Author: "Florian Reizine" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Florian Reizine"' showing total 65 results

Start Over Author "Florian Reizine"

65 results on '"Florian Reizine"'

1. Covid-19-associated pulmonary aspergillosis in mechanically ventilated patients: incidence and outcome in a French multicenter observational cohort (APICOVID)

Author: Luc Desmedt, Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Johann Auchabie, Julien Lorber, Béatrice La Combe, Pierre Kergoat, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Ergreteau, Philippe Seguin, Maëlle Martin, Jean Reignier, Jean-Baptiste Lascarrou, and Emmanuel Canet
Subjects: Invasive pulmonary aspergillosis, COVID‑19, Mechanical ventilation, Intensive care unit, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Recent studies identified coronavirus disease 2019 (COVID-19) as a risk factor for invasive pulmonary aspergillosis (IPA) but produced conflicting data on IPA incidence and impact on patient outcomes. We aimed to determine the incidence and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) in mechanically ventilated patients. Methods We performed a multicenter retrospective observational cohort study in consecutive adults admitted to 15 French intensive care units (ICUs) in 2020 for COVID-19 requiring mechanical ventilation. CAPA was diagnosed and graded according to 2020 ECMM/ISHAM consensus criteria. The primary objective was to determine the incidence of proven/probable CAPA, and the secondary objectives were to identify risk factors for proven/probable CAPA and to assess associations between proven/probable CAPA and patient outcomes. Results The 708 included patients (522 [73.7%] men) had a mean age of 65.2 ± 10.8 years, a median mechanical ventilation duration of 15.0 [8.0–27.0] days, and a day-90 mortality rate of 28.5%. Underlying immunosuppression was present in 113 (16.0%) patients. Corticosteroids were used in 348 (63.1%) patients. Criteria for probable CAPA were met by 18 (2.5%) patients; no patient had histologically proven CAPA. Older age was the only factor significantly associated with probable CAPA (hazard ratio [HR], 1.04; 95% CI 1.00–1.09; P = 0.04). Probable CAPA was associated with significantly higher day-90 mortality (HR, 2.07; 95% CI 1.32–3.25; P = 0.001) but not with longer mechanical ventilation or ICU length of stay. Conclusion Probable CAPA is a rare but serious complication of severe COVID-19 requiring mechanical ventilation and is associated with higher day-90 mortality. Graphical Abstract
Published: 2024
Full Text: View/download PDF

2. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author: Giuseppe Rossi, Jon Salmanton-García, Chiara Cattaneo, Francesco Marchesi, Julio Dávila-Valls, Sonia Martín-Pérez, Federico Itri, Alberto López-García, Andreas Glenthøj, Maria Gomes da Silva, Caroline Besson, Monia Marchetti, Barbora Weinbergerová, Ozren Jaksic, Moraima Jiménez, Yavuz M. Bilgin, Jaap Van Doesum, Francesca Farina, Pavel Žák, Luisa Verga, Graham P. Collins, Valentina Bonuomo, Jens Van Praet, Marcio Nucci, Stef Meers, Ildefonso Espigado, Nicola S. Fracchiolla, Toni Valković, Christian Bjørn Poulsen, Natasha Čolović, Giulia Dragonetti, Marie-Pierre Ledoux, Carlo Tascini, Caterina Buquicchio, Ola Blennow, Francesco Passamonti, Marina Machado, Jorge Labrador, Rafael F. Duarte, Martin Schönlein, Lucia Prezioso, Iker Falces-Romero, Austin Kulasekararaj, Carolina Garcia-Vidal, Noemí Fernández, Ghaith Abu-Zeinah, Irati Ormazabal-Vélez, Tatjana Adžić-Vukičević, Klára Piukovics, Igor Stoma, Annarosa Cuccaro, Gabriele Magliano, Tomáš Szotkowski, Tomás-José González-López, Shaimaa El-Ashwah, Rui Bergantim, Uluhan Sili, Johan Maertens, Fatih Demirkan, Cristina De Ramón, Verena Petzer, Maria Ilaria Del Principe, Milan Navrátil, Michelina Dargenio, Guldane Cengiz Seval, Michail Samarkos, Zdeněk Ráčil, László Imre Pinczés, Tobias Lahmer, Alessandro Busca, Gustavo-Adolfo Méndez, Antonio Vena, Monika M. Biernat, Maria Merelli, Maria Calbacho, Aleksandra Barać, Martina Bavastro, Alessandro Limongelli, Osman Ilhan, Dominik Wolf, Gökçe Melis Çolak, Ramón García-Sanz, Ziad Emarah, Bojana Mišković, Stefanie K. Gräfe, Miloš Mladenović, Tommaso Francesco Aiello, Lucía Núñez-Martín-Buitrago, Anna Nordlander, Elena Arellano, Giovanni Paolo Maria Zambrotta, Emanuele Ammatuna, Alba Cabirta, Maria Vittoria Sacchi, Raquel Nunes Rodrigues, Ditte Stampe Hersby, Michaela Hanakova, Laman Rahimli, Raul Cordoba, Oliver A. Cornely, Livio Pagano, Joyce MARQUES DE ALMEIDA, José-Ángel HERNÁNDEZ-RIVAS, Anna GUIDETTI, Olimpia FINIZIO, Zlate STOJANOSKI, Milche CVETANOSKI, Joseph MELETIADIS, Nick DE JONGE, Darko ANTIĆ, Natasha ALI, Maria Chiara TISI, Laura SERRANO, Gaëtan PLANTEFEVE, Nina KHANNA, Martin HOENIGL, Martin ČERŇAN, Carolina MIRANDA-CASTILLO, María FERNÁNDEZ-GALÁN, Alexandra SERRIS, Nurettin ERBEN, Rémy DULÉRY, Avinash AUJAYEB, Mario Virgilio PAPA, Jan NOVÁK, Mario DELIA, Giuseppe SAPIENZA, Florian REIZINE, Ali S. OMRANI, Roberta DI BLASI, Sylvain LAMURE, Ľuboš DRGOŇA, Nicola COPPOLA, Josip BATINIĆ, Murtadha AL-KHABORI, José-María RIBERA-SANTA SUSANA, Monica PIEDIMONTE, Jorge LOUREIRO-AMIGO, Guillemette FOUQUET, Rita FAZZI, François DANION, Jörg SCHUBERT, Baerbel HOELL-NEUGEBAUER, Nathan C. BAHR, Ayel Omar YAHIA, Ana TORRES-ATIENZA, Ikhwan RINALDI, Marina POPOVA, Hans-Beier OMMEN, Maria Enza MITRA, Malgorzata MIKULSKA, Ira LACEJ, Sofya KHOSTELIDI, Sein WIN, Donald VINH, Modar SALEH, Juergen PRATTES, Pavel JINDRA, Fabio GUOLO, Roberta DELLA PEPA, Ekaterina CHELYSHEVA, Przemyslaw ZDZIARSKI, Vivien WAI-MAN, Andrés SOTO-SILVA, Hans Martin ORTH, Sandra MALAK, Lisset LORENZO DE LA PEÑA, Martin KOLDITZ, Chi Shan KHO, Christopher H. HEATH, Ana GROH, Eleni GAVRIILAKI, Monica FUNG, Matthias EGGER, Elizabeth DE KORT, Erik DE CABO, Tania CUSHION, Fazle Rabbi CHOWDHURY, M. Mansour CEESAY, Mathias BREHON, Gina VARRICCHIO, Agostino TAFURI, María-Josefa JIMÉNEZ-LORENZO, Nikolai KLIMKO, Panagiotis TSIRIGOTIS, Anastasia ANTONIADOU, and Maria VEHRESCHILD
Subjects: Elderly, SARS-CoV-2, Hematological malignancy, High-risk patient, COVID-19, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.
Published: 2023
Full Text: View/download PDF

3. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022Research in context

Author: Jon Salmanton-García, Francesco Marchesi, Francesca Farina, Barbora Weinbergerová, Federico Itri, Julio Dávila-Valls, Sonia Martín-Pérez, Andreas Glenthøj, Ditte Stampe Hersby, Maria Gomes da Silva, Raquel Nunes Rodrigues, Alberto López-García, Raúl Córdoba, Yavuz M. Bilgin, Iker Falces-Romero, Shaimaa El-Ashwah, Ziad Emarah, Caroline Besson, Milena Kohn, Jaap Van Doesum, Emanuele Ammatuna, Monia Marchetti, Jorge Labrador, Giovanni Paolo Maria Zambrotta, Luisa Verga, Ozren Jaksic, Marcio Nucci, Klára Piukovics, Alba Cabirta-Touzón, Moraima Jiménez, Elena Arellano, Ildefonso Espigado, Ola Blennow, Anna Nordlander, Stef Meers, Jens van Praet, Tommaso Francesco Aiello, Carolina Garcia-Vidal, Nicola Fracchiolla, Mariarita Sciumè, Guldane Cengiz Seval, Pavel Žák, Caterina Buquicchio, Carlo Tascini, Stefanie K. Gräfe, Martin Schönlein, Tatjana Adžić-Vukičević, Valentina Bonuomo, Chiara Cattaneo, Summiya Nizamuddin, Martin Čerňan, Gaëtan Plantefeve, Romane Prin, Tomas Szotkovski, Graham P. Collins, Michelina Dargenio, Verena Petzer, Dominik Wolf, Natasha Čolović, Lucia Prezioso, Toni Valković, Francesco Passamonti, Gustavo-Adolfo Méndez, Uluhan Sili, Antonio Vena, Martina Bavastro, Alessandro Limongelli, Rafael F. Duarte, Marie-Pierre Ledoux, Milche Cvetanoski, Zlate Stojanoski, Marina Machado, Josip Batinić, Gabriele Magliano, Monika M. Biernat, Nikola Pantić, Christian Bjørn Poulsen, Annarosa Cuccaro, Maria Ilaria Del Principe, Austin Kulasekararaj, Irati Ormazabal-Vélez, Alessandro Busca, Fatih Demirkan, Marriyam Ijaz, Nikolai Klimko, Igor Stoma, Sofya Khostelidi, Noemí Fernández, Ali S. Omrani, Rui Bergantim, Nick De Jonge, Guillemette Fouquet, Milan Navrátil, Ghaith Abu-Zeinah, Michail Samarkos, Johan Maertens, Cristina De Ramón, Anna Guidetti, Ferenc Magyari, Tomás José González-López, Tobias Lahmer, Olimpia Finizio, Natasha Ali, László Imre Pinczés, Esperanza Lavilla-Rubira, Alessandra Romano, Maria Merelli, Mario Delia, Maria Calbacho, Joseph Meletiadis, Darko Antić, José-Ángel Hernández-Rivas, Joyce Marques de Almeida, Murtadha Al-Khabori, Martin Hoenigl, Maria Chiara Tisi, Nina Khanna, Aleksandra Barać, Noha Eisa, Roberta Di Blasi, Raphaël Liévin, Carolina Miranda-Castillo, Nathan C. Bahr, Sylvain Lamure, Mario Virgilio Papa, Ayel Yahya, Avinash Aujayeb, Jan Novák, Nurettin Erben, María Fernández-Galán, José-María Ribera-Santa Susana, Ikhwan Rinaldi, Rita Fazzi, Monica Piedimonte, Rémy Duléry, Yung Gonzaga, Andrés Soto-Silva, Giuseppe Sapienza, Alexandra Serris, Ľuboš Drgoňa, Ana Groh, Laura Serrano, Eleni Gavriilaki, Athanasios Tragiannidis, Juergen Prattes, Nicola Coppola, Vladimir Otašević, Miloš Mladenović, Mirjana Mitrović, Bojana Mišković, Pavel Jindra, Sofia Zompi, Maria Vittoria Sacchi, Carolin Krekeler, Maria Stefania Infante, Daniel García-Bordallo, Gökçe Melis Çolak, Jiří Mayer, Marietta Nygaard, Michaela Hanáková, Zdeněk Ráčil, Matteo Bonanni, Philipp Koehler, Laman Rahimli, Oliver A. Cornely, Livio Pagano, Francisco Javier Martín-Vallejo, Przemyslaw Zdziarski, Hossein Zarrinfer, Jana Wittig, Sein Win, Vivien Wai-Man, Benjamín Víšek, Donald C. Vinh, Maria Vehreschild, Gina Varricchio, Panagiotis Tsirigotis, Ana Torres-Tienza, Alina Daniela Tanase, Agostino Tafuri, Maria Stamouli, Jiří Sramek, Carole Soussain, Ayten Shirinova, Jörg Schubert, Enrico Schalk, Mohammad Reza Salehi, Modar Saleh, Giorgio Rosati, Elisa Roldán, Florian Reizine, Mayara Rêgo, Isabel Regalado-Artamendi, Marina Popova, Fernando Pinto, Laure Philippe, Hans Martin Orth, Hans-Beier Ommen, Aleš Obr, Lucía Núñez-Martín-Buitrago, Nicolas Noël, Julia Neuhann, Gianpaolo Nadali, Julia A. Nacov, Ana M. Munhoz Alburquerque, Maria Enza Mitra, Malgorzata Mikulska, Sibylle Mellinghoff, Ben Mechtel, Juan-Alberto Martín-González, Sandra Malak, Jorge Loureiro-Amigo, Lisset Lorenzo De La Peña, Giulia Liberti, Marianne Landau, Ira Lacej, Martin Kolditz, Chi Shan Kho, Reham Abdelaziz Khedr, Meinolf Karthaus, Linda Katharina Karlsson, María-Josefa Jiménez-Lorenzo, Macarena Izuzquiza, Baerbel Hoell-Neugebauer, Raoul Herbrecht, Christopher H. Heath, Fabio Guolo, Jan Grothe, Antonio Giordano, Sergey Gerasymchuk, Ramón García-Sanz, Nicole García-Poutón, Vaneuza Araújo Moreira Funke, Monica Fung, Charlotte Flasshove, Luana Fianchi, Jenna Essame, Matthias Egger, Bernard Drenou, Giulia Dragonetti, Maximilian Desole, Roberta Della Pepa, Bénédicte Deau Fischer, Elizabeth De Kort, Erik De Cabo, François Danion, Etienne Daguindau, Tania Cushion, Louise Cremer, Marianna Criscuolo, Gregorio Cordini, Antonella Cingolani, Fabio Ciceri, Fazle Rabbi Chowdhury, Ekaterina Chelysheva, Adrien Chauchet, Louis Yi Ann Chai, M. Mansour Ceesay, Elena Busch, Mathias Brehon, Davimar M.M. Borducchi, Stephen Booth, Serge Bologna, Caroline Berg Venemyr, Rebeca Bailén-Almorox, Anastasia Antoniadou, Amalia N. Anastasopoulou, and Fevzi Altuntaş
Subjects: Vaccination, ICU, COVID-19, Haematological malignancy, Immunosuppression, Medicine (General), R5-920
Abstract: Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.
Published: 2024
Full Text: View/download PDF

4. Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia

Author: Nicolas Massart, Emma Plainfosse, Yanis Benameur, Clarisse Dupin, Florence Legall, Anne Cady, Frederic Gourmelin, François Legay, Nicolas Barbarot, Eric Magalhaes, Pierre Fillatre, Aurélien Frerou, and Florian Reizine
Subjects: Critical care, Pneumonia, Acquired infection, Pulmonary aspergillosis, Prediction score, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP. Methods Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort. Results Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia
Published: 2023
Full Text: View/download PDF

5. Prophylactic platelet transfusion response in critically ill patients: a prospective multicentre observational study

Author: Florian Reizine, Sarah Le Marec, Anthony Le Meur, Maëlys Consigny, Florian Berteau, Laetitia Bodenes, Marie Geslain, Zoe McQuilten, Catherine Le Niger, Julien Huntzinger, Philippe Seguin, Jean-Baptiste Thibert, David Simon, Jean Reignier, Pierre-Yves Egreteau, Jean-Marc Tadié, Olivier Huet, Pierre Asfar, Stephan Ehrmann, and Cécile Aubron
Subjects: Platelet transfusion response, Prophylactic transfusion, Critically ill patient, Bleeding, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes. Methods This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18–24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensitivity analyses were conducted in patients with and without haematology malignancy and chemotherapy. Results Poor platelet transfusion response occurred in 349 of the 472 (73.9%) prophylactic platelet transfusions and in 141/181 (77.9%) patients. The mixed-effect model identified haemoglobin at ICU admission (odds ratio (OR): 0.79 [95% confidence interval (CI) 0.7–0.89]) and body mass index (BMI) (OR: 0.93 [0.89–0.98]) being positively and independently associated with platelet transfusion response, while a haematological malignancy (OR 1.93 [1.09–3.43]), sepsis as primary ICU admission diagnosis (OR: 2.81 [1.57–5.03]), SOFA score (OR 1.10 [1.03; 1.17]) and maximum storage duration of platelet (OR: 1.24 [1.02–1.52]) were independently associated with a suboptimal platelet increment. Clinical outcomes did not differ between groups, nor the requirement for red blood cells. Poor platelet transfusion response was found in 93.5% of patients with haematology malignancy and chemotherapy. Conclusions In this study of critically ill patients, of whom more than half had bone marrow failure, almost three quarters of prophylactic platelet transfusions led to suboptimal platelet increment measured 18 to 24 h following platelet transfusion. Platelet storage duration was the only factor associated with poor platelet response that may be accessible to intervention. Trial registration in October 2017: ClinicalTrials.gov: NCT03325140.
Published: 2023
Full Text: View/download PDF

6. Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study

Author: Pauline Guillot, Flora Delamaire, Arnaud Gacouin, Benoit Painvin, Caroline Piau, Florian Reizine, Mathieu Lesouhaitier, Jean-Marc Tadié, and Adel Maamar
Subjects: Community-acquired pneumonia, Legionella, Antibiotic stewardship, Critically ill patients, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). Methods We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. Results Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. Conclusion Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.
Published: 2023
Full Text: View/download PDF

7. Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome in the intensive care unit: a case report

Author: Félicie Belicard, Nicolas Belhomme, Simon Bouzy, Clémence Saillard, Fabienne Nedelec, Jean-Baptiste Mear, Samuel Ardois, Cedric Pastoret, Florian Reizine, Christophe Camus, and Benoit Painvin
Subjects: VEXAS syndrome, Vacuoles, Autoinflammatory disease, Cardiac arrest, ICU, Sweet’s syndrome, Medicine
Abstract: Abstract Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the literature. Here, we describe the case of a patient with known Sweet’s syndrome admitted to the intensive care unit and for whom a vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome was diagnosed, allowing for appropriate treatment and the patient’s discharge and recovery. Case presentation A 70-year-old male White patient was hospitalized in the intensive care unit following an intrahospital cardiac arrest. History started a year before with repeated deep vein thrombosis and episodes of skin eruption compatible with Sweet’s syndrome. After a course of oral steroids, fever and inflammatory syndrome relapsed with onset of polychondritis, episcleritis along with neurological symptoms and pulmonary infiltrates. Intrahospital hypoxic cardiac arrest happened during patient’s new investigations, and he was admitted in a critical state. During the intensive care unit stay, he presented with livedoid skin lesions on both feet. Vasculitis was not proven; however, cryoglobulinemia screening came back positive. Onset of pancytopenia was explored with a myelogram aspirate. It showed signs of dysmyelopoiesis and vacuoles in erythroid and myeloid precursors. Of note, new deep vein thrombosis developed, despite being treated with heparin leading to the diagnosis of heparin-induced thrombocytopenia. The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1-mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. Corticosteroids and anti-IL1 infusion were started with satisfactory results supporting patient’s discharge from intensive care unit to the internal medicine ward. Conclusions Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome should be suspected in male patients presenting with inflammatory symptoms, such as fever, skin eruption, chondritis, venous thromboembolism, and vacuoles in bone marrow precursors. Patients with undiagnosed vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome may present with organ failure requiring hospitalization in intensive care unit, where screening for UBA1 mutation should be performed when medical history is evocative. Multidisciplinary team involvement is highly recommended for patient management, notably to start appropriate immunosuppressive treatments.
Published: 2023
Full Text: View/download PDF

8. Anticoagulation strategy and safety in critically ill COVID-19 patients: a French retrospective multicentre study

Author: Pauline Lamouche-Wilquin, Léa Perrin, Morgane Pere, Matthieu Raymond, Pierre Asfar, Cedric Darreau, Florian Reizine, Gwenhaël Colin, Agathe Delbove, Johann Auchabie, Baptiste Hourmant, Aurélien Frérou, Béatrice La Combe, Jean Morin, Pierre Kergoat, Julien Lorber, Pierre-Yves Egreteau, Jérome Souchard, Emmanuel Canet, and Jean-Baptiste Lascarrou
Subjects: COVID-19, Anticoagulation strategies, Venous thromboembolism, Deep vein thrombosis, Pulmonary embolism, Intensive care unit, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract Background Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. Methods We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. Results Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52–1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79–1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38–0.80; p
Published: 2023
Full Text: View/download PDF

