Author: "CHRU Tours" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"CHRU Tours"' showing total 1,811 results

Start Over Author "CHRU Tours" Topic humans

1,811 results on '"CHRU Tours"'

1. Inhibition of T-antigen expression promoting glycogen synthase kinase 3 impairs merkel cell carcinoma cell growth

Author: Thibault Kervarrec, Bhavishya Sarma, Eva-Maria Sarosi, Carolin Schulte, Christian Adam, Sonja Hesbacher, David Schrama, Roland Houben, Sabine Popp, Department of Dermatology, Venerology and Allergology, Universitätsklinikum Würzburg, Département de Pathologie [CHRU Tours], Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This research was funded by grants from the German Cancer Aid (70112438) and the German Research Foundation (HO5280/2-2)., Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Cancer Research, Skin Neoplasms, Pyridines, GSK3 knockout, Cell, Merkel cell polyomavirus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Targeted therapy, Glycogen Synthase Kinase 3, Mice, 03 medical and health sciences, 0302 clinical medicine, GSK-3, Cell Line, Tumor, medicine, Animals, Humans, GSK3 knockdown, Antigens, Viral, Tumor, GSK3A, GSK3B, Gene knockout, Cell Proliferation, 030304 developmental biology, 0303 health sciences, biology, Cell growth, Merkel cell carcinoma, Chemistry, food and beverages, medicine.disease, biology.organism_classification, 3. Good health, Carcinoma, Merkel Cell, Gene Expression Regulation, Neoplastic, Pyrimidines, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Polyomavirus
Abstract: International audience; Merkel cell carcinoma is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). Since proliferation of MCPyV-positive MCC tumor cells strictly depends on expression of the virus-encoded T antigens (TA), these proteins theoretically represent ideal targets for different kinds of therapeutic approaches. Here we developed a cell-based assay to identify compounds which specifically inhibit growth of MCC cells by repressing TA expression. Applying this technique we screened a kinase inhibitor library and identified six compounds targeting glycogen synthase kinase 3 (GSK3) such as CHIR99021 as suppressors of TA transcription in MCC cells. Involvement of GSK3 alpha and -beta in the regulation of TA-expression was confirmed by combining GSK3A knockout with inducible GSK3B shRNA knockdown since double knockouts could not be generated. Finally, we demonstrate that CHIR99021 exhibits in vivo antitumor activity in an MCC xenograft mouse model suggesting GSK3 inhibitors as potential therapeutics for the treatment of MCC in the future.
Published: 2022

2. Involvement of chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells

Author: Ingrid Langer, F. Guerif, Pascal Froment, Alice Bongrani, Claire Petit, Anthony Estienne, Namya Mellouk, Joëlle Dupont, Christelle Ramé, Ingrid Plotton, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Infertility, Embryology, medicine.medical_specialty, endocrine system diseases, [SDV]Life Sciences [q-bio], CMKLR1, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, In vivo, Internal medicine, medicine, Animals, Humans, Chemerin, Receptor, Progesterone, 030304 developmental biology, 0303 health sciences, Granulosa Cells, 030219 obstetrics & reproductive medicine, biology, business.industry, Obstetrics and Gynecology, Cell Biology, Progesterone secretion, medicine.disease, Follicular fluid, female genital diseases and pregnancy complications, In vitro, Follicular Fluid, Reproductive Medicine, biology.protein, Intercellular Signaling Peptides and Proteins, Female, Receptors, Chemokine, Chemokines, business, Polycystic Ovary Syndrome
Abstract: Polycystic ovarian syndrome (PCOS) is the main cause of infertility in women. It is frequently associated with reduced progesterone production by human luteinised granulosa cells (hlGCs). However, the molecular mechanisms involved in these steroidogenesis alterations in PCOS patients are unclear. In a dihydrotestosterone-induced PCOS mouse model, steroid production is maintained in the setting of chemokine-like receptor 1 (Cmklr1) knockout. Thus, chemerin and chemerin receptors in terms of expression and progesterone regulation could be different in control and PCOS hlGCs. We first confirmed that progesterone levels in both plasma (P < 0.0001) and follicular fluid (FF) (P < 0.0001) were significantly reduced in PCOS normal weight women compared to control women. These data were associated with a lower STAR mRNA expression in both in vivo (P < 0.0001) and in vitro (P < 0.0001) hlGCs from PCOS women. Secondly, chemerin FF levels (P < 0.0001) and RARRES2 (P < 0.05) and CMKLR1 (P < 0.0001) mRNA levels in GCs were higher in PCOS normal weight patients. Thirdly, treatment of hlGCs with a specific nanobody (the VHH CA4910) targeting the human receptor for CMKLR1 leading to its inactivation abolished chemerin-induced progesterone inhibition, suggesting the involvement of CMKLR1 in this process. Furthermore, the inhibition of progesterone secretion induced by chemerin was two-fold higher in PCOS hlGCs (P < 0.05). Moreover, the VHH CA4910 reinstated a normal progesterone secretion with lower concentrations in PCOS hlGCs, suggesting a different chemerin sensitivity between PCOS and control hlGCs. Thus, chemerin, through CMKLR1, could be involved in the steroidogenesis alterations in PCOS hlGCs.
Published: 2021

3. Disability in a medieval village community: A unique case of facial dysmorphism

Author: Hélène Coqueugniot, Elisabeth Zadora-Rio, Boris Laure, Estelle Herrscher, Samuel Bédécarrats, Valentin Miclon, Matthieu Gaultier, Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de l'archéologie du département d'Indre-et-Loire (SADIL), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), This work was funded by UMR CITERES 7324 – LAT., Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), École Pratique des Hautes Études (EPHE), Miclon, Valentin, Centre National de la Recherche Scientifique (CNRS)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Archeology, medicine.medical_specialty, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Paleopathology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Population, Disease, Deafness, Care, Pathology and Forensic Medicine, Social life, 03 medical and health sciences, Facial dysmorphism, Treacher-Collins syndrome, Isotopes, medicine, Humans, 0601 history and archaeology, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, 060101 anthropology, Bone collagen, Nitrogen Isotopes, Osteology, CT-scan, 06 humanities and the arts, Semiology, medicine.disease, Diet, [SHS.ANTHRO-BIO] Humanities and Social Sciences/Biological anthropology, Archaeology, [SHS.HIST] Humanities and Social Sciences/History, Female, [SHS.HIST]Humanities and Social Sciences/History, Psychology, Treacher Collins syndrome, Mandibulofacial Dysostosis, Clinical psychology
Abstract: International audience; Archaeological excavations carried out in the 1990s in the former rural parish of Rigny (Indre-et-Loire, France) uncovered 1738 graves. Among the individuals discovered, a female adult presents a series of cranial deformities characteristic of an extremely rare pathology, til then unknown in the archaeological record: the Treacher-Collins syndrome. It induces facial dysmorphism and is generally associated with hearing loss or even conductive deafness of the patient due to malformations of the hearing system.The retrospectif diagnosis of this individual was based on macroscopic analysis and computed tomography (CTscan). The use of 3D imaging made it possible to explore the impact of the pathology on the individual's hearing.In addition to the functional implications, the negative impacts of facial dysmorphic disorders in the social sphere are well known in today's societies while they are poorly documented for the medieval period.During this period, diet was an important social marker. The analysis of the individual affected by this syndrome’s diet, compared to those of other members of the Rigny village community, provide an opportunity to discuss the social significance of disability in a rural context in the Middle Ages. In this perspective, the isotopic ratios of carbon and nitrogen in this individual's bone collagen were compared to those of forty-seven other individuals found on the site.Archaeological, paleopathological and biochemical information are relevant to better characterize the functional repercussions of this syndrome on the Rigny individual and also to discuss the integration of this individual into this medieval village community.
Published: 2021

4. Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Author: Timothée Bruel, Karl Stéfic, Yann Nguyen, Donatella Toniutti, Isabelle Staropoli, Françoise Porrot, Florence Guivel-Benhassine, William-Henry Bolland, Delphine Planas, Jérôme Hadjadj, Lynda Handala, Cyril Planchais, Matthieu Prot, Etienne Simon-Lorière, Emmanuel André, Guy Baele, Lize Cuypers, Luc Mouthon, Hugo Mouquet, Julian Buchrieser, Aymeric Sève, Thierry Prazuck, Piet Maes, Benjamin Terrier, Laurent Hocqueloux, Olivier Schwartz, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Centre National de Référence du VIH [Tours] - laboratoire associé (CNR VIH), Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France / National Reference Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Régional d'Orléans (CHRO), Work in the O.S. lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and ANR Coronamito and IDISCOVR. Work in the UPBI facility is funded by grant ANR-10-INSB-04-01 and the Région Ȋle-de-France program DIM1Health. D.P. is supported by the Vaccine Research Institute. P.M. acknowledges the support of a COVID-19 research grant from 'Fonds Wetenschappelijk Onderzoek' /Research Foundation Flanders (grant G0H4420N) and 'Internal Funds KU Leuven' (grant 3M170314). E.S.-L. acknowledges funding from the INCEPTION program (Investissements d’Avenir grant ANR-16-CONV-0005)., We thank the European Health Emergency Preparedness and Response Authority (HERA) for supporting the work being done at Institut Pasteur and UK Leuven. We thank the patients who participated in this study. We thank members of the Virus and Immunity Unit for discussions and help. We thank Ludivine Grzelak for her help in creating an illustration of SARS-CoV-2 variant mutations. We thank N. Aulner and the UtechS Photonic BioImaging (UPBI) core facility (Institut Pasteur), a member of the France BioImaging network, for image acquisition and analysis. The Opera system was co-funded by Institut Pasteur and the Région Ȋle-de-France (DIM1Health). We thank F. Peira, V. Legros, and L. Courtellemont for their help with the cohorts. UZ Leuven, as a national reference center for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged. We thank Hélène Péré and David Veyer for their help in sequencing viral strains and helpful discussions., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), ANR-21-CO14-0007,CoronaMito,Conséquences de l'infection par le SRAS-CoV-2 sur la fonction mitochondriale(2021), and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
Subjects: Omicron, SARS-CoV-2, Antibody-Dependent Cell Cytotoxicity, antibodies, Humans, COVID-19, Antibodies, Monoclonal, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, neutralization, ADCC, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology
Abstract: The emergence of novel Omicron lineages, such as BA.5, may impact the therapeutic efficacy of anti-SARS-CoV-2 neutralizing monoclonal antibodies (mAbs). Here, we evaluated the neutralization and ADCC activity of 6 therapeutic mAbs against Delta, BA.2, BA.4 and BA.5 isolates. The Omicron sub-variants escaped most of the antibodies but remained sensitive to Bebtelovimab and Cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 displayed identical neutralization profiles. Sotrovimab was the most efficient at eliciting ADCC. We also analyzed 121 sera from 40 immunocompromised individuals up to 6 months after infusion of 1200 mg of Ronapreve (Imdevimab + Casirivimab), and 300 or 600 mg of Evusheld (Cilgavimab + Tixagevimab). Sera from Ronapreve-treated individuals did not neutralize Omicron subvariants. Evusheld-treated individuals neutralized BA.2 and BA.5, but titers were reduced by 41- and 130-fold, respectively, compared to Delta. A longitudinal evaluation of sera from Evusheld-treated patients revealed a slow decay of mAb levels and neutralization. The decline was more rapid against BA.5. Our data shed light on the antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.
Published: 2022

5. The endocytic recycling compartment serves as a viral factory for hepatitis E virus

Author: Cyrine Bentaleb, Kévin Hervouet, Claire Montpellier, Charline Camuzet, Martin Ferrié, Julien Burlaud-Gaillard, Stéphane Bressanelli, Karoline Metzger, Elisabeth Werkmeister, Maliki Ankavay, Nancy Leon Janampa, Julien Marlet, Julien Roux, Clarence Deffaud, Anne Goffard, Yves Rouillé, Jean Dubuisson, Philippe Roingeard, Cécile-Marie Aliouat-Denis, Laurence Cocquerel, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Morphogénèse et antigénicité du VIH et du virus des Hépatites [MAVIVH - U1259 Inserm - CHRU Tours ], Institut de Biologie Intégrative de la Cellule [I2BC], Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS], BIOTEM [Apprieu], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), 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), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institute of Microbiology [University of Lausanne] (IMUL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université de Tours, Plateformes Lilloises en Biologie et Santé - UMS 2014 - US 41 (PLBS), and This work has been funded by Inserm-Transfert (MAT-PI-17006), Pasteur Institute of Lille (DiagHepE), Region Hauts-de-France (DiagHepE), ANRS and the University of Tours.
Subjects: medicine.drug_class, viruses, Viral factories, [SDV]Life Sciences [q-bio], Endocytic recycling, RNA-dependent RNA polymerase, Infectious particles, Biology, medicine.disease_cause, Monoclonal antibody, Virus, Antibodies, Cellular and Molecular Neuroscience, 03 medical and health sciences, Hepatitis E virus, Viral factory, viral factories, medicine, Electron microscopy, Humans, AlphaFold2, Molecular Biology, 030304 developmental biology, Pharmacology, 0303 health sciences, 030306 microbiology, ORF2 capsid protein, Antibodies, Monoclonal, virus diseases, Biological Transport, Cell Biology, medicine.disease, Virology, digestive system diseases, 3. Good health, Endocytic recycling compartment, Rab11, Capsid, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Capsid Proteins, Viral hepatitis, Viral Replication Compartments
Abstract: Background & AimsAlthough Hepatitis E virus (HEV) is the major leading cause of enterically transmitted viral hepatitis worldwide, many gaps remain in the understanding of the HEV lifecycle. Notably, viral factories induced by HEV have not been documented yet and it is currently unknown whether HEV infection leads to cellular membrane modelling as many positive-strand RNA viruses. HEV genome encodes three proteins, the ORF1 replicase, the ORF2 capsid protein and the ORF3 protein involved in virion egress. Previously, we demonstrated that HEV produces different ORF2 isoforms including the virion-associated ORF2i form. Here, we aimed to probe infectious particles and viral factories in HEV-producing cells, using antibodies directed against the different ORF2 isoforms.MethodsWe generated monoclonal antibodies that specifically recognize the particle-associated ORF2i form, and antibodies that recognize the different ORF2 isoforms. We used them in confocal and electron microscopy approaches to probe viral factories in HEV-producing cells. We performed an extensive colocalization study of viral proteins with subcellular markers. We analyzed the impact of silencing Rab11, a central player of the endocytic recycling compartment (ERC).ResultsOne of the antibodies, named P1H1 and targeting the N-terminus of ORF2i, recognized delipidated HEV particles. Confocal and ultrastructural microscopy analyses of HEV-producing cells revealed an unprecedented HEV-induced membrane network containing tubular and vesicular structures. These subcellular structures were enriched in ORF2 and ORF3 proteins, and were dependent on the ORF3 expression and ORF2i capsid protein assembly. Colocalization and silencing analyses revealed that these structures are derived from the ERC.ConclusionsOur study reveals that HEV hijacks the ERC and forms a membrane network of vesicular and tubular structures that might be the hallmark of HEV infection.Lay summaryHepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide but many steps of its lifecycle are still elusive. Thanks to the development of new antibodies that recognize the different forms of the HEV capsid protein, we were able to visualize vesicular and tubular structures that were established by the virus in the host cell. In addition, extensive efforts to identify these structures led us to conclude that HEV hijacks the endocytic recycling compartment of the cell to form this network of vesicles and tubules, which might be the hallmark of HEV infection.
Published: 2022

