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1. Immunogenicity and efficacy of heterologous ChAdOx1–BNT162b2 vaccination

Author

Vincent Legros, Thierry Walzer, Jacqueline Marvel, Jean-Baptiste Fassier, Loïc Peyrot, Sophie Trouillet-Assant, Nicolas Guibert, Véronique Barateau, Thierry Defrance, Bruno Pozzetto, Thibault Andrieu, Bruno Lina, Sophia Djebali, Melyssa Yaugel-Novoa, Solène Denolly, Martine Valette, François-Loïc Cosset, Antonin Bal, Karen Brengel-Pesce, Amélie Massardier-Pilonchery, Omran Allatif, Thomas Bourlet, Bertrand Boson, Marine Villard, Stéphane Paul, 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), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], ANR-16-CE15-0002,MEMO-SIGN,IMPACT DE LA FORMULATION VACCINALE SUR LA COMPOSITION DES COMPARTMENTS LYMPHOCYTAIRES A MEMOIRE TFH ET B(2016), and ANR-21-COVR-0038,COVIDIgS,Comparaison du role des anticorps IgA/IgM systémique et muqueux dans la physiopathologie et la sévérité de la COVID-19(2021)

Subjects
Adult, Male, MALADIE, COVID19, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Priming (immunology), Heterologous, Hospitals, University, Memory T Cells, Memory B Cells, Immunity, ChAdOx1 nCoV-19, SANTE, Humans, Medicine, BNT162 Vaccine, VIRAL INFECTION, Multidisciplinary, biology, SARS-CoV-2, business.industry, Incidence, Immunogenicity, Vaccination, COVID-19, Middle Aged, Antibodies, Neutralizing, Regimen, Spike Glycoprotein, Coronavirus, Immunology, biology.protein, Female, France, Antibody, business, Immunologic Memory, RNA VACCINES, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities have recommended that patients under the age of 55 who received one dose of ChAdOx1-S-nCoV-19 vaccine receive a second dose of Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here, we show that the heterologous ChAdOx1-S-nCoV-19/BNT162b2 combination confers better protection against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection than the homologous BNT162b2/BNT162b2 combination in a real-world observational study of healthcare workers (n=13121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody (Ab) responses but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity, regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential was correlated with increased frequencies of switched and activated memory B cells recognizing the SARS-CoV-2 Receptor Binding Domain (RBD). The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immune compromised individuals.

Published
2021
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2. The ROX index as a predictor of standard oxygen therapy outcomes in thoracic trauma

Author

Juliette Balbo, Mathieu Bard, Guillaume Giordano-Orsini, Vincent Legros, Adrien Cornillon, Thierry Floch, Jean-Marc Malinovsky, Daphne Michelet, Lukshe Kanagaratnam, and Julien Coffinet

Subjects
Adult, Male, Thoracic Injuries, medicine.medical_treatment, Youden's J statistic, Intensivist, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, ROX index, Oxygen therapy, Intubation, Intratracheal, Humans, Medicine, Intubation, 030212 general & internal medicine, Thoracic trauma, Aged, Retrospective Studies, Original Research, Outcome, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, RC86-88.9, Trauma center, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Respiration, Artificial, Oxygen, Treatment Outcome, Initial phase, Anesthesia, Emergency Medicine, Female, Standard oxygen therapy, business
Abstract

Background Thoracic trauma is commonplace and accounts for 50–70% of the injuries found in severe trauma. Little information is available in the literature as to timing of endotracheal intubation. The main objective of this study was to assess the accuracy of the ROX index in predicting successful standard oxygen (SO) therapy outcomes, and in pre-empting intubation. Methods Patient selection included all thoracic trauma patients treated with standard oxygen who were admitted to a Level I trauma center between January 1, 2013 and April 30, 2020. Successful standard SO outcomes were defined as non-requirement of invasive mechanical ventilation within the 7 first days after thoracic trauma. Results One hundred seventy one patients were studied, 49 of whom required endotracheal intubation for acute respiratory distress (28.6%). A ROX index score ≤ 12.85 yielded an area under the ROC curve of 0.88 with a 95% CI [0.80–0.94], 81.63sensitivity, 95%CI [0.69–0.91] and 88.52 specificity, 95%CI [0.82–0.94] involving a Youden index of 0.70. Patients with a median ROX index greater than 12.85 within the initial 24 h were less likely to require mechanical ventilation within the initial 7 days of thoracic trauma. Conclusion We have shown that a ROX index greater than 12.85 at 24 h was linked to successful standard oxygen therapy outcomes in critical thoracic trauma patients. It is our belief that an early low ROX index in the initial phase of trauma should heighten vigilance on the part of the attending intensivist, who has a duty to optimize management.

Published
2021

3. Use of BRASS in sedated critically-ill patients as a predictable mortality factor: BRASS-ICU

Author

Lukshe Kanagaratnam, Philippe Mateu, Jean-Christophe Farkas, Thierry Floch, Jérémy Rosman, Bruno Mourvillier, Vincent Legros, Bruno Lafont, Mathieu Bard, and Quentin Candelier

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Critical Illness, Sedation, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Hypnotics and Sedatives, Prospective Studies, Mortality, Aged, Critically ill, business.industry, General Medicine, Middle Aged, Intensive Care Units, 030104 developmental biology, Neurology, Emergency medicine, Delirium, Female, Observational study, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Brain Stem
Abstract

Objectives: To demonstrate that a BRASS score≥ 3 at admission of intubated, ventilated and sedated patients is predictive of mortalityMethods: we have realized an Observational prospective multicen...

Published
2020
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4. Crimean-Congo hemorrhagic fever: a growing threat to Europe

Author

Natalia Freitas, Vincent Legros, and François-Loïc Cosset

Subjects
Europe, Ixodidae, Spain, Hemorrhagic Fever Virus, Crimean-Congo, Animals, Humans, Hemorrhagic Fever, Crimean, General Medicine
Abstract

Tick-borne infectious diseases are increasing, driven by geographic expansion of ticks. Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the family Nairoviridae that poses serious threat to public health. CCHFV can cause severe forms of hemorrhagic fever with high case fatality rates (CFR) (10-40%) and can be transmitted from human to human. Until a few years ago, no cases of CCHF had been reported in western Europe. However, high seropositivity rates in wildlife and detection of multiple strains of CCHFV in ticks in Spain suggest that CCHFV enzootic cycle has been established in some areas of southwestern Europe. As far as CCHFV-associated morbidity and mortality are concerned, there are no approved therapeutic options or US/EU licensed vaccines for treatment. Here we discuss some eco-epidemiological aspects as well as public health and socio-economic impacts associated with CCHFV circulation and outbreaks. We also emphasize that it has become essential to identify key inter-species transmission processes of this group of pathogens, to understand basic molecular mechanisms of their replication, and to define their pathogenic potentials.Partout dans le monde, les maladies infectieuses transmises par les tiques sont en augmentation, en raison de l’expansion géographique de ces dernières. Le virus de la fièvre hémorragique de Crimée-Congo (CCHFV) est un virus de la famille des Nairoviridae transmis par les tiques et constitue une menace importante pour la santé publique. Il est responsable de graves fièvres hémorragiques associées à des taux de létalité élevés (10–40%), une transmission d’homme à homme possible et une absence d’options thérapeutiques approuvées ou de vaccins homologués en Espagne et dans l’Union européenne. Jusqu’à il y a quelques années, aucun cas de CCHFV n’avait été signalé en Europe occidentale. Cependant, les taux élevés de séroprévalence chez les animaux sauvages et la détection de multiples souches du CCHFV chez des tiques en Espagne suggèrent que le cycle enzootique du CCHFV s’est déjà établi dans certaines régions du sud-ouest de l’Europe. Outre la morbidité et la mortalité associées à la FHCC, il n’existe pas d’options thérapeutiques approuvées ni de vaccins homologués aux États-Unis et dans l’UE pour son traitement. Nous discutons ici des aspects éco-épidémiologiques ainsi que des impacts socio-économiques et de santé publique associés à la circulation et aux foyers du FHCC. Nous soulignons également qu’il est maintenant devenu essentiel d’identifier les principaux processus de transmission inter-espèces de ce groupe d’agents pathogènes, de comprendre les mécanismes moléculaires de leur réplication et de définir leur potentiel pathogène.

Published
2022

5. Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

Author

Solène Lerolle, Natalia Freitas, François-Loïc Cosset, Vincent Legros, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), 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)-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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016)

Subjects
Bunyaviridae, [SDV]Life Sciences [q-bio], Virion, Review, Genome, Viral, Genomics, interferon, Bunyaviridae Infections, Virus Replication, Microbiology, bunyaviruses, restriction factors, QR1-502, Immunity, Innate, Receptors, Pattern Recognition, Host-Pathogen Interactions, Interferon Type I, Immune Tolerance, Animals, Humans, viral countermeasures, innate immunity, Biomarkers
Abstract

International audience; The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells.

Published
2021
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6. Impact of the SARS-COV-2 outbreak on epidemiology and management of major traumain France: a registry-based study (the COVITRAUMA study)

Author

Jean-Denis Moyer, Arthur James, Clément Gakuba, Mathieu Boutonnet, Emeline Angles, Emmanuel Rozenberg, Jean Bardon, Thomas Clavier, Vincent Legros, Marie Werner, Quentin Mathais, Véronique Ramonda, Pierre Le Minh, Yann Berthelot, Clélia Colas, Julien Pottecher, Tobias Gauss, and the Traumabase Group, Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anesthésie réanimation [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), Service de Soins Intensifs [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), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service Anesthésie et soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Reims (CHU Reims), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), 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)-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), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), CHU de Toulouse, Pole d'anesthésie Réanimation, Hôpital Paule de Viguier, Toulouse F-31059, France, CHU Toulouse [Toulouse], Capgemini [Paris], Capgemini, Department of Anesthesiology, Intensive care and Perioperative medicine - Hautepierre Hospital, Strasbourg, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle d'anesthésie Réanimation [CHU de Toulouse], and Gestionnaire, HAL Sorbonne Université 5

Subjects
Adult, Male, medicine.medical_specialty, Critical Care and Intensive Care Medicine, Trauma, 03 medical and health sciences, 0302 clinical medicine, Trauma Centers, Health care, Pandemic, Epidemiology, Humans, Medicine, Registries, 030212 general & internal medicine, Traumacenter, Disease management (health), Pandemics, Original Research, Retrospective Studies, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, SARS-CoV-2, business.industry, Major trauma, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Disease Management, Outbreak, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, lcsh:RC86-88.9, medicine.disease, 3. Good health, Hospitalization, Communicable Disease Control, Emergency medicine, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Emergency Medicine, Female, France, business, Delivery of Health Care
Abstract

Background Emerging evidence suggests that the reallocation of health care resources during the COVID-19 pandemic negatively impacts health care system. This study describes the epidemiology and the outcome of major trauma patients admitted to centers in France during the first wave of the COVID-19 outbreak. Methods This retrospective observational study included all consecutive trauma patients aged 15 years and older admitted into 15 centers contributing to the TraumaBase® registry during the first wave of the SARS-CoV-2 pandemic in France. This COVID-19 trauma cohort was compared to historical cohorts (2017–2019). Results Over a 4 years-study period, 5762 patients were admitted between the first week of February and mid-June. This cohort was split between patients admitted during the first 2020 pandemic wave in France (pandemic period, 1314 patients) and those admitted during the corresponding period in the three previous years (2017–2019, 4448 patients). Trauma patient demographics changed substantially during the pandemic especially during the lockdown period, with an observed reduction in both the absolute numbers and proportion exposed to road traffic accidents and subsequently admitted to traumacenters (348 annually 2017–2019 [55.4% of trauma admissions] vs 143 [36.8%] in 2020 p Conclusions During this first wave of COVID-19 in France, and more specifically during lockdown there was a significant reduction of patients admitted to designated trauma centers. Despite the reallocation and reorganization of medical resources this reduction prevented the saturation of the trauma rescue chain and has allowed maintaining a high quality of care for trauma patients.

Published
2021
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7. EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): study protocol for a multicentre, observational trial

Author

Weiss, Raphael, Saadat-Gilani, Khaschayar, Kerschke, Laura, Wempe, Carola, Meersch, Melanie, Zarbock, Alexander Hichem Makhloufi, Anis, Cherak, Lamine Lakhel Ghanem, Zohier, Gouaglia, Dina Nasrine Guadouri, Fayrouz Naouel Hama, Mustafa, Kara, Omayma, Saadi, Rachida, Sakhraoui, Fadila, Bourou, Abdelhadi, Cherifi, Rahmoune Ghania Sadaoui, Amel, Ouyahia, Ilhem, Ouahab, Souad, Bouaoud, Meriem, Abdoun, Anisse, Tidjane, Benali, Tabeti, Nabil, Boudjenan-Serradj, Carlos Jose Pérez Rivera, Paulo, Cabrer, Julián, Corso, Juan Pablo García, Sharon, Idarraga, Christopher, Montoya, Rafael, Figueroa, Eduar, Aldana, María Alejandra Torrado, Peng, Ke, Zheng-Min, Ma, Yu-Fan, Yang, Ya-Juan, Zhu, Peter, Sklienka, Michal, Frelich, Vojtech, Jarkulis, Pavel, Sevcik, Vojtech, Vodicka, Mohamed Gamal Elbahnasawy, Shady, Elsalhawy, Sara, Motawea, Zeinab, Othman, Mohamed, Sahma, Ahmed Mahmoud Nafea, Nermin, Ahmed, Doaa Ali Attia, Moataz Maher Emara, Mohamed Mamdouh Bonna, Mohamed Ahmed Gabr, Amany Ismail Tarbay, Ibrahim Abdelmonaem Abdehaleem, Esraa Elsayed Mohamed, Amr Mahmoud Eldeeb, Ahmed Mohamed Abbas, John Ashraf Magdy, Zyad Hassan Hamed, Hany Mostafa Esmaeil Osman, Mostafa Samy Abbas, Oliver, Joannes-Boyau, Nicolas, Barraud, Corentin, Berthelot, Thibault, Camus, Anissa, Dahmi, Mylène, Defaye, Sébastien, Derville, Younes, El-Boustani, Elsa, Deloge, Hélène, Jacob, Simon, Monziols, Fred, Priem, Jean-Jacques, Robin, Vincent, Legros, Therry, Floch, Salvatore, Muccio, Claire, Geneve, Marie Lim Legouge, Stéphanie Tao Mauny, Willy, Mfam, Léa, Pascot, Christophe, Aveline, Mireille, Chartier, Benjamin, Duteurtre, Jean Francois Gautier, Aidren Le Cousin, Pierre, Vautier, Julien, Nadaud, Nathalie, Begel, Claire-Annissa, Chekirine, Vincent, Derlon, Elodie, Grein, Marie-Annick, Lehair, Laurent, Magazzeni, Philippe, Magazzeni, Carsten, Potter, Catherine, Roth, Florence, Voivret, Thomas, Rimmelé, Valérie, Cerro, Stéphanie, Suria, Jamil, Elmawieh, Annabelle, Stoclin, Cédric, Cirenei, Gregoire, Andrieu, Sven, Couloumy, Jeremy, Falcone, Marion, Fajardy, Arsène, Gagneuil, Emeline, Girardet, Agnès, Mazereeuw, Sébastien, Ponsonnard, Pierre-Yves, Egreteau, Mélanie, Bertel, Simon, Bocher, Vanessa, Carn, Lenaïg Le Guen, Guillaume Le Loup, Montaine, Lefevre, Carole, Ichai, Amanita, Diop, Vanessa, Jean-Michel, Sylvie, Devlieger, Juliette, Duthoit, Mohamed El Kadiri, Maxime, Léger, Viviane, Cassisa, Sigismond, Lasocki, Charline, Masson, Emmanuel, Rineau, Pierre, Verrier, Axel, Coquerel, Philippe, Montravers, Enora, Atchade, Charles-Edouard, Rochon, Céline, Delerue, Vidal, Quentin, Vanessa, Latry, Nina, Queixalos, Vincent, Cottenceau, Thierry, Braun, Saad, Bouzoubaa, Basile, Christ, Audrey, Geiger, Joachim, Gomille, Vianney, Kieffer, Simone, Mangeant, Christelle, Prochilo, Christian, Schmitt, Stefan, Skwirba, Hubert, Grand, Frédérique, Boury, Nicolas, Mayeur, Marie, Pasquie, Pierre, Garçon, Vincent, Bruckert, Vincent, Arnould, Mona, Bonciu, Thibault, Chapelle, Luc, Facchino, Florence, Fagot-Gandet, Andrea, Iachim, Elena, Mannu, Olivier, Perus, Rémi, Plattier, Romain, Rozier, Gaël, Pradel, Michel, Boudinaud, Marie-Hélène, Hausermann, My Hue Nguyen, Andersen, Ramorasata, Amélie, Barreau, Anne-Hélène, Boivin, Céline, Ravry, Nicolas, Mottard, Johanne, Beuvelot, Florence Prunier Bossion, Olivier, Desebbe, Alexander, Zarbock, Christian, Dörr, Thilo Caspar von Groote, Mira, Küllmar, Christina, Massoth, Melanie, Meersch, Khaschayar, Saadat-Gilani, Raphael, Weiss, Carola, Wempe, Sebastian, Ziemann, Linda, Grüßer, Ana, Kowark, Pia, Wittig, Timo, Brandenburger, Thomas, Dimski, Niklas, Döhmen, Laura, Huthmann, Daniela, Kaierle, Claude, Pelletier, Manon, Schleß, Andreas, Hohn, Sebastian, Cleophas, Stephanie, Haunhorst, Marina, Jansen, Alexandra, Schmitt, Julia, Soisch, Kilian, Sturm, Peter, Rosenberger, Alexander, Bendig, Lena, Flohr, Helene, Häberle, Pascal, Hofmann, Jonathan, Kuhle, Nora Michaela Leser, Kathrin, Pfister, Stefanie, Prohaska, Franziska, Sennholz, Lena, Stetz, Kathrin, Weber, Sebastian, Stehr, Stephan, Klaus, Marco, Sadlo, Matthias, Boschin, Christian, Sengelhoff, Ulrich Michael Göbel, Jan Gerrit Haaker, Carina-Kristin, Göttker, Matthias, Gründel, Matthias, Heringlake, Romina, Baumgärtel, Astrid, Berggren, Madeleine, Gülzow, Lennart, Muras, Hauke, Paarmann, Serge, Thal, Alexander, Bentley, Dschamil, El-Masri, Anne, Sebastiani, Eleni, Arnaoutoglou, Maria, Ntalouka, Paula, Stratigopoulou, Anastasia, Analytis, Efthymios, Mavrommatis, Petros, Tzimas, Agathi, Karakosta, Danai, Pantazi, Antonia, Dimakopoulou, Katerina, Dimitropoulou, Orestis, Ioannidis, Humam, Jalaawiy, Aeshah, Anwar, Hashim Talib Hashim, Hogir Imad Rasheed Aldawoody, Andrea, Cortegiani, Giulia, Catalisano, Gilia, Ingoglia, Mariachiara, Ippolito, De Rosa, Silvia, Lucia, Cattin, Andrea, Bianchin, Marisa, Barone, Gianluca, Paternoster, Salvatore Lucio Cutuli, Andrea, Russo, Liliana, Sollazzi, Laura, Cascarano, Massimo, Antonelli, Paola, Aceto, Bruno, Romanò, Savino, Spadaro, Vincenzo Francesco Tripodi, Michele, Rossi, Rosamaria, Scappatura, Maria Cristina Vadalà, Diego, Fiume, Maria Teresa Strano, Giulia, Oddo, Clemente, Santorsola, Bilal Abu Hussain, Adnan Raed Alnaser, Anas Hassouneh Ghassan, Khaled, Hasanein, Mohammed, Theab, Seokyung, Shin, Seungho, Jung, Kyuho, Lee, Sung Mee Jung, Jongyoon, Baek, Muhammed, K Elhadi, Issa, Abuzeid, Mohammed, Albaraesi, Sarah, Aldressi, Wegdan, Khalel, Eman, Abdulwahed, Akram Abdulhamid Ashur Abujrad, Amer, Almaghrabi, Muhand Mohammed Alteleeb, Entisar Ahmed Ali Alshareea, Marwa Isa Biala, Abdulqudus, Deeknah, Dooua Ali Gheddim, Reem, Ghmagh, Nawras Salih Ali AbuIkhrays, Marwa, Sinan, Enas, Soula, Sumayyah Ghayth Bahroun, Khawla, Derwish, Aya Munir Mohamed, Eman Sayed Younes, Rayet Al Islam Benjouira, Mohamed, Aliwa, Najwa Abdullah Altashani, Mohammed Omar Alteb, Ahmed, Msherghi, Fatima, Alagelli, Sufyan, Albarouni, Ahmed, Albishti, Sarah, Aljamal, Mohamed, Alsori, Taha, Ekhuja, Suha, Elzwai, Mohammed, Ghula, Tahani, Mustafa, Ahmed, Tuwaib, Haifa, Zriba, Hamza Mahmoud Agilla, Toky Andriamahefa Rafanomezantsoa, Anne Marie Camilleri Podesta, Denise Mifsud Bonnici, Tiziana, Pirotta, Gilberto Adrián Gasca López, Maja Mojsova Mijovska, Tatjana, Davitkovska, Aleksandra, Gavrilovska, Sanja, Lukikj, Marija, Vesova, Dina, Zafirova, Sarah, Amro, Baraa N, F Hajjaj, Muawia, Alkhazendar, Yousuf, Barakat, Sewar Abdulaziz Elejla, Ahmed, Elhissi, Ahmed, Khader, Ali, Salem, Rita de Freitas Regufe, André Filipe de Oliveira Eloy, Lisbete Marisa Neto Cordeiro Perdigão, Evgeny, Grigoriev, Artem, Ivkin, Roman, Kornelyuk, Michael, Yaroustovsky, Marina, Abramyan, Ekaterina, Komardina, Nataliya, Lesteva, Medina, Aybazova, Elmira, Kumykova, Svetlana, Lesina, Gennady, Rybakov, Alexey, Shestov, Abdulnaser Ahmad Ahmad Barmou, Bushra Lotfi Altayeb Ahmed, Aisha Mohammad Eliyas, Yousra, Emadeldin, Alexander, Kaserer, Clara, Castellucci, Julian, Rössler, Samira, Akbas, Andreja Möller Petrun, Irena, Gregorcic, Vesna, Sok, Roman, Čičak, Elizabeth, Bárcena, Antonio, Guisado, Ismail, Wi, Javier Ripollés Melchor, Ángel, Becerra-Bolaños, Sergio, Cabrera-Doreste, Ancor, Domínguez-Arbelo, María Candelaria Delgado-Alonso, Virginia, Muiño-Palomar, Aurelio, Rodríguez-Pérez, Javier Mata Estévez, Maria Begona Covas Munoz, Juan Mulet Matas, Sara Perez Palao, Maria Dolores Mira Quirós, Alisia Cezara Teslev, Mercedes Garcia Alvarez, Marga, Argilaga, María, Campos, Albert, Bainac, Astrid, Batalla, Marta, Giné, Gracia, Herránz, Ignacio, Hinojal, Margarita Logroño Ejea, Noelia de la Rosa Ruiz, María Gastaca Abasolo, Carla Rosario Houhton Acuna, Ibai Iriarte Zaranton, Ana, Mendigurenmurua, María José Munoz Sanz, Erika Olea de la Fuente, María Pilar Pérez Vaquero, Ana Soto Iglesias, Ana Ugarte Mieres, Alaitz Urtiaga Urrestizala, Lourdes, Ferreira, Félix, Lobato, Marta Aguado Sevilla, Andres, Erazo, Pere, Miró, Sergi, Sabaté, Diana, Vernetta, Berta Castellano Paulis, Anabel Adell Perez, Marta Aseguinolaza Pagola, Elena delVal Peciña, Ainhoa Garmendia Odriozola, Amaia Lopetegi Aizpurua, Olatz Pavón Piquer, Pilar Plou Garcia, Paula Ortega Rezola, Antia Osorio Lopez, Isabel de la Calle Gil, Rosalía Navarro Casado, Peter, Adamove, Roser Bayona Domenge, Francho Miguel Blasco Blasco, Adriana Alexandra Rueda Villamizar, Maria Antonia Perelló Llaneras, Jose Ignacio García-Sánchez, Laura Fernandez Téllez, Sara García Zamorano, Natalia Gijón Herreros, Andrea Rodriguez Esteve, Pablo Monedero Rodríguez, Isabel García Trigo, Agustín, Alcaraz, Andrea Lara Jiménez, Iñigo, Rubio, Nuria, García, Raquel, Callejas, Angel Manuel Candela Toha, Eli, Claros, Pilar, Cobeta, Pascual, Crespo, Trini, Dorado, Elena, Elías, Javier, Felices, Diego, Gil, María, Gómez, Nuria, Mané, María, Martín, Adolfo, Martínez, Lucía, Pereira, Alberto Balvis Noemí Samaranch, Ana, Serrano, Carlos, Tiscar, Judith, Villahoz, Patricia Galán Menéndez, Elena, Cardona, Anna, Conesa, Veronica, Estepa, Patricia, Galán, Laura Llinares Espí, Yuri Loaiza Aldeán, Susana, Manrique, Víctor Morales Ariza, Laura Villarino Villa, Elfayadh Saidahmed Mohamed Amed Suliman, Hytham, Hamid, Ahmed Mohamed Ibrahim, Modather Mohamed Saeed, Orhan Sungur Mukadder, Demet, Altun, Nur, Canbolat, Müşerref Beril Dinçer, Tulay Özkan Seyhan, Serap Aktaş Yıldırım, Müzeyyen, İyigün, Davut, Yapıcı, Levent, Özdemir, Aslinur, Sagun, Neval, Boztug, Yesim, Cetintas, Bora, Dinc, Emel, Gündüz, Hakkı, Ünlügenç, Demet Lafli Tunay, Deniz, Karakaya, Burhan, Dost, Ozgur, Komurcu, Özlem Korkmaz Dilmen, Eren Fatma Akcil, Yusuf, Tunali, Gülay, Ok, Eda Tok Alsina, Özge, Hakli, Cengiz, Polat, Namigar, Turgut, Nurcan, Kızılcık, Özge, Köner, Öznur, Şen, Nurdan, Aydin, Burcu, Basaran, Emre Sertac Bingul, Yavuz, Gürkan, Kamil, Darcin, Semra, Ugur, Kemal Tolga Saracoglu, Asli, Demir, Özgök, Aysegül, Eda, Balci, Behic, Girgin, Aygun, Guler, Ümit, Karadeniz, Nihal, Özaslan, Yigit Özay Hülya, Namik, Ozcan, Aysun, Postaci, Mehmet, Sahap, Nevriye, Salman, Özlem, Sağır, Bulent, Atik, Murat, Bicakcioglu, Hafize Fisun Demir, Ugün, Fatih, Nazan, Kocaoglu, Hüseyin Ilksen Toprak, Duygu Demiröz Aslan, Yusuf Ziya Colak, Mustafa Soner Ozcan, Mehmet, Yilmaz, Umran, Karaca, Sevtap Hekimoglu Sahin, Özlem Ersoy Karka, Gizem Demir Şenoğlu, Süheyla Erkoç Karadağ, Neslihan, Alkis, Volkan, Baytaş, Engin, Erturk, Ali, Akdogan, Ahmet, Besir, Dilek, Kutanis, Sedat, Saylan, Ersagun, Tugcugil, Pinar, Ayvat, Berrin, Günaydın, Beyza Mehri Büyükgebiz, Omer Faruk Boran, Feyza, Calisir, Yavuz, Orak, Bahar Kuvaki Balkan, Sibel, Büyükcoban, Erol, Gökel, Sakize Ferim Günenc, Sule, Özbilgin, Suna, Göre, Selcan, Akesen, Seda, Cansabuncu, Natalia, Momot, Anna, Panchenko, Jean-Francois, Pittet, Kristen, Rutledge, Tıp Fakültesi, Weiss, R, Saadat-Gilani, K, Kerschke,L, Wempe,C, Meersch, M, Zarbock, A, Cortegiani, A, and Ippolito, M

Subjects
Epidemiology, urologic and male genital diseases, acute renal failure, Adult Intensive & Critical Care, Anaesthesia, Cohort Studies, surgery, chronic renal failure, Humans, Multicenter Studies as Topic, Prospective Studies, adult intensive & critical care, urogenital system, Incidence, General Medicine, Acute Kidney Injury, female genital diseases and pregnancy complications, critical care, Renal Replacement Therapy, Observational Studies as Topic, epidemiology, Acute Renal Failure, Surgery, adult intensive &amp, Chronic Renal Failure
Abstract

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Published
2021

8. Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient

Author

Sophie Deguelte, Vincent Legros, Guillaume Cadiot, Brigitte Delemer, Marine Perrier, Hedia Brixi, R. Kianmanesh, Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), and Université de Reims Champagne-Ardenne (URCA)

Subjects
Male, Peptic Ulcer, endocrine system, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Peptic, Proton-pump inhibitor, Gastroenterology, Hypomagnesemia, Zollinger-Ellison Syndrome, 03 medical and health sciences, 0302 clinical medicine, Gastrectomy, Internal medicine, Multiple Endocrine Neoplasia Type 1, medicine, Humans, Multiple endocrine neoplasia, ComputingMilieux_MISCELLANEOUS, Gastrinoma, Frailty, Hepatology, business.industry, Stomach, Proton Pump Inhibitors, Middle Aged, medicine.disease, digestive system diseases, Zollinger-Ellison syndrome, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Gastric acid, 030211 gastroenterology & hepatology, business, Magnesium Deficiency, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.

Published
2021
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9. The interplays between Crimean-Congo hemorrhagic fever virus (CCHFV) M segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity

Author

Natalia Freitas, Friedemann Weber, Solène Lerolle, François-Loïc Cosset, Gregory Neveu, Solène Denolly, Vincent Legros, Camille Lévy, Margot Enguehard, Eric Bergeron, Stephanie Devignot, Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), 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)-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), Justus-Liebig-Universität Gießen (JLU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Université de Lyon, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), This work performed in the laboratory of FLC was supported by the French National Research Agency (ANR), the IDEXLYON (ANR-16-IDEX-0005) and the LabEx Ecofect (ANR-11-LABX-0048) of the 'Université de Lyon' (http://ecofect.universite-lyon.fr/), within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the ANR. VL received financial support from the 'IDEXLYON IMPULSION 2019' project (ANR-16-IDEX-0005) of the ‘‘Université de Lyon', within the program ‘‘Investissements d’Avenir' (ANR-16-IDEX-0005) and from the 'Global Health Impulsion 2020' project of VetAgro Sup. FW is supported by the CCHVaccine consortium that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 732732, and by the Swedish Research Council (Vetenskapsrådet, VR) section Research Environment, Infection Biology (contract number 2018-05766)., ANR-16-IDEX-0005,IDEXLYON,IDEXLYON(2016), ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Bodescot, Myriam, IDEXLYON - - IDEXLYON2016 - ANR-16-IDEX-0005 - IDEX - VALID, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
Cell Membranes, Glycobiology, Golgi Apparatus, Biochemistry, Virions, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biology (General), chemistry.chemical_classification, Infectivity, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Secretory Pathway, 030302 biochemistry & molecular biology, 3. Good health, Transport protein, Protein Transport, Cell Processes, Hemorrhagic Fever Virus, Crimean-Congo, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, symbols, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cellular Structures and Organelles, Research Article, QH301-705.5, Immunology, Biology, Viral Structure, Transfection, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, symbols.namesake, Virology, Cell Line, Tumor, Genetics, Humans, Molecular Biology Techniques, Molecular Biology, Secretory pathway, 030304 developmental biology, Glycoproteins, Viral Structural Proteins, Virus Assembly, Biology and Life Sciences, Membrane Proteins, Protein Secretion, Proteins, Cell Biology, Golgi apparatus, RC581-607, Secretory protein, chemistry, Membrane protein, Parasitology, Immunologic diseases. Allergy, Glycoprotein, Gene Deletion
Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that has become a serious threat to the public health. CCHFV has a single-stranded, tripartite RNA genome composed of L, M, and S segments. Cleavage of the M polyprotein precursor generates the two envelope glycoproteins (GPs) as well as three secreted nonstructural proteins GP38 and GP85 or GP160, representing GP38 only or GP38 linked to a mucin-like protein (MLD), and a double-membrane-spanning protein called NSm. Here, we examined the relevance of each M-segment non-structural proteins in virus assembly, egress and infectivity using a well-established CCHFV virus-like-particle system (tc-VLP). Deletion of MLD protein had no impact on infectivity although it reduced by 60% incorporation of GPs into particles. Additional deletion of GP38 abolished production of infectious tc-VLPs. The loss of infectivity was associated with impaired Gc maturation and exclusion from the Golgi, showing that Gn is not sufficient to target CCHFV GPs to the site of assembly. Consistent with this, efficient complementation was achieved in cells expressing MLD-GP38 in trans with increased levels of preGc to Gc conversion, co-targeting to the Golgi, resulting in particle incorporation and restored infectivity. Contrastingly, a MLD-GP38 variant retained in the ER allowed preGc cleavage but failed to rescue miss-localization or infectivity. NSm deletion, conversely, did not affect trafficking of Gc but interfered with Gc processing, particle formation and secretion. NSm expression affected N-glycosylation of different viral proteins most likely due to increased speed of trafficking through the secretory pathway. This highlights a potential role of NSm in overcoming Golgi retention and facilitating CCHFV egress. Thus, deletions of GP38 or NSm demonstrate their important role on CCHFV particle production and infectivity. GP85 is an essential viral factor for preGc cleavage, trafficking and Gc incorporation into particles, whereas NSm protein is involved in CCHFV assembly and virion secretion., Author summary Orthonairoviruses, like the lethal Crimean-Congo hemorrhagic fever virus (CCHFV), encode secreted glycoproteins, such as GP38, in addition to virion envelope glycoproteins (Gn and Gc) that are processed by internal cleavage of the viral M segment encoded polyprotein. CCHFV MLD-GP38 proteins (GP160/GP85) also include an N-terminal domain encompassing a mucin-like protein that is released from GP38 by Furin. The protective effect of non-neutralizing monoclonal antibodies targeting GP38 against lethal CCHFV challenge previously highlighted the importance of GP38 in CCHFV replication. CCHFV also encodes a double-membrane-spanning protein (NSm) of unknown function, located between the Gn and Gc on the polyprotein. To investigate the roles of these so-called accessory proteins encoded by the CCHFV M-segment in virus formation and infectivity, we generated several M-segment deletion mutants and tested them in a CCHFV transcription-entry-competent virus-like particle (tc-VLP) system. Here, we demonstrate that GP38 is crucial for Gc biogenesis, interaction with Gn and trafficking to the Golgi, and that its deletion abrogates formation of infectious particles. We also show that NSm increases the rate of protein trafficking through the secretory pathway with altered N-glycosylation profiles that are advantageous for efficient virus release. These data advanced our understanding of GP38 and NSm roles and CCHFV-host interactions.

Published
2020
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10. Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients

Author

Christian Meyer, Walter Land, Vincent Legros, Gérard Audibert, Raphael Carapito, Béatrice Uring-Lambert, Alain Meyer, Erik Sauleau, Bernard Geny, Seiamak Bahram, Marie Borel, Pierre Diemunsch, Julien Pottecher, Eric Noll, Sébastien Gette, Elisabeth Gaertner, Gestionnaire, Hal Sorbonne Université, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Anesthésie réanimation [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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
medicine.medical_treatment, Medicine (miscellaneous), [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Neutrophil extracellular traps, Extracellular Traps, law.invention, Study Protocol, 0302 clinical medicine, Injury Severity Score, Randomized controlled trial, law, Multicenter Studies as Topic, Pharmacology (medical), Prospective Studies, Hypoxia, Randomized Controlled Trials as Topic, 0303 health sciences, lcsh:R5-920, Respiratory Distress Syndrome, Rehabilitation, Acute respiratory distress syndrome, Incidence, Dornase alfa, Institutional review board, Recombinant Proteins, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, lcsh:Medicine (General), medicine.drug, Adult, medicine.medical_specialty, Randomization, Lung injury, Placebo, 03 medical and health sciences, Double-Blind Method, medicine, Deoxyribonuclease I, Humans, 030304 developmental biology, Aerosols, business.industry, 030208 emergency & critical care medicine, Multiple trauma, Bayes Theorem, Respiration, Artificial, Clinical trial, Clinical Trials, Phase III as Topic, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency medicine, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Wounds and Injuries, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Hypoxaemia
Abstract

Background Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients. Methods TRAUMADORNASE will be an institution-led, multicentre, double-blinded, placebo-controlled randomized trial in ventilated trauma patients. The primary trial objective is to demonstrate a reduction in the incidence of moderate-to-severe hypoxaemia in severe trauma patients during the first 7 days from 45% to 30% by providing aerosolized dornase alfa as compared to placebo. The secondary objectives are to demonstrate an improvement in lung function and a reduction in morbidity and mortality. Randomization of 250 patients per treatment arm will be carried out through a secure, web-based system. Statistical analyses will include a descriptive step and an inferential step using fully Bayesian techniques. The study was approved by both the Agence Nationale de la Sécurité du Médicament et des Produits de Santé (ANSM, on 5 October 2018) and a National Institutional Review Board (CPP, on 6 November 2018). Participant recruitment began in March 2019. Results will be published in international peer-reviewed medical journals. Discussion If early administration of inhaled dornase alfa actually reduces the incidence of moderate-to-severe hypoxaemia in patients with severe trauma, this new therapeutic strategy may be easily implemented in many clinical trauma care settings. This treatment may facilitate ventilator weaning, reduce the burden of trauma-induced lung inflammation and facilitate recovery and rehabilitation in severe trauma patients. Trial registration ClinicalTrials.gov, NCT03368092. Registered on 11 December 2017.

Published
2020
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11. Report of One-Year Prospective Surveillance of SARS-CoV-2 in Dogs and Cats in France with Various Exposure Risks: Confirmation of a Low Prevalence of Shedding, Detection and Complete Sequencing of an Alpha Variant in a Cat

Author

Solène Denolly, Meriadeg Ar Gouilh, Matthieu Fritz, Bryce Leterrier, Emilie Krafft, François-Loïc Cosset, Angeli Kodjo, Sophie Levaltier, Sophie Angelloz-Pessey, Eric M. Leroy, Nicolas Nesi, Sandrine Corbet, Bertrand Boson, and Vincent Legros

Subjects
Male, medicine.medical_specialty, prevalence, Physiology, Context (language use), Cat Diseases, Real-Time Polymerase Chain Reaction, Microbiology, Asymptomatic, Article, Serology, Dogs, Virology, Epidemiology, medicine, Animals, Humans, Dog Diseases, Prospective Studies, Viral shedding, skin and connective tissue diseases, variants, CATS, Sequence Analysis, RNA, SARS-CoV-2, Transmission (medicine), business.industry, fungi, Zoonosis, COVID-19, Pets, sequencing, zoonosis, medicine.disease, QR1-502, Virus Shedding, body regions, Infectious Diseases, Cats, RNA, Viral, France, medicine.symptom, business
Abstract

Despite the probable zoonotic origin of SARS-CoV-2, only limited research efforts have been made to understand the role of companion animals in SARS-CoV-2 epidemiology. According to recent serological prevalence studies, human-to-companion animal transmission is quite frequent, which led us to consider that the risk of SARS-CoV-2 transmission from animal to human, albeit negligible in the present context, may have been underestimated. In this study, we provide the results of a prospective survey that was conducted to evaluate the SARS-CoV-2 isolation rate by qRT-PCR in dogs and cats with different exposure risks and clinical statuses. From April 2020 to April 2021, we analyzed 367 samples and investigated the presence of SARS-CoV-2 RNA using qRT-PCR. Only four animals tested positive, all of them being cats. Three cats were asymptomatic and one presented a coryza-like syndrome. We describe in detail the infection in two cats and the associated clinical characteristics. Importantly, we obtained SARS-CoV-2 genomes from one infected animal and characterized them as Alpha variants. This represents the first identification of the SARS-CoV-2 Alpha variant in an infected animal in France.

Published
2021
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12. Differentiation-dependent susceptibility of human muscle cells to Zika virus infection

Author

Gillian Butler-Browne, Jim Zoladek, Ingo Riederer, Quentin Giai Gianetto, Philippe Roingeard, Patricia Jeannin, Julien Burlaud-Gaillard, Pierre-Emmanuel Ceccaldi, Mariette Matondo, Valérie Choumet, Thibault Chaze, Vincent Legros, Vincent Mouly, Philippe V. Afonso, Antoine Gessain, Mariela-Natacha Gonzàlez, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université de Tours, Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Centre National de la Recherche Scientifique (CNRS)-Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en myologie, 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), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris], This work was supported by a Pasteur-Fiocruz grant. VL was supported by a fellowship from the 'Fondation pour la Recherche Médicale' (FRM), IR and MG by CNPq/Ciências sem Fronteiras program, CNPq/Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM). FOCEM - Mercosur Structural Convergence Fund 03/11. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), Matondo, Mariette, Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), UMRS974, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche en Myologie, 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), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)

Subjects
Proteomics, Pulmonology, RC955-962, Apoptosis, Pathology and Laboratory Medicine, Zika virus, 0302 clinical medicine, Medical Conditions, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Arctic medicine. Tropical medicine, MESH: Proteins, Chikungunya, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Zika Virus Infection, Stem Cells, MESH: Proteomics, 3. Good health, Medical Microbiology, Arboviral Infections, Viral Pathogens, Interferon Type I, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Public aspects of medicine, Cellular Types, MESH: Zika Virus, Microbiology, 03 medical and health sciences, Respiratory Disorders, MESH: Zika Virus Infection, Humans, Microbial Pathogens, MESH: Humans, Flaviviruses, MESH: Host-Pathogen Interactions, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, Chikungunya Infection, Proteins, medicine.disease, Tropical Diseases, Virology, MESH: Cell Line, 030104 developmental biology, Biological Tissue, Interferon type I, Developmental Biology, 0301 basic medicine, RNA viruses, MESH: Cell Death, MESH: Interferon Type I, MESH: Muscle Cells, Viral Diseases, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, medicine.disease_cause, Virus Replication, Dengue fever, Myoblasts, Cytopathogenic Effect, Viral, Medicine and Health Sciences, Morphogenesis, Myocyte, Cytopathic effect, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Muscle Fibers, Skeletal, Cell Death, Myogenesis, Cell Differentiation, Muscle Differentiation, Infectious Diseases, Cell Processes, Viruses, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Disease Susceptibility, Stem cell, RA1-1270, Pathogens, Anatomy, medicine.drug, Research Article, Neglected Tropical Diseases, MESH: Cell Differentiation, 030231 tropical medicine, Muscle Tissue, MESH: Disease Susceptibility, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Stem Cells, Biology, Cell Line, medicine, MESH: Myoblasts, Muscle Cells, MESH: Virus Replication, Cell Biology, Zika Virus, biology.organism_classification, MESH: Cytopathogenic Effect, Viral, Respiratory Infections
Abstract

Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, that may be involved in the physiopathological course of the infection. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human primary myoblasts that can be differentiated into myotubes, we found that myoblasts can be productively infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection, suggesting a differentiation-dependent susceptibility. Infection was accompanied by a caspase-independent cytopathic effect, associated with paraptosis-like cytoplasmic vacuolization. Proteomic profiling was performed 24h and 48h post-infection in cells infected with two different isolates. Proteome changes indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, and differentiation-dependent restriction of infection from myoblasts to myotubes. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences in ZIKV infection pathogenesis., Author summary Muscle cells are potential targets of many arboviruses, such as Ross River, Dengue, Sindbis, and chikungunya viruses, and may be involved in the disease manifestation. During the recent outbreak of Zika virus (ZIKV), myalgia was one of the most frequently reported symptoms. We investigated the susceptibility of human muscle cells to ZIKV infection. Using an in vitro model of human muscle stem cells (myoblasts) that can be differentiated into differentiated muscle cells (myotubes), we found that myoblasts can be infected by ZIKV. In contrast, myotubes were shown to be resistant to ZIKV infection. Infection induced the death of infected cells. Protein levels 24h and 48h post-infection indicate that ZIKV infection induces an upregulation of proteins involved in the activation of the Interferon type I pathway, and a downregulation of protein synthesis. This work constitutes the first observation of primary human muscle cells susceptibility to ZIKV infection, muscle stem cells being susceptible while differentiated muscle cells are resistant. Since myoblasts constitute the reservoir of stem cells involved in reparation/regeneration in muscle tissue, the infection of muscle cells and the viral-induced alterations observed here could have consequences during ZIKV infection.

Published
2020
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13. Productive Infection of Mouse Mammary Glands and Human Mammary Epithelial Cells by Zika Virus

Author

Vincent Legros, Patricia Jeannin, Antoine Gessain, Mathieu Hubert, Pierre-Emmanuel Ceccaldi, Thomas Montange, Aurélie Chiche, Aurore Vidy, Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plasticité cellulaire et Modélisation des Maladies / Cellular Plasticity and Disease Modelling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), This research received no external funding. M.H. was the recipient of a PhD fellowship from the French ministry of education and research, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], 030231 tropical medicine, lcsh:QR1-502, primary cells, Biology, Breast milk, Virus Replication, myoepithelial cells, Virus, lcsh:Microbiology, Article, dissemination, Zika virus, Cell Line, 03 medical and health sciences, Mice, luminal cells, 0302 clinical medicine, Pregnancy, Virology, Animals, Humans, mammary glands, Mammary Glands, Human, Fetus, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Milk, Human, Transmission (medicine), tropism, Myoepithelial cell, Epithelial Cells, Viral Load, biology.organism_classification, Infectious Disease Transmission, Vertical, 3. Good health, Viral Tropism, 030104 developmental biology, Infectious Diseases, Mammary Epithelium, RNA, Viral, Female, Viral load
Abstract

International audience; Zika virus (ZIKV) belongs to the large category of arboviruses. Surprisingly, several human-to-human transmissions of ZIKV have been notified, either following sexual intercourse or from the mother to fetus during pregnancy. Importantly, high viral loads have been detected in the human breast milk of infected mothers, and the existence of breastfeeding as a new mode of mother-to-child transmission of ZIKV was recently hypothesized. However, the maternal origin of infectious particles in breast milk is currently unknown. Here, we show that ZIKV disseminates to the mammary glands of infected mice after both systemic and local exposure with differential kinetics. Ex vivo, we demonstrate that primary human mammary epithelial cells were sensitive and permissive to ZIKV infection in this study. Moreover, by using in vitro models, we prove that mammary luminal-and myoepithelial-phenotype cell lines are both able to produce important virus progeny after ZIKV exposure. Our data suggest that the dissemination of ZIKV to the mammary glands and subsequent infection of the mammary epithelium could be one mechanism of viral excretion in human breast milk.

Published
2019
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14. Optic Nerve and Perioptic Sheath Diameter (ONSD), Eyeball Transverse Diameter (ETD) and ONSD/ETD Ratio on MRI in Large Middle Cerebral Artery Infarcts: A Case-Control Study

Author

Vincent Legros, Mathieu Bard, Lukshe Kanagaratnam, Damien Jolly, Guillaume Giordano-Orsini, Sophie Lefour, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Hôpital universitaire Robert Debré [Reims], and CCSD, Accord Elsevier

Subjects
Male, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Decompressive craniectomy, Eye, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine.artery, medicine, Humans, Optic nerve and perioptic sheath diameter, Transverse diameter, Stroke, Retrospective Studies, business.industry, Rehabilitation, Significant difference, Case-control study, Infarction, Middle Cerebral Artery, Optic Nerve, Middle Aged, Prognosis, medicine.disease, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Middle cerebral artery, Optic nerve, Female, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, Nuclear medicine, business, 030217 neurology & neurosurgery, MRI, Orbit (anatomy)
Abstract

International audience; Background: Despite recent progress in the multidisciplinary management of large middle cerebral artery infarcts, the neurological prognosis remains worrying in a non-negligible number of cases. The objective of this study is to analyze the contribution of optic nerve and perioptic sheath measurement on MRI to the acute phase of large middle cerebral artery infarcts.Methods: A retrospective case-control study between January 2008 and December 2019 in a single academic medical center was performed. Cases and controls were selected by interrogation of International Classification of Diseases (ICD), 10th edition, with ischemic stroke as criterion (code I64). Decompressive hemicraniectomy was a criterion for large middle cerebral artery infarcts (cases). Cases were matched with controls (1:3) based on age (± 5 years), sex, and year of hospitalization (± 2 years) The examinations were performed on 3T MRI (Siemens IRM 3T Magnetom).Optic nerve and perioptic sheath diameter was calculated using electronic calipers, 3 mm behind retina and in a perpendicular vector with reference to the orbit in axial 3D TOF sequence.Results: Of 2612 patients, 22 patients met all the criteria of large middle cerebral artery infarcts and they were paired with 44 controls. Patients were mainly women, mean age of 53.6 years. There is a significant difference in the size of the optic nerve and perioptic sheath diameter measured on MRI at patient's admission (right: 5.13 ± 0.2 mm vs. 4.80 mm ± 0.18, p

Published
2021
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15. Faster onset of bronchodilation with formoterol than with salmeterol in patients with stable, moderate to severe COPD: results of a randomized, double-blind clinical study

Author

Jacques P.H.M. Creemers, Vincent LeGros, Nikolaos Siafakas, Denise Till, Louis P.M. Greefhorst, John Kottakis, Demosthenes Bouros, Tim Overend, Giovanni Della Cioppa, Günter Rapatz, Riccardo Pistelli, and Violette Leclerc

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, Time Factors, Diseases of the respiratory system, Pulmonary Disease, Chronic Obstructive, Double-Blind Method, Formoterol Fumarate, Bronchodilation, medicine, Humans, Albuterol, Salmeterol Xinafoate, Aged, Aerosols, COPD, Cross-Over Studies, Inhalation, RC705-779, business.industry, Area under the curve, respiratory system, Middle Aged, medicine.disease, Crossover study, respiratory tract diseases, Bronchodilator Agents, Ethanolamines, Anesthesia, Female, Salmeterol, Formoterol, business, medicine.drug, circulatory and respiratory physiology
Abstract

OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1AUC*0-1 h).DESIGN: A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.SETTING: Five centres in four countries -- one centre each in France, Greece and Italy, and two centres in the Netherlands.PATIENTS: Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV11.17 L (range 0.56 to 1.77 L).INTERVENTIONS: Patients inhaled single doses of formoterol dry powder (12 and 24 μg), single doses of salmeterol (50 and 100 μg) and matching placebo on five separate days.MAIN RESULTS: The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1AUC*0-1 h, showed that formoterol 12 μg was statistically significantly superior to salmeterol 50 μg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol.CONCLUSIONS: Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD.

Published
2002

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