.94]Pa, P = .006) and to NCFB (G’ = 4.99[1.49–10.49]Pa, P = .003; G’’ = 1.46[0.71–2.47]Pa, P = .002).Conclusion: In muco-obstructive lung diseases, rheology predicts sputum eosinophilia and is correlated with mucin concentrations, regardless of the underlying disease.Clinical trial registration: (registrar, website, and registration number), where applicable NCT04081740.
Published: 2022

2. Using intracellular SCGB1A1-sorted, formalin-fixed club cells for successful transcriptomic analysis

Author: Charlotte Vernisse, Aurélie Petit, Véronique Pantesco, Pascal Chanez, Delphine Gras, Edouard Tuaillon, Christophe Duperray, Isabelle Vachier, Said Assou, Arnaud Bourdin, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Hôpital Nord [CHU - APHM], EFS, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), MRI-Montpellier RIO Imaging, and MORNET, Dominique
Subjects: Paraffin Embedding, Tissue Fixation, Gene Expression Profiling, [SDV]Life Sciences [q-bio], Biophysics, Cell Biology, Flow Cytometry, Club cells, Transcriptomic analysis, Biochemistry, [SDV] Life Sciences [q-bio], SCGB1A1 sorting, Formaldehyde, RNA quality, Humans, Uteroglobin, RNA, Messenger, Transcriptome, Bronchioles, Molecular Biology
Abstract: International audience; As opposed to surface marker staining, certain cell types can only be recognized by intracellular markers. Intracellular staining for use in cell sorting remains challenging. Fixation and permeabilization steps for intracellular staining and the presence of RNases notably affect preservation of high-quality mRNA. We report the work required for the optimization of a successful protocol for microarray analysis of intracellular target-sorted, formalin-fixed human bronchial club cells. Cells obtained from differentiated air-liquid interface cultures were stained with the most characteristic intracellular markers for club cell (SCGB1A1+) sorting. A benchmarked intracellular staining protocol was carried out before flow cytometry. The primary outcome was the extraction of RNA sufficient quality for microarray analysis as assessed by Bioanalyzer System. Fixation with 4% paraformaldehyde coupled with 0.1% Triton/0.1% saponin permeabilization obtained optimal results for SCGB1A1 staining. Addition of RNase inhibitors throughout the protocol and within the appropriate RNA extraction kit (Formalin-Fixed-Paraffin-Embedded) dramatically improved RNA quality, resulting in samples eligible for microarray analysis. The protocol resulted in successful cell sorting according to specific club cell intracellular marker without using cell surface marker. The protocol also preserved RNA of sufficient quality for subsequent microarray transcriptomic analysis, and we were able to generate transcriptomic signature of club cells.
Published: 2022

3. Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder

Author: Marjolaine Willems, Benjamin Durand, Boris Keren, Kristina Pilekær Sørensen, Rosanna Weksberg, Magalie Barth, Christina Fagerberg, Cyril Mignot, Laurence Perrin, Lucas Bronicki, Nathalie Drouot, Imene Boujelbene, Marc Abramowicz, Maria Kibaek, Bertrand Isidor, Thierry Bienvenu, Mathilde Nizon, Perrine Charles, Laurent Pasquier, Yann Herault, Marie Christine Birling, Bruno Delobel, Michel Guipponi, Lydie Burglen, Mélanie Fradin, Anne Sophie Denommé, Florence Demurger, Benjamin Cogné, Sébastien Moutton, Allan Bayat, Frederic Tran Mau Them, Christèle Dubourg, Alice Goldenberg, Christine Francannet, Jean-Louis Mandel, Laurence Faivre, Jérémie Courraud, Anne Marie Guerrot, Julia Metreau, Loréline Genschik, Bénédicte Demeer, Marie Vincent, Mathilde Renaud, Julien Thevenon, Sandrine Passemard, Christine Coubes, Amélie Piton, David Geneviève, Maria del Mar Muniz Moreno, Bénédicte Gérard, Estelle Colin, Valérie Layet, Michèle Mathieu-Dramard, Salima El Chehadeh, Katrine M Johannesen, Julie D. Thompson, Cathrine Elisabeth Tronhjem, Pascale Saugier, Elise Schaefer, Eric Chater-Diehl, Séverine Drunat, Rikke S. Møller, Paul Kuentz, Claire Feger, Albert David, Antonio Vitobello, Marlène Rio, Khaoula Khachnaoui, Joane Svane, Stéphane Auvin, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Hospital for sick children [Toronto] (SickKids), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Universitaire de Genève, Children's hospital of Eastern Ontario Research Institute [Ottawa, canada] (CHEO), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Robert Debré, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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, Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), The Danish Epilepsy Centre Filadelfia [Dianalund, Denmark], University of Southern Denmark (SDU), Odense University Hospital (OUH), CHU Amiens-Picardie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Odense University Hospital [Odense, Denmark], Centre Hospitalier Universitaire [Grenoble] (CHU), Groupe Hospitalier du Havre, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Clinique de la Souris, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Hôpital Cochin [AP-HP], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), 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)-Centre National de la Recherche Scientifique (CNRS)-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)-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)-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), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), University of Toronto, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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 ), 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), Agence de Biomédecine, Fondation APLM, Fondation Maladies Rares and Fondation Jérome Lejeune, univOAK, Archive ouverte, 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), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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), and 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)
Subjects: [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], DYRK1A, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Protein Serine-Threonine Kinases, Biology, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Mice, 03 medical and health sciences, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual Disability, medicine, Animals, Humans, Missense mutation, Kinase activity, Gene, Genetics (clinical), Cellular localization, 030304 developmental biology, Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Protein-Tyrosine Kinases, medicine.disease, Phenotype, Human genetics, 3. Good health, 030220 oncology & carcinogenesis, Microcephaly
Abstract: Purpose: DYRK1A syndrome is among the most frequent monogenic forms of intellectual disability (ID). We refined the molecular and clinical description of this disorder and developed tools to improve interpretation of missense variants, which remains a major challenge in human genetics. Methods: We reported clinical and molecular data for 50 individuals with ID harboring DYRK1A variants and developed (1) a specific DYRK1A clinical score; (2) amino acid conservation data generated from 100 DYRK1A sequences across different taxa; (3) in vitro overexpression assays to study level, cellular localization, and kinase activity of DYRK1A mutant proteins; and (4) a specific blood DNA methylation signature. Results: This integrative approach was successful to reclassify several variants as pathogenic. However, we questioned the involvement of some others, such as p.Thr588Asn, still reported as likely pathogenic, and showed it does not cause an obvious phenotype in mice. Conclusion: Our study demonstrated the need for caution when interpreting variants in DYRK1A, even those occurring de novo. The tools developed will be useful to interpret accurately the variants identified in the future in this gene. Graphic abstract: [Figure not available: see fulltext.]
Published: 2021

4. Isthmocèle : définition, diagnostic, facteurs de risque, prévention, symptômes, complications, et traitements

Author: Antoine Torre, E. Verspyck, Jim G Thornton, Samir Hamamah, P Crochet, Arnaud Fauconnier, I. Thomassin, Service de gynécologie et obstétrique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Développement embryonnaire précoce humain et pluripotence EmbryoPluripotency (UMR 1203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CHU 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), Service d'Imageries Radiologiques et Interventionnelles [CHU Tenon] (IRIS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Les auteurs remercient Andrea Kaelin et Olivier Limot pour leur soutien dans la r?daction de cet article.
Subjects: Gynecology, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, business.industry, Prevention, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, Definition, Caesarean scar niche, female genital diseases and pregnancy complications, 3. Good health, Treatment, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, Diagnosis, Medicine, 030212 general & internal medicine, business, reproductive and urinary physiology
Abstract: Resume Objectifs Etablir un etat des lieux sur la definition, le diagnostic, les facteurs de risque, les symptomes, et les traitements de l’isthmocele. Methodes Revue de la litterature, reflexions critiques, et conseils pragmatiques. Resultats La definition de l’isthmocele n’est pas consensuelle. Certains proposent une indentation ≥ 2 mm du myometre de la cicatrice de cesarienne, mais cet aspect present chez plus de la moitie des uterus cicatriciels ne prend pas en compte les symptomes de la femme. La methode de diagnostic la plus performante semble etre l’echographie ± hysterosonographie. Les situations a risque d’isthmocele sont l’uterus multicicatriciel, la cesarienne pendant le travail avec une incision trop basse, et l’uterus retroverse. Les symptomes de l’isthmocele sont des saignements gynecologiques anormaux et des douleurs pelviennes, et leur presence signe le « syndrome de la cicatrice de cesarienne ». Les risques d’une grossesse en cas d’isthmocele ont ete peu etudies, mais elle ne semble pas contre-indiquee, meme si l’isthmocele n’est pas traite. Le traitement de l’isthmocele est avant tout chirurgical, conservateur, et semble reserve aux patientes symptomatiques, et aux infertilites secondaires en echec de traitement. Les patientes avec myometre residuel ≥ 2,5 mm peuvent beneficier d’un traitement hysteroscopique de premiere intention, tandis qu’on proposera un abord cœlioscopique ou vaginal dans les autres cas. Conclusions Une definition pragmatique de l’isthmocele maladie en incluant la presence de symptomes est le pre-requis necessaire a la prise en charge des femmes. Le traitement est avant tout chirurgical, conservateur ou non suivant le desir de grossesse ulterieur.
Published: 2021

5. Phenotypic Associations of PSTPIP1 Sequence Variants in PSTPIP1-Associated Autoinflammatory Diseases

Author: Guilaine Boursier, Maryam Piram, Isabelle Touitou, Cécile Rittore, Guillaume Sarrabay, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Sainte Justine [Montréal], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, 0301 basic medicine, Proband, Dermatology, Biochemistry, 03 medical and health sciences, Broad spectrum, 0302 clinical medicine, Acne Vulgaris, Humans, Medicine, Molecular Biology, Gene, Genetic Association Studies, Adaptor Proteins, Signal Transducing, Sequence (medicine), Genetics, Arthritis, Infectious, business.industry, Hereditary Autoinflammatory Diseases, Cell Biology, Pathogenicity, medicine.disease, Phenotype, Pyoderma Gangrenosum, 3. Good health, Cytoskeletal Proteins, 030104 developmental biology, 030220 oncology & carcinogenesis, Sterile arthritis, Female, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Pyoderma gangrenosum
Abstract: International audience; Pathogenic variants in the PSTPIP1 gene cause pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. They were also identified in a broad spectrum of phenotypes. As their interpretation is sometimes challenging, we discuss the genotype-phenotype association in PSTPIP1-associated autoinflammatory diseases (PAIDs) in light of a recent consensus classification of variant pathogenicity. Only 7 of 39 (18%) of the PSTPIP1 variants found in all reported cases and our national reference center (161 patients [114 probands]) were pathogenic. They were clearly associated with PAPA and PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome (PAMI), reflecting a variable clinical expression of PAIDs.
Published: 2021