9. Association of early dexamethasone therapy with mortality in critically Ill COVID-19 patients: a French multicenter study

Author: Matthieu Raymond, Aurélie Le Thuaut, Pierre Asfar, Cédric Darreau, Florian Reizine, Gwenhaël Colin, Charly Dano, Julien Lorber, Baptiste Hourmant, Agathe Delbove, Aurélien Frérou, Jean Morin, Pierre Yves Egreteau, Philippe Seguin, Jean Reignier, Jean-Baptiste Lascarrou, and Emmanuel Canet
Subjects: COVID-19, Dexamethasone, Mortality, Intubation, Ventilator-associated pneumonia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Key messages What is already known on this topic Dexamethasone decreased day-28 mortality in the randomised controlled trial RECOVERY in patients admitted for COVID-19, including 74% who required oxygen and 16% invasive mechanical ventilation (iMV). Other trials targeting critically ill patients did not replicate this finding, leaving uncertainty about the benefits of dexamethasone. What this study adds In our large observational cohort of critically ill COVID-19 patients, of whom 61% required iMV, early systemic dexamethasone was not associated with lower day-28 mortality compared to no steroids. However, early dexamethasone was associated with less need for iMV, more days alive and off iMV, and a higher frequency of ventilator-associated pneumonia in the iMV sub-group. How this study might affect research, practice, or policy This study suggests that early dexamethasone may be warranted in critically ill COVID-19 patients, provided those receiving iMV are monitored closely for ventilatory-associated pneumonia.
Published: 2022
Full Text: View/download PDF

10. Acquired agitation in acute respiratory distress syndrome with COVID-19 compared to influenza patients: a propensity score matching observational study

Author: Adel Maamar, Clémence Liard, Willelm Doucet, Florian Reizine, Benoit Painvin, Flora Delamaire, Valentin Coirier, Quentin Quelven, Pauline Guillot, Mathieu Lesouhaitier, Jean Marc Tadié, and Arnaud Gacouin
Subjects: Covid-19, Influenza, ARDS, ICU, Agitation, Encephalopathy, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background A growing body of evidence reports that agitation and encephalopathy are frequent in critically ill Covid-19 patients. We aimed to assess agitation’s incidence and risk factors in critically ill ARDS patients with Covid-19. For that purpose, we compared SARS-CoV-2 acute respiratory distress syndrome (ARDS) patients with a population of influenza ARDS patients, given that the influenza virus is also known for its neurotropism and ability to induce encephalopathy. Methods We included all the patients with laboratory-confirmed Covid-19 infection and ARDS admitted to our medical intensive care unit (ICU) between March 10th, 2020 and April 16th, 2021, and all the patients with laboratory-confirmed influenza infection and ARDS admitted to our ICU between April 10th, 2006 and February 8th, 2020. Clinical and biological data were prospectively collected and retrospectively analyzed. We also recorded previously known factors associated with agitation (ICU length of stay, length of invasive ventilation, SOFA score and SAPS II at admission, sedative and opioids consumption, time to defecation). Agitation was defined as a day with Richmond Agitation Sedation Scale greater than 0 after exclusion of other causes of delirium and pain. We compared the prevalence of agitation among Covid-19 patients during their ICU stay and in those with influenza patients. Results We included 241 patients (median age 62 years [53–70], 158 males (65.5%)), including 146 patients with Covid-19 and 95 patients with Influenza. One hundred eleven (46.1%) patients had agitation during their ICU stay. Patients with Covid-19 had significantly more agitation than patients with influenza (respectively 80 patients (54.8%) and 31 patients (32.6%), p
Published: 2022
Full Text: View/download PDF

11. Multiple-site decontamination regimen decreases acquired infection incidence in mechanically ventilated COVID-19 patients

Author: Nicolas Massart, Florian Reizine, Pierre Fillatre, Philippe Seguin, Béatrice La Combe, Aurélien Frerou, Pierre-Yves Egreteau, Baptiste Hourmant, Pierre Kergoat, Julien Lorber, Jerome Souchard, Emmanuel Canet, Guillaume Rieul, Yannick Fedun, Agathe Delbove, and Christophe Camus
Subjects: Critical care, Pneumonia, Bacteremia, Mortality, COVID-19, Selective digestive decontamination, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation. Methods We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC. Results During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p
Published: 2022
Full Text: View/download PDF

12. Antifungal management in ICU: careful follow-up of voriconazole prescription needed!

Author: Florian Reizine and Jean-Pierre Gangneux
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2023
Full Text: View/download PDF

13. Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS

Author: Pauline Lamouche-Wilquin, Jérôme Souchard, Morgane Pere, Matthieu Raymond, Pierre Asfar, Cédric Darreau, Florian Reizine, Baptiste Hourmant, Gwenhaël Colin, Guillaume Rieul, Pierre Kergoat, Aurélien Frérou, Julien Lorber, Johann Auchabie, Béatrice La Combe, Philippe Seguin, Pierre-Yves Egreteau, Jean Morin, Yannick Fedun, Emmanuel Canet, Jean-Baptiste Lascarrou, and Agathe Delbove
Subjects: Mechanical ventilation, SARS-CoV-19, Nosocomial pneumonia, Dexamethasone, Methylprednisolone, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Rationale Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. Objectives To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). Methods We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. Measurements and main results Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05–1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61; P = 0.0003). Conclusions Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.
Published: 2022
Full Text: View/download PDF

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

Author: Virginie Pascal, Marine Dupont, Paco de Rouault, David Rizzo, Delphine Rossille, Robin Jeannet, Thomas Daix, Bruno François, Steve Genebrier, Marie Cornic, Guillaume Monneret, Fabienne Venet, Juliette Ferrant, Mikael Roussel, Florian Reizine, Mathieu Le Souhaitier, Jean-Marc Tadié, Karin Tarte, Jean Feuillard, and Michel Cogné
Subjects: Immunology, Respiratory medicine, Science
Abstract: Summary: To understand the fine differential elements that can lead to or prevent acute respiratory distress syndrome (ARDS) in COVID-19 patients, it is crucial to investigate the immune response architecture. We herein dissected the multiple layers of B cell responses by flow cytometry and Ig repertoire analysis from acute phase to recovery. Flow cytometry with FlowSOM analysis showed major changes associated with COVID-19 inflammation such as an increase of double-negative B-cells and ongoing plasma cell differentiation. This paralleled COVID-19-driven expansion of two disconnected B-cell repertoires. Demultiplexing successive DNA and RNA Ig repertoire patterns characterized an early expansion of IgG1 clonotypes with atypically long and uncharged CDR3, the abundance of this inflammatory repertoire being correlated with ARDS and likely pejorative. A superimposed convergent response included convergent anti-SARS-CoV-2 clonotypes. It featured progressively increasing somatic hypermutation together with normal-length or short CDR3 and it persisted until a quiescent memory B-cell stage after recovery.
Published: 2023
Full Text: View/download PDF

15. Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection

Author: Hind Hamzeh-Cognasse, Alexandre Mansour, Florian Reizine, Patrick Mismetti, Isabelle Gouin-Thibault, and Fabrice Cognasse
Subjects: Platelets, Innate immunity, CD40L, Inflammation, SARS-CoV2, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background The SARS-CoV-2 virus is the causing agent of the Coronavirus disease 2019 (COVID-19) characterized by a huge pro-inflammatory response and coagulation disorders that may lead to for its severe forms, in organ failure or even death. As major players of thrombo-inflammation, platelets release large amounts of immunomodulatory molecules and regulate leukocyte and endothelial activity, which are both altered in COVID-19. Altogether, this makes platelets a very likely actor of the thrombo-inflammatory complications of COVID-19. Thus, we propose to identify a platelet inflammatory signature of severe COVID-19 specifically modulated throughout the course of the disease. Methods Luminex technology and enzyme-linked immunosorbent assay were used to assess plasma levels of platelet inflammatory markers in patients with severe acute respiratory syndrome coronavirus 2 infection on admission and for 14 days afterwards. Results In accordance with the observations of other teams, we evidence that the plasma levels of the platelet soluble (s)CD40L is significantly elevated in the early stages of the disease. Interestingly we observe that the plasma level of sCD40L decreases overtime while that of sCD62P increases significantly. Conclusions Our data suggest that there is a platelet signature of inflammatory response to SARS-COv-2 infection which varies overtime and could serve as monitoring biomarkers of patient inflammatory state. Clinical trial registration number: 2020-A01100-39; title: Human Ab Response & immunoMONItoring of COVID-19 Patients, registration date: 05/25/2020; URL of the registry: https://clinicaltrials.gov/ct2/history/NCT04373200?V_5=View .
Published: 2021
Full Text: View/download PDF

16. Clinical spectrum and risk factors for mortality among seawater and freshwater critically ill drowning patients: a French multicenter study

Author: Florian Reizine, Agathe Delbove, Alexandre Dos Santos, Laetitia Bodenes, Pierre Bouju, Pierre Fillâtre, Aurélien Frérou, Guillaume Halley, Olivier Lesieur, Maud Jonas, Florian Berteau, Jean Morin, David Luque-Paz, Rémy Marnai, Anthony Le Meur, Cécile Aubron, Jean Reignier, Jean-Marc Tadié, and Arnaud Gacouin
Subjects: Drowning, ICU, ARDS, Saltwater, Freshwater, Cardiac arrest, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Drowning is a global threat and one of the leading causes of injury around the world. The impact of drowning conditions including water salinity on patients’ prognosis remains poorly explored in Intensive Care Units (ICUs) patients. Methods We conducted a retrospective multicenter study on patients admitted to 14 ICUs in the west of France from January 2013 to January 2020. We first compared demographic and clinical characteristics at admission as well as clinical courses of these patients according to the salinity of drowning water. Then, we aimed to identify variables associated with 28-day survival using a Cox proportional hazard model. Results Of the 270 consecutive included patients, drowning occurred in seawater in 199 patients (73.7%) and in freshwater in 71 patients (26.3%). Day-28 mortality was observed in 55 patients (20.4%). Freshwater was independently associated with 28-day mortality (Adjusted Hazard Ratio (aHR) 1.84 [95% Confidence Interval (CI) 1.03–3.29], p = 0.04). A higher proportion of freshwater patients presented psychiatric comorbidities (47.9 vs. 19.1%; p
Published: 2021
Full Text: View/download PDF

