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1. Characterization through scanning electron microscopy and μFourier transform infrared spectroscopy of microcalcifications present in fine needle aspiration smears

Author: Henry, Lucas, Bazin, Dominique, Policar, Clotilde, Haymann, Jean-Philippe, Daudon, Michel, Frochot, Vincent, Mathonnet, Muriel, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Sorbonne Université (SU), Université Paris-Saclay, Laboratoire de Physique des Solides (LPS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], ENS-PSL (LH's PhD fellowship)Fondation pour la Recherche Biomédicale (project DEI20151234413), and Policar, Clotilde
Subjects: Thyroid, [CHIM.INOR] Chemical Sciences/Inorganic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Microscopie électronique à balayage, Spectroscopie infrarouge, Nodule, Smears, Building and Construction, Ponctions, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Scanning electron microscopy. Mots-clés. Thyroïde, [CHIM.OTHE] Chemical Sciences/Other, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Electrical and Electronic Engineering, [CHIM.OTHE]Chemical Sciences/Other, Infrared spectroscopy
Abstract: International audience; In this contribution, we have characterized for the first time (to the best of our knowledge), microcalcifications present in fine needle aspiration (FNA) smears of thyroid nodules. Abnormal deposits were analysed through Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscopy (FE-SEM) in order to obtain their chemical composition as well as their morphology at the micrometer scale. Thirty-one samples coming from 13 patients were investigated comprising five cases of papillary carcinoma, two of Graves’ disease, and six of adenomatous goitre. The smears were also stained for analysis of the cellular characteristics of these lesions for classifying according to the Bethesda classification. Two mineral species, amorphous and nanocrystallised apatite calcium phosphate, have been identified with very different morphologies. Moreover, FE-SEM observations at the micrometer scale underline the presence of different kinds of abnormal deposits.
Published: 2022

2. Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation

Author: Eline Lemerle, Jeanne Lainé, Marion Benoist, Gilles Moulay, Anne Bigot, Clémence Labasse, Angéline Madelaine, Alexis Canette, Perrine Aubin, Jean-Michel Vallat, Norma B Romero, Marc Bitoun, Vincent Mouly, Isabelle Marty, Bruno Cadot, Laura Picas, Stéphane Vassilopoulos, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microscopie Electronique [IBPS] (IBPS-ME), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université Grenoble Alpes (UGA), Hôpital Dupuytren [CHU Limoges], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM), ANR-21-CE13-0018,CLASS,Plaques de clathrine: Structure, fonction et implication dans les maladies neuromusculaires(2021), and ANR-18-CE17-0006,DynaTher,Thérapie par modulation de l'expression de la Dynamine 2(2018)
Subjects: General Immunology and Microbiology, General Neuroscience, [SDV]Life Sciences [q-bio], General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience; Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of a plasma membrane invagination, the T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although the precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in T-tubule formation and mutations of several of their constituents induce muscle weakness and myopathies. Here, we demonstrate that, at the plasma membrane, Bin1 and caveolae composed of caveolin-3 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Bin1 expression lead to the formation of both rings and tubes and we show that Bin1 forms scaffolds on which caveolae accumulate to form the initial T-tubule. Cav3 deficiency caused by either gene silencing or pathogenic mutations results in defective ring formation and perturbed Bin1-mediated tubulation that may explain defective T-tubule organization in mature muscles. Our results uncover new pathophysiological mechanisms that may prove relevant to myopathies caused by Cav3 or Bin1 dysfunction.
Published: 2023

3. Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study)

Author: Huang, S., Vignon, P., Mekontso-Dessap, A., Tran, S., Prat, G., Chew, M., Balik, M., Sanfilippo, Filippo, Banauch, G., Clau-Terre, F., Morelli, A., De Backer, D., Cholley, B., Slama, M., Charron, C., Goudelin, M., Bagate, F., Bailly, P., Blixt, P. -J., Masi, P., Evrard, B., Orde, S., Mayo, P., Mclean, A. S., Vieillard-Baron, A., Welsh, A. -M., Didriksson, H., Zerbib, Y., Brault, C., Bodenes, L., Ferriere, N., Clavier, S., Ma, I., La Via, L., Dezio, V., Rius, J. B., Palomares, J. R., Piscioneri, F., Giglioli, S., Banauch-Mayer, S., Francois, B., Fedoux, A. -L., Daix, T., The University of Sydney, Hôpital Dupuytren [CHU Limoges], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Hôpital Ambroise Paré [AP-HP], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Linköping University (LIU), Charles University [Prague] (CU), AOU Policlinico Vittorio-Emanuele [Catania, Italia], University of Massachusetts System (UMASS), Vall d'Hebron University Hospital [Barcelona], Terza University of Rome, Université libre de Bruxelles (ULB), 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 Amiens-Picardie, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Donald and Barbara Zucker School of Medicine at Hofstra/Northwell [Hempstead, NY, USA], 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, and DESSAIVRE, Louise
Subjects: Coronavirus, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Echocardiography, Cardiac function, COVID-19, Intensive care unit, Critical Care and Intensive Care Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR\,>\,4), pulmonary embolism (OR\,>\,5) and increased PaCO(2). Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.
Published: 2022

4. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Author: Schenone, Laurence, Houillier, Caroline, Tanguy, Marie Laure, Choquet, Sylvain, Agbetiafa, Kossi, Ghesquières, Hervé, Damaj, Gandhi, Schmitt, Anna, Bouabdallah, Krimo, Ahle, Guido, Gressin, Remy, Cornillon, Jérôme, Houot, Roch, Marolleau, Jean-Pierre, Fornecker, Luc-Matthieu, Chinot, Olivier, Peyrade, Frédéric, Bouabdallah, Reda, Moluçon-Chabrot, Cécile, Gyan, Emmanuel, Chauchet, Adrien, Casasnovas, Olivier, Oberic, Lucie, Delwail, Vincent, Abraham, Julie, Roland, Virginie, Waultier-Rascalou, Agathe, Willems, Lise, Morschhauser, Franck, Fabbro, Michel, Ursu, Renata, Thieblemont, Catherine, Jardin, Fabrice, Tempescul, Adrian, Malaise, Denis, Touitou, Valérie, Nichelli, Lucia, Le Garff-Tavernier, Magali, Plessier, Aurélie, Bourget, Philippe, Bonmati, Caroline, Wantz-Mézières, Sophie, Giordan, Quentin, Dorvaux, Véronique, Charron, Cyril, Jabeur, Waliyde, Hoang-Xuan, Khê, Taillandier, Luc, Soussain, Carole, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau = Paris Brain Institute (ICM), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hématologie, Institut Curie, Site Saint-Cloud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], UNICANCER, CHU Bordeaux [Bordeaux], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Saint Jean de Perpignan, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cancer de Montpellier (ICM), Hopital Saint-Louis [AP-HP] (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), 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 de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], CHU Necker - Enfants Malades [AP-HP], Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Mercy, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Ambroise Paré [AP-HP], Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Automatique de Nancy (CRAN), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), and We thank the clinicians involved in the French National 'Lymphome Oculo-Cérébral' LOC network, part of the network for rare cancers of the central nervous system, 'RENOCLIP-LOC Network', approved by the French National Institute of Cancer (INCa).
Subjects: Transplantation, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n\,=\,147) or at relapse (n\,=\,119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n\,=\,64), thiotepa-busulfan (n\,=\,24), BCNU-etoposide-cytarabine-melphalan (BEAM, n\,=\,36) and thiotepa-busulfan-cyclophosphamide (n\,=\,142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.
Published: 2022

5. Peripheral neuropathy and livedoid vasculopathy

Author: Antoine Soulages, Thierry Maisonobe, Pascal Auzou, Antoine Petit, Yves Allenbach, Stéphane Barète, Sophie Skopinski, Emmanuel Ribeiro, Marie-Laure Jullié, Laurence Lamant, Françoise Brevet, Xavier Soulages, Jean-Michel Vallat, Marie-Laure Martin-Négrier, Guilhem Solé, Fanny Duval, Louis Carla, Gwendal Le Masson, Stéphane Mathis, Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Pellegrin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), and Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Vasculitis, [SDV]Life Sciences [q-bio], Livedoid Vasculopathy, Mononeuropathies, Peripheral Nervous System Diseases, Middle Aged, Neurology, Humans, Female, Neurology (clinical), Aged, Skin
Abstract: Livedoid vasculopathy (LV) is a chronic dermatosis associated with micro-thrombosis of the vessels of the dermis, leading to ischemic lesions and painful skin ulcerations of the lower limbs. This thrombosing occlusive vasculopathy, clearly distinct from 'classical vasculitis' (not related to alteration of vessel walls), may lead to peripheral neuropathy.To clarify the main clinical, electrophysiological and pathological characteristics of peripheral neuropathy linked to LV.We presented a series of personal cases of peripheral neuropathy due to LV. We also conducted a review of the literature (since the first description of LV in 1974) using multiple combinations of keywords from 'PubMed', 'Google Scholar' and 'ScienceDirect' databases according to the 'Preferred Reporting Items for Systematic reviews and Meta-Analyses' guidelines.We identified 16 patients (6 personal cases and 10 cases from the medical literature). Our personal cases were five females and one male, with a median age (at the onset of cutaneous signs of LV) of 38 (range 25-62). Several types of skin lesions of the lower limbs were observed. Median age at the onset of peripheral neuropathy symptoms was 48 years (range 29-66), with a main clinical and electrophysiological pattern of mononeuropathy multiplex.We observed a typical pattern of peripheral neuropathy, mostly mononeuropathy multiplex, whose pathophysiology might be related to occlusions of the small vessels of the nerves, as seen in the dermis. Moreover, LV may also be associated with other types of peripheral neuropathies (sometimes of autoimmune etiology) not directly related to the skin lesions.The 'ischemic form' of peripheral neuropathy linked to LV is mainly responsible for sensory disturbances (with multifocal distribution), sometimes for motor disturbances. This type of peripheral neuropathy has to be distinguished from 'classical vasculitic neuropathies' which are usually treated with antithrombotic therapies.
Published: 2022

6. On Behalf of the SFGM-TC: Retrospective Comparison of Reduced and Higher Intensity Conditioning for High-Risk Myelodysplastic Syndrome Treated With Allogeneic Stem-Cell Transplantation

Author: Hélène Labussière-Wallet, Stephanie Nguyen-Quoc, Amandine Luc, Thomas Remen, Jacques-Olivier Bay, Edouard Forcade, Rémi Dulery, Marie-Thérèse Rubio, Célestine Simand, Micha Srour, Maud d'Aveni, Ambroise Marçais, Sabine Furst, Arnaud Campidelli, Patrice Ceballos, Etienne Daguindau, Marie Robin, Pascal Turlure, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Eloi, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hématologie Biologique [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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Dupuytren [CHU Limoges], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Necker - Enfants Malades [AP-HP], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, 03 medical and health sciences, 0302 clinical medicine, Conditioning regimen, Risk Factors, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Transplantation, Homologous, Overall survival, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, medicine.disease, Survival Analysis, Allogeneic stem cell transplantation, 3. Good health, Fludarabine, Transplantation, Covariate adjustment using the propensity, medicine.anatomical_structure, Graft-versus-host disease, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Propensity score matching, Female, Bone marrow, Stem cell, business, Myelodysplastic syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Busulfan, 030215 immunology, medicine.drug
Abstract: International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.
Published: 2022

7. Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

Author: Jennifer Saliba, Chanez Manseur, Hugo Groult, Hussein Akil, Mona Tannoury, Danielle Troutaud, Thierry Maugard, Jean Feuillard, Ingrid Arnaudin, Chantal Jayat-Vignoles, Rougier Caron, Nathalie, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Faculty of Sciences [Lebanese University] | Faculté des Sciences [Université Libanaise], Lebanese University [Beirut] (LU), La Rochelle Université (ULR), and Hôpital Dupuytren [CHU Limoges]
Subjects: PD-L1, [SDV]Life Sciences [q-bio], Pharmaceutical Science, EBV latency III B-cells, very-low-molecular-weight fucoidan, [SDV] Life Sciences [q-bio], fucoidan, Drug Discovery, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, DLBCLs, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, actin network, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Pharmacology, Toxicology and Pharmaceutics (miscellaneous), [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract: International audience; Epstein–Barr virus (EBV) infects 95% of the world’s population and persists latently in the body. It immortalizes B-cells and is associated with lymphomas. LCLs (lymphoblastoid cell lines, EBV latency III B-cells) inhibit anti-tumoral T-cell response following PD-L1 overexpression (programmed death-ligand 1 immune checkpoint). Many cancer cells, including some DLBCLs (diffuse large B-cell lymphomas), also overexpress PD-L1. Immunotherapies are based on inhibition of PD-L1/PD-1 interactions but present some dose-dependent toxicities. We aim to find new strategies to improve their efficiency by decreasing PD-L1 expression. Fucoidan, a polysaccharide extracted from brown seaweed, exhibits immunomodulatory and anti-tumor activities depending on its polymerization degree, but data are scarce on lymphoma cells or immune checkpoints. LCLs and DLBCLs cells were treated with native fucoidan (Fucus vesiculosus) or original very-low-molecular-weight fucoidan formulas (vLMW-F). We observed cell proliferation decrease and apoptosis induction increase with vLMW-F and no toxicity on normal B- and T-cells. We highlighted a decrease in transcriptional and PD-L1 surface expression, even more efficient for vLMW than native fucoidan. This can be explained by actin network alteration, suggesting lower fusion of secretory vesicles carrying PD-L1 with the plasma membrane. We propose vLMW-F as potential adjuvants to immunotherapy due to their anti-proliferative and proapoptotic effects and ability to decrease PD-L1 membrane expression.
Published: 2023
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8. Concordance entre la stratégie thérapeutique proposée en RCP initiale et le traitement effectivement réalisé pour les CBPNC de stade III non-résecables : résultats initiaux de l'étude OBSTINATE (GFPC 06-2019)

Author: Ricordel, C, Anota, A, Auliac, JB, Bernardi, M, Falchero, L, Vergnenegre, A, Guisier, F, De Chabot, G, Geier, M, Demaegdt, A, Decroisette, C, Abdiche, S, Le Treut, J, Kaluzinski, L, Chouaid, C, Bylicki, O, Greillier, L, 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), CHU Pontchaillou [Rennes], Direction de la Recherche Clinique et de l'Innovation [HCL, Lyon] (DRCI / CLCC Léon-Bérard), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Service de Pneumologie [CHI Créteil], CHI Créteil, Centre Hospitalier du Pays d'Aix, Centre Hospitalier de Villefranche sur Saône, Partenaires INRAE, Hôpital Dupuytren [CHU Limoges], CHU Rouen, Normandie Université (NU), Laboratoire d'Informatique, du Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), CH Vannes, Radiation Oncology Department [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier de Bigorre [Tarbes], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Libourne, Hôpital Européen de Marseille (HEM), Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC), Centre Hospitalier Intercommunal de Créteil (CHIC), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], and Groupe Français de Pneumo-Cancérologie
Subjects: [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; L'objectif principal de l'étude OBSTINATE (GFPC 06-2019) est d'évaluer prospectivement la Qualité de Vie (QdV) au cours de la prise en charge du CBNPC de stade III non-résecable en condition de pratique courante. Les CBNPC de stade III constituent un groupe très hétérogène de situations cliniques, pour lesquelles les prises en charge thérapeutiques sont souvent multimodales. La reproductibilité des décisions thérapeutiques validées en RCP a d'ailleurs été récemment mise en question dans ce contexte a. L'objet de la présente analyse est d'explorer la concordance entre la proposition validée en RCP initiale et les traitements reçus par les patients dans le cadre de l'étude nationale non-interventionnelle OBSTINATE (GFPC 06-2019).
Published: 2023

9. Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study

Author: François-Daniel Ardellier, Seyyid Baloglu, Magdalena Sokolska, Vincent Noblet, François Lersy, Olivier Collange, Jean-Christophe Ferré, Adel Maamar, Béatrice Carsin-Nicol, Julie Helms, Maleka Schenck, Antoine Khalil, Augustin Gaudemer, Sophie Caillard, Julien Pottecher, Nicolas Lefèbvre, Pierre-Emmanuel Zorn, Muriel Matthieu, Jean Christophe Brisset, Clotilde Boulay, Véronique Mutschler, Yves Hansmann, Paul-Michel Mertes, Francis Schneider, Samira Fafi-Kremer, Mickael Ohana, Ferhat Meziani, Nicolas Meyer, Tarek Yousry, Mathieu Anheim, François Cotton, Hans Rolf Jäger, Stéphane Kremer, Fabrice Bonneville, Gilles Adam, Guillaume Martin-Blondel, Jérémie Pariente, Thomas Geeraerts, Hélène Oesterlé, Federico Bolognini, Julien Messie, Ghazi Hmeydia, Joseph Benzakoun, Catherine Oppenheim, Jean-Marc Constans, Serge Metanbou, Adrien Heintz, Blanche Bapst, Imen Megdiche, Lavinia Jager, Patrick Nesser, Yannick Talla Mba, Thomas Tourdias, Juliette Coutureau, Céline Hemmert, Philippe Feuerstein, Nathan Sebag, Sophie Carre, Manel Alleg, Claire Lecocq, Emmanuel Schmitt, René Anxionnat, François Zhu, Géraud Forestier, Aymeric Rouchaud, Pierre-Olivier Comby, Frederic Ricolfi, Pierre Thouant, Sylvie Grand, Alexandre Krainik, Isaure de Beaurepaire, Grégoire Bornet, Audrey Lacalm, Patrick Miailhes, Julie Pique, Claire Boutet, Xavier Fabre, Béatrice Claise, Sonia Mirafzal, Laure Calvet, Hubert Desal, Jérome Berge, Grégoire Boulouis, Apolline Kazemi, Nadya Pyatigorskaya, Augustin Lecler, Suzana Saleme, Myriam Edjlali-Goujon, Basile Kerleroux, Jean-Christophe Brisset, Samir Chenaf, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University College of London [London] (UCL), Nouvel Hôpital Civil de Strasbourg, Département de Neuroradiology [Rennes], Neuroimagerie: méthodes et applications (EMPENN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHU Pontchaillou [Rennes], Service de Médecine Intensive et Réanimation [Strasbourg], CHU Strasbourg, Département de Radiologie [Bichat] (DR- Bichat), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Groupe d'Analyse des Itinéraires et des Niveaux Salariaux (GAINS), Le Mans Université (UM), Les Hôptaux universitaires de Strasbourg (HUS), Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Louis Pasteur [Colmar] (CH Colmar), Hôpital Sainte-Anne [Paris], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), SFNR-COVID Group, CHU Henri Mondor [Créteil], Hôpital Marie Madeleine [Forbach] (CHIC Unisanté+), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier de Haguenau, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital privé d’Antony, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Clermont-Ferrand, and Société Française de Neuroradiologie [Paris] (SFNR)
Subjects: Multicenter Study, Radiological and Ultrasound Technology, Cerebrovascular Circulation, COVID-19, Radiology, Nuclear Medicine and imaging, Neuroimaging, Neurology (clinical), Magnetic Resonance Imaging, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background and purpose: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences.Methods: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex.Results: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p=0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies.Conclusion: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.
Published: 2023

10. Association between Initial Treatment Strategy and Long-Term Survival in Pulmonary Arterial Hypertension

Author: Vincent Cottin, David Montani, Jérémie Pichon, Martine Reynaud-Gaubert, Xavier Jaïs, Pascal Magro, Gérald Simonneau, Florence Parent, Fabrice Bauer, Marianne Riou, Laurent Bertoletti, Pamela Moceri, Ari Chaouat, Andrei Seferian, Antoine Beurnier, Sébastien Renard, Pierre Mauran, Delphine Horeau-Langlard, Pascal de Groote, Laurent Savale, Mitja Jevnikar, Sophie Bulifon, Pascal Roblot, Hélène Bouvaist, Yuanchao Feng, Patrice Poubeau, Sylvain Palat, Zhiying Liang, Emmanuel Bergot, François Picard, Etienne-Marie Jutant, C. Chabanne, Olivier Sitbon, Athénaïs Boucly, Grégoire Prévot, Jean-François Mornex, Cécile Tromeur, Marc Humbert, Bruno Degano, Claire Dauphin, Arnaud Bourdin, Olivier Sanchez, Nicolas Favrolt, Jason Weatherald, Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), CHU Rouen, Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie (UNICAEN), Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], 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), Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Calgary, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Nord Laennec [CHU Nantes], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Reims (CHU Reims), American Memorial Hospital (Hôpital des enfants) [Reims], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Hôpital Dupuytren [CHU Limoges], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), Nouvel Hôpital Civil de Strasbourg, Centre hospitalier universitaire de Poitiers (CHU Poitiers), 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), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrative du Tissu Osseux (LBTO), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, 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), and MORNET, Dominique
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, medicine.disease, survival, Pulmonary hypertension, 3. Good health, [SDV] Life Sciences [q-bio], pulmonary arterial hypertension, Internal medicine, pulmonary hypertension, Long term survival, therapeutics, Cardiology, Medicine, Initial treatment, business
Abstract: International audience; Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. Survival was assessed according to the initial strategy: monotherapy, dual therapy, or triple-combination therapy (two oral medications and a parenteral prostacyclin). Measurements and Main Results: Among 1,611 enrolled patients, 984 were initiated on monotherapy, 551 were initiated on dual therapy, and 76 were initiated on triple therapy. The triple-combination group was younger and had fewer comorbidities but had a higher mortality risk. The survival rate was higher with the use of triple therapy (91% at 5 yr) as compared with dual therapy or monotherapy (both 61% at 5 yr) (P < 0.001). Propensity score matching of age, sex, and pulmonary vascular resistance also showed significant differences between triple therapy and dual therapy (10-yr survival, 85% vs. 65%). In high-risk patients (n = 243), the survival rate was higher with triple therapy than with monotherapy or dual therapy, whereas there was no difference between monotherapy and double therapy. In intermediate-risk patients (n = 1,134), survival improved with an increasing number of therapies. In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.
Published: 2021

11. Toxoplasmosis in patients with an autoimmune disease and immunosuppressive agents: A multicenter study and literature review

Author: Marie-Fleur Durieux, Jean-Guillaume Lopez, Maher Banjari, Karine Passebosc-Faure, Marie-Pierre Brenier-Pinchart, Luc Paris, Gilles Gargala, Sabine Berthier, Julie Bonhomme, Cathy Chemla, Isabelle Villena, Pierre Flori, Emilie Fréalle, Coralie L’Ollivier, Florian Lussac-Sorton, José Gilberto Montoya, Estelle Cateau, Christelle Pomares, Loïc Simon, Dorothée Quinio, Florence Robert-Gangneux, Hélène Yera, Marc Labriffe, Anne-Laure Fauchais, Marie-Laure Dardé, Hôpital Dupuytren [CHU Limoges], Assistance Publique - Hôpitaux de Marseille (APHM), Service de Parasitologie Mycologie [CHU Limoges], CHU Limoges, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), COVID-Mucor study group, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Microbiologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Service des Agents Infectieux et Hygiène [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Parasitologie-Mycologie, Nice, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, 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], and The French National Reference Center for Toxoplasmosis received financial support by Santé Publique France (the national public health agency, https://www.santepubliquefrance.fr) for genotyping study, but no author has personally received grant.
Subjects: Infectious Diseases, Adrenal Cortex Hormones, Toxoplasmosis, Cerebral, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Humans, Multicenter Studies as Topic, Toxoplasma, Immunosuppressive Agents, Autoimmune Diseases
Abstract: Background Cases of Toxoplasma reactivation or more severe primary infection have been reported in patients receiving immunosuppressive (IS) treatment for autoimmune diseases (AID). The purpose of this study was to describe features of toxoplasmosis occurring in patients with AID treated by IS therapy, excluded HIV-positive and transplant patients. Methods A multicenter descriptive study was conducted using data from the French National Reference Center for Toxoplasmosis (NRCT) that received DNA extracts or strains isolated from patients, associated with clinical data. Other cases were retrieved through a questionnaire sent to all French parasitology and internal medicine departments. Furthermore, a systematic literature review was conducted. Results 61 cases were collected: 25 retrieved by the NRCT and by a call for observations and 36 from a literature review. Half of the cases were attributed to reactivation (50.9%), and most of cases (49.2%) were cerebral toxoplasmosis. The most common associated AID were rheumatoid arthritis (28%) and most frequent treatments were antimetabolites (44.3%). Corticosteroids were involved in 60.7% of cases. Patients had a favorable outcome (50.8%) but nine did not survive. For 12 cases, a successful Toxoplasma strain characterization suggested the possible role of this parasitic factor in ocular cases. Conclusion Although this remains a rare condition, clinicians should be aware for the management of patients and for the choice of IS treatment.
Published: 2022

12. First clinical description of letermovir resistance mutation in cytomegalovirus UL51 gene and potential impact on the terminase complex structure

Author: Clotilde Muller, Valentin Tilloy, Emilie Frobert, Linda Feghoul, Isabelle Garrigue, Quentin Lepiller, Audrey Mirand, Egor Sidorov, Sébastien Hantz, Sophie Alain, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpital Dupuytren [CHU Limoges], 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), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne, CNRS, LMGE, 63000 Clermont–Ferrand, France, Czech Statistical Office (CZSO), Jan Evangelista Purkyne University (UJEP), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], and CHU Limoges
Subjects: Pharmacology, Viral Proteins, Endodeoxyribonucleases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Drug Resistance, Viral, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Quinazolines, Cytomegalovirus, Humans, Acetates, Antiviral Agents
Abstract: Letermovir (LMV) is a human cytomegalovirus (HCMV) terminase inhibitor indicated as prophylaxis for HCMV-positive stem-cell recipients. Its mechanism of action involves at least the viral terminase proteins pUL56, pUL89 and pUL51. Despite its efficiency, resistance mutations were characterized in vitro and in vivo, largely focused on pUL56. To date, mutations in pUL51 in clinical resistance remain to be demonstrated.The pUL51 natural polymorphism was described by sequencing 54 LMV-naive strains and was compared to UL51 HCMV genes from 16 patients non-responding to LMV therapy (prophylaxis or curative). Recombinant viruses were built by «en-passant» mutagenesis to measure the impact of the new mutations on antiviral activity and viral growth. Structure prediction was performed by homology modeling. The pUL51 final-model was analyzed and aligned with the atomic coordinates of the monomeric HSV-1 terminase complex (PDB:6M5R).Among the 16 strains from treated-patients with LMV, 4 never described substitutions in pUL51 (D12E, 17del, A95V, V113L) were highlighted. These substitutions had no impact on viral fitness. Only UL51-A95V conferred 13.8-fold increased LMV resistance level by itself (IC50 = 29.246 ± 0.788).As an isolated mutation in pUL51 in a clinical isolate can lead to LMV resistance, genotyping for resistance should involve sequencing of the pUL51, pUL56 and pUL89 genes. With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.
Published: 2022

13. First Case of Lethal Encephalitis in Western Europe Due to European Bat Lyssavirus Type 1

Author: Hervé Bourhy, Pascal Cozette, Béatrice Regnault, Anne Jamet, Mathilde Duchesne, Delphine Chrétien, Philippe Pérot, Vallat Jean-Michel, Danielle Seilhean, Marianne Leruez, Laurent Dacheux, Marc Eloit, Isabelle Plu, Eric Troadec, Bruno Evrard, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris], Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), Hôpital Dupuytren [CHU Limoges], Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropathologie [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), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Centre National de Référence de la Rage - National Reference Center Rabies (CNR), Centre collaborateur de l'OMS - Rage / World Health Organization Collaboration Centres - Rabies (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), École nationale vétérinaire d'Alfort (ENVA), This work was supported by Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID)., The authors thank Thomas Bigot for the use of the bioinformatic pipeline Microseek and Sarah Temmam, Yves Gaudin and Jennifer Richardson for helpful discussions, Laurent Magy, Thomas Daix, Bruno Francois, and Sophie Alain for reviewing the manuscript, Lauriane Kergoat and Simon Bonas for their excellent technical help, as well as Santé Publique France for the financial support of the National Reference Center for Rabies., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), Institut du Cerveau = Paris Brain Institute (ICM), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Cité (UPCité), École nationale vétérinaire - Alfort (ENVA), Pérot, Philippe, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Microbiology (medical), [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Rabies, 030231 tropical medicine, Next Generation Sequencing, Context (language use), medicine.disease_cause, Virus, Mice, 03 medical and health sciences, 0302 clinical medicine, Chiroptera, Rhabdoviridae Infections, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Medicine, Lyssavirus, Metatranscriptomics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, business.industry, Rabies virus, medicine.disease, biology.organism_classification, Virology, 3. Good health, Europe, Titer, 030104 developmental biology, Infectious Diseases, European bat lyssavirus type 1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Encephalitis, Antibody, business
Abstract: Background Inaccurate diagnosis of encephalitis is a major issue as immunosuppressive treatments can be deleterious in case of viral infection. The European bat lyssavirus type 1 (EBLV-1), a virus related to rabies virus, is endemic in European bats. No human case has yet been reported in Western Europe. A 59-year-old patient without specific past medical history died from encephalitis. A colony of bats lived in an outbuilding of his house. No diagnosis was made using standard procedures. Methods We used a next generation sequencing (NGS) based transcriptomic protocol to search for pathogens in autopsy samples (meninges and brain frontal lobe). Results were confirmed by polymerase chain reaction (PCR) and by antibody testing in serum. Immunochemistry was used to characterize inflammatory cells and viral antigens in brain lesions. Cells and mice were inoculated with brain extracts for virus isolation. Results The patient’s brain lesions were severe and diffuse in white and gray matter. Perivascular inflammatory infiltrates were abundant and rich in plasma cells. NGS identified European bat lyssavirus type 1a in brain, which was confirmed by PCR. A high titer of neutralizing antibodies was found in serum. No viral antigen was detected, and the virus could not be isolated by cell culture or by mouse inoculation. Conclusions The patient died from European bat lyssavirus type 1a infection. NGS was key to identifying this unexpected viral etiology in an epidemiological context that did not suggest rabies. People exposed to bats should be strongly advised to be vaccinated with rabies vaccines, which are effective against EBLV-1.
Published: 2021

14. Demultiplexing Ig repertoires by parallel mRNA/DNA sequencing shows major differential alterations in severe COVID-19

Author: Pascal, Virginie, Dupont, Marine, de Rouault, Paco, Rizzo, David, Rossille, Delphine, Jeannet, Robin, Daix, Thomas, François, Bruno, Genebrier, Steve, Cornic, Marie, Monneret, Guillaume, Venet, Fabienne, Ferrant, Juliette, Roussel, Mikael, Reizine, Florian, Souhaitier, Mathieu, Tadié, Jean-Marc, Tarte, Karin, Feuillard, Jean, Cogné, Michel, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpital Dupuytren [CHU Limoges], 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), Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), CHU Pontchaillou [Rennes], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Etablissement Français du Sang Bretagne, and EFS
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], Immunology, Respiratory medicine
Abstract: To understand the fine differential elements that can lead to or prevent acute respiratory distress syndrome (ARDS) in COVID-19 patients, it is crucial to investigate the immune response architecture. We herein dissected the multiple layers of B cell responses by flow cytometry and Ig repertoire analysis from acute phase to recovery. Flow cytometry with FlowSOM analysis showed major changes associated with COVID-19 inflammation such as an increase of double-negative B-cells and ongoing plasma cell differentiation. This paralleled COVID-19-driven expansion of two disconnected B-cell repertoires. Demultiplexing successive DNA and RNA Ig repertoire patterns characterized an early expansion of IgG1 clonotypes with atypically long and uncharged CDR3, the abundance of this inflammatory repertoire being correlated with ARDS and likely pejorative. A superimposed convergent response included convergent anti-SARS-CoV-2 clonotypes. It featured progressively increasing somatic hypermutation together with normal-length or short CDR3 and it persisted until a quiescent memory B-cell stage after recovery.
Published: 2023

15. Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France

Author: Herpe, Guillaume, Lederlin, Mathieu, Naudin, Mathieu, Ohana, Mickaël, Chaumoitre, Kathia, Gregory, Jules, Vilgrain, Valérie, Freitag, Cornelia Anna, De Margerie-Mellon, Constance, Flory, Violaine, Ludwig, Marie, Mondot, Lydiane, Fitton, Isabelle, Jacquier, Alexis, Raymond, Robert, Ardilouze, Paul, Petit, Isabelle, Gervaise, Alban, Bayle, Olivier, Crombe, Arielle, Mekuko sokeng, Magloire, Thomas, Clément, Henry, Geraldine, Bliah, Virginie, Le Tat, Thomas, Guillot, Marc-Samir, Gendrin, Paul, Garetier, Marc, Bertolle, Estelle, Montagne, Catherine, Langlet, Benjamin, Kalaaji, Abdulrazak, Kayayan, Hampar, Desmots, Florian, Dhaene, Benjamin, Saulnier, Pierre-Jean, Guillevin, Remy, Bartoli, Jean-Michel, Beregi, Jean-Paul, Tasu, Jean Pierre, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Data Analysis and Computations Through Imaging Modeling-Mathématiques, Imagerie, Santé (DACTIM-MIS), Laboratoire de Mathématiques et Applications (LMA-Poitiers), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], CHU Pontchaillou [Rennes], Nouvel Hôpital Civil de Strasbourg, Assistance Publique - Hôpitaux de Marseille (APHM), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hopital Saint-Louis [AP-HP] (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier de la Côte Basque (CHCB), Département de Radiologie adultes [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Hôpital d'Instruction des Armées Legouest, Service de Santé des Armées, Imagerie Guilloz [CHRU Nancy] (Service d'imagerie Guilloz), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Saint-Joseph [Marseille], Clinique Emilie de Vialar, Centre Hospitalier [Douai, Nord], Centre Hospitalier Rives De Seine (CHRDS), Hôpital d'Instruction des Armées Begin, Hôpital d'instruction des Armées Percy, Service de Radiologie et Imagerie Médicale [CHU Limoges], CHU Limoges, Hôpital Dupuytren [CHU Limoges], Hôpital d'Instruction des Armées Clermont Tonnerre, Hôpital d’Argenteuil, Centre hospitalier Pierre Le Damany - Lannion, Centre hospitalier de Lannion, Institut Bergonié [Bordeaux], UNICANCER, Centre hospitalier Lucien Hussel, Hôpital d'Instruction des Armées Laveran, CHU Tivoli, 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), and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Adult, Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Chest ct, Sensitivity and Specificity, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030218 nuclear medicine & medical imaging, Thoracic Imaging, Young Adult, MESH: SARS-CoV-2, Tomography, X-Ray Computed / methods, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, Child, Letters to the Editor, Prospective cohort study, Aged, Original Research, Aged, 80 and over, SARS-CoV-2, business.industry, COVID-19, MESH: Female, France / epidemiology, Middle Aged, Radiography, Thoracic / methods, Thorax, medicine.disease, Communications, MESH: Adolescent, COVID-19 / diagnostic imaging, COVID-19 / epidemiology, Child, Preschool, Reverse transcription polymerase chain reaction, Pneumonia, Tomography x ray computed, 030220 oncology & carcinogenesis, Female, Radiography, Thoracic, France, Radiology, Tomography, X-Ray Computed, business
Abstract: International audience; The role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student t test, χ2 test, and Pearson correlation coefficient. P < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful.
Published: 2021

16. New structural variations responsible for Charcot-Marie-Tooth disease: The first two large KIF5A deletions detected by CovCopCan software

Author: Ioanna Pyromali, Sylvie Bourthoumieu, Franck Sturtz, Guilhem Solé, Paco Derouault, Mélanie Fradin, Fanny Duval, Constantin Gomes, Nesrine Benslimane, Anne-Sophie Lia, Alexandre Perani, Angélique Nizou, Frédéric Favreau, Corinne Magdelaine, Maintenance Myélinique et Neuropathies Périphériques (MMNP), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Biochimie et Génétique Moléculaire [CHU Limoges], CHU Limoges, Hôpital Dupuytren [CHU Limoges], Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Pontchaillou [Rennes], and CHU de Bordeaux Pellegrin [Bordeaux]
Subjects: [SDV]Life Sciences [q-bio], Next Generation Sequencing, Disease, medicine.disease_cause, Biochemistry, Copy Number Variants, Tooth disease, Exon, 0302 clinical medicine, Structural Biology, Gene duplication, KIF5A, Genetics, CMT2, 0303 health sciences, Mutation, Structural variations, CMT, Neonatal-Intractable-MYoclonus, Charcot-Marie-Tooth type 2, SV, Distal-Spinal-Muscular-Atrophy, 3. Good health, Computer Science Applications, Hereditary-Spastic-Paraplegia-type-10, NGS, Biotechnology, Charcot-Marie-Tooth, Sequence analysis, CNV, Biophysics, Biology, CovCopCan, HSP10, 03 medical and health sciences, SNV, medicine, Indel, Gene, Structural Variant, DSMA, 030304 developmental biology, Amyotrophic Lateral Sclerosis, NEIMY, Non-Allelic Homologous Recombination, NAHR, Single Nucleotide Variant, ALS, 030217 neurology & neurosurgery, TP248.13-248.65
Abstract: International audience; Next-generation sequencing (NGS) allows the detection of mutations in inherited genetic diseases, like the Charcot-Marie-Tooth disease (CMT) which is the most common hereditary peripheral neuropathy. The majority of mutations detected by NGS are single nucleotide variants (SNVs) or small indels, while structural variants (SVs) are often underdiagnosed. PMP22 was the first gene described as being involved in CMT via a SV of duplication type. To date, more than 90 genes are known to be involved in CMT, with mainly SNVs and short indels described. Herein targeted NGS and the CovCopCan bioinformatic tool were used in two unrelated families, both presenting with typical CMT symptoms with pyramidal involvement. We have discovered two large SVs in KIF5A, a gene known to cause axonal forms of CMT (CMT2) in which no SVs have yet been described. In the first family, the patient presented with a large deletion of 12 kb in KIF5A from Chr12:57,956,278 to Chr12:57,968,335 including exons 2-15, that could lead to mutation c.(130-943_c.1717-533del), p.(Gly44_Leu572del). In the second family, two cases presented with a large deletion of 3 kb in KIF5A from Chr12:57,974,133 to Chr12:57,977,210 including exons 24-28, that could lead to mutation c.(2539-605_*36 + 211del), p.(Leu847_Ser1032delins33). In addition, bioinformatic sequence analysis revealed that a NAHR (Non-Allelic-Homologous-Recombination) mechanism, such as those in the PMP22 duplication, could be responsible for one of the KIF5A SVs and could potentially be present in a number of other patients. This study reveals that large KIF5A deletions can cause CMT2 and highlights the importance of analyzing not only the SNVs but also the SVs during diagnosis of neuropathies.
Published: 2021

17. No Geographical Inequalities in Survival for Sarcoma Patients in France: A Reference Networks’ Outcome?

Author: Yohan Fayet, Christine Chevreau, Gauthier Decanter, Cécile Dalban, Pierre Meeus, Sébastien Carrère, Leila Haddag-Miliani, François Le Loarer, Sylvain Causeret, Daniel Orbach, Michelle Kind, Louis-Romée Le Nail, Gwenaël Ferron, Hélène Labrosse, Loïc Chaigneau, François Bertucci, Jean-Christophe Ruzic, Valérie Le Brun Ly, Fadila Farsi, Emmanuelle Bompas, Sabine Noal, Aurore Vozy, Agnes Ducoulombier, Clément Bonnet, Sylvie Chabaud, Françoise Ducimetière, Camille Tlemsani, Mickaël Ropars, Olivier Collard, Paul Michelin, Justine Gantzer, Pascale Dubray-Longeras, Maria Rios, Pauline Soibinet, Axel Le Cesne, Florence Duffaud, Marie Karanian, François Gouin, Raphaël Tétreau, Charles Honoré, Jean-Michel Coindre, Isabelle Ray-Coquard, Sylvie Bonvalot, Jean-Yves Blay, Centre Léon Bérard [Lyon], Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut Claudius Regaud, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Sud Saint Pierre [Ile de la Réunion], Hôpital Dupuytren [CHU Limoges], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Galilée (Galilée), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], 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), CHU Pontchaillou [Rennes], Université de Rennes (UR), Hôpital privé de la Loire, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Hospitalier Universitaire de Reims (CHU Reims), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Lyon, Institut du Cancer de Montpellier (ICM), Pôle chirurgical et interventionnel [Gustave Roussy], Université Paris sciences et lettres (PSL), ARC Foundation [PGA1*20160203865], INCA (French National Cancer Institute) [SHSESP16-063], SIRIC LYriCAN [INCa-DGOS-Inserm_12563], INCa, DGOS, and EURACAN European Reference Network [EC 739521]
Subjects: spatial inequalities, Cancer Research, reference networks, Oncology, rare cancers, remoteness, social deprivation, France, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Simple Summary As patients with rare cancers face specific problems, reference networks have been developed in several European countries and then at the European level to improve their management. In some cases, the specialized centers belonging to reference networks provide remote services (specialized diagnosis review, discussion in the Multidisciplinary Tumour Board, etc.) to increase access to these services. Using data from the national sarcoma reference network implemented in France (NETSARC+), the IGeAS research program assesses the potential of its organization to address the geographical inequalities in cancer management. We analyze the individual, clinical, and geographical determinants of the overall survival of sarcoma patients in France. We found no association between the overall survival of sarcoma patients and variables measuring their social deprivation, remoteness from reference centers, and geographical context. Following previous results from the research program, this study suggests that reference network organization should be considered to reduce cancer inequalities. The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGeAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGeAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.
Published: 2022
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18. Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial

Author: Aparicio, T., Bouché, O., Etienne, P. L., Barbier, E., Mineur, L., Desgrippes, R., Guerin-Meyer, V., Hocine, F., Martin, J., Le Brun-Ly, V., Cretin, J., Desramé, J., Rinaldi, Y., Cany, L., Falandry, C., Lefevre, L. B., Marous, M., Terrebonne, E., Mosser, L., Turpin, J., Turpin, A., Bauguion, L., Reichling, C., Eynde, M., Carola, E., Hiret, S., UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service d'oncologie médicale, UCL - (SLuc) Service d'hépato-gastro-entérologie, CarMeN, laboratoire, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Privé des Côtes d'Armor (HPCA), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fédération Francophone de Cancérologie Digestive (FFCD), Institut Sainte Catherine [Avignon], CH de Saint-Malo [Broussais], Service d'Oncologie Médicale [Angers], Centre Paul Papin, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Simone Veil de Beauvais [Beauvais], Clinique François Chénieux, Hôpital Dupuytren [CHU Limoges], Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), Hôpital privé Jean Mermoz [Lyon], Hôpital Européen [Fondation Ambroise Paré - Marseille], Clinique Francheville [Périgueux], 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'oncogénétique [Centre georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, CHU de la Martinique [Fort de France], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Clinique Sainte Isabelle [Abbeville, France], Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CH Colmar, Cliniques Universitaires Saint-Luc [Bruxelles], Groupe Hospitalier Public du Sud de l'Oise [Creil] (GHPSO), CRLCC René Gauducheau, and Département d'oncologie médicale [Saint Herblain]
Subjects: Geriatric evaluation, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Hepatology, Older, Gastroenterology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Adjuvant chemotherapy, Colon cancer
Abstract: International audience; BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.
Published: 2022

19. Mirror, Mirror on the Wall, Which Is the Fairest of Them All? Comparing the Hill, Sips, Koble–Corrigan, and Liu Adsorption Isotherms

Author: Khim Hoong Chu, Jean Debord, Michel Harel, Jean-Claude Bollinger, Honeychem Research, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Hôpital Dupuytren [CHU Limoges], Université de Limoges (UNILIM), Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Energy, General Chemical Engineering, Adsorption isotherms, [CHIM]Chemical Sciences, General Chemistry, Adsorption, Industrial and Manufacturing Engineering, Dyes and pigments, Isotherms
Abstract: Experimental equilibrium data for the adsorption of water contaminants on solid surfaces are generally correlated using suitable isotherm expressions. In most cases, adsorption isotherms are used empirically with the primary aim of finding the best fitting ones. The literature of adsorptive water decontamination is replete with such isotherm comparisons, usually evaluated on the basis of some statistical metrics such as R2 and RMSE. For example, several studies have compared and ranked the isotherm equations of Hill, Sips, Koble–Corrigan, and Liu. These comparative evaluations imply that the four isotherms possess different data fitting abilities, and consequently it is possible to identify the most accurate one. The present study argues that this commonly held notion is incorrect. It demonstrates that the four isotherms provide the same results when fitted to three previously published data sets. This finding suggests that the four isotherms are mathematically equivalent despite apparent differences in their formulations. Indeed, a mathematical analysis unequivocally shows that the Hill, Sips, Koble–Corrigan, and Liu isotherms can be represented by a single generic equation with three arbitrary fitting parameters. As such, the four isotherms must provide exactly the same fit to a given set of isotherm data.
Published: 2022

20. Routine use of 16S rRNA PCR and subsequent sequencing from blood samples in septic shock: about two case reports of Capnocytophaga canimorsus infection in immunocompetent patients

Author: Alexandre Martins-Baltar, Sylvain Meyer, Olivier Barraud, Fabien Garnier, Marie-Cécile Ploy, Philippe Vignon, Bruno François, Hôpital Dupuytren [CHU Limoges], CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Malbec, Odile
Subjects: [SDV]Life Sciences [q-bio], Ceftriaxone, Polymerase Chain Reaction, Shock, Septic, Dog bite, Dacarbazine, [SDV] Life Sciences [q-bio], Dogs, Infectious Diseases, Purpura Fulminans, RNA, Ribosomal, 16S, Septic shock, Diagnosis, Animals, Humans, Capnocytophaga canimorsus, Sequencing, Bites and Stings, Gram-Negative Bacterial Infections, 16S rRNA PCR, Capnocytophaga
Abstract: Background Capnocytophaga canimorsus infection happens frequently in immunosuppressed patients with reported domestic animal bites. Clinical presentation ranges from simple cellulitis to fulminant septic shock with disseminated intravascular coagulopathy, with an overall mortality of 30%. Conventional blood culture is often negative as this is a slow-growing pathogen. Nevertheless, the increasing use of 16S rRNA gene amplification and Sanger sequencing allows a much more rapid diagnostic confirmation. We present two case reports where 16S rRNA gene sequencing helped to diagnose Capnocytophaga canimorsus infection. Case presentation Case 1: A 53-year-old man with a history of non-cirrhotic chronic alcohol consumption was admitted to the intensive care unit (ICU) for septic shock and disseminated intravascular coagulopathy (DIC) of unknown origin. Blood cultures remained negative and a 16S rRNA PCR was performed leading to the identification of Capnocytophaga Canimorsus on day 4. Targeted antibiotic therapy with ceftriaxone for 14 days lead to overall recovery. Afterwards, the patient recalled a dog bite 2 days before hospitalization with a punctiform necrotic wound localized on a finger, which was not obvious at admission. Case 2: A 38-year-old man arrived to the emergency department for acute alcohol intoxication and history of a dog bite 2 days before. At admission, septic shock with purpura fulminans was diagnosed and required ICU hospitalization, invasive mechanical ventilation, vasopressor support and renal replacement therapy due to the rapid clinical deterioration. In the context of septic shock with purpura fulminans, DIC and recent dog bite, the diagnosis of Capnocytophaga canimorsus septic shock was suspected, and early confirmed by 16S rRNA PCR coupled to Sanger sequencing on day 2. Blood cultures became only positive for Capnocytophaga canimorsus 5 days after admission. Ceftriaxone alone was infused for 10 days in total, and the patient was discharged from the ICU on day 25. Conclusions 16S rRNA gene PCR proves an important diagnostic tool when facing a sepsis of unknown origin. In these two cases of septic shock related to Capnocytophaga canimorsus, initial blood cultures remained negative at 24 h, whereas the diagnosis was achieved by 16S rRNA PCR sequencing performed from blood samples obtained at admission.
Published: 2022

21. Development of a new serotyping ELISA for Toxoplasma gondii type II, type III and Africa 1 lineages using in silico peptide discovery methods, well categorized feline and human outbreak serum samples

Author: Hüseyin Can, Ayşegül Aksoy Gökmen, Mert Döşkaya, Sedef Erkunt Alak, Aysu Değirmenci Döşkaya, Muhammet Karakavuk, Ahmet Efe Köseoğlu, Tuğba Karakavuk, Ceren Gül, Mervenur Güvendi, Aytül Gül, Adnan Yüksel Gürüz, Selçuk Kaya, Aurélien Mercier, Cemal Ün, Ege university, Izmir Katip Celebi University (IKCU), Neuroépidémiologie Tropicale (NET), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-CHU Limoges-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpital Dupuytren [CHU Limoges], Institut de Recherche pour le Développement (IRD), Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM), and Grelier, Elisabeth
Subjects: Genotyping, Genotype, Strains, Antigens, Protozoan, Enzyme-Linked Immunosorbent Assay, Infectious and parasitic diseases, RC109-216, Infections, Sequences, Disease Outbreaks, parasitic diseases, Animals, Humans, Polymorphic Peptides, Serotyping, Research, South, Europe, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cats, Tachyzoites, GRA7, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, GRA6, Peptide ELISA, Peptides, Toxoplasma, Toxoplasmosis
Abstract: Background Discovery of new Toxoplasma gondii serotyping epitopes is important due to reports showing the influence of genotype on the severity of toxoplasmosis. In Turkey, genotypes belonging to type II, type III and Africa 1 lineages were mainly detected. The present study focused on to find out epitopes with high discriminative capacity to serotype these genotypes using well characterized strains isolated from Turkey. Methods To meet this objective, GRA6 and GRA7 genes were sequenced from strains belonging to the type II, III and Africa 1 lineages, and B cell epitopes inside these sequences were predicted by Bcepred and additional docking analysis was performed with B cell receptor. Based on these analyses, 22 peptides harboring lineage specific epitopes were synthesized. Then, the serotyping potency of these peptides was tested using peptide ELISA and well categorized serum samples collected from stray cats infected with genotypes of the different lineages type II (n:9), III (n:1) and Africa 1 (n:1). As a result of peptide-ELISA, a serotyping schema was constructed with peptides that show high discriminative capacity and this assay was validated by sera collected from humans after an outbreak (n:30) and mother/newborn pair sera (n:3). Later, the validated serotyping schema was used to serotype a larger group of human (n:38) and cat (n:24) sera. Results Among 22 peptides, GRA6II/c, GRA7III/d, and GRA6 Africa 1/b epitopes have shown discriminative capacity. During the validation of peptide-ELISA, the serotype of toxoplasmosis outbreak and mother/newborn cases were detected to be serotype II. Moreover, the analyses in a larger group showed that serotype II was prevalent in humans and stray cats. Conclusions Overall, the results showed that the serotyping schema could be successfully used to serotype T. gondii infections caused by type II, III and Africa 1 genotype., Izmir Katip Celebi Scientific Research Projects Coordination Unit [2018-ONAPTIPF-0006], This study was supported by a project given by the Izmir Katip Celebi Scientific Research Projects Coordination Unit (Project number: 2018-ONAPTIPF-0006) to AAG.
Published: 2022

22. Distinct B-Cell Specific Transcriptional Contexts of the BCL2 Oncogene Impact Pre-Malignant Development in Mouse Models

Author: Lina Zawil, Tiffany Marchiol, Baptiste Brauge, Alexis Saintamand, Claire Carrion, Elise Dessauge, Christelle Oblet, Sandrine Le Noir, Frédéric Mourcin, Mylène Brousse, Paco Derouault, Mehdi Alizadeh, Yolla El Makhour, Céline Monvoisin, Julien Saint-Vanne, Simon Léonard, Stéphanie Durand-Panteix, Karin Tarte, Michel Cogné, Chard-Hutchinson, Xavier, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Rôle de la classe des Ig / BCR dans les interactions cellulaires supportant la mémoire immune et impact immunopathologique - - Ig-MemImpact2016 - ANR-16-CE15-0019 - AAPG2016 - VALID, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), 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 Dupuytren [CHU Limoges], Lebanese University [Beirut] (LU), CHU Pontchaillou [Rennes], LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Fondation ARC pour la Recherche sur le Cancer [PGA RF20180207070], Institut National du cancer [INCA 2018-133], Agence Nationale de la Recherche (ANR) [ANR-16-CE15-0019-01/03], Leukemia Lymphoma Society [TRP 6593-20], Rennes Metropole, LabEx IGO program - 'Investment into the Future' French Government program [ANR-11-LABX-0016], ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), and ANR-16-CE15-0019,Ig-MemImpact,Rôle de la classe des Ig / BCR dans les interactions cellulaires supportant la mémoire immune et impact immunopathologique(2016)
Subjects: [SDV] Life Sciences [q-bio], Cancer Research, oncogene deregulation, Oncology, germinal center, [SDV]Life Sciences [q-bio], translocation, lymphoma, plasmacytosis
Abstract: International audience; Simple Summary Beyond the classical t(14;18) translocation associated with follicular lymphoma, BCL2 is deregulated in multiple B-cell malignancies, including some cases of myeloma, and through diverse genetic anomalies. It is currently unclear how the various deregulation patterns mechanistically impact the phenotype of theses malignancies. We designed two different BCL2 deregulation models in transgenic mice, whereby the oncogene was either associated with the IgH3 ' RR superenhancer, as in t(14;18), or inserted into the kappa light chain locus. We compared the impact of these models on B-cell fate and lymphoid tissues. Linkage to the IgH superenhancer showed a quite specific impact on germinal center B cell populations. The Ig kappa model was much less specific and strongly boosted the plasma cell in-flow and the accumulation of long-lived plasma cells. Upregulated expression of the anti-apoptotic BCL2 oncogene is a common feature of various types of B-cell malignancies, from lymphoma to leukemia or myeloma. It is currently unclear how the various patterns of deregulation observed in pathology eventually impact the phenotype of malignant B cells and their microenvironment. Follicular lymphoma (FL) is the most common non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells, and its major hallmark is the t(14:18) translocation occurring in B cell progenitors and placing the BCL2 gene under the control of the immunoglobulin heavy chain locus regulatory region (IgH 3 ' RR), thus exposing it to constitutive expression and hypermutation. Translocation of BCL2 onto Ig light chain genes, BCL2 gene amplification, and other mechanisms yielding BCL2 over-expression are, in contrast, rare in FL and rather promote other types of B-cell lymphoma, leukemia, or multiple myeloma. In order to assess the impact of distinct BCL2 deregulation patterns on B-cell fate, two mouse models were designed that associated BCL2 and its full P1-P2 promoter region to either the IgH 3 ' RR, within a "3 ' RR-BCL2" transgene mimicking the situation seen in FL, or an Ig light chain locus context, through knock-in insertion at the Ig kappa locus ("Ig kappa-BCL2" model). While linkage to the IgH 3 ' RR mostly yielded expression in GC B-cells, the Ig kappa-driven up-regulation culminated in plasmablasts and plasma cells, boosting the plasma cell in-flow and the accumulation of long-lived plasma cells. These data demonstrate that the timing and level of BCL2 deregulation are crucial for the behavior of B cells inside GC, an observation that could strongly impact the lymphomagenesis process triggered by secondary genetic hits.
Published: 2022

23. Small vessel disease and collaterals in ischemic stroke patients treated with thrombectomy

Author: Géraud Forestier, Rémi Agbonon, Nicolas Bricout, Wagih Benhassen, Guillaume Turc, Martin Bretzner, Marco Pasi, Joseph Benzakoun, Pierre Seners, Thomas Personnic, Laurence Legrand, Denis Trystram, Christine Rodriguez-Regent, Andreas Charidimou, Natalia S. Rost, Serge Bracard, Frédéric Clarençon, Omer F. Eker, Norbert Nighoghossian, Charlotte Cordonnier, Catherine Oppenheim, Olivier Naggara, Hilde Henon, Grégoire Boulouis, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Dupuytren [CHU Limoges], GHU Paris Psychiatrie et Neurosciences, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHU Pitié-Salpêtrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Université de Lyon, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CarMeN, laboratoire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Aged, 80 and over, Male, Collateral circulation, Radiological and Ultrasound Technology, [SDV]Life Sciences [q-bio], Cerebral small vessel disease, Middle Aged, Brain Ischemia, Stroke, [SDV] Life Sciences [q-bio], Magnetic resonance imaging, Neurology, Cerebral Small Vessel Diseases, Humans, Female, Radiology, Nuclear Medicine and imaging, Prospective Studies, Neurology (clinical), Aged, Ischemic Stroke, Retrospective Studies, Thrombectomy
Abstract: International audience; BACKGROUND AND PURPOSE: To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS). METHODS: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals' adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0-2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores. RESULTS: A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52-0.89] and aOR 0.66; 95%CI [0.5-0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20-0.79]). CONCLUSION: Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals.
Published: 2022

24. Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation

Author: Michel Longy, Christine Maugard, Elisabeth Luporsi, Capucine Delnatte, Séverine Eon-Marchais, Marion Gauthier-Villars, Juana Beauvallet, Noura Mebirouk, Muriel Belotti, Alain Lortholary, Sophie Lejeune-Dumoulin, Christine Lasset, Isabelle Mortemousque, Yves-Jean Bignon, François Eisinger, Sylvie Mazoyer, Valérie Bonadona, Jean-Marc Limacher, Anne Tardivon, Paul Gesta, Sandra Fert-Ferrer, Fabienne Lesueur, Dorothée Le Gal, Jean Chiesa, Florent Soubrier, Pascaline Berthet, Laurence Faivre, Bruno Buecher, Nadine Andrieu, Juliette Coignard, Julie Tinat, Thierry Frebourg, Isabelle Coupier, Sophie Giraud, Laure Barjhoux, Catherine Noguès, Séverine Audebert-Bellanger, Claude Adenis-Lavignasse, Chrystelle Colas, Maximiliano Ribeiro Guerra, Laurence Venat-Bouvet, Eve Cavaciuti, Anne Floquet, Pascal Pujol, Francesca Damiola, Anne Fajac, Jean-Pierre Fricker, Hélène Dreyfus, Dominique Stoppa-Lyonnet, Marie-Gabrielle Dondon, Laurence Gladieff, Olivier Caron, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Federal University of Juiz de Fora (UFIJ), Institut Gustave Roussy (IGR), AP-HP. Université Paris Saclay, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Catherine-de-Sienne [Nantes] (CCS), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), CHU Dijon, 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, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital de Mercy, Centre René Gauducheau, CRLCC René Gauducheau, 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), Centre Léon Bérard [Lyon], Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Bergonié [Bordeaux], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Ramsay Générale de Santé - Hôpital Privé La Louvière, Hôpital Dupuytren [CHU Limoges], Institut Sainte Catherine [Avignon], hôpital couple-enfant [CHU Grenoble Alpes], Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Morvan [Brest], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Groupement Hospitalier Lyon-Est (GHE), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital pasteur [Colmar], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU de Bordeaux Pellegrin [Bordeaux], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital René HUGUENIN (Saint-Cloud), CHU Rouen, Normandie Université (NU), Hôpital Edouard Herriot [CHU - HCL], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), MINES ParisTech - École nationale supérieure des mines de Paris, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), COLO, Mouniati, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Risk, Oncology, medicine.medical_specialty, DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Genes, BRCA2, Genes, BRCA1, Breast Neoplasms, X-ray exposure, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surgical oncology, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Risk factor, RC254-282, High-risk population, Pregnancy, DNA repair genes, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Middle Aged, medicine.disease, 3. Good health, Radiography, [SDV] Life Sciences [q-bio], Low dose, 030220 oncology & carcinogenesis, Mutation, Female, business, Research Article
Abstract: Background Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation. Methods We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC. Results Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure. Conclusion Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene. Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.
Published: 2021

25. Practice patterns for chronic hypoparathyroidism: data from patients and physicians in France

Author: Bertocchio, Jean-Philippe, Grosset, Natalie, Groussin, Lionel, Kamenicky, Peter, Larceneux, Fabrice, Lienhardt-Roussie, Anne, Linglart, Agnès, Maruani, Gérard, Miralli, Eric, Pattou, François, Seervai, Riyad N.H., Sido, Coralie, Silve, Caroline, Vilfaillot, Aurélie, Tabarin, Antoine, Vantyghem, Marie-Christine, Houillier, Pascal, Beaume, Julie, Figueres, Lucile, Bobot, Mickaël, Laforcade, Louis, ayari, hamza, Dolley‐Hitze, Thibault, Gueutin, Victor, Braconnier, Antoine, Golbin, Léonard, Citarda, Salvatore, Seret, Guillaume, Belaïd, Lisa, Cohen, Raphaël, Luque, Yosu, Seervai, Riyad, Overs, Camille, Bertocchio, Jean‐Philippe, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Référence des Maladies Rares du Métabolisme du Phosphore et du Calcium and Filière de Santé Maladies Rares (OSCAR), 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), Hypoparathyroïdisme France, Hôpital Cochin [AP-HP], Physiologie et physiopathologie endocriniennes (PHYSENDO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Dauphine Recherches en Management (DRM), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Hôpital Dupuytren [CHU Limoges], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Recherche translationnelle sur le diabète - U 1190 (RTD), 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), Baylor College of Medicine (BCM), Baylor University, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Bordeaux [Bordeaux], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Physiologie et physiopathologie endocriniennes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Paris sciences et lettres (PSL), and HAL-SU, Gestionnaire
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, physicians, Endocrinology, Diabetes and Metabolism, hypoparathyroidism, practice patterns, 030209 endocrinology & metabolism, hypocalcemia, RC648-665, Diseases of the endocrine glands. Clinical endocrinology, 3. Good health, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, epidemiological studies, Internal Medicine, [SHS.GESTION]Humanities and Social Sciences/Business administration, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Context Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines. Objective To describe the physicians’ practice patterns and their compliance with international guidelines. Design The cohort studies included were Épi-Hypo (118 physicians and 107 patients, from September 2016 to December 2019) and ePatients (110 patients, November 2019). Methods Internet-based cohorts involving all settings at a nationwide level (France). Participants were (i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the (ii) Épi-Hypo study (Épi-Hypo 2019 patients), or (iii) Hypoparathyroidism France, the national representative association (ePatients). Results The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%), or miscellaneous (4%) and 45% were practicing in public universities. The median number of pharmaceutical drug classes prescribed was three per patient. The combination of active vitamin D and calcium salt was given to 59 and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32 and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion. Conclusions The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target other specialists as well as endocrinologists. Full adherence to the guidelines is low in France.
Published: 2021

26. Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study

Author: Anne Veinstein, Jean Paul Mira, Benoit Misset, Jean Reignier, Kader Ouchenir, Hugo Bellut, Frédéric Jacobs, Yves Le Tulzo, Anthony Dugard, Shidasp Siami, Raphaël Porcher, Armelle Mathonnet, Sebastien Preau, Jean Philippe Rigaud, Pierre Asfar, Bertrand Souweine, Arnaud Galbois, Joel Cousson, Florent Dewavrin, Bruno Mégarbane, Olivier Baldesi, Jean Pierre Bedos, E. Varon, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier de Versailles André Mignot (CHV), 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), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Université Paris Descartes, Sorbonne Paris Cité, 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), CHI Créteil, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Pontchaillou [Rennes], Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la source, Hôpital Dupuytren [CHU Limoges], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Louis Pasteur [Chartres], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier du Pays d'Aix, Service de réanimation polyvalente [Centre Hospitalier de Dieppe], Centre hospitalier de Dieppe, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre hospitalier Saint-Joseph [Paris], AP-HP - Hôpital Antoine Béclère [Clamart], Centre hospitalier [Valenciennes, Nord], Hôpital Cochin [AP-HP], and dormoy, valerian
Subjects: medicine.medical_specialty, Severe community-acquired pneumonia, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Intensive care, Internal medicine, Pneumococcal bacteraemia, Streptococcus pneumoniae, Case fatality rate, medicine, Blood culture, 030212 general & internal medicine, 0303 health sciences, medicine.diagnostic_test, RC86-88.9, 030306 microbiology, business.industry, Research, Pneumococcal pneumonia, Medical emergencies. Critical care. Intensive care. First aid, Odds ratio, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Pneumonia, Macrolides, business, Fluoroquinolones
Abstract: Background The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. Methods This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. Results Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. Conclusion Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.
Published: 2021

27. Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)—Comparison With ISCVT Cohort

Author: Véronique Le Cam Duchez, Fausto Viader, Thierry Moulin, Gaëlle Godeneche, Isabelle Crassard, Elisabeth André-Kerneis, Catherine Ternisien, Sophie Laplanche, Brigitte Martin-Bastenaire, Benoit Guillon, Mathieu Zuber, Fernando Pico, Frédéric Klapczynski, Agnès Le Querrec, Ludovic Drouet, Nicolas Gaillard, Thomas Tarek Husein, Emilie Scavazza, Lelia Grunebaum, Bertrand Roussel, M. Berruyer, Sandrine Canaple, Laurent Derex, Aude Triquenot Bagan, Catherine Trichet, Gwénaëlle Runavot, Valérie Wolff, Magali Donnard, Marianne Barbieux-Guillot, Emmanuelle Robinet-Borgomino, Hong-An Allano, Sophie Cluet-Dennetiere, Philippe Tassan, Francisco Macian-Montoro, François Rouanet, Emmanuel Ellie, Geneviève Freyburger, Guillaume Mourey, Raphaël Marlu, Pierre-Emmanuel Morange, Jean-Yves Peeltier, Fanny Menard, Service de neurologie [Amiens], CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence national des angiœdèmes (CREAK), CHU Grenoble-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), 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 de la Timone [CHU - APHM] (TIMONE), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de la Côte Basque (CHCB), Pôle des Neurosciences Cliniques [Bordeaux], CHU Bordeaux [Bordeaux], Laboratoire d'Hématologie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Sud Saint Pierre [Ile de la Réunion], Hôpitaux Universitaires Paris Nord Val-de-Seine (HUPNVS), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-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), Hôpital Dupuytren [CHU Limoges], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Saint-Joseph [Paris], Service de Biologie [GH Saint-Joseph - APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pediatrics, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], cerebral veins, medicine.disease, Thrombosis, prospective observational study, Venous thrombosis, Neurology, Radiological weapon, Cohort, Etiology, medicine, sinus, Neurology. Diseases of the nervous system, Neurology (clinical), Risk factor, Prospective cohort study, business, RC346-429, thrombosis, French cohort, Rare disease, Original Research
Abstract: Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown.Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort.Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al.Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients.Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.
Published: 2021
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28. Sentinel node involvement with or without completion axillary lymph node dissection: treatment and pathologic results of randomized SERC trial

Author: Gilles Houvenaeghel, Monique Cohen, Pédro Raro, Jérémy De Troyer, Pierre Gimbergues, Christine Tunon de Lara, Vivien Ceccato, Véronique Vaini-Cowen, Christelle Faure-Virelizier, Frédéric Marchal, Tristan Gauthier, Eva Jouve, Pierrick Theret, Claudia Regis, Philippe Gabelle, Julia Pernaut, Francesco Del Piano, Gauthier D’Halluin, Stéphane Lantheaume, Emile Darai, Bassoodéo Beedassy, Caroline Dhainaut-Speyer, Xavier Martin, Sophie Girard, Richard Villet, Emilie Monrigal, Théophile Hoyek, Jean-François Le Brun, Pierre-Emmanuel Colombo, Agnès Tallet, Jean-Marie Boher, SERC trial group, 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), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Bergonié [Bordeaux], Institut Jean Godinot [Reims], Polyclinique du Parc Rambot, Centre Léon Bérard [Lyon], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Hôpital Dupuytren [CHU Limoges], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier de Saint-Quentin, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Groupe Hospitalier Mutualiste [Grenoble] (GHM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Hôpital privé Sainte-Marie - Ramsay Générale de Santé, Centre Hospitalier Alpes Léman (CHAL), Groupe Hospitalier Diaconesses Croix Saint-Simon, Clinique Clémentville [Montpellier], Centre hospitalier d'Auxerre (CHA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, 'Cancer, Biomedicine & Society' group (SESSTIM - U1252 INSERM - AMU - UMR 259 IRD), 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)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-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)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille Nord de France (COMUE)-UNICANCER, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier d'Auxerre, and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, 0302 clinical medicine, Medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, In patient, Total Mastectomy, RC254-282, 030304 developmental biology, Cancer, 0303 health sciences, business.industry, Significant difference, Axillary Lymph Node Dissection, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Sentinel node, 3. Good health, Surgery, Clinical trial, Breast conservative surgery, Oncology, 030220 oncology & carcinogenesis, Surgical oncology, business, Mastectomy
Abstract: Based on results of clinical trials, completion ALND (cALND) is frequently not performed for patients with breast conservation therapy and one or two involved sentinel nodes (SN) by micro- or macro-metastases. However, there were limitations despite a conclusion of non-inferiority for cALND omission. No trial had included patients with SN macro-metastases and total mastectomy or with >2 SN macro-metastases. The aim of the study was too analyze treatment delivered and pathologic results of patients included in SERC trial. SERC trial is a multicenter randomized non-inferiority phase-3 trial comparing no cALND with cALND in cT0-1-2, cN0 patients with SN ITC (isolated tumor cells) or micro-metastases or macro-metastases, mastectomy or breast conservative surgery. We randomized 1855 patients, 929 to receive cALND and 926 SLNB alone. No significant differences in patient’s and tumor characteristics, type of surgery, and adjuvant chemotherapy (AC) were observed between the two arms. Rates of involved SN nodes by ITC, micro-metastases, and macro-metastases were 5.91%, 28.12%, and 65.97%, respectively, without significant difference between two arms for all criteria. In multivariate analysis, two factors were associated with higher positive non-SN rate: no AC versus AC administered after ALND (OR = 3.32, p 2 involved SN versus ≤2 (OR = 3.45, p = 0.0258). Crude rates of positive NSN were 17.62% (74/420) and 26.45% (73/276) for patient’s eligible and non-eligible to ACOSOG-Z0011 trial. No significant differences in patient’s and tumor characteristics and treatment delivered were observed between the two arms. Higher positive-NSN rate was observed for patients with AC performed after ALND (17.65% for SN micro-metastases, 35.22% for SN macro-metastases) in comparison with AC administered before ALND.
Published: 2021

29. Treatment of 120 adult osteosarcoma patients with metachronous and synchronous metastases: A retrospective series of the French Sarcoma Group

Author: Jean-Yves Blay, Antoine Italiano, Florence Duffaud, Sophie Piperno-Neumann, Emmanuelle Bompas, Corinne Delcambre, Christine Chevreau, Julien Mancini, Jean-Emmanuel Kurtz, Pascaline Boudou-Rouquette, Pauline Soibinet-Oudot, Christine Le Maignan, Axel Le Cesne, Valérie Lebrun, Elise Lavit, Mihaela Aldea, Nicolas Isambert, Nelly Firmin, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Curie [Paris], Institut du Cancer de Montpellier (ICM), Institut Bergonié [Bordeaux], UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CHU Strasbourg, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Dupuytren [CHU Limoges], Institut Jean Godinot [Reims], Institut Claudius Regaud, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Institut de Recherche pour le Développement (IRD), 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), Centre Léon Bérard [Lyon], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Malbec, Odile
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Adolescent, [SDV]Life Sciences [q-bio], Bone Neoplasms, Systemic therapy, Metastasis, Neoplasms, Multiple Primary, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Progression-free survival, 030304 developmental biology, Retrospective Studies, 0303 health sciences, Osteosarcoma, Lung, treatment, business.industry, Neoplasms, Second Primary, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, medicine.anatomical_structure, 030220 oncology & carcinogenesis, metastatic osteosarcomas, Female, Sarcoma, prognosis, business
Abstract: International audience; Treatment options for metastatic osteosarcomas are scarce. Following failure of standard first line therapy, patients who relapse present a challenging treatment dilemma, and have a poor prognosis. Surgical removal of all metastases is essential. A retrospective analysis of patients with metastatic osteosarcomas was conducted in 15 French Sarcoma Group centers. From January 2009 to December 2018, we identified 120 adult patients; 36 with synchronous and 84 with metachronous metastases with 74 males and 46 females. Mean age was 30 years (18-53). Metastatic sites were lung, bone and other in 91, 11 and 24 patients, respectively. Mean time to first metachronous metastases was 22 months (4-97). All patients except 13 (10.8%) with metachronous metastases received a first line systemic treatment for relapse, and 39 patients (32.5%) were included in a clinical trial. Eighty-one patients (67.5%) had local treatment of distant metastases. Median progression free survival (PFS) and overall survival (OS) were 5.5 (95% CI 4.6-6.4) and 20.5 months (95% CI 13.2-27.7) respectively for the overall group. In multivariate analysis, more than five metastases, time to first metastases
Published: 2021

30. A unique Toxoplasma gondii haplotype accompanied the global expansion of cats

Author: Lokman Galal, Frédéric Ariey, Meriadeg Ar Gouilh, Marie-Laure Dardé, Azra Hamidović, Franck Letourneur, Franck Prugnolle, Aurélien Mercier, Prugnolle, Franck, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), 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), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Parasitologie Mycologie [CHU Limoges], CHU Limoges, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), PRES Sorbonne Paris Cité, Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Ecologie et Evolution de la Santé (CREES), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Hôpital Dupuytren [CHU Limoges], Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)
Subjects: Felidae, Multidisciplinary, Toxoplasmosis, Animal, Haplotypes, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Cats, General Physics and Astronomy, Animals, General Chemistry, Americas, Toxoplasma, General Biochemistry, Genetics and Molecular Biology
Abstract: Toxoplasma gondii is a cyst-forming apicomplexan parasite of virtually all warm-blooded species, with all true cats (Felidae) as definitive hosts. It is the etiologic agent of toxoplasmosis, a disease causing substantial public health burden worldwide. Few intercontinental clonal lineages represent the large majority of isolates worldwide. Little is known about the evolutionary forces driving the success of these lineages, the timing and the mechanisms of their global dispersal. In this study, we analyse a set of 156 genomes and we provide estimates of T. gondii mutation rate and generation time. We elucidate how the evolution of T. gondii populations is intimately linked to the major events that have punctuated the recent history of cats. We show that a unique haplotype, whose length represents only 0.16% of the whole T. gondii genome, is common to all intercontinental lineages and hybrid populations derived from these lineages. This haplotype has accompanied wildcats (Felis silvestris) during their emergence from the wild to domestic settlements, their dispersal in the Old World, and their expansion in the last five centuries to the Americas. The selection of this haplotype is most parsimoniously explained by its role in sexual reproduction of T. gondii in domestic cats.
Published: 2021

31. Valeurs normales des diamètres de l'aorte abdominale en population générale d'Afrique Sub-Saharienne

Author: Vandroux, David, Houehanou, Corine, Saka, D., SONOU, A., Magne, Julien, Houinato, Dismand, Preux, Pierre-Marie, Aboyans, Victor, Lacroix, Philippe, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [CHU Limoges], CHU Limoges, Laboratory of Chronic and Neurological Diseases Epidemiology (LEMACEN), University of Abomey Calavi (UAC), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), Hôpital Dupuytren [CHU Limoges], and Grelier, Elisabeth
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

32. Title: AA amyloidosis complicating monoclonal gammopathies, an unusual feature validating the concept of 'monoclonal gammopathy of inflammatory significance'? Authors: Alexandre Terré¹ , ¹³ https://orcid.org/0000-0002-8295-9068, Magali Colombat²

Author: Terré, Alexandre, Colombat, Magali, Cez, Alexandre, Martin, Claire, Diet, Carine, Brechignac, Sabine, Oghina, Silvia, Bodez, Diane, Faguer, Stanislas, Savey, Léa, Galland, Joris, Boffa, Jean‐jacques, Grateau, Gilles, Jaccard, Arnaud, Buob, David, Georgin‐lavialle, Sophie, Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Toulouse [Toulouse], Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Saint-Louis de La Rochelle (CH La Rochelle), CHU Henri Mondor, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre cardiologique du Nord (CCN), Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Service de Pathologie [CHU Tenon], HAL-SU, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Monoclonal gammopathies, Mass-spectrometry, AL amyloidosis, paraproteinemia, AA amyloidosis and monoclonal gammopathies AA amyloidosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; IntroductionAL amyloidosis is caused by the proliferation of an immunoglobulin-secreting B cell clone. AA amyloidosis is a rare complication of chronic inflammation. However, some patients present with diseases combining monoclonal immunoglobulin production and chronic inflammation. The aim of this work was to describe cases of AA amyloidosis associated with monoclonal gammopathies.Patients and methodsWe reviewed all patients reported in French national amyloid centres presenting with AA amyloidosis and monoclonal gammopathy and performed a literature review. The quality of AA amyloidosis diagnosis and the causal relationship with monoclonal gammopathy were assessed.ResultsIn total, four patients from our centres and eight from the literature fulfilled the inclusion criteria. The haematological disorders presenting with monoclonal gammopathy were as follows: Waldenström macroglobulinaemia (n = 8), Schnitzler syndrome (n = 2), multiple myeloma (n = 1) and monoclonal gammopathy of undetermined significance (n = 1). Treatment strategies varied among the cases, with the treatment of the haematological disorder in 4 and anti-inflammatory treatment in 2.ConclusionMonoclonal gammopathies might be a rare and poorly known cause of AA amyloidosis. Such monoclonal gammopathies could be named “monoclonal gammopathies of inflammatory significance.”
Published: 2021

33. SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration

Author: Barbier, Mathieu, Camuzat, Agnès, Hachimi, Khalid El, Guegan, Justine, Rinaldi, Daisy, Lattante, Serena, Houot, Marion, Sánchez-Valle, Raquel, Sabatelli, Mario, Antonell, Anna, Molina-Porcel, Laura, Clot, Fabienne, Couratier, Philippe, van der Ende, Emma, van der Zee, Julie, Manzoni, Claudia, Camu, William, Cazeneuve, Cécile, Sellal, François, Didic, Mira, Golfier, Véronique, Pasquier, Florence, Duyckaerts, Charles, Rossi, Giacomina, Bruni, Amalia C, Alvarez, Victoria, Gómez-Tortosa, Estrella, de Mendonça, Alexandre, Graff, Caroline, Masellis, Mario, Nacmias, Benedetta, Oumoussa, Badreddine Mohand, Jornea, Ludmila, Forlani, Sylvie, Van Deerlin, Viviana, Rohrer, Jonathan D, Gelpi, Ellen, Rademakers, Rosa, Van Swieten, John, Le Guern, Eric, Van Broeckhoven, Christine, Ferrari, Raffaele, Génin, Emmanuelle, Brice, Alexis, Ber, Le, Isabelle Alexis Brice, Sophie, Auriacombe, Serge, Belliard, Anne, Bertrand, Anne, Bissery, Fre ́ de, ́ ric Blanc, Marie-Paule, Boncoeur, Ste, ́ phanie Bombois, Claire Boutoleau-Bretonnie` re, Agne`, s Camuzat, Mathieu, Ceccaldi, Marie, Chupin, Philippe, Couratier, Olivier, Colliot, Vincent, Deramecourt, Mira, Didic, Bruno, Dubois, Charles, Duyckaerts, Fre ́ de, ́ rique Etcharry-Bouyx, Aure, ́ lie Guignebert-Funkiewiez, Maı ̈te, ́ Formaglio, ́ ronique Golfier, Ve, Marie-Odile, Habert, Didier, Hannequin, Lucette, Lacomblez, Julien, Lagarde, ́ raldine Lautrette, Ge, Isabelle Le Ber, Benjamin Le Toullec, Richard, Levy, Marie-Anne, Mackowiak, Bernard-Franc ̧ois Michel, Florence, Pasquier, Thibaud, Lebouvier, Carole Roue, ́ -Jagot, Christel Thauvin- Robinet, Catherine, Thomas-Anterion, Je ́ re, ́ mie Pariente, Franc ̧ois Salachas, Sabrina, Sayah, Franc ̧ois Sellal, Assi-Herve, ́ Oya, Daisy, Rinaldi, Adeline, Rollin-Sillaire, Martine, Vercelletto, David, Wallon, Armelle, Rametti-Lacroux, Raffaele, Ferrari, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Adaikalavan, Ramasamy, Kwok, John B. J., Carol Dobson- Stone, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Olivier, Piguet, Lauren, Bartley, Elizabeth, Thompson, Isabel Herna, ́ ndez, Agustı ́n Ruiz, Merce`, Boada, Barbara, Borroni, Alessandro, Padovani, Carlos, Cruchaga, Cairns, Nigel J., Luisa, Benussi, Giuliano, Binetti, Roberta, Ghidoni, Gianluigi, Forloni, Diego, Albani, Daniela, Galimberti, Chiara, Fenoglio, Maria, Serpente, Elio, Scarpini, ́ n, Jordi Clarimo, Alberto Lleo, ́, Rafael, Blesa, Maria Landqvist Waldo, ̈, Karin, Nilsson, Christer, Nilsson, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Jordan, Grafman, Morris, Christopher M., Johannes, Attems, Griffiths, Timothy D., Mckeith, Ian G., Thomas, Alan J., Pietro, Pietrini, Edward, Uey, Wassermann, Eric M., Atik, Baborie, Evelyn, Jaros, Tierney, Michael C., Pau, Pastor, Cristina, Razquin, Sara, Ortega-Cubero, Elena, Alonso, Robert, Perneczky, Janine, Diehl-Schmid, Panagiotis, Alexopoulos, Alexander, Kurz, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Ekaterina, Rogaeva, Peter St George-Hyslop, Giacomina, Rossi, Fabrizio, Tagliavini, Giorgio, Giaccone, Rowe, James B., Schlachetzki, Johannes C. M., James, Uphill, John, Collinge, Simon, Mead, Adrian, Danek, Van Deerlin, Vivianna M., Murray, Grossman, Trojanowski, John Q., Julie van der Zee, Christine Van Broeckhoven, Cappa, Stefano F., Isabelle, Leber, Alexis, Brice, Benedetta, Nacmias, Sandro, Sorbi, Silvia, Bagnoli, Irene, Piaceri, Nielsen, Jørgen E., Hjermind, Lena E., Matthias, Riemenschneider, Manuel, Mayhaus, Bernd, Ibach, Gilles, Gasparoni, Sabrina, Pichler, Wei, Gu, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Maria Grazia Spillantini, Morris, Huw R., Patrizia, Rizzu, Peter, Heutink, Snowden, Julie S., Sara, Rollinson, Anna, Richardson, Alexander, Gerhard, Bruni, Amalia C., Raffaele, Maletta, Francesca, Frangipane, Chiara, Cupidi, Livia, Bernardi, Maria, Anfossi, Maura, Gallo, Maria Elena Conidi, Nicoletta, Smirne, Rosa, Rademakers, Matt, Baker, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., David, Knopman, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Howard, Rosen, van Swieten, John C., Dopper, Elise G. P., Harro, Seelaar, Pijnenburg, Yolande A. L., Philip, Scheltens, Giancarlo, Logroscino, Rosa, Capozzo, Valeria, Novelli, Puca, Annibale A., Massimo, Franceschi, Alfredo, Postiglione, Graziella, Milan, Paolo, Sorrentino, Mark, Kristiansen, Huei-Hsin, Chiang, Caroline, Graff, Adeline, Rollin, Dimitrios, Kapogiannis, Luigi, Ferrucci, Stuart, Pickering-Brown, Singleton, Andrew B., John, Hardy, Parastoo, Momeni., Neurology, Amsterdam Neuroscience - Neurodegeneration, Institut du Cerveau = Paris Brain Institute (ICM), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Dupuytren [CHU Limoges], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Molecular Neurology (VIB-UAntwerp), University of Antwerp (UA), University College of London [London] (UCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Yves le Foll, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Hospital Central de Asturias, Institute of Health Research of Principado de Asturias (ISPA), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Karolinska University Hospital [Stockholm], Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione Don Carlo Gnocchi, Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), 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), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, 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), The French clinical and genetic Research network on FTLD/FTLD-ALS and PREVDEMALS, The International Frontotemporal Dementia Genomics Consortium, The European Early Onset Dementia (EU -EOD) Consortium, Brainbank Neuro-CEB Neuropathology Network, and Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS
Subjects: Adult, Male, TDP-43, C9orf72, SLITRK2, amyotrophic lateral sclerosis, frontotemporal dementia, Nerve Tissue Proteins, Settore MED/03 - GENETICA MEDICA, Polymorphism, Single Nucleotide, Cohort Studies, Genes, X-Linked, 80 and over, Medicine, Dementia, Humans, Allele, Age of Onset, Polymorphism, Aged, Aged, 80 and over, biology, C9orf72 Protein, business.industry, Membrane Proteins, MESH: Frontotemporal Lobar Degeneration / epidemiology, Frontotemporal Lobar, Degeneration / genetics, Genes, X-Linked / genetics, Genome-Wide Association Study / methods, Frontotemporal lobar degeneration, Single Nucleotide, Middle Aged, X-Linked, medicine.disease, Amyotrophic lateral sclerosis, Minor allele frequency, Genes, Immunology, Synaptophysin, biology.protein, Female, MESH: Adult, C9orf72 Protein / genetics, Frontotemporal Lobar Degeneration / diagnosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Human medicine, Neurology (clinical), MESH: Humans, Membrane Proteins / genetics, Nerve Tissue Proteins / genetics, Polymorphism, Single Nucleotide / genetics, Age of onset, Frontotemporal Lobar Degeneration, business, Frontotemporal dementia, Genome-Wide Association Study
Abstract: The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.
Published: 2021

34. Sudden coma onset following simultaneous bilateral carotid occlusion

Author: Gregoire Boulouis, Antoine Dusonchet, François Lun, Géraud Forestier, Hôpital Dupuytren [CHU Limoges], Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GHU Paris Psychiatrie et Neurosciences, FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Neurologie - Unité Neuro-Vasculaire [Site d'Orsay] (GH Nord-Essonne), Groupe Hospitalier Nord Essonne [Longjumeau], Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Carotid Artery Diseases, Endovascular interventions, 030204 cardiovascular system & hematology, Imaging, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Neurocritical care, Medicine, Humans, Carotid Stenosis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Coma, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Ischemic stroke, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Neurointensive care, Functional recovery, General Medicine, CAROTID OCCLUSION, Stroke, Treatment Outcome, Anesthesia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carotid Artery, Internal
Abstract: International audience; No abstract available
Published: 2021

35. Normal values of aortic root diameters en Sub-Saharan Africans: the TAHES study

Author: Vandroux, David, Houehanou, Corinne, Saka, D., Sonou, A., Magne, Julien, Houinato, Dismand, Preux, Pierre-Marie, Aboyans, Victor, Lacroix, Philippe, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [CHU Limoges], CHU Limoges, Laboratory of Chronic and Neurological Diseases Epidemiology (LEMACEN), University of Abomey Calavi (UAC), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Hôpital Dupuytren [CHU Limoges], European Society of cardiology (ESC), and Grelier, Elisabeth
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

36. In Vitro Antimicrobial Susceptibility Profiles of Gram-Positive Anaerobic Cocci Responsible for Human Invasive Infections

Author: Guérin, François, Dejoies, Loren, Degand, Nicolas, Guet-Revillet, Hélène, Janvier, Frédéric, Corvec, Stéphane, Barraud, Olivier, Guillard, Thomas, Walewski, Violaine, Gallois, Emmanuelle, Cattoir, Vincent, Group, on behalf of the GMC Study, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Universitaire de Reims (CHU Reims), Groupe Hospitalier Hôpitaux Universitaires Paris Seine-Saint-Denis [Bobigny] (GH HUPSSD), Institut Gustave Roussy (IGR), Microbiologie, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), ARN régulateurs bactériens et médecine (BRM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This research received no external funding., dormoy, valerian, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Microbiology (medical), Peptoniphilus, Imipenem, food.ingredient, Cefotaxime, QH301-705.5, [SDV]Life Sciences [q-bio], ved/biology.organism_classification_rank.species, Biology, Microbiology, Article, 03 medical and health sciences, food, Parvimonas micra, Virology, medicine, polycyclic compounds, antimicrobial resistance, Biology (General), 030304 developmental biology, 0303 health sciences, 030306 microbiology, ved/biology, Peptostreptococcus anaerobius, GPAC, Clindamycin, Anaerococcus, Amoxicillin, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Finegoldia magna, 3. Good health, [SDV] Life Sciences [q-bio], medicine.drug, Piperacillin
Abstract: The aim of this multicentre study was to determine the in vitro susceptibility to anti-anaerobic antibiotics of Gram-positive anaerobic cocci (GPAC) isolates responsible for invasive infections in humans. A total of 133 GPAC isolates were collected in nine French hospitals from 2016 to 2020. All strains were identified to the species level (MALDI-TOF mass spectrometry, 16S rRNA sequencing). Minimum inhibitory concentrations (MICs) of amoxicillin, piperacillin, cefotaxime, imipenem, clindamycin, vancomycin, linezolid, moxifloxacin, rifampicin, and metronidazole were determined by the reference agar dilution method. Main erm-like genes were detected by PCR. The 133 GPAC isolates were identified as follows: 10 Anaerococcus spp., 49 Finegoldia magna, 33 Parvimonas micra, 30 Peptoniphilus spp., and 11 Peptostreptococcus anaerobius. All isolates were susceptible to imipenem, vancomycin (except 3 P. micra), linezolid and metronidazole. All isolates were susceptible to amoxicillin and piperacillin, except for P. anaerobius (54% and 45% susceptibility only, respectively). MICs of cefotaxime widely varied while activity of rifampicin, and moxifloxacin was also variable. Concerning clindamycin, 31 were categorized as resistant (22 erm(A) subclass erm(TR), 7 erm(B), 1 both genes and 1 negative for tested erm genes) with MICs from 8 to &gt, 32 mg/L. Although GPACs are usually susceptible to drugs commonly used for the treatment of anaerobic infections, antimicrobial susceptibility should be evaluated in vitro.
Published: 2021
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37. A single-arm multicentre phase II trial of doxorubicin in combination with trabectedin in the first-line treatment for leiomyosarcoma with long-term follow-up and impact of cytoreductive surgery

Author: Anne Floquet, Frédéric Selle, Esma Saada-Bouzid, Benjamin Lacas, Olivier Collard, Christine Chevreau, François Bertucci, Patricia Pautier, C. Delcambre, Maud Toulmonde, P Soulier, Didier Cupissol, Valerie Lebrun-Ly, Florence Duffaud, Emmanuelle Bompas, C. Guillemet, Jérôme Alexandre, N. Isambert, A. Le Cesne, Nicolas Penel, Sophie Piperno-Neumann, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Institut Bergonié [Bordeaux], UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Dupuytren [CHU Limoges], CRLCC Paul Papin, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital de la Timone [CHU - APHM] (TIMONE), Bertucci, François, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Leiomyosarcoma, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, doxorubicin plus trabectedin, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Doxorubicin, education, Trabectedin, Original Research, Chemotherapy, education.field_of_study, business.industry, Soft tissue, Cytoreduction Surgical Procedures, leiomyosarcoma, medicine.disease, Confidence interval, Surgery, first-line chemotherapy, Oncology, Female, business, Pegfilgrastim, Follow-Up Studies, medicine.drug
Abstract: Background Uterine leiomyosarcomas (U-LMSs) and soft tissue leiomyosarcomas (ST-LMSs) are rare tumours with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with manageable toxicity. Herein, we report the updated and long-term results of progression-free survival (PFS) and overall survival (OS). Patients and methods Patients received 60 mg/m2 intravenous doxorubicin followed by trabectedin 1.1 mg/m2 as a 3-h infusion on day 1 and pegfilgrastim on day 2, every 3 weeks, up to six cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results One-hundred and eight patients were enrolled, mainly with metastatic disease (85%), and 20 patients (18.5%) had surgical resection of metastases after chemotherapy. With a median follow-up of 7.2 years [95% confidence interval (CI) 6.9-8.2 years], the median PFS was 10.1 months (95% CI 8.5-12.6 months) in the whole population, and 8.3 months (95% CI 7.4-10.3 months) and 12.9 months (95% CI 9.2-14.1 months) for U-LMSs and ST-LMSs, respectively. The median OS was 34.4 months (95% CI 26.9-42.7 months), 27.5 months (95% CI 17.9-38.2 months), and 38.7 months (95% CI 31.0-52.9 months) for the whole population, U-LMSs, and ST-LMSs, respectively. The median OS of the patients with resected metastases was not reached versus 31.6 months in the overall population without surgery (95% CI 23.9-35.4 months). Conclusions These updated results confirm the impressive efficiency of the doxorubicin plus trabectedin combination given in first-line therapy for patients with locally advanced/metastatic LMS in terms of PFS and OS. Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing the doxorubicin plus trabectedin combination versus doxorubicin alone in first-line therapy in metastatic LMSs, are pending., Highlights • Long-term results on PFS and OS of doxorubicin and trabectedin in first-line treatment for advanced leiomyosarcoma. • The update confirms the impressive efficiency of the doxo+trab in terms of PFS and OS. • Results of a randomized phase-III study comparing dox+trab combination versus doxo alone in first-line therapy in metastatic LMS are pending.
Published: 2021

38. National Health Care data system analysis of glaucoma surgery activity in France in 2016

Author: Magali Bouisse, Tristan Bourcier, P.-Y. Robert, Patrice François, Julie Dufournet, Bastien Boussat, Alain M. Bron, Florent Aptel, Vincent Daien, Christophe Chiquet, CHU Grenoble, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire Gui de Chauliac (CHU Gui de Chauliac), CHU Strasbourg, Université de Strasbourg (UNISTRA), and Hôpital Dupuytren [CHU Limoges]
Subjects: Adult, medicine.medical_specialty, National Health Programs, genetic structures, medicine.medical_treatment, Glaucoma, Ophthalmologic Surgical Procedures, surgery, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Glaucoma surgery, Humans, Trabeculectomy, nationwide study, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Aged, Aged, 80 and over, National health, Ophthalmologists, business.industry, General surgery, Incidence (epidemiology), General Medicine, Middle Aged, medicine.disease, eye diseases, 3. Good health, Ophthalmology, glaucoma, Private practice, Public hospital, 030221 ophthalmology & optometry, epidemiology, France, business, 030217 neurology & neurosurgery
Abstract: International audience; PURPOSE: To describe the glaucoma surgery offer in France in 2016. METHODS: We used the French National Health Care System database to identify all medical procedures carried out in 2016. The study investigated the entire population aged 30 years and older that had undergone glaucoma surgery, alone or combined with another surgery. We calculated the incidence of surgeries per 100 000 inhabitants 30 years of age and older performed by ophthalmologists carrying out at least 50 procedures annually, the number of surgeons doing these surgeries, the mean age of these practitioners, and the number of surgeons older than 55 years. RESULTS: In 2016, 16 854 glaucoma surgeries were performed in patients aged 30 years and older, for an incidence of 40.8 per 100 000 inhabitants aged 30 years and older. The most frequent procedure performed was trabeculectomy followed by non-penetrating deep sclerectomy (16.7 and 11.7, respectively, per 100 000 inhabitants 30 years of age and older). Private practice glaucoma surgery accounted for 47% of the activity of surgeons performing at least 50 surgeries per year and 60% of the total surgical activity. Of the private practice ophthalmologists performing at least 50 glaucoma surgery procedures per year, 58.5% were over 55 years of age, and 23.5% of public hospital ophthalmologists were over 55 years of age. CONCLUSIONS: This study demonstrates that surgeons performing glaucoma surgeries are often older. It is necessary to take note of the country's educational capacity to ensure that the number of ophthalmological surgeons remains adapted to demand.
Published: 2021

39. Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin plus Paclitaxel for Vulnerable Older Adult Women with Ovarian Cancer:A GINECO/GCIG Randomized Clinical Trial

Author: Frédérique Rousseau, Olivier Tredan, E. Malaurie, Aude-Marie Savoye, Pierre-Emmanuel Brachet, Claire Falandry, Jørn Herrstedt, Robert Sverdlin, Laurence Venat-Bouvet, Eric Pujade-Lauraine, Emmanuelle Bourbouloux, Alain Lortholary, Fabien Tinquaut, Loic Mourey, Gilles Freyer, Véronique D'Hondt, Marie-Ange Mouret-Reynier, Laetitia Stefani, Alain Zannetti, Domenica Lorusso, 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), Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire et du sein [Paris] (GINECO), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), IRCCS Istituto Nazionale dei Tumori [Milano], Zealand University Hospital [Roskilde, Denmark], Institut Jean Godinot [Reims], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CRLCC René Gauducheau, Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cancer de Montpellier (ICM), Hôpital privé du Confluent [Nantes], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Cholet (CHC), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Dupuytren [CHU Limoges], Centre Léon Bérard [Lyon], Institut Claudius Regaud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), and CarMeN, laboratoire
Subjects: Cancer Research, medicine.medical_specialty, Combination therapy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Internal medicine, Medicine, Data monitoring committee, 030212 general & internal medicine, Chemotherapy, business.industry, Chemotherapy regimen, Carboplatin, 3. Good health, Discontinuation, [SDV] Life Sciences [q-bio], Oncology, chemistry, 030220 oncology & carcinogenesis, business
Abstract: Importance: Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. Objective: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer. Design, Setting, and Participants: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. Interventions: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m 2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m 2, on days 1, 8, and 15 every 4 weeks. Main Outcomes and Measures: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death. Results: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). Conclusions and Relevance: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02001272.
Published: 2021

40. Questions non résolues sur la maladie thrombo-embolique veineuse. Consensus de la Société française de médecine vasculaire (SFMV)

Author: M. Maufus, Philippe Lacroix, A. Bura-Rivière, J.-L. Gillet, D. Brisot, M. Elias, J.-P. Galanaud, Gilles Pernod, Jean Luc Bosson, Antoine Elias, Stéphane Zuily, A. Sevestre, A. Diard, Laurent Bertoletti, Denis Wahl, Paul Frappé, Isabelle Quéré, P. Ouvry, C. Jurus, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, CH Pierre Oudot Bourgoin-Jallieu, CHU Amiens-Picardie, University of Toronto, Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de Rangueil, CHU Toulouse [Toulouse], Clinique du Tonkin, Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Université Jean Monnet [Saint-Étienne] (UJM)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2019

41. Factors influencing the mid-term radiological and functional outcomes of 41 post-fracture bipolar radial head arthroplasty cases at a mean follow-up of 87 months

Author: Guillaume Vergnenegre, Christian Mabit, Pierre-Sylvain Marcheix, Jérémy Hardy, Jean-Louis Charissoux, Céline Cuenca, and Hôpital Dupuytren [CHU Limoges]
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Elbow, Periprosthetic, Arthroplasty, [SPI.MAT]Engineering Sciences [physics]/Materials, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Elbow Joint, medicine, Humans, Orthopedics and Sports Medicine, Range of Motion, Articular, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, 030222 orthopedics, business.industry, 030229 sport sciences, [CHIM.MATE]Chemical Sciences/Material chemistry, Middle Aged, 3. Good health, Surgery, Treatment Outcome, medicine.anatomical_structure, Humeroulnar joint, Radiological weapon, Ligament, Radial head fracture, Implant, Radius Fractures, business, Follow-Up Studies
Abstract: Introduction When treating comminuted radial head fractures that cannot be adequately fixed, the next option is arthroplasty (radial head replacement). We hypothesized that the radiological and functional outcomes of bipolar mobile cup radial head arthroplasty is not influenced by the length of follow-up but instead by the correct positioning of the implant intraoperatively and by the presence of associated bone or ligament injuries. Patients and methods Between May 1998 and December 2016, 82 cases of radial head arthroplasty were performed at our hospital. The mean age of patients at the time of arthroplasty was 53 years (22–81). Ligament or bone injuries complicated the radial head fractures in 70% of patients. Results For the final assessment, 41 patients were reviewed and included in the statistical analysis with a mean of 82 months (12–228). The mean MEPS at the final assessment was 88.7 (61–100). There were 23 excellent, 9 good, 9 average and 0 poor results. The average DASH score was 18.7 (0–55). The average VAS for pain was 1.0 (0–5). Five patients (12%) required surgical revision, including one implant change. Our statistical analysis found no relationship between follow-up time and functional outcomes. The appearance of periprosthetic radiolucent lines was not affected by the length of follow-up. Associated bone or ligament injuries significantly increased the probability of periprosthetic radiolucent lines, humeroulnar joint degeneration and decentering of the implanted cup. Radiological evidence of a suspended implant was associated with significantly worse functional outcomes. Conclusion This study confirms the long-term stability of the clinical outcomes of radial head arthroplasty. There was no relationship between worsening radiological appearance of the implant and the clinical outcomes. It is critical that this implant not be oversized or suspended, as this can trigger premature capitellar erosion and painful stiffness of the operated elbow. Level of evidence IV; systematic retrospective analysis.
Published: 2021

42. Endoscopic characterization of colorectal neoplasia with different published classifications: comparative study involving CONECCT classification

Author: Bonniaud, Paul, Jacques, Jérémie, Lambin, Thomas, Gonzalez, Jean-Michel, Dray, Xavier, Coron, Emmanuel, Leblanc, Sarah, Chevaux, Jean-Baptiste, Léger-Nguyen, Florence, Hamel, Benjamin, Lienhart, Isabelle, Rivory, Jérôme, Ponchon, Thierry, Saurin, Jean-Christophe, Monzy, Frédéric, Legros, Romain, Lépilliez, Vincent, Subtil, Fabien, Barret, Maximilien, Pioche, Mathieu, HAL-SU, Gestionnaire, Hospices Civils de Lyon (HCL), Hôpital Dupuytren [CHU Limoges], Société Française d'Endoscopie Digestive, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Clinique Jean-Mermoz, Hôpital privé Jean Mermoz, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Clinique du Val d'Ouest, Hôpital Villefranche sur Saône, Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, Hôpital-Clinique Claude-Bernard [Metz], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Original article, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Pharmacology (medical), RC799-869, Diseases of the digestive system. Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background and study aims The aim of this study was to validate the COlorectal NEoplasia Classification to Choose the Treatment (CONECCT) classification that groups all published criteria (including covert signs of carcinoma) in a single table. Patients and methods For this multicenter comparative study an expert endoscopist created an image library (n = 206 lesions; from hyperplastic to deep invasive cancers) with at least white light Imaging and chromoendoscopy images (virtual ± dye based). Lesions were resected/biopsied to assess histology. Participants characterized lesions using the Paris, Laterally Spreading Tumours, Kudo, Sano, NBI International Colorectal Endoscopic Classification (NICE), Workgroup serrAted polypS and Polyposis (WASP), and CONECCT classifications, and assessed the quality of images on a web-based platform. Krippendorff alpha and Cohen’s Kappa were used to assess interobserver and intra-observer agreement, respectively. Answers were cross-referenced with histology. Results Eleven experts, 19 non-experts, and 10 gastroenterology fellows participated. The CONECCT classification had a higher interobserver agreement (Krippendorff alpha = 0.738) than for all the other classifications and increased with expertise and with quality of pictures. CONECCT classification had a higher intra-observer agreement than all other existing classifications except WASP (only describing Sessile Serrated Adenoma Polyp). Specificity of CONECCT IIA (89.2, 95 % CI [80.4;94.9]) to diagnose adenomas was higher than the NICE2 category (71.1, 95 % CI [60.1;80.5]). The sensitivity of Kudo Vi, Sano IIIa, NICE 2 and CONECCT IIC to detect adenocarcinoma were statistically different (P Conclusions The CONECCT classification currently offers the best interobserver and intra-observer agreement, including between experts and non-experts. CONECCT IIA is the best classification for excluding presence of adenocarcinoma in a colorectal lesion and CONECCT IIC offers the better compromise for diagnosing superficial adenocarcinoma.
Published: 2021

43. Digestive perforations related to endoscopy procedures: a local management charter based on local evidence and experts' opinion

Author: Bertrand, G., Rivory, J., Robert, M., Saurin, J. C., Pelascini, É, Monneuse, O., Gruner, L., Poncet, G., Valette, P. J., Gimonet, H., Rostain, F., Ber, Charles-Éric, Bouffard, Y., Boibieux, A., Ciochina, M., Landel, V., Boyer, H., Jacques, J., Ponchon, T., Pioche, M., Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), 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 Edouard Herriot [CHU - HCL], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Direction de la Recherche Clinique et de l'Innovation [HCL, Lyon] (DRCI / CLCC Léon-Bérard), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Hôpital Dupuytren [CHU Limoges], and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Pharmacology (medical)
Abstract: Background and study aims Perforations are a known adverse event of endoscopy procedures; a proposal for appropriate management should be available in each center as recommended by the European Society of Gastrointestinal Endoscopy. The objective of this study was to establish a charter for the management of endoscopic perforations, based on local evidence. Patients and methods Patients were included if they experienced partial or complete perforation during an endoscopic procedure between 2008 and 2018 (retrospectively until 2016, then prospectively). Perforations (size, location, closure) and management (imagery, antibiotics, surgery) were analyzed. Using these results, a panel of experts was asked to propose a consensual management charter. Results A total of 105 patients were included. Perforations occurred mainly during therapeutic procedures (91, 86.7%). Of the perforations, 78 (74.3 %) were diagnosed immediately and managed during the procedure; 69 of 78 (88.5 %) were successfully closed. Closures were more effective during therapeutic procedures (60 of 66, 90.9 %) than during diagnostic procedures (9 of 12, 75.0 %, P = 0.06). Endoscopic closure was effective for 37 of 38 perforations (97.4 %) Conclusions Detection and closure of perforations during endoscopic procedure had a better outcome compared to delayed perforations; perforations
Published: 2021

44. Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain

Author: Manuella Schaller, Patrick Kieffert, Nadine Attal, Jean-Paul Nguyen, Serge Perrot, Gisèle Pickering, Emmanuelle Kuhn, Virginie Corand-Dousset, Claudia Sommer, Thomas R. Tölle, Juan Fernando Ramirez-Gil, Patrick Ginies, Alain Serrie, Eric Viel, Patrick Houéto, Emmanuel Chevrillon, Stéphanie Ranque Garnier, Thibault Riant, Claire Delorme, Gaelle Martiné-Fabre, Rodrigue Deleens, Baptiste Bessiere, Didier Bouhassira, Clémence Dal-Col, Caroline Maindet, Cécile Delval, Christian Gov, Physiopathologie et Pharmacologie Clinique de la Douleur (LPPD), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Polyclinique de Limoges - site François Chénieux [Limoges], CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Clinique Bretéché [Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital de Mercy, Centre Hospitalier Aunay-Bayeux (CH Aunay-Bayeux), CHU Rouen, Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Air liquide France Industrie, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV]Life Sciences [q-bio], Analgesic, Nitrous Oxide, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, 030202 anesthesiology, law, Germany, Administration, Inhalation, medicine, Humans, Depression (differential diagnoses), business.industry, 3. Good health, Blockade, Oxygen, Treatment Outcome, Anesthesiology and Pain Medicine, Neurology, Anesthesia, Neuropathic pain, Quality of Life, Neuralgia, Anxiety, France, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: International audience; ABSTRACT: Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain. Copyright
Published: 2021

45. Menstrual Toxic Shock Syndrome: A French Nationwide Multicenter Retrospective Study

Author: Damien Contou, Gwenhaël Colin, Brendan Travert, Sébastien Jochmans, Marie Conrad, Jean-Baptiste Lascarrou, Benoit Painvin, Alexis Ferré, David Schnell, Béatrice La Combe, Rémi Coudroy, Stephan Ehrmann, Jérôme Rambaud, Arnaud Wiedemann, Pierre Asfar, Pierre Kalfon, Emmanuel Guérot, Sébastien Préau, Laurent Argaud, Florence Daviet, Jean Dellamonica, Audrey Dupont, Muriel Fartoukh, Toufik Kamel, Gaetan Beduneau, Florence Canouï-Poitrine, Emmanuelle Boutin, Gérard Lina, Armand Mekontso Dessap, Anne Tristan, Nicolas de Prost, French m-TSS Study Group, Centre Hospitalier Victor Dupouy, CH Départemental Vendée, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Melun (CHM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Laboratoire Lasers, Plasmas et Procédés photoniques (LP3), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Angoulême (CH Angoulême), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), 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), 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), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Réanimation polyvalente [Chartres], Hôpital Louis Pasteur [Chartres], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation (ORLEANS - Réa), Centre Hospitalier Régional d'Orléans (CHRO), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU), 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), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), 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 Henri Mondor, CarMeN, laboratoire, Centre Hospitalier de Melun, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Staphylococcus aureus, medicine.medical_specialty, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030106 microbiology, Disease, law.invention, Sepsis, Menstruation, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Intensive care, medicine, Humans, 030212 general & internal medicine, Child, menstrual toxic shock syndrome, Retrospective Studies, Superantigens, Critically ill, business.industry, Medical record, Tracheal intubation, Toxic shock syndrome, Retrospective cohort study, Staphylococcal Infections, tampon, bacterial infections and mycoses, Institutional review board, medicine.disease, Shock, Septic, Intensive care unit, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Infectious Diseases, Icu, Female, Observational study, menstruation, business
Abstract: Background Studies describing the clinical features and short-term prognosis of patients admitted to the intensive care unit (ICU) for menstrual toxic shock syndrome (m-TSS) are lacking. Methods This was a multicenter retrospective cohort study of patients with a clinical diagnosis of m-TSS admitted between 1 January 2005 and 31 December 2020 in 43 French pediatric (n = 7) or adult (n = 36) ICUs. The aim of the study was to describe the clinical features and short-term prognosis, as well as to assess the 2011 Centers for Disease and Control (CDC) diagnostic criteria, in critically ill patients with m-TSS. Results In total, 102 patients with m-TSS (median age, 18 years; interquartile range, 16–24 years) were admitted to 1 of the participating ICUs. All blood cultures (n = 102) were sterile. Methicillin-sensitive Staphylococcus aureus grew from 92 of 96 vaginal samples. Screening for superantigenic toxin gene sequences was performed for 76 of the 92 vaginal samples positive for S. aureus (83%), and toxic shock syndrome toxin 1 was isolated from 66 strains (87%). At ICU admission, no patient met the 2011 CDC criteria for confirmed m-TSS, and only 53 (52%) fulfilled the criteria for probable m-TSS. Eighty-one patients (79%) were treated with antitoxin antibiotic therapy, and 8 (8%) received intravenous immunoglobulins. Eighty-six (84%) patients required vasopressors, and 21 (21%) tracheal intubation. No patient required limb amputation or died in the ICU. Conclusions In this large multicenter series of patients included in ICUs for m-TSS, none died or required limb amputation. The CDC criteria should not be used for the clinical diagnosis of m-TSS at ICU admission.
Published: 2021

46. Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL

Author: Gaël Piton, Arnaud W. Thille, Damien Contou, Laura Federici, Bertrand Guidet, Jean Reignier, Julie Badin, Erwan I'her, Dalila Benzekri-Llefevre, Pascal Beuret, Riad Chelha, Suela Demiri, Christophe Vinsonneau, Michel Djibré, Juliette Masse, Nicolas Terzi, Francois Thouy, Juliette Audibert, Olivier Lesieur, Stephan Ehrmann, Hassene Rahmani, Alexandre Boyer, Saad Nseir, Denis Frasca, Christophe Girault, Jean-Pierre Frat, René Robert, Martial Thyrault, Jean-Pierre Quenot, Laurent Argaud, Christophe Guitton, Didier Thevenin, Nadia Aissaoui, Khaldoune Kuteifan, 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, 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 de Blois (CH Blois), CHU Rouen, Normandie Université (NU), Centre Hospitalier Le Mans (CH Le Mans), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Roanne (CH Roanne), CH de Roanne, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional d'Orléans (CHRO), Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Strasbourg (UNISTRA), CHU Strasbourg, 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), Université de Lyon, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), 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), 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), Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis [CHU Limoges] (Réseau CRICS-TRIGGERSEP ), Hôpital Dupuytren [CHU Limoges], Hôpital Saint-Louis de La Rochelle (CH La Rochelle), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier de Lens, Centre Hospitalier Victor Dupouy, CHU Grenoble, Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe Hospitalier Nord Essonne [Longjumeau], Centre Hospitalier de Béthune Beuvry (CH Béthune Beuvry), Hôpital Louis Pasteur [Chartres], Université catholique de Lille (UCL), Groupe hospitalier Pellegrin, CHU Saint-Antoine [AP-HP], Centre Hospitalier Privé Claude Galien - Ramsay Santé, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, 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), 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-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Blois (CHB), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), 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 (IMT Atlantique), and CarMeN, laboratoire
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life, law, Informed consent, Oxygen therapy, medicine, Humans, respiratory medicine (see thoracic medicine), 030212 general & internal medicine, Prospective Studies, Prospective cohort study, adult intensive & critical care, Noninvasive Ventilation, business.industry, Oxygen Inhalation Therapy, Intensive Care, General Medicine, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Oxygen, Intensive Care Units, 030228 respiratory system, medical ethics, Propensity score matching, Emergency medicine, Quality of Life, Observational study, business, Respiratory Insufficiency, Cohort study
Abstract: IntroductionA palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient’s quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders.Methods and analysisThis is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score.Ethics and disseminationThe study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03673631
Published: 2021

47. Bicentric evaluation of stabilizing sampling tubes for assessment of monocyte HLA-DR expression in clinical samples

Author: Martin Cour, Sarah Hamada, Guillaume Monneret, Laurent Argaud, Thomas Daix, Morgane Gossez, Fabienne Venet, Robin Jeannet, Bruno François, Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Inflammasome NLRP3 et réponse immunitaire au sepsis - NLRP3 inflammasome and immune response to sepsis (NLRP3), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université de Lyon-Université de Lyon, CarMeN, laboratoire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), 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), 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), 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 de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3)
Subjects: 0301 basic medicine, medicine.medical_specialty, Histology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Urology, Monocytes, Pathology and Forensic Medicine, Specimen Handling, law.invention, Flow cytometry, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, HLA-DR, Humans, Medicine, Edetic Acid, Whole blood, medicine.diagnostic_test, business.industry, Monocyte, Immunosuppression, Cell Biology, HLA-DR Antigens, medicine.disease, Flow Cytometry, Intensive care unit, Staining, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hla-dr, monocyte, business, Covid-19, Cytometry, Blood sampling
Abstract: BackgroundDiminished expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR), measured by standardized flow cytometry procedure, is a reliable indicator of immunosuppression in severely injured intensive care unit patients. As such, it is used as stratification criteria in clinical trials evaluating novel immunostimulating therapies. Pre-analytical constraints relative to the short delay between blood sampling and flow cytometry staining have nevertheless limited its use in multicentric studies. The objective of the present work was to compare mHLA-DR expression between whole blood samples simultaneously drawn in EDTA or Cyto-Chex® BCT tubes.MethodsIn 2 university hospitals, mHLA-DR was assessed in fresh whole blood from septic patients (n = 12) and healthy donors (n = 6) simultaneously sampled on EDTA and Cyto-Chex® BCT tubes. Staining was performed immediately after sampling and after blood storage at room temperature.ResultsWe observed the remarkable stability of mHLA-DR results when blood was collected in Cyto-Chex® BCT tubes (until 48-72 h). On baseline values, despite good correlation between tubes (r = 0.98, p< 0.001), mHLA-DR expression was systematically lower with Cyto-Chex® BCT.ConclusionThe present reports confirms the great potential of Cyto-Chex® BCT tubes to delay mHLA-DR staining in centers without rapid access to flow cytometry facilities. However, a 30 % gap exists between results obtained with EDTA and Cyto-Chex® BCT tubes. As current thresholds for clinical decisions were obtained with EDTA samples, further studies are needed to confirm clinical thresholds with Cyto-Chex® BCT tubes.
Published: 2021

48. Relevance of Brain Regions' Eloquence Assessment in Patients With a Large Ischemic Core Treated With Mechanical Thrombectomy

Author: Basile, Kerleroux, Joseph, Benzakoun, Kévin, Janot, Cyril, Dargazanli, Dimitri Daly, Eraya, Wagih, Ben Hassen, François, Zhu, Benjamin, Gory, Jean-Francois, Hak, Charline, Perot, Lili, Detraz, Romain, Bourcier, Rouchaud, Aymeric, Géraud, Forestier, Gaultier, Marnat, Florent, Gariel, Pasquale, Mordasini, Pierre, Seners, Guillaume, Turc, Johannes, Kaesmacher, Catherine, Oppenheim, Olivier, Naggara, Gregoire, Boulouis, Jean Christophe, Labour, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), GHU Paris Psychiatrie et Neurosciences, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Gui de Chauliac [Montpellier], 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 Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital Dupuytren [CHU Limoges], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, University of Bern, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Gui de Chauliac [CHU Montpellier], CHU Rothschild [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, 610 Medicine & health, Brain tissue, 030204 cardiovascular system & hematology, Logistic regression, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Internal medicine, medicine, Humans, Infarct core, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Ischemic Stroke, Retrospective Studies, Thrombectomy, Aged, 80 and over, Core (anatomy), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Middle Aged, Magnetic Resonance Imaging, Mechanical thrombectomy, Treatment Outcome, Infarction, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, 610 Medizin und Gesundheit, Perfusion, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: ObjectiveIndividualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT.MethodsWe performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0–3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models.ResultsA total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0–3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0–3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant (p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant.ConclusionsConsidering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit.Classification of EvidenceThis study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months.
Published: 2021
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49. Increased Risk of Parkinson's Disease in Women after Bilateral Oophorectomy

Author: Maryline Le Noan-Lainé, Isabelle Benatru, Marianne Canonico, Alexis Elbaz, Frédéric Moisan, Danièle Ranoux, Giancarlo Pesce, Audrey Bonaventure, HAL UVSQ, Équipe, 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, 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Dupuytren [CHU Limoges], Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Agence Française de Sécurité Sanitaire de l'Environnement et du Travail, AFSSET Agence Nationale de la Recherche, ANR Institut National de la Santé et de la Recherche Médicale, Inserm Mutualité Sociale Agricole, MSA, This study was supported by Institut National de la Santé et de la Recherche Médicale (INSERM) and the Mutualité Sociale Agricole (MSA), and funded by the Agence Nationale de la Recherche (ANR), Agence Française de Sécurité Sanitaire de l'Environnement et du Travail (AFSSET), and France Parkinson., and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, medicine.medical_specialty, Parkinson's disease, medicine.medical_treatment, Ovariectomy, [SDV]Life Sciences [q-bio], Neurological examination, Disease, Coffee, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, bilateral oophorectomy, Epidemiology, Odds Ratio, Medicine, Humans, medicine.diagnostic_test, business.industry, Obstetrics, Parkinson Disease, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Menopause, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, Case-Control Studies, Female, epidemiology, Neurology (clinical), Hormone therapy, women, business, 030217 neurology & neurosurgery
Abstract: Background Results regarding the association between hormonal exposure and risk of Parkinson's disease (PD) are heterogeneous. Objectives To investigate the association of reproductive life characteristics with PD among postmenopausal women. Methods The PARTAGE case-control included 130 female cases and 255 age-matched female controls. Information on gynecological history was obtained from a standardized questionnaire and PD was validated by neurological examination. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. Results After adjustment for education level, smoking status, professional exposure to pesticides, and coffee and alcohol drinking, bilateral oophorectomy (OR = 3.55, 95%CI = 1.75-7.20), but neither menopause before age 50 years (OR = 1.24, 95%CI = 0.74-2.09) nor hormone therapy (HT; OR = 1.07, 95%CI = 0.62-1.86), was associated with PD. Conclusion Our findings suggest that bilateral oophorectomy is associated with increased risk of PD. © 2021 International Parkinson and Movement Disorder Society.
Published: 2021

50. Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older

Author: Corinne Haioun, Hassan Farhat, Christophe Bonnet, René-Olivier Casasnovas, Peggy Dartigues-Cuillères, Fontanet Bijou, Gilles Salles, Hervé Maisonneuve, Julie Abraham, Ronan Le Calloch, Pierre Feugier, Mathieu Puyade, Jerome Paget, Gianmatteo Pica, Bettina Fabiani, Philippe Ruminy, Gandhi Damaj, Fabrice Jardin, Frederic Peyrade, Elodie Gat, Lucie Oberic, Agathe Waultier-Rascalou, Sandra Malak, Catherine Thieblemont, Hervé Tilly, 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), Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), 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), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Unité de neurophysiologie [CHU Saint-Antoine], 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), 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), Hôpital Dupuytren [CHU Limoges], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Métropole Savoie [Chambéry], Laboratoire d'Hématologie Biologique [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), CHU Henri Mondor, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Versailles André Mignot (CHV), Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital René HUGUENIN (Saint-Cloud), and The Lymphoma Academic Research Organisation [Lyon] (LYSARC)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, 3. Good health, Lymphoma, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, hemic and lymphatic diseases, medicine, Rituximab, Doxorubicin, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug, Lenalidomide
Abstract: PURPOSE: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP. PATIENTS AND METHODS: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP. CONCLUSION: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.
Published: 2021

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