6. Clinical and pathological dermatological features of deficiency of adenosine deaminase 2: A multicenter, retrospective, observational study

Author: Nathalie Franck, Nicolas Dupin, A. Bonhomme, Floriane Kouby, Guilaine Boursier, Viviane Queyrel, Gabrielle Goldman-Lévy, Annick Barbaud, Isabelle Touitou, Stéphanie Ducharme-Bénard, Guillaume Sarrabay, Groupe d'étude des maladies systémiques en dermatologie, Sophie Georgin-Lavialle, Antoine Fayand, Didier Bessis, Camille Francès, François Chasset, Philippe Moguelet, Sylvie Fraitag, Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), Service d'Anatomie et cytologie pathologiques [CHU Tenon], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Groupe d'étude des maladies systémiques en dermatologie and Centre de référence des maladies auto-inflammatoires et des amyloses d'origine inflammatoire, CCSD, Accord Elsevier, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: Adult, medicine.medical_specialty, Adolescent, Adenosine Deaminase, Biopsy, [SDV]Life Sciences [q-bio], MEDLINE, Dermatology, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Young adult, Child, Pathological, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Skin, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, Hereditary Autoinflammatory Diseases, Retrospective cohort study, ADENOSINE DEAMINASE 2, medicine.disease, Polyarteritis Nodosa, 3. Good health, Adenosine deaminase deficiency, [SDV] Life Sciences [q-bio], Intercellular Signaling Peptides and Proteins, Observational study, business
Abstract: International audience; No abstract available
Published: 2020

7. A Randomized Prospective Study Comparing Anti–T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients

Author: Antoine Durrbach, Vincent Pernin, Nicolas Congy, Moglie Lequintrec, Pierre Merville, Nassim Kamar, Lionel Couzi, Laetitia Albano, Arnaud Del Bello, Anne Laure Hebral, Benoit Lepage, L. Esposito, Amandine Darres, Elisabeth Cassuto, PINIER, CHRISTINE, 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), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Unité de Soutien Méthodologique à la Recherche (USMR), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Le service de Néphrologie-Dialyse-Transplantation, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Allergologie et d'Immunologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Néphrologie et transplantation d'organes CHU Rangueil TOULOUSE, Service d'épidémiologie [Toulouse], CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Service d'immunologie CHU RANGEUIL TOULOUSE
Subjects: medicine.medical_specialty, Basiliximab, medicine.drug_class, 030232 urology & nephrology, basiliximab, kidney transplantation, 030204 cardiovascular system & hematology, Monoclonal antibody, DSA, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Prospective cohort study, highly sensitized, Kidney transplantation, Kidney, biology, business.industry, induction therapy, medicine.disease, Confidence interval, 3. Good health, Transplantation, medicine.anatomical_structure, Nephrology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, biology.protein, Antibody, business, Grafalon, medicine.drug
Abstract: Background Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies. Methods This prospective pilot randomized French multicenter study aimed to compare anti–T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included. Results Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%–37.1%) and 18.8% (95% CI, 8.9%–37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%–34.8%) and 28.2% (95% CI, 14.2%–51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell–mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups. Conclusion This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution., Graphical abstract
Published: 2020

8. Challenges of autoimmune rheumatic disease treatment during the COVID-19 pandemic: A review

Author: Grange, Lucile, Guilpain, Philippe, Truchetet, Marie-Elise, Cracowski, Jean-Luc, Pharmacology And Therapeutics, French Society Of, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CCSD, Accord Elsevier, Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), and Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2)
Subjects: [SDV]Life Sciences [q-bio], RA, rheumatoid arthritis, Disease, Pharmacologie, 030226 pharmacology & pharmacy, Dexamethasone, SLE, systemic lupus erythematosus, 0302 clinical medicine, Chloroquine, Pandemic, COVID-19, novel coronavirus disease 2019, Pharmacology (medical), ANCA, anti-neutrophil cytoplasmic antibodies, bDMARDS, biological disease-modifiyng antirheumatic drugs, NSAIDs, non steroidal anti-inflammatory drugs, TNF, tumor necrosis factor, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, tsDMARDS, targeted synthetic disease modifying antirheumatic drugs, Incidence, TCZ, tocilizumab, Anti-Inflammatory Agents, Non-Steroidal, Dexaméthasone, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ICU, intensive care unit, 3. Good health, Polyarthrite rhumatoïde, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Rhumatologie, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Rheumatoid arthritis, Coronavirus Infections, csDMARDS, conventional synthetic disease modifying antirheumatic drugs, Hydroxychloroquine, medicine.drug, medicine.medical_specialty, IL6, interleukin 6, Pneumonia, Viral, Article, WHO, World Health Organization, Autoimmune Diseases, 03 medical and health sciences, Immune system, Rheumatology, Rheumatic Diseases, Internal medicine, medicine, Humans, IL1, interleukin 1, Intensive care medicine, Pandemics, ARDS, acute respiratory distress syndrome, MERS-COV, middle East respiratory syndrome coronavirus, Pharmacology, SSc, systemic sclerosis, business.industry, COVID-19, HCQ, hydroxychloroquine, medicine.disease, JAK, Janus kinase (inhibitors), RNA, ribonucleic acid, SARS-COV2, severe acute respiratory syndrome coronavirus 2, business
Abstract: Since December 2019, the COVID-19 pandemic has become a major public health problem. To date, there is no evidence of a higher incidence of COVID in patients with autoimmune rheumatic diseases and we support the approach of maintaining chronic rheumatological treatments. However, once infected there is a small but significant increased risk of mortality. Among the different treatments, NSAIDs are associated with higher rates of complications, but data for other drugs are conflicting or incomplete. The use of certain drugs for autoimmune inflammatory rheumatisms appears to be a potentially interesting options for the treatment. The rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines (Il1, IL6, TNFα) in severe forms of the disease. Notably, patients on chloroquine or hydroxychloroquine as a treatment for their autoimmune rheumatic disease are not protected from COVID-19., Depuis décembre 2019, la pandémie de COVID-19 est devenue un problème majeur de santé publique. À ce jour, il n’y a aucune preuve d’une incidence plus élevée de COVID chez les patients atteints de maladies rhumatismales auto-immunes et nous soutenons l’approche consistant à maintenir les traitements rhumatologiques chroniques. Cependant, une fois infecté, il y a un risque accru de mortalité faible mais significatif. Parmi les différents traitements, les AINS sont associés à des taux plus élevés de complications, mais les données pour d’autres médicaments sont contradictoires ou incomplètes. L’utilisation de certains médicaments pour les rhumatismes inflammatoires auto-immuns semble être une option potentiellement intéressante pour le traitement. La raison de leur utilisation est basée sur l’emballement du système immunitaire et la sécrétion de cytokines pro-inflammatoires (Il1, IL6, TNFα) dans les formes graves de la maladie. Notamment, les patients sous chloroquine ou hydroxychloroquine comme traitement de leur maladie rhumatismale auto-immune ne sont pas protégés contre la COVID-19.
Published: 2020

9. [Modelling the bronchial epithelium in chronic obstructive pulmonary disease using human induced pluripotential stem cells]

Author: Mathieu Fieldes, Isabelle Vachier, Said Assou, Aurélie Fort, Engi Ahmed, J. De Vos, Charlotte Vernisse, Arnaud Bourdin, Chloé Bourguignon, Joffrey Mianné, MORNET, Dominique, 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), 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), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-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), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, business.industry, [SDV]Life Sciences [q-bio], Chronic obstructive pulmonary disease, Bronchial epithelium, Différenciation dirigée, Épithélium bronchique, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Molecular biology, respiratory tract diseases, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Cellule souche pluripotente induite humaine, 030228 respiratory system, Human induced pluripotential stem cells, Directed differentiation, Bronchopneumopathie chronique obstructive, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Medicine, 030212 general & internal medicine, business
Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease leading to irreversible destruction of the terminal bronchioles. Although the precise patho-physiological mechanisms remain to be elucidated, the bronchial epithelium seems to play a pivotal role in the disease. Recent studies have highlighted a great heterogeneity among COPD patients, with various disease courses including, in about half the cases, an origin in childhood. Modelling of COPD is a major goal but currently available models are imperfect. Our work aims to create a new in vitro cellular model to study the pathology of the disease. The differentiation of human induced pluripotential stem cells (hiPSCs) in bronchial epithelium is a step towards a better understanding of the developmental origin and the identification of new therapeutic targets., La bronchopneumopathie chronique obstructive (BPCO) est une atteinte chronique des voies aériennes distales caractérisée par une destruction irréversible des bronchioles terminales. Bien que les mécanismes physiopathologiques demeurent incompris à ce jour, l’épithélium bronchique semble être le chef d’orchestre de la maladie. De récentes études ont montré l’existence de différentes trajectoires de la maladie incluant dans la moitié des cas une origine pédiatrique. La modélisation de la BPCO constitue donc un enjeu majeur mais les modèles actuels sont imparfaits. La différenciation des cellules souches pluripotentes induites humaines (hiPSC) en épithélium bronchique représente un nouvel outil pour étudier les racines pédiatriques de la maladie et identifier de nouvelles cibles thérapeutiques.
Published: 2020

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

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

11. Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities

Author: Yannis Duffourd, Catherine Sarret, B. Catteau, Rachel G. Knox, Chloé Quélin, Cyril Mignot, Martin Chevarin, P. Callier, Diana Rodriguez, Alexis Arzimanoglou, Robert Olaso, David Geneviève, Arthur Sorlin, Sylvie Odent, Christel Thauvin, Victoria E. R. Parker, Pierre Vabres, Louise Goujon, Malika Keddar, Melissa Riachi, Sylvie Fraitag, Laurence Faivre, Emmanuelle Blanchard, Satyamaanasa Polubothu, Marie-Line Jacquemont, Jean-Baptiste Rivière, Anne Boland, Jean-François Deleuze, Paul Rollier, Véronique Darmency, Marie-Hélène Aubriot-Lorton, Yline Capri, V. Carmignac, Daniel Amram, Catherine Vincent-Delorme, Paul Kuentz, Marc Delepine, Didier Bessis, Robert K. Semple, Sarah Grotto, Veronica A. Kinsler, Laurent Guibaud, Christophe Philippe, Jean-Benoît Courcet, Apollo - University of Cambridge Repository, 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, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Cambridge [UK] (CAM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), 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), CHU Pontchaillou [Rennes], AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHI Créteil, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), University of Edinburgh, and BOHAUD, FRANCOISE
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Melanocyte, Mechanistic Target of Rapamycin Complex 1, Article, 03 medical and health sciences, Tuberous sclerosis, Epilepsy, 0302 clinical medicine, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Megalencephaly, Genetics (clinical), PI3K/AKT/mTOR pathway, Hypopigmentation, business.industry, Mosaicism, TOR Serine-Threonine Kinases, Macrocephaly, Correction, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Immunostaining
Abstract: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex.
Published: 2021

12. Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19

Author: Lucy Kundura, Sandrine Gimenez, Renaud Cezar, Sonia André, Mehwish Younas, Yea-Lih Lin, Pierre Portalès, Claire Lozano, Charlotte Boulle, Jacques Reynes, Thierry Vincent, Clément Mettling, Philippe Pasero, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Géraud Claret, Sandra Duvnjak, Paul Loubet, Albert Sotto, Tu-Anh Tran, Jérôme Estaquier, Pierre Corbeau, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Laboratoire de Bioingénierie et NanoSciences (LBN), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Virulence Bactérienne et Infections Chroniques (VBIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval), and ANR-21-COVR-0024,ACT-LONG-COVID,Caractérisation clinique et biologique du syndrome d'activation mastocytaire dans le COVID long et prédisposition génétique(2021)
Subjects: T-Lymphocytes, Immunology, ACE2, Apoptosis, MESH: Lymphopenia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphopenia, Humans, MESH: COVID-19, Immunology and Allergy, MESH: SARS-CoV-2, DNA oxidation, Programmed cell death, MESH: DNA Damage, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, SARS-CoV-2, Angiotensin II, COVID-19, MESH: Reactive Oxygen Species, MESH: T-Lymphocytes, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oxidative stress, Angiotensin II receptor, MESH: Angiotensin II, MESH: Apoptosis COVID-19, Antioxidant, Reactive Oxygen Species, DNA Damage
Abstract: International audience; Background: Lymphopenia is predictive of survival in patients with coronavirus disease 2019 (COVID-19).Objective: The aim of this study was to understand the cause of the lymphocyte count drop in severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: Monocytic production of reactive oxygen species (ROSs) and T-cell apoptosis were measured by flow cytometry, DNA damage in PBMCs was measured by immunofluorescence, and angiotensin II (AngII) was measured by ELISA in patients infected with SARS-CoV-2 at admission to an intensive care unit (ICU) (n 5 29) or not admitted to an ICU (n 5 29) and in ageand sex-matched healthy controls.Results: We showed that the monocytes of certain patients with COVID-19 spontaneously released ROSs able to induce DNA damage and apoptosis in neighboring cells. Of note, high ROS production was predictive of death in ICU patients. Accordingly, in most patients, we observed the presence of DNA damage in up to 50% of their PBMCs and T-cell apoptosis. Moreover, the intensity of this DNA damage was linked to lymphopenia. SARS-CoV-2 is known to induce the internalization of its receptor, angiotensin-converting enzyme 2, which is a protease capable of catabolizing AngII. Accordingly, in certain patients with COVID-19 we observed high plasma levels of AngII. When looking for the stimulus responsible for their monocytic ROS production, we revealed that AngII triggers ROS production by monocytes via angiotensin receptor I. ROSs released by AngII-activated monocytes induced DNA damage and apoptosis in neighboring lymphocytes.Conclusion: We conclude that T-cell apoptosis provoked via DNA damage due to the release of monocytic ROSs could play a major role in COVID-19 pathogenesis.
Published: 2022

13. Cell-based therapy against prion diseases

Author: Sylvain Lehmann, Carole Crozet, Aroa Relaño-Ginés, 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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Programmed cell death, animal diseases, Cell, Inflammation, Biology, Mesenchymal Stem Cell Transplantation, 030226 pharmacology & pharmacy, Prion Diseases, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Drug Discovery, medicine, Animals, Humans, Secretion, Pharmacology, Microglia, Neurogenesis, Mesenchymal stem cell, Neural stem cell, nervous system diseases, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Cancer research, medicine.symptom, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Despite multiple efforts to find treatments, prion diseases are still incurable. The currently available therapeutic strategies are mostly based on compounds to inhibit pathological PrP (PrPSc) accumulation, and cellular PrP (PrPC) conversion into PrPSc. However, they cannot reverse the pathological changes already present in the brain. Cell-based therapeutic strategies could promote the repair of the pre-existing brain damage. The few available data come mostly from preclinical studies using neural stem cells, bone marrow-derived microglia and mesenchymal stem cells, as cell sources. Moreover, the benefits of cell-based therapeutic strategies could be linked not only to the replacement of damaged cells, but also to the secretion of trophic factors by the grafted cells that might modulate inflammation, cell death, or endogenous neurogenesis.
Published: 2019

14. Boundaries between familial Mediterranean fever and juvenile spondyloarthritis: Analysis of three French retrospective cohorts

Author: Isabelle Touitou, Véronique Hentgen, Isabelle Koné-Paut, P. Dusser, Maryam Piram, Sophie Georgin-Lavialle, Linda Rossi-Semerano, Caroline Galeotti, Bilade Cherqaoui, CHU Montpellier, 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), Service de Rhumatologie [CHU Bicêtre], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Male, 0301 basic medicine, Heterozygote, Pediatrics, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Familial Mediterranean fever, Gout Suppressants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rheumatology, Spondylarthritis, Ethnicity, Humans, Medicine, Colchicine, Juvenile Spondyloarthritis, Child, ComputingMilieux_MISCELLANEOUS, HLA-B27 Antigen, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Infant, DNA, Somewhat difficult, Pyrin, MEFV, medicine.disease, Familial Mediterranean Fever, 3. Good health, 030104 developmental biology, chemistry, Child, Preschool, Mutation, Female, France, business
Abstract: Children with Familial Mediterranean fever may suffer from musculoskeletal involvement, somewhat difficult to distinguish from juvenile spondyloarthritis. The association of these two diseases has been scarcely reported in children. Objective of this work was to define the association of familial Mediterranean fever and juvenile spondyloarthritis in France.Three cohorts of children with familial Mediterranean fever, juvenile spondyloarthritis, familial Mediterranean fever related juvenile spondyloarthritis, were retrospectively identified in the French reference center of auto-inflammatory diseases. Familial Mediterranean fever was defined according to Tel-Hashomer or Turkish pediatric criteria with at least one exon-10 MEFV-gene mutation. Juvenile spondyloarthritis was defined according to ILAR criteria. Patients with familial Mediterranean fever or juvenile spondyloarthritis were respectively compared to familial Mediterranean fever related juvenile spondyloarthritis patients.Sixteen children were identified as having familial Mediterranean fever related juvenile spondyloarthritis. The male/female-ratio was 0.6, with median age at spondyloarthritis onset of 7.5years (3-16years). All carried at least one M694V variant in MEFV gene; 16.7% were HLA-B27-carriers. Compared to 83 familial Mediterranean fever patients, familial Mediterranean fever related juvenile spondyloarthritis patients had less frequently fever (P0.01) and more frequently arthritis (P0.05), enthesitis (P0.001), inflammatory back pain (P0.001), inadequate response to colchicine (P0.05). Compared to 20 juvenile spondyloarthritis patients, familial Mediterranean fever related juvenile spondyloarthritis patients less often received non-steroidal anti-inflammatory drugs (P0.01) and anti-tumor necrosis factor drugs (P0.001).Familial Mediterranean fever may be associated with typical pattern of juvenile spondyloarthritis. These patients, with less response to colchicine, should be diagnosed earlier and treated as for jSpA.
Published: 2018

15. Plasma and CSF biomarkers for the diagnosis of Alzheimer's disease in adults with Down syndrome: a cross-sectional study

Author: Maria Carmona-Iragui, Isabel Barroeta, Susana Fernández, Christophe Hirtz, Alberto Lleó, Laura Videla, Juan Fortea, Sylvain Lehmann, Olivia Belbin, Constance Delaby, Rafael Blesa, Mony J. de Leon, Jordi Pegueroles, Bessy Benejam, Daniel Alcolea, Aleksandra Maleska Maceski, Sebastián Videla, Laia Muñoz, Jordi Clarimón, 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), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Hospital de la Santa Creu i Sant Pau, Fundació Catalana de Síndrome de Down [Barcelona], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), and Institute of Health Carlos III, Fundació La Marató de TV3, Fundació Bancaria Obra Social La Caixa, Fundació Catalana Síndrome de Down, and Fundació Víctor Grífols i Lucas.
Subjects: Adult, Male, 0301 basic medicine, Down syndrome, medicine.medical_specialty, Population, Prodromal Symptoms, tau Proteins, Comorbidity, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Neurofilament Proteins, Internal medicine, medicine, Humans, Dementia, education, education.field_of_study, Amyloid beta-Peptides, business.industry, Area under the curve, Middle Aged, medicine.disease, 3. Good health, Cross-Sectional Studies, 030104 developmental biology, Biomarker (medicine), Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Down Syndrome, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Blood sampling
Abstract: International audience; BACKGROUND:Diagnosis of Alzheimer's disease in Down syndrome is challenging because of the absence of validated diagnostic biomarkers. We investigated the diagnostic performance of plasma and CSF biomarkers in this population.METHODS:We did a cross-sectional study of adults aged 18 years and older with Down syndrome enrolled in a population-based health plan in Catalonia, Spain. Every person with Down syndrome assessed in the health plan was eligible to enter the Down Alzheimer Barcelona Neuroimaging Initiative, and those with a plasma or CSF sample available were included in this study. Participants underwent neurological and neuropsychological examination and blood sampling, and a subset underwent a lumbar puncture. Adults with Down syndrome were classified into asymptomatic, prodromal Alzheimer's disease, or Alzheimer's disease dementia groups by investigators masked to biomarker data. Non-trisomic controls were a convenience sample of young (23-58 years) healthy people from the Sant Pau Initiative on Neurodegeneration. Amyloid-β (Aβ)1-40, Aβ1-42, total tau (t-tau), 181-phosphorylated tau (p-tau; only in CSF), and neurofilament light protein (NfL) concentrations were measured in plasma with a single molecule array assay and in CSF with ELISA. Plasma and CSF biomarker concentrations were compared between controls and the Down syndrome clinical groups. Diagnostic performance was assessed with receiver operating characteristic curve analyses between asymptomatic participants and those with prodromal Alzheimer's disease and between asymptomatic participants and those with Alzheimer's disease dementia.FINDINGS:Between Feb 1, 2013, and Nov 30, 2017, we collected plasma from 282 participants with Down syndrome (194 asymptomatic, 39 prodromal Alzheimer's disease, 49 Alzheimer's disease dementia) and 67 controls; CSF data were available from 94 participants (54, 18, and 22, respectively) and all 67 controls. The diagnostic performance of plasma biomarkers was poor (area under the curve [AUC] between 0·53 [95% CI 0·44-0·62] and 0·74 [0·66-0·82]) except for plasma NfL concentrations, which had an AUC of 0·88 (0·82-0·93) for the differentiation of the asymptomatic group versus the prodromal Alzheimer's disease group and 0·95 (0·92-0·98) for the asymptomatic group versus the Alzheimer's disease dementia group. In CSF, except for Aβ1-40 concentrations (AUC 0·60, 95% CI 0·45-0·75), all biomarkers had a good performance in the asymptomatic versus prodromal Alzheimer's disease comparison: AUC 0·92 (95% CI 0·85-0·99) for Aβ1-42, 0·81 (0·69-0·94) for t-tau, 0·80 (0·67-0·93) for p-tau, and 0·88 (0·79-0·96) for NfL. Performance of the CSF biomarkers was optimal in the asymptomatic versus Alzheimer's disease dementia comparison (AUC ≥0·90 for all except Aβ1-40 [0·59, 0·45-0·72]). Only NfL concentrations showed a strong correlation between plasma and CSF biomarker concentrations in participants with Down syndrome (rho=0·80; p
Published: 2018

16. Nano-flow vs standard-flow: Which is the more suitable LC/MS method for quantifying hepcidin-25 in human serum in routine clinical settings?

Author: Pauline Bros, Christophe Hirtz, Jérôme Vialaret, Alexia Picas, Sylvain Lehmann, Constance Delaby, 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), Plateforme de Protéomique Clinique, and CHU Saint-Eloi
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Hepcidin, Clinical settings, Standard LC, 01 natural sciences, Biochemistry, Mass Spectrometry, Analytical Chemistry, 03 medical and health sciences, Hepcidins, Limit of Detection, Liquid chromatography–mass spectrometry, Nano, Humans, Nanotechnology, Sample preparation, Chromatography, High Pressure Liquid, Detection limit, Reproducibility, Chromatography, biology, Chemistry, Iron deficiency, Nano LC, 010401 analytical chemistry, Reproducibility of Results, Cell Biology, General Medicine, Middle Aged, 3. Good health, 0104 chemical sciences, 030104 developmental biology, Linear Models, biology.protein, Biomarker (medicine), Female
Abstract: International audience; Hepcidin-25 peptide is a biomarker which is known to have considerable clinical potential for diagnosing iron-related diseases. Developing analytical methods for the absolute quantification of hepcidin is still a real challenge, however, due to the sensitivity, specificity and reproducibility issues involved. In this study, we compare and discuss two MS-based assays for quantifying hepcidin, which differ only in terms of the type of liquid chromatography (nano LC/MS versus standard LC/MS) involved. The same sample preparation, the same internal standards and the same MS analyzer were used with both approaches. In the field of proteomics, nano LC chromatography is generally known to be more sensitive and less robust than standard LC methods. In this study, we established that the performances of the standard LC method are equivalent to those of our previously developed nano LC method. Although the analytical performances were very similar in both cases. The standard-flow platform therefore provides the more suitable alternative for accurately determining hepcidin in clinical settings.
Published: 2018

17. Le déficit en mévalonate kinase en 2016

Author: Guillaume Sarrabay, Isabelle Touitou, Sophie Georgin-Lavialle, Caroline Galeotti, Isabelle Koné-Paut, 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Bicêtre, and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: 030203 arthritis & rheumatology, Mevalonate kinase deficiency, Cerebellar ataxia, Psychomotor retardation, biology, business.industry, [SDV]Life Sciences [q-bio], Hyper-IgD syndrome, Gastroenterology, Mevalonate kinase, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Mevalonic aciduria, Immunology, Failure to thrive, Internal Medicine, medicine, biology.protein, 030212 general & internal medicine, medicine.symptom, business, Periodic fever syndrome, ComputingMilieux_MISCELLANEOUS
Abstract: Mevalonate kinase deficiency is a rare, autosomal recessive, auto-inflammatory disease. This results from mutations in the gene MVK coding for the enzyme mevalonate kinase. This enzyme is involved in cholesterol and isoprenoids synthesis. Depending partially of the residual activity of the mevalonate kinase, the clinical spectrum realizes a continuum which extends from the mild phenotype of the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to a lethal form of mevalonic aciduria. The HIDS is characterized by recurrent episodes of fever with an intense inflammatory syndrome, accompanied with lymphadenopathy, abdominal pain, diarrhea, arthralgia, hepatomegaly, splenomegaly and skin rash. The first attack more frequently takes place in the first year of life, even during the neonatal period, where it can be confused with a maternofetal infection. There is furthermore in mevalonate aciduria a psychomotor retardation, a failure to thrive, a cerebellar ataxia, a dysmorphic syndrome and a reduction of the visual acuity. The diagnosis is based on the mevalonic aciduria during febrile attack. Genetics confirm the diagnosis in more than 80 % of the cases. The dosage of IgD, low sensitive and specific, has no interest. There is no reference treatment. The less severe forms can be treated by non-steroidal anti-inflammatory drugs or steroids during febrile attacks. The most severe patients can be treated by biotherapy: antagonists of IL-1, TNF-α and IL-6.
Published: 2018

18. Recent Advances in Hepatotoxicity of Non Steroidal Anti-inflammatory Drugs

Author: Lucy Meunier, Dominique Larrey, 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aiello, Mélisande, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: hepatotoxicity, Variable severity, Pharmacogenomic Variants, Specialties of internal medicine, Drug-induced hepatitis, Bioinformatics, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Non-steroidal-anti-inflammatory drugs, Animals, Humans, Medicine, Genetic Predisposition to Disease, Acute liver injury, Hepatology, business.industry, Anti-Inflammatory Agents, Non-Steroidal, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Prognosis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, NSAID, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Phenotype, Liver, RC581-951, Non steroidal anti inflammatory, Pharmacogenetics, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030211 gastroenterology & hepatology, Chemical and Drug Induced Liver Injury, business
Abstract: International audience; Non-steroidal-anti-inflammatory drugs (NSAIDs) make a heterogenous pharmaco-therapeutic class of drugs among the most used drugs worldwide with various indications, modes of administration and increasing automedication. NSAIDs can cause acute liver injury with variable severity. The recent identification of genetic markers might facilitate the diagnosis and the prediction of hepatotoxicity risk.
Published: 2018

19. Towards a routine application of Top-Down approaches for label-free discovery workflows

Author: Gary Kruppa, Alain J. van Gool, Hans J. C. T. Wessels, Detlev Suckau, Rainer Paape, Pierre-Olivier Schmit, Jérôme Vialaret, Christophe Hirtz, Audrey Gabelle, Marshall Bern, Jason Wood, Sylvain Lehmann, Bruker Daltonique, Unité de Recherche Protéomique (PROTEOMIQUE), Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Radboud University Medical Center [Nijmegen], 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), Bruker, Bruker Daltonik GmbH, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Proteomics, 0301 basic medicine, Proteome, Clinical proteomics, Biophysics, Disease, Computational biology, Biology, Bioinformatics, Biochemistry, Mass Spectrometry, Statistical power, Workflow, Cohort Studies, 03 medical and health sciences, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Neurogranin, Biomarker discovery, Top-down label-free proteoform profiling, Ultra-high resolution Q-Tof, Proteins, Neurodegenerative Diseases, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], medicine.disease, 030104 developmental biology, Sample size determination, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Alzheimer disease, Alzheimer's disease, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Thanks to proteomics investigations, our vision of the role of different protein isoforms in the pathophysiology of diseases has largely evolved. The idea that protein biomarkers like tau, amyloid peptides, ApoE, cystatin, or neurogranin are represented in body fluids as single species is obviously over-simplified, as most proteins are present in different isoforms and subjected to numerous processing and post-translational modifications. Measuring the intact mass of proteins by MS has the advantage to provide information on the presence and relative amount of the different proteoforms. Such Top-Down approaches typically require a high degree of sample pre-fractionation to allow the MS system to deliver optimal performance in terms of dynamic range, mass accuracy and resolution. In clinical studies, however, the requirements for pre-analytical robustness and sample size large enough for statistical power restrict the routine use of a high degree of sample pre-fractionation. In this study, we have investigated the capacities of current-generation Ultra-High Resolution Q-Tof systems to deal with high complexity intact protein samples and have evaluated the approach on a cohort of patients suffering from neurodegenerative disease. Statistical analysis has shown that several proteoforms can be used to distinguish Alzheimer disease patients from patients suffering from other neurodegenerative disease.SIGNIFICANCE:Top-down approaches have an extremely high biological relevance, especially when it comes to biomarker discovery, but the necessary pre-fractionation constraints are not easily compatible with the robustness requirements and the size of clinical sample cohorts. We have demonstrated that intact protein profiling studies could be run on UHR-Q-ToF with limited pre-fractionation. The proteoforms that have been identified as candidate biomarkers in the-proof-of concept study are derived from proteins known to play a role in the pathophysiology process of Alzheimer disease.
Published: 2018

20. Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41–BEVANEC randomized phase II study

Author: Thomas Walter, Guillaume Cadiot, Alice Gangloff, Catherine Lombard-Bohas, Aurélie Ferru, Céline Lepère, Astrid Lièvre, Nadia Bouarioua, Vincent Hautefeuille, Jean-Yves Scoazec, Farid Elhajbi, Romain Coriat, Victoire Granger, C. Lepage, Olivier Dubreuil, Jean-Emmanuel Kurtz, Eric Assenat, Denis Smith, Laetitia Dahan, David Malka, Olivia Hentic, Guillaume Roquin, Karine Le Malicot, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pontchaillou [Rennes], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hépato-Gastro-Entérologie [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 Amiens-Picardie, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Michallon, Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université de Lille-UNICANCER, and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Leucovorin, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Drug Administration Schedule, Gastroenteropancreatic, FOLFIRI, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Intestinal Neoplasms, medicine, Humans, Etoposide, Hepatology, business.industry, Gastroenterology, medicine.disease, Survival Analysis, Carboplatin, Carcinoma, Neuroendocrine, 3. Good health, Pancreatic Neoplasms, Clinical trial, Neuroendocrine Tumors, Regimen, Treatment Outcome, 030104 developmental biology, chemistry, Research Design, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Camptothecin, Female, Fluorouracil, France, business, Progressive disease, medicine.drug
Abstract: IF 3.061; International audience; Introduction : Patients with gastroenteropancreatic (GEP), metastatic or locally advanced, non-resectable, grade 3 poorly-differentiated neuroendocrine carcinoma (NEC) are treated with cisplatin (or carboplatin)-etoposide in first-line palliative chemotherapy (CT1). However, nearly all patients will develop resistance and there is no standard second-line treatment.Aim :PRODIGE 41–BEVANEC is an academic randomized, phase II study designed to evaluate the efficacy of bevacizumab in combination with FOLFIRI after failure of CT1 in unknown primary NEC and GEP-NEC.Materials and methods : The main eligibility criteria are age ≥18 years, metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 3 GEP-NEC, and documented progressive disease during or after CT1 therapy.Results : A total of 124 patients will be randomly assigned (1:1) to receive either 5 mg/kg bevacizumab with FOLFIRI, or FOLFIRI alone, every 14 days until disease progression or unacceptable toxicity. The hypothesis is to demonstrate a 6-month overall survival for at least 50% of the patients in bevacizumab arm versus 35% in the control arm (FOLFIRI alone). Secondary endpoints are objective response, response duration, progression-free survival, toxicity, and biochemical response.Conclusion :The study is currently opened in France (NCT02820857). The first patient was randomized on September 6, 2017.
Published: 2018

21. B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation

Author: Marjolaine Willems, Olivier Prodhomme, Guillaume Captier, Thomas Guignard, Anne Boland, Kevin Yauy, Ikram Taleb Arrada, Vincent Meyer, Frédéric Tran Mau-Them, Jean-François Deleuze, Patricia Blanchet, Christian Herlin, Jean-Baptiste Rivière, Mouna Barat-Houari, Elodie Sanchez, Yannis Duffourd, Christine Coubes, David Geneviève, Marie-Pascale Le Gac, Jean-Michel Faure, Centre de Référence Anomalies du Développement et Syndromes Malformatifs (CHU de Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), 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), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Plastic and Craniofacial Pediatric Surgery, Hôpital Lapeyronie [Montpellier] (CHU), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Département d'imagerie pédiatrique (CHU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre pluridisciplinaire de diagnostic prénatal (CHU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre pluridisciplinaire de diagnostic prénatal (CHU de Nîmes), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Montpellier 1 - UFR de Médecine ( UM1 Médecine ), Université Montpellier 1 ( UM1 ), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Lapeyronie [Montpellier] ( CHU ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Département Pédiatrie [CHRU Montpellier], Pôle Femme Mère Enfant [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes)
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Antley-Bixler syndrome, Antley–Bixler syndrome, Connective tissue, Bone and Bones, Ultrasonography, Prenatal, Craniosynostosis, Diagnosis, Differential, Craniosynostoses, 03 medical and health sciences, B3GAT3, medicine, Humans, Genetic Predisposition to Disease, Joint Contracture, Glucuronosyltransferase, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Foot deformity, Genetic Association Studies, Genetics (clinical), Whole Genome Sequencing, Shprintzen-Goldberg syndrome, business.industry, Skull, Shprintzen–Goldberg syndrome, Sequence Analysis, DNA, Syndrome, medicine.disease, 3. Good health, Phenotype, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Mutation (genetic algorithm), business
Abstract: International audience; PurposeBased on prenatal suspicion of the combination of radioulnar or radiohumeral synostosis and a peculiar shape of the skull suggestive of craniosynostosis, we report on six patients from four unrelated consanguineous families in whom Antley-Bixler syndrome was suspected during the prenatal period without mutation in genes known to be associated with the syndrome.MethodsMolecular diagnosis involved whole-exome and gene-panel sequencing.Results:All sequenced patients showed a unique homozygous mutation of c.667G>A, p.Gly223Ser (NM_012200) in the beta-1,3-glucuronyltransferase 3 (B3GAT3) gene known to be involved in linkeropathy syndrome. Linkeropathies correspond to a recently identified group of heterogeneous genetic syndromes along a spectrum of skeletal and connective tissue disorders. These patients featured mainly craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformity, and cardiovascular abnormalities. All died before 1 year of age.ConclusionWe identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome.
Published: 2018

22. Meconial Methanobrevibacter smithii suggests intrauterine methanogen colonization in preterm neonates

Author: Anne Filleron, Pierre Corbeau, Cheick Oumar Guindo, Tu Anh Tran, Youssouf Sereme, Michel Drancourt, Ghiles Grine, Joana Vitte, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), Retiveau, Nolwenn, and Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID
Subjects: Meconium, Microbiology (medical), animal structures, Methanogens, medicine.drug_class, Antibiotics, Gut microbiota, QH426-470, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Gut flora, Microbiology, Neonate, fluids and secretions, Immunology and Microbiology (miscellaneous), Methanobrevibacter smithii, Preterm, Genetics, medicine, Colonization, Typing, biology, biology.organism_classification, Methanogen, QR1-502, Methanobrevibacter, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Infectious Diseases
Abstract: International audience; To understand the dynamics of methanogens in the human intestinal microbiota, we investigated the presence of methanogens in meconium using a polyphasic approach including microscopy and PCR-sequencing in 33 meconium samples collected from 33 pre-term neonates, in accordance with current ethics regulation. In the presence of negative controls, 90.9% samples were real-time PCR-positive for methanogens and 69.7 % were PCR-sequencing positive, identified as Methanobrevibacter (M.) smithii. Further, auto-fluorescent analysis detected methanogens in the two meconium samples analyzed, with a morphology suggesting M. smithii. Multispacer Sequence Typing found M. smithii genotypes ST1 and ST2, previously described as intestinal microbiota inhabitants. C-section delivery and non-use of peripartum antibiotics significantly correlated with PCR-detection of methanogens in meconium. These data position M. smithii among the early inhabitants of the human gut, detectable immediately after birth and suggest the contribution of methanogens to the perinatal development of intestinal microbiota and physiology.
Published: 2021

23. [Systemic Bacillus Calmette-Guerin sepsis manifesting as autoimmunity, 17 months after an intravesical BCG-therapy]

Author: T. Murez, Radjiv Goulabchand, Philippe Guilpain, Sophie Rivière, J. Broner, A. Le Quellec, S. Dufour, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Tuberculosis, BCG-thérapie, Autoimmunity, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Blood vessel prosthesis, medicine, Combined Modality Therapy, 030212 general & internal medicine, BCG-therapy, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, Mycobacterium bovis, CARCINOMA TRANSITIONAL CELL, biology, business.industry, Auto-immunité, medicine.disease, biology.organism_classification, 3. Good health, Infectious Diseases, Immunology, Tuberculoma, business, BCG vaccine
Abstract: International audience
Published: 2017

24. Direct-acting antiviral agent–based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study

Author: Jérôme Dumortier, A. Rohel, Jean-Charles Duclos-Vallée, Christophe Duvoux, Vincent Di Martino, Christine Silvain, Sébastien Dharancy, Danielle Botta-Fridlund, Sylvie Radenne, Maryline Debette-Gratien, Nassim Kamar, Audrey Coilly, Vincent Leroy, Georges-Philippe Pageaux, Armand Abergel, Louis d’Alteroche, Emilie Rossignol, Claire Francoz, Pauline Houssel-Debry, P. Perré, Filomena Conti, Claire Fougerou-Leurent, François Habersetzer, Camille Besch, Christophe Moreno, H. Montialoux, Valérie Canva, Albert Tran, Didier Samuel, Victor de Lédinghen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Paul Brousse, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), 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), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'hépatologie, Service d'hépatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Croix-Rousse [CHU - HCL], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chirurgie Digestive, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, ANRS France Recherche Nord & sud Sida-hiv hépatites, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-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)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Graft Rejection, Male, Sofosbuvir, [SDV]Life Sciences [q-bio], medicine.medical_treatment, kidney transplantation/nephrology, Hepacivirus, 030230 surgery, Liver transplantation, medicine.disease_cause, 0302 clinical medicine, Recurrence, Risk Factors, Immunology and Allergy, liver disease: infectious, Pharmacology (medical), Prospective Studies, Prospective cohort study, education.field_of_study, Graft Survival, Middle Aged, Prognosis, Hepatitis C, 3. Good health, [SDV] Life Sciences [q-bio], kidney failure/injury, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, infectious disease, Hepatitis C virus, Population, clinical research/practice, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Transplantation, business.industry, Kidney Transplantation, Liver Transplantation, Regimen, Immunology, infection and infectious agents - viral: hepatitis C, business, liver transplantation/hepatology, Follow-Up Studies
Abstract: International audience; Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.
Published: 2017

25. Establishment of a collection of human pluripotent stem cell lines (iPSC) from mesenchymal stem cells (MSC) from three healthy elderly donors

Author: Fabienne Becker, P. Pastoureau, Christian Jorgensen, Danièle Noël, Lydiane Pichard, Frédéric De Ceuninck, Jean-Marc Lemaitre, Romain Desprat, Jean-Marc Brondello, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherches SERVIER (IRS), and Retiveau, Nolwenn
Subjects: MESH: Cell Differentiation, Pluripotent Stem Cells, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, QH301-705.5, Cellular differentiation, Induced Pluripotent Stem Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Disease, MESH: Induced Pluripotent Stem Cells, Biology, MESH: Cellular Reprogramming, Cell Line, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Epigenetics, Biology (General), Induced pluripotent stem cell, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, MESH: Aged, MESH: Humans, Cartilage, Mesenchymal stem cell, Cell Differentiation, Mesenchymal Stem Cells, Cell Biology, General Medicine, Cellular Reprogramming, MESH: Cell Line, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, MESH: Mesenchymal Stem Cells, 030104 developmental biology, medicine.anatomical_structure, Cell culture, Cancer research, MESH: Pluripotent Stem Cells, Reprogramming, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; The study of molecular mechanism driving osteoarticular diseases like osteoarthritis or osteoporosis is impaired by the low accessibility to mesenchymal stem cells (MSC) from healthy donors (HD) for differential multi-omics analysis. Advances in cell reprogramming have, however, provided both a new source of human cells for laboratory research and a strategy to erase epigenetic marks involved in cell identity and the development of diseases. To unravel the pathological signatures on the MSC at the origin of cellular drifts during the formation of bone and cartilage, we previously developed iPSC from MSC of osteoarthritis donors. Here we present the derivation of three iPSCs from healthy age matched donors to model the disease and further identify (epi)genomic signatures of the pathology.
Published: 2021

26. Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process

Author: Philippe Robert, Yves Dauvilliers, Sylvain Lehmann, Audrey Gabelle, Isabelle Jaussent, Caroline Grasselli, Sophie Navucet, Christophe Hirtz, Jérôme Vialaret, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), 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), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioprojet-Biotech, Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, 0301 basic medicine, Amyloid, Aging, medicine.medical_specialty, Disease, 03 medical and health sciences, chemistry.chemical_compound, Orexin-A, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Nighttime sleep, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Wakefulness, Cognitive impairment, Aged, Aged, 80 and over, Orexins, Amyloid beta-Peptides, Methylhistamines, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, General Neuroscience, Middle Aged, Sleep in non-human animals, Peptide Fragments, 3. Good health, Orexin, 030104 developmental biology, Endocrinology, chemistry, Alzheimer, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Geriatrics and Gerontology, Sleep, Psychology, Biomarkers, 030217 neurology & neurosurgery, Histamine, Developmental Biology
Abstract: International audience; To better understand how sleep/wake dysregulation affects Alzheimer's disease (AD), we compared the cerebrospinal fluid (CSF) orexin and histamine/tele-methylhistamine (HA/t-MHA) levels of 82 patients (41 probable-AD-high level of evidence, 41 mild cognitive impairment MCI-due-to-AD), 24 other neurologic disorders (OND) and 24 controls. We determined the relationships between these biomarkers, the CSF AD biomarkers concentrations, and the clinical sleep profile. CSF orexin-A but not HA/t-MHA levels were higher in MCI and AD than OND and controls. CSF orexin-A is correlated to CSF amyloid-β42in MCI and AD, independently of age, gender, MMSE, total-tau/phosphorylated-tau, HA or sleep parameters. Nighttime sleep duration was longer in MCI and AD patients than controls. In MCI, nighttime sleep duration negatively correlated with CSF amyloid-β42 and MMSE. To conclude, CSF orexin-A but not HA/t-HMA was upregulated in AD and correlated with amyloid-β42 level. Our data suggested a change in the sleep-wake pattern at an early stage of the disease that needs further investigation to deeply explain the mechanistic interplay between sleep and Alzheimer.
Published: 2017

27. Association of TRAF1-C5 with risk of uveitis in juvenile idiopathic arthritis

Author: Randy Foliwe, Gautier Tejedor, Pierre Le Blay, Yves-Marie Pers, Isabelle Touitou, Michel Rodière, Catherine Ludwig, Christian Jorgensen, Cécile Rittore, Hôpital Lapeyronie [Montpellier] (CHU), 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), CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, musculoskeletal diseases, 0301 basic medicine, medicine.medical_specialty, Anti-nuclear antibody, [SDV]Life Sciences [q-bio], Arthritis, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, TNFAIP3, Uveitis, PTPN22, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, immune system diseases, Internal medicine, Genotype, medicine, Humans, Age of Onset, Child, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, Complement C5, Infant, medicine.disease, TNF Receptor-Associated Factor 1, Arthritis, Juvenile, 3. Good health, 030104 developmental biology, Child, Preschool, Cohort, Female, business
Abstract: Objectives Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. Methods SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. Results No associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P = 0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P Conclusion TRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.
Published: 2017

28. Sol–gel synthesis of collagen-inspired peptide hydrogel

Author: Léa Causse, Gilles Subra, Audrey Bethry, Guillaume Laconde, Jean Martinez, Pascal Verdié, Danièle Noël, Cécile Echalier, Said Jebors, Luc Brunel, Xavier Garric, Hélène Van Den Berghe, Ahmad Mehdi, Baptiste Legrand, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Laboratoire de Chimie Physique Macromoléculaire (LCPM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), 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), Mehdi, Ahmad, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Molécules Thérapeutiques in silico (MTI), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: chemistry.chemical_classification, [CHIM.MATE] Chemical Sciences/Material chemistry, Materials science, Mechanical Engineering, Sequence (biology), Nanotechnology, Peptide, [CHIM.MATE]Chemical Sciences/Material chemistry, 02 engineering and technology, Polymer, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, Buffer (optical fiber), 0104 chemical sciences, chemistry, Tissue engineering, Mechanics of Materials, Covalent bond, PEG ratio, Biophysics, Extracellular, General Materials Science, 0210 nano-technology
Abstract: International audience; Conceiving biomaterials able to mimic the specific environments of extracellular matrices are a prerequisite for tissue engineering applications. Numerous types of polymers (PEG, PLA, etc.) have been used for the design of biocompatible scaffolds, but they are still less efficient than natural biopolymers such as collagen extracts. Chemically modified and loaded with different bioactive factors, biopolymers afford an environment favourable to cell proliferation and differentiation. Unfortunately, they present several drawbacks, such as weak batch-to-batch reproducibility, potential immunogenicity and high cost of production. Herein we propose a fully synthetic covalent hydrogel obtained by sol-gel polymerisation of a silylated peptide. We selected a short and low molecular building-block derived from the consensus collagen sequence [Pro-Hyp-Gly]. Interestingly, the sol-gel process occurs in physiological buffer, enabling the embedment of stem cells. This collagen-inspired hydrogel provides a cell-friendly environment comparable to natural collagen substrates, demonstrating its potency as a biomimetic scaffold.
Published: 2017

29. How to favour efficient networking of teams working in the field of rare diseases? Experience of the CeRéMAI reference centre for auto-inflammatory diseases

Author: Florian Milhavet, Véronique Hentgen, Isabelle Koné-Paut, Isabelle Touitou, 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), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Bicêtre, and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre
Subjects: Male, 0301 basic medicine, Network, 03 medical and health sciences, Intranet, 0302 clinical medicine, Rheumatology, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Information Services, Patient Care Team, 030203 arthritis & rheumatology, Medical education, business.industry, Reference centre, Field (Bourdieu), Hereditary Autoinflammatory Diseases, Auto-inflammatory diseases, Rare diseases, 3. Good health, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Interdisciplinary Communication, France, business
Abstract: International audience
Published: 2017

30. CRISPR-Cas9: A revolution in genome editing in rheumatic diseases

Author: Carine Giovannangeli, Isabelle Duroux-Richard, Florence Apparailly, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Régulation et dynamique des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Biology, Sensitivity and Specificity, 03 medical and health sciences, Rheumatology, Genome editing, Rheumatic Diseases, Animals, Humans, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas, ComputingMilieux_MISCELLANEOUS, Gene Editing, Genetics, Genome, Rheumatism, Genetic Therapy, Genomics, 030104 developmental biology, Gene Targeting, RNA Editing, CRISPR-Cas Systems, Genetic Engineering
Abstract: International audience
Published: 2017

31. The transcriptomic analytical level determines the human monocyte-derived macrophage response toward either the infectious agent or the host

Author: Paul Chuchana, Philippe Nirdé, Frédéric Vezilier, Philippe Holzmuller, Contrôle des maladies animales exotiques et émergentes (UMR CMAEE), Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Recherche pour le Développement (IRD)-Université de Bordeaux (UB), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université de Bordeaux (UB), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Microbiology (medical), Modern medicine, approche transcriptomique, macrophage, Stimulus (physiology), Biology, L73 - Maladies des animaux, Microbiology, Transcriptome, 03 medical and health sciences, Immune system, Genetics, medicine, Humans, analyse par cluster, Molecular Biology, Gene, Pathogen, Cells, Cultured, Ecology, Evolution, Behavior and Systematics, Principal Component Analysis, Gene Expression Profiling, Macrophages, monocyte-derived macrophages, Monocyte, 3. Good health, Gene expression profiling, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, S50 - Santé humaine, Host-Pathogen Interactions, monocyte, Immunology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, pathogen, cluster analysis, agent pathogène
Abstract: Macrophages exhibit multifunctional activity and play a central role in the response to infectious agents. It is commonly accepted that the plasticity of the response of macrophages depends on the type of stimuli. Here we re-evaluate whether the macrophage response is only dependent on the stimulus. We analyzed the transcriptomic profile of monocyte-derived macrophages (MDMs) that were activated with several pathogens and multiple in vitro-stimulations. The transcriptomic data were normalized using matched-pair analysis. Further analysis showed a clustering association with (i) specific signatures of the infectious agent and its strategy as well as (ii) a preponderance of MDM overall responses related to individuals. Currently, the null hypothesis H0 is that the innate MDM response is globally associated with the pathogen. Our results reveal that the global innate MDM response is intrinsically and predominantly associated with the individual. Thus, the hypothesis is supported or negated depending on the transcriptomic analytical level. Author summary In modern medicine, diagnosis is based on objective criteria. Scientists are focused on the common denominators indicative of an infection. Analytical studies are based on this oriented approach, which defines the null hypothesis H0: the host immune response depends on the stimulus. We observe that the macrophage response to a given pathogen represents
Published: 2016

32. The impact of serotonergic system dysfunction on the regulation of P4501A isoforms during liver insufficiency and consequences for thyroid hormone homeostasis

Author: Martine Daujat-Chavanieu, Marta Kot, Polish Academy of Sciences (PAN), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 0301 basic medicine, Gene isoform, Serotonin, Alkylating Agents, Thyroid Hormones, medicine.medical_specialty, CYP1A isoforms, [SDV]Life Sciences [q-bio], CYP1B1, Toxicology, Serotonergic, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Cytochrome P-450 CYP1A2, Internal medicine, Cytochrome P-450 CYP1A1, medicine, Animals, Hepatic Insufficiency, Homeostasis, Diethylnitrosamine, Glucuronosyltransferase, Receptor, ComputingMilieux_MISCELLANEOUS, biology, AhR, Thyroid, Thyroid Hormone Receptors beta, General Medicine, Aryl hydrocarbon receptor, Thyroid hormones, Rats, Metabolism, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Liver, biology.protein, Thyroid Hormone Receptors alpha, Food Science, Hormone
Abstract: This study aimed to evaluate the impact of serotonergic system dysfunction on the regulation of cytochrome P4501A (CYP1A) during liver insufficiency. A rat model of liver insufficiency with a dysfunctional serotonergic system was developed. To induce liver insufficiency, animals were treated with nitrosodiethylamine (DEN) at 50 mg/kg of body weight twice a week for 7 weeks. To induce serotonergic system dysfunction, the animals were fed a tryptophan-free diet for 3 days. Serotonergic system dysfunction during liver insufficiency generated the aryl hydrocarbon receptor (AhR) activation and the “superinduction” of the AhR target genes: CYP1A1 , CYP1B1 and UGT1A , with a concomitant increase in CYP1A1 protein and activity. CYP1A2 gene expression was simultaneously down-regulated, with a concomitant decrease in CYP1A2 protein and activity. A significant reduction in TRβ receptor levels, together with a simultaneous increase of TRα receptor gene and protein level (mainly TRα2 isoform) after serotonergic system dysfunction, suggests that the serotoninergic system is involved in the regulation of CYP1A isoforms without influence from thyroid hormones during liver insufficiency. The interplay between the serotonergic system and the regulation of CYP1A isoforms, which are downstream targets of AhR activation, is dependent on hepatic function and can be observed without influence from thyroid hormones.
Published: 2016

33. 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

34. First and repeat liver resection for primary and recurrent intrahepatic cholangiocarcinoma

Author: Francis Navarro, Philippe Bachellier, Elie Oussoultzoglou, Jean Michel Fabre, Edoardo Rosso, Regis Souche, Pietro Addeo, Astrid Herrero, Service Médico-Chirurgical des Maladies de l'Appareil Digestif et de Transplantation Hépatique, CHU Saint-Eloi, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], 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), and Université de Montpellier (UM)
Subjects: Male, Survival, medicine.medical_treatment, Bile Duct Neoplasm, 030230 surgery, Gastroenterology, Cholangiocarcinoma, 0302 clinical medicine, Risk Factors, Recurrent Cholangiocarcinoma, Intrahepatic Cholangiocarcinoma, Intrahepatic cholangiocarcinoma, Aged, 80 and over, Risk factors for recurrence, Liver resection, Tumor size, Recurrent Intrahepatic Cholangiocarcinoma, General Medicine, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Recurrent cholangiocarcinoma, Median survival, Adult, Reoperation, medicine.medical_specialty, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Actuarial survival, Resection, 03 medical and health sciences, Internal medicine, medicine, Hepatectomy, Humans, Risk factor, Repeat hepatectomy, Survival analysis, Aged, Retrospective Studies, R0 resection, Hepatology, business.industry, Retrospective cohort study, Survival Analysis, Surgery, Bile Duct Neoplasms, Neoplasm Recurrence, Local, business
Abstract: International audience; BACKGROUND:Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC.METHODS:Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed.RESULTS:The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76).CONCLUSIONS:Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival.
Published: 2016

35. Hypercalcémie révélant une sarcoïdose chez un enfant

Author: M. Kinné, Tu-Anh Tran, R. Salet, S. Baron Joly, L. Saumet, A. Filleron, 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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: 030203 arthritis & rheumatology, Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, [SDV]Life Sciences [q-bio], 030225 pediatrics, Pediatrics, Perinatology and Child Health, Medicine, business, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Resume La sarcoidose est une granulomatose systemique d’origine indeterminee, dont le diagnostic repose sur une triade classique : un tableau clinique et radiologique evocateur, la mise en evidence de granulomes tuberculoides sans necrose caseeuse a l’histologie et l’elimination des autres granulomatoses, en particulier la tuberculose. Cette maladie est rare dans la population generale, notamment chez l’enfant chez lequel peu de cas avec hypercalcemie ont ete decrits. Nous rapportons le cas d’un enfant de 14 ans ayant presente une sarcoidose ganglionnaire et medullaire revelee par une alteration de l’etat general avec hypercalcemie. En l’absence d’orientation etiologique initiale et devant l’hypercalcemie severe (jusqu’a 3,28 mmol/L), l’adolescent a recu un traitement par hyperhydratation, diuretiques et biphosphonates ayant donne un bon resultat. La revue de litterature des cas similaires publies depuis 1990 a permis de colliger 23 cas (incluant le notre) dont nous avons compare les donnees cliniques, epidemiologiques, biologiques, iconographiques et histopathologiques. Les enfants presentant une sarcoidose associee a une hypercalcemie sont plus jeunes que ceux sans hypercalcemie. Les atteintes classiques, notamment pulmonaires, ganglionnaires et cutanees permettent d’orienter plus rapidement vers le diagnostic. La corticotherapie est proposee habituellement pour traiter la sarcoidose et notamment l’hypercalcemie. En conclusion, la sarcoidose de l’enfant reste difficile a diagnostiquer (delai diagnostique allant de 3 mois a plusieurs annees). Cela est du a sa faible incidence et au caractere non specifique des symptomes ; la classique triade n’est pas toujours presente. Une sarcoidose doit etre recherchee devant une hypercalcemie de cause indeterminee chez l’enfant.
Published: 2016

36. Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives

Author: Christian Jorgensen, Yves-Marie Pers, Danièle Noël, Maxime Ruiz, 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), Département de Rhumatologie[Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie
Subjects: Stromal cell, [SDV]Life Sciences [q-bio], Biomedical Engineering, Context (language use), Osteoarthritis, Mesenchymal Stem Cell Transplantation, Bioinformatics, Regenerative medicine, Rheumatic diseases, Rheumatology, Trophic factors, Humans, Medicine, Orthopedics and Sports Medicine, ComputingMilieux_MISCELLANEOUS, miRNA, Stem cell transplantation for articular cartilage repair, Inflammation, Tissue Engineering, business.industry, Regeneration (biology), Mesenchymal stem cell, medicine.disease, 3. Good health, Review article, Immunology, Mesenchymal stem cells, business
Abstract: SummaryOsteoarthritis (OA) is the most common form of degenerative arthritis, mainly characterized by the degradation of articular cartilage and associated with subchondral bone lesions. Novel therapeutic approaches for OA include cell-based therapies that have become thriving areas of research and development. In this context, mesenchymal stem or stromal cells (MSCs) have gained much interest based on their trophic and immunomodulatory properties that can help tissue repair/regeneration. The present review article discusses the interest of using MSCs in cell-therapy approaches with a focus on the mechanisms by which MSCs might exhibit a therapeutic potential in OA. Special attention is given to the anti-inflammatory function of MSCs and on miRNA modulation in OA for possible future innovative strategies. The paper also presents the current data on the undergoing MSCs-based clinical trials in OA.
Published: 2015

37. Lack of anti-inflammatory and anti-catabolic effects on basal inflamed osteoarthritic chondrocytes or synoviocytes by adipose stem cell-conditioned medium

Author: Christian Jorgensen, Elena Gabusi, Cristina Manferdini, Sandrine Fleury-Cappellesso, Danièle Noël, Francesca Paolella, Francesco Grassi, Marie Maumus, Gina Lisignoli, Istituto Ortopedico Rizzoli di Bologna, 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), EFS, This study was financially supported by the Seventh Framework Programme ADIPOA, Health-2009-1.4-3 project number 241719, European Project: 241719,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,ADIPOA(2010), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Cartilage, Articular, Male, endocrine system, medicine.medical_specialty, [SDV]Life Sciences [q-bio], animal diseases, Biomedical Engineering, Adipose tissue, CCL3, CCL2, 03 medical and health sciences, Chondrocytes, 0302 clinical medicine, Rheumatology, Internal medicine, Osteoarthritis, Adipocytes, medicine, Humans, Orthopedics and Sports Medicine, Interleukin 8, Conditioned-medium, Cells, Cultured, Aged, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, Metalloproteinase, Chemistry, Stem Cells, Synovial Membrane, hemic and immune systems, Osteoarthritis, Knee, Adipose stem cells, Synoviocytes, eye diseases, CXCL1, medicine.anatomical_structure, ADAMTS4, Endocrinology, Culture Media, Conditioned, Immunology, Female, Synovial membrane, tissues, Stem Cell Transplantation
Abstract: International audience; ObjectiveTo define whether good manufacturing practice (GMP)-clinical grade adipose stem cell (ASC)-derived conditioned medium (CM) is as effective as GMP-ASC in modulating inflammatory and catabolic factors released by both osteoarthritis (OA) chondrocytes or synoviocytes.MethodsOA chondrocytes and synoviocytes were treated with ASC-CM or co-cultured with ASC. Inflammatory factors (IL6, CXCL1/GROα,CXCL8/IL8, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES) and proteinases, such as metalloproteinase (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS4, ADAMTS5) and their tissue metalloproteinase inhibitors (TIMP1, TIMP3) were evaluated by qRT-PCR or immunoassays. The involvement of prostaglandin E2 (PGE2) was also analyzed.ResultsMost ASC-CM ratios tested did not decrease IL6, CCL2/MCP-1, CCL3/MIP1-α, CCL5/RANTES on basal inflamed chondrocytes or synoviocytes in contrast to what we found using ASC in co-culture. CXCL8/IL8 and CXCL1/GROα were not decreased by ASC-CM on synoviocytes but were only partially reduced on chondrocytes. Moreover, ASC-CM was less efficient both on basal inflamed OA chondrocytes and synoviocytes in reducing proteinases, such as MMP13, ADAMTS4, ADAMTS5 and increasing TIMP1 and TIMP3 compared to ASC in co-culture. The different ratios of ASC-CM contain lower amounts of PGE2 which were not sufficient to reduce inflammatory factors.ConclusionsThese data show that ASC-CM has a limited ability to decrease inflammatory and proteinases factors produced by OA chondrocytes or synoviocytes. ASC-CM is not sufficient to recapitulate the beneficial effect demonstrated using ASC in co-culture with inflamed OA chondrocytes and synoviocytes and shows that their use in clinical trials is fundamental to counteract OA progression.
Published: 2015

38. Functional heterogeneity in the pineal projection neurons of zebrafish

Author: Elise Cau, Patrick Blader, Clair Chaigne, Dora Sapède, CAU, Elise, 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), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de neurogénétique, Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR122, Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Melanopsin, endocrine system, Cell type, [SDV]Life Sciences [q-bio], Population, Notch signaling pathway, Pineal Gland, 03 medical and health sciences, Cellular and Molecular Neuroscience, Pineal gland, 0302 clinical medicine, Interneurons, medicine, Animals, Photoreceptor Cells, education, Projection (set theory), Molecular Biology, Zebrafish, ComputingMilieux_MISCELLANEOUS, Neurons, education.field_of_study, biology, Cell Biology, biology.organism_classification, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, nervous system, Neuroscience, 030217 neurology & neurosurgery, Function (biology), Signal Transduction
Abstract: The zebrafish pineal organ is a photoreceptive structure containing two main neuronal populations (photoreceptors and projections neurons). Here we describe a subpopulation of projection neurons that expresses the melanopsin gene, opn4xa. This new pineal cell type, that displays characteristics of both projection neurons and photoreceptors, share a similar dependency for BMP and Notch signalling pathways with classical non-photosensitive projection neurons (PN). Functionally, however, whereas classical, opn4xa-negative PNs display an achromatic LIGHT OFF response, the novel cell type we describe exhibit a LIGHT ON character that is elicited by green and blue light. Taken together, our data suggest a previously unanticipated heterogeneity in the projection neuron population in the zebrafish pineal organ raising the question of the importance of these differences in pineal function.
Published: 2020

39. Pediatric Miller Fisher Syndrome Complicating an Epstein–Barr Virus Infection

Author: Anne Filleron, Sandrine Baron-Joly, Céline Communal, Tu-Anh Tran, Randa Salet, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, 0301 basic medicine, Epstein-Barr Virus Infections, Ataxia, Adolescent, Mononucleosis, [SDV]Life Sciences [q-bio], medicine.disease_cause, behavioral disciplines and activities, Virus, Serology, 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, hemic and lymphatic diseases, medicine, Humans, Epstein–Barr virus infection, ComputingMilieux_MISCELLANEOUS, Miller Fisher Syndrome, Guillain-Barre syndrome, business.industry, Polyradiculoneuropathy, medicine.disease, Epstein–Barr virus, Virology, 3. Good health, 030104 developmental biology, Neurology, Pediatrics, Perinatology and Child Health, Immunology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background Miller Fisher syndrome, a variant of Guillain–Barre syndrome, is an acute inflammatory demyelinating polyradiculoneuropathy that may occur weeks after a bacterial or viral infection. Campylobacter jejuni and Haemophilus influenzae are frequently reported etiological agents. Patient Description We describe a boy with Miller Fisher syndrome following Epstein-002DBarr virus primary infectious mononucleosis. He presented with bilateral dysfunction of several cranial nerves and hyporeflexia of the limbs but without ataxia. Miller Fisher syndrome was confirmed by the presence of anti-GQ1b antibodies in a blood sample. Epstein–Barr virus was identified by polymerase chain reaction and serology. Conclusion Epstein-Barr virus should be considered as a Miller Fisher syndrome's causative agent. The physiopathology of this condition may involve cross-reactive T-cells against Epstein-Barr virus antigens and gangliosides.
Published: 2016

40. In Reply to ‘Benefit of Eculizumab Compared to Standard of Care Still Unproven in C3 Glomerulopathy’

Author: Fadi Fakhouri, Moglie Le Quintrec, Véronique Frémeaux-Bacchi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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 en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and Retiveau, Nolwenn
Subjects: medicine.medical_specialty, Standard of care, 030232 urology & nephrology, MEDLINE, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Glomerulopathy, medicine, MESH: Glomerulonephritis, Membranoproliferative, MESH: Standard of Care, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, MESH: Kidney Diseases, MESH: Humans, business.industry, Glomerulonephritis, Eculizumab, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Antibodies, Monoclonal, Humanized, Nephrology, Monoclonal, business, medicine.drug
Abstract: International audience
Published: 2018

41. Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Author: Laurence Chiche, Mustapha Adham, Jeanâ€Robert Delpero, Patrick Pessaux, Emmanuel Boleslawski, Daniel Azoulay, Denis Chatelain, Michel Scotté, Karim Boudjema, Alexis Laurent, Jean-Marc Regimbeau, Philippe Bachellier, Gérard Pascal, Jeanâ€Yves Mabrut, Momar Diouf, Olivier Farges, Gennaro Nuzzo, Christian Letoublon, Georges Mantion, Jeanâ€Francois Gigot, Yvesâ€Patrice Le Treut, Artigas Raventos, Francis Navarro, Michel Rivoire, Ahmet Ayav, David Fuks, CHU Amiens-Picardie, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Hôpital Claude Huriez [Lille], CHU Lille, Centre Léon Bérard [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Herrada, Anthony
Subjects: Male, Curative resection, Time Factors, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Kaplan-Meier Estimate, 030230 surgery, Cholangiocarcinoma, 0302 clinical medicine, Risk Factors, Odds Ratio, Registries, Young adult, Aged, 80 and over, Gastroenterology, Middle Aged, Tumor Burden, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Resection, Young Adult, 03 medical and health sciences, medicine, Hepatectomy, Humans, Aged, Retrospective Studies, Chi-Square Distribution, Hepatology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, Original Articles, Odds ratio, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Surgery, Bile Ducts, Intrahepatic, Logistic Models, Bile Duct Neoplasms, Tumour size, Multivariate Analysis, Lymph Node Excision, business, Chi-squared distribution
Abstract: International audience; INTRODUCTION:As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.METHODS:Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death 30 mm was independently associated with death
Published: 2015

42. Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis

Author: Yves-Marie Pers, Marie Godfrin-Valnet, Joseph Lambert, Roxane Schaub, Clémentine Fortunet, Daniel Wendling, Béatrice Pallot Prades, Elodie Constant, Waafa Bourichi, Philippe Gaudin, Christian Jorgensen, Hubert Marotte, Jean-Francis Maillefert, CHU Montpellier, 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), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, and Service de Rhumatologie (CHU de Dijon)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Humanized, Arthritis, Rheumatoid, Eular response, chemistry.chemical_compound, Tocilizumab, Rheumatology, Age groups, Internal medicine, Daily practice, medicine, Humans, Elderly patient, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, University hospital, 3. Good health, Treatment Outcome, chemistry, Antirheumatic Agents, Rheumatoid arthritis, Female, business
Abstract: To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice.We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test.Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P0.01) compared to the younger patient group (65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups.In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results.
Published: 2015

43. Response to Li and Zhang: Infevers, a human gene mutation database for autoinflammatory diseases including disseminated superficial actinic porokeratosis

Author: Isabella Touitou, Florian Milhavet, Laurence Cuisset, 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Zhàng, MEDLINE, Dermatology, Gene mutation, Disseminated superficial actinic porokeratosis, medicine.disease, Biochemistry, medicine, business, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2014

44. Daclatasvir Plus Peginterferon and Ribavirin Is Noninferior to Peginterferon and Ribavirin Alone, and Reduces the Duration of Treatment for HCV Genotype 2 or 3 Infection

Author: Scott Fung, Fiona McPhee, Stanislas Pol, Serena Zaltron, Alnoor Ramji, Victor de Ledinghen, David Cohen, Harvey A Tatum, Stephen D. Shafran, Dominique Larrey, Christophe Hézode, Gloria Taliani, E. Cooney, Peggy Hagens, Nina Weis, Albert Tran, Hugh Harley, Maurizia Rossana Brunetto, Stephanie Noviello, Samuel S. Lee, Gregory J. Dore, Wayne Ghesquiere, Eric Lawitz, Eric Hughes, Simone I. Strasser, Dennis Hernandez, Jacob George, Texas Liver Institute [San Antonio], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth)- The University of Texas Health Science Center at Houston (UTHealth), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Alberta, Centre Hospitalier Universitaire de Nice (CHU Nice), 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), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Pyrrolidines, Peginterferon-alfa, Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, chemistry.chemical_compound, Genotype, Combination Therapy, Imidazoles, virus diseases, Valine, Middle Aged, Recombinant Proteins, 3. Good health, NS5A Replication Complex Inhibitor, RNA, Viral, Drug Therapy, Combination, Female, medicine.drug, Adult, medicine.medical_specialty, Daclatasvir, Adolescent, Combination therapy, Hepatitis C virus, Alpha interferon, Placebo, Antiviral Agents, Double-Blind Method, Internal medicine, Ribavirin, medicine, Humans, Antiviral, Aged, DAA, Hepatology, business.industry, Interferon-alpha, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, digestive system diseases, chemistry, Immunology, Carbamates, business
Abstract: International audience; BACKGROUND & AIMS:Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in 70%-80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy.METHODS:Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24).RESULTS:Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above -20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy.CONCLUSIONS:Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.
Published: 2015

45. Lack of Efficacy of an Inhibitor of PDE4 in Phase 1 and 2 Trials of Patients With Nonalcoholic Steatohepatitis

Author: Christopher P. Day, Frederik Nevens, Dominique Larrey, Pierre Bedossa, Mihai Voiculescu, Lawrence Serfaty, Stephen D. Ryder, Gabriele I. Kirchner, Klaudia Traudtner, Jun Takeda, Liliana Preotescu, Guruprasad P. Aithal, Sven Francque, Victor de Lédinghen, Pavel Trunecka, Vlad Ratziu, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM, U773, Biomedical Research Center Bichat Beaujon, Université Paris Diderot - Paris 7 (UPD7), Antwerp University Hospital [Edegem] (UZA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Hospitals Leuven [Leuven], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Regensburg, Institute for Clinical and Experimental Medicine (IKEM), and Newcastle University [Newcastle]
Subjects: Male, Nonalcoholic steatohepatitis, Pharmacology, Gastroenterology, Placebos, MESH: Aged, 80 and over, Non-alcoholic Fatty Liver Disease, Clinical endpoint, Alanine aminotransferase, MESH: Treatment Outcome, media_common, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Alanine Transaminase, Middle Aged, Treatment Outcome, MESH: Young Adult, Female, Adult, Drug, medicine.medical_specialty, Adolescent, media_common.quotation_subject, MESH: Placebos, Cmax, Fatty Liver Disease, Placebo, MESH: Phosphodiesterase 4 Inhibitors, digestive system, Young Adult, MESH: Aspartate Aminotransferases, Internal medicine, medicine, Humans, Aspartate Aminotransferases, Adverse effect, Aged, MESH: Adolescent, MESH: Humans, Hepatology, MESH: Non-alcoholic Fatty Liver Disease, business.industry, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, digestive system diseases, Treatment, Clinical trial, MESH: Alanine Transaminase, Phosphodiesterase 4 Inhibitors, Human medicine, PDE4, business, MESH: Female, Therapeutic Targets
Abstract: International audience; Background & aims: ASP9831 is a phosphodiesterase-4 inhibitor developed to treat nonalcoholic steatohepatitis (NASH); it showed potent anti-inflammatory and antifibrotic effects in preclinical studies. We evaluated the efficacy and safety of ASP9831 in patients with NASH.Methods: In a phase 1 trial, we determined the optimal therapeutic window of ASP9831 in healthy volunteers and evaluated 2 doses (50 and 100 mg) in patients with NASH. Based on the positive outcomes of the phase 1 study, we performed a phase 2 trial to compare the biochemical effects of ASP9831 vs placebo. Patients with NASH were assigned randomly to groups given either 50 mg (n = 33) or 100 mg (n = 33) ASP9831 twice daily, or placebo (n = 30), for 12 weeks. The primary end point was the mean percentage change, from baseline to the end of ASP9831 administration, in serum level of alanine aminotransferase (ALT); secondary outcomes included changes in aspartate aminotransferase (AST) levels, ratio of AST:ALT, and various biomarkers of NASH.Results: After 12 weeks of administration, there was no significant change in mean serum levels of ALT (P = .42) or AST (P = .20) or other biomarkers in any group, and no significant differences were observed among groups. Most adverse events were mild; gastrointestinal disorders occurred more frequently in the ASP9831 groups than the placebo group.Conclusions: Despite a relevant mechanism of action, ASP9831 did not significantly alter the biochemical markers of NASH, compared with placebo, in a clinical trial. This highlights the difficulties of developing therapeutics for NASH and the need for more extensive preclinical testing of mechanisms of potential drug candidates. Clinicaltrialsregister.eu: 2005-001687-31; EudraCT numbers: 2007-002114-19.
Published: 2014

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