17. Venoarterial extracorporeal membrane oxygenation induces early immune alterations

Author: Aurélien Frerou, Mathieu Lesouhaitier, Murielle Gregoire, Fabrice Uhel, Arnaud Gacouin, Florian Reizine, Caroline Moreau, Aurélie Loirat, Adel Maamar, Nicolas Nesseler, Amedeo Anselmi, Erwan Flecher, Jean-Philippe Verhoye, Yves Le Tulzo, Michel Cogné, Mikael Roussel, Karin Tarte, and Jean-Marc Tadié
Subjects: VA-ECMO, Immunosuppression, MDSC, Lymphocyte exhaustion, Lymphopenia, Acquired infections, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides heart mechanical support in critically ill patients with cardiogenic shock. Despite important progresses in the management of patients under VA-ECMO, acquired infections remain extremely frequent and increase mortality rate. Since immune dysfunctions have been described in both critically ill patients and after surgery with cardiopulmonary bypass, VA-ECMO initiation may be responsible for immune alterations that may expose patients to nosocomial infections (NI). Therefore, in this prospective study, we aimed to study immune alterations induced within the first days by VA-ECMO initiation. Methods We studied immune alterations induced by VA-ECMO initiation using cytometry analysis to characterize immune cell changes and enzyme-linked immunosorbent assay (ELISA) to explore plasma cytokine levels. To analyze specific changes induced by VA-ECMO initiation, nine patients under VA-ECMO (VA-ECMO patients) were compared to nine patients with cardiogenic shock (control patients). Results Baseline immune parameters were similar between the two groups. VA-ECMO was associated with a significant increase in circulating immature neutrophils with a significant decrease in C5a receptor expression. Furthermore, we found that VA-ECMO initiation was followed by lymphocyte dysfunction along with myeloid-derived suppressor cells (MDSC) expansion. ELISA analysis revealed that VA-ECMO initiation was followed by an increase in pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α along with IL-10, a highly immunosuppressive cytokine. Conclusion VA-ECMO is associated with early immune changes that may be responsible for innate and adaptive immune alterations that could confer an increased risk of infection.
Published: 2021
Full Text: View/download PDF

18. Toward the personalized and integrative management of voriconazole dosing during COVID-19-associated pulmonary aspergillosis

Author: Brendan Le Daré, Christelle Boglione-Kerrien, Florian Reizine, Jean-Pierre Gangneux, and Astrid Bacle
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2021
Full Text: View/download PDF

19. Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV-2 infection

Author: Mikael Roussel, Juliette Ferrant, Florian Reizine, Simon Le Gallou, Joelle Dulong, Sarah Carl, Matheiu Lesouhaitier, Murielle Gregoire, Nadège Bescher, Clotilde Verdy, Maelle Latour, Isabelle Bézier, Marie Cornic, Angélique Vinit, Céline Monvoisin, Birgit Sawitzki, Simon Leonard, Stéphane Paul, Jean Feuillard, Robin Jeannet, Thomas Daix, Vijay K. Tiwari, Jean Marc Tadié, Michel Cogné, and Karin Tarte
Subjects: Medicine (General), R5-920
Abstract: Summary: Acute respiratory distress syndrome (ARDS) is the main complication of coronavirus disease 2019 (COVID-19), requiring admission to the intensive care unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS differs from other causes of ARDS remains unknown. To address this question, here, we build 3 cohorts of patients categorized in COVID-19−ARDS+, COVID-19+ARDS+, and COVID-19+ARDS−, and compare, by high-dimensional mass cytometry, their immune landscape. A cell signature associating S100A9/calprotectin-producing CD169+ monocytes, plasmablasts, and Th1 cells is found in COVID-19+ARDS+, unlike COVID-19−ARDS+ patients. Moreover, this signature is essentially shared with COVID-19+ARDS− patients, suggesting that severe COVID-19 patients, whether or not they experience ARDS, display similar immune profiles. We show an increase in CD14+HLA-DRlow and CD14lowCD16+ monocytes correlating to the occurrence of adverse events during the ICU stay. We demonstrate that COVID-19-associated ARDS displays a specific immune profile and may benefit from personalized therapy in addition to standard ARDS management.
Published: 2021
Full Text: View/download PDF

20. Purpura fulminans

Author: Florian Reizine, Lea Picard, Caroline Piau, and Jean‐Marc Tadié
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2021
Full Text: View/download PDF

21. Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients

Author: Pierre Le Balc’h, Kieran Pinceaux, Charlotte Pronier, Philippe Seguin, Jean-Marc Tadié, and Florian Reizine
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Published: 2020
Full Text: View/download PDF

22. Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Author: Bruno Giraudeau, Samir Jaber, Fabienne Tamion, Jean-François Timsit, Nicolas Terzi, Jean-Pierre Quenot, Jérôme Devaquet, Saad Nseir, Didier Thévenin, Alain Combes, Mai-Anh Nay, Gael Piton, Bertrand Guidet, Jean Reignier, Agathe Delbove, Jean-Paul Mira, Laurent Argaud, Christophe Leroy, Djillali Annane, Samuel Groyer, Florian Reizine, Pierre Asfar, Jack Richecoeur, Walter Picard, Michael Darmon, Emmanuelle Mercier, Amélie Le Gouge, Jean-Baptiste Lascarrou, Yannick Hourmant, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Christophe Cracco, Vincent Das, Matthieu Debarre, Sebastian Voicu, Nadia Aissaoui-Balanant, Louis-Marie Dumont, Johanna Oziel, Olivier Gontier, Fabien Lambiotte, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Gaetan Plantefeve, Anne Renault, Laurent Guérin, Jean Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Guillaume Thiéry, Nathalie Thieulot-Rolin, François Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, and Diane Maugars
Subjects: Medicine
Abstract: Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03573739.
Published: 2021
Full Text: View/download PDF

23. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial

Author: Emmanuel Nowak, Olivier Huet, Christophe Guitton, Stephan Ehrmann, Arnaud W Thille, Pierre Bailly, Pierre-Yves Egreteau, Guillaume Grillet, Florian Reizine, and S Jaber
Subjects: Medicine
Abstract: Introduction The use of sedation in intensive care units (ICUs) is necessary and ubiquitous. The impact of sedation strategy on outcome, particularly when delivered early after initiation of mechanical ventilation, is unknown. Evidence is increasing that volatile anaesthetic agents could be associated with better outcome. Their use in delirium prevention is unknown.Methods and analysis This study is an investigator-initiated, prospective, multicentre, two-arm, randomised, control, open-trial comparing inhaled sedation strategy versus intravenous sedation strategy in mechanically ventilated patients in ICU. Two hundred and fifty patients will be randomly assigned to the intravenous sedation group or inhaled sedation group, with a 1:1 ratio in two groups according to the sedation strategy. The primary outcome is the occurrence of delirium assessed using two times a day confusion assessment method for the ICU (CAM-ICU). Secondary outcomes include cognitive and functional outcomes at 3 and 12 months.Ethics and dissemination The study has been approved by the Regional Ethics Committee (CPP Ouest) and national authorities (ANSM). The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04341350
Published: 2021
Full Text: View/download PDF

24. Short-term survival of acute respiratory distress syndrome patients due to influenza virus infection alone: a cohort study

Author: Arnaud Gacouin, Mathieu Lesouhaitier, Florian Reizine, Charlotte Pronier, Murielle Grégoire, Benoit Painvin, Adel Maamar, Vincent Thibault, Yves Le Tulzo, and Jean Marc Tadié
Subjects: Medicine
Abstract: Background Influenza virus (IV)-related pathophysiology suggests that the prognosis of acute respiratory distress syndrome (ARDS) due to IV could be different from the prognosis of ARDS due to other causes. However, the impact of IV infection alone on the prognosis of ARDS patients compared to that of patients with other causes of ARDS has been poorly assessed. Methods We compared the 28-day survival from the diagnosis of ARDS with an arterial oxygen tension/inspiratory oxygen fraction ratio ≤150 mmHg between patients with and without IV infection alone. Data were collected prospectively and analysed retrospectively. We first performed survival analysis on the whole population; second, patients with IV infection alone were compared with matched pairs using propensity score matching. Results The cohort admitted from October 2009 to March 2020 consisted of 572 patients, including 73 patients (13%) with IV alone. On the first 3 days of mechanical ventilation, nonpulmonary Sequential Organ Failure Assessment scores were significantly lower in patients with IV infection than in the other patients. After the adjusted analysis, IV infection alone remained independently associated with lower mortality at day 28 (hazard ratio 0.51, 95% CI 0.26–0.99, p=0.047). Mortality at day 28 was significantly lower in patients with IV infection alone than in other patients when propensity score matching was used (20% versus 38%, p=0.02). Conclusions Our results suggest that patients with ARDS following IV infection alone have a significantly better prognosis at day 28 and less severe nonpulmonary organ dysfunction than do those with ARDS from causes other than IV infection alone.
Published: 2020
Full Text: View/download PDF

25. Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients

Author: Pierre-Jean Ferron, Brendan Le Daré, Julie Bronsard, Clara Steichen, Elodie Babina, Romain Pelletier, Thierry Hauet, Isabelle Morel, Karin Tarte, Florian Reizine, Bruno Clément, Bernard Fromenty, and Thomas Gicquel
Subjects: molecular networking, hydroxychloroquine, drug metabolism, HepaRG, COVID-19, fatty liver, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.
Published: 2021
Full Text: View/download PDF

26. Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Author: Florian Reizine, Kieran Pinceaux, Mathieu Lederlin, Brice Autier, Hélène Guegan, Arnaud Gacouin, David Luque-Paz, Christelle Boglione-Kerrien, Astrid Bacle, Brendan Le Daré, Yoann Launey, Mathieu Lesouhaitier, Benoit Painvin, Christophe Camus, Alexandre Mansour, Florence Robert-Gangneux, Sorya Belaz, Yves Le Tulzo, Jean-Marc Tadié, Adel Maamar, and Jean-Pierre Gangneux
Subjects: COVID-19, influenza, pulmonary aspergillosis, CAPA, IAPA, corticosteroids, Biology (General), QH301-705.5
Abstract: Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.
Published: 2021
Full Text: View/download PDF