6. Broadly neutralizing anti-HIV-1 antibodies tether viral particles at the surface of infected cells

Author: Jérémy Dufloo, Cyril Planchais, Stéphane Frémont, Valérie Lorin, Florence Guivel-Benhassine, Karl Stefic, Nicoletta Casartelli, Arnaud Echard, Philippe Roingeard, Hugo Mouquet, Olivier Schwartz, Timothée Bruel, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité [Paris] (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Institut Pasteur, Agence Nationale de la Recherche (France), Ministére de l'Education Nationale de la Recherche et de la Technologie (France), and Université de Tours
Subjects: MESH: Epitopes, T-Lymphocytes, Science, viruses, General Physics and Astronomy, HIV Infections, MESH: Host Microbial Interactions, HIV Antibodies, General Biochemistry, Genetics and Molecular Biology, Cell Line, MESH: Antibodies, Neutralizing, MESH: HIV-1, Epitopes, MESH: Antibody-Dependent Cell Cytotoxicity, Humans, MESH: Broadly Neutralizing Antibodies, Multidisciplinary, MESH: Humans, Host Microbial Interactions, MESH: HIV Antibodies, Antibody-Dependent Cell Cytotoxicity, Virion, env Gene Products, Human Immunodeficiency Virus, virus diseases, General Chemistry, MESH: HIV Infections, Antibodies, Neutralizing, MESH: Cell Line, MESH: T-Lymphocytes, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, MESH: Virion, MESH: env Gene Products, Human Immunodeficiency Virus, Broadly Neutralizing Antibodies
Abstract: Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells., O.S. is funded by Institut Pasteur, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), “TIMTAMDEN” ANR-14-CE14-0029, “CHIKV-Viro-Immuno” ANR-14-CE14-0015-01, and the Gilead HIV cure program. J.D. is funded by a Ph.D grant from the French Ministry of Higher Education and Research. H.M. is funded by the Institut Pasteur, the Milieu Intérieur Program (ANR-10-LABX-69-01), INSERM, ANRS, and Gilead HIV cure program. C.P. was supported by an ANRS fellowship. A.E. and S.F. are funded by Institut Pasteur, CNRS, and ANRS (ANRS-21020 AP2020-2). P.R. is funded by INSERM, Université de Tours and ANRS.
Published: 2022

7. Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

Author: Arnaud W, Thille, Arnaud, Gacouin, Rémi, Coudroy, Stephan, Ehrmann, Jean-Pierre, Quenot, Mai-Anh, Nay, Christophe, Guitton, Damien, Contou, Guylaine, Labro, Jean, Reignier, Gael, Pradel, Gaëtan, Beduneau, Laurence, Dangers, Clement, Saccheri, Gwénaël, Prat, Guillaume, Lacave, Nicholas, Sedillot, Nicolas, Terzi, Béatrice, La Combe, Jean-Paul, Mira, Antoine, Romen, Marie-Ange, Azais, Anahita, Rouzé, Jérôme, Devaquet, Agathe, Delbove, Martin, Dres, Jeremy, Bourenne, Alexandre, Lautrette, Joe, de Keizer, Stéphanie, Ragot, Jean-Pierre, Frat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Victor Dupouy, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Henri Mondor d'Aurillac, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Grenoble, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Groupe Hospitalier Bretagne Sud (GHBS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Pau, Centre Hospitalier Loire Vendée Océan, CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Supported by a grant (18-007) from the Programme Hospitalier de Recherche Clinique National 2018 of the French Ministry of Health., REVA Research Network: Anne Veinstein, Delphine Chatellier, Florence Boissier, Maeva Rodriguez, Céline Deletage, Céline Abonneau, Adel Maamar, Florian Reizine, Jean-Marc Tadie, Charlotte Salmon-Gandonniere, Emmanuelle Mercier, Stefan Mankikian, Pascal Andreu, Marine Jacquier, Marie Labruyère, Dalila Benzekri-Lefevre, Grégoire Muller, Armelle Mathonnet, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Gaëtan Plantefève, Paul Desaint, Radj Cally, Pierre Oudeville, Valentin Pointurier, Yannick Rabouel, Gauthier Blonz, Maité Agbakou, Thi My-Hue Nguyen, Marie-Hélène Hausermann, Christophe Girault, Dorothée Carpentier, Chloé Combe, Amélie Renou, Jean Dellamonica, Lucas Morand, Pierre Bailly, Christelle Teiten, Marine Paul, Hugo Bellut, Clio Torres, Camille Bouisse, Guillaume Rigault, Louis-Marie Galerneau, Pierre Bouju, Roland Smoning, Driss Laghlam, Morgane Bertrix, Alexandre Massri, Ugo Gouedard, Saad Nseir, Benjamin Zuber, Yannick Fedun, Côme Bureau, Julien Carvelli, Guillaume Gayraud, Quentin Levrat, Emmanuel Vivier, Christophe Leroy, Laurent Argaud, Alexandre Demoule, Gaetan Beduneau, Jean Dellamonica, Claude Guerin, Samir Jaber, Armand Mekontso-Dessap, Alain Mercat, Saad Nseir, Jean Roeseler, Matthieu Schmidt, Nicolas Terzi, Arnaud W Thille, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), and MORNET, Dominique
Subjects: Positive-Pressure Respiration, [SDV] Life Sciences [q-bio], Recurrence, Respiration, [SDV]Life Sciences [q-bio], Airway Extubation, Humans, General Medicine, Respiratory Insufficiency, Respiration, Artificial, Ventilator Weaning
Abstract: International audience; Background: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).
Published: 2022

8. Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial

Author: Diguisto, Caroline, Le Gouge, Amelie, Marchand, Marie-Sara, Megier, Pascal, Ville, Yves, Haddad, Georges, Winer, Norbert, Arthuis, Chloé, Doret, Muriel, Debarge, Veronique Houfflin, Flandrin, Anaig, Delmas, Hélène Laurichesse, Gallot, Denis, Mares, Pierre, Vayssiere, Christophe, Sentilhes, Loïc, Cheve, Marie-Therese, Paumier, Anne, Durin, Luc, Schaub, Bruno, Equy, Veronique, Giraudeau, Bruno, Perrotin, Franck, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maternité Olympe de Gouges [CHRU Tours], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aix-Marseille Université - École de maïeutique (AMU SMPM EM), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Le Mans (CH Le Mans), Polyclinique de l’Atlantique, Partenaires INRAE, Elsan Polyclinique du Parc - Caen, CHU de la Martinique [Fort de France], CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université de Tours (UT)
Subjects: Male, Uterine Artery, Pregnancy Trimester, First, Multidisciplinary, Pre-Eclampsia, Aspirin, Pregnancy, [SDV]Life Sciences [q-bio], Infant, Newborn, Humans, Birth Weight, Female
Abstract: Introduction This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia. Methods This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death. Results The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes. Conclusion Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia. Trial registration (NCT0172946).
Published: 2022

9. Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study

Author: Baptiste Le Calvez, Benoit Tessoullin, Loïc Renaud, Carmen Botella-Garcia, Micha Srour, Steven Le Gouill, Gaelle Guillerm, Rémy Gressin, Stéphanie Nguyen Quoc, Sabine Furst, Adrien Chauchet, David Sibon, Philippe Lewalle, Xavier Poiré, Natacha Maillard, Alban Villate, Michael Loschi, Jérôme Paillassa, Yves Beguin, Rémy Dulery, Jean-Jacques Tudesq, Amandine Fayard, Marie C. Béné, Vincent Camus, Patrice Chevallier, Amandine Le Bourgeois, Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Université de Lille, Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Cliniques universitaires St Luc [Bruxelles], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Laboratoire d'Hematologie [CHU Nantes], and Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Adult, Lymphoma, B-Cell, Oncology, Recurrence, [SDV]Life Sciences [q-bio], Remission Induction, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine, Retrospective Studies
Abstract: Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.
Published: 2022

10. Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors

Author: Jim Zoladek, Julien Burlaud-Gaillard, Maxime Chazal, Sophie Desgraupes, Patricia Jeannin, Antoine Gessain, Nathalie Pardigon, Mathieu Hubert, Philippe Roingeard, Nolwenn Jouvenet, Philippe V. Afonso, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Tours (UT), 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), Virologie (CNRS - UMR3569), Signalisation antivirale - Virus sensing and signaling, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity, This work was supported by a Pasteur-Fiocruz grant and the 'Investissement d’Avenir' as part of a 'Laboratoire d’Excellence' (LabEx) French research program: Integrative Biology of Emerging Infectious Diseases (ANR10-LBX-62 IBEID). Jim Zoladek and Sophie Desgraupes were the recipients of Ph.D. fellowships from the ED562-BioSPC and the French ministry of education and research., We thank Nicoletta Casartelli for her help on HIV-1-related experiments. We thank Florence Guivel-Benhassine for help with virus titration, Charlotte Calvet for help with sample preparation for scanning electron microscopy, Sylvie Van der Werf for the SARS-CoV-2 isolate used in this study, and Nicolas Escriou for the gift of a SARS-CoV-2 spike antibody. We thank Stéphane Roche for his biochemistry-related input and discussions on the project. We thank Pierre-Emmanuel Ceccaldi for his input and discussions on the project., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Afonso, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Virologie (CNRS-UMR3569), and Virus et Immunité - Virus and immunity (CNRS-UMR3569)
Subjects: Microbiology (medical), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Immunology and Microbiology, Ecology, Physiology, Zika Virus Infection, flavivirus, Cell Biology, Zika Virus, Antiviral Agents, Lipids, Membrane Fusion, antimicrobial peptides, Infectious Diseases, Zika, Claudin-1, Claudins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, claudin, Humans, Peptides
Abstract: International audience; Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from the N-terminal sequences of claudin-7 and claudin-1, named CL7.1 and CL1.1, respectively, that inhibited ZIKV infection in a panel of human cell lines. Using cell-to-cell fusion assays, we demonstrated that these peptides blocked the ZIKV E-mediated membrane fusion. A comparison of the antiviral efficacy of CL1.1 and CL7.1 pointed to the importance of the peptide amphipathicity. Electron microscopic analysis revealed that CL1.1 altered the ultrastructure of the viral particles likely by binding the virus lipid envelope. However, amphipathicity could not fully explain the antiviral activity of CL1.1. In silico docking simulations suggested that CL1.1 may also interact with the E protein, near its stem region. Overall, our data suggested that claudin-derived peptides inhibition may be linked to simultaneous interaction with the E protein and the viral lipid envelope. Finally, we found that CL1.1 also blocked infection by yellow fever and Japanese encephalitis viruses but not by HIV-1 or SARS-CoV-2. Our results provide a basis for the future development of therapeutics against a wide range of endemic and emerging flaviviruses. IMPORTANCE Zika virus (ZIKV) is a flavivirus transmitted by mosquito bites that have spread to the Pacific Islands and the Americas over the past decade. The infection remains asymptomatic in most cases but can cause severe neurological disorders. ZIKV is a major public health threat in areas of endemicity, and there is currently no specific antiviral drug or vaccine available. We identified two antiviral peptides deriving from the N-terminal sequences of claudin-7 and claudin-1 with the latter being the most effective. These peptides block the envelope-mediated membrane fusion. Our data suggested that the inhibition was likely achieved by simultaneously interacting with the viral lipid envelope and the E protein. The peptides also inhibited other flaviviruses. These results could provide the basis for the development of therapies that might target a wide array of flaviviruses from current epidemics and possibly future emergences.
Published: 2022

11. Metabolically healthy obesity and cardiovascular events: A nationwide cohort study

Author: Alexandre Bodin, Gregory Y.H. Lip, Julien Herbert, Pierre Henri Ducluzeau, Carl Semaan, Grégoire Fauchier, Denis Angoulvant, Arnaud Bisson, Laurent Fauchier, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Aalborg University [Denmark] (AAU), University of Liverpool, and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, obesity, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Population, heart failure, 030204 cardiovascular system & hematology, Lower risk, Brain Ischemia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, Metabolically healthy obesity, Internal Medicine, medicine, Humans, atrial fibrillation, Obesity, 030212 general & internal medicine, Myocardial infarction, education, Obesity, Metabolically Benign, ischaemic stroke, education.field_of_study, diabetes, business.industry, Hazard ratio, medicine.disease, 3. Good health, Stroke, myocardial infarction, Female, business, Cohort study
Abstract: Aims Whether obesity is associated with a higher risk of cardiovascular events in the absence of metabolic risk factors is a matter of debate. We evaluated the associations among metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. Methods All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (myocardial infarction, heart failure [HF], ischemic stroke or cardiovascular death, MACE-HF) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and 3 metabolic abnormalities (diabetes mellitus, hypertension, and hyperlipidemia). Hazard ratios for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. Results In total, 2,873,039 individuals were included in the analysis, among whom 272,838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95%CI 1.31-1.37), and AF (HR 1.33, 95%CI 1.30-1.37) compared with individuals with no obesity and 0 metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95%CI 0.87-0.98), ischemic stroke (HR 0.93, 95%CI 0.88-0.98) and cardiovascular death (HR 0.99, 95%CI 0.93-1.04). MHO in men was associated with higher risk of clinical events compared to MH men with normal weight (HR 1.12 to 1.80) while women with MHO had lower risk for most events than MH women with normal weight (HR 0.49 to 0.99). Conclusions In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast they had a higher risk of new-onset HF and new onset AF. Notable differences were however observed in men and women in the sex-stratified analysis. This article is protected by copyright. All rights reserved.
Published: 2021

12. Hypertension in kidney transplantation: a consensus statement of the 'hypertension and the kidney' working group of the European Society of Hypertension

Author: Alexandre Persu, Davide Bolignano, Michel Burnier, Charles J. Ferro, Gérard M. London, Jean-Michel Halimi, Pantelis Sarafidis, Anna Pisano, Alberto Ortiz, Francesca Mallamaci, Nada Kanaan, John Boletis, Patrick Rossignol, Liffert Vogt, Bénédicte Sautenet, Carmine Zoccali, Grégoire Wuerzner, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Universidad Autónoma de Madrid (UAM), Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital, Azienda Ospedaliera Ospedali Civili Riuniti, Lausanne University Hospital, Institute of Clinical Physiology, CNR, Centre Hospitalier Manhès [Fleury-Mérogis], Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University Hospitals Birmingham [Birmingham, Royaume-Uni], Laiko General Hospital, University of Athens School of Medicine, National and Kapodistrian University of Athens (NKUA), Amsterdam UMC - Amsterdam University Medical Center, Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), AO research is supported by FIS/Fondos FEDER (PI17/00257, PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. LV is supported by Senior Kolff grant (18OKG12) of the Dutch Kidney Foundation.This work was planned as part of the activities of the « Kidney and Hypertension » working group of the European Society of Hypertension (ESH)., European Project: PI17/00257, European Project, BOZEC, Erwan, FEDER PI17/00257 - PI17/00257 - INCOMING, ISCIII-RETIC REDinREN RD016/0009 - INCOMING, FEDER PI18/01386 - INCOMING, FEDER PI19/00588 - INCOMING, FEDER PI19/00815 - INCOMING, FEDER DTS18/00032 - INCOMING, KIDNEY ATTACK AC18/00064 - INCOMING, PERSTIGAN AC18/00071 - INCOMING, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de pathologie cardiovasculaire, UCL - (SLuc) Service de néphrologie, Nephrology, ACS - Microcirculation, and APH - Health Behaviors & Chronic Diseases
Subjects: medicine.medical_specialty, Consensus, Ambulatory blood pressure, Physiology, Population, Kidney, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Internal Medicine, medicine, Humans, education, Antihypertensive Agents, Kidney transplantation, education.field_of_study, business.industry, medicine.disease, Kidney Transplantation, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Transplantation, Masked Hypertension, medicine.anatomical_structure, Blood pressure, surgical procedures, operative, Hypertension, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract: International audience; Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.
Published: 2021

13. Heparin‐induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation

Author: Bernard Tardy, François Mullier, Anne Bauters, Thomas Lecompte, B. Tardy-Poncet, Dominique Lasne, Ismail Elalamy, Claire Pouplard, Anne Serre-Sapin, Emilie Presles, Lelia Grunebaum, Pierre-Emmanuel Morange, Martine Alhenc-Gelas, Grégoire Le Gal, Emmanuel de Maistre, Marie-Hélène Horellou, Philippe Nguyen, Christine Mouton, Yves Gruel, Julien Perrin, Andreas Greinacher, Agnès Lillo-Le Louët, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Unité de Pharmacologie Clinique (Pharmaco Clin - SAINT ETIENNE), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Necker - Enfants Malades [AP-HP], 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), Laboratoire d'hématologie, CHU Bordeaux [Bordeaux], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Université d'Ottawa [Ontario] (uOttawa), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Strasbourg, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [Tours], Greifswald University Hospital, Geneva University Hospitals and Geneva University, 'Programme Hospitalier de Recherche Clinique' (French Ministry of Health), UCL - (MGD) Laboratoire de biologie clinique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, thrombocytopenia, heparin, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Internal medicine, Heparin-induced thrombocytopenia, Cardiopulmonary bypass, medicine, Humans, Prospective Studies, Derivation, Receiver operating characteristic, Platelet Count, business.industry, Anticoagulants, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Heparin, pre-test score, medicine.disease, 3. Good health, Cardiac surgery, Pre- and post-test probability, observational study, Observational study, heparin-induced thrombocytopenia, business, medicine.drug
Abstract: International audience; Background Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays.Objective To develop a pretest score for HIT.Design Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839).Setting Thirty-one tertiary hospitals in France, Switzerland, and Belgium.Patients Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts.Measurements Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results.Results Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); >= 40% decrease in platelet count over
Published: 2021

14. Safety and efficacy of the Silk flow diverter: Insight from the DIVERSION prospective cohort study

Author: Florent Gariel, Gaultier Marnat, Xavier Barreau, Patrice Menegon, Romain Bourcier, Laurent Pierot, Lauren Spelle, Alain Bonafé, Francis Turjman, Benjamin Gory, Jérôme Berge, Vincent Costalat, Gregory Gascou, Cyril Dargazanli, Sébastien Soize, Georges Metaxas, Jacques Moret, Léon Ikka, Jildaz Caroff, Aymeric Rouchaud, Christian Mihaela, Nidal Benachour, Michel Piotin, Raphaël Blanc, Hocine Redjem, Elisa Pomero, Alessandra Biondi, Christophe Cognard, Anne-Christine Januel, Jean Darcourt, Adrien Guenego, Philippe Tall, Fabrice Bonneville, Charbel Mounayer, Suzana Saleme, Nader Sourour, Frédéric Clarençon, Charlotte Barbier, Denis Herbreteau, Ana-Paula Narata, Richard Bibi, Serge Bracard, René Anxionnat, Anne-Laure Derelle, Romain Tonnelet, Liang Liao, Emmanuel Chabert, Hervé Brunel, Frederic Ricolfi, Hubert Desal, Zsolt Kulcsar, Christian Taschner, Département de Neuro-Radiologie [Bordeaux] (DNR - Bordeaux), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Limoges, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Départment de Neuroradiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de neuroradiologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Service de neuroradiologie diagnostique et interventionnelle, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University hospital of Zurich [Zurich], University Hospital Freiburg, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and DIVERSION investigators: Vincent Costalat , Gregory Gascou , Cyril Dargazanli, Sébastien Soize, Georges Metaxas, Jacques Moret , Léon Ikka, Jildaz Caroff, Aymeric Rouchaud, Christian Mihaela, Nidal Benachour, Michel Piotin, Raphaël Blanc, Hocine Redjem, Elisa Pomero , Alessandra Biondi, Christophe Cognard, Anne-Christine Januel, Jean Darcourt, Adrien Guenego, Philippe Tall, Fabrice Bonneville , Charbel Mounayer , Suzana Saleme, Nader Sourour, Frédéric Clarençon, Charlotte Barbier, Denis Herbreteau, Ana-Paula Narata, Richard Bibi , Serge Bracard , René Anxionnat , Anne-Laure Derelle, Romain Tonnelet, Liang Liao , Emmanuel Chabert , Hervé Brunel, Frederic Ricolfi, Hubert Desal, Zsolt Kulcsar, Christian Taschner
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Silk, Subgroup analysis, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Aneurysm, Occlusion, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Endovascular treatment, Radiology, Nuclear Medicine and imaging, Prospective Studies, Prospective cohort study, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Flow diverter, Radiological and Ultrasound Technology, business.industry, Endovascular Procedures, Flow diversion, Stent, Intracranial Aneurysm, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Surgery, Treatment Outcome, Stents, Neurology (clinical), Intracranial aneurysms, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background and purpose Flow diverters are considered as an essential tool in the stent-based treatment of complex intracranial aneurysms. We report here a subgroup analysis of the nationwide prospective DIVERSION study to investigate the safety and efficacy of the Silk flow diverter at 12 months follow-up. Methods We performed a subgroup analysis of patients included in the DIVERSION, a national prospective cohort study including all flow diverters placement between 2012 and 2014 in France, and treated with the Silk. The primary outcome was the morbi-mortality at 12 months, including death, morbidity event and aneurysm retreatment within 12 months post-treatment. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran's scale by an independent imaging core laboratory during follow-up. Results A total of 102 procedures involving 101 patients (mean age ± standard deviation, 54.3 ± 13.5 years) harbouring 118 aneurysms (113/118 located in the anterior circulation; mean size 8.2 ± 7.1 mm) were included. During the 12-month follow-up, 34 (33.3%) procedures experienced at least one morbi-mortality event: 3 deaths, 27 morbidity events and 4 retreatments. Overall, 1/3 deaths and 10/27 morbidity events were related to the device and/or the procedure, leading to a specific survival rate and a specific free-morbidity survival rate at 12 months of 98.98% [95% confidence interval, 92.98%–99.86%] and 89.73% [95%CI, 81.71%–94.36%], respectively. The rate of permanent-related neurological deficit was 5.9% within 12 months. One year follow-up imaging showed satisfactory occlusion in 82.2% of cases. Conclusion Flow diversion with the Silk device has a reasonable safety and effectiveness profile for the endovascular treatment of intracranial aneurysms.
Published: 2021

15. Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER)

Author: Jean-Yves Blay, Virgine Westeel, Khê Hoang-Xuan, Philippe Gorphe, Thomas Aparicio, Thierry Lecomte, David Tougeron, Astrid Lièvre, Pierre Michel, Sébastien Gaujoux, Amélie Servettaz, Pascale Mariani, Maxime Hentzien, Michel Ducreux, Léon Maggiori, Firouzé Bani-Sadr, Laura Mansi, Jean Bourhis, Olivier Bouché, Boris Guiu, Christophe Louvet, Florence Huguet, Barbara Seitz-Polski, Juliette Thariat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cooperator Multidisciplinary Oncology Group (GERCOR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Curie [Paris], 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), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Léon Bérard [Lyon], None, University Hospital of Montpellier, Institut Universitaire de Cancérologie [Paris] (IUC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Jonchère, Laurent, CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Cancer Research, Pediatrics, medicine.medical_specialty, COVID-19 Vaccines, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, medicine.disease_cause, Current Perspective, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Pandemic, medicine, Humans, Chemotherapy, education, Coronavirus, education.field_of_study, Radiotherapy, SARS-CoV-2, business.industry, Vaccination, COVID-19, Cancer, medicine.disease, 3. Good health, Radiation therapy, Solid cancers, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business
Abstract: International audience; The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.
Published: 2021

16. Genotypic and Phenotypic Diversity of the Replication-Competent HIV Reservoir in Treated Patients

Author: Alexandre Nicolas, Julie Migraine, Jacques Dutrieux, Maud Salmona, Alexandra Tauzin, Atsuko Hachiya, Jérôme Estaquier, Jean-Michel Molina, François Clavel, Allan J. Hance, Fabrizio Mammano, Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National Hospital Organization Nagoya Medical Center [Nagoya, Japan] (NHONMC), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), 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), and Mammano, Fabrizio
Subjects: CD4-Positive T-Lymphocytes, Microbiology (medical), reservoir, human immunodeficiency virus, treatment, General Immunology and Microbiology, Ecology, Physiology, genotypic diversity, [SDV]Life Sciences [q-bio], HIV Infections, Genome, Viral, Cell Biology, Viral Load, Virus Latency, [SDV] Life Sciences [q-bio], Infectious Diseases, Anti-Retroviral Agents, Proviruses, HIV-1, Genetics, Humans, Viremia, genotypic identification
Abstract: International audience; In HIV infection, viral rebound after treatment discontinuation is considered to originate predominantly from viral genomes integrated in resting CD4+ T lymphocytes. Replication-competent proviral genomes represent a minority of the total HIV DNA. While the quantification of the HIV reservoir has been extensively studied, the diversity of genomes that compose the reservoir was less explored. Here, we measured the genotypic and phenotypic diversity in eight patients with different treatment histories. Between 4 and 14 (mean, 8) individual viral isolates per patient were obtained using a virus outgrowth assay, and their near-full-length genomes were sequenced. The mean pairwise distance (MPD) observed in different patients correlated with the time before undetectable viremia was achieved (r = 0.864, P = 0.0194), suggesting that the complexity of the replication-competent reservoir mirrors that present at treatment initiation. No correlation was instead observed between MPD and the duration of successful treatment (mean, 8 years; range, 2 to 21 years). For 5 of the 8 patients, genotypically identical viral isolates were observed in independent wells, suggesting clonal expansion of infected cells. Identical viruses represented between 25 and 60% of the isolates (mean, 48%). The proportion of identical viral isolates correlated with the duration of treatment (r = 0.822, P = 0.0190), suggesting progressive clonal expansion of infected cells during ART. A broader range of infectivity was also observed among isolates from patients with delayed viremia control (r = 0.79, P = 0.025). This work unveiled differences in the genotypic and phenotypic features of the replication-competent reservoir from treated patients and suggests that delaying treatment results in increased diversity of the reservoir. IMPORTANCE In HIV-infected and effectively treated individuals, integrated proviral genomes may persist for decades. The vast majority of the genomes, however, are defective, and only the replication-competent fraction represents a threat of viral reemergence. The quantification of the reservoir has been thoroughly explored, while the diversity of the genomes has been insufficiently studied. Its characterization, however, is relevant for the design of strategies aiming the reduction of the reservoir. Here, we explored the replication-competent near-full-length HIV genomes of eight patients who experienced differences in the delay before viremia control and in treatment duration. We found that delayed effective treatment was associated with increased genetic diversity of the reservoir. The duration of treatment did not impact the diversity but was associated with higher frequency of clonally expanded sequences. Thus, early treatment initiation has the double advantage of reducing both the size and the diversity of the reservoir.
Published: 2022

17. Rapid SARS-CoV-2 inactivation by mercury and LED UV-C lamps on different surfaces

Author: Marianne Maquart, Julien Marlet, 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Marlet, Julien
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, irradiation, SARS-CoV-2, LED, COVID-19, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Mercury, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, mercury lamp, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, UV-C, inactivation, Physical and Theoretical Chemistry
Abstract: International audience; SARS-CoV-2 remains infectious for several hours on surfaces. It can be inactivated by UV-C irradiation but optimal conditions for rapid inactivation, especially on non-plastic surfaces remains unclear. A SARS-CoV-2 inoculum was irradiated with a UV-C LED (265 nm) or a UV-C mercury lamp (254 nm). Infectivity titers (TCID50/mL) and inactivation rates were then quantified on plastic, steel, tissue, paper and cardboard surfaces. We demonstrated that efficient SARS-CoV-2 inactivation (> 99.999% on plastic and steel, ≥ 99.8% on tissue, paper and cardboard) can be achieved by both a UV-C mercury lamp and a UV-C LED after 30 s of irradiations at 3 cm, corresponding to UV-C doses of 92.85 and 44.7 mJ/cm2, respectively. Inactivation on a plastic surface was more efficient with the mercury UV-C lamp (p < 0.005). The mercury UV-C lamp could be more relevant than the LED in high-risk settings, such as medical care or research laboratories.
Published: 2022

18. Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients

Author: Sonia André, Marne Azarias da Silva, Morgane Picard, Aurélie Alleaume-Buteau, Lucy Kundura, Renaud Cezar, Calaiselvy Soudaramourty, Santa Cruz André, Ana Mendes-Frias, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, António Gil Castro, Paul Loubet, Albert Sotto, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Géraud Claret, Sandra Duvnjak, Tu-Anh Tran, Ouafa Zghidi-Abouzid, Pierre Nioche, Ricardo Silvestre, Pierre Corbeau, Fabrizio Mammano, Jérôme Estaquier, 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), Biomedtech Facilities (UMS 2009 / US36), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universidade do Minho = University of Minho [Braga], ICVS/3B's—PT Government Associate Laboratory [Braga, Portugal], Hospital Escala Braga [Braga, Portugal], CHU de Québec–Université Laval, Université Laval [Québec] (ULaval), Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), and Mammano, Fabrizio
Subjects: CD4-Positive T-Lymphocytes, Cancer Research, SARS-CoV-2, [SDV]Life Sciences [q-bio], Immunology, COVID-19, Apoptosis, Cell Biology, Antibodies, Viral, Immunity, Humoral, [SDV] Life Sciences [q-bio], Cellular and Molecular Neuroscience, Immunoglobulin G, Spike Glycoprotein, Coronavirus, Humans
Abstract: In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that the propensity of CD4 T cells to die may impact the quantity and quality of the humoral response in acutely infected individuals. In addition to specific immunoglobulins (Ig)A, IgM, and IgG against SARS-CoV-2 nucleocapsid (N), membrane (M), and spike (S1) proteins, we assessed the quality of IgG response by measuring the avidity index. Because the S protein represents the main target for neutralization and antibody-dependent cellular cytotoxicity responses, we also analyzed anti-S-specific IgG using S-transfected cells (S-Flow). Our results demonstrated that most COVID-19 patients have a predominant IgA anti-N humoral response during the early phase of infection. This specific humoral response preceded the anti-S1 in time and magnitude. The avidity index of anti-S1 IgG was low in acutely infected individuals compared to convalescent patients. We showed that the percentage of apoptotic CD4 T cells is inversely correlated with the levels of specific IgG antibodies. These lower levels were also correlated positively with plasma levels of CXCL10, a marker of disease severity, and soluble Fas ligand that contributes to T-cell death. Finally, we found lower S-Flow responses in patients with higher CD4 T-cell apoptosis. Altogether, these results demonstrate that individuals with high levels of CD4 T-cell apoptosis and CXCL10 have a poor ability to build an efficient anti-S response. Consequently, preventing CD4 T-cell death might be a strategy for improving humoral response during the acute phase, thereby reducing COVID-19 pathogenicity.
Published: 2022

19. Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells

Author: Sophie-Marie Aicher, Felix Streicher, Maxime Chazal, Delphine Planas, Dongsheng Luo, Julian Buchrieser, Monika Nemcova, Veronika Seidlova, Jan Zukal, Jordi Serra-Cobo, Dominique Pontier, Bertrand Pain, Gert Zimmer, Olivier Schwartz, Philippe Roingeard, Jiri Pikula, Laurent Dacheux, Nolwenn Jouvenet, Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité - Virus and immunity, Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris]-Université Paris Cité (UPCité), University of Veterinary and Pharmaceutical Sciences [Brno] (VFU), Universitat de Barcelona (UB), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Bern, Institute of Virology and Immunology [Mittelhäusern] (IVI), 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), This study was funded by the CNRS (N.J. and O.S.), Institut Pasteur (N.J., L.D., and O.S.), the 'Urgence COVID-19' fundraising campaign of Institut Pasteur (N.J., L.D., and O.S.), the University of Veterinary Sciences Brno (FVHE/Pikula/ITA2021) (J.P.), the FINOVI Fondation (AO13) and Covid IDEX Universite Lyon 1 (B.P.), LabEx Ecofect (ANR-11-LABX-0048) (Do.P.), Labex IBEID (ANR-10-LABX-62-IBEID) (O.S.), ANR/FRM Flash Covid PROTEO-SARS-CoV-2 (O.S.), and IDISCOVR (O.S.). S.-M.A. and De.P. are supported by the Pasteur-Paris University International Ph.D. Program and the Vaccine Research Institute (ANR-10-LABX-77), respectively. D.L. was funded by the Chinese Scholarship Council and Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Girard, Agnès, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, and Vaccine Research Institute [Créteil, France] (VRI)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 630 Agriculture, SARS-CoV-2, Immunology, coronavirus, Virus Replication, Microbiology, Species Specificity, Virology, Insect Science, Chiroptera, bat cells, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animals, Humans, Receptors, Virus, Angiotensin-Converting Enzyme 2, innate immunity
Abstract: Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the ones expressing detectable levels of angiotensin-converting enzyme 2 (ACE2), which serves as the viral receptor in many mammalian species. The resistance to infection was overcome by expression of human ACE2 (hACE2) in three cell lines, suggesting that the restriction to viral replication was due to a low expression of bat ACE2 (bACE2) or the absence of bACE2 binding in these cells. Infectious virions were produced but not released from hACE2-transduced M. myotis brain cells. E. serotinus brain cells and M. myotis nasal epithelial cells expressing hACE2 efficiently controlled viral replication, which correlated with a potent interferon response. Our data highlight the existence of species-specific and cell-specific molecular barriers to viral replication in bat cells. These novel chiropteran cellular models are valuable tools to investigate the evolutionary relationships between bats and coronaviruses. IMPORTANCE Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models. We have generated primary cells and cell lines from several bat species that are relevant for coronavirus research. The various permissivities of the cells to SARS-CoV-2 infection offered the opportunity to uncover some species-specific molecular restrictions to viral replication. All bat cells exhibited a potent entry-dependent restriction. Once this block was overcome by overexpression of human ACE2, which serves at the viral receptor, two bat cell lines controlled well viral replication, which correlated with the inability of the virus to counteract antiviral responses. Other cells potently inhibited viral release. Our novel bat cellular models contribute to a better understanding of the molecular interplays between bat cells and viruses.
Published: 2022

20. Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest Against Leukemia (GOAL) study

Author: Christophe Desprez, Jérémie Riou, Pierre Peterlin, Tony Marchand, Marie-Anne Couturier, Alban Villate, Jean-Baptiste Mear, Patrice Chevalier, Gaelle Guillerm, Emmanuel Gyan, Aline Schmidt-Tanguy, Roland B. Walter, Mathilde Hunault-Berger, Corentin Orvain, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), CHU Pontchaillou [Rennes], Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), and Fred Hutchinson Cancer Research Center [Seattle] (FHCRC)
Subjects: Adult, Cancer Research, Leukemia, Myeloid, Acute, Oncology, [SDV]Life Sciences [q-bio], Antineoplastic Combined Chemotherapy Protocols, Humans, Hematology, Induction Chemotherapy, Goals, Proportional Hazards Models
Abstract: International audience; Several scoring systems have been developed to assess suitability of individual patients for intensive acute myeloid leukemia (AML) therapy. We sought to compare the performance of these scores in a cohort of 428 consecutive adults with AML who received conventional induction chemotherapy in five academic centers in France. All scoring systems identified a subset of patients with increased 28 and 56-day mortality although the prediction accuracy was overall limited with C-statistics of ranging from 0.61 to 0.71 Overall survival (OS) prediction was more limited and restricted to scoring systems that include AML-related parameters. The outcome of 104 patients (24%) considered unsuitable for intensive chemotherapy based on criteria used in recent randomized trials was similar to that of the other 324 patients (28-day mortality, odds ratio [OR] = 1.88, P = 0.2; 56-day mortality, OR = 1.71, P = 0.21; event-free survival, hazard ratio [HR] = 1.08, P = 0.6; OS, HR = 1.25, P = 0.14) with low discrimination (C-statistic: 0.57, 0.56, 0.50, and 0.52 for 28-day, 56-day mortality, EFS, and OS, respectively). Together, our findings indicate that the accuracy of currently available approaches to identify patients at increased risk of early mortality and shortened survival after intensive AML therapy is relatively limited. Caution regarding the use of available scoring systems should be warranted in clinical decision-making.
Published: 2022

21. Management of Central Venous Catheters in Children and Adults on Home Parenteral Nutrition: A French Survey of Current Practice

Author: Julien Gotchac, Florian Poullenot, Dominique Guimber, Emmanuelle Ecochard-Dugelay, Stéphane Schneider, Noël Peretti, Lore Billiauws, Corinne Borderon, Anne Breton, Emilie Chaillou Legault, Cécile Chambrier, Aurélie Comte, Marie-Edith Coste, Djamal Djeddi, Béatrice Dubern, Claire Dupont, Lucile Espeso, Philippe Fayemendy, Nicolas Flori, Ginette Fotsing, Swellen Gastineau, Olivier Goulet, Emeline Guiot, Adam Jirka, Jeanne Languepin, Sabrina Layec, Didier Quilliot, Laurent Rebouissoux, David Seguy, Isabelle Talon, Anne Turquet, Marjolaine Vallee, Stéphanie Willot, Thierry Lamireau, Raphael Enaud, Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], Hôpital Jeanne de Flandre [Lille], Université de Lille, Hôpital Robert Debré, Centre Hospitalier Universitaire de Nice (CHU Nice), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-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 Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Amiens-Picardie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Limoges, Institut du Cancer de Montpellier (ICM), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pontchaillou [Rennes], CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôtel-Dieu de Nantes, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Clinique Saint-Yves [Rennes], CHU Lille, CHU Strasbourg, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital Gatien de Clocheville [Tours] (CHRU Tours), Admin, Oskar, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Toulouse (UT)
Subjects: Adult, Catheterization, Central Venous, Central venous catheter thrombosis, Nutrition and Dietetics, Chronic intestinal failure, equipment and supplies, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, chronic intestinal failure, venous thrombosis, central venous catheter thrombosis, catheter obstruction, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Venous thrombosis, Central Venous Catheters, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Catheter obstruction, Child, Parenteral Nutrition, Home, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Retrospective Studies
Abstract: International audience; Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers' practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers' responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.
Published: 2022
Full Text: View/download PDF

22. Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) under managed care: a clinical and environmental investigation in a French zoological park

Author: Estelle Cateau, Antoine Leclerc, Noémie Cartier, Isabel Valsecchi, Éric Bailly, Ronan Le Senechal, Margaux Becerra, Brice Le Gallou, Rose-Anne Lavergne, Adélaïde Chesnay, Jean-Patrice Robin, Carolyn Cray, Nicolas Goddard, Milan Thorel, Jacques Guillot, Baptiste Mulot, Guillaume Desoubeaux, Service de Parasitologie - Mycologie - Médecine Tropicale, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ZooParc de Beauval, Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Miami Leonard M. Miller School of Medicine (UMMSM), and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Azoles, Antifungal Agents, MICs, microsatellite genotypin, Aspergillus fumigatus, Managed Care Programs, Microbial Sensitivity Tests, General Medicine, Spheniscidae, Fungal Proteins, Infectious Diseases, MESH: Spheniscidae, Drug Resistance, Fungal, birds, Mutation, [SDE]Environmental Sciences, Aspergillus nishimurae, cyp51A, Animals, Aspergillosis, Humans, MESH: Aspergillosis, azole-resistance, Humboldt penguins
Abstract: Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs. The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018–20: all isolates were counted and characterized by sequencing. When identified as Aspergillus fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for minimal inhibitory concentrations (MICs) determination. At the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains. Environmental investigations highlighted the substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and a large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains. Lay summary
Published: 2022

23. No survival improvement in patients with high‐risk multiple myeloma harbouring del(17p) and/or t(4;14) over the two past decades

Author: Carole Barin, Lotfi Benboubker, Cyrille Touzeau, Nicolas Vallet, Olivier Theisen, Pascal Godmer, Thomas Chalopin, Hervé Avet-Loiseau, Olivier Herault, Steven Le Gouill, Marlene Ochmann, Philippe Moreau, Mourad Tiab, Emmanuel Gyan, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de Bretagne Sud - Vannes (UBS Vannes), Université de Bretagne Sud (UBS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Hématologie [Nantes], Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth
Subjects: Adult, Male, Oncology, medicine.medical_specialty, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Text mining, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, In patient, ComputingMilieux_MISCELLANEOUS, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, Chromosome Aberrations, business.industry, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, 030215 immunology
Abstract: International audience; No abstract available
Published: 2021

24. Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting

Author: Lixin Xie, Meilien Tu, Armèle Dornelas de Andrade, Jie Li, Lingyue Gong, Lei Yang, Stephan Ehrmann, James B Fink, Chris Burtin, Guoqiang Jing, Rush University [Chicago], Chang Gung University, Binzhou Medical University (MBBS), Partenaires INRAE, Universiteit Hasselt (UHasselt), Federal University of Pernambuco [Recife], Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRICS-TRIGGERSEP, Li, Jie/0000-0003-0121-1291, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, pulmonary aerosol delivery, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030226 pharmacology & pharmacy, transnasal pulmonary aerosol delivery, Hypoxemia, Aerosol therapy, 03 medical and health sciences, 0302 clinical medicine, Oxygen therapy, Administration, Inhalation, medicine, Cannula, Humans, survey, Mouthpiece, Original Research, Aerosols, hypoxemia, business.industry, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, General Medicine, High-flow nasal cannula, aerosol therapy, transnasal, Bronchodilator Agents, 3. Good health, Clinical Practice, Intensive Care Units, Nebulizer, Concomitant, Emergency medicine, medicine.symptom, business, Nasal cannula
Abstract: BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients. METHODS: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included. RESULTS: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40–50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC (a method shown to reduce inhaled dose), whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier. CONCLUSIONS: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.
Published: 2021

25. Repurposing of Acriflavine to Target Chronic Myeloid Leukemia Treatment

Author: Rawan Nehme, Rawan Hallal, Firas Kobeissy, Maya El Dor, Fabrice Gouilleux, Frédéric Mazurier, Kazem Zibara, ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), American University of Beirut [Beyrouth] (AUB), Université Libanaise, and Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 01 natural sciences, Biochemistry, 03 medical and health sciences, chronic myeloid leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Drug Discovery, Humans, Medicine, Acriflavine, 0101 mathematics, Protein Kinase Inhibitors, ACF, 030304 developmental biology, Pharmacology, 0303 health sciences, drug repurposing, business.industry, Kinase, Organic Chemistry, Drug Repositioning, leukemia, JAK-STAT signaling pathway, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Imatinib, medicine.disease, 3. Good health, 010101 applied mathematics, Leukemia, Drug Resistance, Neoplasm, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer research, STAT protein, Molecular Medicine, anti-tumoral, Signal transduction, anti-leukemic, business, Tyrosine kinase, medicine.drug
Abstract: Drug repurposing has lately received increasing interest in several diseases especially in cancers, due to its advantages in facilitating the development of new therapeutic strategies, by adopting a cost-friendly approach and avoiding the strict Food and Drug Administration (FDA) regulations. Acriflavine (ACF) is an FDA approved molecule that has been extensively studied since 1912 with antiseptic, trypanocidal, anti-viral, anti-bacterial and anti-cancer effects. ACF has been shown to block the growth of solid and hematopoietic tumor cells. Indeed, ACF acts as an inhibitor of various proteins, including DNA-dependent protein kinases C (DNA-PKcs), topoisomerase I and II, hypoxia-inducible factor 1α (HIF-1α), in addition to its recent discovery as an inhibitor of the signal transducer and activator of transcription (STAT). Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the expression of the constitutively active tyrosine kinase BCR-ABL. This protein allows the activation of several signaling pathways known for their role in cell proliferation and survival, such as the JAK/STAT pathway. CML therapy, based on tyrosine kinase inhibitors (TKIs), such as imatinib (IM), is highly effective. However, 15% of patients are refractory to IM, where in some cases, 20-30% of patients become resistant. Thus, we suggest the repurposing of ACF in CML after IM failure or in combination with IM to improve the anti-tumor effects of IM. In this review, we present the different pharmacological properties of ACF along with its anti-leukemic effects in the hope of its repurposing in CML therapy.
Published: 2021

26. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study

Author: Martine Nyunga, Matthieu Turpin, Alexandre Pierre, Anahita Rouzé, Jean-Luc Baudel, Saad Nseir, Pierre Cuchet, Antonio Artigas, Alain Duhamel, Justine Bardin, Gaëtan Plantefève, Mathilde Bouchereau, Iliana Ioannidou, Matthieu Metzelard, Pedro Póvoa, Claire Boulle Geronimi, Antoni Torres, Jean-François Llitjos, Olivier Pouly, Fabienne Tamion, Fabien Lambiotte, Denis Garot, Adrian Ceccato, Nicolas Weiss, Pierre-Edouard Floch, Ignacio Martin-Loeches, Pierre Asfar, Alexandra Beurton, Julien Labreuche, Marie Labruyere, Christophe Vinsonneau, Anastasia Saade, Eleni Magira, Charles-Edouard Luyt, Demosthenes Makris, Jean Reignier, Louis Kreitmann, Edgar Moglia, David Meguerditchian, Armand Mekontso-Dessap, Bruno Mégarbane, Gestionnaire, Hal Sorbonne Université, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of Thessaly [Volos] (UTH), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Centre hospitalier [Valenciennes, Nord], CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier [Douai, Nord], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de cardiologie [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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Saint Philibert [Lomme], Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Saint-Antoine [AP-HP], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), National and Kapodistrian University of Athens (NKUA), Hospices Civils de Lyon (HCL), Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], University of Athens Medical School [Athens], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], CHU de Bordeaux Pellegrin [Bordeaux], Hôpital Henri Mondor, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Victor Dupouy, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Original, [SDV]Life Sciences [q-bio], Respiratory Tract Infections/epidemiology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Influenza, Human/epidemiology, Pneumonia, Ventilator-Associated/epidemiology, Internal medicine, Influenza, Human, medicine, Humans, Ventilator-associated pneumonia, Cumulative incidence, Respiratory Tract Infections, COVID-19/epidemiology, Aged, Retrospective Studies, Ventilators, Mechanical, Respiratory tract infections, SARS-CoV-2, business.industry, Incidence, Incidence (epidemiology), Hazard ratio, Pneumonia, Ventilator-Associated, Correction, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, Ventilator-associated tracheobronchitis, medicine.disease, respiratory tract diseases, 3. Good health, Europe, [SDV] Life Sciences [q-bio], Pneumonia, 030228 respiratory system, Female, Critical illness, business, Cohort study
Abstract: Purpose Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. Methods Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. Results 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. Conclusions The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates. Electronic supplementary material The online version of this article (10.1007/s00134-020-06323-9) contains supplementary material, which is available to authorized users.
Published: 2021

27. Primary lymphedema French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins)

Author: Stéphane Vignes, Juliette Albuisson, Laurence Champion, Joël Constans, Valérie Tauveron, Julie Malloizel, Isabelle Quéré, Laura Simon, Maria Arrault, Patrick Trévidic, Philippe Azria, Annabel Maruani, French National Referral Center for Primary Lymphedema, Hôpital Cognacq-Jay, 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), Institut Curie [Paris], Hôpital Saint-André, CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre national de référence des maladies vasculaires rares, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service des Maladies Cardiaques et Vasculaires [CHU Bordeaux], Service de dermatologie, CHU Saint-Eloi, EDEE, Afi Emiliène, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, medicine.medical_specialty, Complications, [SDV]Life Sciences [q-bio], lcsh:Medicine, Erysipelas, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Pathognomonic, medicine, Humans, Pharmacology (medical), Primary lymphedema, Lymphedema, Position Statement, Child, Genetics (clinical), Skin, business.industry, lcsh:R, General Medicine, Compression garment, medicine.disease, Exercise Therapy, 3. Good health, [SDV] Life Sciences [q-bio], body regions, Treatment, Explorations, Lower Extremity, 030220 oncology & carcinogenesis, Cellulitis, Quality of Life, Female, business, Primary, Patient education
Abstract: Primary lymphedema is a rare chronic pathology associated with constitutional abnormalities of the lymphatic system. The objective of this French National Diagnosis and Care Protocol (Protocole National de Diagnostic et de Soins; PNDS), based on a critical literature review and multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with primary lymphedema. This PNDS, written by consultants at the French National Referral Center for Primary Lymphedema, was published in 2019 (https://has-sante.fr/upload/docs/application/pdf/2019-02/pnds_lymphoedeme_primaire_final_has.pdf). Primary lymphedema can be isolated or syndromic (whose manifestations are more complex with a group of symptoms) and mainly affects the lower limbs, or, much more rarely, upper limbs or external genitalia. Women are more frequently affected than men, preferentially young. The diagnosis is clinical, associating mild or non-pitting edema and skin thickening, as confirmed by the Stemmer’s sign (impossibility to pinch the skin on the dorsal side or the base of the second toe), which is pathognomonic of lymphedema. Limb lymphoscintigraphy is useful to confirm the diagnosis. Other causes of swelling or edema of the lower limbs must be ruled out, such as lipedema. The main acute lymphedema complication is cellulitis (erysipelas). Functional and psychological repercussions can be major, deteriorating the patient’s quality of life. Treatment aims to prevent those complications, reduce the volume with low-stretch bandages, then stabilize it over the long term by exercises and wearing a compression garment. Patient education (or parents of a child) is essential to improve observance.
Published: 2021

28. Chronic Hepatitis C Virus Infection After Kidney Transplantation With or Without Direct-Acting Antivirals in a Real-Life Setting: A French Multicenter Experience

Author: Nicolas Bouvier, Yannick Le Meur, Cyril Garrouste, Dominique Bertrand, Johnny Sayegh, Eloi Chevallier, Matthias Büchler, Sophie Caillard, Joseph Rivalan, Antoine Thierry, Lionel Rostaing, Philippe Gatault, Charlotte Colosio, Jean-Philippe Rerolle, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratory of Immunology, CHRU de Tours, Tours, France, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Nephrology, Reims University Hospital, Reims, France, Centre Hospitalier Universitaire de Rennes (CHU Rennes), Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Male, Ledipasvir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, 030232 urology & nephrology, Antiviral Agents, Gastroenterology, Group A, Virus, Group B, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Kidney transplantation, Retrospective Studies, Fluorenes, Transplantation, business.industry, Imidazoles, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Benzimidazoles, Female, 030211 gastroenterology & hepatology, Surgery, Carbamates, France, business, Viral hepatitis, medicine.drug
Abstract: Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.
Published: 2020

29. Curcumin and NCLX inhibitors share anti-tumoral mechanisms in microsatellite-instability-driven colorectal cancer

Author: Maxime Guéguinou, Sajida Ibrahim, Jérôme Bourgeais, Alison Robert, Trayambak Pathak, Xuexin Zhang, David Crottès, Jacques Dupuy, David Ternant, Valérie Monbet, Roseline Guibon, Hector Flores-Romero, Antoine Lefèvre, Stéphanie Lerondel, Alain Le Pape, Jean-François Dumas, Philippe G. Frank, Alban Girault, Romain Chautard, Françoise Guéraud, Ana J. García-Sáez, Mehdi Ouaissi, Patrick Emond, Olivier Sire, Olivier Hérault, Gaëlle Fromont-Hankard, Christophe Vandier, David Tougeron, Mohamed Trebak, William Raoul, Thierry Lecomte, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Pennsylvania State University (Penn State), Penn State System, Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, 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), University of Cologne, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 (LPCM), Université de Picardie Jules Verne (UPJV), Institut de Recherche Dupuy de Lôme (IRDL), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), This project was partly supported by grants on behalf of the following french department committees of Ligue Contre le Cancer Grand-Ouest: 16 (Charente), 37 (Indre-et-Loire), 49 (Maine-et-Loire), 72 (Sarthe) and 85 (Vendée), ANR-11-LABX-0020,LEBESGUE,Centre de Mathématiques Henri Lebesgue : fondements, interactions, applications et Formation(2011), LESUR, Hélène, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Pharmacology, Curcumin, [SDV]Life Sciences [q-bio], Calcium signaling, Cell Biology, Colorectal cancer, Sodium-Calcium Exchanger, digestive system diseases, Mitochondria, Mitochondrial Proteins, [SDV] Life Sciences [q-bio], Mice, Cellular and Molecular Neuroscience, Animals, Humans, Molecular Medicine, Calcium, Microsatellite Instability, Colorectal Neoplasms, NCLX, Molecular Biology, Microsatellite Repeats
Abstract: Colorectal cancer (CRC) is associated with high mortality worldwide and new targets are needed to overcome treatment resistance. Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of CRC. In this context, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new potential inhibitor of NCLX.In vitro, curcumin exerted strong anti-tumoral activity through its action on NCLX with mtCa2+ and reactive oxygen species overload associated with a mitochondrial membrane depolarization, leading to reduced ATP production and apoptosis through mitochondrial permeability transition pore opening concomitant with G2/M cell cycle arrest. NCLX inhibition with either CGP37157 (a benzodiazepine derivative), small interfering RNA-mediated knock-down or knockout approaches reproduced the effects of curcumin. Altered mitochondrial respiration, cellular aerobic glycolysis and endoplasmic reticulum–mitochondria membrane perturbations participated in these mechanisms. In a xenograft mouse model, NCLX inhibitors decreased CRC tumor growth. Both transcriptomic analysis of The Cancer Genome Atlas dataset and immunohistochemical analysis of tissue microarrays from 381 patients with microsatellite instability (MSI)-driven CRC demonstrated that higher NCLX expression was associated with MSI status and for the first time NCLX expression was significantly associated with recurrence-free survival in MSI CRC patients.Our findings provide strong evidence that blocking NCLX inhibits CRC in vitro and in vivo. We highlight a novel anti-tumoral mechanism of curcumin through its action on NCLX and mitochondria calcium overload that could benefit for therapeutic treatment of patients with MSI CRC.
Published: 2022

30. IL-26 inhibits hepatitis C virus replication in hepatocytes

Author: Élodie Beaumont, Vincent Larochette, Laurence Preisser, Charline Miot, Pascale Pignon, Simon Blanchard, Björn-Thore Hansen, Jonathan Dauvé, Caroline Poli, Minna M. Poranen, Patricia Lamourette, Marc Plaisance, Alain Morel, Helmut Fickenscher, Pascale Jeannin, Philippe Roingeard, Yves Delneste, Molecular and Integrative Biosciences Research Programme, University of Helsinki, Biosciences, Molecular and Translational Virology, 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Christian-Albrechts University of Kiel, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Blanchard, Simon
Subjects: MECHANISM, hepatitis C virus, Il-26, DEFENSE, INCREASES, [SDV]Life Sciences [q-bio], DEPENDENT RNA-POLYMERASE, Hepacivirus, Virus Replication, Antiviral Agents, ANTIMICROBIAL PEPTIDE LL-37, Antiviral defense, INFECTION, Viral replication, Humans, Hepatology, Interleukins, DNA, INTERLEUKIN-10, Hepatitis C, [SDV] Life Sciences [q-bio], CATHELICIDIN, 3121 General medicine, internal medicine and other clinical medicine, CELLS, Hepatocytes, Cytokines
Abstract: Publisher Copyright: © 2021 European Association for the Study of the Liver Background & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3+ lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV. Based on this observation and possible interactions between IL-26 and nucleic acids, we investigated the possibility that IL-26 controlled HCV infection independently of the immune system. Methods: We evaluated the ability of IL-26 to interfere with HCV replication in hepatocytes and investigated the mechanisms by which IL-26 exerts its antiviral activity. Results: We showed that IL-26 penetrated HCV-infected hepatocytes, where it interacted directly with HCV double-stranded RNA replication intermediates, thereby inhibiting viral replication. IL-26 interfered with viral RNA-dependent RNA polymerase activity, preventing the de novo synthesis of viral genomic single-stranded RNA. Conclusions: These findings reveal a new role for IL-26 in direct protection against HCV infection, independently of the immune system, and increase our understanding of the antiviral defense mechanisms controlling HCV infection. Future studies should evaluate the possible use of IL-26 for treating other chronic disorders caused by RNA viruses, for which few treatments are currently available, or emerging RNA viruses. Lay summary: This study sheds new light on the body's arsenal for controlling hepatitis C virus (HCV) infection and identifies interleukin-26 (IL-26) as an antiviral molecule capable of blocking HCV replication. IL-26, which has unique biochemical and structural characteristics, penetrates infected hepatocytes and interacts directly with viral RNA, thereby blocking viral replication. IL-26 is, therefore, a new player in antiviral defenses, operating independently of the immune system. It is of considerable potential interest for treating HCV infection and other chronic disorders caused by RNA viruses for which few treatments are currently available, and for combating emerging RNA viruses.
Published: 2022

31. Genotypic Characterization and Biofilm Production of Group B Streptococcus Strains Isolated from Bone and Joint Infections

Author: Marion Lacasse, Anne-Sophie Valentin, Stéphane Corvec, Pascale Bémer, Anne Jolivet-Gougeon, Chloé Plouzeau, Didier Tandé, Laurent Mereghetti, Louis Bernard, Marie-Frédérique Lartigue, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de bactériologie et d'hygiène hospitalière [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), M.L. was supported by a grant from the University Hospital Center of Tours (France).This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors., and Jonchère, Laurent
Subjects: Microbiology (medical), group B Streptococcus, Genotype, Physiology, [SDV]Life Sciences [q-bio], biofilm, Streptococcus agalactiae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Streptococcal Infections, Genetics, Humans, Adhesins, Bacterial, Phylogeny, General Immunology and Microbiology, Ecology, Cell Biology, bone and joint infections, biochemical phenomena, metabolism, and nutrition, adhesins, [SDV] Life Sciences [q-bio], Infectious Diseases, Biofilms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, pili, Multilocus Sequence Typing, MLST
Abstract: International audience; Bone and joint infections (BJI) represent the second cause of invasive Group B Streptococcus (GBS) infections. Biofilm formation plays a major role in BJI. This study’s aim was to analyze the genetic features and biofilm production of GBS strains. In six French laboratories, 77 GBS strains isolated from BJI and 57 strains from vaginal human colonization (Hcol) were characterized and compared by Multi-Locus Sequence Typing (MLST). PCR was used to search for the adhesins (bsaB, lmb, scpB, fbsA, fbsB, hvgA, bibA, bca, srr-1, and srr-2) and Pilus Islands (PI) related genes (PI-1, PI-2a, PI-2b). Biofilm production was studied by crystal violet assay. Strains were categorized into three groups, based on Specific Biofilm Formation (SBF) values defined as: weak, moderate, or strong producers. Molecular study revealed three major clonal complexes (CC) in BJI strains: CC1 (42%), CC23 (22%) and CC10 (14%). Several associations between CC and adhesin/pili were identified: CC1 with srr2, PI-1 + 2a; CC10 with srr-1, bca, PI-1 + 2a; CC17 with fbsB, hvgA, srr-2, PI-1+PI-2b; CC19 with bibA, srr-1, PI-1 + 2a; CC23 with fbsB, bibA, srr-1, PI-2a. The biofilm production was significantly different according to CC, adhesins and pili gene detection. CC10, CC23 and strains harboring fbsB produce more biofilm than CC1, PI-1 + 2a (independently). Finally, SBF values were significantly stronger for Hcol strains rather than for BJI strains (76% versus 40%). This study revealed that Hcol strains appeared to produce stronger biofilm than BJI strains, though they belonged to similar CCs and had the same adhesin and pili content. IMPORTANCE Bone and joint infections (BJI) are pathologies that can be life-threatening and result in compromised functional prognosis for patients. Relapses are common and often related to biofilm formation. Group B streptococci (GBS) BJI increased since the last decade. However, few data are available on this subject in the literature. Our study aims to highlight genotype and biofilm production of GBS isolates from BJI. Seventy-seven GBS strains isolated from BJI and 57 from asymptomatic human vaginal colonization were characterized by multilocus sequence typing (MLST), adhesins content, nature of the pili and the ability to form biofilm. Our results revealed that vaginal human colonization strains produced stronger biofilm than BJI strains, despite belonging to the same phylogenetic lineage and having the same adhesin and pili content.
Published: 2022

32. Impact of a school-based and primary care-based multicomponent intervention on HPV vaccination coverage among French adolescents: a cluster randomised controlled trial protocol (the PrevHPV study)

Author: Bocquier, Aurélie, Michel, Morgane, Giraudeau, Bruno, Bonnay, Stéphanie, Gagneux-Brunon, Amandine, Gauchet, Aurélie, Gilberg, Serge, Le Duc-Banaszuk, Anne-Sophie, Mueller, Judith E., Chevreul, Karine, Thilly, Nathalie, Raude, Jocelyn, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Robert Debré, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des infections muqueuses (GIMAP), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), Université Paris Cité (UPCité), Centre régional de coordination des dépistages des cancers-Pays de la Loire, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département des sciences humaines et sociales (SHS), The study is conducted with the support of IReSP and with financial support from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé/ National Alliance for Life Sciences & Health) within the framework of the Cancer Plan 2014–2019, and PrevHPV Study group: Nelly Agrinier, Estelle Fall, Céline Pulcini, Sébastien Bruel, Marie Ecollan, Dragos-Paul Hagiu, Josselin Le Bel, Henri Partouche, Juliette Pinot, Louise Rossignol, Arthur Tron, Minghui Zuo, Gaëlle Vareilles, Julie Bros, Catherine Juneau, Marion Branchereau, Elisabeth Botelho-Nevers, Géraldine Jambon, Florian Jeanleboeuf, Julie Kalecinski, Christine Lasset, Laetitia Marie DitAsse, Jonathan Sicsic, Jocelyn Raude, Sandra Chyderiotis, Damien Oudin-Doglioni, Anne-Sophie Barret, Isabelle Bonmarin, Daniel Levy-Bruhl, Clémence Castagnet, Mélanie Simony
Subjects: Public health, Schools, Vaccination Coverage, Adolescent, Primary Health Care, Papillomavirus Infections, Vaccination, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Papillomavirus Vaccines, Medical education & training, Randomized Controlled Trials as Topic
Abstract: IntroductionVaccination is an effective and safe strategy to prevent Human papillomavirus (HPV) infection and related harms. Despite various efforts by French authorities to improve HPV vaccine coverage (VC) these past few years, VC has remained far lower than in most other high-income countries. To improve it, we have coconstructed with stakeholders a school-based and primary care-based multicomponent intervention, and plan to evaluate its effectiveness, efficiency and implementation through a cluster randomised controlled trial (cRCT).Methods and analysisThis pragmatic cRCT uses an incomplete factorial design to evaluate three components applied alone or in combination: (1) adolescents and parents’ education and motivation at school, using eHealth tools and participatory learning; (2) general practitioners’ training on HPV using motivational interviewing techniques and provision of a decision aid tool; (3) free-of-charge access to vaccination at school. Eligible municipalities (clusters) are located in one of 14 preselected French school districts and must have only one secondary school which enrols at least 2/3 of inhabitants aged 11–14 years. A randomisation stratified by school district and deprivation index allocated 90 municipalities into 6 groups of 15. The expected overall sample size estimate is 41 940 adolescents aged 11–14 years. The primary endpoint is the HPV VC (≥1 dose) among adolescents aged 11–14 years, at 2 months, at the municipality level (data from routine databases). Secondary endpoints include: HPV VC (≥1 dose at 6 and 12 months; and 2 doses at 2, 6 and 12 months); differences in knowledge, attitudes, behaviours, and intention among adolescents, parents and general practitioners between baseline and 2 months after intervention (self-administered questionnaires); incremental cost-effectiveness ratio. Implementation measures include dose, fidelity, adaptations, reached population and satisfaction (activity reports and self-administered questionnaires).Ethics and disseminationThis protocol was approved by the French Ethics Committee ‘CPP Sud-Est VI’ on 22 December 2020 (ID-RCB: 2020-A02031-38). No individual consent was required for this type of research; all participants were informed of their rights, in particular not to participate or to oppose the collection of data concerning them. Findings will be widely disseminated (conference presentations, reports, factsheets and academic publications).Trial registration numberNCT04945655.
Published: 2022

33. Heterogeneity of patients with functional/dissociative seizures: Three multidimensional profiles

Author: Coraline Hingray, Deniz Ertan, Markus Reuber, Anne‐Sophie Lother, Jan Chrusciel, Alexis Tarrada, Nathalie Michel, Mylene Meyer, Irina Klemina, Louis Maillard, Stephane Sanchez, Wissam El‐Hage, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Psychothérapique de Nancy [Laxou] (CPN), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Neuroscience, Academic Neurology Unit, University of Sheffield, Centre Médical de la Teppe, Centre hospitalier Troyes (CH Troyes), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), UMR 1253 IBrain Imagerie & Cerveau Equipe 1 : 'Psychiatrie Neuro-Fonctionnelle' (PNF), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Maquin, Didier
Subjects: Adult, Male, [STAT.AP]Statistics [stat]/Applications [stat.AP], Epilepsy, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, comorbid epilepsy, Dissociative Disorders, dissociation, Neurology, [STAT.AP] Statistics [stat]/Applications [stat.AP], Conversion Disorder, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Seizures, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), etiopathogenesis, Prospective Studies, psychological trauma
Abstract: Objective\ud \ud Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis.\ud \ud \ud \ud Methods\ud \ud We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests.\ud \ud \ud \ud Results\ud \ud Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics:\ud \ud 1. A “No/Single Trauma” group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology;\ud \ud 2. A “Cumulative Lifetime Traumas” group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and\ud \ud 3. A “Childhood Traumas” group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation.\ud \ud Significance\ud \ud Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile.
Published: 2022

34. Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Author: Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebík, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, Hugo Mouquet, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Imagopole (CITECH), Institut Pasteur [Paris] (IP), Microscopie Ultrastructurale (Plate-forme), Masaryk University [Brno] (MUNI), Virus et Immunité - Virus and immunity (CNRS-UMR3569), University of Amsterdam [Amsterdam] (UvA), Weill Medical College of Cornell University [New York], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Rockefeller University [New York], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), The NanoImaging Core was created with the help of a grant from the French Government’s Investissements d’Avenir program (EQUIPEX CACSICE - Centre d’analyse de systèmes complexes dans les environnements complexes, ANR-11-EQPX-0008). We thank the NIH AIDS Reagent Program (Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support. The Biomics platform is supported by France Génomique (ANR-10-INBS-09-09) and IBISA. I. Fernández and C. Planchais were recipients of an ANRS postdoctoral fellowship. The J.P. Di Santo laboratory received support from the Vaccine Research Institute (Créteil, France). H. Mouquet received core grants from the Institut Pasteur, Institut national de la santé et de la recherche médicale, and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was supported by the European Research Council Seventh Framework Program (ERC-2013-StG 337146), and by Gilead Sciences HIV Cure Grants (#00397)., ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Medical Microbiology and Infection Prevention, and AII - Infectious diseases
Subjects: Immunology, env Gene Products, Human Immunodeficiency Virus, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, Immunoglobulin A, Epitopes, Mice, Polysaccharides, Immunoglobulin G, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Immunology and Allergy, Animals, Humans, Elite Controllers, Broadly Neutralizing Antibodies
Abstract: International audience; Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
Published: 2022

35. Skin manifestations of COVID‐19 in children: Part 2

Author: C Luca, V Zawar, D van Gysel, M Casals, Angela Hernández-Martín, Annabel Maruani, E Bonifazi, Christine Bodemer, F Mazzotta, T Hubiche, Ramon Grimalt, Isabel Colmenero, A Belloni-Fortina, L Martos-Cabrera, David Andina, I Grozdev, Suzanne G.M.A. Pasmans, A Chiriac, Antonio Torrelo, M P Novoa, M A Morren, M Munisami, Hagen Ott, Carmen Salavastru, Veronica A. Kinsler, A Nanda, M El-Hachem, Andrea Diociaiuti, J Ferrando, L Fertitta, A D Akkaya, Dermatology, Hospital Infantil Universitario Niño Jesús [Madrid, Spain] (HIUNJ), University of Padua [Italy], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bambino Gesù Children’s Hospital [Rome, Italy], Onze Lieve Vrouw Hospital, Université Côte d'Azur (UCA), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hospital Universitari Parc Taulí of Sabadell, Barcelona, Hospital Clinic [Barcelona, Spain], Universitat Internacional de Catalunya [Barcelona] (UIC), Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Great Ormond Street Hospital for Children [London] (GOSH), University of Lausanne (UNIL), Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Children's Hospital 'Auf der Bult', Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Adolescent, Urticaria, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Dermatology, Mucocutaneous Lymph Node Syndrome, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Correspondence, Pandemic, medicine, Humans, Erythema multiforme, Child, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Erythema Multiforme, Skin manifestations, Respiratory distress, SARS-CoV-2, business.industry, COVID-19, Exanthema, medicine.disease, Erythema Multiforme/pathology, Letter To The Editor, Urticaria/pathology, 3. Good health, 030220 oncology & carcinogenesis, Mucocutaneous Lymph Node Syndrome/virology, COVID-19/complications, Presentation (obstetrics), business, Exanthema/pathology
Abstract: The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.
Published: 2020

36. Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy

Author: Shailender Bhatia, A. Marchand, Mahtab Samimi, Thibault Kervarrec, Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pathologie [CHRU Tours], Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Medicine, University of Washington [Seattle], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Skin Neoplasms, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, Locally advanced, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Checkpoint inhibitor, Biomarkers, Tumor, Advanced disease, medicine, Humans, Cytotoxic T cell, Pharmacology (medical), Immune Checkpoint Inhibitors, Aged, skin cancer, integumentary system, Merkel cell carcinoma, business.industry, food and beverages, Merkel Cell Carcinoma, Immunotherapy, medicine.disease, 3. Good health, Carcinoma, Merkel Cell, 030104 developmental biology, Oncology, programmed cell death 1, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, immunotherapy, pembrolizumab, Skin cancer, business
Abstract: International audience; IntroductionMerkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As with other cancers, immune checkpoint inhibitors (CPI), including pembrolizumab, allow durable responses with a manageable safety profile in these patients.Areas coveredThis review describes the rationale for using PD-1/PD-L1 inhibitors in MCC, as well as efficacy and safety results from the three open-label trials investigating pembrolizumab or other PD-1/PD-L1 inhibitors in patients with advanced MCC. Real-life experience and predictive pre-treatment biomarkers are discussed to assess which patients are likely to be candidates for such strategies. Ongoing fields of research include the use of CPI in the adjuvant or neoadjuvant setting and combined strategies in refractory patients.Expert Opinion: CPI have become the standard of care for frontline treatment in patients with advanced MCC. Earlier introduction of CPI in the disease course, including neo-adjuvant and adjuvant settings, is likely to improve the outcomes further. Given the rarity of this cancer, we still need to harmonize efforts in order to conduct large-scale trials and efficiently identify best optimal care.
Published: 2020

37. Switch maintenance chemotherapy versus observation after carboplatin and weekly paclitaxel doublet chemotherapy in elderly patients with advanced non–small cell lung cancer: IFCT-1201 MODEL trial

Author: Didier Debieuvre, Pierre-Jean Souquet, Jean-Louis Pujol, Jérôme Dauba, Jeannick Madelaine, Olivier Molinier, J. Otto, Jacques Le Treut, Fabrice Barlesi, Elisabeth Quoix, Patrick Aldo Renault, Eric Pichon, Alexandra Langlais, Virginie Westeel, L. Moreau, Franck Morin, Jacques Margery, Clarisse Audigier-Valette, Armelle Lavolé, Patrick Dumont, Denis Moro-Sibilot, CHU Strasbourg, Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Le Mans (CH Le Mans), Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier du Pays d'Aix, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Layné, Université Côte d'Azur (UCA), Hôpital pasteur [Colmar], Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Chauny, Partenaires INRAE, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CHU Grenoble, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, Time Factors, medicine.medical_treatment, NSCLC, Deoxycytidine, Carboplatin, chemistry.chemical_compound, Elderly, MESH: Aged, 80 and over, 0302 clinical medicine, Maintenance therapy, MESH: Progression-Free Survival, MESH: Carboplatin, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, MESH: Aged, MESH: Antimetabolites, Antineoplastic, Drug Substitution, Age Factors, MESH: Neoplasm Staging, Progression-Free Survival, 3. Good health, MESH: Maintenance Chemotherapy, MESH: Antineoplastic Combined Chemotherapy Protocols, Pemetrexed, 030220 oncology & carcinogenesis, Disease Progression, Female, MESH: Disease Progression, France, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Paclitaxel, Maintenance, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drug Administration Schedule, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Chemotherapy, MESH: Paclitaxel, MESH: Pemetrexed, Lung cancer, Aged, Neoplasm Staging, MESH: Age Factors, MESH: Humans, Performance status, business.industry, MESH: Time Factors, MESH: Deoxycytidine, medicine.disease, Gemcitabine, MESH: Drug Substitution, MESH: Male, MESH: Lung Neoplasms, MESH: France, 030104 developmental biology, chemistry, business, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.
Published: 2020

38. The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism

Author: Blasco, H., Bessy, C., Plantier, L., Lefevre, A., Piver, E., Bernard, L., Marlet, J., Stefic, K., Benz-de Bretagne, Isabelle, Cannet, P., Lumbu, H., Morel, T., Boulard, P., Andres, C. R., Vourc’h, P., Hérault, O., Guillon, A., Emond, P., Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (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), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), and Marlet, Julien
Subjects: Male, Niacinamide, Pneumonia, Viral, COVID-19, Biomarkers, Virology, Metabolomics, lcsh:Medicine, 02 engineering and technology, Sensitivity and Specificity, Severity of Illness Index, Article, Betacoronavirus, Cytosine, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 0202 electrical engineering, electronic engineering, information engineering, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030212 general & internal medicine, lcsh:Science, Pandemics, Aged, Aged, 80 and over, Multidisciplinary, SARS-CoV-2, lcsh:R, Tryptophan, Reproducibility of Results, Middle Aged, Prognosis, 3. Good health, Early Diagnosis, Metabolome, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, 020201 artificial intelligence & image processing, lcsh:Q, France, Coronavirus Infections
Abstract: BackgroundThe biological mechanisms involved in SARS-CoV-2 infection are only partially understood. Thus we explored the plasma metabolome of patients infected with SARS-CoV-2 to search for diagnostic and/or prognostic biomarkers and to improve the knowledge of metabolic disturbance in this infection.Materials and Methods We analyzed the plasma metabolome of 55 patients infected with SARS-CoV-2 and 45 controls by LC-HRMS at the time of diagnosis (D0). We first evaluated the ability to predict the diagnosis from the metabotype at D0 in an independent population. Next, we assessed the feasibility of predicting the disease evolution at the 7th and 15th day.ResultsPlasma metabolome allowed us to generate a discriminant multivariate model to predict the diagnosis of SARS-CoV-2 in an independent population (accuracy>74%, sensitivity, specificity>75%). We identified the role of the cytosine and tryptophan-nicotinamide pathways in this discrimination. However, metabolomic exploration modestly explained the disease evolution.DiscussionHere, we present the first metabolomic study in SARS-CoV-2 patients which showed a high reliable prediction of early diagnosis. We have highlighted the role of the tryptophan-nicotinamide pathway clearly linked to inflammatory signals and microbiota, and the involvement of cytosine, previously described as a coordinator of cell metabolism in SARS-CoV-2. These findings could open new therapeutic perspectives as indirect targets.
Published: 2020

39. Differential utilization of CD4+ by transmitted/founder and chronic envelope glycoproteins in a MSM HIV-1 subtype B transmission cluster

Author: Olivia Blake, Denys Brand, Nicolas Bellini, Emmanuelle Roch, Fabrizio Mammano, Alain Moreau, Martine Braibant, Julie Migraine, Jean-Christophe Plantier, Mélanie Bouvin-Pley, Marie Leoz, 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), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU), Université de Montréal (UdeM), Institut de Recherches Cliniques de Montréal (IRCM), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mammano, Fabrizio, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Immunology, MESH: Glycoproteins, HIV Infections, Context (language use), Viral quasispecies, CCR5 receptor antagonist, Biology, HIV transmission cluster, MESH: HIV-1, MESH: Homosexuality, Male, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Viral Envelope Proteins, Interferon, Genotype, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Homosexuality, Male, Glycoproteins, Maraviroc, Infectivity, MESH: Humans, Transmission (medicine), envelope glycoproteins, MESH: CD4-Positive T-Lymphocytes, MESH: HIV Infections, Virology, MESH: Male, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Infectious Diseases, chemistry, MESH: Viral Envelope Proteins, HIV-1, CD4 þ binding, genetic bottleneck, medicine.drug
Abstract: International audience; Objective: HIV-1 transmission leads to a genetic bottleneck, with one or a few variants of the donor quasispecies establishing an infection in the new host. We aimed to characterize this bottleneck in more detail, by comparing the properties of HIV envelope glycoproteins from acute and chronic infections within the particular context of a male-to-male transmission cluster. Design: We compared the genotypic and phenotypic properties of envelope glycoproteins from viral variants derived from five study participants from the same transmission cluster. Methods: We used single-genome amplification to generate a collection of full-length env sequences. We then constructed pseudotyped viruses expressing selected Env variants from the quasispecies infecting each study participant and compared their infectivities and sensitivities to various entry inhibitors. Results: The genotypic analyses confirmed the genetic bottleneck expected after HIV transmission, with a limited number of variants identified in four study participants during acute infection. However, the transmitted sequences harbored no evident common signature and belonged to various genetic lineages. The phenotypic analyses revealed no difference in infectivity, susceptibility to the CCR5 antagonist maraviroc, the fusion inhibitor enfurvitide or type-I interferon between viruses from participants with acute and chronic infections. The key property distinguishing transmitted viruses was a higher resistance to soluble CD4 þ , correlated with greater sensitivity to occupation of the CD4 þ receptor by the anti-CD4 þ antibodies LM52 and SK3. Conclusion: These results suggest that envelope glycoproteins from transmitted/ founder viruses bind CD4 þ less efficiently than those of viruses from chronic infections.
Published: 2020

40. Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype 'Acral FibroChondroMyxoid Tumors'

Author: Sébastien Aubert, Jean-Marc Guinebretière, Anne Gomez-Brouchet, François Le Loarer, Jessica Baud, Frédérique Larousserie, Virginie Audard, Gonzague de Pinieux, Corinne Bouvier, Nicolas Macagno, Daniel Pissaloux, Damien Geneste, Franck Tirode, Béatrice Marie, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Bergonié [Bordeaux], UNICANCER, CHU Lille, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital René HUGUENIN (Saint-Cloud), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gall, Valérie, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Nucleolus, [SDV]Life Sciences [q-bio], CD34, Soft Tissue Neoplasms, Biology, Receptors, G-Protein-Coupled, Pathology and Forensic Medicine, Fingers, Thrombospondin 1, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, Stroma, Eosinophilic, medicine, Humans, Oncogene Fusion, Neoplasms, Connective Tissue, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Myoepithelial cell, Soft tissue, Middle Aged, Toes, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Acral soft tissue tumors are common neoplasms, a subset of which pose a diagnostic challenge. We report 10 cases of a previously unrecognized acral benign soft tissue tumor. These tumors arose on the fingers and toes and involved bone in half of cases. Histologically, the tumors were lobulated and displayed an abundant stroma made of variable fibrous, chondroid and myxoid material reminiscent of cartilaginous or myoepithelial differentiation. Tumor cells harbored small round to reniform nuclei with clear chromatin and inconspicuous nucleoli along with scant eosinophilic cytoplasm. The cells were mostly arranged haphazardly in the stroma but also in small clusters. No mitotic activity was detected. No specific feature was identified in recurrent cases. By immunohistochemistry, the cells consistently stained for CD34 (10/10), ERG (9/10), and SOX9 (7/10). Whole RNA sequencing identified a previously undescribed recurrent in frame THBS1-ADGRF5 gene fusion in all cases. The transcript was confirmed by RT-PCR and was not found in the control group of mimickers including soft tissue chondromas. We propose the name of Acral FibroChondroMyxoid Tumors for this new entity.
Published: 2020

41. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

Author: Le Meur, Yannick, Badet, Lionel, Essig, Marie, Thierry, Antoine, Büchler, Matthias, Drouin, Sarah, Deruelle, Charles, Morelon, Emmanuel, Pesteil, Francis, Delpech, Pierre-Olivier, Boutin, Jean-Michel, Renard, Felix, Barrou, Benoit, Delpech, Pierre‐Olivier, Boutin, Jean‐Michel, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'urologie [Hôpital Edouard-Herriot, CHU-HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service d'Urologie [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), CHRU de Brest, service de chirurgie urologique et de la transplantation reinale (CHU - BREST - Urologie), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service d'urologie [CHU de Poitiers], Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [Poitiers], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, delayed graft function (DGF), Organ Preservation Solutions, 030232 urology & nephrology, Ischemia, Urology, Cold storage, Renal function, kidney transplantation/nephrology, 030230 surgery, Kidney, clinical research/practice, Cold Ischemia Time, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, organ transplantation in general, Pharmacology (medical), Adverse effect, Transplantation, Machine perfusion, business.industry, Graft Survival, clinical trial, Organ Preservation, medicine.disease, Kidney Transplantation, Thrombosis, Tissue Donors, 3. Good health, Oxygen, Perfusion, ischemia reperfusion injury (IRI), [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.
Published: 2020

42. Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

Author: Aurélia Poujois, Rodolphe Sobesky, Wassilios G. Meissner, Anne-Sophie Brunet, Emmanuel Broussolle, Chloé Laurencin, Laurence Lion-François, Olivier Guillaud, Alain Lachaux, François Maillot, Jérémie Belin, Ephrem Salamé, Claire Vanlemmens, Bruno Heyd, Céline Bellesme, Dalila Habes, Christophe Bureau, Fabienne Ory-Magne, Pascal Chaine, Jean-Marc Trocello, Daniel Cherqui, Didier Samuel, Victor de Ledinghen, Jean-Charles Duclos-Vallée, France Woimant, National reference Centre for Wilson's Disease [Paris] (CRMR Wilson), Service de neurologie [Univ. Paris VII], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, Département d'hépatologie, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe de Recherche en Economie Théorique et Appliquée (GREThA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Badji Mokhtar de Annaba, CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Hôpital Purpan [Toulouse], and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, Liver transplantation, Severity of Illness Index, Disability Evaluation, Young Adult, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Hepatolenticular Degeneration, Liver Function Tests, Modified Rankin Scale, Internal medicine, Severity of illness, Humans, Medicine, Survival rate, Retrospective Studies, medicine.diagnostic_test, business.industry, Parkinsonism, Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, Liver Transplantation, 3. Good health, Survival Rate, Female, 030211 gastroenterology & hepatology, Neurology (clinical), business, Liver function tests, 030217 neurology & neurosurgery
Abstract: ObjectiveTo evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation.MethodsFrench patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed.ResultsEighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p< 0.0001 andp= 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p= 0.0007). Severe sepsis (p= 0.011) and intensive care unit admission (p= 0.001) before LT were significantly associated with death.ConclusionsLT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk.Classification of evidenceThis study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
Published: 2020

43. Criteria for inclusion in programs of functional restoration for chronic low back pain: Pragmatic Study

Author: Marina Assadourian, Laure Gossec, Bruno Fautrel, Johann Beaudreuil, B. Duplan, Sophia Ascione, Pierre Letellier, Laetitia Morardet, Arnaud Dupeyron, Florian Bailly, Nada Ibrahim-Nasser, Isabelle Griffoul, Antoine Potel, Myrianne Le Ralle, Violaine Foltz, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Euromov (EuroMov), Université de Montpellier (UM), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [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), and Herrada, Anthony
Subjects: Male, 030506 rehabilitation, Chronic pain, Anxiety, Hospital Anxiety and Depression Scale, 0302 clinical medicine, Medicine, Orthopedics and Sports Medicine, Practice Patterns, Physicians', 10. No inequality, Referral and Consultation, Pain Measurement, Public health, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Depression, Rehabilitation, Middle Aged, Combined Modality Therapy, 3. Good health, Oswestry Disability Index, Sick leave, Chronic low back pain, Female, France, Sick Leave, medicine.symptom, 0305 other medical science, Adult, medicine.medical_specialty, Referral, 03 medical and health sciences, Humans, Exercise, Physical activity, business.industry, Patient Selection, Odds ratio, medicine.disease, Cross-Sectional Studies, Logistic Models, Multivariate Analysis, Physical therapy, Observational study, Self Report, business, Low Back Pain, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: International audience; Background: Individuals with chronic low back pain (cLBP) may benefit from multimodal functional restoration programs (FRPs).Objective: The aim of this study was to analyze characteristics of individuals with cLBP who were referred or not to an FRP. Because cLBP is a bio-psycho-social disorder, medical and social parameters were analysed.Methods: This was an observational cross-sectional study performed in 2017 in 6 tertiary centres in France. Consecutive individuals with cLBP visiting a rheumatologist or physical medicine and rehabilitation physician were included. Individuals referred or not to an FRP were compared by demographic characteristics, duration of sick leave over the past year, self-reported physical activity>1h/week, pain (numeric rating scale 0-10), anxiety/depression (Hospital Anxiety and Depression Scale), disability (Oswestry Disability Index) and kinesiophobia (Tampa Kinesiophobia Scale). Univariate and multivariate logistic regression analyses were performed, estimating odds ratios (ORs) and 95% confidence intervals (CIs).Results: We included 147 individuals with cLBP. The mean (SD) age was 49 (12) years and 88 (60%) were women; 58 (38%) were referred to an FRP. On multivariate analysis, referral to an FRP was associated with reduced pain level (OR: 0.95, 95% CI: 0.91-0.99, for each 1-point increase in pain score), self-reported lack of physical activity (OR: 0.84, 95% CI: 0.72-0.98) and longer sick leave (OR: 1.03, 95% CI: 1.01-1.05, for 30 more days of sick leave).Conclusion: In this multicentric observational study, referral to an FRP was linked to pain, self-reported physical activity and sick leave but not medical characteristics assessed. These findings confirm the bio-psycho-social approach of FRPs for cLBP.
Published: 2020

44. Current results of left ventricular assist device therapy in France: the ASSIST-ICD registry

Author: Hoang Minh Tam, Marylou Para, Olivier Chavanon, Clément Delmas, Marie Cecile Bories, Constance Verdonk, Vlad Gariboldi, Magali Michel, Fabrice Colas, Marie Bielefeld, Amedeo Anselmi, Martin Kloeckner, Jean-Philippe Verhoye, Thierry Bourguignon, André Vincentelli, Stéphane Boulé, Fabrice Vanhuyse, Michel Kindo, Julien Guihaire, Camille Dambrin, Annette Belin, Costin Radu, Nicolas D'Ostrevy, Hugues Blangy, Jérôme Jouan, Jean-François Obadia, Pierre-Yves Litzler, Vincent Galand, Gerard Babatasi, Edeline Pelcé, Laurent Barandon, Mathieu Pernot, Benjamin Duband, Philippe Rouvière, Philippe Gaudard, Nicolas Lellouche, Thomas Senage, Erwan Flecher, Aude Boignard, Fabien Garnier, Raphaël P. Martins, Matteo Pozzi, Frédéric Anselme, Thibaud Genet, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Les Hôpitaux Universitaires de Strasbourg (HUS), 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), Service de chirurgie thoracique et cardio-vasculaire, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Université de Montpellier (UM), Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Michallon, Clinique de chirurgie cardiaque, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Service de cardiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Service de chirurgie cadiovasculaire et thoracique [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), Hôpital Henri Mondor, CHU Henri Mondor, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Clermont-Ferrand, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes], Fédération Française de Cardiologie, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor [Créteil], and MORNET, Dominique
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Temporal trends, Outcomes, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Clinical endpoint, Humans, Cumulative incidence, Registries, Retrospective Studies, Heart Failure, business.industry, Cardiogenic shock, General Medicine, equipment and supplies, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Surgery, Transplantation, Treatment Outcome, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Ventricular assist device, Life support, Left ventricular assist devices, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Heart-Assist Devices, Implant, Cardiology and Cardiovascular Medicine, business, Destination therapy
Abstract: OBJECTIVES Our goal was to provide a picture of left ventricular assist device (LVAD) activity in France between 2007 and 2016 based on the multicentric ASSIST-ICD registry. METHODS We retrospectively collected 136 variables including in-hospital data, follow-up survival rates and adverse events from 671 LVAD recipients at 20 out of 24 LVAD implant centres in France. The average follow-up time was 1.2 years (standard deviation: 1.4); the total follow-up time was 807.5 patient-years. RESULTS The included devices were the HeartMate II®, HeartWare LVAS® or Jarvik 2000®. The overall likelihood of being alive while on LVAD support or having a transplant (primary end point) at 1, 2, 3 and 5 years postimplantation was 65.2%, 59.7%, 55.9% and 47.7%, respectively, given a cumulative incidence of 29.2% of receiving a transplant at year 5. At implantation, 21.5% of patients were on extracorporeal life support. The overall rate of cardiogenic shock at implantation was 53%. The major complications were driveline infection (26.1%), pump pocket or cannula infection (12.6%), LVAD thrombosis (12.2%), ischaemic (12.8%) or haemorrhagic stroke (5.4%; all strokes 18.2%), non-cerebral haemorrhage (9.1%) and LVAD exchange (5.2%). The primary end point (survival) was stratified by age at surgery and by the type of device used, with inference from baseline profiles. The primary end point combined with an absence of complications (secondary end point) was also stratified by device type. CONCLUSIONS The ASSIST-ICD registry provides a real-life picture of LVAD use in 20 of the 24 implant centres in France. Despite older average age and a higher proportion of patients chosen for destination therapy, survival rates improved compared to those in previous national registry results. This LVAD registry contrasts with other international registries because patients with implants have more severe disease, and the national policy for graft attribution is distinct. We recommend referring patients for LVAD earlier and suggest a discussion of the optimal timing of a transplant for bridged patients (more dismal results after the second year of support?).
Published: 2020

45. Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double‐blind, controlled study

Author: P. Bernard, Sophie Leducq, F. Boralevi, A. Le Gouge, Loïc Vaillant, F. Pascal, Camille Francès, Jean-Christophe Fricain, S. Agbo-Godeau, Mahtab Samimi, T. Passeron, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Stomatologie et Chirurgie Maxillo-facial [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), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], 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), French Ministry of Social Affairs and Health (French National Programme of Clinical Research [PHRC]), 2005, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Food intake, medicine.medical_specialty, Administration, Topical, [SDV]Life Sciences [q-bio], Betamethasone dipropionate, Dermatology, Betamethasone, Ointments, Double blind, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, medicine, Humans, Psoriasis, Adverse effect, Sirolimus, business.industry, 030206 dentistry, Odds ratio, 3. Good health, Treatment Outcome, Infectious Diseases, Clinical recurrence, Neoplasm Recurrence, Local, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, After treatment, Lichen Planus, Oral, medicine.drug
Abstract: International audience; Background Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series.Objectives To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial.Methods Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase(R) or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events.Results During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis).Conclusion Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.
Published: 2020

46. Ein Prototyp der transienten Hochfrequenz-Elastografie zur Beurteilung der Haut (Dermis) -Fibrose: Eine diagnostische Studie bei Patienten mit venöser Insuffizienz und Kontrollprobanden

Author: Emilie Vierron, Laurent Machet, Thibault Kervarrec, Frédéric Ossant, Frédéric Patat, Geoffroy Faleweei, Caroline Chartier, Paul-Armand Dujardin, Gabriela Georgescou, Valérie Gissot, Marie-Christine Machet, Valerie Tauveront, Yassine Mofid, Annabel Maruani, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie (TOURS - Radio), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHRU Tours], Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Liver Cirrhosis, Skin score, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Physical examination, chronic venous disorders - high frequency transient elastography - skin fibrosis - dermis thickness - young’s Modulus, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Dermis, Fibrosis, Humans, Medicine, Radiology, Nuclear Medicine and imaging, In patient, Skin, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Ultrasound, medicine.disease, medicine.anatomical_structure, ROC Curve, Venous Insufficiency, Elasticity Imaging Techniques, Radiology, business, Transient elastography, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: High-frequency transient elastography (HF-TE) is a noninvasive technique for assessing shear-wave speed and finally elasticity in thin tissue such as the skin. It has never been validated for monitoring fibrotic skin diseases. The purpose was to evaluate the potential of HF-TE to assess skin fibrosis in patients with chronic venous disorders (CVD). This clinical study enrolled 48 patients at various stages of CVD and 48 paired healthy volunteers. Subjects underwent a clinical examination with an evaluation of Rodnan's fibrosis skin score. We studied the dermis thickness measured using ultrasound (US) and elasticity measurements using cutometer and HF-TE studied according to 3 cutaneous zones positioned on the leg. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnosis performance for a combined parameter (PRL) based on a logistic regression model using both elasticity and dermal thickness. Patients with CVD had significantly higher values of skin elasticity than healthy subjects, 134.5 kPa and 132.1 kPa vs. 91.3 kPa, respectively. The dermis thickness also increased with escalation in CVD stage for all studied zones. The PRL parameter had an AUC value of 0.79 for all zones and stages of CVD clustered. The discriminating power of PRL increased with escalation of the CVD stage; with an AUC value of up to 0.89 for evolved stages, and a sensitivity and specificity of 0.79 and 0.89, respectively. HF-TE, coupled with a US measurement of dermis thickness, made it possible to propose a new biomarker, which proved to be a good diagnostic tool for skin fibrosis.ZIEL: Die transiente Hochfrequenz-Elastografie (HF-TE), eine nichtinvasive Technik zur Beurteilung der Scherwellengeschwindigkeit und nicht zuletzt der Elastizität von dünnem Gewebe wie der Haut, wurde noch nie für das Monitoring fibrotischer Hautkrankheiten validiert. Ziel war es, die Leistungsfähigkeit der HF-TE bei der Beurteilung der Hautfibrose bei Patienten mit chronisch-venöser Insuffizienz (CVI) zu untersuchen. Für diese klinische Studie wurden 48 Patienten mit CVI in verschiedenen Stadien zusammen mit 48 gesunden Probanden gepaart aufgenommen. Bei allen wurde eine klinische Untersuchung mit dem Rodnan-Fibrose-Hautscore durchgeführt. Wir untersuchten die Dermisdicke mittels Ultraschalls (US) und führten Elastizitätsbestimmungen mit dem Cutometer und der HF-TE an 3 Hautbereichen am Bein durch. Die Fläche unter der ROC-Kurve (AUC) wurde berechnet, um die diagnostische Leistung für einen kombinierten Parameter (PRL) zu bewerten, der auf einem logistischen Regressionsmodell unter Einbeziehung sowohl der Elastizität als auch der Hautdicke basierte. Patienten mit CVI hatten signifikant höhere Werte der Hautelastizität mit 134,5 kPa und 132,1 kPa gegenüber gesunden Probanden mit 91,3 kPa. Die Dermisdicke nahm mit dem Anstieg der CVI-Stadien in allen untersuchten Bereichen zu. Der PRL hatte einen AUC-Wert von 0,79 für alle Bereiche und Stadien des CVI-Clusters. Die Trennschärfe des PRL nahm mit dem Anstieg der CVI-Stadien zu; mit einem AUC-Wert von bis zu 0,89 für fortgeschrittene Stadien sowie einer Sensitivität von 0,79 und einer Spezifität von 0,89. Die HF-TE zusammen mit der US-Bestimmung der Dermisdicke erwies sich als gutes Diagnosewerkzeug bei Hautfibrose und kann als möglicher neuer Biomarker dienen.
Published: 2020

47. Immunobiology of Merkel cell carcinoma

Author: Antoine Touzé, Thibault Kervarrec, Mahtab Samimi, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pathologie [CHRU Tours], Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0301 basic medicine, Cancer Research, Skin Neoplasms, Carcinogenesis, [SDV]Life Sciences [q-bio], Cell of origin, medicine.medical_treatment, Merkel cell polyomavirus, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, medicine, Carcinoma, Animals, Humans, Immune Evasion, biology, Merkel cell carcinoma, business.industry, Immunotherapy, medicine.disease, biology.organism_classification, 3. Good health, Carcinoma, Merkel Cell, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Skin cancer, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Purpose of review: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, which is associated in 80% of cases with the Merkel cell polyomavirus (MCPyV). Advanced stages respond to immune checkpoint inhibitors in 50% of cases. Major issues remain unanswered regarding its oncogenesis and optimal treatment.Recent findings: MCPyV-negative and MCPyV-positive MCCs have been hypothesized to derive from distinct cells, although the cell of origin remains a matter of debate. The crucial role the MCPyV small T oncoprotein was recently confirmed by its ability to inactivate p53, together with its contribution to the metastatic progression. In advanced cases, tumoral microenvironment may adequately predict responses to immunotherapies, and several mechanisms of primary and secondary resistance have been investigated.Summary: Identifying the mechanisms of oncogenesis allow experimentation of new therapeutic targets, which remain mandatory even at the era of immunotherapies. Although new insights in the mechanisms of primary and secondary resistance pave the way for development of further immunotherapy strategies, neoadjuvant strategies may challenge our whole approach of the disease.
Published: 2020

48. Management of neuropathic pain induced by surgery: Review of the literature by a group of experts specialized in pain management, anesthesia and surgery

Author: Gisèle Pickering, M. Navez, T. Lansaman, Alain Serrie, M. Prudhomme, Serge Perrot, E. Viel, Jacques Medioni, Michel Lantéri-Minet, C. Delorme, A. Legras, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Aunay-Bayeux (CH Aunay-Bayeux), Hôpital Raymond Poincaré [AP-HP], Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre d'Evaluation et de traitement de la douleur, AP-HP, Hôpital Cochin, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CCSD, Accord Elsevier, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Adult, medicine.medical_specialty, Lidocaine, Epidemiology, Breast surgery, medicine.medical_treatment, MESH: Neuralgia, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Pain Measurement, Neuropathic pain, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Risk Factors, Kinesitherapy, medicine, Humans, Pain Management, MESH: Pain, Postoperative, Neurostimulation, Pain Measurement, Pain, Postoperative, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, MESH: Adult, Chronic postsurgical neuropathic pain, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Pain management, Expert group, 3. Good health, Surgery, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Risk factors, 030220 oncology & carcinogenesis, Anesthesia, Neuralgia, 030211 gastroenterology & hepatology, Capsaicin, business, MESH: Pain Management, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Chronic postsurgical neuropathic pain (CPSNP) is frequent. While prevalence varies considerably according to type of operation and means of evaluation, it can reach 37% following breast surgery. Identification of risk factors related to the procedure and to the patient and taking into account the development of new, minimally invasive surgical techniques is increasingly nerve-sparing and reduces the likelihood of injury. CPSNP diagnosis in daily practice is facilitated by simple and quickly usable tools such as the NP4 4-question test. Management is based on pharmacological (analgesics, antiepileptics, antidepressants, local anesthetics) and non-pharmacological (kinesitherapy, neurostimulation, psychotherapy) approaches. In light of the present review of the literature, the authors, who constitute an expert group specialized in pain management, anesthesia and surgery, express their support for topical treatments (lidocaine, capsaicin) in treatment of localized postsurgical neuropathic pain in adults.
Published: 2020

49. Ophthalmological findings in children with autism spectrum disorder

Author: Joëlle Malvy, Frédérique Bonnet-Brilhault, Marine Siwiaszczyk, Magali Batty, R.K. Khanna, Sophie Arsene, Klara Kovarski, Pierre-Jean Pisella, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, Pediatrics, medicine.medical_specialty, Visual acuity, genetic structures, Visual Acuity, Diagnostic Techniques, Ophthalmological, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, mental disorders, Intellectual disability, medicine, Humans, 0501 psychology and cognitive sciences, Prospective Studies, Autism spectrum disorder, Child, Strabismus, Prospective cohort study, Children, Eye diseases, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, medicine.disease, Sensory Systems, Social relation, Clinical trial, Refractive errors, Ophthalmology, Child, Preschool, [SCCO.PSYC]Cognitive science/Psychology, 030221 ophthalmology & optometry, Eye disorder, Female, medicine.symptom, business, 050104 developmental & child psychology
Abstract: Purpose Eye pathology could be related to atypical visual behaviours and impaired social communication through visual cues in children with autism spectrum disorder (ASD). The main purpose of this prospective study was to assess ophthalmological disorders in children with ASD and to investigate the relationships with intellectual disability (ID) and ASD severity. Methods In this prospective study, comprehensive ophthalmological and oculomotor examinations were performed. ASD severity and verbal and performance intelligence quotients were determined using adapted scales. These clinical data were compared between groups of children based on the presence or absence of ophthalmological disorders and the achievement or not of visual acuity (VA) testing by using non-parametric statistical tests. Results Amongst a sample of 51 children, ophthalmological disorders were found in 39% of cases, with 35% having significant refractive errors and 10% presenting with strabismus. Children with ASD and ophthalmological disorders had significantly lower verbal (29.8 +/- 14.7 compared with 44.3 +/- 21.5; p = 0.010) and performance quotients (57.8 +/- 18.3 compared with 67.59 +/- 20; p = 0.049) but no significant result was found between the presence of ophthalmological disorders and ASD severity, level of communication and social contact, or modulating behaviour when changes occur. Children who did not achieve monocular VA testing (39%) had significantly lower verbal (25.1 +/- 9.7 compared with 46.1 +/- 20.9; p < 0.001) and performance quotients (52.7 +/- 17 compared with 69.8 +/- 18.8; p = 0.001), also presented higher social interaction impairment (p = 0.002), and expressed more important behavioural signs (p = 0.007). Conclusions Ophthalmological disorders are frequently found in children with ASD, especially in those with ID. Ophthalmologists and child psychiatrists should pay attention to perform ophthalmological examination in children with ASD since eye disorders might remain undetected. A comprehensive examination by a paediatric ophthalmologist would help to improve the individual clinical description and the global intervention.
Published: 2020

50. 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

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

1,811 results on '"CHRU Tours"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources