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1. MIF Involvement in AML (MIFAML)

Author: Institut National de la Santé Et de la Recherche Médicale, France, CHRU Tours: centre Hospitalier Universitaire de Tours, and Gustave Roussy, Cancer Campus, Grand Paris
Published: 2022

2. Low serum neutralization of Omicron variants a month after AZD7442 prophylaxis initiation

Author: Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Lévy, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio]
Published: 2023

3. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller

Author: Molinos-Albert, Luis, Baquero, Eduard, Bouvin-Pley, Mélanie, Lorin, Valerie, Charre, Caroline, Planchais, Cyril, Dimitrov, Jordan, Monceaux, Valérie, Vos, Matthijn, Group, Anrs Visconti, Hocqueloux, Laurent, Berger, Jean-Luc, Seaman, Michael, Braibant, Martine, Avettand-Fenoël, Véronique, Sáez-Cirión, Asier, Mouquet, Hugo, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Plateforme technologique Nanoimagerie / Nanoimaging Technological Platform, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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), 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 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), Réservoirs viraux et contrôle immunitaire / Viral reservoirs and immune control, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Hôpital La Source [Orléans] (HLSO), Centre Hospitalier Universitaire de Reims (CHU Reims), Beth Israel Deaconess Medical Center [Boston] (BIDMC), and Harvard Medical School [Boston] (HMS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the 324GDIR327 V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies.
Published: 2023

4. Performance of French medico-administrative databases in epidemiology of infectious diseases: a scoping review

Author: Tassi, Marc-Florent, Le Meur, Nolwenn, Stéfic, Karl, Grammatico-Guillon, Leslie, 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), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)
Subjects: Medico-administrative data, Scoping review, Validation studies, Public Health, Environmental and Occupational Health, Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SNDS, Capture recapture studies
Abstract: The development of medico-administrative databases over the last few decades has led to an evolution and to a significant production of epidemiological studies on infectious diseases based on retrospective medical data and consumption of care. This new form of epidemiological research faces numerous methodological challenges, among which the assessment of the validity of targeting algorithm. We conducted a scoping review of studies that undertook an estimation of the completeness and validity of French medico-administrative databases for infectious disease epidemiological research. Nineteen validation studies and nine capture-recapture studies were identified. These studies covered 20 infectious diseases and were mostly based on the evaluation of hospital claimed data. The evaluation of their methodological qualities highlighted the difficulties associated with these types of research, particularly those linked to the assessment of their underlying hypotheses. We recall several recommendations relating to the problems addressed, which should contribute to the quality of future evaluation studies based on medico-administrative data and consequently to the quality of the epidemiological indicators produced from these information systems.
Published: 2023

5. Version francaise des recommandations de la declaration d'Ottawa sur la conception et la conduite ethique d'essais randomises en clusters, dans le contexte legislatif francais

Author: A. Bourmaud, A. Fianu, C. Kervan, A. Verga-Gérard, I. Fournel, A. Dumas, J. Mancini, F. Alla, A. Omorou, B. Giraudeau, Centre d'Investigation Clinique 1426 (CIC 1426), 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), Hôpital Robert Debré, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Sud Saint Pierre [Ile de la Réunion], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut des sciences de la santé publique [Marseille] (ISSPAM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), 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), 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Ethics, Informed Consent, Epidemiology, Cluster randomized trial, Public Health, Environmental and Occupational Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; INTRODUCTION: There is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement". METHOD: . The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group. RESULTS: . This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples. CONCLUSION: Without interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.; INTRODUCTION : Il existe une littérature croissante sur les défis éthiques soulevés par les essais randomisés en clusters (ou en grappes). Cette spécificité n'est pas prise en compte dans les textes réglementaires qui régissent la recherche, ce qui est source de difficultés pour les chercheurs utilisant ces schémas expérimentaux. La Déclaration d'Ottawa (Weijer et al. 2012) vise à fournir des conseils détaillés sur l’éthique de la conception, de la conduite et de l’évaluation des essais en clusters. Elle a pour objectif d'aider l'ensemble des acteurs de la recherche (parties prenantes et décideurs) à prendre des décisions éclairées en termes d’éthique relative à la particularité de ces schémas expérimentaux. Il semble que cette déclaration internationale ne soit pas assez accessible auprès de l'ensemble des acteurs français de la recherche en santé. L'objectif de cet article est de proposer à ces professionnels une traduction française de l’« Ottawa Statement », contextualisée et illustrée. METHODE : Le groupe de travail « Design complexe » du réseau RECaP (Recherche en épidémiologie clinique et en santé publique) a réalisé ce travail. Une première version a été discutée par les auteurs au travers de plusieurs réunions. Elle a été complétée par des explications contextuelles et par des exemples d’études françaises actuellement menées par les auteurs. La dernière version a été obtenue par consensus et validée par le groupe. RESULTATS : Ce travail présente les 15 recommandations regroupées en sept grandes questions : quelle justification pour le design en clusters ? Comment soumettre à un comité d’éthique ? Comment identifier les participants à la recherche ? Quand et comment obtenir un consentement éclairé ? Qui sont les personnes référentes ? Comment évaluer les bénéfices et les risques ? Comment protéger les personnes vulnérables ? Chacune de ces recommandations porte spécifiquement sur les essais en clusters. Ces recommandations sont expliquées et détaillées au travers d'exemples. CONCLUSION : Ce travail permet de fournir un cadre pour la mise en place, la conduite et l’évaluation éthique des essais randomisés en clusters en France. Sans ingérence dans les lois actuelles françaises. Dans le contexte actuel, il est indispensable que l'ensemble des groupes concernés puissent appuyer leurs décisions sur des recommandations en accord avec les principes élémentaires de l’éthique de la recherche en santé.
Published: 2023

6. Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool

Author: Tran Mau-Them, Frédéric, Delanne, Julian, Denommé-Pichon, Anne-Sophie, Safraou, Hana, Bruel, Ange-Line, Vitobello, Antonio, Garde, Aurore, Nambot, Sophie, Bourgon, Nicolas, Racine, Caroline, Sorlin, Arthur, Moutton, Sébastien, Marle, Nathalie, Rousseau, Thierry, Sagot, Paul, Simon, Emmanuel, Vincent-Delorme, Catherine, Boute, Odile, Colson, Cindy, Petit, Florence, Legendre, Marine, Naudion, Sophie, Rooryck, Caroline, Prouteau, Clément, Colin, Estelle, Guichet, Agnès, Ziegler, Alban, Bonneau, Dominique, Morel, Godelieve, Fradin, Mélanie, Lavillaureix, Alinoé, Quelin, Chloé, Pasquier, Laurent, Odent, Sylvie, Vera, Gabriella, Goldenberg, Alice, Guerrot, Anne-Marie, Brehin, Anne-Claire, Putoux, Audrey, Attia, Jocelyne, Abel, Carine, Blanchet, Patricia, Wells, Constance F., Deiller, Caroline, Nizon, Mathilde, Mercier, Sandra, Vincent, Marie, Isidor, Bertrand, Amiel, Jeanne, Dard, Rodolphe, Godin, Manon, Gruchy, Nicolas, Jeanne, Médéric, Schaeffer, Elise, Maillard, Pierre-Yves, Payet, Frédérique, Jacquemont, Marie-Line, Francannet, Christine, Sigaudy, Sabine, Bergot, Marine, Tisserant, Emilie, Ascencio, Marie-Laure, Binquet, Christine, Duffourd, Yannis, Philippe, Christophe, Faivre, Laurence, Thauvin-Robinet, Christel, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon) (UF6254), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Nord, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de référence Maladies Rares CLAD-Ouest [Rennes], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Génétique Clinique, Hôpital Femme Mère Enfant, Centre Hospitalier Universitaire de Lyon, Service de Gynécologie et Obstétrique [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Génétique et Centre de Diagnostic Anténatal, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Equipe Maladies Génétiques de L'Enfant et de L'Adulte, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Embryology and genetics of human malformation, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Génétique Médicale et Clinique, Hôpital Necker-Enfants Malades, Unité Fonctionnelle de Génétique Médicale, Cytogénétique, Génétique Médicale et Biologie de La Reproduction, Centre Hospitalier Intercommunal Poissy-Saint-Germain-en-Laye, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, UMR 1253 IBrain Imagerie & Cerveau Equipe 2 : 'Neurogénomique & Physiopathologie neuronale' (NPN), 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), CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Médicale, Pôle Femme, Mère, Enfants CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Pôle Femme, Mère, Enfants, CHU de La Réunion-GH Sud Réunion-Saint-Pierre-CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Génétique Clinique Prénatale, Département de Génétique Médicale, Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), and This work was supported by grants from Dijon University Hospital, the ISITE-BFC (PIA ANR), the European Union through the FEDER programs, and the AnDDI-Rares network for ES performed in this study.
Subjects: prenatal, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, chromosomal microarray, exome sequencing (ES), diagnostic yield, Genetics, Molecular Medicine, fetal, Genetics (clinical)
Abstract: Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.
Published: 2023

7. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Author: Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), 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), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), 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 Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio]
Abstract: Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
Published: 2023

8. Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study

Author: Sandrine Kerneis, Jean-Michel Escoffre, John J. Galvin, Ayache Bouakaz, Antoine Presset, Corentin Alix, Edward Oujagir, Antoine Lefèvre, Patrick Emond, Hélène Blasco, David Bakhos, Service ORL et chirurgie cervico-faciale [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), The House Institute Foundation [Los Angeles, CA, USA] (THIF), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), UMR 1253 IBrain Imagerie & Cerveau Equipe 2 : 'Neurogénomique & Physiopathologie neuronale' (NPN), 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), House Institute Foundation (HIF-121-5), and Escoffre, Jean-Michel
Subjects: inner ear, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Pharmaceutical Science, sonoporation, perilymph, round window membrane, metabolomics
Abstract: International audience; Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker® microbubbles (MBs; VisualSonics—Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 108 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.
Published: 2023

9. 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

10. 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

11. 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

12. Exploring Radiologic Criteria for Glioma Grade Classification on the BraTS Dataset

Author: Benoit Tremblais, Benoit Gianelli, Pascal Bourdon, Jean-Philippe Cottier, Rémy Guillevin, Claire Boutet, Carole Guillevin, Jean-Noël Vallée, Christine Fernandez-Maloigne, Paul Dequidt, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers - Faculté de Sciences fondamentales et appliquées, Université de Poitiers, Laboratoire commun Imagerie Métabolique Multi-Noyaux Multi-Organes (I3M), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Siemens Healthineers, Digital Services, Digital Technology and Innovation, Synthèse et analyse d'images (XLIM-ASALI), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques et Applications (LMA-Poitiers), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Amiens-Picardie, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: 0206 medical engineering, Population, Biomedical Engineering, Biophysics, 02 engineering and technology, Prediction score, World health, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Histogram, Glioma, Machine learning, Classifier (linguistics), Glioma grading, Medicine, education, education.field_of_study, Radiomics, business.industry, Virtual biopsy, Pattern recognition, medicine.disease, 020601 biomedical engineering, 3. Good health, Support vector machine, Automatic classification, Artificial intelligence, business
Abstract: International audience; Objectives: Glioma grading using maching learning on magnetic resonance data is a growing topic. According to the World Health Organization (WHO), the classification of glioma discriminates between low grade gliomas (LGG), grades I, II; and high grade gliomas (HGG), grades III, IV, leading to major issues in oncology for therapeutic management of patients. A well-known dataset for machine-based grade prediction is the MICCAI Brain Tumor Segmentation (BraTS) dataset. However this dataset is not divided into WHO-defined LGG and HGG, since it combines grades I, II and III as “lower grades gliomas”, while its HGG category only presents grade IV glioblastoma multiform. In this paper we want to train a binary grade classifier and investigate the consistency of the original BraTS labels with radiologic criteria using machine-aided predictions.Material and methods: Using WHO-based radiomic features, we trained a SVM classifier on the BraTS dataset, and used the prediction score histogram to investigate the behaviour of our classifier on the lower grade population. We also asked 5 expert radiologists to annotate BraTS images between low (as opposed to lower) grade and high grade glioma classes, resulting in a new groundtruth.Results: Our first training reached 84.1% accuracy. The prediction score histogram allows us to identify the radiologically high grade patients among the original lower grade population of the BraTS dataset. Training another SVM on our new radiologically WHO-aligned groundtruth shows robust performances despite important class imbalance, reaching 82.4% accuracy.Conclusion: Our results highlight the coherence of radiologic criteria for low grade versus high grade classification under WHO terms. We also show how the histogram of prediction scores and crossed prediction scores can be used as tools for data exploration and performance evaluation. Therefore, we propose to use our radiological groundtruth for future development on binary glioma grading.
Published: 2021

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Inhaled bacteriophage therapy in a porcine model of pneumonia caused by <scp> Pseudomonas aeruginosa </scp> during mechanical ventilation

Author: Céline Barc, Mickaël Riou, Yonatan Perez, Antoine Guillon, Jeoffrey Pardessus, Laurent Mereghetti, Elsa Bodier-Montagutelli, Emilie Dalloneau, Camille Thorey, Nathalie Heuzé-Vourc'h, Sandrine Le Guellec, Laurent Vecellio, Maria Cabrera, Youenn Jouan, Guillaume L'Hostis, Cindy Fevre, 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), Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Pherecydes Pharma, 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-virologie [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DTF-Aerodrug, DTF, public grant overseen by the Direction Générale des Armées (DGA)-France - Project RAPID—Pneumophage grant, Chanteloup, Nathalie Katy, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, 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: Phage therapy, Swine, medicine.drug_class, medicine.medical_treatment, Antibiotics, medicine.disease_cause, pseudomonas aeruginosa, Microbiology, Bacteriophage, Mice, 03 medical and health sciences, 0302 clinical medicine, bacteriophage, In vivo, medicine, Animals, pneumonia, Bacteriophages, Pseudomonas Infections, Phage Therapy, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, Mechanical ventilation, inhalation, 0303 health sciences, ventilation-associated pneumonia, biology, 030306 microbiology, Pseudomonas aeruginosa, business.industry, biology.organism_classification, medicine.disease, Respiration, Artificial, 3. Good health, Pneumonia, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030228 respiratory system, Lytic cycle, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pseudomonas Phages, business
Abstract: International audience; Background and purpose: Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models. We used a pig model of pneumonia caused by P. aeruginosa that recapitulates essential features of human disease to study the antimicrobial efficacy of nebulized-phage therapy.Experimental approach: (i) Lysis kinetic assays were performed to evaluate in vitro phage antibacterial efficacy against P. aeruginosa and select relevant combinations of lytic phages. (ii) The efficacy of the phage combinations was investigated in vivo (murine model of P. aeruginosa lung infection). (iii) We determined the optimal conditions to ensure efficient phage delivery by aerosol during mechanical ventilation. (iv) Lung antimicrobial efficacy of inhaled-phage therapy was evaluated in pigs, which were anesthetized, mechanically ventilated and infected with P. aeruginosa.Key results: By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, which resulted in a rapid and marked reduction in P. aeruginosa density (1.5 Log reduction, p
Published: 2021