27. Is the COVID-19 Pandemic a Good Time to Include Aspergillus Molecular Detection to Categorize Aspergillosis in ICU Patients? A Monocentric Experience

Author: Jean-Pierre Gangneux, Florian Reizine, Hélène Guegan, Kieran Pinceaux, Pierre Le Balch, Emilie Prat, Romain Pelletier, Sorya Belaz, Mathieu Le Souhaitier, Yves Le Tulzo, Philippe Seguin, Mathieu Lederlin, Jean-Marc Tadié, and Florence Robert-Gangneux
Subjects: invasive aspergillosis, putative, probable, COVID-19, Sars-CoV-2, ICU, Biology (General), QH301-705.5
Abstract: (1) Background: The diagnosis of invasive aspergillosis (IA) in an intensive care unit (ICU) remains a challenge and the COVID-19 epidemic makes it even harder. Here, we evaluated Aspergillus PCR input to help classifying IA in SARS-CoV-2-infected patients. (2) Methods: 45 COVID-19 patients were prospectively monitored twice weekly for Aspergillus markers and anti-Aspergillus serology. We evaluated the concordance between (I) Aspergillus PCR and culture in respiratory samples, and (II) blood PCR and serum galactomannan. Patients were classified as putative/proven/colonized using AspICU algorithm and two other methods. (3) Results: The concordance of techniques applied on respiratory and blood samples was moderate (kappa = 0.58 and kappa = 0.63, respectively), with a higher sensitivity of PCR. According to AspICU, 9/45 patients were classified as putative IA. When incorporating PCR results, 15 were putative IA because they met all criteria, probably with a lack of specificity in the context of COVID-19. Using a modified AspICU algorithm, eight patients were classified as colonized and seven as putative IA. (4) Conclusion: An appreciation of the fungal burden using PCR and Aspergillus serology was added to propose a modified AspICU algorithm. This proof of concept seemed relevant, as it was in agreement with the outcome of patients, but will need validation in larger cohorts.
Published: 2020
Full Text: View/download PDF

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

Author: Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
Subjects: Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio]
Abstract: Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
Published: 2023

29. Prevention of acquired invasive fungal infection with decontamination regimen in mechanically ventilated ICU patients: a pre/post observational study

Author: Nicolas Massart, Florian Reizine, Clarisse Dupin, François Legay, Eleonore Legris, Anne Cady, Guillaume Rieul, Nicolas Barbarot, Eric Magahlaes, and Pierre Fillatre
Subjects: Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, General Medicine
Abstract: Invasive fungal infections acquired in the intensive care unit (AFI) are life-threating complications of critical illness. However, there is no consensus on antifungal prophylaxis in this setting. Multiple site decontamination is a well-studied prophylaxis against bacterial and fungal infections. Data on the effect of decontamination regimens on AFI are lacking. We hypothesised that multiple site decontamination could decrease the rate of AFI in mechanically ventilated patients. We conducted a pre/post observational study in 2 ICUs, on adult patients who required mechanical ventilation for >24 h. During the study period, multiple-site decontamination was added to standard of care. It consists of amphotericin B four times daily in the oropharynx and the gastric tube along with topical antibiotics, chlorhexidine body wash and nasal mupirocin. In 870 patients, there were 27 AFI in 26 patients. Aspergillosis accounted for 20/143 of ventilator-associated pneumonia and candidemia for 7/75 of ICU-acquired bloodstream infections. There were 3/308 (1%) patients with AFI in the decontamination group and 23/562 (4%) in the standard-care group (p = 0.011). In a propensity-score matched analysis, there were 3/308 (1%) and 16/308 (5%) AFI in the decontamination group and the standard-care group respectively (p = 0.004) (3/308 vs 11/308 ventilator-associated pulmonary aspergillosis, respectively [p = 0.055] and 0/308 vs 6/308 candidemia, respectively [p = 0.037]). Acquired fungal infection is a rare event, but accounts for a large proportion of ICU-acquired infections. Our study showed a preventive effect of decontamination against acquired fungal infection, especially candidemia.Take home messageAcquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia).Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections.Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI.Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI. Acquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia). Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections. Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI. Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI.
Published: 2023
Full Text: View/download PDF

30. Author response for 'Citrulline enteral administration markedly reduces immunosuppressive extrafollicular plasma cell differentiation in a preclinical model of sepsis'

Author: null Juliette Gauthier, null Murielle Grégoire, null Florian Reizine, null Mathieu Lesouhaitier, null Yoni Desvois, null Gevorg Ghukasyan, null Caroline Moreau, null Patricia Amé, null Karin Tarte, null Jean‐Marc Tadié, and null Céline Delaloy
Published: 2022

31. CT findings of COVID-19-associated pulmonary aspergillosis: a systematic review and individual patient data analysis

Author: Wonju Hong, P. Lewis White, Matthijs Backx, Jean-Pierre Gangneux, Florian Reizine, Philipp Koehler, Robbert G. Bentvelsen, María Luján Cuestas, Hamed Fakhim, Jung Im Jung, Young Kyung Lee, Nishil R. Dalsania, Ravi Karan Patti, Soon Ho Yoon, Hallym University, University Hospital of Wales (UHW), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], University of Cologne, Amphia Ziekenhuis = Amphia Hospital [Breda, The Netherlands] (AZ=AH), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Isfahan University of Medical Sciences [Iran] (MUI), Catholic University of Korea, Asan Medical Center [Seoul], University of Ulsan, Maimonides Medical Center, Seoul National University Hospital, None, and Jonchère, Laurent
Subjects: Data Analysis, Male, [SDV]Life Sciences [q-bio], COVID-19, X-ray computed, Middle Aged, [SDV] Life Sciences [q-bio], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Coronavirus 2019, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Aspergillosis, Radiology, Nuclear Medicine and imaging, Pulmonary Aspergillosis, Tomography, X-Ray Computed, Lung, Tomography, Aged
Abstract: International audience; PURPOSE: Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities. RESULTS: The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%). CONCLUSION: CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.
Published: 2022

32. Herpesviridae systemic reactivation in patients with COVID-19-associated ARDS

Author: Vincent Thibault, Jean-Marc Tadié, Florian Reizine, Charlotte Pronier, Arnaud Gacouin, Adel Maamar, and Clémence Liard
Subjects: Microbiology (medical), ARDS, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), General Medicine, medicine.disease, medicine.disease_cause, Virology, Herpesviridae, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, 030228 respiratory system, Medicine, 030212 general & internal medicine, business
Published: 2022

33. Clinical and microbiological features of drowning-associated pneumonia: a retrospective multicentre cohort study

Author: Florian Reizine, Agathe Delbove, Pierre Tattevin, Alexandre Dos Santos, Laetitia Bodenes, Pierre Bouju, Pierre Fillâtre, Aurélien Frérou, Guillaume Halley, Olivier Lesieur, Patricia Courouble, Florian Berteau, Jean Morin, Flora Delamaire, Rémy Marnai, Anthony Le Meur, Cécile Aubron, Jean Reignier, Arnaud Gacouin, Jean-Marc Tadié, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Microbiology (medical), Drowning, [SDV]Life Sciences [q-bio], Microorganisms, General Medicine, Pneumonia, Cohort Studies, Hospitalization, Intensive Care Units, Critical care, Infectious Diseases, Humans, Hospital Mortality, Antimicrobial strategy, Retrospective Studies
Abstract: International audience; Objective: Pneumonia is the most frequent infectious complication in patients who have experienced drowning that requires intensive care unit (ICU) admission. We aimed to describe clinical, microbiological, and therapeutic data as well as predictors and impacts of such pneumonia on patients' outcomes.Methods: We conducted a retrospective, multicentre study (2013-2020) of 270 consecutive patients admitted for drowning to 14 ICUs in Western France. Their baseline characteristics and outcomes were compared according to the occurrence of drowning-associated pneumonia (DAP), defined as pneumonia diagnosed within 48 hours of ICU admission. A Cox regression model was used to compare survival on day 28, and logistic regression was used to identify risk factors for DAP. Microbiological characteristics and empirical antibacterial treatment were also analysed.Results: Among the 270 patients admitted to the ICU for drowning, 101 (37.4%) and 33 (12.2%) experienced pneumonia and microbiologically proven DAP, respectively. The occurrence of pneumonia was associated with higher severity scores at ICU admission (median Simplified Acute Physiology Score II, 34 [interquartile range {IQR}, 25-55] vs. 45 [IQR, 28-67]; p 0.006) and longer ICU length of stay (2 days [IQR, 1-3] vs. 4 days [IQR, 2-7]; p < 0.001). The 28-day mortality rate was higher among these patients (29/101 [28.7%] vs. 26/169 [15.4%]; p 0.013). Microbiologically proven DAP remained associated with higher 28-day mortality after adjustments for cardiac arrest and water salinity (adjusted hazard ratio, 1.86 [95% CI, 1.06-3.28]; p 0.03). A microbiological analysis of respiratory samples showed a high proportion of gram-negative bacilli (23/56; 41.1%), with a high prevalence of amoxicillin-clavulanate resistance (12/33; 36.4%).Conclusions: Pneumonia is a common complication in patients admitted in the ICU for drowning and is associated with increased mortality.
Published: 2022

34. Characteristics and outcome of varicella-zoster virus central nervous system infections in adults

Author: Y. Le Tulzo, M Tas, Florian Reizine, A. Le Bot, Charlotte Pronier, François Bénézit, Pierre Tattevin, P. Fillâtre, Matthieu Revest, Alice Ballerie, Patrick Jego, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CH Yves LE FOLL, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), Herpesvirus 3, Human, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Acyclovir, medicine.disease_cause, Antiviral Agents, Herpes Zoster, Virus, Immunocompromised Host, 03 medical and health sciences, Central Nervous System Infections, 0302 clinical medicine, Interquartile range, medicine, Humans, Meningitis, 030212 general & internal medicine, Aciclovir, Aged, Retrospective Studies, business.industry, Varicella zoster virus, Meningoencephalitis, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, 3. Good health, Infectious Diseases, Encephalitis, Varicella-zoster virus, Female, business, medicine.drug
Abstract: International audience; We conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011).
Published: 2021

35. SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage

Author: Joelle Dulong, Kieran Pinceaux, Claude Bendavid, Benoit Painvin, Mikael Roussel, Pierre Tattevin, Murielle Gregoire, Yoann Launey, Simon Le Gallou, Jean-Marc Tadié, Audrey Le Bot, Thomas Lebouvier, Berengère Cador-Rousseau, Karin Tarte, Christophe Camus, Adel Maamar, Caroline Moreau, Mathieu Lesouhaitier, Mathieu Lederlin, Michel Cogné, Delphine Rossille, Arnaud Gacouin, Matthieu Revest, Florian Reizine, Yves Le Tulzo, Alice Ballerie, Maelle Latour, Clotilde Verdy, Chard-Hutchinson, Xavier, CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University hospital of Rennes, France, Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale, Agence Nationale de la Recherche (ANR, Flash CoViD 'HARMONICOV ') grantFrench National Research Agency (ANR), Fondation de l'Avenir grant (Prix des donateurs, Mutualite Fonction Publique), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-20-COVI-0039,HARMONICOV,Immunomonitoring haute définition & caractérisation d'anticorps spécifiques chez des patients CoV-2 critiques versus en rémission(2020)
Subjects: Male, 0301 basic medicine, ARDS, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Lymphocyte, MDSC, Immunology, Arginine, Severity of Illness Index, law.invention, 03 medical and health sciences, 0302 clinical medicine, Cross infection, law, Lymphopenia, medicine, Humans, Immunology and Allergy, Prospective Studies, Lymphocytes, Aged, Mechanical ventilation, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, Myeloid-Derived Suppressor Cells, Mortality rate, Immunosuppression, Middle Aged, medicine.disease, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Arginase, Pneumonia, 030104 developmental biology, medicine.anatomical_structure, Original Article, Female, Covid-19, business, 030215 immunology
Abstract: Purpose The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. Methods A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. Results We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. Conclusions The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-020-00920-5.
Published: 2021

36. Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction

Author: Florian Reizine, Murielle Grégoire, Mathieu Lesouhaitier, Valentin Coirier, Juliette Gauthier, Céline Delaloy, Elise Dessauge, Florent Creusat, Fabrice Uhel, Arnaud Gacouin, Frédéric Dessauge, Cécile Le Naoures, Caroline Moreau, Claude Bendavid, Yoann Daniel, Kilian Petitjean, Valérie Bordeau, Claire Lamaison, Caroline Piau, Vincent Cattoir, Mikael Roussel, Bernard Fromenty, Christian Michelet, Yves Le Tulzo, Jaroslaw Zmijewski, Ronan Thibault, Michel Cogné, Karin Tarte, Jean-Marc Tadié, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Etablissement Français du Sang Bretagne, EFS, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), 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), ARN régulateurs bactériens et médecine (BRM), Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), University of Alabama at Birmingham [ Birmingham] (UAB), This work was supported by funding from the Société de Réanimation de Langue Française (SRLF, Bourses Master 2 SRLF). We also thank the animal house Animalerie Rennaise Centre d’Hébergement et d’Expérimentation (ARCHE) platform and H2P2 platform (Structure Fédérative de Recherche [SFR] Biosit), and Aude Bodin for her help with mitochondrial functions analysis., Jonchère, Laurent, and Center of Experimental and Molecular Medicine
Subjects: Immunosuppression Therapy, Multidisciplinary, Myeloid-Derived Suppressor Cells, T-Lymphocytes, [SDV]Life Sciences [q-bio], Biological Availability, T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Arginine, Lymphocyte Activation, T-Lymphocytes, Regulatory, Mitochondria, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Disease Models, Animal, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, Sepsis, Immune Tolerance, Animals, Cytokines, Citrulline, Female
Abstract: International audience; Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.
Published: 2022

37. Selective digestive decontamination to reduce the high rate of ventilator-associated pneumonia in critical COVID-19

Author: Christophe Camus, Pierre Tattevin, Paul Jaubert, Achille Kouatchet, David Luque-Paz, Florian Reizine, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), None, 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 ), and Jonchère, Laurent
Subjects: High rate, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, [SDV]Life Sciences [q-bio], 010102 general mathematics, Ventilator-associated pneumonia, 030208 emergency & critical care medicine, General Medicine, Critical Care and Intensive Care Medicine, medicine.disease, 01 natural sciences, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Selective digestive decontamination, medicine, 0101 mathematics, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022

38. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Author: Gilles Nevez, Brice Autier, Jean-Pierre Gangneux, Yves Cohen, Nadine François, Cécile Aubron, Emmanuel Canet, Sophie Brun, Alexandre Alanio, Philippe Seguin, Nicolas Terzi, Bruno Mégarbane, Jean-François Timsit, Romain Pelletier, Marie Soulié, Dorothée Quinio, Estelle Sabourin, Nicolas de Prost, Juliette Guitard, Frederique Boquel, Valérie Letscher-Bru, Jeff Morcet, Stephan Ehrmann, Guillaume Voiriot, Solène Le Gal, Florent Morio, Bruno Laviolle, Jean-Christophe Richard, Laurent Argaud, Estelle Cateau, Marion Blaize, Matthieu Lesouhaitier, Patrice Le Pape, Carole Schwebel, Florent Wallet, Jordan Leroy, Jean-Ralph Zahar, Ana Novara, Hélène Guegan, Béatrice Riu-Poulenc, Florence Robert-Gangneux, Jean Menotti, Eric Dannaoui, Sorya Belaz, Yves Le Tulzo, Muriel Cornet, Saad Nseir, Ferhat Meziani, Damien Dupont, Boualem Sendid, Antoine Monsel, Florian Reizine, Xavier Iriart, Francoise Botterel, Arnaud Fekkar, Charles-Edouard Luyt, Cécile Garnaud, Melek Manai, Lionel Lamhaut, Jean-Marc Tadié, Julien Mayaux, Sylvie Paulus, Florence Persat, Marie-Elisabeth Bougnoux, Christophe Hennequin, Christine Bonnal, Arnaud W. Thille, Antoine Berry, Sandrine Houze, Guillaume Desoubeaux, Centre Hospitalier Universitaire [Rennes], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Avicenne [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Necker - Enfants Malades [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, and CarMeN, laboratoire
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Intensive care, Internal medicine, medicine, Humans, education, Mechanical ventilation, education.field_of_study, Coinfection, SARS-CoV-2, business.industry, Mucormycosis, COVID-19, Articles, Odds ratio, medicine.disease, [SDV] Life Sciences [q-bio], Mycoses, business, Cohort study
Abstract: International audience; BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (\textgreater14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (\textless1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p\textless0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.
Published: 2022

39. Molecular networking for drug toxicities studies: The case of hydroxychloroquine in covid-19 patients

Author: Pierre-Jean Ferron, Brendan Le Daré, Julie Bronsard, Clara Steichen, Elodie Babina, Romain Pelletier, Thierry Hauet, Isabelle Morel, Karin Tarte, Florian Reizine, Bruno Clément, Bernard Fromenty, Thomas Gicquel, Centre Hospitalier Universitaire [Rennes], 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], Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale, Inserm, Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM, HAL UR1, Admin, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Biology (General), Correlation of Data, Spectroscopy, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Fatty Acids, General Medicine, Middle Aged, 3. Good health, Computer Science Applications, Chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Chemical and Drug Induced Liver Injury, HepaRG, Metabolic Networks and Pathways, Hydroxychloroquine, Drug-Related Side Effects and Adverse Reactions, QH301-705.5, Cell Survival, Antiviral Agents, Catalysis, Article, Cell Line, Inorganic Chemistry, 03 medical and health sciences, Fatty liver, Humans, Obesity, Physical and Theoretical Chemistry, Molecular networking, QD1-999, Molecular Biology, 030304 developmental biology, Aged, Drug metabolism, Organic Chemistry, COVID-19, COVID-19 Drug Treatment, Linear Models, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, molecular networking, hydroxychloroquine, drug metabolism, fatty liver
Abstract: International audience; Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Published: 2022

40. Demultiplexing Ig Repertoires by Parallel mRNA/DNA Sequencing Shows Major Differential Alterations in Severe COVID-19

Author: Virginie Pascal, Marine Dupont, Paco de Rouault, David Rizzo, Delphine Rossille, Robin Jeannet, Thomas Daix, Bruno François, Guillaume Monneret, Fabienne Venet, Juliette Ferrant, Mikael Roussel, Florian Reizine, Mathieu Le Souhaitier, Jean-Marc Tadié, Karin Tarte, Jean Feuillard, and Michel Cogné
Published: 2022

41. Respiratory management of drowning-associated acute respiratory failure: a multicentre retrospective cohort study

Author: Florian Reizine, Yannick Fedun, Laetitia Bodenes, Pierre Bouju, Pierre Fillâtre, Aurélien Frérou, Olivier Lesieur, Arnaud Gacouin, and Agathe Delbove
Subjects: Pulmonary and Respiratory Medicine
Published: 2023

42. Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection

Author: Fabrice Cognasse, Florian Reizine, Isabelle Gouin-Thibault, Patrick Mismetti, Hind Hamzeh-Cognasse, Alexandre Mansour, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre d'Investigation Clinique [Rennes] (CIC), 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), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Etablissement français du sang, Auvergne-Loire [Saint-Etienne] (EFS), Etablissement Français du Sang, This work was supported by grants from the French National Blood Service—EFS. This work was supported by the CFTR2 (COVID Fast Track Research Rennes) grant from the University hospital of Rennes, France., Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Adult, Blood Platelets, Male, Platelets, [SDV]Life Sciences [q-bio], Short Report, Inflammation, Infectious and parasitic diseases, RC109-216, Disease, 030204 cardiovascular system & hematology, Virus, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, CD40L, Platelet, SARS-CoV2, Young adult, Aged, 030304 developmental biology, Innate immunity, 0303 health sciences, CD40, Innate immune system, biology, COVID-19, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Infectious Diseases, Immunology, biology.protein, Female, medicine.symptom, Biomarkers
Abstract: Background The SARS-CoV-2 virus is the causing agent of the Coronavirus disease 2019 (COVID-19) characterized by a huge pro-inflammatory response and coagulation disorders that may lead to for its severe forms, in organ failure or even death. As major players of thrombo-inflammation, platelets release large amounts of immunomodulatory molecules and regulate leukocyte and endothelial activity, which are both altered in COVID-19. Altogether, this makes platelets a very likely actor of the thrombo-inflammatory complications of COVID-19. Thus, we propose to identify a platelet inflammatory signature of severe COVID-19 specifically modulated throughout the course of the disease. Methods Luminex technology and enzyme-linked immunosorbent assay were used to assess plasma levels of platelet inflammatory markers in patients with severe acute respiratory syndrome coronavirus 2 infection on admission and for 14 days afterwards. Results In accordance with the observations of other teams, we evidence that the plasma levels of the platelet soluble (s)CD40L is significantly elevated in the early stages of the disease. Interestingly we observe that the plasma level of sCD40L decreases overtime while that of sCD62P increases significantly. Conclusions Our data suggest that there is a platelet signature of inflammatory response to SARS-COv-2 infection which varies overtime and could serve as monitoring biomarkers of patient inflammatory state. Clinical trial registration number: 2020-A01100-39; title: Human Ab Response & immunoMONItoring of COVID-19 Patients, registration date: 05/25/2020; URL of the registry: https://clinicaltrials.gov/ct2/history/NCT04373200?V_5=View.
Published: 2021

43. Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

Author: Christophe Leroy, Agathe Delbove, Guillaume Thiery, Gaëtan Plantefève, Patrice Tirot, Louis Chauvelot, Didier Thevenin, Julien Maizel, Vincent Das, Michael Darmon, Nathalie Thieulot-Rolin, Laurent Guérin, Philippe Letocart, Delphine Chatellier, Francis Schneider, Jérôme Devaquet, Fabien Lambiotte, Jean-Baptiste Lascarrou, Olivier Gontier, Walter Picard, Samir Jaber, Gaël Piton, Isabelle Vinatier, Bruno Giraudeau, Christophe Cracco, Amélie Le Gouge, Jean Pierre Quenot, Nicolas Terzi, Jack Richecoeur, Jean Philippe Rigaud, Sebastian Voicu, Yannick Hourmant, Laurent Brisard, Mai Anh Nay, Jean Reignier, François Tinturier, Djillali Annane, Louis Marie Dumont, Nicolae Vlad Botoc, Thierry Vanderlinden, Florian Reizine, Benjamin Madeux, Pierre Asfar, Samuel Groyer, Fabienne Tamion, Jean Paul Mira, Bertrand Souweine, Saad Nseir, Jean-François Timsit, Bertrand Guidet, Julio Badie, Johanna Oziel, Olivier Martinet, Anne Renault, Frédéric Martino, Christophe Vinsonneau, Diane Maugars, Nadia Aissaoui-Balanant, Michel Sirodot, Laurent Argaud, Hoang Nam Bui, Matthieu Debarre, Alain Combes, Emmanuelle Mercier, Daniel da Silva, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, Calorie, Low protein, Critical Illness, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Informed consent, law, Internal medicine, Diet, Protein-Restricted, Humans, Medicine, 030212 general & internal medicine, adult intensive & critical care, nutrition & dietetics, 2. Zero hunger, Mechanical ventilation, clinical trials, Protein feeding, SARS-CoV-2, business.industry, Intensive Care, COVID-19, General Medicine, Respiration, Artificial, Intensive care unit, 3. Good health, Clinical trial, Shock (circulatory), medicine.symptom, business
Abstract: IntroductionInternational guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysisNUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and disseminationThe NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03573739.
Published: 2021

44. Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV2 infection

Author: Karin Tarte, B. Sawitzki, Isabelle Bezier, Joelle Dulong, Thomas Daix, S. Le Gallou, Juliette Ferrant, Jean Feuillard, Céline Monvoisin, Robin Jeannet, Nadège Bescher, Sarah H. Carl, Murielle Gregoire, A. Vinit, Maelle Latour, Simon Léonard, Mikael Roussel, Florian Reizine, C. Verdy, M. Cornic, Michel Cogné, Mathieu Lesouhaitier, Stéphane Paul, Jean-Marc Tadié, Vijay K. Tiwari, Centre Hospitalier Universitaire [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement Français du Sang Bretagne, EFS, LabEX IGO Immunothérapie Grand Ouest, Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Limoges, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges, Queen's University [Belfast] (QUB), Etablissement français du sang [Rennes] (EFS Bretagne), This work was supported by the University Hospital of Rennes (CHU Rennes), CFTR2 (COVID-19 Fast Track Recherche Rennes) grant (to F.R.) and by the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche (ANR), Flash Covid-19 joint grant ( HARMONICOV to M. Cogné)., ANR-20-COVI-0039,HARMONICOV,Immunomonitoring haute définition & caractérisation d'anticorps spécifiques chez des patients CoV-2 critiques versus en rémission(2020), 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 ), Nantes Université (Nantes Univ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Gestionnaire, Hal Sorbonne Université, and Immunomonitoring haute définition & caractérisation d'anticorps spécifiques chez des patients CoV-2 critiques versus en rémission - - HARMONICOV2020 - ANR-20-COVI-0039 - COVID-19 - VALID
Subjects: Male, Medicine (General), medicine.medical_specialty, ARDS, Sialic Acid Binding Ig-like Lectin 1, [SDV]Life Sciences [q-bio], Lipopolysaccharide Receptors, 030204 cardiovascular system & hematology, Article, Monocytes, General Biochemistry, Genetics and Molecular Biology, S100A9, law.invention, Cohort Studies, Evolution, Molecular, Machine Learning, Immune profiling, 03 medical and health sciences, R5-920, 0302 clinical medicine, Immune system, law, Internal medicine, medicine, Humans, Mass cytometry, Adverse effect, Aged, 030304 developmental biology, Respiratory Distress Syndrome, 0303 health sciences, SARS-CoV-2, business.industry, COVID-19, HLA-DR Antigens, Middle Aged, Th1 Cells, medicine.disease, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Leukocytes, Mononuclear, Female, business, Complication
Abstract: Acute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS differs from other causes of ARDS remains unknown. To address this question, we build 3 cohorts of patients categorize in COVID-19negARDSpos, COVID-19posARDSpos, and COVID-19posARDSneg, and compare their immune landscape analyze by high-dimensional mass cytometry on peripheral blood. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells is found in COVID-19posARDSpos, unlike COVID-19negARDSpos patients. Moreover, this signature is essentially share with COVID-19posARDSneg patients, suggesting that severe COVID-19 patients, whatever they experience or not ARDS, display similar immune profiles. We show an increase in CD14posHLA-DRlow and CD14lowCD16pos monocytes correlate to the occurrence of adverse events during ICU stay. We demonstrate that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalize therapy in addition to standard ARDS management., Graphical Abstract, Roussel et al. characterize the immune profile of COVID-19+ and COVID-19- patients, both presenting an acute respiratory distress syndrome (ARDS) and COVID-19+ without ARDS. They identify a COVID-19 signature associating CD169+S100A9+ monocytes, plasmablasts, and Th1 cells. CD14+HLA-DRlo and CD14loCD16+ monocytes increase during the ICU stay correlate with unfavorable clinical course.
Published: 2021

45. Monitoring Transcutaneously Measured Partial Pressure of CO

Author: Aurélien, Frérou, Adel, Maamar, Sonia, Rafi, Claire, Lhommet, Pierre, Phelouzat, Emmanuel, Pontis, Florian, Reizine, Mathieu, Lesouhaitier, Christophe, Camus, Yves, Le Tulzo, Jean-Marc, Tadié, and Arnaud, Gacouin
Subjects: Oxygen, Noninvasive Ventilation, Critical Illness, Partial Pressure, Intubation, Intratracheal, Humans, Prospective Studies, Carbon Dioxide
Abstract: The risk for severe hypoxemia during endotracheal intubation is a major concern in the ICU, but little attention has been paid to COIn this single-center, prospective, observational study, we recorded [Formula: see text] from preoxygenation to 3 h after the initiation of mechanical ventilation among subjects requiring endotracheal intubation. Subjects were sorted into 3 groups according to the preoxygenation method. We then assessed the link between [Formula: see text] variability and the development of postintubation hypotension.A total of 202 subjects were included in the study. The [Formula: see text] values recorded at endotracheal intubation, at the initiation of mechanical ventilation, and after 30 min and 1 h of mechanical ventilation were significantly higher than those recorded during preoxygenation ([Formula: see text] variability during intubation is significant and differs with the method of preoxygenation. A decrease in [Formula: see text] after the beginning of mechanical ventilation was associated with postintubation hypotension. (ClinicalTrials.gov registration NCT0388430.).
Published: 2021

46. Monitoring Transcutaneously Measured Partial Pressure of CO(2) During Intubation in Critically Ill Subjects

Author: Claire Lhommet, Arnaud Gacouin, Florian Reizine, Mathieu Lesouhaitier, Aurélien Frérou, Yves Le Tulzo, Jean-Marc Tadié, Pierre Phelouzat, Christophe Camus, Sonia Rafi, Adel Maamar, Emmanuel Pontis, CHU Pontchaillou [Rennes], Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Pulmonary and Respiratory Medicine, hypotension, medicine.medical_treatment, [SDV]Life Sciences [q-bio], mechanical ventilation, Critical Care and Intensive Care Medicine, medicine.disease_cause, intensive care unit, intubation, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Oxygen therapy, medicine, Intubation, Mechanical ventilation, business.industry, General Medicine, Intensive care unit, 3. Good health, preoxygenation, 030228 respiratory system, Anesthesia, Breathing, Propofol, business, transcutaneous blood gas monitoring, Nasal cannula, Respiratory minute volume, medicine.drug
Abstract: BACKGROUND: The risk for severe hypoxemia during endotracheal intubation is a major concern in the ICU, but little attention has been paid to CO2 variability. The objective of this study was to assess transcutaneously measured partial pressure of CO2 ( P tcCO 2 ) throughout intubation in subjects in the ICU who received standard oxygen therapy, high-flow nasal cannula oxygen therapy, or noninvasive ventilation for preoxygenation. We hypothesized that the 3 methods differ in terms of ventilation and CO2 removal. METHODS: In this single-center, prospective, observational study, we recorded P tcCO 2 from preoxygenation to 3 h after the initiation of mechanical ventilation among subjects requiring endotracheal intubation. Subjects were sorted into 3 groups according to the preoxygenation method. We then assessed the link between P tcCO 2 variability and the development of postintubation hypotension. RESULTS: A total of 202 subjects were included in the study. The P tcCO 2 values recorded at endotracheal intubation, at the initiation of mechanical ventilation, and after 30 min and 1 h of mechanical ventilation were significantly higher than those recorded during preoxygenation (P P tcCO 2 variability differed significantly according to the preoxygenation method (P P tcCO 2 by > 5 mm Hg within 30 min after the start of mechanical ventilation was independently associated with postintubation hypotension (odds ratio = 2.14 [95% CI 1.03–4.44], P = .039) after adjustments for age, Simplified Acute Physiology Score II, COPD, cardiac comorbidity, the use of propofol for anesthetic induction, and minute ventilation at the start of mechanical ventilation. CONCLUSIONS: P tcCO 2 variability during intubation is significant and differs with the method of preoxygenation. A decrease in P tcCO 2 after the beginning of mechanical ventilation was associated with postintubation hypotension. (ClinicalTrials.gov registration NCT0388430.)
Published: 2021

47. Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With COVID-19 Pneumonia

Author: Charles Tacquard, Alexandre Mansour, Alexandre Godon, Julien Godet, Julien Poissy, Delphine Garrigue, Eric Kipnis, Sophie Rym Hamada, Paul Michel Mertes, Annick Steib, Mathilde Ulliel-Roche, Bélaïd Bouhemad, Maxime Nguyen, Florian Reizine, Isabelle Gouin-Thibault, Marie Charlotte Besse, Nived Collercandy, Stefan Mankikian, Jerrold H. Levy, Yves Gruel, Pierre Albaladejo, Sophie Susen, Anne Godier, P. Albaladejo, N. Blais, F. Bonhomme, A. Borel-Derlon, A. Cohen, J.-P. Collet, E. de Maistre, P. Fontana, D. Garrigue Huet, A. Godier, Y. Gruel, A. Godon, B. Ickx, S. Laporte, D. Lasne, J. Llau, G. Le Gal, T. Lecompte, S. Lessire, J.H. Levy, D. Longrois, S. Madi-Jebara, A. Mansour, M. Mazighi, P. Mismetti, P.E. Morange, S. Motte, F. Mullier, N. Nathan, P. Nguyen, G. Pernod, N. Rosencher, S. Roullet, P.M. Roy, S. Schlumberger, P. Sié, A. Steib, S. Susen, C.A. Tacquard, S. Testa, A. Vincentelli, P. Zufferey, CHU Strasbourg, CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Duke University [Durham], University Hospital of Strasbourg (Hopitaux Universitaires de Strasbourg-Direction de la Recherche Clinique et des Innovations), Université de Rennes (UR), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: BMI, body mass index, [SDV]Life Sciences [q-bio], VTE, venous thromboembolism, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, 030212 general & internal medicine, anticoagulation, Original Research, Incidence (epidemiology), Hazard ratio, INR, international normalized ratio, Vitamin K antagonist, IPTW, inverse probability treatment weighting, ICU, intensive care unit, 3. Good health, Pulmonary embolism, [SDV] Life Sciences [q-bio], Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, Critical Illness, Low molecular weight heparin, HPA, high dose prophylactic anticoagulation, 03 medical and health sciences, Internal medicine, medicine, Humans, CRRT, continuous renal replacement therapy, UFH, unfractionated heparin, APTT, activated partial thromboplastin time, Blood Coagulation, thrombosis, DOAC, direct oral anticoagulant, business.industry, SARS-CoV-2, Anticoagulants, COVID-19, Retrospective cohort study, VKA, vitamin K antagonist, medicine.disease, bleeding, HR, hazard ratio, LMWH, low molecular weight heparin, OR, odds ratio, 030228 respiratory system, COPD, chronic obstructive pulmonary disease, TC, thrombotic complication, business, ECMO, extracorporeal membrane oxygenation
Abstract: International audience; BACKGROUND: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent. RESEARCH QUESTION: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC? STUDY DESIGN AND METHODS: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight. RESULTS: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75). INTERPRETATION: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.
Published: 2021

48. High Prevalence of Fungal Infections in Mechanically Ventilated COVID-19 Patients in the ICU: The French Multicenter MYCOVID Study

Author: Jean-Christophe Richard, Nicolas de Prost, Yves Cohen, Sylvie Paulus, Dorothée Quinio, Melek Manai, Carole Schwebel, Florence Persat, Antoine Berry, Cécile Garnaud, Lionel Lamhaut, Florian Reizine, Jordan Leroy, Hélène Guegan, Béatrice Riu-Poulenc, Jean Marc Tadie, Muriel Cornet, Antoine Monsel, Arnaud Fekkar, Guillaume Desoubeaux, Ferhat Meziani, Marie Soulié, Jean-Pierre Gangneux, Florence Robert-Gangneux, Nicolas Terzi, Mathieu Lesouhaitier, Yves Le Tulzo, Christine Bonnal, Bruno Mégarbane, Valérie Letscher-Bru, Guillaume Voiriot, Gilles Nevez, Brice Autier, Jean-François Timsit, Nadine François, Jean Menotti, Frederique Boquel, Patrice Le Pape, Christophe Hennequin, Xavier Iriart, Estelle Cateau, Charles Edouard Luyt, Francoise Botterel, Florent Wallet, Solène Le Gal, Philippe Seguin, Julien Mayaux, Jean-Ralph Zahar, Marie-Elisabeth Bougnoux, Bruno Laviolle, Estelle Sabourin, Sophie Brun, Jeff Morcet, Laurent Argaud, Juliette Guitard, Emmanuel Canet, Alexandre Alanio, Cécile Aubron, Saad Nseir, Florent Morio, Romain Pelletier, Marion Blaize, Damien Dupont, Ana Novara, Boualem Sendid, Stephan Ehrmann, Sandrine Houze, Eric Dannaoui, Sorya Belaz, and Arnaud W. Thille
Subjects: Mechanical ventilation, medicine.medical_specialty, High prevalence, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Emergency medicine, medicine, business, Dexamethasone, medicine.drug
Published: 2021

49. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial

Author: Pierre-Yves Egreteau, Christophe Guitton, Erwan L'Her, Stephan Ehrmann, Emmanuel Nowak, Samir Jaber, Guillaume Grillet, Olivier Huet, Arnaud W. Thille, Florian Reizine, Pierre Bailly, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CH Morlaix, 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), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, Sedation, medicine.medical_treatment, Trial protocol, delirium & cognitive disorders, Intravenous sedation, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Intensive care, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Multicenter Studies as Topic, Anesthesia, 030212 general & internal medicine, Prospective Studies, adult anaesthesia, adult intensive & critical care, Randomized Controlled Trials as Topic, Mechanical ventilation, business.industry, Ethics committee, Intensive Care, Delirium, General Medicine, Respiration, Artificial, 3. Good health, Intensive Care Units, Emergency medicine, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Open label, business
Abstract: IntroductionThe use of sedation in intensive care units (ICUs) is necessary and ubiquitous. The impact of sedation strategy on outcome, particularly when delivered early after initiation of mechanical ventilation, is unknown. Evidence is increasing that volatile anaesthetic agents could be associated with better outcome. Their use in delirium prevention is unknown.Methods and analysisThis study is an investigator-initiated, prospective, multicentre, two-arm, randomised, control, open-trial comparing inhaled sedation strategy versus intravenous sedation strategy in mechanically ventilated patients in ICU. Two hundred and fifty patients will be randomly assigned to the intravenous sedation group or inhaled sedation group, with a 1:1 ratio in two groups according to the sedation strategy. The primary outcome is the occurrence of delirium assessed using two times a day confusion assessment method for the ICU (CAM-ICU). Secondary outcomes include cognitive and functional outcomes at 3 and 12 months.Ethics and disseminationThe study has been approved by the Regional Ethics Committee (CPP Ouest) and national authorities (ANSM). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04341350
Published: 2021

50. Mass Cytometry and Artificial Intelligence Define CD169 as a Marker of SARS-CoV2-Induced Acute Respiratory Distress Syndrome

Author: Isabelle Bezier, Jean Feuillard, Murielle Gregoire, Juliette Ferrant, Mikael Roussel, Michel Cogné, Maelle Latour, Joelle Dulong, Mathieu Lesouhaitier, Angelique Vinit, Marie Cornic, Simon Léonard, Jean Marc Tadié, Sarah H. Carl, Simon Le Gallou, Florian Reizine, Nadège Bescher, Clothilde Verdy, Vijay K. Tiwari, and Karin Tarte
Subjects: ARDS, business.industry, medicine.disease, Intensive care unit, law.invention, Cog, Informed consent, law, Medicine, Artificial intelligence, Fast track, business, Complication, Adverse effect, Declaration of Helsinki
Abstract: Acute respiratory distress syndrome (ARDS) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite extensive immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS specifically differs from other causes of ARDS remains unknown. To address this crucial question, we built 3 cohorts of patients categorized in COVID-19neg ARDSpos, COVID-19pos ARDSpos, and COVID-19pos ARDSneg, and compared their immune landscape analyzed by high-dimensional mass cytometry on peripheral blood followed by artificial intelligence analysis. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19pos ARDSpos, unlike COVID-19neg ARDSpos patients. Moreover, this signature was essentially shared with COVID-19pos ARDSneg patients, suggesting that severe COVID-19 patients, whatever they experienced or not ARDS, display similar immune profiles. We also showed an increase in CD14pos HLA-DRlow and CD14low CD16pos monocytes correlated to the occurrence of adverse events during ICU stay. Our study demonstrates that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalized therapy in addition to standard ARDS management. Funding: This work was supported by the University hospital of Rennes, CFTR² (COVID-19 Fast Track Recherche Rennes) grant (to F.R.)and by the Fondation pour la Recherche Medicale (FRM) and the Agence Nationale de la Recherche (ANR), Flash Covid-19 joint grant (HARMONICOV to M.Cog.) Conflict of Interest: J.Fer., F.R., S.L.G., J.D., M.Le., M.G., N.B., C.V., M.La., I.B., M.Cor., S.L., J.Feu., M. Cog. declare no competing interest. M.R., S.C., V.K.T., J.M.T., and K.T. are the inventors of a patent EP 20305642.9 “A method for early detection of propensity to severe clinical manifestations Methods” submitted June 11th 2020 under University hospital of Rennes and Scailyte AG names. Ethical Approval: The study design was approved by our ethic committee (CHU Rennes, n°35RC20_9795_HARMONICOV, ClinicalTrials.gov Identifier: NCT04373200) and informed consent was obtained from patients in accordance with the Declaration of Helsinki.
Published: 2020

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

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

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

65 results on '"Florian Reizine"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources