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1. ECMO support as a bridge to lung transplantation is an independent risk factor for bronchial anastomotic dehiscence

Author: Enora Atchade, Mélissa Ren, Sylvain Jean-Baptiste, Alexy Tran Dinh, Sébastien Tanaka, Parvine Tashk, Brice Lortat-Jacob, Maksud Assadi, Gaelle Weisenburger, Hervé Mal, Jean Nicolas Sénémaud, Yves Castier, Christian de Tymowski, and Philippe Montravers
Subjects: Lung transplantation, Bronchial anastomotic dehiscence, Airway complications, Extra corporeal membrane oxygenation, Diseases of the respiratory system, RC705-779
Abstract: Abstract Background Airway complications are frequent after lung transplantation (LT), as they affect up to 23% of recipients. The implication of perioperative extracorporeal membrane oxygenation (ECMO) support and haemodynamic instability has never been specifically assessed. The first aim of this study was to explore the impact of perioperative ECMO support on bronchial anastomotic dehiscence (BAD) at Day 90 after LT. Methods This prospective observational monocentric study analysed BAD in all consecutive patients who underwent LT in the Bichat Claude Bernard Hospital, Paris, France, between January 2016 and May 2019. BAD visible on bronchial endoscopy and/or tomodensitometry was recorded. A univariate analysis was performed (Fisher’s exacts and Mann–Whitney tests), followed by a multivariate analysis to assess independent risk factors for BAD during the first 90 days after LT (p
Published: 2022
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2. eOSCE stations live versus remote evaluation and scores variability

Author: Donia Bouzid, Jimmy Mullaert, Aiham Ghazali, Valentine Marie Ferré, France Mentré, Cédric Lemogne, Philippe Ruszniewski, Albert Faye, Alexy Tran Dinh, Tristan Mirault, and on behalf of Université Paris Cité Osce study group
Subjects: Interrater reliability, Remote objective structured clinical examination, Global ratings, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background Objective structured clinical examinations (OSCEs) are known to be a fair evaluation method. These recent years, the use of online OSCEs (eOSCEs) has spread. This study aimed to compare remote versus live evaluation and assess the factors associated with score variability during eOSCEs. Methods We conducted large-scale eOSCEs at the medical school of the Université de Paris Cité in June 2021 and recorded all the students’ performances, allowing a second evaluation. To assess the agreement in our context of multiple raters and students, we fitted a linear mixed model with student and rater as random effects and the score as an explained variable. Results One hundred seventy observations were analyzed for the first station after quality control. We retained 192 and 110 observations for the statistical analysis of the two other stations. The median score and interquartile range were 60 out of 100 (IQR 50–70), 60 out of 100 (IQR 54–70), and 53 out of 100 (IQR 45–62) for the three stations. The score variance proportions explained by the rater (ICC rater) were 23.0, 16.8, and 32.8%, respectively. Of the 31 raters, 18 (58%) were male. Scores did not differ significantly according to the gender of the rater (p = 0.96, 0.10, and 0.26, respectively). The two evaluations showed no systematic difference in scores (p = 0.92, 0.053, and 0.38, respectively). Conclusion Our study suggests that remote evaluation is as reliable as live evaluation for eOSCEs.
Published: 2022
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3. Temporary ICUs during the COVID-19 pandemic first wave: description of the cohort at a French centre

Author: Nathalie Zappella, Chadi Dirani, Brice Lortat Jacob, Sébastien Tanaka, Elie Kantor, Adnan El Kalai, Yassine Rkik, Aurélie Gouel Cheron, Alexy Tran Dinh, and Philippe Montravers
Subjects: COVID-19, ARDS, Intensive care, Sanitary crisis, Temporary ICU, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background During the COVID-19 first wave in France, the capacity of intensive care unit (ICU) beds almost doubled, mainly because of the opening of temporary ICUs with staff and equipment from anaesthesia. Objectives We aim to investigate if the initial management in temporary ICU is associated with a change in ICU mortality and short-term prognosis. Design Retrospective single-centre cohort study. Setting Surgical ICU of the Bichat Claude Bernard University Hospital during the COVID-19 “first wave” (from 18 March to 10 April 2020). Patients All consecutive patients older than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and/or typical radiological patterns were included during their first stay in the ICU for COVID-19. Intervention Patients were admitted to a temporary ICU if no room was available in the classical ICU and if they needed invasive mechanical ventilation but no renal replacement therapy or Extracorporeal Membrane Oxygenation (ECMO) in the short term. The temporary ICUs were managed by mixed teams (from the ICU and anaesthesiology departments) following a common protocol and staff meetings. Main outcome measure ICU mortality Results Among the 59 patients admitted, 37 (62.7%) patients had initial management in the temporary ICU. They had the same characteristics on admission and the same medical management as patients admitted to the classical ICU. ICU mortality was similar in the 2 groups (32.4% in temporary ICUs versus 40.9% in classical ICUs; p=0.58). SAPS-II and ECMO use were associated with mortality in multivariate analysis but not admission to the temporary ICU. Conclusion In an overload context of the ICU of a geographical area, our temporary ICU model allowed access to intensive care for all patients requiring it without endangering them.
Published: 2022
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4. Prolonged mechanical ventilation after lung transplantation: risks factors and consequences on recipient outcome

Author: Enora Atchade, Aimane Boughaba, Alexy Tran Dinh, Sylvain Jean-Baptiste, Sébastien Tanaka, Léa Copelovici, Brice Lortat-Jacob, Arnaud Roussel, Yves Castier, Jonathan Messika, Hervé Mal, Christian de Tymowski, and Philippe Montravers
Subjects: lung transplantation, intensive care unit, prolonged mechanical ventilation, outcome, one-year mortality, Medicine (General), R5-920
Abstract: BackgroundRisk factors and the incidence of prolonged mechanical ventilation (PMV) after lung transplantation (LT) have been poorly described. The study assessed predictive factors of PMV after LT.MethodsThis observational, retrospective, monocentric study included all patients who received LT in Bichat Claude Bernard Hospital between January 2016 and December 2020. PMV was defined as a duration of MV > 14 days. Independent risk factors for PMV were studied using multivariate analysis. One-year survival depending on PMV was studied using Kaplan Meier and log-rank tests. A p value 5 red blood cell units (p
Published: 2023
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5. Feasibility of large-scale eOSCES: the simultaneous evaluation of 500 medical students during a mock examination

Author: Donia Bouzid, Tristan Mirault, Aiham Ghazali, Léonore Muller, Enrique Casalino, Nathan Peiffer Smadja, Baptiste Auber, Mathias Guerin, Charles Henri Sambet, Isabelle Etienne, Victoire De Lastours, Cécile Badoual, Cédric Lemogne, Philippe Ruszniewski, Université Paris Cité’ OSCE study group, Albert Faye, and Alexy Tran Dinh
Subjects: Objective structured clinical examination, innovative, digital training, medical students, Special aspects of education, LC8-6691, Medicine (General), R5-920
Abstract: The COVID-19 pandemic has led health schools to cancel many on-site training and exams. Teachers were looking for the best option to carry out online OSCEs, and Zoom was the obvious choice since many schools have used it to pursue education purposes. Methods: We conducted a feasibility study during the 2020–2021 college year divided into six pilot phases and the large-scale eOSCEs on Zoom on June 30th, 2021. We developed a specific application allowing us to mass create Zoom meetings and built an entire organization, including a technical support system (an SOS room and catching-up rooms) and teachers’ training sessions. We assessed satisfaction via an online survey. Results: On June 30th, 531/794 fifth-year medical students (67%) participated in a large-scale mock exam distributed in 135 Zoom meeting rooms with the mobilization of 298 teachers who either participated in the Zoom meetings as standardized patients (N =135, 45%) or examiners (N =135, 45%) or as supervisors in the catching-up rooms (N =16, 6%) or the SOS room (N =12, 4%). In addition, 32/270 teachers (12%) experienced difficulties connecting to their Zoom meetings and sought the help of an SOS room member. Furthermore, 40/531 students (7%) were either late to their station or had technical difficulties and declared those issues online and were welcomed in one of the catching-up rooms to perform their eOSCE stations. Additionally, 518/531 students (98%) completed the entire circuit of three stations, and 225/531 students (42%) answered the online survey. Among them, 194/225 (86%) found eOSCES helpful for training and expressed their satisfaction with this experience. Conclusion: Organizing large-scale eOSCEs on Zoom is feasible with the appropriate tools. In addition, eOCSEs should be considered complementary to on-site OSCEs and to train medical students in telemedicine.
Published: 2022
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6. Simultaneous Hospital Outbreaks of New Delhi Metallo-β-Lactamase-Producing Enterobacterales Unraveled Using Whole-Genome Sequencing

Author: Stéphane Lo, Isabelle Lolom, Valérie Goldstein, Marie Petitjean, Emilie Rondinaud, Vincent Bunel-Gourdy, Alexy Tran Dinh, Paul-Henri Wicky, Etienne Ruppé, Camille d’Humières, Jean-Christophe Lucet, and Laurence Armand-Lefèvre
Subjects: whole-genome sequencing, carbapenemase-producing Enterobacterales, outbreak, NDM, Klebsiella pneumoniae, Klebsiella oxytoca, Microbiology, QR1-502
Abstract: ABSTRACT Multidrug-resistant Enterobacterales, including carbapenemase producers, are currently spreading in health care facilities and the community. The Bichat Claude Bernard hospital in Paris faced a prolonged NDM-producing Enterobacterales (NDM-CPE) outbreak. Whole-genome sequencing (WGS) was performed on all isolated NDM-CPE to evaluate its benefits for outbreak surveillance and comprehension. All NDM-CPE isolates collected during the outbreak period (August 2016 to January 2018) were sequenced using the Illumina NextSeq platform. Gene content and core genomes were compared. Genomics results underwent epidemiological analysis which classified NDM-CPE cases as imported (positive sample during the 48 h after admission), hospital acquired, or uncertain. Over the epidemic period, 61 patients were colonized or infected with 81 distinct NDM-CPE isolates. Klebsiella pneumoniae was the most common species (n = 52, 64%), followed by Escherichia coli (13.5%) and other species (22.5%). In all, 43/52 (83%) K. pneumoniae isolates were clonal (≤18 single nucleotide polymorphisms [SNPs] except for three isolates) and belonged to ST307. The IncFIIK [K2:A-/B-] plasmid carrying blaNDM-1 present in all ST307 K. pneumoniae isolates was also detected in 18 other NDM-CPE isolates. Additionally, eight clonal ST144 Klebsiella oxytoca (≤18 SNPs) isolates lacking the epidemic plasmid were observed. The WGS analyses confirmed the acquired and imported cases except for two patients and resolved uncertain cases, which all turned out to be hospital acquisitions. WGS coupled with epidemiological analysis unraveled three epidemic phenomena: mainly the spread of a clonal ST307 K. pneumoniae strain and its conjugative plasmid carrying blaNDM-1 but also the unexpected clonal spread of an ST144 K. oxytoca strain. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) can spread and cause outbreaks in health care facilities, resulting in increased lengths of stay and morbidity. Control of outbreaks requires epidemiological surveillance, usually based on microbiological screening and patient follow-up. These data are sometimes insufficient to identify the routes of dissemination. There is therefore a need for more accurate tools such as whole-genome sequencing (WGS), which allows comparison of isolates but also plasmids carrying resistance with a high definition. In this work, we retrospectively sequenced the genomes of all NDM-producing Enterobacterales isolated during a prolonged NDM outbreak in our hospital. We demonstrated the value of combining WGS with epidemiological data that unveiled the multiple mechanisms of dissemination involved in the outbreak and confirmed transmission cases. This work reinforces the potential of WGS in outbreak surveillance and suggests that it could improve outbreak control if used in real time by confirming transmission cases more rapidly.
Published: 2022
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7. Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia

Author: Céline Monard, Jonathan Pehlivan, Gabriel Auger, Sophie Alviset, Alexy Tran Dinh, Paul Duquaire, Nabil Gastli, Camille d’Humières, Adel Maamar, André Boibieux, Marion Baldeyrou, Julien Loubinoux, Olivier Dauwalder, Vincent Cattoir, Laurence Armand-Lefèvre, Solen Kernéis, and the ADAPT study group
Subjects: Antimicrobials, Antimicrobial stewardship, Pneumonia, Multiplex PCR, Syndromic tests, Biofire® FilmArray®, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). Methods This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. Results We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. Conclusions Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.
Published: 2020
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8. Impact of integrating objective structured clinical examination into academic student assessment: Large-scale experience in a French medical school.

Author: Alexandre Matet, Ludovic Fournel, François Gaillard, Laurence Amar, Jean-Benoit Arlet, Stéphanie Baron, Anne-Sophie Bats, Celine Buffel du Vaure, Caroline Charlier, Victoire De Lastours, Albert Faye, Eve Jablon, Natacha Kadlub, Julien Leguen, David Lebeaux, Alexandre Malmartel, Tristan Mirault, Benjamin Planquette, Alexis Régent, Jean-Laurent Thebault, Alexy Tran Dinh, Alexandre Nuzzo, Guillaume Turc, Gérard Friedlander, Philippe Ruszniewski, Cécile Badoual, Brigitte Ranque, Mehdi Oualha, and Marie Courbebaisse
Subjects: Medicine, Science
Abstract: PurposeObjective structured clinical examinations (OSCE) evaluate clinical reasoning, communication skills, and interpersonal behavior during medical education. In France, clinical training has long relied on bedside clinical practice in academic hospitals. The need for a simulated teaching environment has recently emerged, due to the increasing number of students admitted to medical schools, and the necessity of objectively evaluating practical skills. This study aimed at investigating the relationships between OSCE grades and current evaluation modalities.MethodsThree-hundred seventy-nine 4th-year students of University-of-Paris Medical School participated to the first large-scale OSCE at this institution, consisting in three OSCE stations (OSCE#1-3). OSCE#1 and #2 focused on cardiovascular clinical skills and competence, whereas OSCE#3 focused on relational skills while providing explanations before planned cholecystectomy. We investigated correlations of OSCE grades with multiple choice (MCQ)-based written examinations and evaluations of clinical skills and behavior (during hospital traineeships); OSCE grade distribution; and the impact of integrating OSCE grades into the current evaluation in terms of student ranking.ResultsThe competence-oriented OSCE#1 and OSCE#2 grades correlated only with MCQ grades (r = 0.19, P0.75). Conversely, the behavior-oriented OSCE#3 grades correlated with traineeship skill and behavior grades (r = 0.19, PConclusionThis large-scale French experience showed that OSCE designed to assess a combination of clinical competence and behavioral skills, increases the discriminatory capacity of current evaluations modalities in French medical schools.
Published: 2021
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9. Favorable, arduous or fatal postoperative pathway within 90 days of lung transplantation

Author: Alexy Tran-Dinh, Donia Bouzid, Adnan El Kalai, Enora Atchade, Sébastien Tanaka, Brice Lortat-Jacob, Sylvain Jean-Baptiste, Nathalie Zappella, Sandrine Boudinet, Yves Castier, Hervé Mal, Pierre Mordant, Jonathan Messika, and Philippe Montravers
Subjects: Lung transplantation, Intensive care unit, Mortality, Morbidity, Intraoperative ECMO, Diseases of the respiratory system, RC705-779
Abstract: Abstract Introduction The maximum gain in quality of life after lung transplantation (LT) is expected between six months and one year after LT, as the occurrence of chronic lung allograft dysfunction may mask the beneficial effects beyond one year. Thus, the postoperative period could be the cornerstone of graft success. We sought to describe the factors present before postoperative admission to the ICU and associated with favorable, arduous or fatal pathway within 90 days of LT. Materials and methods We conducted a retrospective single-center study between January 2015 and December 2020. Using multinomial regression, we assessed the demographic, preoperative and intraoperative characteristics of patients associated with favorable (duration of postoperative mechanical ventilation
Published: 2022
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10. Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis

Author: Sébastien Tanaka, Christian De Tymowski, Jules Stern, Donia Bouzid, Nathalie Zappella, Aurélie Snauwaert, Tiphaine Robert, Brice Lortat-jacob, Alexy Tran-dinh, Pascal Augustin, Anne Boutten, Parvine Tashk, Katell Peoc’h, Olivier Meilhac, and Philippe Montravers
Subjects: Medicine, Science
Abstract: Background High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. Results A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Conclusion Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.
Published: 2022

11. Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19

Author: Marine Peyneau, Vanessa Granger, Paul-Henri Wicky, Dounia Khelifi-Touhami, Jean-François Timsit, François-Xavier Lescure, Yazdan Yazdanpanah, Alexy Tran-Dinh, Philippe Montravers, Renato C. Monteiro, Sylvie Chollet-Martin, Margarita Hurtado-Nedelec, and Luc de Chaisemartin
Subjects: Adult, Male, Neutrophils, Science, Severity of Illness Index, Monocytes, Article, Immunocompromised Host, Young Adult, Prognostic markers, Humans, Acute inflammation, Monocytes and macrophages, Aged, Phagocytes, Multidisciplinary, SARS-CoV-2, COVID-19, Viral host response, Middle Aged, Prognosis, Immunity, Innate, Viral infection, Medicine, Female, Granulocytes
Abstract: COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.
Published: 2022

12. Severe necrotizing soft-tissue infection-associated mortality: Have a look at the computed tomography!

Author: Sébastien Tanaka, Michael Thy, Ralph Khoury, Alexy Tran-Dinh, Antoine Khalil, and Philippe Montravers
Subjects: Necrotizing soft-tissue infection, RC86-88.9, Soft Tissue Infections, Sepsis, Research Letter, Humans, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, Fasciitis, Necrotizing, Critical Care and Intensive Care Medicine, Tomography, Computed tomography, Outcome
Published: 2022

13. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis

Author: David Hajage, Alain Combes, Christophe Guervilly, Guillaume Lebreton, Alain Mercat, Arthur Pavot, Saad Nseir, Armand Mekontso-Dessap, Nicolas Mongardon, Jean Paul Mira, Jean-Damien Ricard, Alexandra Beurton, Guillaume Tachon, Loay Kontar, Christophe Le Terrier, Jean Christophe Richard, Bruno Mégarbane, Ruth H. Keogh, Aurélien Belot, Camille Maringe, Clémence Leyrat, Matthieu Schmidt, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Jean Reignier, Amélie Seguin, Charlotte Garret, Emmanuel Canet, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-Ahn Nay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W. Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Fabienne Tamion, Dorothée Carpentier, Déborah Boyer, Gaetan Beduneau, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clément Hoffmann, Nicolas Donat, Anne Chrisment, Rose-Marie Blot, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan LE Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, Sébastian Voicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Meriam Lamraoui, Claire Alessandri, Quentin de Roux, Charles de Roquetaillade, Benjamin G. Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, Thi My Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, Rostane Gaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien Pili Floury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Paris-Saclay, CHU Lille, Hôpital Henri Mondor, Groupe de recherche clinique CARMAS [Créteil] (UPEC/Faculté de Médecine de Créteil), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Foch [Suresnes], CHU Amiens-Picardie, Geneva University Hospital (HUG), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lariboisière-Fernand-Widal [APHP], London School of Hygiene and Tropical Medicine (LSHTM), RICHARD, Jean-Christophe, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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: Pulmonary and Respiratory Medicine, Adult, Respiratory Distress Syndrome, SARS-CoV-2, [SDV]Life Sciences [q-bio], acute respiratory distress syndrome (ARDS), COVID-19, extracorporeal membrane oxygenation, Critical Care and Intensive Care Medicine, Cohort Studies, [SDV] Life Sciences [q-bio], emulated target trial, acute respiratory distress syndrome, Treatment Outcome, surgical procedures, operative, Humans, Retrospective Studies
Abstract: International audience; Rationale: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown.Objectives: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2
Published: 2022
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14. Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia

Author: Jean-Sébastien Casalegno, Céline Monnard, Hanaa Benmansour, Stéphane Bonacorsi, Chloé Plouzeau, Agathe Becker, Guillaume Geslain, Camille d’Humières, Paul Duquaire, Catherine Neuwirth, Lauranne Broutin, Emmanuel Lecorche, Claude-Alexandre Gustave, Carole Lemarié, Laurence Armand-Lefevre, Emmanuelle Vigier, Adel Maamar, Jean-Philippe Lavigne, Jean-Pierre Quenot, Christophe Burucoa, Olivier Dauwalder, Gabriel Auger, Julie Cremniter, Alexy Tran-Dinh, Marion Baldeyrou, Hervé Jacquier, Maxime Pichon, Rafael Mahieu, Claire Poyart, Julien Loubinoux, Solen Kernéis, Manon Lejeune, Jean-François Timsit, Nabil Gastli, Bruno Lina, François Vandenesch, Achille Kouatchet, Vincent Cattoir, Pierre Saint-Sardos, Emmanuelle Cambau, Anthony Michaud, Sophie Alviset, André Boibieux, Aurélie Cointe, Gauthier Péan de Ponfilly, Grégory Destras, Robin Stéphan, Matthieu Daragon, Philippe Montravers, Michael Levy, Vincent Rzepecki, Hélène Pailhoriès, Service de Bactériologie [CHU Cochin, AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de bactériologie (CHU Dijon), Plateau technique de Biologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Bactériologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), 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), Hôpital Robert Debré, Laboratoire de Bactériologie et Hygiène Hospitalière [Rennes], CHU Pontchaillou [Rennes], Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), Hôpital Cochin [AP-HP], ARN régulateurs bactériens et médecine (BRM), 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 ), Meso Scale Diagnostics, The French FA-PP study group includes the following investigators: Sophie Alviset (Paris Cochin), Laurence Armand-Lefèvre (Paris Bichat), Marion Baldeyrou (Rennes), Agathe Becker (Hospices Civils de Lyon), André Boibieux (Hospices Civils de Lyon), Stéphane Bonacorsi (Paris, Robert-Debré), Christophe Burucoa (Poitiers), Emmanuelle Cambau (Paris Lariboisière), Jean-Sébastien Casalegno (Hospices Civils de Lyon), Aurélie Cointe (Paris, Robert-Debré), Julie Cremniter (Poitiers), Grégory Destras (Hospices Civils de Lyon), Paul Duquaire (Hospices Civils de Lyon), Guillaume Geslain (Paris, Robert-Debré), Claude-Alexandre Gustave (Hospices Civils de Lyon), Hervé Jacquier (Paris Lariboisière), Achille Kouatchet (Angers), Emmanuel Lecorche (Paris Lariboisière), Manon Lejeune (Paris Bichat), Bruno Lina (Hospices Civils de Lyon), Rafaël Mahieu (Angers), Adel Maamar (Rennes), Anthony Michaud (Poitiers), Céline Monnard (Hospices Civils de Lyon), Philippe Montravers (Paris Bichat), Catherine Neuwirth (Dijon), Gauthier Péan de Ponfilly (Paris, Lariboisière), Maxime Pichon (Poitiers), Chloé Plouzeau (Poitiers), Claire Poyart (Paris Cochin), Jean-Pierre Quenot (Dijon), Vincent Rzepecki (Nîmes), Robin Stéphan (Nîmes), Jean-François Timsit (Paris Bichat), Alexy Tran-Dinh (Paris Bichat), François Vandenesch (Hospices Civils de Lyon) and Emmanuelle Vigier (Paris Bichat)., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), 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), Université de Rennes 1 (UR1), and 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 )
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Atypical bacteria, Concordance, [SDV]Life Sciences [q-bio], FilmArray pneumonia panel, 030106 microbiology, Gastroenterology, Lower respiratory tract infection, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Multiplex polymerase chain reaction, Diagnosis, medicine, Pneumonia, Bacterial, Humans, 030212 general & internal medicine, medicine.diagnostic_test, biology, Bacteria, business.industry, General Medicine, Syndromic panel, Multiplex PCR, medicine.disease, biology.organism_classification, 3. Good health, Pneumonia, Infectious Diseases, Bronchoalveolar lavage, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Diagnostic Techniques, Sputum, medicine.symptom, business, Multiplex Polymerase Chain Reaction
Abstract: International audience; OBJECTIVES: To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. METHODS: This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. RESULTS: A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%-96.5%) and 96.0% (95% CI 95.5%-96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log(10) in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥10(6) DNA copies/mL grew significantly in culture. CONCLUSIONS: FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia.
Published: 2021
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15. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study

Author: Philippe PETUA, Xavier MONNET, Michael Levy, Alexy Tran Dinh, Rabih Hage, Marie Cantier, Nicolas WEISS, Marc Danguy des Déserts, Nicolas DUFOUR, Adrien Bouglé, Anne Godier, MICHEL CARLES, Laurent Bitker, Benjamin Glenn Chousterman, Olivier Lesieur, Céline Grégoire, Mathieu Page, Christophe LE TERRIER, Stephane Dauger, Hafid Ait-Oufella, Matthieu Daniel, Lionel Lamhaut, Martin Dres, Anatole Harrois, Jean-Pierre QUENOT, Sebastien Preau, Guillaume Louis, Valentin Pointurier, Pierre-Henri Moury, Alexandre Mebazaa, Thibault MARTINEZ, Maxime Léger, Sebastien Gette, Frank Chemouni, Benjamin Rohaut, GUILLAUME VOIRIOT, Nicolas TERZI, David Hajage, Tristan Morichau-Beauchant, International Network (INet), and Mégarbane, Bruno
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Original, medicine.medical_treatment, Critical Illness, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mechanical ventilation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Belgium, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Mortality risk factor, medicine, Humans, Hospital Mortality, Prospective Studies, Prospective cohort study, Outcome, Aged, [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, Respiratory Distress Syndrome, Acute respiratory distress syndrome, business.industry, SARS-CoV-2, Patient Acuity, COVID-19, Middle Aged, Respiration, Artificial, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Emergency medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, business
Abstract: Purpose To describe acute respiratory distress syndrome (ARDS) severity, ventilation management, and the outcomes of ICU patients with laboratory-confirmed COVID-19 and to determine risk factors of 90-day mortality post-ICU admission. Methods COVID-ICU is a multi-center, prospective cohort study conducted in 138 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, adjunctive interventions, ICU length-of-stay, and survival data were collected. Results From February 25 to May 4, 2020, 4643 patients (median [IQR] age 63 [54–71] years and SAPS II 37 [28–50]) were admitted in ICU, with day-90 post-ICU admission status available for 4244. On ICU admission, standard oxygen therapy, high-flow oxygen, and non-invasive ventilation were applied to 29%, 19%, and 6% patients, respectively. 2635 (63%) patients were intubated during the first 24 h whereas overall 3376 (80%) received invasive mechanical ventilation (MV) at one point during their ICU stay. Median (IQR) positive end-expiratory and plateau pressures were 12 (10–14) cmH2O, and 24 (21–27) cmH2O, respectively. The mechanical power transmitted by the MV to the lung was 26.5 (18.6–34.9) J/min. Paralyzing agents and prone position were applied to 88% and 70% of patients intubated at Day-1, respectively. Pulmonary embolism and ventilator-associated pneumonia were diagnosed in 207 (9%) and 1209 (58%) of these patients. On day 90, 1298/4244 (31%) patients had died. Among patients who received invasive or non-invasive ventilation on the day of ICU admission, day-90 mortality increased with the severity of ARDS at ICU admission (30%, 34%, and 50% for mild, moderate, and severe ARDS, respectively) and decreased from 42 to 25% over the study period. Early independent predictors of 90-day mortality were older age, immunosuppression, severe obesity, diabetes, higher renal and cardiovascular SOFA score components, lower PaO2/FiO2 ratio and a shorter time between first symptoms and ICU admission. Conclusion Among more than 4000 critically ill patients with COVID-19 admitted to our ICUs, 90-day mortality was 31% and decreased from 42 to 25% over the study period. Mortality was higher in older, diabetic, obese and severe ARDS patients. Electronic supplementary material The online version of this article (10.1007/s00134-020-06294-x) contains supplementary material, which is available to authorized users.
Published: 2020
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16. Performance of pre-hospital evaluations in ruling out invasive chest stab wounds

Author: Quentin Pellenc, Sébastien Tanaka, Pascal Augustin, Sandrine Boudinet, Philippe Montravers, Yves Castier, Alexy Tran-Dinh, and Elise Guivarch
Subjects: Adult, Male, Emergency Medical Services, medicine.medical_specialty, Critical Care, Thoracic Injuries, Decision Making, Overtriage, Vital signs, Physical examination, Wounds, Stab, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Chest penetrating trauma, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Stab, Trauma Centers, Acute care, medicine, Humans, Prospective Studies, Hemopneumothorax, Original Research, medicine.diagnostic_test, business.industry, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, Perioperative, lcsh:RC86-88.9, medicine.disease, Surgery, Cardiothoracic surgery, Emergency Medicine, Female, Triage, business, Penetrating trauma, Exploratory surgery
Abstract: Background Some guidelines advocate for managing patients with penetrating thoracic wounds in trauma centres with cardiothoracic surgery. This systematic approach is questionable. Only 15% of these patients require surgery. It is known that clinical examination fails to detect hemopneumothorax in penetrating trauma. However, no studies have evaluated the combined diagnostic performance of vital signs and the clinical evaluation of wounds. The clinical characteristics of wounds have not been investigated. We aimed to evaluate the ability of combinations of pre-hospital signs to rule out invasive chest stab trauma. Methods This was a prospective observational study. All consecutive adult patients hospitalized in the perioperative acute care unit of a tertiary university hospital were included. Injury diagnoses were provided by exploratory surgery and imaging tests. Patients with a final diagnosis of invasive wounds (IWs) and patients with only superficial wounds were compared. Data regarding management and outcome were analysed. Results A total of 153 patients were included. After imaging or surgery, 58 (38%) patients were diagnosed with only superficial wounds, and 95 (62%) were diagnosed with thoracic or abdominal IWs. The false-negative rate of pre-hospital evaluations in the diagnosis of IWs was 42% [31–51]IQR25–75. In stable patients, pre-hospital data could not rule out IWs, with a negative predictive value of 58% and a positive predictive value of 70%. Twenty-nine (19%) patients required early emergent cardiothoracic surgery. Among these patients, 8 (28%) had no evidence of IWs in the pre-hospital period. Among the 59 patients without pre-hospital signs of IWs, 19 (33%) underwent at least one emergent procedure. Conclusions The combination of pre-hospital vital signs, visual evaluation of wounds, and physical examination failed to rule out IWs in patients with chest stab wounds. This implies that caution is needed in triage decision-making.
Published: 2020
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17. High-Density Lipoprotein Therapy in Stroke: Evaluation of Endothelial SR-BI-Dependent Neuroprotective Effects

Author: Pierre Amarenco, Lauriane Galle-Treger, Philippe Montravers, Thierry Huby, Olivier Meilhac, Martine Moreau, Angélique Levoye, David Couret, Camille Hoteit, Sandrine Delbosc, Alexy Tran-Dinh, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Pharmacology, lcsh:Chemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Saline, lcsh:QH301-705.5, Spectroscopy, Mice, Knockout, SR-BI, General Medicine, Scavenger Receptors, Class B, stroke, 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], Neuroprotective Agents, medicine.anatomical_structure, Female, HDL receptor, Cellular model, Lipoproteins, HDL, Thiosemicarbazones, Cyclopentanes, high-density lipoprotein, Blood–brain barrier, Neuroprotection, Article, Catalysis, Cell Line, Inorganic Chemistry, 03 medical and health sciences, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, business.industry, Organic Chemistry, Endothelial Cells, blood-brain barrier, In vitro, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, Cell culture, business, 030217 neurology & neurosurgery
Abstract: International audience; High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.
Published: 2021
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18. Lung transplantation for COVID-19-associated ARDS

Author: Pierre Mordant, Alexy Tran-Dinh, Jonathan Messika, and Matthieu Schmidt
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, ARDS, medicine.medical_specialty, Respiratory Distress Syndrome, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.medical_treatment, MEDLINE, COVID-19, medicine.disease, Respiration, Artificial, Correspondence, medicine, Lung transplantation, Humans, business, Intensive care medicine, Lung Transplantation
Published: 2021

19. Altered high-density lipoprotein composition and functions during severe COVID-19

Author: Erick Vélia, Patrick Mavingui, Olivier Meilhac, Floran Begue, Philippe Montravers, Philippe Rondeau, Sébastien Tanaka, Tiphaine Robert, Marie Lagrange-Xelot, Zarouki Mouktadi, Alexy Tran-Dinh, Bryan Veeren, Nicolas Diotel, David Couret, Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de biochimie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Sainte Clotilde, Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Sud Saint Pierre [Ile de la Réunion], This research was funded by FEDER RE0001897 (EU—Région Réunion—French State national counterpart), by Université de La Réunion (COVID-19 emergency seed funding) as well as by the BIOST Fédération., Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Proteomics, Male, Apolipoprotein B, Proteome, Apoptosis, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Tandem Mass Spectrometry, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, biology, Middle Aged, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Tumor necrosis factor alpha, Female, France, Lipoproteins, HDL, medicine.medical_specialty, Science, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Serum amyloid A, Pandemics, Serum Amyloid A Protein, Mass spectrometry, Apolipoprotein A-I, business.industry, Aryldialkylphosphatase, Tumor Necrosis Factor-alpha, SARS-CoV-2, Paraoxonase, Case-control study, COVID-19, Endothelial Cells, Lipid metabolism, 030104 developmental biology, Endocrinology, chemistry, Viral infection, Case-Control Studies, alpha 1-Antitrypsin, biology.protein, high‑density lipoprotein, business, Biomarkers, Chromatography, Liquid
Abstract: Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
Published: 2021
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20. Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France

Author: Emilie Rondinaud, Lotfi Chemali, Stéphane Ruckly, Etienne Ruppé, Alexy Tran-Dinh, Laurence Armand-Lefevre, Charles Burdet, Brice Lortat-Jacob, Camille d’Humières, Jean-François Timsit, Naouale Maataoui, Philippe Montravers, and Juliette Patrier
Subjects: 0301 basic medicine, Bacterial Diseases, Male, Viral Diseases, Pulmonology, Antibiotics, 0302 clinical medicine, Medical Conditions, Medicine and Health Sciences, 030212 general & internal medicine, Lung, Multidisciplinary, Antimicrobials, Drugs, Hematology, Bacterial Infections, Middle Aged, Hospitals, Hospitalization, Intensive Care Units, Infectious Diseases, Medicine, Female, France, Research Article, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, 030106 microbiology, Bacterial translocation, Anaerobic Bacteria, Microbiology, 03 medical and health sciences, Internal medicine, Intensive care, Microbial Control, medicine, Pneumonia, Bacterial, Humans, Aged, Pharmacology, Bacteria, business.industry, Organisms, Biology and Life Sciences, COVID-19, Covid 19, Bloodstream Infections, Bacterial persistence, Pneumonia, medicine.disease, Health Care, Health Care Facilities, Digestive tract, business
Abstract: Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.
Published: 2021

21. Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study

Author: Nathalie Zappella, Sébastien Tanaka, Enora Atchade, Maxime Cournot, Brice Lortat-Jacob, Olivier Meilhac, Donia Bouzid, Aurélie Snauwaert, Pascal Augustin, Alexy Tran-Dinh, Jules Stern, Monique Dehoux, Tiphaine Robert, and Philippe Montravers
Subjects: medicine.medical_specialty, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, law.invention, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, law, Internal medicine, Medicine, Intensive care unit, Mortality, Outcome, medicine.diagnostic_test, business.industry, Septic shock, Research, Reverse cholesterol transport, Low-density lipoprotein, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, chemistry, lipids (amino acids, peptides, and proteins), business, Lipid profile, Lipoprotein
Abstract: Background High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome. Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient’s hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed. Results A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04–1.57) mmol/l; day 1 HDL-C = 0.44 (0.29–0.70) mmol/l; day 3 HDL-C = 0.30 (0.25–0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42–0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91–3.33) mmol/l; day 1 LDL-C = 1.0 (0.58–1.50) mmol/l; day 3 LDL-C = 1.04 (0.64–1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26–2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p p = 0.007, respectively). No link was found between prior lipid profile and mortality. Conclusions We showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.
Published: 2021

22. Implementation of French recommendations for the prevention and the treatment of hospital-acquired pneumonia: a cluster-randomized trial

Author: Achille Sossou, Rémy Bellier, Kevin Lagarde, Alexandre Mansour, Jean-Michel Constantin, Marc Leone, Céline Monard, Brice Fermier, Cedric Carrie, Sigismond Lasocki, Armine Rouhani, Alexy Tran Dinh, Pierre-François Perrigault, Antoine Roquilly, Jerôme Morel, Ghilain Beauplet, Sami Blidi, Claire Dahyot-Fizelier, Christian Isetta, Marie-Anne Vibet, Mathilde Holleville, Philippe Guerci, Clément Gakuba, Fanny Feuillet, Karim Asehnoune, Jeremy Bourenne, Marc Danguy des Déserts, Benjamin G. Chousterman, Karim Lakhal, Alexandru Cupaciu, Arnaud Foucrier, Gerald Chanques, Calypso Mathieu, Adrien Oudotte, Véronique Sébille, Hugues De Courson, Pauline Cailliez, Jonathan Au Duong, Department of Anesthesiology and Critical Care, Hotel Dieu, CHU Nantes, Nantes, Laboratory EA3826, Faculty of Medicine, University of Nantes, Nantes, 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), Département Anesthésie Réanimation, CHU d'Angers, Université d'Angers, Angers, Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire de Beaujon (AP/HP), Beaujon, Intensive Care Unit, Simone Veil Hospital, Blois, Department of Neuro-Critical Care, Pellegrin Hospital, Bordeaux, Surgical and trauma Intensive Care, Pellegrin Hospital, Bordeaux, Department of Anesthesiology and Critical Care, Hospital Inter-Armée Clermont Tonnerre, Brest, Department of Anesthesiology and Critical Care, CHU Caen, Caen, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Department of neuro-critical care, AP/HP, Creteil, Intensive Care Unit, Eaubonne Hospital, Eaubonne, Department of Anesthesiology and Critical Care, Emile Roux Hospital, Le Puy en Velay, Intensive Care Unit, Lorient Hospital, Lorient, Department of Anesthesiology and Critical Care, Hôpital Édouard Herriot, Hospices Civils de Lyon, Lyon, Department of Neuro-Critical Care, Hospices Civils de Lyon, Lyon, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Department of Anesthesiology and Critical Care Medicine, Hôpital Nord, Marseille, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Emergency Intensive Care Unit, Hopital la Timone, Marseille, Department of Anesthesiology and Cardiothoracic Intensive Care, Pierre Zobda-Quitman, Martinique, Department of Anesthesiology and Critical Care, Guillaume and Rene Laennec Hospital, CHU Nantes, Nantes, Severe Burn Intensive Care Unit, Hotel Dieu, CHU Nantes, Nantes, Department of Anesthesiology and Critical Care, Hotel Dieu, CHU Nantes, Surgical Intensive Care Unit, Centre Hospitalier Universitaire, Nancy, Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire de Bichat (AP/ HP), Paris, Department of Anesthesiology and Critical Care, Severe Burn Unit, Centre Hospitalier Universitaire de Lariboisiere (AP/HP), Paris, Anaesthesia Intensive Care Unit, Centre Hospitalier Universitaire de Saint Louis (AP/ HP), Paris, Surgical Intensive Care Unit, Centre Hospitalier Universitaire, Poitiers, Neuro-Intensive Care Unit, Centre Hospitalier Universitaire, Poitiers, Intensive Care Unit, Department of Anesthesiology and Critical Care, Rangueil Hospital, Centre Hospitalier Universitaire, Toulouse, Department of Anesthesiology and Critical Care, Pontchaillou Hospital, CHU Rennes, Rennes, Department of Anesthesiology and Critical Care, CHU Saint Etienne, Saint Etienne, Department of Anesthesiology, Intensive care and Perioperative medicine - Hautepierre Hospital, Strasbourg, Microbiotas Hosts Antibiotics Bacterial Resistances (MiHAR), Université de Nantes, Nantes, DRCI, Plateforme de Méthodologie et de Biostatistique, CHU Nantes, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-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), MORNET, Dominique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Microbiology (medical), medicine.medical_specialty, Critical Care, [SDV]Life Sciences [q-bio], Audit, Hospital-acquired pneumonia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, law, Intensive care, Humans, Medicine, 030212 general & internal medicine, Cluster randomised controlled trial, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, Healthcare-Associated Pneumonia, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, Intensive care unit, Hospitals, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Intensive Care Units, Infectious Diseases, Emergency medicine, business
Abstract: Background We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). Methods This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. Results Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38–56%) in the intervention group and 42% (IQR, 25–53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5–14 days) in the control group and 9 days (IQR, 5–20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69–2.01; P = .10). Conclusions The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. Clinical Trials Registration NCT03348579.
Published: 2020
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23. Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study

Author: Nathalie Zappella, Maksud Assadi, Lauriane Fontaine, Katell Peoc'h, Philippe Montravers, Alexy Tran-Dinh, Tiphaine Robert, Donia Bouzid, Brice Lortat-Jacob, Sébastien Tanaka, Olivier Meilhac, Sylvain Jean-Baptiste, Parvine Tashk, and Christian de Tymowski
Subjects: 0301 basic medicine, Male, Viral Diseases, Pulmonology, 030204 cardiovascular system & hematology, medicine.disease_cause, Gastroenterology, Biochemistry, law.invention, Hospitals, University, chemistry.chemical_compound, 0302 clinical medicine, Medical Conditions, COVID-19, Lipoproteins, Lipid profiles, Intensive care units, Sepsis, Lipids, Pneumonia, Cholesterol, law, Medicine and Health Sciences, Prospective Studies, Prospective cohort study, Multidisciplinary, Incidence (epidemiology), Reverse cholesterol transport, Pneumonia, Ventilator-Associated, Middle Aged, Intensive care unit, Lipid Profiles, Hospitals, Intensive Care Units, Infectious Diseases, Superinfection, Medicine, Female, lipids (amino acids, peptides, and proteins), France, Coronavirus Infections, Research Article, medicine.medical_specialty, Science, Pneumonia, Viral, 03 medical and health sciences, Betacoronavirus, Signs and Symptoms, Internal medicine, medicine, Pneumonia, Bacterial, Humans, Pandemics, Aged, business.industry, SARS-CoV-2, Cholesterol, HDL, Biology and Life Sciences, Proteins, Covid 19, Cholesterol, LDL, medicine.disease, Health Care, 030104 developmental biology, chemistry, Health Care Facilities, Clinical Medicine, business, Lipoprotein
Abstract: IntroductionSevere acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection.MethodsA prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP.ResultsA total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006).ConclusionHDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.
Published: 2020

24. Improved clinical communication OSCE scores after simulation-based training: Results of a comparative study

Author: Alexandre Nuzzo, Alexy Tran-Dinh, Marie Courbebaisse, Hugo Peyre, Patrick Plaisance, Alexandre Matet, Brigitte Ranque, Albert Faye, Victoire de Lastours, and University of Paris OSCE and SBT groups
Subjects: Science, education, Medicine
Abstract: ObjectivesSimulation-based training (SBT) is increasingly used to teach clinical patient-doctor communication skills (CS) to medical students. However, the long-lasting impact of this training has been poorly studied.MethodsIn this observational study we included all fourth-year undergraduate medical students from a French medical school who undertook a CS objective structured clinical examination (OSCE) and who answered a post-examination survey. OSCE scores and students' feedback were compared by whether students had received a specific CS-SBT or not 12 months prior to the OSCE.ResultsA total of 173 students were included in the study. Of them, 97 (56%) had followed the CS-SBT before the OSCE. Students who had undergone CS-SBT had significantly higher CS-OSCE scores in the multivariate analysis compared to untrained students (mean score 7.5/10 ±1.1 vs. 7.0/10 ±1.6, respectively, Cohen's d = 0.4, pConclusionsFourth-year medical students who benefited from a CS-SBT 12 months before examination displayed higher CS-OSCE scores than their counterparts.Practice implicationsThese results support the early introduction of practical training to improve communication skills in undergraduate medical curricula. Studies are required to assess the sustainability of this improvement over time and its effect on further real doctor-patient communication.
Published: 2020

25. The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial

Author: Alexandre Lafourcade, Aude Carillion, David Hajage, Julien Amour, Nora Ait Hamou, Sternocat investigators, Dan Longrois, Ahmed Charfeddine, Jean-Luc Fellahi, Adrien Bouglé, Sophie Provenchère, Sarah Hariri, Christian Latremouille, Alexandre Ouattara, Louis Labrousse, Bruno Riou, Alexy Tran Dinh, Bernard Cholley, Pascal Leprince, Paul Achouh, Alain Remy, Service d'anesthésiologie et soins intensifs [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Service de Chirurgie Thoracique et Cardiovasculaire [CHU Pitié-Salpêtrière], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Service d'urgence de médecine et de chirurgie [CHU Pitié-Salpêtrière], Service de Biostatistique Santé Publique et Information Médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Recherche Magellan, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), and Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM )
Subjects: Male, medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, Placebo, law.invention, Placebos, Postoperative pain, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, Double-Blind Method, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, law, Anesthesiology, medicine, Cardiopulmonary bypass, Humans, Critical care medicine, Anesthetics, Local, Cardiac Surgical Procedures, Infusion Pumps, Aged, Aged, 80 and over, Academic Medical Centers, Local anesthetic, business.industry, 030208 emergency & critical care medicine, Pneumonia, Middle Aged, Cardiac surgery, medicine.disease, Bupivacaine, Sternotomy, 3. Good health, Catheter, 030228 respiratory system, Local anesthetics, Anesthesia, Female, France, business
Abstract: Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage. In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h−1) of l-bupivacaine (12.5 mg h−1) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia. Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the l-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, − 1.3% [95% CI − 3.4; 0.8] P = 0.22). In the predefined subgroup of patients at high risk, l-bupivacaine decreased the incidence of pneumonia (absolute risk difference, − 5.6% [95% CI − 10.0; − 1.1], P = 0.01). After cardiac surgery with sternotomy, continuous wound infusion of l-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients. EudraCT Number: 2011-003292-10; Clinicaltrials.gov Identifier: NCT01648777.
Published: 2019
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26. Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury

Author: Jamila Khallou-Laschet, Dan Longrois, Olivier Corcos, Philippe Montravers, Liliane Louedec, Alexandre Nuzzo, Francesco Andreata, Jean-Baptiste Michel, Antonino Nicoletti, Maksud Assadi, Sandrine Delbosc, Quoc Thang Hoang, Alexy Tran-Dinh, Giuseppina Caligiuri, Hoang, Q, Nuzzo, A, Louedec, L, Delbosc, S, Andreata, F, Khallou-Laschet, J, Assadi, M, Montravers, P, Longrois, D, Corcos, O, Caligiuri, G, Nicoletti, A, Michel, J, and Tran-Dinh, A
Subjects: 0301 basic medicine, Ischemia, Ischemia-reperfusion injury, Peptide binding, 030204 cardiovascular system & hematology, Pharmacology, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, medicine, Extracellular, Superior mesenteric artery, Receptor, business.industry, Research, MED/04 - PATOLOGIA GENERALE, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, 030104 developmental biology, Mesenteric ischemia, CD31, business, Perfusion, Reperfusion injury
Abstract: Background CD31 is a key transmembrane neutrophil immunoregulatory receptor. Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive cleavage and shedding of the most extracellular domains of CD31 into plasma, enhancing the deleterious effect of neutrophil activation. We have evaluated the preventive therapeutic potential of an engineered synthetic octapeptide (P8RI), which restores the inhibitory intracellular signaling of cleaved CD31, in an experimental model of acute mesenteric ischemia/reperfusion. Methods In a randomized, controlled, and experimenter-blinded preclinical study, mesenteric ischemia/reperfusion (I/R) was induced in Wistar rats by superior mesenteric artery occlusion for 30 min followed by 4 h of reperfusion. Three groups of rats were compared: I/R + saline perfusion (I/R controls group, n = 7), I/R + preventive P8RI perfusion (P8RI group, n = 7), and sham-operated rats + saline perfusion (sham group, n = 7). Results Compared with I/R controls, P8RI perfusion significantly decreased intestinal ischemia/reperfusion injury (Chiu’s score, P = 0.01; epithelial area, P = 0.001) and bacterial translocation (plasma Escherichia coli DNA, P = 0.04) and could limit intestinal bleeding (P = 0.09). P8RI decreased neutrophil activation assessed by matrix metalloproteinase-9 release in plasma (P
Published: 2018

27. Detection of Apoptotic Cells in a Rabbit Model with Atherosclerosis-Like Lesions Using the Positron Emission Tomography Radiotracer [F]ML-10

Author: Fabien Hyafil, Alexy Tran-Dinh, Samuel Burg, Sébastien Leygnac, Liliane Louedec, Milan Milliner, Rana Ben Azzouna, Ayelet Reshef, Miri Ben Ami, Olivier Meilhac, and Dominique Le Guludec
Subjects: lcsh:Medical technology, lcsh:Biology (General), lcsh:R855-855.5, lcsh:QH301-705.5
Abstract: [ 18 F]ML-10 (2-(5-fluoro-pentyl)-2-methylmalonic acid) is a positron emission tomography (PET) radiotracer that accumulates in cells presenting apoptosis-specific membrane alterations. The aim of this study was to test whether [ 18 F]ML-10 allows for the detection of apoptotic cells located in atherosclerotic plaques in rabbits. Atherosclerotic plaques were induced in the aortas of five rabbits, and five additional rabbits were used as controls. Activity in the aortas was quantified in vivo and ex vivo. The localization of [ 18 F]ML-10 to the aortic wall was identified by autoradiography. Average target to background ratios measured in vivo by PET were higher in the aortas of atherosclerotic rabbits compared with those of control rabbits (2.00 ± 0.52 vs 1.22 ± 0.30; p < .05). Differences in [ 18 F]ML-10 uptake between atherosclerotic and control aortas were confirmed ex vivo by PET and gamma counting (23.9 ± 11.2 vs 1.1 ± 2.4 counts/pixel; p
Published: 2015

28. Is Night Surgery a Nightmare for Lung Transplantation?

Author: Sébastien Tanaka, Christian De Tymowski, Erevan Dupuis, Alexy Tran-Dinh, Brice Lortat-Jacob, Adela Harpan, Sylvain Jean-Baptiste, Sandrine Boudinet, Chahra-Zad Tahri, Mathilde Salpin, Yves Castier, Pierre Mordant, Hervé Mal, Antoine Girault, Enora Atchade, Philippe Montravers, and the Bichat Lung Transplant Group
Subjects: mortality, lung transplantation, outcome, morbidity, operative time, Specialties of internal medicine, RC581-951
Abstract: Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors’ general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.
Published: 2024
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29. COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure

Author: Clémence Gaudin, Maëlys Born-Bony, Bérengère Villeret, Madeleine Jaillet, Dorothée Faille, Jean-François Timsit, Alexy Tran-Dinh, Philippe Montravers, Bruno Crestani, Ignacio Garcia-Verdugo, and Jean-Michel Sallenave
Subjects: COVID-19, PBMCs, Pseudomonas aeruginosa, neutrophils, proteases, lymphocytes, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionAlthough many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented.MethodsHere, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU).ResultsWe show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads.DiscussionOverall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.
Published: 2024
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30. Downregulation of PGI2 pathway in Pulmonary Hypertension Group-III patients

Author: Yves Castier, Alice Guyard, Heba Abdelazeem, Xavier Norel, Chabha Benyahia, Gulsev Ozen, Salma Mani, Adam M. Silverstein, Amel Bouhadoun, Dan Longrois, Yasmine Amgoud, Alexy Tran-Dinh, Université de Paris (UP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Elevated pulmonary artery pressure, [SDV]Life Sciences [q-bio], Clinical Biochemistry, 030209 endocrinology & metabolism, Prostacyclin, Pharmacology, Pulmonary vein, Lung Disorder, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, Medicine, 030109 nutrition & dietetics, Lung, business.industry, Cell Biology, Hypoxia (medical), medicine.disease, Pulmonary hypertension, 3. Good health, medicine.anatomical_structure, Pulmonary artery, medicine.symptom, business, medicine.drug
Abstract: Pulmonary hypertension (PH) is a progressive and life-threating lung disorder characterized by elevated pulmonary artery pressure and vascular remodeling. PH is classified into five groups, and one of the most common and lethal forms, PH Group-III is defined as PH due to lung diseases and/or hypoxia. Due to the lack of studies in this group, PH-specific drug therapies including prostacyclin (PGI2) analogues have not been approved or recommended for use in these patients. PGI2 is synthesized by the PGI2 synthase (PGIS) enzyme, and its production is determined by measuring its stable metabolite, 6-keto-PGF1α. An impaired PGI2 pathway has been observed in PH animal models and in PH Group-I patients; however, there are contradictory results. The aim of this study is to determine whether PH Group-III is associated with altered expression of PGIS and production of PGI2 in humans. To explore this hypothesis, we measured PGIS expression (by western blot) and PGI2 production (by ELISA) in a large variety of preparations from the pulmonary circulation including human pulmonary artery, pulmonary vein, distal lung tissue, pulmonary artery smooth muscle cells (hPASMC), and bronchi in PH Group-III (n = 35) and control patients (n = 32). Our results showed decreased PGIS expression and/or 6-keto-PGF1α levels in human pulmonary artery, hPASMC, and distal lung tissue derived from PH Group-III patients. Moreover, the production of 6-keto-PGF1α from hPASMC positively correlated with PGIS expression and was inversely correlated with mean pulmonary artery pressure. On the other hand, PH Group-III pulmonary veins and bronchi did not show altered PGI2 production compared to controls. The deficit in PGIS expression and/or PGI2 production observed in pulmonary artery and distal lung tissue in PH Group-III patients may have important implications in the pathogenesis and treatment of PH Group-III.
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31. Improving clinical suspicion of acute mesenteric ischemia among patients with acute abdomen: a cross-sectional study from an intestinal stroke center

Author: Alexandre Nuzzo, Katell Peoc’h, Prabakar Vaittinada Ayar, Alexy Tran-Dinh, Emmanuel Weiss, Yves Panis, Maxime Ronot, Lorenzo Garzelli, Philippine Eloy, Iannis Ben Abdallah, Yves Castier, and Olivier Corcos
Subjects: Intestinal ischemia, Colon ischemia, Ischemic colitis, Peritonitis, Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Early diagnosis of acute mesenteric ischemia (AMI) is essential for a favorable outcome. Selection of patients requiring a dedicated multiphasic computed tomography (CT) scan remains a clinical challenge. Methods In this cross-sectional diagnostic study conducted from 2016 to 2018, we compared the presentation of AMI patients admitted to an intestinal stroke center to patients with acute abdominal pain of another origin admitted to the emergency room (controls). Results We included 137 patients—52 with AMI and 85 controls. Patients with AMI [median age: 65 years (interquartile range 55–74)] had arterial and venous AMI in 65% and 35% of cases, respectively. Relative to controls, AMI patients were significantly older, more likely to have risk factors or a history of cardiovascular disease, and more likely to present with sudden-onset and morphine-requiring abdominal pain, hematochezia, guarding, organ dysfunction, higher white blood cell and neutrophil counts, and higher plasma C-reactive protein (CRP) and procalcitonin concentrations. On multivariate analysis, two independent factors were associated with the diagnosis of AMI: the sudden-onset (OR = 20, 95%CI 7–60, p
Published: 2023
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32. Personalized risk predictor for acute cellular rejection in lung transplant using soluble CD31

Author: Alexy Tran-Dinh, Quentin Laurent, Guillaume Even, Sébastien Tanaka, Brice Lortat-Jacob, Yves Castier, Hervé Mal, Jonathan Messika, Pierre Mordant, Antonino Nicoletti, Philippe Montravers, Giuseppina Caligiuri, and Ian Morilla
Subjects: Medicine, Science
Abstract: Abstract We evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO2/FiO2) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a “peace-maker” at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31). The study included 40 lung transplant recipients, seven (17.5%) of whom experienced ACR. We modelled the plasma levels of sCD31 as a nonlinear dependent variable of the PaO2/FiO2 and respiratory SOFA over time using multivariate and multimodal models. A deep convolutional network classified the time series models of each individual associated with the risk of ACR to each individual in the cohort.
Published: 2022
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33. Accuracy of citrulline, I-FABP and d-lactate in the diagnosis of acute mesenteric ischemia

Author: Alexandre Nuzzo, Kevin Guedj, Sonja Curac, Claude Hercend, Claude Bendavid, Nathalie Gault, Alexy Tran-Dinh, Maxime Ronot, Antonino Nicoletti, Yoram Bouhnik, Yves Castier, Olivier Corcos, Katell Peoc’h, and The SURVI (Structure d’URgences Vasculaires Intestinales) Research Group (French Intestinal Stroke Center)
Subjects: Medicine, Science
Abstract: Abstract Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI—citrulline, intestinal fatty acid-binding protein (I-FABP), and d-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients—50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 μmol/L (12.0–26.0) vs. 23.3 μmol/L (18.3–29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58–0.78). No statistical difference was found in plasma I-FABP and plasma d-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and d-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.
Published: 2021
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34. Lipoprotein concentration in patients requiring extracorporeal membrane oxygenation

Author: Sébastien Tanaka, Christian De Tymowski, Nathalie Zappella, Aurélie Snauwaert, Tiphaine Robert, Brice Lortat-Jacob, Yves Castier, Alexy Tran-Dinh, Parvine Tashk, Donia Bouzid, Marylou Para, Quentin Pellenc, Enora Atchade, Olivier Meilhac, and Philippe Montravers
Subjects: Medicine, Science
Abstract: Abstract Extracorporeal membrane oxygenation (ECMO), a relevant technology for patients with acute respiratory distress syndrome (ARDS) or acute cardiac failure (ACF), is a frequent cause of systemic inflammatory response syndrome. During sepsis, HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) concentrations decrease, and an association between low lipoprotein levels and poor outcomes was reported. There are no data from patients undergoing ECMO. The goal of this study was to characterize the lipoprotein profiles of ICU patients requiring ECMO. All consecutive patients admitted for ARDS or ACF requiring ECMO were prospectively included. Daily lipoprotein levels and short-term prognosis outcome were assessed. 25 patients were included. On admission, lipoprotein concentrations were low, under the reference values ([HDL-C] = 0.6[0.4–0.8]mmol/L;[LDL-C] = 1.3[1.0–1.7]mmol/L). A statistically significant rise in lipoproteins overtime was observed during the ICU stay. We found no relationship between lipoproteins concentrations and mortality on Day-28 (p = 0.689 and p = 0.979, respectively). Comparison of surviving patients with non-surviving patients did not reveal any differences in lipoproteins concentrations. Stratification between septic and non-septic patients demonstrated that septic patients had lower lipoproteins concentrations on admission (HDL-C: 0.5[0.3–0.6]mmol/l vs 0.8[0.6–0.9]mmol/l, p = 0.003; LDL-C: 1.1[0.9–1.5]mmol/l vs 1.5[1.3–2.6]mmol/l; p = 0.012), whereas these two groups were comparable in terms of severity and outcomes. HDL-C concentrations during ICU hospitalization were also significantly lower in the septic group than in the non-septic group (p = 0.035). In conclusion, Lipoprotein concentrations are low in patients requiring ECMO but are not associated with poor outcomes. The subpopulation of septic patients had lower lipoprotein levels overtime, which reinforces the potential key-role of these particles during sepsis.
Published: 2021
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35. Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study

Author: Sébastien Tanaka, Jules Stern, Donia Bouzid, Tiphaine Robert, Monique Dehoux, Aurélie Snauwaert, Nathalie Zappella, Maxime Cournot, Brice Lortat-Jacob, Pascal Augustin, Enora Atchade, Alexy Tran-Dinh, Olivier Meilhac, and Philippe Montravers
Subjects: Sepsis, High-density lipoprotein, Low-density lipoprotein, Mortality, Intensive care unit, Outcome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome. Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient’s hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed. Results A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04–1.57) mmol/l; day 1 HDL-C = 0.44 (0.29–0.70) mmol/l; day 3 HDL-C = 0.30 (0.25–0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42–0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91–3.33) mmol/l; day 1 LDL-C = 1.0 (0.58–1.50) mmol/l; day 3 LDL-C = 1.04 (0.64–1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26–2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p
Published: 2021
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36. Altered high-density lipoprotein composition and functions during severe COVID-19

Author: Floran Begue, Sébastien Tanaka, Zarouki Mouktadi, Philippe Rondeau, Bryan Veeren, Nicolas Diotel, Alexy Tran-Dinh, Tiphaine Robert, Erick Vélia, Patrick Mavingui, Marie Lagrange-Xélot, Philippe Montravers, David Couret, and Olivier Meilhac
Subjects: Medicine, Science
Abstract: Abstract Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.
Published: 2021
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37. Performance of pre-hospital evaluations in ruling out invasive chest stab wounds

Author: Pascal Augustin, Elise Guivarch, Quentin Pellenc, Yves Castier, Sandrine Boudinet, Sebastien Tanaka, Philippe Montravers, and Alexy Tran-Dinh
Subjects: Chest penetrating trauma, Stab, Overtriage, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Some guidelines advocate for managing patients with penetrating thoracic wounds in trauma centres with cardiothoracic surgery. This systematic approach is questionable. Only 15% of these patients require surgery. It is known that clinical examination fails to detect hemopneumothorax in penetrating trauma. However, no studies have evaluated the combined diagnostic performance of vital signs and the clinical evaluation of wounds. The clinical characteristics of wounds have not been investigated. We aimed to evaluate the ability of combinations of pre-hospital signs to rule out invasive chest stab trauma. Methods This was a prospective observational study. All consecutive adult patients hospitalized in the perioperative acute care unit of a tertiary university hospital were included. Injury diagnoses were provided by exploratory surgery and imaging tests. Patients with a final diagnosis of invasive wounds (IWs) and patients with only superficial wounds were compared. Data regarding management and outcome were analysed. Results A total of 153 patients were included. After imaging or surgery, 58 (38%) patients were diagnosed with only superficial wounds, and 95 (62%) were diagnosed with thoracic or abdominal IWs. The false-negative rate of pre-hospital evaluations in the diagnosis of IWs was 42% [31–51]IQR25–75. In stable patients, pre-hospital data could not rule out IWs, with a negative predictive value of 58% and a positive predictive value of 70%. Twenty-nine (19%) patients required early emergent cardiothoracic surgery. Among these patients, 8 (28%) had no evidence of IWs in the pre-hospital period. Among the 59 patients without pre-hospital signs of IWs, 19 (33%) underwent at least one emergent procedure. Conclusions The combination of pre-hospital vital signs, visual evaluation of wounds, and physical examination failed to rule out IWs in patients with chest stab wounds. This implies that caution is needed in triage decision-making.
Published: 2020
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38. High-density lipoproteins during sepsis: from bench to bedside

Author: Sébastien Tanaka, David Couret, Alexy Tran-Dinh, Jacques Duranteau, Philippe Montravers, Anna Schwendeman, and Olivier Meilhac
Subjects: Endothelium, High-density lipoprotein (HDL), Inflammation, Intensive care unit (ICU), Lipopolysaccharide (LPS), Sepsis, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract High-density lipoproteins (HDLs) represent a family of particle characterized by the presence of apolipoprotein A-I (apoA-I) and by their ability to transport cholesterol from peripheral tissues back to the liver conferring them a cardioprotective function. HDLs also display pleiotropic properties including antioxidant, anti-apoptotic, anti-thrombotic, anti-inflammatory, or anti-infectious functions. Clinical data demonstrate that HDL cholesterol levels decrease rapidly during sepsis and that these low levels are correlated with morbi-mortality. Experimental studies emphasized notable structural and functional modifications of HDL particles in inflammatory states, including sepsis. Finally, HDL infusion in animal models of sepsis improved survival and provided a global endothelial protective effect. These clinical and experimental studies reinforce the potential of HDL therapy in human sepsis. In this review, we will detail the different effects of HDLs that may be relevant under inflammatory conditions and the lipoprotein changes during sepsis and we will discuss the potentiality of HDL therapy in sepsis.
Published: 2020
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39. Bacteraemia Is Associated with Increased ICU Mortality in the Postoperative Course of Lung Transplantation

Author: Alexy Tran-Dinh, Marion Guiot, Sébastien Tanaka, Brice Lortat-Jacob, Enora Atchade, Nathalie Zappella, Pierre Mordant, Yves Castier, Hervé Mal, Gaelle Weisenburger, Jonathan Messika, Nathalie Grall, and Philippe Montravers
Subjects: lung transplantation, bacteraemia, intensive care unit, Therapeutics. Pharmacology, RM1-950
Abstract: We aimed to describe the prevalence, risk factors, morbidity and mortality associated with the occurrence of bacteraemia during the postoperative ICU stay after lung transplantation (LT). We conducted a retrospective single-centre study that included all consecutive patients who underwent LT between January 2015 and October 2021. We analysed all the blood cultures drawn during the postoperative ICU stay, as well as samples from suspected infectious sources in case of bacteraemia. Forty-six bacteria were isolated from 45 bacteraemic patients in 33/303 (10.9%) patients during the postoperative ICU stay. Staphylococcus aureus (17.8%) was the most frequent bacteria, followed by Pseudomonas aeruginosa (15.6%) and Enterococcus faecium (15.6%). Multidrug-resistant bacteria accounted for 8/46 (17.8%) of the isolates. The most common source of bacteraemia was pneumonia (38.3%). No pre- or intraoperative risk factor for bacteraemia was identified. Recipients who experienced bacteraemia required more renal replacement therapy, invasive mechanical ventilation, norepinephrine support, tracheotomy and more days of hospitalization during the ICU stay. After adjustment for age, sex, type of LT procedure and the need for intraoperative ECMO, the occurrence of bacteraemia was associated with a higher mortality rate in the ICU (aOR = 3.55, 95% CI [1.56–8.08], p = 0.003). Bacteraemia is a major source of concern for lung transplant recipients.
Published: 2022
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40. Dynamic Changes in Microbial Composition During Necrotizing Soft-Tissue Infections in ICU Patients

Author: Michael Thy, Sébastien Tanaka, Alexy Tran-Dinh, Lara Ribeiro, Brice Lortat-Jacob, Julia Donadio, Nathalie Zappella, Mouna Ben-Rehouma, Parvine Tashk, Aurelie Snauwaert, Enora Atchade, Nathalie Grall, and Philippe Montravers
Subjects: necrotizing soft-tissue infections (NSTI), intensive care unit (ICU), sepsis, multidrug-resistant (MDR) bacteria, outcome, antimicrobial therapy, Medicine (General), R5-920
Abstract: Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries.Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses.Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50–68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1–7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate.Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.
Published: 2021
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41. Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France.

Author: Camille d'Humières, Juliette Patrier, Brice Lortat-Jacob, Alexy Tran-Dinh, Lotfi Chemali, Naouale Maataoui, Emilie Rondinaud, Etienne Ruppé, Charles Burdet, Stéphane Ruckly, Philippe Montravers, Jean-François Timsit, and Laurence Armand-Lefevre
Subjects: Medicine, Science
Abstract: Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.
Published: 2021
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42. Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study.

Author: Sébastien Tanaka, Christian De Tymowski, Maksud Assadi, Nathalie Zappella, Sylvain Jean-Baptiste, Tiphaine Robert, Katell Peoc'h, Brice Lortat-Jacob, Lauriane Fontaine, Donia Bouzid, Alexy Tran-Dinh, Parvine Tashk, Olivier Meilhac, and Philippe Montravers
Subjects: Medicine, Science
Abstract: IntroductionSevere acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection.MethodsA prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP.ResultsA total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006).ConclusionHDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.
Published: 2020
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43. First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation

Author: Sébastien Tanaka, Floran Begue, Bryan Veeren, Alexy Tran-Dinh, Tiphaine Robert, Parvine Tashk, Brice Lortat-Jacob, Dorothée Faille, Luc de Chaisemartin, Nathalie Zappella, Enora Atchade, Laura Kramer, Philippe Montravers, and Olivier Meilhac
Subjects: COVID-19, lipoprotein, HDL, proteomics, CER-001, case-report, Biology (General), QH301-705.5
Abstract: High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.
Published: 2022
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44. Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury

Author: Quoc Thang Hoang, Alexandre Nuzzo, Liliane Louedec, Sandrine Delbosc, Francesco Andreata, Jamila Khallou-Laschet, Maksud Assadi, Philippe Montravers, Dan Longrois, Olivier Corcos, Giuseppina Caligiuri, Antonino Nicoletti, Jean-Baptiste Michel, and Alexy Tran-Dinh
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background CD31 is a key transmembrane neutrophil immunoregulatory receptor. Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive cleavage and shedding of the most extracellular domains of CD31 into plasma, enhancing the deleterious effect of neutrophil activation. We have evaluated the preventive therapeutic potential of an engineered synthetic octapeptide (P8RI), which restores the inhibitory intracellular signaling of cleaved CD31, in an experimental model of acute mesenteric ischemia/reperfusion. Methods In a randomized, controlled, and experimenter-blinded preclinical study, mesenteric ischemia/reperfusion (I/R) was induced in Wistar rats by superior mesenteric artery occlusion for 30 min followed by 4 h of reperfusion. Three groups of rats were compared: I/R + saline perfusion (I/R controls group, n = 7), I/R + preventive P8RI perfusion (P8RI group, n = 7), and sham-operated rats + saline perfusion (sham group, n = 7). Results Compared with I/R controls, P8RI perfusion significantly decreased intestinal ischemia/reperfusion injury (Chiu’s score, P = 0.01; epithelial area, P = 0.001) and bacterial translocation (plasma Escherichia coli DNA, P = 0.04) and could limit intestinal bleeding (P = 0.09). P8RI decreased neutrophil activation assessed by matrix metalloproteinase-9 release in plasma (P
Published: 2018
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45. Clinical characteristics and prognosis of bacteraemia during postoperative intra-abdominal infections

Author: Adel Alqarni, Elie Kantor, Nathalie Grall, Sebastien Tanaka, Nathalie Zappella, Mathieu Godement, Lara Ribeiro-Parenti, Alexy Tran-Dinh, and Philippe Montravers
Subjects: Intra-abdominal infection, Postoperative infection, Bacteraemia, Outcome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Bloodstream infections of abdominal origin are usually associated with poor prognosis. We assessed the clinical and microbiological characteristics of critically ill patients admitted to the intensive care unit (ICU) for postoperative intra-abdominal infection (PIAI) and analysed the influence of bacteraemia on their outcome. Methods All consecutive PIAI patients admitted to the ICU between 1999 and 2014 were prospectively analysed. Bacteraemic patients (at least one positive blood culture in the 24 h preceding/following surgery) were compared with non-bacteraemic patients. Demographic characteristics, underlying disease, severity scores at the time of reoperation, microbiological results, therapeutic management, outcome, and survival were recorded. Results are expressed as median (interquartile range (IQR)) or proportions. Results Overall, 343 patients (54% male, 62 (49–73) years old) with PIAI were analysed, including 64 (19%) bacteraemic patients. Immunosuppression and cancer were more frequent in bacteraemic patients (p
Published: 2018
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46. Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study

Author: Nicolas, Nesseler, Guillaume, Fadel, Alexandre, Mansour, Marylou, Para, Pierre-Emmanuel, Falcoz, Nicolas, Mongardon, Alizée, Porto, Astrid, Bertier, Bruno, Levy, Cyril, Cadoz, Pierre-Grégoire, Guinot, Olivier, Fouquet, Jean-Luc, Fellahi, Alexandre, Ouattara, Julien, Guihaire, Vito-Giovanni, Ruggieri, Philippe, Gaudard, François, Labaste, Thomas, Clavier, Kais, Brini, Nicolas, Allou, Corentin, Lacroix, Juliette, Chommeloux, Guillaume, Lebreton, Michael A, Matthay, Sophie, Provenchere, Erwan, Flécher, André, Vincentelli, James T, Ross, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nanomédecine Régénérative (NanoRegMed), 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), CHU Strasbourg, Nouvel Hôpital Civil de Strasbourg, 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), Hôpital Henri Mondor, Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Bicêtre, 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 Cardiologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Marie-Lannelongue, Groupe Hospitalier Paris Saint-Joseph (hpsj), Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Institut Mutualiste de Montsouris (IMM), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, ECMOSARS Investigators: Marc Pierrot, Sidney Chocron, Guillaume Flicoteaux, Philippe Mauriat, Hadrien Roze, Olivier Huet, Marc-Olivier Fischer, Claire Alessandri, Raphel Bellaïche, Ophélie Constant, Quentin de Roux, André Ly, Arnaud Meffert, Jean-Claude Merle, Lucile Picard, Elena Skripkina, Thierry Folliguet, Antonio Fiore, Nicolas d'Ostrevy, Marie-Catherine Morgan, Maxime Nguyen, Lucie Gaide-Chevronnay, Nicolas Terzi, Gwenhaël Colin, Olivier Fabre, Arash Astaneh, Justin Issard, Elie Fadel, Dominique Fabre, Antoine Girault, Iolande Ion, Jean Baptiste Menager, Delphine Mitilian, Olaf Mercier, François Stephan, Jacques Thes, Jerôme Jouan, Thibault Duburcq, Valentin Loobuyck, Sabrina Manganiello, Mouhammed Moussa, Agnes Mugnier, Natacha Rousse, Olivier Desebbe, Roland Henaine, Matteo Pozzi, Jean-Christophe Richard, Zakaria Riad, Christophe Guervilly, Sami Hraiech, Laurent Papazian, Matthias Castanier, Charles Chanavaz, Sebastien Gette, Guillaume Louis, Erick Portocarrero, Nicolas Bischoff, Antoine Kimmoun, Mathieu Mattei, Pierre Perez, Alexandre Bourdiol, Yannick Hourmant, Pierre-Joachim Mahé, Bertrand Rozec, Mickaël Vourc'h, Stéphane Aubert, Florian Bazalgette, Claire Roger, Pierre Jaquet, Brice Lortat-Jacob, Pierre Mordant, Patrick Nataf, Juliette Patrier, Morgan Roué, Romain Sonneville, Alexy Tran-Dinh, Paul-Henri Wicky, Charles Al Zreibi, Bernard Cholley, Yannis Guyonvarch, Sophie Hamada, Claudio Barbanti, Anatole Harrois, Jordi Matiello, Thomas Kerforne, Nicolas Brechot, Alain Combes, Jean Michel Constantin, Cosimo D'Alessandro, Pierre Demondion, Alexandre Demoule, Martin Dres, Muriel Fartoukh, Guillaume Hekimian, Charles Juvin, Pascal Leprince, David Levy, Charles Edouard Luyt, Marc Pineton de Chambrun, Matthieu Schmidt, Thibaut Schoell, Pierre Fillâtre, Nicolas Massart, Roxane Nicolas, Maud Jonas, Charles Vidal, Salvatore Muccio, Dario Di Perna, Bruno Mourvillier, Amedeo Anselmi, Karl Bounader, Maxime Esvan, Claire Fougerou-Leurent, Yoann Launey, Thomas Lebouvier, Alessandro Parasido, Florian Reizine, Philippe Seguin, Emmanuel Besnier, Dorothée Carpentier, Anne Olland, Fanny Bounes, Vincent Minville, Antoine Guillon, Yannick Fedun, James T Ross, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), CHU Toulouse [Toulouse], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), University of California [San Francisco] (UCSF), University of California, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Claude Bernard Lyon 1 (UCBL)
Subjects: Cohort Studies, Male, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Extracorporeal Membrane Oxygenation, [SDV]Life Sciences [q-bio], COVID-19, Humans, Respiratory Insufficiency, Pandemics, Retrospective Studies
Abstract: Background Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non–COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. Methods The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. Results Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. Conclusions In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2022
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47. Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

Author: Dres, Martin, Hajage, David, Lebbah, Said, Kimmoun, Antoine, Pham, Tai, Béduneau, Gaëtan, Combes, Alain, Mercat, Alain, Guidet, Bertrand, Demoule, Alexandre, Schmidt, Matthieu, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Hôpital Bicêtre, 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, Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Saint-Antoine [AP-HP], COVID-ICU investigators: Alain Mercat, Pierre Asfar, François Beloncle, Julien Demiselle, Tài Pham, Arthur Pavot, Xavier Monnet, Christian Richard, Alexandre Demoule, Martin Dres, Julien Mayaux, Alexandra Beurton, Cédric Daubin, Richard Descamps, Aurélie Joret, Damien Du Cheyron, Frédéric Pene, Jean-Daniel Chiche, Mathieu Jozwiak, Paul Jaubert, Guillaume Voiriot, Muriel Fartoukh, Marion Teulier, Clarisse Blayau, Erwen L'Her, Cécile Aubron, Laetitia Bodenes, Nicolas Ferriere, Johann Auchabie, Anthony Le Meur, Sylvain Pignal, Thierry Mazzoni, Jean-Pierre Quenot, Pascal Andreu, Jean-Baptiste Roudau, Marie Labruyère, Saad Nseir, Sébastien Preau, Julien Poissy, Daniel Mathieu, Sarah Benhamida, Rémi Paulet, Nicolas Roucaud, Martial Thyrault, Florence Daviet, Sami Hraiech, Gabriel Parzy, Aude Sylvestre, Sébastien Jochmans, Anne-Laure Bouilland, Mehran Monchi, Marc Danguy des Déserts, Quentin Mathais, Gwendoline Rager, Pierre Pasquier, Reignier Jean, Seguin Amélie, Garret Charlotte, Canet Emmanuel, Jean Dellamonica, Clément Saccheri, Romain Lombardi, Yanis Kouchit, Sophie Jacquier, Armelle Mathonnet, Mai-AhnNay, Isabelle Runge, Frédéric Martino, Laure Flurin, Amélie Rolle, Michel Carles, Rémi Coudroy, Arnaud W Thille, Jean-Pierre Frat, Maeva Rodriguez, Pascal Beuret, Audrey Tientcheu, Arthur Vincent, Florian Michelin, Marie Anne Melone, Maxime Gauzi, Arnaud Guilbert, Geoffrey Kouadri, Valérie Gissot, Stéphan Ehrmann, Charlotte Salmon Gandonniere, Djlali Elaroussi, Agathe Delbove, Yannick Fedun, Julien Huntzinger, Eddy Lebas, Grâce Kisoka, Céline Grégoire, Stella Marchetta, Bernard Lambermont, Laurent Argaud, Thomas Baudry, Pierre-Jean Bertrand, Auguste Dargent, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Alexis Ferre, Antoine Gros, Guillaume Lacave, Fabrice Bruneel, Mathilde Neuville, Jérôme Devaquet, Guillaume Tachon, Richard Gallot, Riad Chelha, Arnaud Galbois, Anne Jallot, Ludivine Chalumeau Lemoine, Khaldoun Kuteifan, Valentin Pointurier, Louise-Marie Jandeaux, Joy Mootien, Charles Damoisel, Benjamin Sztrymf, Matthieu Schmidt, Alain Combes, Juliette Chommeloux, Charles Edouard Luyt, Frédérique Schortgen, Leon Rusel, Camille Jung, Florent Gobert, Damien Vimpere, Lionel Lamhaut, Bertrand Sauneuf, Liliane Charrrier, Julien Calus, Isabelle Desmeules, Benoît Painvin, Jean-Marc Tadie, Vincent Castelain, Baptiste Michard, Jean-Etienne Herbrecht, Mathieu Baldacini, Nicolas Weiss, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Pierre-Henri Moury, Anne-Charlotte Savida, Emmanuel Couadau, Mathieu Série, Nica Alexandru, Cédric Bruel, Candice Fontaine, Sonia Garrigou, Juliette Courtiade Mahler, Maxime Leclerc, Michel Ramakers, Pierre Garçon, Nicole Massou, Ly Van Vong, Juliane Sen, Nolwenn Lucas, Franck Chemouni, Annabelle Stoclin, Alexandre Avenel, Henri Faure, Angélie Gentilhomme, Sylvie Ricome, Paul Abraham, Céline Monard, Julien Textoris, Thomas Rimmele, Florent Montini, Gabriel Lejour, Thierry Lazard, Isabelle Etienney, Younes Kerroumi, Claire Dupuis, Marine Bereiziat, Elisabeth Coupez, François Thouy, Clémet Hoffmann, Nicolas Donat, Violaine Muller, Thibault Martinez, Antoine Kimmoun, Audrey Jacquot, Matthieu Mattei, Bruno Levy, Ramin Ravan, Loïc Dopeux, Jean-Mathias Liteaudon, Delphine Roux, Brice Rey, Radu Anghel, Deborah Schenesse, Vincent Gevrey, Jermy Castanera, Philippe Petua, Benjamin Madeux, Otto Hartman, Michael Piagnerelli, Anne Joosten, Cinderella Noel, Patrick Biston, Thibaut Noel, Gurvan L E Bouar, Messabi Boukhanza, Elsa Demarest, Marie-France Bajolet, Nathanaël Charrier, Audrey Quenet, Cécile Zylberfajn, Nicolas Dufour, Buno Mégarbane, SqébastianVoicu, Nicolas Deye, Isabelle Malissin, François Legay, Matthieu Debarre, Nicolas Barbarot, Pierre Fillatre, Bertrand Delord, Thomas Laterrade, Tahar Saghi, Wilfried Pujol, Pierre Julien Cungi, Pierre Esnault, Mickael Cardinale, Vivien Hong Tuan Ha, Grégory Fleury, Marie-Ange Brou, Daniel Zafimahazo, David Tran-Van, Patrick Avargues, Lisa Carenco, Nicolas Robin, Alexandre Ouali, Lucie Houdou, Christophe Le Terrier, Noémie Suh, Steve Primmaz, Jérome Pugin, Emmanuel Weiss, Tobias Gauss, Jean-Denis Moyer, Catherine Paugam Burtz, Béatrice La Combe, Rolland Smonig, Jade Violleau, Pauline Cailliez, Jonathan Chelly, Antoine Marchalot, Cécile Saladin, Christelle Bigot, Pierre-Marie Fayolle, Jules Fatséas, Amr Ibrahim, Dabor Resiere, Rabih Hage, Clémentine Cholet, Marie Cantier, Pierre Trouiler, Philippe Montravers, Brice Lortat-Jacob, Sebastien Tanaka, Alexy Tran Dinh, Jacques Duranteau, Anatole Harrois, Guillaume Dubreuil, Marie Werner, Anne Godier, Sophie Hamada, Diane Zlotnik, Hélène Nougue, Armand Mekontso-Dessap, Guillaume Carteaux, Keyvan Razazi, Nicolas De Prost, Nicolas Mongardon, Olivier Langeron, Eric Levesque, Arié Attias, Charles de Roquetaillade, Benjamin G Chousterman, Alexandre Mebazaa, Etienne Gayat, Marc Garnier, Emmanuel Pardo, Lea Satre-Buisson, Christophe Gutton, Elise Yvin, Clémence Marcault, Elie Azoulay, Michael Darmon, Hafid Ait Oufella, Geoffroy Hariri, Tomas Urbina, Sandie Mazerand, Nicholas Heming, Francesca Santi, Pierre Moine, Djillali Annane, Adrien Bouglé, Edris Omar, Aymeric Lancelot, Emmanuelle Begot, Gaétan Plantefeve, Damien Contou, Hervé Mentec, Olivier Pajot, Stanislas Faguer, Olivier Cointault, Laurence Lavayssiere, Marie-Béatrice Nogier, Matthieu Jamme, Claire Pichereau, Jan Hayon, Hervé Outin, François Dépret, Maxime Coutrot, Maité Chaussard, Lucie Guillemet, Pierre Goffin, Romain Thouny, Julien Guntz, Laurent Jadot, Romain Persichini, Vanessa Jean-Michel, Hugues Georges, Thomas Caulier, Gaël Pradel, Marie-Hélène Hausermann, ThiMy Hue Nguyen-Valat, Michel Boudinaud, Emmanuel Vivier, Sylvène Rosseli, Gaël Bourdin, Christian Pommier, Marc Vinclair, Simon Poignant, Sandrine Mons, Wulfran Bougouin, Franklin Bruna, Quentin Maestraggi, Christian Roth, Laurent Bitker, François Dhelft, Justine Bonnet-Chateau, Mathilde Filippelli, Tristan Morichau-Beauchant, Stéphane Thierry, Charlotte Le Roy, Mélanie Saint Jouan, Bruno Goncalves, Aurélien Mazeraud, Matthieu Daniel, Tarek Sharshar, Cyril Cadoz, RostaneGaci, Sébastien Gette, Guillaune Louis, Sophe-Caroline Sacleux, Marie-Amélie Ordan, Aurélie Cravoisy, Marie Conrad, Guilhem Courte, Sébastien Gibot, Younès Benzidi, Claudia Casella, Laurent Serpin, Jean-Lou Setti, Marie-Catherine Besse, Anna Bourreau, Jérôme Pillot, Caroline Rivera, Camille Vinclair, Marie-Aline Robaux, Chloé Achino, Marie-Charlotte Delignette, Tessa Mazard, Frédéric Aubrun, Bruno Bouchet, Aurélien Frérou, Laura Muller, Charlotte Quentin, Samuel Degoul, Xavier Stihle, Claude Sumian, Nicoletta Bergero, Bernard Lanaspre, Hervé Quintard, Eve Marie Maiziere, Pierre-Yves Egreteau, Guillaume Leloup, Florin Berteau, Marjolaine Cottrel, Marie Bouteloup, Matthieu Jeannot, Quentin Blanc, Julien Saison, Isabelle Geneau, Romaric Grenot, Abdel Ouchike, Pascal Hazera, Anne-Lyse Masse, Suela Demiri, Corinne Vezinet, Elodie Baron, Deborah Benchetrit, Antoine Monsel, Grégoire Trebbia, Emmanuelle Schaack, Raphaël Lepecq, Mathieu Bobet, Christophe Vinsonneau, Thibault Dekeyser, Quentin Delforge, Imen Rahmani, Bérengère Vivet, Jonathan Paillot, Lucie Hierle, Claire Chaignat, Sarah Valette, Benoït Her, Jennifier Brunet, Mathieu Page, Fabienne Boiste, Anthony Collin, Florent Bavozet, Aude Garin, Mohamed Dlala, Kais Mhamdi, Bassem Beilouny, Alexandra Lavalard, Severine Perez, Benoit Veber, Pierre-Gildas Guitard, Philippe Gouin, Anna Lamacz, Fabienne Plouvier, Bertrand P Delaborde, Aïssa Kherchache, Amina Chaalal, Jean-Damien Ricard, Marc Amouretti, Santiago Freita-Ramos, Damien Roux, Jean-Michel Constantin, Mona Assefi, Marine Lecore, Agathe Selves, Florian Prevost, Christian Lamer, Ruiying Shi, Lyes Knani, Sébastien PiliFloury, Lucie Vettoretti, Michael Levy, Lucile Marsac, Stéphane Dauger, Sophie Guilmin-Crépon, Hadrien Winiszewski, Gael Piton, Thibaud Soumagne, Gilles Capellier, Jean-Baptiste Putegnat, Frédérique Bayle, Maya Perrou, Ghyslaine Thao, Guillaume Géri, Cyril Charron, Xavier Repessé, Antoine Vieillard-Baron, Mathieu Guilbart, Pierre-Alexandre Roger, Sébastien Hinard, Pierre-Yves Macq, Kevin Chaulier, Sylvie Goutte, Patrick Chillet, Anaïs Pitta, Barbara Darjent, Amandine Bruneau, Sigismond Lasocki, Maxime Leger, Soizic Gergaud, Pierre Lemarie, Nicolas Terzi, Carole Schwebel, Anaïs Dartevel, Louis-Marie Galerneau, Jean-Luc Diehl, Caroline Hauw-Berlemont, Nicolas Péron, Emmanuel Guérot, Abolfazl Mohebbi Amoli, Michel Benhamou, Jean-Pierre Deyme, Olivier Andremont, Diane Lena, Julien Cady, Arnaud Causeret, Arnaud De La Chapelle, Christophe Cracco, Stéphane Rouleau, David Schnell, Camille Foucault, Cécile Lory, Thibault Chapelle, Vincent Bruckert, Julie Garcia, Abdlazize Sahraoui, Nathalie Abbosh, Caroline Bornstain, Pierre Pernet, Florent Poirson, Ahmed Pasem, Philippe Karoubi, Virginie Poupinel, Caroline Gauthier, François Bouniol, Philippe Feuchere, Florent Bavozet, Anne Heron, Serge Carreira, Malo Emery, Anne Sophie Le Floch, Luana Giovannangeli, Nicolas Herzog, Christophe Giacardi, Thibaut Baudic, Chloé Thill, Said Lebbah, Jessica Palmyre, Florence Tubach, David Hajage, Nicolas Bonnet, Nathan Ebstein, Stéphane Gaudry, Yves Cohen, Julie Noublanche, Olivier Lesieur, Arnaud Sément, Isabel Roca-Cerezo, Michel Pascal, Nesrine Sma, Gwenhaël Colin, Jean-Claude Lacherade, Gauthier Bionz, Natacha Maquigneau, Pierre Bouzat, Michel Durand, Marie-Christine Hérault, Jean-Francois Payen, and dres, martin
Subjects: [SDV] Life Sciences [q-bio], Acute respiratory distress syndrome, Frailty, [SDV]Life Sciences [q-bio], Old patients, COVID-19, Intensive care unit, Mortality, Intubation
Abstract: International audience; Abstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO 2 /FiO 2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO 2 /FiO 2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p
Published: 2021
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