23. CT-based volumetric assessment of rotator cuff muscle in shoulder arthroplasty preoperative planning

Author: Luc Favard, Valérie Burdin, François Boux de Casson, Jean-David Werthel, George S. Athwal, Gilles Walch, Jean Chaoui, Hôpital Ambroise Paré [AP-HP], Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Wright Medical/Tornier, Département lmage et Traitement Information (IMT Atlantique - ITI), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Schulich School of Medicine and Dentistry, University of Western Ontario (UWO), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), IMASCAP Shoulder Augmented Surgery (Entreprise) (IMASCAP), Stryker Orthopaedics, Styker, Centre Orthopédique Santy Lyon, Centre Orthopédique Santy - Lyon, Hôpital privé Jean-Mermoz [Lyon] (Ramsay-GDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: medicine.medical_specialty, muscle volume, medicine.medical_treatment, Muscle volume, rotator cuff muscle, occupation ratio, 03 medical and health sciences, 0302 clinical medicine, Atrophy, atrophy, 3d ct scan, Medicine, Balance (ability), Orthopedic surgery, 030222 orthopedics, Preoperative planning, business.industry, Shoulder & Elbow, 3D CT scan, General Engineering, musculoskeletal system, medicine.disease, Rotator cuff muscle, Arthroplasty, fatty infiltration, volumetric analysis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, shoulder arthroplasty, Radiology, Fatty infiltration, business, RD701-811, tangent sign, 030217 neurology & neurosurgery
Abstract: Aims The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561.
Published: 2021

24. Energetic dysfunction in sepsis: a narrative review

Author: Guillaume Voiriot, Mehdi Oualha, Peter Radermacher, Sébastien Preau, Aurelien Flatres, Steve Lancel, Youenn Jouan, Stein Silva, Nicolas de Prost, Lara Zafrani, Eric Azabou, Dominique Vodovar, Jérémie Joffre, Fabrice Huel, Boris Jung, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), CHU Necker - Enfants Malades [AP-HP], CHU Tenon [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), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [San Francisco] (UCSF), University of California, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, CHU Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitätsklinikum Ulm - University Hospital of Ulm, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Système immunitaire et neuroinflammation [CRSA], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [AP-HP], SFB 1149 and GRK 2203/Deutsche Forschungsgemeinschaft, MORNET, Dominique, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Organ dysfunction, Cardiomyopathy, Review, 030204 cardiovascular system & hematology, Mitochondrion, Critical Care and Intensive Care Medicine, Bioinformatics, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Lipid oxidation, Septic shock, medicine, Energetic dysfunction, Immunodeficiency, business.industry, RC86-88.9, Acute kidney injury, Correction, Medical emergencies. Critical care. Intensive care. First aid, medicine.disease, 3. Good health, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, Metabolism, medicine.symptom, business, Infection, Mitochondrial dysfunction
Abstract: BackgroundGrowing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.Main textSepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.ConclusionsRecent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
Published: 2021

25. 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

26. 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

27. 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

28. Outcome of long gap esophageal atresia at 6 years: A prospective case control cohort study

Author: Agate Bourg, Frédéric Gottrand, Benoit Parmentier, Julie Thomas, Anne Lehn, Christian Piolat, Arnaud Bonnard, Rony Sfeir, Julie Lienard, Véronique Rousseau, Myriam Pouzac, Agnès Liard, Philippe Buisson, Aurore Haffreingue, Louis David, Sophie Branchereau, Véronique Carcauzon, Nicolas Kalfa, Marc-David Leclair, Hubert Lardy, Sabine Irtan, François Varlet, Thomas Gelas, Diana Potop, Marie Auger-Hunault, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Strasbourg, Service de chirurgie pédiatrique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Régional d'Orléans (CHRO), CHU Rouen, Normandie Université (NU), CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université Lille Nord (France), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Le Mans (CH Le Mans), Hôpital Lapeyronie [Montpellier] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université de Lille, Inserm, CHU Lille, Centre hospitalier universitaire de Poitiers [CHU Poitiers], Lille Inflammation Research International Center (LIRIC) - U995, Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Centre Hospitalier Universitaire de Nancy [CHU Nancy], Centre Hospitalier Régional d'Orléans [CHRO], Hôpital Lapeyronie [Montpellier] [CHU], Centre hospitalier universitaire de Nantes [CHU Nantes], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], and Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Subjects: [SDV]Life Sciences [q-bio], Pediatrics, Perinatology and Child Health, Surgery, General Medicine
Abstract: International audience; Background data: EA is the most frequent congenital esophageal malformation. Long gap EA remains a therapeutic challenge for pediatric surgeons. A case case-control prospective study from a multi-institutional national French data base was performed to assess the outcome, at age of 1 and 6 years, of long gap esophageal atresia (EA) compared with non-long gap EA/tracheo-esophageal fistula (TEF). The secondary aim was to assess whether initial treatment (delayed primary anastomosis of native esophagus vs. esophageal replacement) influenced mortality and morbidity at ages 1 and 6 years.Methods: A multicentric population-based prospective study was performed and included all patients who underwent EA surgery in France from January 1, 2008 to December 31, 2010. A comparative study was performed with non-long gap EA/TEF patients. Morbidity at birth, 1 year, and 6 years was assessed.Results: Thirty-one patients with long gap EA were compared with 62 non-long gap EA/TEF patients. At age 1 year, the long gap EA group had longer parenteral nutrition support and longer hospital stay and were significantly more likely to have complications both early post-operatively and before age 1 year compared with the non-long gap EA/TEF group. At 6 years, digestive complications were more frequent in long gap compared to non-long gap EA/TEF patients. Tracheomalacia was the only respiratory complication that differed between the groups. Spine deformation was less frequent in the long gap group. There were no differences between conservative and replacement groups at ages 1 and 6 years except feeding difficulties that were more common in the native esophagus group.Conclusions: Long gap strongly influenced digestive morbidity at age 6 years.Keywords: Complications; Dysphagia; Esophageal atresia; Esophageal replacement; Gastro-esophageal reflux disease; Long gap esophageal atresia; Midterm outcomes.
Published: 2022

29. 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

30. 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

31. Intensive care unit-to-unit capacity transfers are associated with increased mortality: no hasty conclusions in the event of a crisis

Author: Benoit Painvin, Stephan Ehrmann, Arnaud W. Thille, Jean-Marc Tadié, 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), None, Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine
Abstract: International audience; Comment on doi: 10.1186/s13613-022-01003-x
Published: 2022

32. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial

Author: Julie Mankikian, Agnès Caille, Martine Reynaud-Gaubert, Marie-Sara Agier, Julien Bermudez, Philippe Bonniaud, Raphael Borie, Pierre-Yves Brillet, Jacques Cadranel, Isabelle Court-Fortune, Bruno Crestani, Marie-Pierre Debray, Emmanuel Gomez, Anne Gondouin, Sandrine Hirschi-Santelmo, Dominique Israel-Biet, Stéphane Jouneau, Karine Juvin, Julie Leger, Mallorie Kerjouan, Charles-Hugo Marquette, Jean-Marc Naccache, Hilario Nunes, Laurent Plantier, Grégoire Prevot, Sébastien Quetant, Julie Traclet, Victor Valentin, Yurdagul Uzunhan, Lidwine Wémeau-Stervinou, Theodora Bejan-Angoulvant, Vincent Cottin, Sylvain Marchand-Adam, CHU Trousseau [Tours], 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 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), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Hôpital Avicenne [AP-HP], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), 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), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, 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), Hôpital Pontchaillou, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier Saint-Joseph [Paris], Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], 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), CHU Grenoble, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Lille, EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), PHRC national, and This study was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique) 2015
Subjects: Pulmonary and Respiratory Medicine, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: BackgroundStandard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first step therapies while rituximab is used as rescue therapy.MethodsIn a randomised, double blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune feature) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinico-biological data and a NSIP-like HRCT pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for six months. The primary endpoint was the change in percent of predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary endpoints included progression-free survival (PFS) up to 6 months and safety.FindingsBetween January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se1.13) in the rituximab+MMF group and −2.01 (se1.17) in the placebo+MMF group (between-group difference, 3.60 [95% CI 0.41 to 6.80]; p=0.0273). PFS was better in the rituximab+MMF group (crude HR 0.47 [95%CI 0.23 to 0.96]; p=0.03). Serious adverse events occurred in 26 patients of the rituximab+MMF group (41%) and in 23 of the placebo+MMF group (39%). Nine infections were reported in the rituximab+MMF group (five bacterial infections, 3 viral infections, 1 other) and four bacterial infections in the placebo+MMF group.InterpretationCombination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must consider the risk of viral infection.
Published: 2023

33. 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

34. Three‐dimensional structures of avian beta‐microseminoproteins: insight from the chicken egg‐specific beta‐microseminoprotein 3 paralog

Author: Bertrand Castaing, Mégane Bregeon, Valérie Labas, Magali Chessé, Karine Loth, Nicolas Guyot, Hervé Meudal, Thierry Moreau, Sophie Réhault-Godbert, Franck Coste, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Biologie des Oiseaux et Aviculture (BOA), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Plate-forme Phénotypage par imagerie in/ex vivo de l'Animal à la Molécule (Plate-forme PIXANIM), Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Orléans (UO), Région Centre Val de Loire : MUSE Project (Grant No. 2014-00094512) and Grant No. 2013-00082978, European Regional Development Fund (ERDF): SMHART Project, 35069, Conseil Régional du Centre, INRAE, INSERM, ANR-11-BSV5-0020,SPOREPAIR,Caractérisation d'une enzyme radicalaire de réparation de l'ADN : la lyase du photoproduit des spores(2011), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Université de Tours (UT)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), REHAULT-GODBERT, Sophie, BLANC - Caractérisation d'une enzyme radicalaire de réparation de l'ADN : la lyase du photoproduit des spores - - SPOREPAIR2011 - ANR-11-BSV5-0020 - BLANC - VALID, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-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: Models, Molecular, 0301 basic medicine, crystal structure, animal structures, QH301-705.5, Eggs, [SDV]Life Sciences [q-bio], Crystallography, X-Ray, Proteomics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Affinity chromatography, Animals, MSMB, Amino Acid Sequence, paralogs, Biology (General), Research Articles, biology, Phylogenetic tree, Embryogenesis, Prostatic Secretory Proteins, biology.organism_classification, [SDV] Life Sciences [q-bio], 030104 developmental biology, Biochemistry, 030220 oncology & carcinogenesis, Neognathae, birds, beta‐microseminoproteins, egg, Chickens, Sequence Alignment, MSMB3, Function (biology), Research Article, Egg white
Abstract: Beta‐microseminoproteins (MSMBs) are small disulfide‐rich proteins that are conserved among vertebrates. These proteins exhibit diverse biological activities and were mainly reported to play a role in male fertility, immunity, and embryogenesis. In this work, we focused on the chicken MSMB3 protein that was previously depicted as an egg antibacterial protein. We report that MSMB3 protein is exclusively expressed in the reproductive tissues of laying hens (in contrast to chicken MSMB1 and MSMB2 paralogs), to be incorporated in the egg white during the process of egg formation. We also showed that chicken MSMB3 possesses highly conserved orthologs in bird species, including Neognathae and Palaeognathae. Chicken MSMB3 was purified from egg white using heparin affinity chromatography and was analyzed by top‐down and bottom‐up proteomics. Several proteoforms could be characterized, and a homodimer was further evidenced by NMR spectroscopy. The X‐ray structure of chicken MSMB3 was solved for the first time, revealing that this protein adopts a novel dimeric arrangement. The highly cationic MSMB3 protein exhibits a distinct electrostatic distribution compared with chicken MSMB1 and MSMB2 structural models, and with published mammalian MSMB structures. The specific incorporation of MSMB3 paralog in the egg, and its phylogenetic conservation in birds together with its peculiar homodimer arrangement and physicochemical properties, suggests that the MSMB3 protein has evolved to play a critical role during the embryonic development of avian species. These new data are likely to stimulate research to elucidate the structure/function relationships of MSMB paralogs and orthologs in the animal kingdom., Beta‐microseminoproteins (MSMBs) are small proteins conserved among vertebrates. The chicken genome contains three MSMB paralogs, which exhibit distinct tissue expression profiles, with chicken beta‐MSMB 3 (MSMB3) protein being egg‐specific. Collectively, results from protein sequence analysis, mass spectrometry analysis, and 3D structure data highlight that chicken MSMB3 possesses specific features that may be related to its presumed role in avian reproduction.
Published: 2021

35. Lipid profile of bovine grade-1 blastocysts produced either in vivo or in vitro before and after slow freezing process

Author: Pascal Salvetti, Daniel Le Bourhis, Patrick Emond, Virginie Maillard, Laurene Le Berre, Samuel Buff, Sébastien Elis, Laurent Schibler, Antoine Lefèvre, Thierry Joly, Olivier Desnoës, Sarah Janati Idrissi, Allice, 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), ISARA-Lyon, Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Interactions Cellules Environnement - UR (ICE), 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 de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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: 0301 basic medicine, Male, Embryology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, animal structures, Science, [SDV.SA.ZOO]Life Sciences [q-bio]/Agricultural sciences/Zootechny, Fertilization in Vitro, Glycerophospholipids, Cryopreservation, Article, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, Andrology, Embryo Culture Techniques, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sex Factors, Embryo cryopreservation, In vivo, Developmental biology, medicine, Animals, Triglycerides, Animal biotechnology, Principal Component Analysis, 030219 obstetrics & reproductive medicine, Multidisciplinary, medicine.diagnostic_test, Lysophosphatidylcholines, Embryo, Lipidome, In vitro, 030104 developmental biology, Lysophosphatidylcholine, Blastocyst, chemistry, Lipidomics, embryonic structures, Medicine, Cattle, Female, Lipid profile, Oxidation-Reduction
Abstract: Currently, in vitro embryo production (IVP) is successfully commercially applied in cattle. However, the high sensitivity of embryos to cryopreservation in comparison to in vivo (IVD) embryos slows the dissemination of this biotechnology. Reduced cryotolerance is frequently associated with lipid accumulation in the cytoplasm mainly due to in vitro culture conditions. The objective of this study was to evaluate the lipid composition of biopsied and sexed embryos, produced either in vivo or in vitro from the same Holstein heifers before and after a slow freezing protocol. Lipid extracts were analysed by liquid chromatography-high resolution mass spectrometry, which enabled the detection of 496 features. Our results highlighted a lipid enrichment of IVP embryos in triglycerides and oxidised glycerophospholipids and a reduced abundance in glycerophospholipids. The slow freezing process affected the lipid profiles of IVP and IVD embryos similarly. Lysophosphatidylcholine content was reduced when embryos were frozen/thawed. In conclusion, the embryonic lipid profile is impacted by IVP and slow freezing protocols but not by sex. Lysophosphatidylcholine seemed highly sensitive to cryopreservation and might contribute to explain the lower quality of frozen embryos. Further studies are required to improve embryo freezability by modulating the lipidome.
Published: 2021

36. 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

37. 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

38. 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

39. 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

40. 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

41. Risk Factors for Recurrence of Borderline Ovarian Tumours after Conservative Surgery and Impact on Fertility: A Multicentre Study by the Francogyn Group

Author: Adele Ozenne, Marion De Berti, Gilles Body, Xavier Carcopino, Olivier Graesslin, Yohan Kerbage, Cherif Akladios, Cyrille Huchon, Alexandre Bricou, Camille Mimoun, Emilie Raimond, Lobna Ouldamer, Service de Gynécologie-Obstétrique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Service de gynécologie-obstétrique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Université de Reims Champagne-Ardenne (URCA), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Risques cliniques et sécurité en santé des femmes et en santé périnatale (RISCQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Service de gynécologie-obstétrique [Hôpital Jean Verdier, Bondy], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie et obstétrique [Hopital Lariboisière - Paris], 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 Cité (UPCité), and HAL UVSQ, Équipe
Subjects: fertility, recurrence, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, ovarian tumours, conservative treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, peritoneal staging, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Introduction: Borderline ovarian tumours (BOT) represent 10–20% of epithelial tumours of the ovary. Although their prognosis is excellent, the recurrence rate can be as high as 30%, and recurrence in the infiltrative form accounts for 3% to 5% of recurrences. Affecting, in one third of cases, women of childbearing age, the surgical strategy with ovarian conservation is now recommended despite a significant risk of recurrence. Few studies have focused exclusively on patients who have received ovarian conservative treatment in an attempt to identify factors predictive of recurrence and the impact on fertility. The objective of this study was to identify the risk factors for recurrence of BOT after conservative treatment and the impact on fertility. Material and methods: This was a retrospective, multicentre study of women who received conservative surgery for BOT between February 1997 and September 2020. We divided the patients into two groups, the “R group” with recurrence and the “NR group” without recurrence. Results: Of 175 patients included, 35 had a recurrence (R group, 20%) and 140 had no recurrence (NR group, 80%). With a mean follow-up of 30 months (IQ 8–62.5), the overall recurrence rate was 20%. Recurrence was BOT in 17.7% (31/175) and invasive in 2.3% (4/175). The mean time to recurrence was 29.5 months (IQ 16.5–52.5). Initial complete peritoneal staging (ICPS) was performed in 42.5% of patients (n = 75). In multivariate analysis, age at diagnosis, nulliparity, advanced FIGO stage, the presence of peritoneal implants, and the presence of a micropapillary component for serous tumours were factors influencing the occurrence of recurrence. The post-surgery fertility rate was 67%. Conclusion: This multicentre study is to date one of the largest studies analysing the risk factors for recurrence of BOT after conservative surgery. Five risk factors were found: age at diagnosis, nulliparity, advanced FIGO stage, the presence of implants, and a micropapillary component. Only 25% of the patients with recurrence underwent ICPS. These results reinforce the interest of initial peritoneal staging to avoid ignoring an advanced tumour stage.
Published: 2022

42. 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
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43. 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

44. Childhood trauma increases vulnerability to attempt suicide in adulthood through avoidant attachment

Author: H, Ihme, E, Olié, P, Courtet, W, El-Hage, X, Zendjidjian, P, Mazzola-Pomietto, J-L, Consoloni, C, Deruelle, R, Belzeaux, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation FondaMental [Créteil], 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), 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), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), ANR-17-EURE-0029,nEURo*AMU,Marseille NeuroSchool, une formation d'excellence(2017), deruelle, christine, and Marseille NeuroSchool, une formation d'excellence - - nEURo*AMU2017 - ANR-17-EURE-0029 - EURE - VALID
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Childhood abuse, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Attachment, Affective disorder, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Clinical Psychology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Mediation analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Suicide attempts, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Childhood trauma and affective disorders are known risk factors for adult suicidal behavior. Studies have shown a mediating effect of insecure attachment on the effect of childhood trauma and suicidal behavior but so far it is not clear whether this effect is related to an attachment dimension (anxiety, avoidance).Aim: The present study sought to examine the mediating effect of attachment anxiety and avoidance on suicidal behavior.Methods: We analyzed data on childhood trauma, attachment style, depression severity, presence of prior suicide attempts and current suicide ideation from 96 patients diagnosed with an affective disorder. Two mediation analyses were conducted to assess the effect of childhood trauma on 1) prior suicide attempts and 2) current suicidal ideation through its effect on attachment.Results: We found that childhood trauma had a complete mediated effect on the presence of prior suicide attempts through its effect on avoidant attachment (a1b1 = 0.0120, 95%-CI [0.0031, 0.0276]). However, only emotional abuse had a direct influence on suicidal ideation (c' = 0.0273, p < 0.01) without any indirect effect of anxious or avoidant attachment.Limitations: Variables were not assessed in a prospective way and sample size was small.Conclusions: Our findings suggest that individuals with avoidant attachment and childhood trauma are likely to present a high suicide risk. Since avoidant attachment is associated with altered perceptions and eventual rejection of social support, we recommend to screen for attachment early and to engage patients in therapeutical approaches focusing on the client-therapist alliance.
Published: 2022

45. 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

46. Distribution of Achromobacter species in 12 French cystic fibrosis centers in 2020 by a retrospective MALDI-TOF MS spectrum analysis

Author: Thomas Garrigos, Manon Dollat, Arnaud Magallon, Anaïs Folletet, Julien Bador, Maryam Abid, Marlène Amara, Clémence Beauruelle, Olivier Belmonte, Pierre Boyer, Emilie Cardot-Martin, Anne-Gaëlle Cauchie, Sylvie Colin de Verdière, Claire Daurel, Cécile Gaudru, Farida Hamdad, Geneviève Héry-Arnaud, Baptiste Hoellinger, Claudie Lamoureux, Marie-Frédérique Lartigue, Damasie Malandain, Océane Marchand, Caroline Piau, Sandrine Picot, Hélène Revillet, Zeina Sabouni, Catherine Neuwirth, Lucie Amoureux, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Versailles André Mignot (CHV), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-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), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Université de Strasbourg (UNISTRA), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Versailles, 78000 Le Chesnay, France, parent, Hôpital Foch [Suresnes], Service de Microbiologie [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), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Amiens-Picardie, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), CHU Strasbourg, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Faculté de Médecine Purpan, CHU Toulouse [Toulouse], Laboratoire Chrono-environnement (UMR 6249) (LCE), 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)-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), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Microbiology (medical), [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Achromobacter, ST137, DES, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Maldi-TOF, cystic fibrosis, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], identification, epidemiology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, mass spectrometry
Abstract: International audience; Achromobacter spp. are nonfermenting Gram-negative bacilli mainly studied among cystic fibrosis (CF) patients. The identification of the 19 species within the genus is time-consuming (nrdA-sequencing), thus data concerning the distribution of the species are limited to specific studies. Recently, we built a database using MALDI-TOF mass spectrometry (MS) (Bruker) that allows rapid and accurate species identification and detection of the multiresistant epidemic clones: A xylosoxidans ST137 spreading among CF patients in various French and Belgium centers, and A. ruhlandii DES in Denmark. Here, we first assessed whether species identification could be achieved with our database solely by analysis of MS spectra without availability of isolates. Then, we conducted a multicentric study describing the distribution of Achromobacter species and of the clone ST137 among French CF centers. We collected and analyzed with our local database the spectra of Achromobacter isolates from 193 patients (528 samples) from 12 centers during 2020. In total, our approach enabled to conclude for 502/528 samples (95.1%), corresponding to 181 patients. Eleven species were detected, only five being involved in chronic colonization, A. xylosoxidans (86.4%), A. insuavis (9.1%), A. mucicolens (2.3%), A. marplatensis (1.1%) and A. genogroup 3 (1.1%). This study confirmed the high prevalence of A. xylosoxidans in chronic colonizations and the circulation of the clone A. xylosoxidans ST137 in France: four patients in two centers. The present study is the first to report the distribution of Achromobacter species from CF patients samples using retrospective MALDI-TOF/MS data. This easy approach could enable future large-scale epidemiological studies.
Published: 2022

47. Immune-mediated thrombotic thrombocytopenic purpura prognosis is affected by blood pressure

Author: Adrien Joseph, Martin Eloit, Elie Azoulay, Gilles Kaplanski, François Provot, Claire Presne, Alain Wynckel, Steven Grangé, Éric Rondeau, Frédéric Pène, Yahsou Delmas, Alexandre Lautrette, Christelle Barbet, Christiane Mousson, Jean‐Philippe Coindre, Pierre Perez, Matthieu Jamme, Jean‐François Augusto, Pascale Poullin, Frédéric Jacobs, Khalil El Karoui, Cécile Vigneau, Marc Ulrich, Tarik Kanouni, Moglie Le Quintrec, Mohamed Hamidou, Simon Ville, Anne Charvet‐Rumpler, Mario Ojeda‐Uribe, Pascal Godmer, Véronique Fremeaux‐Bacchi, Agnès Veyradier, Jean‐Michel Halimi, Paul Coppo, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Bretonneau, Hôpital Gatien de Clocheville [Tours] (CHRU Tours), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Larrey, AP-HP - Hôpital Antoine Béclère [Clamart], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre hospitalier [Valenciennes, Nord], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), 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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Gatien de Clocheville [Tours], CHU Saint-Antoine [AP-HP], École pratique des hautes études (EPHE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Robert Debré Paris, Hôpital Robert Debré, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, 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, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chard-Hutchinson, Xavier, and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV] Life Sciences [q-bio], hypertension, [SDV]Life Sciences [q-bio], hemolytic uremic syndrome, blood pressure, complement, thrombotic microangiopathies, Hematology, prognosis, thrombotic thrombocytopenic purpura, ADAMTS13
Abstract: International audience; BACKGROUND: The prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear. METHODS: Using a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort’s blood pressure profile to assess its impact on prognosis and diagnostic performances. RESULTS: Patients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p
Published: 2022

48. 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

49. 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

50. 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

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